DSHS Authors: Research Articles by DSHS Staff
This page provides information about DSHS Authors: Research Articles by DSHS Staff .
DSHS Authors: Research Articles by DSHS Staff
The following list of journal citations includes peer-reviewed research articles that have been written by staff of the Texas Department of State Health Services in the last four years.
For more information about these articles or for a full-text copy, contact the Medical and Research Library by email or call 512-776-7559.
If you are a DSHS author and have published a research article, textbook, or book chapter and you would like it to be included in this list, email the Medical and Research Library.
DSHS Authors by Year
(In date order with the most recent first).
Shumate C, et al. Epidemiologic features of preterm birth among infants with trisomy 21 in Texas, 1999-2018. Am J Med Genet A. 2026 Jan;200(1):93-101. doi:10.1002/ajmg.a.64229 Epub 2025 Aug 21.
Abstract
The rate of preterm birth among infants with trisomy 21 (22%) is around twice that among the general population (10%). We conducted a descriptive epidemiologic study to address the gap in knowledge on what maternal and infant factors are associated with preterm birth among infants with trisomy 21. Singleton infants with trisomy 21 born between 1999 and 2018 were identified from the Texas Birth Defects Registry. We used multivariable logistic regression to assess associations between preterm birth and 14 maternal and infant characteristics. Statistically significant associations were observed between preterm birth and maternal race/ethnicity, maternal age, maternal birthplace, prenatal care, smoking, infant sex, and infant delivery year. For instance, preterm birth was associated with maternal age (adjusted odds ratio [aOR] 1.44, 95% CI: 1.23-1.70 for ≥ 40 vs. 25-29 years) and prenatal care (aOR 1.59, 95% CI: 1.25-2.03 for no care versus any care). Our findings contribute toward a better understanding of the risk profile of preterm birth among infants with trisomy 21 and can guide further research on risk factors and potential interventions for reducing preterm birth rates in this population.
Gardner E, et al. Sensitivity of cancer registry linkage with missing or incomplete social security number and implications for cancer cohorts. Epidemiology. 2026 Jan 1;37(1):73-76. doi:10.1097/EDE.0000000000001913 Epub 2025 Sep 9.
Abstract
Background: Linking cancer cohort participants to state cancer registries typically relies on personally identifiable information, including social security numbers (SSN), which uniquely identify individuals. However, complete SSN collection can be limited due to privacy concerns. This study evaluates the sensitivity of cancer registry linkage using partial or missing SSN and examines differences by demographic characteristics.
Methods: Using data from 284,361 participants in the Cancer Prevention Study-3, we conducted probabilistic linkages with cancer registries in Georgia, Ohio, and Texas using Match*Pro software. Participants were linked using combinations of personally identifiable information: complete SSN, partial SSN (last four digits), and missing SSN. We compared the sensitivity of linkages before and after manual review and stratified by sex, age, and race-ethnicity.
Results: Before manual review, the sensitivity for missing and partial SSNs was 92.5%. Sensitivity improved to 98.6% for missing SSN and 98.8% for partial SSN after manual review. We observed no notable heterogeneity by sex, age, or race-ethnicity, with sensitivity exceeding 87% across all subgroups. Manual review substantially reduced uncertain matches, contributing to high linkage accuracy.
Conclusion: This study demonstrates that high sensitivity in cancer registry linkage can be achieved without a complete SSN, provided other personally identifiable information (e.g., name, date of birth, longitudinal address) is available. These findings support the feasibility of accurate cancer case identification in cohorts with limited SSN data, particularly for historically marginalized populations, and underscore the importance of designing inclusive population-based cancer studies.
Salinas VA, Archer NP, Lustri LR, et al. Evaluating differences in nonsyndromic orofacial clefts by infant sex: National Birth Defects Prevention Study, 1997-2011. J Pediatr. 2026 Jan;288:114567. doi:10.1016/j.jpeds.2025.114567 Epub 2025 Mar 28.
Abstract
Objective: To investigate nongenetic factors that may contribute to observed differences in nonsyndromic orofacial clefts by infant sex.
Study design: Using data for 1997-2011 deliveries from the National Birth Defects Prevention Study, a case-control study, we separately examined associations between 23 maternal factors and cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP) using multivariable logistic regression stratified by infant sex.
Results: We compared 2986 infants with CL/P and 1557 with CP to 11 271 control infants without birth defects. After adjusting for maternal age at conception and education, lower odds of nonsyndromic orofacial clefts were observed among male infants of non-Hispanic Black mothers (CL/P adjusted odds ratio [aOR]: 0.36; 95% confidence interval [CI]: 0.28-0.45; CP aOR: 0.56; 95% CI: 0.41-0.76) and of Hispanic mothers (CL/P aOR: 0.84; 95% CI: 0.73-0.96; CP aOR: 0.57; 95% CI: 0.45-0.72) compared with non-Hispanic White mothers. Similar, though attenuated, lower odds of nonsyndromic orofacial clefts were observed among female infants of non-Hispanic Black mothers, but no association was observed among female infants of Hispanic mothers. Differences in associations between maternal education and nutrient intake (carbohydrate, energy, total lipids/fat, vitamin E, and zinc) and CL/P, as well as maternal vitamin C intake and CP, were also observed by infant sex.
Conclusions: Associations between nonsyndromic orofacial clefts and minority racial and ethnic groups were attenuated or nonexistent among female infants compared with male infants. Sex-specific differences of CL/P appear more susceptible to environmental factors (eg, maternal education and nutrient intake) than sex-specific differences of CP.
(In date order with the most recent first):
Allred RP, Yantz C, Jeon H, Howell R, Kilburn M, Shumate C. Utility of electronic case reporting for case identification in Texas birth defects surveillance. Birth Defects Res. 2025 Dec;117(12):e70004. doi:10.1002/bdr2.70004
Abstract
Background: The utility of electronic case reporting (eCR) in birth defects surveillance is unknown. This evaluation assessed whether electronic initial case reports (eICRs) can serve as a potential case identification source and how eICRs compare to electronic health records (EHRs) in capturing demographic and diagnostic information.
Methods: Cases were identified from the Texas Birth Defects Registry's eCR data stream. Upon case confirmation, the EHR was requested and abstracted following routine abstraction processes. Next, the eICR html file was abstracted. The number, range, and mean of coded birth defects, as well as pre- and postnatal procedures were calculated for both data sources. Concordance between abstracted variables from the EHR and the eICR was evaluated for non-missing data using weighted kappa agreement statistics in SAS.
Results: There were many missing data from the eICR. Fewer birth defects and pre- and postnatal procedures were reported in the eICR compared to the EHR. Most variables had low concordance, while a few variables had high concordance (e.g., infant sex [kappa = 0.95], infant birthdate [kappa = 0.99], primary defect code/diagnosis [kappa = 0.83 using 6-digit British Pediatric Association [BPA] codes; kappa = 0.92, 4-digit BPA codes]).
Conclusions: eCR may be a viable source for timely potential case identification and may also facilitate timelier referral to social services among eligible cases. eCR data files are not standardized across facilities, lack critical variables permitting examination of birth defect risk factors, and are generally not a comprehensive resource for all pertinent data related to a birth defect case.
Betancourt D, et al. Nicotine consumption and folate insufficiency in pregnancy: a population-based cross-sectional study. J Matern Fetal Neonatal Med. 2025 Dec;38(1):2577231. doi:10.1080/14767058.2025.2577231
Abstract
Objective: Tobacco smoking and folate insufficiency are both risk factors associated with adverse pregnancy outcomes, but their association in pregnancy remains unclear. This study investigated the association between tobacco smoking and folate insufficiency in pregnant women in the U.S.
Methods: Data from nine consecutive cycles of the National Health and Nutrition Examination Survey (2003-2020) were analyzed. Smoking status was derived from serum cotinine levels, and folate insufficiency was determined based on World Health Organization guidelines. The Rao-Scott test of independence was used to assess the prevalence of smoking and folate insufficiency across sociodemographic subgroups, and survey-weighted logistic regression models were used to evaluate the association between smoking and folate insufficiency.
Results: Both smoking and red blood cell (RBC) folate insufficiency showed high prevalence among non-Hispanic Black subgroups with an education level of high school or less. Compared to pregnant nonsmokers, pregnant smokers faced increased odds of RBC folate insufficiency (OR: 1.87; 95% CI: 1.10, 3.19). Approximately 3.6% (95% CI: 1.4, 6.4%) of cases of RBC folate insufficiency among pregnant women in the U.S. were associated with active smoking.
Conclusions: Tobacco smoking increases the risk of insufficient folate stores among pregnant women. However, healthcare providers should assess the folate status of all pregnant women and consider proactive screening, such as RBC folate testing, complemented by integrated strategies addressing tobacco use and nutritional risk. Proactive screening for smokers should be revisited once the prevalence of insufficient folate stores has been reduced at the population level.
Shumate C, et al. Structural birth defects and leukemia risk in children with Down syndrome. Sci Rep. Published online December 11, 2025. doi:10.1038/s41598-025-31340-3
Abstract
Birth defects are associated with increased cancer risk in the general pediatric population, yet their impact on leukemia risk in children with Down syndrome (DS) remains uncertain. We assessed this using data from 26,660 children with DS in the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study. Among them, 71.9% had at least one major birth defect, predominantly involving the cardiac (64.2%), musculoskeletal (21%), and gastrointestinal systems (6.8%). The cumulative incidence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) was comparable in children with and without co-occurring defects. Adjusted hazard ratios (aHR) for ALL and AML in children with versus without co-occurring major birth defects were 1.12 (95% confidence interval [CI]: 0.80-1.56) and 1.09 (95% CI: 0.76-1.58), respectively. Overall, no consistent patterns were seen between organ system-level defects and ALL. However, in terms of specific defects, we identified that anophthalmia/microphthalmia (aHR: 2.83, 95% CI: 1.16-6.92) was associated with ALL and tetralogy of Fallot (aHR: 2.40, 95% CI: 1.27-4.55) was associated with AML. While children with DS experience a higher prevalence of birth defects, these defects do not appear to strongly influence leukemia risk, unlike the elevated risk observed in the general pediatric population (< 18 years).
LaPoint H, Cao L, Baldwin T, Gainey Y, et al. A novel commensal Neisseria species harboring the gonococcal diagnostic marker DR-9 causes false-positive Roche cobas NAAT results. J Clin Microbiol. 2025 Dec 17;63(12):e0102225. doi:10.1128/jcm.01022-25
Abstract
Neisseria gonorrhoeae (Ng), the etiologic agent of gonorrhea, is the second most reported bacterial sexually transmitted infection globally. In the USA, nucleic acid amplification tests (NAATs) are considered the gold standard for diagnosis. Although NAATs are sensitive and offer high throughput, cross-reactivity with commensal Neisseria can compromise specificity. Here, we report the isolation and characterization of a novel commensal Neisseria sp. from the oropharynx of a patient with suspected gonococcal treatment failure. An initial diagnosis was made using the Roche cobas CT/NG test on the cobas 8800 system, which repeatedly yielded positive results post-treatment. A confirmatory Aptima Combo 2 (AC2, Hologic) test was negative, and multiple culture attempts failed to isolate Ng. Instead, a commensal Neisseria strain was recovered. Whole-genome sequencing revealed this isolate shared partial genomic identity with several Neisseria spp., including Ng, and carried a distinct region encoding the gonococcal diagnostic marker DR-9, the target of cobas assays. Cross-reactivity was confirmed with the cobas 4800 and 6800 platforms, but not with the AC2 assay targeting 16S rRNA. We discuss the possible origins of the DR-9 marker on this strain as well as examine its antimicrobial susceptibility profile and genomic resistance markers. These findings highlight the potential for misdiagnosis and unnecessary treatment when commensal Neisseria species harbor Ng diagnostic targets. Our study underscores the need for genomic surveillance of Ng and commensal Neisseria, not only to monitor diagnostic performance but also to track commensals that may serve as reservoirs of antimicrobial resistance determinants and contribute to the spread of resistance.
IMPORTANCE
Accurate diagnosis of gonorrhea is critical for effective treatment and antimicrobial stewardship. Nucleic acid amplification tests, the mainstay of gonococcal diagnostic testing, can yield false-positive results due to genetic overlap between Neisseria gonorrhoeae and commensal Neisseria species, especially from extragenital sites like the oropharynx. Prior studies, such as Hopkins et al. (2023), have recognized this limitation and proposed supplemental tests to improve specificity for oropharyngeal specimens. Here, we describe a novel commensal Neisseria strain isolated from a patient with suspected treatment failure that harbors the gonococcal diagnostic marker DR-9. This case highlights the need for confirmatory testing using an alternate gene target in cases where repeated positive tests are obtained with extragenital specimens and demonstrates the need for improved test specificity, particularly for anatomical sites such as the pharynx, which has high commensal diversity. Enhanced molecular surveillance of commensal Neisseria populations will be vital for understanding and minimizing diagnostic cross-reactivity.
Koops A, Howell R, Allred RP, Jeon HN, Shumate C. Staff experiences with electronic initial case reports for birth defects surveillance in Texas. Birth Defects Res. 2025 Dec;117(12):e70002. doi:10.1002/bdr2.70002
Abstract
Background: Electronic case reporting (eCR) is increasingly used by public health agencies to support disease surveillance. Its utility for birth defects surveillance remains unexplored. This project aimed to evaluate birth defects surveillance staff experiences and perceptions of eCR data to identify its challenges, benefits, and opportunities for improvement in birth defects surveillance.
Methods: Two virtual, 1-h focus groups were conducted with 15 staff from the Texas Birth Defects Registry (TBDR) who had participated in a pilot evaluation of electronic initial case reports (eICRs). The focus groups explored staff experiences with identifying and abstracting cases from eICRs and how these experiences compared to abstraction from electronic health records (EHRs). Discussions followed a structured interview guide with six broad question categories. Detailed notes were taken during the sessions and analyzed using thematic analysis to identify common themes and patterns.
Results: Thematic analysis identified six key themes related to the eICR: Structure; Quality and Completeness; Comparison with EHRs; Technical and Workflow Challenges; Usefulness and Potential Applications; and Recommendations to Strengthen its Utility for Birth Defect Surveillance.
Conclusions: Staff reported that while eCR offers potential advantages, such as serving as a data source for case-finding, significant challenges remain. These include issues with eICR structure, data completeness, and integration into existing workflows. Recommended improvements include better organization of eICR data, inclusion of additional clinical details, and development of standardized abstraction protocols. These findings can inform strategies to optimize eCR for birth defects surveillance and point to the need for national guidelines.
Benjamin RH, Ludorf KL, Allred RP, et al. Maternal folic acid supplement use, folate intake, and preterm birth among infants with spina bifida. Birth Defects Res. 2025 Dec;117(12):e70008. doi:10.1002/bdr2.70008
Abstract
Background: We sought to assess the extent to which folic acid supplementation and dietary folate intake are associated with preterm delivery among infants with spina bifida.
Methods: We conducted a retrospective population-based study using the National Birth Defects Prevention Study (NBDPS; 1999-2011) and the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 2014-2019). We utilized robust Poisson regression to calculate the risk ratio (RR) and 95% confidence interval (CI) for the associations between preterm birth (< 37 weeks) and maternal use of folic acid-containing supplements, dietary folate intake quartile, and a combined variable accounting for supplementation and dietary folate status.
Results: Among 1199 infants with spina bifida (1011 in NBDPS, 188 in BD-STEPS), 217 (18.1%) were born preterm. There were no statistically significant associations between preterm birth and lack of supplementation (RR 1.24, 95% CI: 0.92-1.69) or maternal dietary folate intake quartile (RRs 1.12-1.39). The combination of lack of supplementation and low dietary folate intake had the strongest association with preterm birth (RR 1.73, 95% CI: 1.01-2.96), compared to women who took supplements and had higher dietary folate intake.
Conclusions: Our findings suggest a modestly elevated risk of preterm birth among infants with spina bifida born to women with the combination of no supplementation and low dietary folate intake. Future work confirming these findings and further investigating the timing of supplementation could help elucidate whether low folate intake is a risk factor for preterm birth in spina bifida-affected pregnancies.
Stuteville H, et al. Clinical outcomes of pediatric metformin exposures reported to the National Poison Data System®. Clin Toxicol (Phila). Published online 2025 Nov 26. doi:10.1080/15563650.2025.2587773
Abstract
Introduction: Prior studies suggest metformin exposures in young pediatric patients are low risk, and a triage threshold of 85 mg/kg can be used to reduce unnecessary evaluations. Our objective was to analyze single-substance metformin exposures using the National Poison Data System® to describe the clinical course, outcome, and mg/kg dose of metformin exposures in children under six years old. The secondary objective was to describe outcomes in patients divided into safe (≤85 mg/kg reported dose) and caution (>85 mg/kg reported dose) categories.
Methods: Using the National Poison Data System®, we analyzed single-substance metformin exposures from 2011-2021 in patients under six years old. We defined two categories of metformin overdose patients: safe (≤85 mg/kg reported dose), who could be managed at home, and caution (>85 mg/kg reported dose), who should be sent to a healthcare facility. Data were summarized with medians with interquartile ranges for continuous variables and percentages for categorical variables.
Results: There were 8,762 single-substance metformin exposures reported from 2011-2021. Most patients (6,493, 74.1%) were managed in a non-healthcare setting. Critical care admissions accounted for 73 (3.4%) exposures. For the 1,270 (14.5%) patients who had mg/kg data available, 1,081 (85.1%) were in the safe category with ingestions ≤85 mg/kg, while 189 (14.9%) were in the caution category with ingestions >85 mg/kg.
Discussion: Data were limited due to 59.4% of cases missing follow-up information. However, in patients with follow-up information available, most cases were managed on site (74.1%) and only 2.5% of cases required hospitalization. Caution range patients had ten times more admissions (6%) than safe range patients (0.6%).
Conclusion: Most exploratory pediatric single-agent metformin exposures were safe and could be managed at home. The ≤85 mg/kg threshold identifies exposures with expected good outcome requiring little to no medical management.
Broussard K, et al. Public health response to the first locally acquired malaria outbreaks in the US in 20 years. JAMA Netw Open. 2025;8(10):e2535719. Published online 2025 Oct 1. doi:10.1001/jamanetworkopen.2025.35719
Abstract
Importance: In 2023, the US reported 10 locally acquired mosquito-transmitted malaria cases of 4 genetic lineages in 4 states, the first such outbreaks detected in 20 years and the largest in 35 years.
Objective: To present the investigations, interventions, and challenges in the public health response to the malaria outbreaks and provide recommendations for future outbreaks.
Design, setting, and participants: This qualitative study was an interdisciplinary public health response to the locally acquired malaria outbreaks in May to December 2023 and included case investigations, enhanced case finding, polymerase chain reaction analysis of captured Anopheles spp mosquitoes for Plasmodium spp parasites, and novel targeted amplicon sequencing of Plasmodium spp in patient blood samples. Public health interventions included incident command activation, clinician outreach, community awareness, and vector control. Patient data were acquired through public health surveillance as part of National Notifiable Disease Surveillance.
Exposure: Plasmodium vivax-infected and Plasmodium falciparum-infected Anopheles spp mosquitoes.
Main outcomes and measures: Confirmed malaria infection via blood film microscopy and polymerase chain reaction, presence of Plasmodium spp in Anopheles spp mosquitoes, and genetic markers associated with an endemic region of origin and parasite strain relatedness via targeted amplicon sequencing.
Results: The study included 10 patients (mean [SD] age of 39.5 [15.0] years; 7 male [70%]) from Florida, Texas, Maryland, and Arkansas with locally acquired mosquito-transmitted malaria and 783 Anopheles spp mosquitoes across 4 states. No patient had a recent history of international travel or blood-borne exposures. Outbreak cases had epidemiologic links within but not across state lines. P vivax was detected in 3 Anopheles crucians in Florida. Sequencing data showed that all Florida P vivax cases shared the same Plasmodium strain. The Texas and Arkansas P vivax cases were genetically distinct from each other and from Florida's cases. All 9 P vivax strains had genetic signatures that were consistent with Central and South American origin. Maryland's P falciparum parasites were consistent with African origin. The outbreaks were contained.
Conclusions and relevance: In this qualitative study of locally transmitted malaria, outbreaks remained contained to individual counties, with Florida's P vivax cases linked to a single strain distinct from those in other states. Sustained Plasmodium spp transmission is unlikely in the US, though increases in global travel and migration, population, temperatures, and persistence of Anopheles spp vectors may increase risk for locally acquired malaria. Clinicians should prescribe chemoprophylaxis for patients traveling to endemic regions, ensure timely diagnosis and treatment, and facilitate public health reporting. Researching US Anopheles spp ecology and control methods while accelerating efforts to reduce malaria globally could mitigate future risk.
Robertson A, Lustri L, Salinas V, Bojes HK, et al. Spatially informed wastewater differentiation among locations during an ongoing measles outbreak in Texas, USA. ACS Environ Au. 2025;5(6):543-549. Published online 2025 Sep 16. doi:10.1021/acsenvironau.5c00122
Abstract
Though reverse transcription-quantitative polymerase chain reaction (RT-qPCR), RT digital PCR (RT-dPCR), and RT digital droplet PCR (RT-ddPCR) are commonly used for wastewater-based epidemiology and surveillance (WBE/WBS), differences among the platforms exist. While RT-ddPCR has been suggested as an ideal approach to use globally for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monitoring, access to RT-qPCR instrumentation is more widely available in many regions, and it is more economical. Subsequently, a larger number of studies have used RT-qPCR for SARS-CoV-2 wastewater monitoring, along with additional pathogens that can be detected with WBS. In this study, we employed RT-qPCR and RT-dPCR platforms for the comparative detection of vaccine (A genotype Edmonston) and wild-type (D8 genotype) measles RNA from wastewater in nearby cities separated by <50 km during an ongoing measles outbreak in Texas, USA, in addition to several other locations up to 30-1400 km from the outbreak location. The limit of detection (LOD) for each methodology was evaluated using a synthetic gBlock DNA gene fragment of known concentrations, with comparable LODs identified for both the RT-dPCR (∼0.5 gc/μL) and RT-qPCR (∼0.4 gc/μL) platforms. Using composite supernatant-solid wastewater samples, RNA aliquots were analyzed on each platform in parallel. The RT-qPCR platform demonstrated a higher detection rate than RT-dPCR for the vaccine strain quantified in wastewater samples, with equivalent detections for the wild-type strain in both platforms, and notable differences in the gene copies quantified in wastewater based on the platform. Our study identifies that regardless of PCR methodology employed, WBS is a particularly valuable approach for the spatially informed differentiation of measles during rapid response to an active outbreak.
Shuford J, Shetty V, Bridendolph A, Plantenga M, Hans E, Tillman W, et al. Pediatric influenza-associated encephalopathy and acute necrotizing encephalopathy - United States, 2024-25 influenza season. MMWR Morb Mortal Wkly Rep. 2025;74(36):556-564. Published online 2025 Sep 25. doi:10.15585/mmwr.mm7436a1
Abstract
In January 2025, CDC received several reports of deaths among children aged <18 years with a severe form of influenza-associated encephalopathy (IAE) termed acute necrotizing encephalopathy (ANE). Because no national surveillance for IAE currently exists, CDC requested notification of U.S. pediatric IAE cases from clinicians and health departments during the 2024-25 influenza season, a high-severity season with a record number of pediatric influenza-associated deaths. Among 192 reports of suspected IAE submitted to CDC, 109 (57%) were categorized as IAE, 37 (34%) of which were subcategorized as ANE, and 72 (66%) as other IAE; 82 reports did not meet IAE criteria and were categorized as other influenza-associated neurologic disease. The median age of children with IAE was 5 years and 55% were previously healthy, 74% were admitted to an intensive care unit, and 19% died; 41% of children with ANE died. Only 16% of children with IAE who were vaccination-eligible had received the 2024-25 influenza vaccine. Health care providers should consider IAE in children with encephalopathy or altered level of consciousness and a recent or current febrile illness when influenza viruses are circulating. Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including severe neurologic disease such as IAE and ANE.
Ward KC, et al. Sensitivity of cancer registry linkage with missing or incomplete social security number and implications for cancer cohorts. Epidemiology. Published online 2025 Sept 9. doi:10.1097/EDE.0000000000001913
Abstract
Background: Linking cancer cohort participants to state cancer registries typically relies on personally identifiable information, including Social Security Numbers (SSN), which uniquely identify individuals. However, complete SSN collection can be limited due to privacy concerns. This study evaluates the sensitivity of cancer registry linkage using partial or missing SSN and examines differences by demographic characteristics.
Methods: Using data from 284,361 participants in the Cancer Prevention Study-3 (CPS-3), we conducted probabilistic linkages with cancer registries in Georgia, Ohio, and Texas using Match*Pro software. Participants were linked using combinations of personally identifiable information: complete SSN, partial SSN (last four digits), and missing SSN. We compared the sensitivity of linkages before and after manual review and stratified by sex, age, and race-ethnicity.
Results: Before manual review, sensitivity for missing and partial SSN was 92.5%. Sensitivity improved to 98.6% for missing SSN and 98.8% for partial SSN after manual review. We observed no notable heterogeneity by sex, age, or race-ethnicity, with sensitivity exceeding 87% across all subgroups. Manual review substantially reduced uncertain matches, contributing to high linkage accuracy.
Shumate C, et al. Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births. Neuro Oncol. 2025 Sep 8;27(7):1910-1922. doi:10.1093/neuonc/noaf087
Abstract
Background: Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs.
Methods: We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from 9 states (n = 22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed < 20 years. Cox regression analyses were conducted separately by congenital anomaly for anomaly-CBT combinations with at least 5 co-occurring cases. We conducted analyses for any CBT and separately for astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, medulloblastoma, mixed and unspecified gliomas, and primitive neuroectodermal tumors.
Results: There were 6,247 children diagnosed with a CBT. Having any major structural anomaly was associated with risk of any CBT and across all subgroups (aHR range: 1.48-3.69) except ependymoma, particularly among children diagnosed with a tumor by 1 year of age. Of the 66 anomaly-CBT combinations analyzed, 42 were significant (P < .05), including 25 in an earlier version of this study and 16 novel associations (aHR range: 1.46-525). Anomaly-CBT associations also differed by astrocytoma histology.
Conclusions: We observed consistent evidence that having a structural congenital anomaly increases risk of developing a CBT, particularly in infancy, which may provide insights into etiology.
Waldrup KA, Suarez V, et al. Survey of fleas and ticks for Rickettsia rickettsii and Rickettsia typhi in the El Paso community and other areas in Texas, New Mexico, and Ciudad Juarez, Mexico. Am J Trop Med Hyg. 2025 Sep 3;113(3):659-665.. doi: 10.4269/ajtmh.24-0709. Published online June 17, 2025.
Abstract
This survey was conducted with the aim of determining the public health risk of Rocky Mountain spotted fever and murine typhus in the urban and peri-urban areas of El Paso, as well as other areas in Texas, southern New Mexico, and Ciudad Juarez, Mexico. The approach was to assess the diversity of tick and flea species, determine if the ticks and fleas were infected with Rickettsia rickettsii and Rickettsia typhi (R. typhi), respectively, and assess previous human infection with Rickettsia species. Ticks and fleas were collected from domestic and wild animals and tested using a nested polymerase chain reaction assay. Human plasma samples were also tested for antibodies using an indirect fluorescence assay. Among 203 fleas, including Pulex irritans, Echidnophaga gallinacea, and Ctenocephalides felis (C. felis), collected from wild and domestic small mammals, only one pool of four C. felis collected from a dog in the El Paso community was positive for Rickettsia felis. All 194 Rhipicephalus sanguineus ticks collected from stray and domestic dogs in the El Paso community, southern Doña Ana County, and Ciudad Juarez were negative for Rickettsia spp. In Travis County, Texas, a total of 207 ticks collected from white-tailed deer, including 196 Ixodes scapularis and 11 Dermacentor albipictus, were negative for Rickettsia spp. pathogens. Among 375 archived human plasma samples collected in the El Paso community, only two were positive for R. typhi antibodies. These preliminary findings suggested that tick- and flea-borne diseases were not a major health risk in the El Paso community or the other areas included in this survey.
Shumate CJ, Nguyen J, et al. Long-term survival among children with trisomy 13 and trisomy 18 by cytogenetic status. JAMA Netw Open. 2025;8(9):e2529885. Published online 2025 Sep 2. doi:10.1001/jamanetworkopen.2025.29885
Abstract
Importance: Trisomy 13 (T13) and trisomy 18 (T18) are chromosomal abnormalities with high mortality rates in the first year of life. Understanding differences in long-term survival between children with full vs mosaic or partial trisomy is crucial for prognosis and health care planning.
Objective: To examine the differences in 10-year survival between children with full T13 and T18 vs those with mosaic or partial trisomy.
Design, setting, and participants: This retrospective, population-based cohort study assessed liveborn infants with T13 and T18 in the Texas Birth Defects Registry (deliveries from January 1, 1999, to December 31, 2008). Follow-up was through December 31, 2018 (the last date available at the time of analyses) to allow for 10 years of follow-up for all infants. All analyses were conducted from January 1, 2022, to December 31, 2024.
Exposures: Cytogenetic status (full trisomy vs mosaic or partial trisomy).
Main outcomes and measures: The primary outcome was survival to 10 years of age, assessed using Kaplan-Meier survival estimates. The association between cytogenetic status and mortality by 10 years of age was assessed using Cox proportional hazards regression to generate hazard ratios (HRs). Population attributable fraction was calculated to determine the percentage of survival attributable to mosaic or partial trisomy status.
Results: The study cohort included 798 infants (463 female infants [58.0%]; mean [SD] maternal age, 30.9 [8.0] years) with T13 (n = 295) or T18 (n = 503). Among all cases with T13, 25 infants (8.5%; 95% CI, 5.5%-12.3%) survived to 10 years of age. Similarly, among all infants with T18, 43 (8.6%; 95% CI, 6.3%-11.3%) survived to 10 years of age. Kaplan-Meier survival estimates to 10 years of age were statistically significantly higher among children with mosaic or partial trisomy (13 [25.0%] and 14 [43.8%], respectively) compared with full trisomy (12 [4.9%] and 29 [6.6%], respectively) (both P < .001). Infants with full trisomy had statistically significantly increased 10-year mortality hazards compared with those with mosaic or partial trisomy for both T13 (HR, 2.00; 95% CI, 1.42-2.82) and T18 (HR, 3.34; 95% CI, 2.08-5.38). The results of the calculated proportion of 10-year survival due to the presence of nonfull trisomy status (population attributable fraction) was 41.7% for children with T13 and 27.9% for children with T18.
Conclusions and relevance: The findings of this cohort study of infants with T13 and T18 support differences in long-term survival based on cytogenetic status and emphasize the need to potentially reassess the context of these conditions generally being considered incompatible with life, particularly for those with mosaic trisomies. These findings offer context surrounding treatment decisions, such as withholding interventions, for affected infants in the future.
Shumate C, Allred R, Dixon A, Betancourt D, Yantz C, Howell R, Gandhi H, Kilburn M, et al. Trends in the prevalence of Down syndrome (Trisomy 21) in Texas by maternal race/ethnicity and maternal age groups, 1999-2020. Am J Med Genet A. 2025 Sep;197(9):e64109. doi: 10.1002/ajmg.a.64109 Published online 2025 May 4.
Down syndrome (DS) is a common chromosomal aneuploidy characterized by intellectual disability. Older maternal age is the strongest known risk factor for DS. The purpose of this study was to describe DS prevalence among major racial/ethnic groups stratified by maternal age, and to assess trends in prevalence over time in Texas. Cases with DS diagnoses delivered between 1999 and 2020 were identified from the Texas Birth Defects Registry (TBDR). Birth prevalence and crude prevalence ratios (PRs) by maternal race/ethnicity, maternal education, residence along the Texas-Mexico border, and Texas public health region (PHR) were calculated. Trends over time were assessed using Joinpoint. DS prevalence was significantly lower among mothers < 35 years compared to those 35+ years. Hispanic mothers, mothers with less than high school education, and mothers residing along the Texas-Mexico border had consistently higher PRs. Joinpoint analyses revealed significant increases in DS prevalence over time among non-Hispanic Black and Hispanic mothers. These findings identified significant increases in DS prevalence among non-Hispanic Black and Hispanic mothers compared to non-Hispanic White mothers, suggesting a potential widening of racial/ethnic differences in DS occurrence. Further research is needed to explore underlying drivers of these trends and to address differences in DS prevalence.
Miller P, et al. Circulating T-cell receptor excision circles at birth and risk of childhood cancers. Cancers (Basel). 2025;17(17):2903. Published online 2025 Sep 4. doi:10.3390/cancers17172903
Abstract
Background: T-cell receptor excision circles (TRECs) are measured in newborn screening programs in the United States to identify severe combined immunodeficiency (SCID). We hypothesized that relatively low TREC levels at birth, even within the normal range, could indicate compromised immunity and higher susceptibility to childhood cancers.
Methods: We conducted a case-control study using linked data from the newborn screening programs and cancer registries in California and Texas to examine the association between TREC levels and risk of childhood cancer. The study included 2196 cancer cases and 10,980 controls from California and 1186 cancer cases and 5890 controls from Texas.
Results: In California, acute myeloid leukemia cases had significantly lower TREC levels compared with their matched controls (p = 0.0051), while in Texas, acute lymphocytic leukemia cases had significantly higher TREC levels compared with their matched controls (p = 0.0034). However, each association was not replicated in the other state, and other cancer types did not show significant differences in TREC levels between cases and controls.
Conclusions: We did not observe consistent associations between TREC levels at birth and childhood cancer risk. A possible explanation for the lack of more clear-cut differences in TREC levels between cases and matched controls might be the complex etiology of childhood cancers. The results underscore the need for longitudinal studies that incorporate additional immune biomarkers to understand the immunologic basis of childhood cancer development.
Betancourt D, Shumate C, et al. Assessing the impact of social factors on survival among infants born with transposition of the great arteries, tetralogy of Fallot, and diaphragmatic hernia in Texas, 2011-2019. Matern Child Health J. 2025 Sep;29(9):1293-1306. doi:10.1007/s10995-025-04126-2 Published online 2025 Jul 9.
Abstract
Introduction: Social factors impact survival for infants with birth defects. This analysis describes the impact of social factors on one-year survival for infants with congenital diaphragmatic hernia (CDH), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF).
Methods: Survival estimates were generated using the Kaplan-Meier method and the log-rank test with 0.05 significance stratified by social factors for infants born 2011-2019 with CDH (N = 942), TGA (N = 1,102), or TOF (N = 1,545). Crude hazard ratios (HR) and adjusted hazard ratios (AHR) with 95% confidence intervals (CI) were calculated for infant death using the Cox proportional hazards models.
Results: One-year survival was 88.7% for TOF, 88.0% for TGA, and 72.7% for CDH. Infants with CDH whose mother resided along the Texas-Mexico border had an increased risk of death compared to non-border residents (HR = 1.68, p =.003). Lower maternal education attainment was associated with increased risk of death for infants with TGA (HR = 1.75, p =.002) or TOF (HR = 1.54, p =.005) compared to infants whose mother had more than a high school education. Maternal Hispanic ethnicity increased the risk of death for infants with TGA (HR = 1.75, p =.005) or TOF (HR = 1.74, p =.002) compared to NH White infants.
Shumate C, et al. Epidemiologic features of preterm birth among infants with trisomy 21 in Texas, 1999-2018. Am J Med Genet A. 2025 Aug 21:e64229. doi: 10.1002/ajmg.a.64229. Published online 2025 Aug 21.
The rate of preterm birth among infants with trisomy 21 (22%) is around twice that among the general population (10%). We conducted a descriptive epidemiologic study to address the gap in knowledge on what maternal and infant factors are associated with preterm birth among infants with trisomy 21. Singleton infants with trisomy 21 born between 1999 and 2018 were identified from the Texas Birth Defects Registry. We used multivariable logistic regression to assess associations between preterm birth and 14 maternal and infant characteristics. Statistically significant associations were observed between preterm birth and maternal race/ethnicity, maternal age, maternal birthplace, prenatal care, smoking, infant sex, and infant delivery year. For instance, preterm birth was associated with maternal age (adjusted odds ratio [aOR] 1.44, 95% CI: 1.23-1.70 for ≥ 40 vs. 25-29 years) and prenatal care (aOR 1.59, 95% CI: 1.25-2.03 for no care versus any care). Our findings contribute toward a better understanding of the risk profile of preterm birth among infants with trisomy 21 and can guide further research on risk factors and potential interventions for reducing preterm birth rates in this population.
Tanksley S, et al. Evidence regarding metachromatic leukodystrophy newborn screening. Pediatrics. doi: 10.1542/peds.2025-073188. Published online 2025 Aug 12.
Abstract
Metachromatic leukodystrophy (MLD) is a lysosomal disorder affecting about 1 per 100,000 newborns. It is caused by biallelic variations in the arylsulfatase A (ARSA) gene, leading to deficiency of ARSA enzyme activity leading to elevation of sulfatides. Most affected individuals have the late-infantile or early-juvenile phenotype, associated with significant and progressive neurologic degeneration and death. For these phenotypes, treatment with a lentiviral gene therapy in infancy can improve survival and motor function. However, in the absence of screening or an affected older sibling, most cases are diagnosed much later. A two-tiered newborn screen, based on the presence of elevated sulfatides in dried-blood spots followed by finding low ARSA enzyme activity, can accurately identify newborns with the early-onset phenotypes of MLD for timely gene therapy. An MLD screening study with consent is ongoing in 8 hospitals in New York City and population-based newborn screening has been implemented in several regions in Europe. Although the false-positive rate is low, only one of these MLD newborn screening activities, in Hannover, Germany, has reported identifying cases. At least four newborn screening programs in the United States are in the process of implementing MLD screening.
Tanksley S, et al. Evidence regarding Duchenne muscular dystrophy newborn screening. Pediatrics. doi: 10.1542/peds.2025-073192. Published online 2025 Aug 12.
Abstract
Variants in the DMD gene, located on the X chromosome, cause Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD reportedly affects about 2 per 10,000 newborn males, leading to progressive weakness and premature death, typically from respiratory or cardiac complications. The average age of diagnosis in the United States (US) over the past four decades has been 4.5 to 5 years. The availability of targeted therapies and the long diagnostic odyssey have led to advocacy for newborn screening (NBS). Studies of caregivers of children with DMD describe support for NBS. Meeting abstracts, which may have bias, suggest earlier identification in a child following DMD diagnosis in an older brother improves outcomes. Ohio and Minnesota include DMD NBS, and other states are planning implementation. DMD NBS is based on measuring the muscle isoform of creatine kinase (CK-MM), which is elevated due to muscle damage. Infants with borderline CK-MM levels can be retested after at least one week to determine if elevations are birth related. Molecular analysis in infants with significantly elevated CK-MM can identify DMD variants associated with DMD or BMD. Screening accuracy depends on the testing algorithm. Although treatment with glucocorticoids or related medications can improve outcomes for DMD despite side effects, the optimal age of initiation is unclear. Efficacy of the Food and Drug Administration-approved gene therapy has not been established, and it has a rare risk of hepatotoxicity. Genotype-specific exon-skipping medications, indicated for 27% of cases, may improve outcomes, but clinical benefit is not definitively established.
Monterosso A, Archer N, et al. Cancer incidence and trends in US adults with HIV. JAMA Oncol. 2025 Aug 1;11(8):855-863. doi: 10.1001/jamaoncol.2025.1589.
Abstract
Importance: People with HIV are living longer due to improvements in antiretroviral therapy over the last 2 decades. Current age-specific estimates of cancer risk among people with HIV may inform cancer prevention and clinical guidelines for this population.
Objective: To estimate cancer incidence rates (IRs) using a population-based linkage of HIV and cancer registries.
Design, setting, and participants: This population-based cohort study used data from 12 US states, Washington, DC, and Puerto Rico from 2001 to 2019. People with HIV and the general population in the HIV/AIDS Cancer Match Study were included in the analysis, which occurred between October 2023 and December 2024.
Main outcomes and measures: Age-standardized IRs (per 100 000 person-years) were calculated across calendar periods (2001 to 2004, 2005 to 2009, 2010 to 2014, and 2015 to 2019) and incidence rate ratios (IRRs) across calendar periods using adjusted Poisson regression. Standardized incidence ratios (SIRs) were estimated for 2010 to 2014 and 2015 to 2019, and age group-specific cancer incidence and SIRs were estimated for 2010 to 2019.
Results: The analysis included 7.2 million person-years among 847 107 people with HIV (5.3 million person-years among males [73%]). Comparing years 2015 to 2019 to years 2010 to 2014, incidence of diffuse large B-cell lymphoma (DLBCL) decreased 23% (IRR, 0.77; 95% CI, 0.70-0.84), Kaposi sarcoma (KS) decreased 24% (IRR, 0.76; 95% CI, 0.69-0.84), Hodgkin lymphoma decreased 25% (IRR, 0.75; 95% CI, 0.65-0.86), and cancers of the lung decreased 17% (IRR, 0.83; 95% CI, 0.77-0.90) and liver decreased 25% (IRR, 0.75; 95% CI, 0.67-0.84). Among people with HIV aged 70 to 84 years, IRs were highest for cancers of the prostate (448.01; 95% CI, 404.26-495.20), lung (269.79; 95% CI, 240.86-301.24), female breast (202.29; 95% CI, 155.79-258.32), liver (82.82; 95% CI, 67.16-101.03), and colon (107.57; 95% CI, 89.61-128.08), exceeding the IRs for DLBCL (41.83; 95% CI, 30.95-55.31) and KS (15.37; 95% CI, 9.11-24.29). From 2015 to 2019, risk remained significantly elevated in people with HIV for several cancer types, including KS (SIR, 213.87; 95% CI, 198.81-229.73), Hodgkin lymphoma (SIR, 6.29; 95% CI, 5.68-6.94), DLBCL (SIR, 5.25; 95% CI, 5.25-6.01), cancers of the anus (SIR, 17.07; 95% CI, 16.01-18.17), vulva (SIR, 11.40; 95% CI, 9.60-13.44), liver (SIR, 1.89; 95% CI, 1.74-2.05), and lung (SIR, 1.59; 95% CI, 1.51-1.68). For nearly all these cancers, SIRs significantly declined with increasing age.
Conclusions and relevance: In this cohort study, significant declines in the incidence and relative risk for cancers among people with HIV demonstrate continued progress in HIV treatment and cancer prevention. These estimates may provide insight into the priorities for prevention and early detection of cancer as the population of people with HIV enters ages with greater risk for cancer.
Gardner E, et al. Sex differences in cancer mortality among solid organ transplant recipients. Int J Cancer. 2025 Aug 1;157(3):427-435. doi: 10.1002/ijc.35415 Epub 2025 May 9.
Abstract
Males have increased mortality after a cancer diagnosis than females, possibly due to poorer immunosurveillance. We tested whether the female survival advantage is lost with immunosuppression by evaluating 17,048 cancer patients (68% male) with a prior solid organ transplant using data from the US Transplant Cancer Match Study and 1,221,914 cancer patients (58% male) from the general population using data from the Surveillance, Epidemiology, and End Results Program. We evaluated 13 solid cancers that occur in both sexes. We compared mortality due to cancer in males and females using a male:female hazard ratio (M:F HR) derived from Cox proportional hazards models adjusted for age, race/ethnicity, diagnosis year, stage, and cancer treatment. Among cancer patients in the general population, males had higher cancer-specific mortality than females for cancers of the lip, stomach, colorectum, anus, liver, lung, skin, brain, and thyroid, with M:F HRs ranging from 1.06 to 1.59. Only colorectal cancer showed an attenuation in the female mortality advantage in transplant recipients (M:F HRTransplant: 0.89; 95% CI: 0.77, 1.03; vs. M:F HRGenPop: 1.07; 95% CI: 1.06, 1.08; P-interaction = 0.007). Among kidney cancer patients, the female mortality advantage was stronger in the transplant population (M:F HRTransplant: 1.33; 95% CI: 1.11, 1.60; M:F HRGenPop: 1.02; 95% CI: 0.99, 1.04; P-interaction = 0.003). Overall, we did not find consistent evidence that the female advantage in cancer mortality is weakened among immunosuppressed transplant recipients, suggesting that non-immune factors contribute to the female advantage among cancer patients in the general population.
Evert N, Dang T, Prot E, et al. Fungal meningitis in U.S. patients who received epidural anesthesia in Matamoros, Mexico. Clin Infect Dis. 2025 Jul 22:ciaf399. doi: 10.1093/cid/ciaf399
Abstract
Background: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in U.S. patients who received epidural anesthesia in Matamoros, Mexico.
Methods: Early epidemiological information suggested U.S. patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in two Matamoros clinics. U.S. patients known to have received surgery at these clinics during January 1-May 13, 2023, (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, including use of the experimental antifungal fosmanogepix. Whole genome sequencing was conducted on outbreak isolates.
Results: U.S. public health officials attempted to contact 233 potentially exposed U.S. residents who underwent surgeries, mostly cosmetic, in Mexico, reaching 170 (73%). Of those, 104 (61%) reported receiving epidural anesthesia and were therefore considered potentially at risk for fungal meningitis. At least 30/104 (29%) at-risk patients received a diagnostic lumbar puncture; 24 (23 women, 17 Hispanic or Latino) were diagnosed with fungal meningitis, and six were not. Twelve (50%) with fungal meningitis died. All cases involved epidural anesthesia administered by the same anesthesiologist in Mexico. Whole genome sequencing showed that patient isolates of Fusarium from the two implicated clinics in Matamoros, Mexico, were genetically closely related.
Conclusions: Clinicians should maintain suspicion for fungal meningitis in patients with negative bacterial culture, viral culture and molecular testing with a history of epidural anesthesia for any reason.
Monterosso A, et al. Differences in trends in cancer incidence rates among people with HIV during 2001-2019 by race and ethnicity and by risk group in the United States. Clin Infect Dis. 2025 Jul 18;80(6):1355-1364. doi: 10.1093/cid/ciae555
Abstract
Background: It is unclear whether cancer risk among people with human immunodeficiency virus (HIV, PWH) has declined equally across all racial/ethnic and transmission risk groups.
Methods: We used data on PWH aged ≥20 years from the HIV/AIDS Cancer Match Study during 2001-2019. We used Poisson regression to assess time trends in incidence rates for each cancer site by racial/ethnicity and risk groups, adjusting for age, registry, and sex. We also estimated adjusted rate ratios across racial and ethnic and risk groups in 2001-2004 and 2015-2019.
Results: Trends in age-standardized rates differed across racial/ethnic groups and across risk groups for some cancers. For example, liver cancer rates declined 23% per 5-year period among White PWH, 11% among Black PWH, and 18% among Hispanic PWH. Anal cancer rates declined among men who have sex with men, were stable among people who inject drugs, and increased among other risk groups. Between 2001-2004 and 2015-2019, the relative difference in cancer incidence rates by race/ethnicity increased for Hodgkin lymphoma (HL) and liver cancer but decreased for non-Hodgkin lymphoma (NHL); by risk group, relative differences increased for NHL and liver cancer and decreased for HL and lung and anal cancers.
Conclusions: Among PWH in the United States during 2001-2019, HL, lung, liver, and cervical cancer rate trends were different across racial/ethnic groups. HL, lung, anal, and liver cancer rate trends were different across risk groups. Future work should examine underlying causes of the differences in trends.
Bolling BG, et al. Identifying environmental drivers of Aedes aegypti and Aedes albopictus abundance in the Dallas-Fort Worth metroplex using Random Forest modeling. J Med Entomol. 2025 Jul 17;62(4):789-799. doi: 10.1093/jme/tjaf036 Published online 2025 Apr 10.
Abstract
Aedes aegypti and Aedes albopictus are 2 medically important vectors that have established populations globally. In the United States, Ae. aegypti populations declined post-Ae. albopictus introduction, though both species now can be readily found throughout the Southern US. Despite overlapping distributions, there are few studies that investigate and compare the drivers of abundance at spatial scales relevant to mosquito control and surveillance districts. To address this limitation, we analyzed longitudinal mosquito surveillance data from the Dallas-Fort Worth metroplex, Texas. Dallas-Fort Worth metroplex is an area of interest due to its rapid population growth, diverse environmental conditions, and prior history with epidemic West Nile virus transmission. We trained a Random Forest model on a subset of Ae. aegypti and Ae. albopictus data and meteorological and sociodemographic variables from Tarrant and Dallas counties to predict the abundance of both species within the Dallas-Fort Worth metroplex. Additionally, we interpolated predictions to map mosquito abundance at unsampled locations. We found that Ae. aegypti abundance was positively correlated with hot and dry conditions within densely populated locations, with mean abundance peaking in the 33rd to the 44th weeks of the year. Ae. albopictus abundance was positively correlated with cooler temperatures in higher socio-economic locations with lower human population density, with mean abundance peaking in the 19th to the 32nd weeks of the year. Our results suggest that the diversity of the Dallas-Fort Worth metroplex's environmental conditions enable Ae. aegypti and Ae. albopictus to exploit differential niche spaces, which has the potential to influence vector control strategies and disease prevention efforts.
Abdul-Hamid C, et al. Invited review: The One Health challenges and opportunities of the H5N1 outbreak in dairy cattle in the United States. J Dairy Sci. 2025 Jul;108(7):6513-6537. doi:10.3168/jds.2024-26222 Published online April 28, 2025.
Abstract
The outbreak of H5N1 in dairy cattle in the United States revealed challenges in identification and management of a novel disease. The virus showed an exceptional ability to spread between farms and among cows within a farm. The impact of the virus on dairy cattle varied from nonclinical to severe clinical signs and death. Many dairy producers did not report clinical signs in their cows or test for the virus. Cats and peridomestic birds on many affected dairies died from viral exposure. Dairy workers showed signs of conjunctivitis, which was confirmed to be due to H5N1. With the disease affecting multiple species and showing efficient cow-to-cow transmission, the situation only worsened. There was a negative impact on the relationships among dairy producers, dairy workers, poultry producers, and veterinarians, in which professional and personal relationships were severed and some experienced loss of employment. The regulatory response varied by geographic location, and in some states, animal health and human health authorities elevated producer fears of consequences of reporting. Authorities did quickly confirm that pasteurization inactivated the virus in dairy products and showed that it was very rarely detected in beef from affected cows. In this review, we will describe the relationships among the dairy industry and animal and human health and why the H5N1 outbreak requires a One Health perspective of all stakeholders in order to address it effectively.
Rollo S, Wang C, Tuladhar R, et al. Genetic characterization of Plasmodium vivax linked to autochthonous malaria transmission in the US (2023) using Illumina AmpliSeq technology: a genetic epidemiology study. Lancet Reg Health Am. 2025 Jun 21;48:101159. doi: 10.1016/j.lana.2025.101159
Abstract
Background: Malaria is a mosquito borne disease caused by parasites of the genus Plasmodium. In 2023, the United States (US) experienced nine cases of autochthonous Plasmodium vivax malaria transmission; seven in Florida, one in Texas, and another in Arkansas. These were the first autochthonous cases since 2003 when a cluster was identified in Florida. The aim of this study was to genetically characterize the implicated P. vivax isolates in order to complement epidemiologic investigations of these cases.
Methods: A custom Illumina AmpliSeq sequencing panel capturing 495 amplicons was designed. This panel was used to ascertain whether these 2023 cases were related, and assess if they were associated with a single or separate introduction events. Sequence data were hierarchically clustered and a Naïve Bayes classification approach was used to assign genotypes to a probable geographic origin based on 113 'geo-informative' SNPs captured by the panel. Genotypes associated with the 2023 Arkansas, Texas, and Florida cases were clustered alongside those sequenced from archived blood samples from the 2003 Florida case-patients, a set of reference strains, and other travel-associated specimens. Microsatellite analysis was performed on a subset of samples from these autochthonous cases to complement the AmpliSeq analysis.
Findings: The 2023 autochthonous Florida cases were genetically linked as were the 2003 Florida cases. The 2023 and 2003 Florida clusters were genetically distinct, and the two Florida clusters were distinct from the 2023 Texas and Arkansas cases, which were also distinct from each other. These genotypes classified to the Central or South American region using the Naïve Bayes classifier, including those from the 2003 cluster.
Interpretation: These data support that at least three distinct P. vivax introduction events in the US in 2023, involving parasites possessing genetic signatures consistent with Central or South America.
Monterosso A, Archer N, et al. Cancer incidence and trends in US adults with HIV. JAMA Oncol. 2025 Jun 12:e251589. doi:10.1001/jamaoncol.2025.1589 Published online June 12, 2025.
Abstract
Importance: People with HIV are living longer due to improvements in antiretroviral therapy over the last 2 decades. Current age-specific estimates of cancer risk among people with HIV may inform cancer prevention and clinical guidelines for this population.
Objective: To estimate cancer incidence rates (IRs) using a population-based linkage of HIV and cancer registries.
Design, setting, and participants: This population-based cohort study used data from 12 US states, Washington, DC, and Puerto Rico from 2001 to 2019. People with HIV and the general population in the HIV/AIDS Cancer Match Study were included in the analysis, which occurred between October 2023 and December 2024.
Main outcomes and measures: Age-standardized IRs (per 100 000 person-years) were calculated across calendar periods (2001 to 2004, 2005 to 2009, 2010 to 2014, and 2015 to 2019) and incidence rate ratios (IRRs) across calendar periods using adjusted Poisson regression. Standardized incidence ratios (SIRs) were estimated for 2010 to 2014 and 2015 to 2019, and age group-specific cancer incidence and SIRs were estimated for 2010 to 2019.
Results: The analysis included 7.2 million person-years among 847 107 people with HIV (5.3 million person-years among males [73%]). Comparing years 2015 to 2019 to years 2010 to 2014, incidence of diffuse large B-cell lymphoma (DLBCL) decreased 23% (IRR, 0.77; 95% CI, 0.70-0.84), Kaposi sarcoma (KS) decreased 24% (IRR, 0.76; 95% CI, 0.69-0.84), Hodgkin lymphoma decreased 25% (IRR, 0.75; 95% CI, 0.65-0.86), and cancers of the lung decreased 17% (IRR, 0.83; 95% CI, 0.77-0.90) and liver decreased 25% (IRR, 0.75; 95% CI, 0.67-0.84). Among people with HIV aged 70 to 84 years, IRs were highest for cancers of the prostate (448.01; 95% CI, 404.26-495.20), lung (269.79; 95% CI, 240.86-301.24), female breast (202.29; 95% CI, 155.79-258.32), liver (82.82; 95% CI, 67.16-101.03), and colon (107.57; 95% CI, 89.61-128.08), exceeding the IRs for DLBCL (41.83; 95% CI, 30.95-55.31) and KS (15.37; 95% CI, 9.11-24.29). From 2015 to 2019, risk remained significantly elevated in people with HIV for several cancer types, including KS (SIR, 213.87; 95% CI, 198.81-229.73), Hodgkin lymphoma (SIR, 6.29; 95% CI, 5.68-6.94), DLBCL (SIR, 5.25; 95% CI, 5.25-6.01), cancers of the anus (SIR, 17.07; 95% CI, 16.01-18.17), vulva (SIR, 11.40; 95% CI, 9.60-13.44), liver (SIR, 1.89; 95% CI, 1.74-2.05), and lung (SIR, 1.59; 95% CI, 1.51-1.68). For nearly all these cancers, SIRs significantly declined with increasing age.
Conclusions and relevance: In this cohort study, significant declines in the incidence and relative risk for cancers among people with HIV demonstrate continued progress in HIV treatment and cancer prevention. These estimates may provide insight into the priorities for prevention and early detection of cancer as the population of people with HIV enters ages with greater risk for cancer.
Shumate CJ, et al. Longitudinal trends in pediatric survival by congenital heart defect in Texas, 1999 to 2017. JACC Adv. 2025;4(6 Pt 1):101812. doi: 10.1016/j.jacadv.2025.101812 Published online May 19, 2025.
Abstract
Background: Despite previously improved survival among children with congenital heart defects (CHDs), U.S. population-level evaluations of survival within recent years are scarce.
Objectives: The purpose of this study was to describe the survival landscape among children with CHDs in a large population-based birth defects registry overall and by CHD lesion.
Methods: This population-based cohort study evaluated 1999 to 2017 live births with ≥1 major CHD in the statewide Texas Birth Defects Registry. Variables included CHD lesion, demographics, gestational age at birth (term/preterm), low birthweight (<2,500 g at birth), among others. Kaplan-Meier analyses were used to describe survival to 7 days, 28 days, 1 year, 5 years, and 10 years of life. Kaplan-Meier survival estimates were generated for 1-year survival for CHDs overall by lesion, using log-rank tests assessing differences by exposure.
Results: Of 61,656 children with CHDs, survival was 98.1% and 90.7% at 7 days and 10 years, respectively, and substantially varied by lesion (range, 50.0% to 97.3% 10-year survival). Survival longitudinally improved for complex lesions including hypoplastic left heart syndrome (48.7% 1-year survival for cases born 1999-2004 vs 64.8% in 2014-2017; P < 0.0001). One-year survival differed by maternal race/ethnicity (eg, 58.3% for cases with complex pulmonary atresia born to non-Hispanic Black mothers vs 80.5% for non-Hispanic White mothers, P = 0.01), sex, gestational age, birthweight, and extracardiac defect status.
Conclusions: One-year survival improved for most CHDs over recent decades, although survival varies widely by CHD and characteristics. Findings have implications for clinical counseling, population-level resource and research planning, and reinforce the need for mitigation of disparities among individuals with CHDs.
Shumate C, et al. All genetic subtypes of B-cell acute lymphoblastic leukemia exhibit increased incidence rates in children with Down syndrome. Leukemia. 2025 Jun;39(6):1516-1519. doi:10.1038/s41375-025-02602-w Published online April 11, 2025.
No abstract available.
Betancourt D, et al. Maternal, reproductive and perinatal factors and the risks of birth defects: traditional and emerging factors. Reprod Biomed Online. 2025 Jun;50(6):104781. doi: 10.1016/j.rbmo.2024.104781 Published online December 24, 2024.
Abstract
Research question: Does an association exist between maternal, reproductive and perinatal factors, and the risks of major non-chromosomal birth defects?
Design: This population-based cohort study included 1,126,058 naturally conceived singleton live births (21,644 with and 1,104,414 without a major non-chromosomal defect) who were born between 2004 and 2018 in New York, Texas, Massachusetts and North Carolina. All study children were linked to their respective state birth defect registries to identify major birth defects diagnosed within the first year of life, and to state death records. Children with chromosomal defects were excluded. Genitourinary defects were only evaluated in boys. Placental and bleeding issues included placenta previa, placental abruption, uterine bleeding and other excessive bleeding, and, at delivery, blood transfusion or unplanned hysterectomy. Adjusted odds ratios and 95% confidence intervals were modelled using logistic regression.
Results: Among major non-chromosomal defects, the highest significant risks were with pre-gestational diabetes (adjusted OR 2.48, 95% CI 2.25 to 2.74), followed by placental or bleeding issues (adjusted OR 1.82, 95% CI 1.66 to 1.99); this pattern was also evident for congenital heart defects, blastogenesis defects, orofacial defects, gastrointestinal defects and musculoskeletal defects. Hypertension (pre-gestational and gestational), prior caesarean delivery, older maternal age and higher body mass index were also significant risk factors.
Conclusions: The risk factors most strongly associated with major non-chromosomal birth defects were pre-gestational diabetes and placental or bleeding issues; other significantly increased risks were hypertension (pre-gestational and gestational), prior caesarean delivery, older maternal age and pre-pregnancy body mass index 30 kg/m2 or above.
Betancourt D, Shumate C, Yantz C, Gandhi H, Drummond-Borg M, Kubenka C, et al. Self-reported access to specialized genetics providers among families of young children with birth defects in Texas. Am J Med Genet A. 2025 Jun;197(6):e64022. doi:10.1002/ajmg.a.64022 Published online February 17, 2025.
Abstract
Specialized genetics providers can help families of children with birth defects understand their child's condition and guide their medical treatment. The Birth Defects Epidemiology and Surveillance Branch (BDESB) routinely connects young children from the Texas Birth Defects Registry (TBDR) with select birth defects to agency social workers for assistance. Beginning in November 2022, social workers asked parents they reached: "Has the parent or child met with a geneticist or genetic counselor (or visited a genetics clinic)?". Responses were tabulated, overall and by select characteristics of interest. A chi-square test was used to evaluate if these characteristics were associated (p < 0.05) with self-reported access to a specialized genetics provider. Among the 400 families reached, 261 (65%) did not recall accessing specialized genetics providers. Lower access was observed among children with spina bifida or encephalocele, isolated birth defects, children without medical insurance, children meeting CDC developmental milestones, and younger mothers. Lower access was also observed in certain areas of the state, including the Texas-Mexico border. Our findings suggest that, in Texas, more than half (65%) of families of children with select birth defects are not accessing specialized genetics providers, and additional research is needed to work toward increasing access.
Shumate C, et al. Low Apgar score and risk of neonatal mortality among infants with birth defects. Am J Perinatol. 2025 Jun;42(8):1024-1034. doi: 10.1055/a-2452-0047 Published online November 25, 2024.
Abstract
The Apgar score is a clinical tool to assess newborn health at delivery and has shown utility in predicting neonatal mortality in the general population, but its predictive ability in neonates with birth defects remains unexplored. As such, we aimed to investigate the performance of the 5-minute Apgar score in predicting neonatal mortality among neonates with a spectrum of major birth defects.Data for neonates with birth defects born between 1999 and 2017 were obtained from the Texas Birth Defect Registry. We generated receiver operating characteristic curves and corresponding area under the curve (AUC) values for neonatal mortality (death within the first 28 days of life) by 5-minute Apgar score (<7 vs. ≥7) to measure discrimination capacity. We performed secondary analyses to determine the predictive ability of the Apgar score: (1) among infants with an isolated birth defect and (2) separately in preterm and term neonates.Low Apgar score yielded substantial predictive ability for neonatal mortality, with 25 out of 26 AUC values > 0.70 across a spectrum of defect categories. High predictive ability was consistent among neonates with isolated defects, and preterm and term neonates. The Apgar score is likely useful for predicting neonatal mortality among most neonates with birth defects. Despite small sample sizes limiting some secondary analyses, the findings emphasize the potential continued use of the Apgar score as a rapid clinical assessment tool for newborns with birth defects. Continued research may refine the Apgar score's application in this important population, both in clinical practice and population health research. Predictive models suggest the 5-minute Apgar score (<7) is predictive of neonatal mortality. Consistent results were observed across spectrum of birth defect categories. Secondary analyses (e.g., preterm infants) yielded similarly consistent results.
Sullivan B, et al. Three cases of adolescent orf virus skin and soft tissue infection in Southeast Texas. Pediatr Infect Dis J. 2025 May 9:10.1097/INF.0000000000004851. doi: 10.1097/INF.0000000000004851 Epub ahead of print.
Abstract
We report 3 adolescents who presented to a tertiary care hospital in Houston, Texas, with cutaneous skin lesions after contact with sheep and/or goats. The cases presented a diagnostic challenge initially but were later suspected or confirmed as orf virus infection after consultation with infectious diseases specialists.
Miller P, et al. Examining demographic, geographic, and temporal patterns of melanoma incidence in Texas from 2000 to 2018: retrospective study. JMIR Cancer. 2025 May 2;11:e67902. doi: 10.2196/67902
Abstract
Background: Melanoma currently ranks as the fifth leading cancer diagnosis and is projected to become the second most common cancer in the United States by 2040. Melanoma detected at earlier stages may be treated with less-risky and less-costly therapeutic options.
Objective: This study aims to analyze temporal and spatial trends in melanoma incidence by stage at diagnosis (overall, early, and late) in Texas from 2000 to 2018, focusing on demographic and geographic variations to identify high-risk populations and regions for targeted prevention efforts.
Methods: We used melanoma incidence data from all 254 Texas counties from the Texas Cancer Registry (TCR) from 2000 to 2018, aggregated by county and year. Among these, 250 counties reported melanoma cases during the period. Counties with no cases reported in a certain year were treated as having no cases. Melanoma cases were classified by SEER Summary Stage and stratified by the following four key covariates: age, sex, race and ethnicity, and stage at diagnosis. Incidence rates (IRs) were calculated per 100,000 population, and temporal trends were analyzed using joinpoint regression to determine average annual percentage changes (AAPCs) with 95% CIs for the whole time period (2000-2018), the most recent 10-year period (2009-2018), and the most recent 5-year period (2014-2018). Heat map visualizations were developed to assess temporal trends by patient age, year of diagnosis, stage at diagnosis, sex, and race and ethnicity. Spatial cluster analysis was conducted using Getis-Ord Gi* statistics to identify county-level geographic clusters of high and low melanoma incidence by stage at diagnosis.
Results: A total of 82,462 melanoma cases were recorded, of which 74.7% (n=61,588) were early stage, 11.3% (n=9,352) were late stage, and 14% (n=11,522) were of unknown stage. Most cases were identified as males and non-Hispanic White individuals. Melanoma IRs increased from 2000 to 2018, particularly among older adults (60+ years; AAPC range 1.20%-1.84%; all P values were <.001), males (AAPC 1.59%; P<.001), and non-Hispanic White individuals (AAPC of 3.24% for early stage and 2.38% for late stage; P<.001 for early stage and P = .03 for late state). Early-stage diagnoses increased while the rates of late-stage diagnoses remained stable for the overall population. The spatial analysis showed that urban areas had higher early-stage incidence rates (P=.06), whereas rural areas showed higher late-stage incidence rates (P=.05), indicating possible geographic-based differences in access to dermatologic care.
Conclusions: Melanoma incidence in Texas increased over the study time period, with the most-at-risk populations being non-Hispanic White individuals, males, and individuals aged 50 years and older. The stable rates of late-stage melanoma among racial and ethnic minority populations and rural populations highlight potential differences in access to diagnostic care. Future prevention efforts may benefit from increasing access to dermatologic care in areas with higher rates of late-stage melanoma at diagnosis.
Shuford JA, et al. NEJM outbreaks update - H5N1: a view from the States. N Engl J Med. 2025 Apr 3;392(13):e37.
doi:10.1056/NEJMe2502863 Epub 2025 Mar 12.
No abstract available.
Freedenberg D, et al. Cystic fibrosis newborn screening: a systematic review-driven consensus guideline from the United States Cystic Fibrosis Foundation. Int J Neonatal Screen. 2025 Apr 2;11(2):24. doi: 10.3390/ijns11020024
Abstract
Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in diagnosing infants with CF: (1) The CF Foundation recommends the use of a floating immunoreactive trypsinogen (IRT) cutoff over a fixed IRT cutoff; (2) The CF Foundation recommends using a very high IRT referral strategy in CF newborn screening programs whose variant panel does not include all CF-causing variants in CFTR2 or does not have a variant panel that achieves at least 95% sensitivity in all ancestral groups within the state; (3) The CF Foundation recommends that CF newborn screening algorithms should not limit CFTR variant detection to the F508del variant or variants included in the American College of Medical Genetics-23 panel; (4) The CF Foundation recommends that CF newborn screening programs screen for all CF-causing CFTR variants in CFTR2; (5) The CF Foundation recommends conducting CFTR variant screening twice weekly or more frequently as resources allow; (6) The CF Foundation recommends the inclusion of a CFTR sequencing tier following IRT and CFTR variant panel testing to improve the specificity and positive predictive value of CF newborn screening; (7) The CF Foundation recommends that both the primary care provider and the CF specialist be notified of abnormal newborn screening results. Through implementation, it is anticipated that these recommendations will result in improved sensitivity, equity, and timeliness of CF newborn screening, leading to improved health outcomes for all individuals diagnosed with CF following newborn screening and a decreased burden on families.
Tanksley S, et al. Evidence and recommendation for infantile Krabbe disease newborn screening. Pediatrics. 2025 Apr 1;155(4):e2024069152. doi:10.1542/peds.2024-069152
Abstract
Krabbe disease (KD), which affects 0.3-2.6 per 100 000 live births, is an autosomal recessive lysosomal disorder caused by variants in the GALC gene that reduce galactosylceramidase (GALC) activity, leading to psychosine accumulation, cerebral white matter degeneration, and peripheral neuropathy. The most common form, infantile KD (IKD), has onset by 12 months with irritability, feeding difficulty, neurologic regression, and, when untreated, death in early childhood. Hematopoietic stem cell transplantation (HSCT) for IKD approximately 1 month after birth can improve long-term survival but has about a 10% risk of mortality within 100 days, and affected individuals can still have significant functional impairment. Newborn screening for KD is based on low GALC levels in dried-blood spots. Second-tier testing to assess whether an elevated psychosine concentration is present in the same dried-blood spot improves the specificity of screening for IKD. Without newborn screening, diagnosis of IKD is generally made after significant clinical symptoms develop, past when HSCT can be effective. The benefit of newborn detection of later-onset phenotypes of KD is uncertain. In 2024, the US Secretary of Health and Human Services added IKD to the Recommended Uniform Screening Panel after a recommendation by the Advisory Committee on Heritable Disorders in Newborns and Children. For IKD newborn screening to be as effective as possible, it is important to have systems in place to support families in making challenging decisions soon after diagnosis about whether to pursue HSCT and to ensure rapid access to HSCT if chosen.
Abdul-Hamid C, et al. Beta-lactamase-producing Escherichia coli in migratory geese at West Texas recreational parks. Comp Immunol Microbiol Infect Dis. 2025 Apr;118:102320. doi:10.1016/j.cimid.2025.102320 Published online February 10, 2025.
Abstract
This study aimed to determine the prevalence, and the genomic characteristics of beta-lactamase-Resistant Escherichia coli isolated from the feces of migratory geese at one health interface in West Texas. A descriptive study was conducted. We collected geese feces (n = 165), water (n = 118), and soil (n = 74) from 22 recreational parks in West Texas. We used Chromogenic agar to isolate extended-spectrum beta-lactamase (ESBL)-Resistant-E. coli. We used the whole genome sequencing (WGS) method to determine the genomic characteristics of selected E. coli isolates. Among 357 samples, 12.61 % (95 %CI: 9.34-16.50) were positive for ESBL- Resistant-E. coli. From WGS of 20 E. coli isolates, 19 isolates harbored at least 1 beta-lactamase gene including blaCTX-M-1, blaCTX-M-65, blaCTX-M-14, blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, blaCTX-M-32, blaTEM-1A, blaTEM-1B. Most of the isolates carried genes conferring resistance to tetracyclines-(tet(A), tet(B)), aminoglycosides-(aac(3)-IIa, aph(6)-Id, aph(3')-Ia, aadA1), sulfonamides-(sul1,sul2), amphenicol-(floR), trimethoprim-(dfrA1, dfrA14, dfrA17) and streptogramin-B(MLSB) agent-(mph(A)). 13 isolates showed chromosomal mutations in the promoter region G of the ampC beta-lactamase gene. We detected sixteen incompatibility plasmid groups and 60 virulence genes, which are related to adherence, exotoxin, invasion, and nutrition/metabolic factors. Genome analysis showed that all isolates were genetically similar to human E. coli isolates. The study showed that migratory geese at recreational parks can be reservoirs of resistant bacteria with diverse serotypes and sequence types of E. coli isolates. Based on the findings, the detection of a multidrug-resistant E. coli strain reinforces the importance of adequate hygiene practices for humans and pet animals after visiting recreational parks.
Shumate CJ, et al. Risk of carcinomas among children and adolescents with birth defects. Cancer Epidemiol. 2025 Apr;95:102748. doi:10.1016/j.canep.2025.102748 Published online January 22, 2025.
Abstract
Background: Birth defects are associated with childhood cancer, but little is known regarding pediatric carcinomas, a group of especially rare tumors.
Methods: We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for any carcinoma, as well as thyroid, hepatocellular, and renal carcinoma specifically, up to 18 years of age among children with major, non-syndromic anomalies or chromosomal/genetic syndromes, relative to unaffected children.
Results: Our registry-linkage study included nine states and 21,933,476 children between 1990 and 2018: 641,827 with non-syndromic anomalies, and 49,619 with syndromes. Carcinomas were diagnosed in 833 children, including 35 with non-syndromic anomalies and eight with syndromes. The hazard of carcinoma was increased both among children with non-syndromic anomalies (HR: 1.7, CI: 1.2-2.4; N = 35) and syndromes (HR: 4.7, CI: 2.3-9.5; N = 7). Hepatocellular carcinoma was associated with non-syndromic anomalies (HR: 4.6, CI: 2.2-9.7; N = 8) and syndromes (HR: 8.0, CI: 1.1-58.1; N < 5). The hazard of renal carcinoma was markedly increased in children with tuberous sclerosis (HR 59.6, CI: 23.7-149.5; N = 5), a known cause of renal cancer. Thyroid carcinoma was not associated with non-syndromic anomalies or syndromes.
Conclusion: Birth defects are associated with hepatocellular and renal carcinoma in children.
Salinas VA, Archer NP, Lustri LR, et al. Evaluating differences in non-syndromic orofacial clefts by infant sex: National Birth Defects Prevention Study, 1997-2011. J Pediatr. doi:10.1016/j.jpeds.2025.114567 Published online March 28, 2025.
Abstract
Objective: To investigate non-genetic factors that may contribute to observed differences in non-syndromic orofacial clefts by infant sex.
Study design: Using data for 1997-2011 deliveries from the National Birth Defects Prevention Study, a case-control study, we separately examined associations between 23 maternal factors and cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP) using multivariable logistic regression stratified by infant sex.
Results: We compared 2,986 infants with CL/P and 1,557 with CP to 11,271 control infants without birth defects. After adjusting for maternal age at conception and education, lower odds of non-syndromic orofacial clefts were observed among male infants of non-Hispanic Black mothers (CL/P aOR: 0.36; 95% CI: 0.28 - 0.45; CP aOR: 0.56; 95% CI: 0.41 - 0.76) and of Hispanic mothers (CL/P aOR: 0.84; 95% CI: 0.73 - 0.96; CP aOR: 0.57; 95% CI: 0.45 - 0.72) compared with non-Hispanic White mothers. Similar, though attenuated, lower odds of non-syndromic orofacial clefts were observed among female infants of non-Hispanic Black mothers, but no association was observed among female infants of Hispanic mothers. Differences in associations between maternal education and nutrient intake (carbohydrate, energy, total lipids/fat, Vitamin E, and zinc) and CL/P, as well as maternal vitamin C intake and CP, were also observed by infant sex.
Conclusions: Associations between non-syndromic orofacial clefts and minority racial and ethnic groups were attenuated or non-existent among female infants compared with male infants. Sex-specific differences of CL/P appear more susceptible to environmental factors (eg, maternal education and nutrient intake) than sex-specific differences of CP.
Shumate C, et al. Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births. Neuro Oncol. doi:10.1093/neuonc/noaf087 Published online March 26, 2025.
Abstract
Background: Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs.
Methods: We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from nine states (n=22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed <20 years. Cox regression analyses were conducted separately by congenital anomaly for anomaly-CBT combinations with at least 5 co-occurring cases. We conducted analyses for any CBT and separately for astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, medulloblastoma, mixed and unspecified gliomas, and primitive neuroectodermal tumors.
Results: There were 6,247 children diagnosed with a CBT. Having any major structural anomaly was associated with risk of any CBT and across all subgroups (aHR range: 1.48-3.69) except ependymoma, particularly among children diagnosed with a tumor by 1 year of age. Of the 66 anomaly-CBT combinations analyzed, 42 were significant (p<0.05), including 25 in an earlier version of this study and 16 novel associations (aHR range: 1.46-525). Anomaly-CBT associations also differed by astrocytoma histology.
Conclusions: We observed consistent evidence that having a structural congenital anomaly increases risk of developing a CBT, particularly in infancy, which may provide insights into etiology.
Waldrup KA, et al. Monitoring for respiratory viruses among wild canids, Texas. One Health. 2025;20:100974. doi:10.1016/j.onehlt.2025.100974 Published online January 13, 2025.
The cross-species transmission of respiratory viruses such as SARS-CoV-2 and avian influenza underscores the need for novel respiratory virus surveillance at the human-animal interface. In this 2023 pilot study we examined oral and rectal swab samples from 15 deceased wild animals for novel respiratory viruses. We used virus molecular techniques, culture and next-generation nucleotide sequencing to search for and characterize viruses in the Coronaviridae and Orthomyxoviridae families. Through these activities we detected and characterized one canine coronaviruses (CCoVs) each from a gray fox (Urocyon cinereorgenteus) and a feral dog (Canis lupus familiaris). The gray fox CCoV sequence clustered with other CCoVs reported in other canids from other regions of the world. The feral dog CCoV sequence was closely related to CCoVs reported in Brazil and the United Kingdom. This pilot study demonstrated the usefulness of a noninvasive monitoring approach in detecting and characterizing respiratory viruses among wild canids.
Canfield MA, et al. Prediction of preterm birth among infants with orofacial cleft defects. Cleft Palate Craniofac J. 2025 Jan;62(1):35-43. doi:10.1177/10556656231198945 Published online September 6, 2023.
Abstract
Objective: To develop risk prediction models for preterm birth among infants with orofacial clefts.
Design: Data from the Texas Birth Defects Registry for infants with orofacial clefts born between 1999-2014 were used to develop preterm birth predictive models. Logistic regression was used to consider maternal and infant characteristics, and internal validation of the final model was performed using bootstrapping methods. The area under the curve (AUC) statistic was generated to assess model performance, and separate predictive models were built and validated for infants with cleft lip and cleft palate alone. Several secondary analyses were conducted among subgroups of interest.
Setting: State-wide, population-based Registry data.
Patients/participants: 6774 infants with orofacial clefts born in Texas between 1999-2014.
Main outcome measure(s): Preterm birth among infants with orofacial clefts.
Results: The final predictive model performed modestly, with an optimism-corrected AUC of 0.67 among all infants with orofacial clefts. The optimism-corrected models for cleft lip (with or without cleft palate) and cleft palate alone had similar predictive capability, with AUCs of 0.66 and 0.67, respectively. Secondary analyses had similar results, but the model among infants with delivery prior to 32 weeks demonstrated higher optimism-corrected predictive capability (AUC = 0.74).
Conclusions: This study provides a first step towards predicting preterm birth risk among infants with orofacial clefts. Identifying pregnancies affected by orofacial clefts at the highest risk for preterm birth may lead to new avenues for improving outcomes among these infants.
(In date order with the most recent first):
Miller P, et al. Cancers with epidemiologic signatures of viral oncogenicity among immunocompromised populations in the United States. J Natl Cancer Inst. 2024;116(12):1983-1991. doi:10.1093/jnci/djae159
Abstract
Background: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV and solid organ transplant recipients, 2 immunosuppressed populations, may help identify novel etiologic relationships with infectious agents.
Methods: We used 2 linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified according to site and histology codes. Standardized incidence ratios were used to compare risk in people with HIV and solid organ transplant recipients with the general population. For selected cancer entities, incidence rate ratios were calculated for indicators of immunosuppression within each population.
Results: We identified 38 047 cancer cases in solid organ transplant recipients and 53 592 in people with HIV, yielding overall standardized incidence ratios of 1.66 (95% confidence interval [CI] = 1.65 to 1.68) and 1.49 (95% CI = 1.47 to 1.50), respectively. A total of 43 cancer entities met selection criteria, including conjunctival squamous cell carcinoma (people with HIV standardized incidence ratio = 7.1, 95% CI = 5.5 to 9.2; solid organ transplant recipients standardized incidence ratio = 9.4, 95% CI = 6.8 to 12.6). Sebaceous adenocarcinoma was elevated in solid organ transplant recipients (standardized incidence ratio = 16.2, 95% CI = 14.0 to 18.6) and, among solid organ transplant recipients, associated with greater risk in lung and heart transplant recipients compared with recipients of other organs (incidence rate ratio = 2.3, 95% CI = 1.7 to 3.2). Salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma showed elevated risk in solid organ transplant recipients (standardized incidence ratio = 3.9, 4.7, and 3.2, respectively) but not in people with HIV. However, risks for these cancers were elevated following an AIDS diagnosis among people with HIV (incidence rate ratio = 2.4, 4.3, and 2.0, respectively).
Conclusions: Elevated standardized incidence ratios among solid organ transplant recipients and people with HIV, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival squamous cell carcinoma, sebaceous adenocarcinoma, salivary gland tumors, malignant fibrous histiocytoma, and intrahepatic cholangiocarcinoma.
Shumate CJ, et al. Epidemiology of coloboma: prevalence and patterns in Texas, 1999-2014. Birth Defects Res. 2024;116(11):e2413. doi:10.1002/bdr2.2413
Abstract
Background: Coloboma is a rare congenital malformation in which part of the tissue that makes up the eye is missing and may cause visual impairment or blindness. Little is known about the epidemiology of this condition. Therefore, we obtained data from the Texas Birth Defects Registry on children identified with coloboma for the period 1999-2014.
Methods: Using information on all live births from the same period, prevalence ratios (PRs) for selected demographic and clinical factors were used to estimate associations using Poisson regression among cases with coloboma. Coloboma cases were divided into subgroups to explore patterns of co-occurring defects and syndromes. All variables significant in unadjusted models (p < 0.05) were included in multivariable models to evaluate adjusted PRs (aPRs).
Results: We identified 1587 cases with coloboma, of whom 934 (58.8%) were nonsyndromic, and 474 (29.9%) were isolated. When considering all identified cases, factors associated with significant differences in prevalence included plurality (multiple vs. singleton aPR = 1.4, 95% CI: 1.1-1.8); maternal education (college or greater vs. less than high school aPR = 0.7, 95% CI: 0.6-0.9); maternal race/ethnicity (Hispanic vs. non-Hispanic White aPR = 0.9, 95% CI: 0.8-1.0); and maternal diabetes (yes vs. no aPR = 1.3, 95% CI: 1.0-1.6). There was a notable increase in the birth prevalence of coloboma during the study period (p-for-trend < 0.001). Effect estimates were similar across the different subgroups.
Conclusion: In our large population, we identified several factors associated with the prevalence of coloboma. These findings may help define subgroups of women more likely to have children affected by coloboma, which could inform improved screening efforts.
Allred RP, Aguilar-Martinez J, Howell R, et al. Epidemiology of Macrocephaly in the Texas Birth Defects Registry, 1999-2019. Birth Defects Res. 2024;116(11):e2415. doi:10.1002/bdr2.2415
Abstract
Background: Macrocephaly is a clinical observation denoted as an occipitofrontal head circumference exceeding two standard deviations above same age and sex norms. By its definition, macrocephaly occurs in approximately 3% of the population. Descriptive epidemiologic evaluations of macrocephaly are lacking in the literature. The primary objective of this study was to describe the prevalence of macrocephaly captured by the Texas Birth Defects Registry (TBDR) by infant sex, rural/urban residence, and select maternal characteristics.
Methods: Cases of TBDR between 1999 and 2019 with a six-digit Centers for Disease Control modified-British Pediatric Association (BPA) code of 742.400 (enlarged brain/head, large head, macrocephaly, megalencephaly) were identified. All pregnancy outcomes and diagnostic certainties were included. Prevalence (per 10,000 live births) and 95% confidence intervals (CIs) were calculated using a Poisson table by rural/urban residence, infant sex, maternal age, education, race/ethnicity, history of diabetes, and body mass index (BMI). Prevalence calculations were repeated across multiple sensitivity analyses including (1) definite, isolated cases excluding those with indication of being either "benign" or "familial", (2) definite, non-isolated cases, (3) definite non-isolated cases excluding chromosomal and syndromic cases, and (4) definite, proportionate (at birth) cases. A secondary objective was to describe the most common co-occurring congenital defects among definite, non-isolated cases.
Results: Overall, between 1999 and 2019, 14,637 cases of macrocephaly were identified in the TBDR resulting in a prevalence of 18.12/10,000 live births (95% CI: 17.83-18.42). Most cases were live born (99%), had a definite diagnosis (87%), and were non-isolated (57%). Prevalence was significantly higher among males, among those with an urban residence, and among mothers who were older, Non-Hispanic White, who had greater than high school education, who had a history of diabetes, and who were obese. Prevalence patterns remained consistent across all sensitivity analyses. The most common co-occurring congenital defects among definite, non-isolated cases were minor and primarily included skull and facial bone anomalies (e.g., plagiocephaly [18%]).
Conclusions: To our knowledge, this is the first epidemiologic evaluation of macrocephaly in a birth defects registry. The long-term clinical impact of isolated macrocephaly is not well understood and should be the focus of future investigations.
Gonzales ER, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans. N Engl J Med. Published online December 31, 2024. doi:10.1056/NEJMoa2414610
Abstract
Background: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States.
Methods: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit.
Results: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%).
Conclusions: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.).
Canfield M, et al. Low Apgar Score and Risk of Neonatal Mortality among Infants with Birth Defects. Am J Perinatol. Published online November 25, 2024. doi:10.1055/a-2452-0047
Abstract
Objective: The Apgar score is a clinical tool to assess newborn health at delivery and has shown utility in predicting neonatal mortality in the general population, but its predictive ability in neonates with birth defects remains unexplored. As such, we aimed to investigate the performance of the 5-minute Apgar score in predicting neonatal mortality among neonates with a spectrum of major birth defects.
Study design: Data for neonates with birth defects born between 1999 and 2017 were obtained from the Texas Birth Defect Registry. We generated receiver operating characteristic curves and corresponding area under the curve (AUC) values for neonatal mortality (death within the first 28 days of life) by 5-minute Apgar score (<7 vs. ≥7) to measure discrimination capacity. We performed secondary analyses to determine the predictive ability of the Apgar score: (1) among infants with an isolated birth defect and (2) separately in preterm and term neonates.
Results: Low Apgar score yielded substantial predictive ability for neonatal mortality, with 25 out of 26 AUC values > 0.70 across a spectrum of defect categories. High predictive ability was consistent among neonates with isolated defects, and preterm and term neonates.
Conclusion: The Apgar score is likely useful for predicting neonatal mortality among most neonates with birth defects. Despite small sample sizes limiting some secondary analyses, the findings emphasize the potential continued use of the Apgar score as a rapid clinical assessment tool for newborns with birth defects. Continued research may refine the Apgar score's application in this important population, both in clinical practice and population health research.
Monterosso A, et al. Differences in trends in cancer incidence rates among people with HIV during 2001-2019 by race and ethnicity and by risk group in the United States. Clin Infect Dis. Published online November 7, 2024. doi:10.1093/cid/ciae555
Abstract
Background: Cancer risk among people with HIV (PWH) has declined over time as a result of antiretroviral therapy, but it is unclear whether all racial/ethnic groups and transmission risk groups have experienced equal declines.
Methods: We used data on PWH aged ≥20 years old from the HIV/AIDS Cancer Match Study during 2001-2019. We used Poisson regression to assess time trends in incidence rates for each cancer site by racial/ethnicity and risk group, adjusting for age, registry, and sex. We also estimated adjusted rate ratios across racial and ethnic and risk groups in 2001-2004 and 2015-2019.
Results: Trends in age-standardized rates differed across Black, White and Hispanic PWH, and across risk groups for some cancers. For example, liver cancer rates declined 23% per 5-year period among White PWH, 11% in Black PWH and 18% in Hispanic PWH. Anal cancer rates declined among men who have sex with men, were stable among people who inject drugs, and increased among other risk groups Between 2001-2004 and 2015-2019, relative difference in cancer incidence rates by race/ethnicity increased for HL and liver cancer but decreased for NHL; by risk group, relative differences increased for NHL and liver cancer, and decreased for HL, lung and anal cancers.
Conclusions: Among PWH in the US, during 2001-2019, HL, lung, liver, and cervical cancer rate trends were different across racial/ethnic groups. HL, lung, anal, and liver cancer rates trends were different across risk groups. Future work should examine underlying causes of the differences in trends.
Shumate CJ, et al. Survival of children with critical congenital heart defects in the national birth defects prevention study. Birth Defects Res. 2024;116(9):e2394. doi:10.1002/bdr2.2394
Abstract
Background: Critical congenital heart defects (CCHDs) are associated with considerable morbidity and mortality. This study estimated survival of children with nonsyndromic CCHDs and evaluated relationships between exposures of interest and survival by CCHD severity (univentricular or biventricular function).
Methods: This analysis included 4380 infants with CCHDs (cases) born during 1999-2011 and enrolled in the National Birth Defects Prevention Study, a multisite, population-based case-control study of major birth defects. Cases were linked to state death files. Nonparametric Kaplan-Meier survival functions were used to estimate 1- and 5-year survival probabilities overall and by severity group (univentricular/biventricular) stratified by demographic and clinical exposure variables of interest. The log-rank test was used to determine whether stratified survival curves were equivalent. Survival and 95% confidence intervals (CIs) were also estimated using Cox proportional hazards modeling adjusted for maternal age, education, race/ethnicity, study site, and birth year.
Results: One- and five-year survival rates were 85.8% (CI 84.7-86.8) and 83.7% (CI 82.5-84.9), respectively. Univentricular 5-year survival was lower than biventricular case survival [65.3% (CI 61.7-68.5) vs. 89.0% (CI 87.8-90.1; p < 0.001)]. Clinical factors (e.g. preterm birth, low birthweight, and complex/multiple defects) were associated with lower survival in each severity group. Sociodemographic factors (non-Hispanic Black race/ethnicity, <high school education, smoking, and lower household income) were only associated with survival among biventricular cases.
Conclusions: Mortality among children with CCHDs occurred primarily in the first year of life. Survival was lower for those with univentricular defects, and social determinants of health were most important in predicting survival for those with biventricular defects.
Shuford JA, Pont SJ, et al. Factors associated with elevated SARS-CoV-2 immune response in children and adolescents. Front Pediatr. 2024;12:1393321. Published 2024 Aug 15. doi:10.3389/fped.2024.1393321
Abstract
Background: Understanding the distinct immunologic responses to SARS-CoV-2 infection among pediatric populations is pivotal in navigating the COVID-19 pandemic and informing future public health strategies. This study aimed to identify factors associated with heightened antibody responses in children and adolescents to identify potential unique immune dynamics in this population
Methods: Data collected between July and December 2023 from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a statewide prospective population-based antibody survey among 1-to-19-year-old participants, were analyzed. Each participant had the following data available for analysis: (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for Nucleocapsid protein antibodies (Roche N-test), (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test), and (3) self-reported antigen/PCR COVID-19 test results, vaccination, and health status. Statistical analysis identified associations between participant characteristics and spike antibody quartile group.
Results: The analytical sample consisted of 411 participants (mean age 12.2 years, 50.6% female). Spike antibody values ranged from a low of 6.3 U/ml in the lowest quartile to a maximum of 203,132.0 U/ml in the highest quartile in the aggregate sample. Older age at test date (OR = 1.22, 95% CI: 1.12, 1.35, p < .001) and vaccination status (primary series/partially vaccinated, one or multiple boosters) showed significantly higher odds of being in the highest spike antibody quartile compared to younger age and unvaccinated status. Conversely, fewer days since the last immunity challenge showed decreased odds (OR = 0.98, 95% CI: 0.96, 0.99, p = 0.002) of being in the highest spike antibody quartile vs. more days since last immunity challenge. Additionally, one out of every three COVID-19 infections were asymptomatic.
Conclusions: Older age, duration since the last immunity challenge (vaccine or infection), and vaccination status were associated with heightened spike antibody responses, highlighting the nuanced immune dynamics in the pediatric population. A significant proportion of children/adolescents continue to have asymptomatic infection, which has important public health implications.
Shumate CJ, et al. Enhancing the classification of congenital heart defects for outcome association studies in birth defects registries. Birth Defects Res. 2024;116(8):e2393. doi:10.1002/bdr2.2393
Abstract
Introduction: Traditional strategies for grouping congenital heart defects (CHDs) using birth defect registry data do not adequately address differences in expected clinical consequences between different combinations of CHDs. We report a lesion-specific classification system for birth defect registry-based outcome studies.
Methods: For Core Cardiac Lesion Outcome Classifications (C-CLOC) groups, common CHDs expected to have reasonable clinical homogeneity were defined. Criteria based on combinations of Centers for Disease and Control-modified British Pediatric Association (BPA) codes were defined for each C-CLOC group. To demonstrate proof of concept and retention of reasonable case counts within C-CLOC groups, Texas Birth Defect Registry data (1999-2017 deliveries) were used to compare case counts and neonatal mortality between traditional vs. C-CLOC classification approaches.
Results: C-CLOC defined 59 CHD groups among 62,262 infants with CHDs. Classifying cases into the single, mutually exclusive C-CLOC group reflecting the highest complexity CHD present reduced case counts among lower complexity lesions (e.g., 86.5% of cases with a common atrium BPA code were reclassified to a higher complexity group for a co-occurring CHD). As expected, C-CLOC groups had retained larger sample sizes (i.e., representing presumably better-powered analytic groups) compared to cases with only one CHD code and no occurring CHDs.
Archer NP, et al. Reporting tumor genomic test results to SEER registries via linkages. J Natl Cancer Inst Monogr. 2024;2024(65):168-179. doi:10.1093/jncimonographs/lgae013
Abstract
Background: Precision medicine has become a mainstay of cancer care in recent years. The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program has been an authoritative source of cancer statistics and data since 1973. However, tumor genomic information has not been adequately captured in the cancer surveillance data, which impedes population-based research on molecular subtypes. To address this, the SEER Program has developed and implemented a centralized process to link SEER registries' tumor cases with genomic test results that are provided by molecular laboratories to the registries.
Methods: Data linkages were carried out following operating procedures for centralized linkages established by the SEER Program. The linkages used Match*Pro, a probabilistic linkage software, and were facilitated by the registries' trusted third party (an honest broker). The SEER registries provide to NCI limited datasets that undergo preliminary evaluation prior to their release to the research community.
Results: Recently conducted genomic linkages included OncotypeDX Breast Recurrence Score, OncotypeDX Breast Ductal Carcinoma in Situ, OncotypeDX Genomic Prostate Score, Decipher Prostate Genomic Classifier, DecisionDX Uveal Melanoma, DecisionDX Preferentially Expressed Antigen in Melanoma, DecisionDX Melanoma, and germline tests results in Georgia and California SEER registries.
Conclusions: The linkages of cancer cases from SEER registries with genomic test results obtained from molecular laboratories offer an effective approach for data collection in cancer surveillance. By providing de-identified data to the research community, the NCI's SEER Program enables scientists to investigate numerous research inquiries.
Stuteville H, et al. An analysis of clinical outcomes of exploratory pediatric metformin ingestions reported to the Texas poison center network from 2011 to 2021. Hosp Pharm. 2024;59(4):465-470. doi:10.1177/00185787241230628
Abstract
Background: Poison centers develop triage threshold guidelines for pediatric metformin ingestions. Our network uses 1700 mg, or 85 mg/kg.
Objective: To describe the dose, clinical course, and outcomes for inadvertent metformin ingestions in children 5 years old and younger reported to our statewide poison center network.
Methods: We searched the poison center database 2011 to 2021 for metformin ingestions in patients 5 years and younger. Variables included age, sex, weight, dose, symptoms, outcome, and more. We used descriptive statistics with medians and interquartile ranges (IQR) for continuous variables.
Results: Of 669 cases, exposures by age were 208 (31.1%) 1 to 2 years, and 275 (41.1%) 2 years. Weight was recorded in 342 (51.1%) (median 13.5 kg; IQR: 3.7 kg), and dose in 149 (22.3%) (median 500 mg; IQR: 500 mg). Milligram/kilogram values were available for 103 (15.4%) with median 42.4 mg/kg, IQR: 39 mg/kg. Most (647, 98.5%) exposures were unintentional. Most (445/669, 66.5%) were managed at a non-healthcare facility, while 204 (30.7%) were already at or referred to a healthcare facility. Of these 204 patients, 169 (82.8%) were evaluated and treated at the emergency department and discharged. Four (2%) were admitted to critical care, and 7 (3.4%) to the ward. Medical outcomes by effect were 5 (0.7%) minor, 2 (0.3%) moderate, 253 (37.8%) none, 292 (43.6%) not followed (minimal effects possible), and no major effects or deaths. Of 20 clinical occurrences reported, vomiting was most common (8, 1.2%).
Conclusion: Despite little recorded dosage information, pediatric metformin ingestions under 85 mg/kg had predominantly uneventful medical outcomes.
Merengwa E, et al. Clusters of emerging multidrug-resistant organisms in US health care facilities during the initial months of the SARS-CoV-2 pandemic. Am J Infect Control. Published online July 30, 2024. doi:10.1016/j.ajic.2024.07.013
Abstract
Background: Outbreaks of emerging multidrug-resistant organisms (eMDROs), including carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Candida auris, have been reported among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. We describe eMDRO clusters in SARS-CoV-2 units and associated infection control (IC) practices early in the SARS-CoV-2 pandemic.
Methods: We conducted a retrospective survey of a convenience sample of health departments in 11 states to describe clusters of eMDROs that began before November 1, 2020 and involved SARS-CoV-2 units. Cluster characteristics and IC practices during the cluster period were assessed using a standardized outbreak report form, and descriptive analyses were performed.
Results: Overall, 18 eMDRO clusters (10 carbapenem-resistant Enterobacterales, 6 C auris, 1 carbapenem-resistant Pseudomonas aeruginosa, and 1 carbapenem-resistant A baumannii) in 18 health care facilities involving 397 patients were reported from 10 states. During the cluster period, 60% of facilities reported a shortage of isolation gowns, 69% extended use of gowns, and 67% reported difficulty obtaining preferred disinfectants. Reduced frequency of hand hygiene audits was reported in 85% of acute care hospitals during the cluster period compared with before the pandemic.
Conclusions: Changes in IC practices and supply shortages were identified in facilities with eMDRO outbreaks during the SARS-CoV-2 pandemic and might have contributed to eMDRO transmission.
Shumate CJ, et al. Demographic differences and potential bias from automated occupation coding among mothers of babies born with or without cleft lip and/or cleft palate in the Texas Birth Defects Registry. J Occup Environ Med. Published online July 16, 2024. doi:10.1097/JOM.0000000000003189
Abstract
Objective: To compare maternal demographics based on occupation coding status and evaluate potential bias by excluding manually coded occupations.
Methods: This case-control study assessed cases with clefts obtained from the Texas Birth Defects Registry. The NIOSH Industry and Occupation Computerized Coding System automatically coded occupations, with manual coding for unclassified cases. Maternal demographics were tabulated by occupation coding status (manual vs. automatic). Logistic regression examined associations between major occupation groups and clefts.
Results: Automatic coding covered over 90% of all mothers. Building, grounds cleaning, and maintenance occupations, and office and administrative support occupations were significantly associated with cleft lip with or without cleft palate, even after excluding manually coded occupations.
Conclusion: We found consistent associations before and after excluding manually coded data for most comparisons, suggesting that machine learning can facilitate occupation-related birth defects research.
Archer NP, Drummond-Borg M, Freedenberg D, Shumate C, Langlois PH, Canfield MA, et al. Newborn screening analytes and structural birth defects among 27,000 newborns. PLoS One. 2024;19(7):e0304238. Published 2024 Jul 5. doi:10.1371/journal.pone.0304238
Abstract
Background: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects.
Methods: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, were assessed using regression analysis.
Findings: Of the 27,643 births identified, 20,205 had at least one of the 39 birth defects of interest (cases) as identified by the Texas Birth Defects Registry, while 7,438 did not have a birth defect (controls). Among 1,404 analyte-birth defect associations evaluated, 377 were significant in replication analysis. Analytes most consistently associated with birth defects included the phenylalanine/tyrosine ratio (N = 29 birth defects), tyrosine (N = 28 birth defects), and thyroxine (N = 25 birth defects). Birth defects most frequently associated with a range of analytes included gastroschisis (N = 29 analytes), several cardiovascular defects (N = 26 analytes), and spina bifida (N = 23 analytes).
Conclusions: Several significant and novel associations were observed between newborn screening analytes and birth defects. While some findings could be consequences of the defects themselves or to the care provided to infants with these defects, these findings could help to elucidate mechanisms underlying the etiology of some birth defects.
Miller P, et al. Cancers with epidemiologic signatures of viral oncogenicity among immunocompromised populations in the United States. J Natl Cancer Inst. Published online July 2, 2024. doi:10.1093/jnci/djae159
Abstract
Background: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents.
Methods: We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population.
Findings: We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively).
Interpretation: Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma.
Singer R, Williams C, Nwanguma A, et al. Determining barriers to submitting antimicrobial-resistant isolates among hospitals in Texas Public Health Region 8. J Infect Prev. 2024;25(4):120-125. doi:10.1177/17571774241235101
Abstract
Background: The Antimicrobial Resistance Laboratory Network (AR Lab Network) was developed by the CDC to detect emerging antimicrobial-resistant (AR) threats and prevent outbreaks. However, low submission rates of AR isolates limit the potential of the AR Lab Network to address antimicrobial resistance (AMR).
Aim: The aim of this study was to investigate barriers to submission of AR isolates in acute care hospitals (ACHs) and critical access hospitals (CAHs) within Texas Public Health Region 8 (PHR8) counties.
Methods: A survey was designed and emailed to laboratory professionals to identify barriers to AR isolate submission. Responses were analyzed using 2-sided Fisher's exact tests to identify associations between responses and respondent characteristics.
Results: Of the 33 hospitals within PHR8 invited to participate in the survey, responses were received from 21, a response rate of 63.6%. Lack of awareness of the AR Lab Network was the most frequently cited barrier to submission (65.4% of respondents). Other reported barriers to submission included lack of laboratory staff time (57.7%), lack of training with the submission process (34.6%), lack of personnel certified to ship infectious substances (23.1%), and lack of laboratory/shipping supplies (23.1%).
Canfield MA, et al. A multicountry analysis of prevalence and mortality among neonates and children with bladder exstrophy. Am J Perinatol. 2024 Jul;41(9):1143-1154. doi:10.1055/s-0042-1748318. Epub 2022 May 29. doi:10.1055/s-0042-1748318
Abstract
Objective: Bladder exstrophy (BE) is a rare but severe birth defect affecting the lower abdominal wall and genitourinary system. The objective of the study is to examine the total prevalence, trends in prevalence, and age-specific mortality among individuals with BE.
Study design: We conducted a retrospective cohort study. Data were analyzed from 20 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research in 16 countries. Live births, stillbirths, and elective terminations of pregnancy for fetal anomaly (ETOPFA) diagnosed with BE from 1974 to 2014. Pooled and program-specific prevalence of BE per 100,000 total births was calculated. The 95% confidence intervals (CI) for prevalence were estimated using Poisson approximation of binomial distribution. Time trends in prevalence of BE from 2000 to 2014 were examined using Poisson regression. Proportion of deaths among BE cases was calculated on the day of birth, day 2 to 6, day 7 to 27, day 28 to 364, 1 to 4 years, and ≥5 years. Mortality analysis was stratified by isolated, multiple, and syndromic case status.
Results: The pooled total prevalence of BE was 2.58 per 100,000 total births (95% CI = 2.40, 2.78) for study years 1974 to 2014. Prevalence varied over time with a decreasing trend from 2000 to 2014. The first-week mortality proportion was 3.5, 17.3, and 14.6% among isolated, multiple, and syndromic BE cases, respectively. The majority of first-week mortality occurred on the first day of life among isolated, multiple, and syndromic BE cases. The proportion of first-week deaths was higher among cases reported from programs in Latin America where ETOPFA services were not available.
Conclusion: Prevalence of BE varied by program and showed a decreasing trend from 2000 to -2014. Mortality is a concern among multiple and syndromic cases, and a high proportion of deaths among cases occurred during the first week of life.
Magee C, Browning C, Stokes-Walters R, Maxwell L, Buendia J, Bhakta N. Supporting local public health and planning professionals to implement built environment changes: a technical assistance program to promote physical activity in Texas. Prev Chronic Dis. 2024 Jun 20;21:E45. doi:10.5888/pcd21.230420.
Built environment approaches that improve active transportation infrastructure and environmental design can increase physical activity. Funded by the Centers for Disease Control and Prevention, the Texas Department of State Health Services rejuvenated the Texas Plan4Health program from 2018 to 2023 to expand such approaches in Texas by providing technical assistance to teams of local public health professionals and planners to identify and implement projects connecting people to everyday destinations via active transport in their communities. However, the COVID-19 pandemic prompted Texas Plan4Health to modify the delivery of technical assistance to accommodate restrictions on travel and in-person gatherings. We used qualitative methods to conduct a postintervention process evaluation to describe the modified technical assistance process, understand the experiences of the 4 participating communities, and identify short-term outcomes and lessons learned. Texas Plan4Health helped communities overcome common barriers to built environment change, facilitated collaboration across community public health and planning professionals, and educated professionals about active transportation infrastructure and the relationship between their disciplines, thereby increasing community capacity to implement built environment improvements. This outcome, however, was mediated by the pre-existing resources and previous experiences with active transportation planning among the participating communities. Public health practitioners seeking to improve active transportation infrastructure and environmental design for physical activity should consider community-engaged approaches that advance partnership-building and collaborative experiential education among public health, planning, and other local government representatives, directing particular attention and additional training toward communities with fewer resources.
Shetty V, Rollo SN, Martinez DL, Raj S, Gonzales ER, et al. Highly pathogenic avian influenza A(H5N1) virus infection in a dairy farm worker. N Engl J Med. 2024 Jun 6;390(21):2028-2029. doi:10.1056/NEJMc2405371.
To the Editor:
Sporadic human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus, with a wide spectrum of clinical severity and a cumulative case fatality of more than 50%, have been reported in 23 countries over more than 20 years. HPAI A(H5N1) clade 2.3.4.4b viruses have spread widely among wild birds worldwide since 2020–2021, resulting in outbreaks in poultry and other animals. Recently, HPAI A(H5N1) clade 2.3.4.4b viruses were identified in dairy cows, and in unpasteurized milk samples, in multiple U.S. states. We report a case of HPAI A(H5N1) virus infection in a dairy farm worker in Texas.
Marengo LK, et al. Prevalence and descriptive epidemiology of choanal atresia and stenosis in Texas, 1999-2018. Am J Med Genet A. 2024 Jun;194(6):e63549. doi:10.1002/ajmg.a.63549. Epub 2024 Feb 5.
Abstract
Choanal atresia and stenosis are common causes of congenital nasal obstruction, but their epidemiology is poorly understood. Compared to bilateral choanal atresia/stenosis, unilateral choanal atresia/stenosis is generally diagnosed later and might be under-ascertained in birth defect registries. Data from the population-based Texas Birth Defects Registry and Texas vital records, 1999-2018, were used to assess the prevalence of choanal atresia/stenosis. Poisson regression models were used to evaluate associations with infant and maternal characteristics in two analytic groups: isolated choanal atresia/stenosis (n = 286) and isolated, bilateral choanal atresia/stenosis (n = 105). The overall prevalence of choanal atresia/stenosis was 0.92/10,000, and the prevalence of isolated choanal atresia/stenosis was 0.37/10,000 livebirths. Variables associated with choanal atresia/stenosis in one or both analytic groups included infant sex, pregnancy plurality, maternal race/ethnicity, maternal age, and maternal residence on the Texas-Mexico border. In general, adjusted prevalence ratios estimated from the two analytic groups were in the same direction but tended to be stronger in the analyses restricted to isolated, bilateral defects. Epidemiologic studies of isolated choanal atresia/stenosis should consider focusing on cases with bilateral defects, and prioritizing analyses of environmental, social, and structural factors that could account for the association with maternal residence on the Texas-Mexico border.
Nguyen JM, Drummond-Borg M, et al. Classification of isolated versus multiple birth defects: An automated process for population-based registries. Am J Med Genet A. 2024 May 21:e63714. doi:10.1002/ajmg.a.63714. Epub ahead of print.
Abstract
Epidemiologic studies of birth defects often conduct separate analyses for cases that have isolated defects (e.g., spina bifida only) and cases that have multiple defects (e.g., spina bifida and a congenital heart defect). However, in some instances, cases with additional defects (e.g., spina bifida and clubfoot) may be more appropriately considered as isolated because the co-occurring defect (clubfoot) is believed to be developmentally related to the defect of interest. Determining which combinations should be considered isolated can be challenging and potentially resource intensive for registries. Thus, we developed automated classification procedures for differentiating between isolated versus multiple defects, while accounting for developmentally related defects, and applied the approach to data from the Texas Birth Defects Registry (1999-2018 deliveries). Among 235,544 nonsyndromic cases in Texas, 89% of cases were classified as having isolated defects, with proportions ranging from 25% to 92% across 43 specific defects analyzed. A large proportion of isolated cases with spina bifida (44%), lower limb reduction defects (44%), and holoprosencephaly (32%) had developmentally related defects. Overall, our findings strongly support the need to account for isolated versus multiple defects in risk factor association analyses and to account for developmentally related defects when doing so, which has implications for interpreting prior studies.
Shuford JA, Pont SJ, et al. Baseline characteristics of SARS-CoV-2 vaccine non-responders in a large population-based sample. PLoS One. 2024;19(5):e0303420. Published 2024 May 13. doi:10.1371/journal.pone.0303420
Abstract
Introduction: Studies indicate that individuals with chronic conditions and specific baseline characteristics may not mount a robust humoral antibody response to SARS-CoV-2 vaccines. In this paper, we used data from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a longitudinal state-wide seroprevalence program that has enrolled more than 90,000 participants, to evaluate the role of chronic diseases as the potential risk factors of non-response to SARS-CoV-2 vaccines in a large epidemiologic cohort.
Methods: A participant needed to complete an online survey and a blood draw to test for SARS-CoV-2 circulating plasma antibodies at four-time points spaced at least three months apart. Chronic disease predictors of vaccine non-response are evaluated using logistic regression with non-response as the outcome and each chronic disease + age as the predictors.
Results: As of April 24, 2023, 18,240 participants met the inclusion criteria; 0.58% (N = 105) of these are non-responders. Adjusting for age, our results show that participants with self-reported immunocompromised status, kidney disease, cancer, and "other" non-specified comorbidity were 15.43, 5.11, 2.59, and 3.13 times more likely to fail to mount a complete response to a vaccine, respectively. Furthermore, having two or more chronic diseases doubled the prevalence of non-response.
Conclusion: Consistent with smaller targeted studies, a large epidemiologic cohort bears the same conclusion and demonstrates immunocompromised, cancer, kidney disease, and the number of diseases are associated with vaccine non-response. This study suggests that those individuals, with chronic diseases with the potential to affect their immune system response, may need increased doses or repeated doses of COVID-19 vaccines to develop a protective antibody level.
Stuteville H, et al. Fasciotomy following North American pit viper envenomation in Texas 2004-2021. Clin Toxicol (Phila). 2024;62(5):314-321. doi:10.1080/15563650.2024.2338559
Abstract
Introduction: North American pit viper envenomation occurs over 4,000 times annually in the United States, with polyvalent Fab antivenom being the primary treatment. Fasciotomy is occasionally performed due to concerns about compartment syndrome. We utilized our direct access to Texas Poison Center Network data to create a new snakebite abstraction form and database on relevant available information between 2004 and 2021 and to identify, describe, and estimate the incidence of fasciotomy following pit viper envenomation in Texas.
Methods: We searched the Texas Poison Center Network database for cases during 2004-2021 using keywords such as fasciotomy, surgery, compartment pressure, and compartment syndrome. Descriptive statistics summarized the data.
Results: Of 16,911 reported envenomations, 0.69 percent involved fasciotomies (n = 117). Most common bite sites were digits/hands and lower extremities. Patients who underwent fasciotomy were typically male, aged 20-59, and 10 years younger than the total snakebite population. Only 6 percent of reported compartment syndrome cases had a compartment pressure measurement. Antivenom was administered in 101 (86.3 percent) cases, 92 (91.1 percent) of which received only Fab antivenom product. Patients with bites from rattlesnakes (47.9 percent) were associated with most fasciotomies.
Discussion: Our findings suggest a potential increase in snakebite exposures, accompanied by a decrease in fasciotomies. Overall, copperheads constituted the majority of snakebites, but most fasciotomies were from rattlesnake envenomations (47.9 percent). In this cohort, compartment syndrome diagnosis and decisions regarding fasciotomy were primarily based on clinical evaluation/surgeon expertise without compartment pressure measurements. Despite the efficacy of antivenom, only 86.3 percent of patients in our study received antivenom.
Conclusions: Fasciotomy after North American pit viper envenomation in Texas is uncommon (0.69 percent) and has decreased over time, possibly due to increased antivenom use or surgeon comfort with nonsurgical management.
Nash N, et al. Provider perspectives: identification and follow-up of infants who are deaf or hard of hearing. Am J Perinatol. 2024;41(S 01):e694-e710. doi:10.1055/a-1932-9985
Abstract
Objective: Without timely screening, diagnosis, and intervention, hearing loss can cause significant delays in a child's speech, language, social, and emotional development. In 2019, Texas had nearly twice the average rate of loss to follow-up (LFU) or loss to documentation (LTD; i.e., missing documentation of services received) among infants who did not pass their newborn hearing screening compared to the United States overall (51.1 vs. 27.5%). We aimed to identify factors contributing to LFU/LTD among infants who do not pass their newborn hearing screening in Texas.
Study design: Data were collected through semistructured qualitative interviews with 56 providers along the hearing care continuum, including hospital newborn hearing screening program staff, audiologists, primary care physicians, and early intervention (EI) program staff located in three rural and urban public health regions in Texas. Following recording and transcription of the interviews, we used qualitative data analysis software to analyze themes using a conventional content analysis approach.
Results: Frequently cited barriers included problems with family access to care, difficulty contacting patients, problems with communication between providers and referrals, lack of knowledge among providers and parents, and problems using the online reporting system. Providers in rural areas more often mentioned problems with family access to care and contacting families compared to providers in urban areas.
Conclusion: These findings provide insight into strategies that public health professionals and health care providers can use to work together to help further increase the number of children identified early who may benefit from EI services.
Yoo K, et al. NTCA guidelines for respiratory isolation and restrictions to reduce transmission of pulmonary tuberculosis in community settings. Clin Infect Dis. Published online April 18, 2024. doi:10.1093/cid/ciae199
No abstract available.
Shumate CJ, et al. Direct potable reuse and birth defects prevalence in Texas: An augmented synthetic control method analysis of data from a population-based birth defects registry. Environ Epidemiol. 2024;8(2):e300. Published 2024 Mar 18. doi:10.1097/EE9.0000000000000300
Abstract
Background: Direct potable reuse (DPR) involves adding purified wastewater that has not passed through an environmental buffer into a water distribution system. DPR may help address water shortages and is approved or is under consideration as a source of drinking water for several water-stressed population centers in the United States, however, there are no studies of health outcomes in populations who receive DPR drinking water. Our objective was to determine whether the introduction of DPR for certain public water systems in Texas was associated with changes in birth defect prevalence
Methods: We obtained data on maternal characteristics for all live births and birth defects cases regardless of pregnancy outcome in Texas from 2003 to 2017 from the Texas Birth Defects Registry and birth and fetal death records. The ridge augmented synthetic control method was used to model changes in birth defect prevalence (per 10,000 live births) following the adoption of DPR by four Texas counties in mid-2013, with county-level data on maternal age, percent women without a high school diploma, percent who identified as Hispanic/Latina or non-Hispanic/Latina Black, and rural-urban continuum code as covariates.
Results: There were nonstatistically significant increases in prevalence of all birth defects collectively (average treatment effect in the treated = 53.6) and congenital heart disease (average treatment effect in the treated = 287.3) since June 2013. The estimated prevalence of neural tube defects was unchanged.
Conclusions: We estimated nonstatistically significant increases in birth defect prevalence following the implementation of DPR in four West Texas counties. Further research is warranted to inform water policy decisions.
Pont SJ, et al. Prozone masks elevated SARS-CoV-2 antibody level measurements. PLoS One. 2024;19(3):e0301232. Published 2024 Mar 28.
doi:10.1371/journal.pone.0301232
Abstract
We report a prozone effect in measurement of SARS-CoV-2 spike protein antibody levels from an antibody surveillance program. Briefly, the prozone effect occurs in immunoassays when excessively high antibody concentration disrupts the immune complex formation, resulting in a spuriously low reported result. Following participant inquiries, we observed anomalously low measurement of SARS-CoV-2 spike protein antibody levels using the Roche Elecsys® Anti-SARS-CoV-2 S immunoassay from participants in the Texas Coronavirus Antibody Research survey (Texas CARES), an ongoing prospective, longitudinal antibody surveillance program. In July, 2022, samples were collected from ten participants with anomalously low results for serial dilution studies, and a prozone effect was confirmed. From October, 2022 to March, 2023, serial dilution of samples detected 74 additional cases of prozone out of 1,720 participants' samples. Prozone effect may affect clinical management of at-risk populations repeatedly exposed to SARS-CoV-2 spike protein through multiple immunizations or serial infections, making awareness and mitigation of this issue paramount.
Salinas V, Bojes HK, et al. Influences of 23 different equations used to calculate gene copies of SARS-CoV-2 during wastewater-based epidemiology. Sci Total Environ. 2024;917:170345. doi:10.1016/j.scitotenv.2024.170345
Abstract
Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the use of wastewater-based surveillance (WBS) has increased dramatically along with associated infrastructure globally. However, due to the global nature of its application, and various workflow adaptations (e.g., sample collection, water concentration, RNA extraction kits), numerous methods for back-calculation of gene copies per volume (gc/L) of sewage have also emerged. Many studies have considered the comparability of processing methods (e.g., water concentration, RNA extraction); however, for equations used to calculate gene copies in a wastewater sample and subsequent influences on monitoring viral trends in a community and its association with epidemiological data, less is known. Due to limited information on how many formulas exist for the calculation of SARS-CoV-2 gene copies in wastewater, we initially attempted to quantify how many equations existed in the referred literature. We identified 23 unique equations, which were subsequently applied to an existing wastewater dataset. We observed a range of gene copies based on use of different equations, along with variability of AUC curve values, and results from correlation and regression analyses. Though a number of individual laboratories appear to have independently converged on a similar formula for back-calculation of viral load in wastewater, and share similar relationships with epidemiological data, differential influences of various equations were observed for variation in PCR volumes, RNA extraction volumes, or PCR assay parameters. Such observations highlight challenges when performing comparisons among WBS studies when numerous methodologies and back-calculation methods exist. To facilitate reproducibility among studies, the different gc/L equations were packaged as an R Shiny app, which provides end users the ability to investigate variability within their datasets and support comparisons among studies.
Mundis SJ, et al. The L1014F knockdown resistance mutation is not a strong correlate of phenotypic resistance to pyrethroids in Florida populations of Culex quinquefasciatus. Insects. 2024;15(3):197. Published 2024 Mar 15. doi:10.3390/insects15030197
Abstract
Culex quinquefasciatus is an important target for vector control because of its ability to transmit pathogens that cause disease. Most populations are resistant to pyrethroids and often to organophosphates, the two most common classes of active ingredients used by public health agencies. A knockdown resistance (kdr) mutation, resulting in an amino acid change from a leucine to phenylalanine in the voltage gated sodium channel, is one mechanism contributing to the pyrethroid resistant phenotype. Enzymatic resistance has also been shown to play a very important role. Recent studies have shown strong resistance in populations even when kdr is relatively low, which indicates that factors other than kdr may be larger contributors to resistance. In this study, we examined, on a statewide scale (over 70 populations), the strength of the correlation between resistance in the CDC bottle bioassay and the kdr genotypes and allele frequencies. Spearman correlation analysis showed only moderate (-0.51) or weak (-0.29) correlation between the kdr genotype and permethrin or deltamethrin resistance, respectively. The frequency of the kdr allele was an even weaker correlate than genotype. These results indicate that assessing kdr in populations of Culex quinquefasciatus is not a good surrogate for phenotypic resistance testing.
Patel K, et al. Descriptive summary of fatal work-related injuries, Western States, 2011-2017. J Occup Environ Hyg. 2024 Mar;21(3):189-201. Epub 2024 Feb 26. doi:10.1080/15459624.2024.2302470
Abstract
Work-related deaths are a persistent occupational health issue that can be prevented. However, prevention opportunities can be hampered by a lack of adequate public health resources. The Western States Occupational Network (WestON) is a network of federal, state, and local occupational health professionals that includes a 19-state region of the United States. To encourage public health collaboration, WestON partners examined work-related fatalities within the region. Fatality counts (numerators) were obtained from the U.S. Bureau of Labor Statistics (BLS) Census of Fatal Occupational Injuries restricted-access research files for all workers ages ≥15 years and fatally injured in WestON states from 2011 through 2017. Estimates of full-time equivalent hours worked (FTE) (denominators) were retrieved from the BLS Current Population Survey. Annual average fatality rates were calculated as number of fatalities per 100,000 FTE over the study period. Rates were stratified by state, select demographics, industry sector, and event/exposure types. Pearson chi-squared tests and rate ratios with 95% confidence probability limits were used to assess rate differences. All analyses were conducted using SAS v.9.4. From 2011 through 2017, the annual average overall occupational fatality rate for the WestON region was 3.5 fatalities per 100,000 FTE, comparable to the overall U.S. fatality rate. Male workers had a fatality rate almost 10 times higher than female workers in the region. Fatality rates increased with successive age groups. Alaska and New Mexico had significantly higher fatality rates for all racial/ethnic groups compared to respective regional rates. Wyoming, North Dakota, and Montana had the three highest occupational fatality rates among foreign-born workers. Agriculture/forestry/fishing, mining/oil/gas extraction, and transportation/warehousing/utilities were industry sector groups with the three highest fatality rates regionally. Transportation-related incidents were the most frequent event type associated with occupational fatalities for all 19 states. Work-related fatalities are a crosscutting occupational public health priority. This analysis can be an impetus for collaborative multistate initiatives among a dynamic and varied occupational public health network to better meet the needs of a rapidly changing workforce.
Miller P, et al. Real-world use of antiretroviral therapy and risk of cancer among people with HIV in Texas. AIDS. 2024 Mar 1;38(3):379-386. Epub 2023 Nov 22. doi:10.1097/QAD.0000000000003770
Abstract
Background: Combination antiretroviral therapy (cART) may reduce cancer risk among people with HIV (PWH), but cancer-specific associations are incompletely understood.
Methods: We linked HIV and cancer registries in Texas to a national prescription claims database. cART use was quantified as the proportion of days covered (PDC). Cox proportional hazards models assessed associations of cancer risk with cART usage, adjusting for demographic characteristics, AIDS status, and time since HIV report.
Results: We evaluated 63 694 PWH followed for 276 804 person-years. The median cART PDC was 21.4% (interquartile range: 0.0-59.8%). cART use was associated with reduced risk of Kaposi sarcoma [adjusted hazard ratio (aHR) 0.48, 95% confidence interval (CI) 0.34-0.68 relative to unexposed status] and non-Hodgkin lymphoma (aHR 0.41, 95% CI 0.31-0.53), liver cancer (aHR 0.61, 95% CI 0.39-0.96), anal cancer (aHR 0.65, 95% CI 0.46-0.92), and a miscellaneous group of 'other' cancers (aHR 0.80, 95% CI 0.66-0.98). In contrast, cART-exposed status was not associated with risk for cervical, lung, colorectal, prostate or breast cancers.
Conclusion: In a large HIV cohort incorporating data from prescription claims, cART was associated with greatly reduced risks of Kaposi sarcoma and non-Hodgkin lymphoma, and to a lesser degree, reduced risks of liver and anal cancers. These associations likely reflect the beneficial effects of HIV suppression and improved immune control of oncogenic viruses. Efforts to increase cART use and adherence may further decrease cancer incidence among PWH.
Lee R, Wang C, et al. Descriptive analysis of targeted carbapenemase genes and antibiotic susceptibility profiles among carbapenem-resistant Acinetobacter baumannii tested in the Antimicrobial Resistance Laboratory Network-United States, 2017-2020. Microbiol Spectr. 2024 Feb 6;12(2):e0282823. Epub 2024 Jan 4. doi:10.1128/spectrum.02828-23
Abstract
The Centers for Disease Control and Prevention has classified CRAB as an urgent public health threat. In this paper, we used a collection of >6,000 contemporary clinical isolates to evaluate the phenotypic and genotypic properties of CRAB detected in the United States. We describe the frequency of specific carbapenemase genes detected, antimicrobial susceptibility profiles, and the distribution of CRAB isolates categorized as multidrug resistant, extensively drug-resistant, or difficult to treat. We further discuss the proportion of isolates showing susceptibility to Food and Drug Administration-approved agents. Of note, 84% of CRAB tested harbored at least one class A, B, or D carbapenemase genes targeted for detection and 83% of these carbapenemase gene-positive CRAB were categorized as extensively drug resistant. Fifty-four percent of CRAB isolates without any of these carbapenemase genes detected were still extensively drug-resistant, indicating that infections caused by CRAB are highly resistant and pose a significant risk to patient safety regardless of the presence of one of these carbapenemase genes.
Canfield MA, et al. Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017. Birth Defects Res. 2024 Feb;116(2):e2306. doi:10.1002/bdr2.2306
Abstract
Background: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population.
Methods: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age.
Results: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic.
Conclusions: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.
Shumate C, Canfield MA, et al. Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: A population-based assessment in seven million children. Cancer. 2024 Feb 1;130(3):467-475. Epub 2023 Oct 3. doi:10.1002/cncr.35041
Abstract
Background: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study.
Methods: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age.
Results: In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70).
Conclusions: This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.
Monterosso A, et al. Severe anal intraepithelial neoplasia trends and subsequent invasive anal cancer in the United States. J Natl Cancer Inst. 2024 Jan 10;116(1):97-104. doi:10.1093/jnci/djad176
Abstract
Background: Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex.
Methods: We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis.
Results: Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively.
Conclusions: Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis.
Monterosso A, et al. Risk of hepatocellular carcinoma in people with HIV in the United States, 2001-2019. J Natl Cancer Inst. 2024 Jan 10;116(1):61-68. doi:10.1093/jnci/djad172
Abstract
Background: People with HIV have higher risk of hepatocellular carcinoma than the general population, partly because of higher prevalence of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
Methods: We calculated standardized incidence ratios for hepatocellular carcinoma in people with HIV by comparing rates from people with HIV in the HIV/AIDS Cancer Match Study, a population-based HIV and cancer registry linkage, to those in the general population. We used multivariable Poisson regression to estimate adjusted incidence rate ratios among people with HIV and linked the Texas HIV registry with medical claims data to estimate adjusted odds ratios (AORs) of HBV and HCV in hepatocellular carcinoma patients with logistic regression.
Results: Compared with the general population, hepatocellular carcinoma rates in people with HIV were elevated 2.79-fold (n = 1736; 95% confidence interval [CI] = 2.66 to 2.92). Hepatocellular carcinoma rates decreased statistically significantly from 2001-2004 to 2015-2019 (P < .001). Compared with men who have sex with men, hepatocellular carcinoma risk was elevated 4.28-fold among men who injected drugs (95% CI = 3.72 to 4.93) and 1.83-fold among women who injected drugs (95% CI = 1.49 to 2.26). In Texas, 146 hepatocellular carcinoma cases among people with HIV were linked to claims data: 25% HBV positive, 59% HCV positive, and 13% coinfected with HBV and HCV. Compared with men who had sex with men, people who inject drugs had 82% decreased odds of HBV (AOR = 0.18, 95% CI = 0.05 to 0.63) and 2 times the odds of HCV (AOR = 20.4, 95% CI = 3.32 to 125.3).
Conclusions: During 2001-2019, hepatocellular carcinoma risk declined among people with HIV, though rates remain statistically significantly elevated compared with the general population, particularly among people who inject drugs. Prevention and treatment of HBV/HCV are needed to reduce hepatocellular carcinoma risk among people with HIV.
Archer NP, et al. Factors associated with infant sex and preterm birth status for selected birth defects from the National Birth Defects Prevention Study, 1997-2011. Birth Defects Res. 2024 Jan;116(1):e2294. Epub 2023 Dec 28. doi:10.1002/bdr2.2294
Abstract
Background: Birth defects and preterm birth co-occur, with some overlapping risk factors. Many birth defects and preterm births tend to have a male preponderance. We explored potential risk factors impacting sex and preterm (<37 weeks of gestation) birth differences among infants with selected birth defects delivered from 1997 to 2011 using data from the National Birth Defects Prevention Study (NBDPS).
Methods: The NBDPS was a large multisite, population-based case-control study. Using random forests, we identified important predictors of male preterm, female preterm, and male term, each compared with female term births for each birth defect. Using logistic regression, we estimated odds ratios for associations between important predictors and sex-preterm birth status by birth defect.
Results: We examined 11,379 infants with nine specific birth defects. The top 10 most important predictors of sex-preterm birth status from the random forests varied greatly across the birth defects and sex-preterm comparisons within a given defect group, with several being novel factors. However, one consistency was that short interpregnancy interval was associated with sex-preterm birth status for many of the studied birth defects. Although obesity has been identified as a risk factor for preterm birth and birth defects in other research, it was not associated with sex-preterm birth status for any of the examined defects.
Conclusions: We confirmed expected associations for sex-preterm birth status differences and found new potential risk factors for further exploration among the studied birth defects.
Shumate C, Bojes H, Patel K, Canfield M, et al. Racial and ethnic differences in infant survival for hydrocephaly-Texas, 1999-2017. Birth Defects Res. 2024 Jan;116(1):e2285. Epub 2023 Dec 18. doi:10.1002/bdr2.2285
Abstract
Background: Congenital hydrocephaly, an abnormal accumulation of fluid within the ventricular spaces at birth, can cause disability or death if untreated. Limited information is available about survival of infants born with hydrocephaly in Texas. Therefore, the purpose of the study was to calculate survival estimates among infants born with hydrocephaly without spina bifida in Texas.
Methods: A cohort of live-born infants delivered during 1999-2017 with congenital hydrocephaly without spina bifida was identified from the Texas Birth Defects Registry. Deaths within 1 year of delivery were identified using vital and medical records. One-year infant survival estimates were generated for multiple descriptive characteristics using the Kaplan-Meier method. Crude hazard ratios (HRs) for one-year survival among infants with congenital hydrocephaly by maternal and infant characteristics and adjusted HRs for maternal race and ethnicity were estimated using Cox proportional hazard models.
Results: Among 5709 infants born with congenital hydrocephaly without spina bifida, 4681 (82%) survived the first year. The following characteristics were associated with infant survival: maternal race and ethnicity, clinical classification (e.g., chromosomal or syndromic), preterm birth, birth weight, birth year, and maternal education. In the multivariable Cox proportional hazards model, differences in survival were observed by maternal race and ethnicity after adjustment for other maternal and infant characteristics. Infants of non-Hispanic Black (HR: 1.28, 95% CI: 1.04-1.58) and Hispanic (HR: 1.31, 95% CI: 1.12-1.54) women had increased risk for mortality, compared with infants of non-Hispanic White women.
Conclusions: This study showed infant survival among a Texas cohort differed by maternal race and ethnicity, clinical classification, gestational age, birth weight, birth year, and maternal education in infants with congenital hydrocephaly without spina bifida. Findings confirm that mortality continues to be common among infants with hydrocephaly without spina bifida. Additional research is needed to identify other risk factors of mortality risk.
Monterosso A, et al. Survival by sex and HIV status in patients with anal cancer in the USA between 2001 and 2019: a retrospective cohort study. Lancet HIV. 2024 Jan;11(1):e31-e41. Epub 2023 Dec 8. doi:10.1016/S2352-3018(23)00257-6
Abstract
Background: The risk of anal cancer is increased among people with HIV, particularly men who have sex with men. Estimating survival by HIV status and sex and identifying groups at high risk is crucial for documenting prognostic differences between populations. We aimed to compare all-cause and anal cancer-specific survival in patients with anal cancer with and without HIV, stratified by sex, and to identify predictors of survival, stratified by HIV status.
Methods: In this retrospective cohort study, we used data from the HIV/AIDS Cancer Match Study of 13 population-based HIV and cancer registries throughout the USA. We included individuals aged 20-79 years diagnosed with invasive anal cancer between 2001 and 2019. To estimate associations between HIV status and both all-cause and anal cancer-specific mortality overall, we used Cox proportional hazards models, adjusting for year of and age at diagnosis, sex, race and ethnicity, histology, cancer stage, region, and treatment. We also calculated sex-specific adjusted hazard ratios (HRs). By HIV status, we identified characteristics associated with mortality. Models among people with HIV were further adjusted for AIDS status and HIV transmission risk group.
Findings: Between Jan 1, 2001, and Dec 31, 2019, 1161 (43·6%) of 2662 patients with anal cancer and HIV and 7722 (35·4%) of 21 824 patients without HIV died. HIV was associated with a 1·35 times (95% CI 1·24-1·47) increase in all-cause mortality among male patients and a 2·47 times (2·10-2·90) increase among female patients. Among patients with HIV, all-cause mortality was increased among non-Hispanic Black individuals (adjusted HR 1·19, 95% CI 1·04-1·38), people with AIDS (1·36, 1·10-1·68), people who inject drugs (PWID; 1·49, 1·17-1·90), patients with adenocarcinoma (2·74, 1·82-4·13), and those with no or unknown surgery treatment (1·34, 1·18-1·53). HIV was associated with anal cancer-specific mortality among female patients only (1·52, 1·18-1·97). Among patients with HIV, anal cancer-specific mortality was increased among patients with adenocarcinoma (3·29, 1·89-5·72), those with no or unknown treatment (1·59, 1·17-2·17), and PWID (1·60, 1·05-2·44).
Interpretation: HIV was associated with all-cause mortality among patients with anal cancer, especially women. Anal cancer-specific mortality was elevated among female patients with HIV. As screening for anal cancer becomes more widespread, examining the effects of screening on survival by HIV status and sex is crucial.
Funding: US National Cancer Institute Intramural Research Program.
Shumate CJ, Canfield MA, et al. Prevalence of congenital anomalies according to maternal race and ethnicity, Texas, 1999-2018. Birth Defects Res. 2024 Jan;116(1):e2274. Epub 2023 Nov 28. doi:10.1002/bdr2.2274
Abstract
Background: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.
Methods: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for maternal age, education, body mass index, and previous livebirths. We performed a two-stage analysis with a Bonferroni-adjusted p < 1.7 × 10-4 in the initial screening phase to identify anomalies with statistically significant variation.
Results: There were 7,698,768 livebirths and 1,187,385 anomalies diagnosed in 368,393 cases. The prevalence of any monitored congenital anomaly was similar among offspring of non-Hispanic White (referent), non-Hispanic Black (PR 0.98, CI 0.96-1.00), and Hispanic (PR 0.95, CI 0.93-0.96) women. We observed statistically significant racial/ethnic variation for 42 anomalies. Marked differences were observed when comparing offspring of non-Hispanic Black to non-Hispanic White women with respect to polydactyly (PR 4.38, CI 4.07-4.72), pyloric stenosis (PR 0.34, CI 0.29-0.40), and aortic valve atresia/stenosis (PR 0.51, CI 0.36-0.72).
Conclusions: Birth prevalence of many major congenital anomalies varies by maternal race and ethnicity. While the reasons for these differences are likely multifactorial, a thorough understanding of racial and ethnic disparities is useful to stimulate etiologic research.
Allred RP, Nguyen J, Agopian AJ, Canfield MA, Shumate CJ. An epidemiologic study of penoscrotal transposition by maternal characteristics using data from the Texas birth defects registry. Birth Defects Res. 2024 Jan;116(1):e2270. Epub 2023 Nov 6. doi:10.1002/bdr2.2270
Abstract
Background: Penoscrotal transposition (PST) is an uncommon urogenital malformation in which the penis is mal-positioned to be inferior to the scrotum. The purpose of this study was to explore PST risk by maternal characteristics and to describe co-occurring congenital abnormalities in the Texas Birth Defects Registry (TBDR).
Methods: We conducted a population-based descriptive study examining occurrence of PST in the TBDR between 1999 and 2019. The primary outcome variable was PST diagnosis during infancy. Descriptive variables included maternal age, education, and race/ethnicity. Prevalence ratios (PRs) were calculated within each maternal variable category using Poisson regression. Counts and percentages of cases with select co-occurring congenital abnormalities were also calculated.
Results: Overall, 251 infants had PST, providing a prevalence of 0.61/10,000 live male births (95% CI: 0.53-0.68). PST prevalence was significantly lower among infants of mothers who had lower educational attainment (<high school vs. >high school), who were younger (<25 vs. 25-34), and who were Hispanic (vs. non-Hispanic White) and was significantly higher among older mothers (35+ vs. 25-39). Hypospadias was the most common co-occurring genitourinary anomaly, affecting close to 70% of cases.
Conclusions: To our knowledge, this is the first investigation exploring the prevalence of PST in a population-based birth defects registry. Our findings help to understand the risk for PST among select maternal demographic characteristics and may assist in generating hypotheses about the underlying etiology of this condition for future work.
Langlois PH, et al. Outcomes up to age 36 months after congenital Zika virus infection-U.S. states. Pediatr Res. 2024 Jan;95(2):558-565. Epub 2023 Sep 1. doi:10.1038/s41390-023-02787-9
Abstract
Background: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure.
Methods: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively.
Results: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay.
Conclusion: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families.
Impact: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.
Bascom JT, Stephens SB, Lupo PJ, et al. Scientific impact of the National Birth Defects Prevention Network multistate collaborative publications. Birth Defects Res. 2024 Jan;116(1):e2225. Epub 2023 Jul 26. doi:10.1002/bdr2.2225
Abstract
Background: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact.
Methods: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated.
Results: NBDPN publications focused on prevalence estimates (N = 17), surveillance methods (N = 11), risk factor associations (N = 10), mortality and other outcomes among affected individuals (N = 6), and descriptive epidemiology of various birth defects (N = 5). The most cited publications were those that reported on prevalence estimates for a spectrum of defects and those that assessed changes in neural tube defects (NTD) prevalence following mandatory folic acid fortification in the United States.
Conclusions: Results from multistate NBDPN publications have provided critical information not available through other sources, including US prevalence estimates of major birth defects, folic acid fortification and NTD prevention, and improved understanding of defect trends and surveillance efforts. Until a national birth defects surveillance program is established in the United States, NBDPN collaborative publications remain an important resource for investigating birth defects and informing decisions related to health services planning of secondary disabilities prevention and care.
(In date order with the most recent first).
Archer NA, et al. Factors associated with infant sex and preterm birth status for selected birth defects from the National Birth Defects Prevention Study, 1997-2011. Birth Defects Res. Published online December 28, 2023. doi:10.1002/bdr2.2294
Abstract
Background: Birth defects and preterm birth co-occur, with some overlapping risk factors. Many birth defects and preterm births tend to have a male preponderance. We explored potential risk factors impacting sex and preterm (<37 weeks of gestation) birth differences among infants with selected birth defects delivered from 1997 to 2011 using data from the National Birth Defects Prevention Study (NBDPS).
Methods: The NBDPS was a large multisite, population-based case-control study. Using random forests, we identified important predictors of male preterm, female preterm, and male term, each compared with female term births for each birth defect. Using logistic regression, we estimated odds ratios for associations between important predictors and sex-preterm birth status by birth defect.
Results: We examined 11,379 infants with nine specific birth defects. The top 10 most important predictors of sex-preterm birth status from the random forests varied greatly across the birth defects and sex-preterm comparisons within a given defect group, with several being novel factors. However, one consistency was that short interpregnancy interval was associated with sex-preterm birth status for many of the studied birth defects. Although obesity has been identified as a risk factor for preterm birth and birth defects in other research, it was not associated with sex-preterm birth status for any of the examined defects.
Conclusions: We confirmed expected associations for sex-preterm birth status differences and found new potential risk factors for further exploration among the studied birth defects.
Garcia B, et al. A cluster investigation of Candida auris among hospitalized incarcerated patients. Antimicrob Steward Healthc Epidemiol. 2023 Dec 19;3(1):e244. doi:10.1017/ash.2023.520
Abstract
Objective: Investigate and mitigate a cluster of Candida auris cases among incarcerated patients in a maximum-security prison hospital utilizing contact tracing, screening, whole genome sequencing, and environmental sampling and decontamination.
Design: Outbreak investigation.
Setting: Inpatient prison hospital affiliated with an academic tertiary referral center.
Patients: Inmates of the Texas Department of Criminal Justice.
Methods: Epidemiologic and environmental investigations were conducted including contact tracing, point prevalence surveys, and environmental sampling. Whole genome sequencing was performed on positive patient isolates.
Results: Following a clinical case of C. auris fungemia, 344 patients underwent C. auris surveillance screening. Eight (2.3%) patients were identified with C. auris colonization. All patients were male. Our index patient was the only clinical case and death. Whole genome sequencing was performed on the nine patient isolates. All isolates were clade III (Africa) and clustered together with the largest SNP difference being 21. Environmental cultures from 7 of 61 rooms (11.5%) were positive following terminal disinfection with bleach. Sites nearest to the patient were most often positive including the hospital bed rails and bedside table. The transmission cluster was successfully mitigated within 60 days of identification.
Conclusions: Implementation of an aggressive surveillance and decontamination program resulted in mitigation of a C. auris transmission cluster among our incarcerated patients. This investigation provides valuable insight into C. auris transmission in the incarcerated population, which is not considered a classic high-risk population as well as the challenges faced to stop transmission in a facility that requires the use of shared patient environments.
Shumate C, Bojes H, Canfield M, et al. Racial and ethnic differences in infant survival for hydrocephaly-Texas, 1999-2017. Birth Defects Res. Published online December 18, 2023. doi:10.1002/bdr2.2285
Abstract
Background: Congenital hydrocephaly, an abnormal accumulation of fluid within the ventricular spaces at birth, can cause disability or death if untreated. Limited information is available about survival of infants born with hydrocephaly in Texas. Therefore, the purpose of the study was to calculate survival estimates among infants born with hydrocephaly without spina bifida in Texas.
Methods: A cohort of live-born infants delivered during 1999-2017 with congenital hydrocephaly without spina bifida was identified from the Texas Birth Defects Registry. Deaths within 1 year of delivery were identified using vital and medical records. One-year infant survival estimates were generated for multiple descriptive characteristics using the Kaplan-Meier method. Crude hazard ratios (HRs) for one-year survival among infants with congenital hydrocephaly by maternal and infant characteristics and adjusted HRs for maternal race and ethnicity were estimated using Cox proportional hazard models.
Results: Among 5709 infants born with congenital hydrocephaly without spina bifida, 4681 (82%) survived the first year. The following characteristics were associated with infant survival: maternal race and ethnicity, clinical classification (e.g., chromosomal or syndromic), preterm birth, birth weight, birth year, and maternal education. In the multivariable Cox proportional hazards model, differences in survival were observed by maternal race and ethnicity after adjustment for other maternal and infant characteristics. Infants of non-Hispanic Black (HR: 1.28, 95% CI: 1.04-1.58) and Hispanic (HR: 1.31, 95% CI: 1.12-1.54) women had increased risk for mortality, compared with infants of non-Hispanic White women.
Conclusions: This study showed infant survival among a Texas cohort differed by maternal race and ethnicity, clinical classification, gestational age, birth weight, birth year, and maternal education in infants with congenital hydrocephaly without spina bifida. Findings confirm that mortality continues to be common among infants with hydrocephaly without spina bifida. Additional research is needed to identify other risk factors of mortality risk.
Nyachoti DO, et al. Fwelo P, Springer AE, Kelder SH. Association between Gross National Income per capita and COVID-19 vaccination coverage: a global ecological study. BMC Public Health. 2023 Dec 4;23(1):2415. doi:10.1186/s12889-023-17241-y
Abstract
Background: Coronavirus 2019 (COVID-19) pandemic has claimed over six million lives and infected more than 650 million people globally. Public health agencies have deployed several strategies, including rolling out vaccination campaigns to curb the pandemic, yet a significant proportion of the global population has not received the COVID-19 vaccine. We assessed differences in COVID-19 vaccination coverage by Gross National Income (GNI) per capita of WHO members (i.e., countries, areas, and territories, n = 192) and by WHO member regions (n = 6).
Methods: Using an ecological study design, we analyzed publicly available data from the WHO website merged with the World Bank's GNI per capita data. We included a total of 192 WHO members and six WHO regions in the analysis. We utilized negative binomial regression to assess the associations between the GNI per capita and COVID-19 vaccination coverage (cumulative number of persons fully vaccinated and/or received at least one dose of the vaccine per 100 population), and ANOVA test to assess the differences in vaccination coverage per WHO regions.
Results: Low GNI per capita WHO members had significantly lower full vaccination coverage (aRR 0.30, 95% CI 0.22-0.40) compared to high GNI per capita WHO members. These members were also 66% less likely to receive at least one dose of the vaccine (aRR 0.34, 0.26-0.44) relative to high GNI per capita WHO members. Africa region had a significantly lower fully vaccination coverage (aRR 0.71, 95% CI 0.36-0.54) and received at least one dose of the COVID-19 vaccine (aRR 0.78, 95% CI 0.62-0.99) than Europe region. Conversely, the Western Pacific region had significantly higher fully vaccination coverage (aRR 1.40 95% CI 1.12-1.74) and received at least one dose of COVID-19 vaccines (aRR 1.40 95% CI 1.14-1.73) relative to European region.
Conclusion: WHO members with low GNI per capita and the African region reported significantly lower COVID-19 vaccination coverage than those with high GNI per capita or other regions. Efforts to strengthen and promote COVID-19 vaccination in low-income WHO countries and African region should be scaled up.
Shuford JA, Pont SJ, et al. RE: Incidence of SARS-CoV-2 breakthrough infections after vaccination in adults: a population-based survey through 1 March 2023. Open Forum Infect Dis. 2023 Nov 29;10(12):ofad564. doi:10.1093/ofid/ofad564
Abstract
Dear Editor,
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic unfolds and new variants emerge, updating estimates of breakthrough infection after primary series vaccination is essential. This letter updates the previous report on the incidence of breakthrough infections through July 1, 2022, across 5 pandemic waves in Texas.
Morrison A, et al. Multistate outbreak of turtle-associated salmonellosis highlights ongoing challenges with the illegal sale and distribution of small turtles. Zoonoses Public Health. 2023 Dec;70(8):684-691. Epub 2023 Sep 29. doi:10.1111/zph.13080
Abstract
The sale and distribution of small turtles (shell length <4 inches) as pets has been banned in the United States since 1975 because of the risk of Salmonella transmission, especially to children. Despite this 48-year-old ban, salmonellosis outbreaks continue to be linked to contact with small turtles. During investigations of turtle-associated outbreaks, information regarding the turtle farm of origin is difficult to obtain because turtles are commonly sold by transient vendors. During 2020-2021, public health officials investigated a multistate illness outbreak caused by Salmonella enterica serotype Typhimurium linked to pet small turtles. Cases were defined as a laboratory-confirmed Salmonella Typhimurium infection highly related (within 0-6 allele differences) to the outbreak strain based on whole-genome sequencing analysis by core-genome multilocus sequence typing with illness onset occurring during 27 August 2020-14 May 2021. Forty-three patients were identified from 12 states; of these, 35% (15/43) were children <5 years old. Among patients with available information, 37% (14/38) were hospitalized, and one death was reported. Seventy-four percent (25/34) of patients reported turtle exposure in the week before illness onset, and 84% (16/19) specified exposure to small turtles. The outbreak strain was isolated from samples collected from a Pennsylvania patient's small turtle tank. Two patients reported purchasing their small turtles from pet stores. Salmonella Braenderup was isolated from samples collected from small turtles and their habitat at one of these stores; however, at that time, this strain was not associated with any human illnesses. This investigation was notable because of the documented sale of small turtles from several pet stores combined with the identification of a single small turtle supplier to these pet stores. The high proportion of children involved in this outbreak highlights the continued need to educate the pet industry as well as parents and caregivers about the risk of turtle-associated salmonellosis especially in children. Understanding and addressing the persisting challenges related to the illegal sale and distribution of small turtles could reduce the burden of turtle-associated salmonellosis.
Shumate CJ, Canfield MA, et al. Prevalence of congenital anomalies according to maternal race and ethnicity, Texas, 1999-2018. Birth Defects Res. Published online November 28, 2023. doi:10.1002/bdr2.2274
Abstract
Background: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.
Methods: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for maternal age, education, body mass index, and previous livebirths. We performed a two-stage analysis with a Bonferroni-adjusted p < 1.7 × 10-4 in the initial screening phase to identify anomalies with statistically significant variation.
Results: There were 7,698,768 livebirths and 1,187,385 anomalies diagnosed in 368,393 cases. The prevalence of any monitored congenital anomaly was similar among offspring of non-Hispanic White (referent), non-Hispanic Black (PR 0.98, CI 0.96-1.00), and Hispanic (PR 0.95, CI 0.93-0.96) women. We observed statistically significant racial/ethnic variation for 42 anomalies. Marked differences were observed when comparing offspring of non-Hispanic Black to non-Hispanic White women with respect to polydactyly (PR 4.38, CI 4.07-4.72), pyloric stenosis (PR 0.34, CI 0.29-0.40), and aortic valve atresia/stenosis (PR 0.51, CI 0.36-0.72).
Conclusions: Birth prevalence of many major congenital anomalies varies by maternal race and ethnicity. While the reasons for these differences are likely multifactorial, a thorough understanding of racial and ethnic disparities is useful to stimulate etiologic research.
Canfield MA, Shumate CJ, et al. Associations between birth defects with neural crest cell origins and pediatric embryonal tumors. Cancer. 2023 Nov 15;129(22):3595-3602. Epub 2023 Jul 11. doi:10.1002/cncr.34952
Background: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.
Methods: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education.
Results: The risk of embryonal tumors among those with BDNCOs was 0.09% (co-occurring n = 105) compared to 0.03% (95% CI, 0.03%-0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5-5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3-22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3-4.2) and nephroblastoma (2.9; 95% CI, 1.9-4.4) were elevated. There was no notable HRM by the aforementioned factors.
Conclusions: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.
Canfield MA, Shumate CJ, et al. An epidemiologic study of penoscrotal transposition by maternal characteristics using data from the Texas birth defects registry. Birth Defects Res. Published online November 6, 2023. doi:10.1002/bdr2.2270
Abstract
Background: Penoscrotal transposition (PST) is an uncommon urogenital malformation in which the penis is mal-positioned to be inferior to the scrotum. The purpose of this study was to explore PST risk by maternal characteristics and to describe co-occurring congenital abnormalities in the Texas Birth Defects Registry (TBDR).
Methods: We conducted a population-based descriptive study examining occurrence of PST in the TBDR between 1999 and 2019. The primary outcome variable was PST diagnosis during infancy. Descriptive variables included maternal age, education, and race/ethnicity. Prevalence ratios (PRs) were calculated within each maternal variable category using Poisson regression. Counts and percentages of cases with select co-occurring congenital abnormalities were also calculated.
Results: Overall, 251 infants had PST, providing a prevalence of 0.61/10,000 live male births (95% CI: 0.53-0.68). PST prevalence was significantly lower among infants of mothers who had lower educational attainment (<high school vs. >high school), who were younger (<25 vs. 25-34), and who were Hispanic (vs. non-Hispanic White) and was significantly higher among older mothers (35+ vs. 25-39). Hypospadias was the most common co-occurring genitourinary anomaly, affecting close to 70% of cases.
Conclusions: To our knowledge, this is the first investigation exploring the prevalence of PST in a population-based birth defects registry. Our findings help to understand the risk for PST among select maternal demographic characteristics and may assist in generating hypotheses about the underlying etiology of this condition for future work.
Canfield MA, Shumate CJ, et al. Survival of neonates, infants, and children with birth defects: a population-based study in Texas, 1999-2018. Lancet Reg Health Am. 2023 Oct 18:27:100617. doi:10.1016/j.lana.2023.100617
Abstract
Background: Birth defects are a leading cause of neonatal, infant, and childhood mortality, but recent population-based survival estimates for a spectrum in the U.S. are lacking.
Methods: Using the statewide Texas Birth Defects Registry (1999-2017 births) and vital records linkage to ascertain deaths, we conducted Kaplan-Meier analyses to estimate survival probabilities at 1, 7, and 28 days, and 1, 5, and 10 years. We evaluated survival in the full cohort of infants with any major defect and for 30 specific conditions. One-year survival analyses were stratified by gestational age, birth year, and case classification.
Findings: Among 246,394 live-born infants with any major defect, the estimated survival probabilities were 98.9% at 1 day, 95.0% at 1 year, and 93.9% at 10 years. Ten-year survival varied by condition, ranging from 36.9% for holoprosencephaly to 99.3% for pyloric stenosis. One-year survival was associated with increasing gestational age (e.g., increasing from 46.9% at <28 weeks to 95.8% at ≥37 weeks for spina bifida). One-year survival increased in more recent birth years for several defect categories (e.g., increasing from 86.0% among 1999-2004 births to 93.1% among 2014-2017 births for unilateral renal agenesis/dysgenesis) and was higher among infants with an isolated defect versus those with multiple defects.
Interpretation: This study describes short- and long-term survival outcomes from one of the largest population-based birth defect registries in the world and highlights improved survival over time for several conditions. Our results may lend insight into future healthcare initiatives aimed at reducing mortality in this population.
Funding: This study was funded in part by a Centers for Disease Control and Prevention (CDC) birth defects surveillance cooperative agreement with the Texas Department of State Health Services and Health Resources and Services Administration (HRSA) Block Grant funds.
Shumate CJ, et al. Neighborhood deprivation and neural tube defects. Epidemiology. 2023 Nov 1;34(6):774-785. 2023 Nov 1;34(6):774-785. doi:10.1097/EDE.0000000000001655
Abstract
Background: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk.
Methods: The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery.
Results: Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity.
Conclusions: Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida.
Nyachoti DO, et al. Association of social vulnerability and COVID-19 mortality rates in Texas between 15 March 2020, and 21 July 2022: an ecological analysis. Int J Environ Res Public Health. 2023 Oct 27;20(21):6985. doi:10.3390/ijerph20216985
Abstract
Background: Despite the key role of social vulnerability such as economic disadvantage in health outcomes, research is limited on the impact of social vulnerabilities on COVID-19-related deaths, especially at the state and county level in the USA.
Methods: We conducted a cross-sectional ecologic analysis of COVID-19 mortality by the county-level Minority Health Social Vulnerability Index (MH SVI) and each of its components in Texas. Negative binomial regression (NBR) analyses were used to estimate the association between the composite MH SVI (and its components) and COVID-19 mortality.
Results: A 0.1-unit increase in the overall MH SVI (IRR, 1.27; 95% CI, 1.04-1.55; p = 0.017) was associated with a 27% increase in the COVID-19 mortality rate. Among the MH SVI component measures, only low socioeconomic status (IRR, 1.55; 95% CI, 1.28-1.89; p = 0.001) and higher household composition (e.g., proportion of older population per county) and disability scores (IRR, 1.47; 95% CI, 1.29-1.68; p < 0.001) were positively associated with COVID-19 mortality rates.
Conclusions: This study provides further evidence of disparities in COVID-19 mortality by social vulnerability and can inform decisions on the allocation of social resources and services as a strategy for reducing COVID-19 mortality rates and similar pandemics in the future.
Monterosso A, Miller P, et al. Real-world use of antiretroviral therapy and risk of cancer among people living with HIV in Texas. AIDS. Published online October 27, 2023. doi:10.1097/QAD.0000000000003770
Abstract
Background: Combination antiretroviral therapy (cART) may reduce cancer risk among people living with HIV (PLWH), but cancer-specific associations are incompletely understood.
Methods: We linked HIV and cancer registries in Texas to a national prescription claims database. cART use was quantified as the proportion of days covered (PDC). Cox proportional hazards models assessed associations of cancer risk with cART usage, adjusting for demographic characteristics, AIDS status, and time since HIV report.
Results: We evaluated 63,694 PLWH followed for 276,804 person-years. The median cART PDC was 21.4% (interquartile range: 0.0%-59.8%). cART use was associated with reduced risk of Kaposi sarcoma (adjusted hazard ratio [aHR] 0.48, 95%CI 0.34-0.68 relative to unexposed status) and non-Hodgkin lymphoma (0.41, 0.31-0.53), liver cancer (0.61, 0.39-0.96), anal cancer (0.65, 0.46-0.92), and a miscellaneous group of "other" cancers (0.80, 0.66-0.98). In contrast, cART-exposed status was not associated with risk for cervical, lung, colorectal, prostate or breast cancers.
Conclusion: In a large HIV cohort incorporating data from prescription claims, cART was associated with greatly reduced risks of Kaposi sarcoma and non-Hodgkin lymphoma, and to a lesser degree, reduced risks of liver and anal cancers. These associations likely reflect the beneficial effects of HIV suppression and improved immune control of oncogenic viruses. Efforts to increase cART use and adherence may further decrease cancer incidence among PLWH.
Shuford JA, Pont SJ, et al. Long-term immune response to SARS-CoV-2 infection and vaccination in children and adolescents. Pediatr Res. Published online October 24, 2023. doi:10.1038/s41390-023-02857-y
Abstract
Background: This analysis examined the durability of antibodies present after SARS-CoV-2 infection and vaccination in children and adolescents.
Methods: Data were collected over 4 time points between October 2020-November 2022 as part of a prospective population-based cohort aged 5-to-19 years (N = 810). Results of the (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test); and (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test); and (3) self-reported antigen/PCR COVID-19 test results, vaccination and symptom status were analyzed.
Results: N antibody levels reached a median of 84.10 U/ml (IQR: 20.2, 157.7) cutoff index (COI) ~ 6 months post-infection and increased slightly to a median of 85.25 (IQR: 28.0, 143.0) COI at 12 months post-infection. Peak S antibody levels were reached at a median of 2500 U/mL ~6 months post-vaccination and remained for ~12 months (mean 11.6 months, SD 1.20).
Conclusions: This analysis provides evidence of robust durability of nucleocapsid and spike antibodies in a large pediatric sample up to 12 months post-infection/vaccination. This information can inform pediatric SARS-CoV-2 vaccination schedules.
Impact: This study provided evidence of robust durability of both nucleocapsid and spike antibodies in a large pediatric sample up to 12 months after infection. Little is known about the long-term durability of natural and vaccine-induced SARS-CoV-2 antibodies in the pediatric population. Here, we determined the durability of anti-SARS-CoV-2 spike (S-test) and nucleocapsid protein (N-test) in children/adolescents after SARS-CoV-2 infection and/or vaccination lasts at least up to 12 months. This information can inform future SARS-CoV-2 vaccination schedules in this age group.
Huebner EM, Peter B, et al. Preventable deaths during widespread community hepatitis A outbreaks - United States, 2016-2022. MMWR Morb Mortal Wkly Rep. 2023 Oct 20;72(42):1128-1133. doi:10.15585/mmwr.mm7242a1
Abstract
Hepatitis A is acquired through the fecal-oral route and is preventable by a safe and effective vaccine. Although hepatitis A is generally mild and self-limited, serious complications, including death, can occur. Since 2016, widespread hepatitis A outbreaks have been reported in 37 U.S. states, primarily among persons who use drugs and those experiencing homelessness. Nearly twice as many hepatitis A-related deaths were reported during 2016-2022 compared with 2009-2015. CDC analyzed data from 27 hepatitis A outbreak-affected states* that contributed data during August 1, 2016-October 31, 2022, to characterize demographic, risk factor, clinical, and cause-of-death data among 315 outbreak-related hepatitis A deaths from those states. Hepatitis A was documented as an underlying or contributing cause of death on 60% of available death certificates. Outbreak-related deaths peaked in 2019, and then decreased annually through 2022. The median age at death was 55 years; most deaths occurred among males (73%) and non-Hispanic White persons (84%). Nearly two thirds (63%) of decedents had at least one documented indication for hepatitis A vaccination, including drug use (41%), homelessness (16%), or coinfection with hepatitis B (12%) or hepatitis C (31%); only 12 (4%) had evidence of previous hepatitis A vaccination. Increasing vaccination coverage among adults at increased risk for infection with hepatitis A virus or for severe disease from infection is critical to preventing future hepatitis A-related deaths.
Bojes HK, et al. Influence of storage conditions and multiple freeze-thaw cycles on N1 SARS-CoV-2, PMMoV, and BCoV signal. Sci Total Environ. 2023 Oct 20:896:165098. Epub 2023 Jun 29. doi:10.1016/j.scitotenv.2023.165098
Abstract
Wastewater-based epidemiology/wastewater-based surveillance (WBE/WBS) continues to serve as an effective means of monitoring various diseases, including COVID-19 and the emergence of SARS-CoV-2 variants, at the population level. As the use of WBE expands, storage conditions of wastewater samples will play a critical role in ensuring the accuracy and reproducibility of results. In this study, the impacts of water concentration buffer (WCB), storage temperature, and freeze-thaw cycles on the detection of SARS-CoV-2 and other WBE-related gene targets were examined. Freeze-thawing of concentrated samples did not significantly affect (p > 0.05) crossing/cycle threshold (Ct) value for any of the gene targets studied (SARS-CoV-2 N1, PMMoV, and BCoV). However, use of WCB during concentration resulted in a significant (p < 0.05) decrease in Ct for all targets, and storage at -80 °C (in contrast to -20 °C) appeared preferable for wastewater storage signal stability based on decreased Ct values, although this was only significantly different (p < 0.05) for the BCoV target. Interestingly, when Ct values were converted to gene copies per influent sample, no significant differences (p > 0.05) were observed in any of the targets examined. Stability of RNA targets in concentrated wastewater against freeze-thaw degradation supports archiving of concentrated samples for use in retrospective examination of COVID-19 trends and tracing SARS-CoV-2 variants and potentially other viruses, and provides a starting point for establishing a consistent procedure for specimen collection and storage for the WBE/WBS community.
Canfield MA, Langlois PH, et al. Associations between birth defects and childhood and adolescent germ cell tumors according to sex, histologic subtype, and site. Cancer. 2023 Oct 15;129(20):3300-3308. Epub 2023 Jun 27. doi:10.1002/cncr.34906
Abstract
Background: Studies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics.
Methods: Birth defect-GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population-based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. The odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status were estimated by using unconditional logistic regression. All defects were considered collectively and by genetic and chromosomal syndromes and nonsyndromic defects. Stratification was by sex, tumor histology (yolk sac tumor, teratoma, germinoma, and mixed/other), and location (gonadal, extragonadal, and intracranial).
Results: Birth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0% and 2.7% vs. 0.2%, respectively; both p < .001). In multivariable models, GCT risk was increased among children with birth defects (OR, 1.7; 95% CI, 1.3-2.4) and syndromic defects (OR, 10.4; 95% CI, 4.9-22.1). When stratified by tumor characteristics, birth defects were associated with yolk sac tumors (OR, 2.7; 95% CI, 1.3-5.0) and mixed/other histologies (OR, 2.1; 95% CI, 1.2-3.5) and both gonadal tumors (OR, 1.7; 95% CI, 1.0-2.7) and extragonadal tumors (OR, 3.8; 95% CI, 2.1-6.5). Nonsyndromic defects specifically were not associated with GCTs. In sex-stratified analyses, associations were observed among males but not females.
Conclusions: These data suggest that males with syndromic birth defects are at an increased risk of pediatric GCTs, whereas males with nonsyndromic defects and females are not at an increased risk.
Shumate C, Canfield MA, et al. Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: a population-based assessment in seven million children. Cancer. Published online October 3, 2023. doi:10.1002/cncr.35041
Abstract
Background: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study.
Methods: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age.
Results: In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70).
Conclusions: This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.
Patel M, et al. Texas tobacco quitline knowledge, attitudes, and practices within healthcare agencies serving individuals with behavioral health needs: A multimethod study. Prev Med Rep. 2023 May 24:35:102256. doi:10.1016/j.pmedr.2023.102256
Abstract
Patients with behavioral health conditions have disproportionately high tobacco use rates and face significant barriers to accessing evidence-based tobacco cessation services. Tobacco quitlines are an effective and accessible resource, yet they are often underutilized. We identify knowledge, practices, and attitudes towards the Texas Tobacco Quitline (TTQL) within behavioral healthcare settings in Texas. Quantitative and qualitative data were collected in 2021 as part of a statewide needs assessment in behavioral healthcare settings. Survey respondents (n = 125) represented 23 Federally Qualified Health Centers, 29 local mental health authorities (LMHAs), 12 substance use treatment programs in LMHAs, and 61 standalone substance use treatment centers (26 people participated in qualitative interviews). Over half of respondents indicated familiarity with the TTQL and believed that the TTQL was helpful for quitting. Qualitative findings reveal potential concerns about inconsistency of services, long wait time, and the format of the quitline. About half of respondents indicated that their center promoted patient referral to TTQL, and few indicated that their center had an electronic referral system with direct TTQL referral capacity. Interview respondents reported overall lack of systematic follow up with patients regarding their use of the TTQL services. Findings suggest the need for (1) increased TTQL service awareness among healthcare providers; (2) further investigation into any changes needed to better serve patients with behavioral health conditions who use tobacco; and (3) electronic health record integration supporting direct referrals and enhanced protocols to support patient follow up after TTQL referral.
Canfield MA, et al. Prediction of preterm birth among infants with orofacial cleft defects. Cleft Palate Craniofac J. Published online September 6, 2023. doi:10.1177/10556656231198945
Abstract
Objective: To develop risk prediction models for preterm birth among infants with orofacial clefts.
Design: Data from the Texas Birth Defects Registry for infants with orofacial clefts born between 1999-2014 were used to develop preterm birth predictive models. Logistic regression was used to consider maternal and infant characteristics, and internal validation of the final model was performed using bootstrapping methods. The area under the curve (AUC) statistic was generated to assess model performance, and separate predictive models were built and validated for infants with cleft lip and cleft palate alone. Several secondary analyses were conducted among subgroups of interest.
Setting: State-wide, population-based Registry data.
Patients/participants: 6774 infants with orofacial clefts born in Texas between 1999-2014.
Main outcome measure(s): Preterm birth among infants with orofacial clefts.
Results: The final predictive model performed modestly, with an optimism-corrected AUC of 0.67 among all infants with orofacial clefts. The optimism-corrected models for cleft lip (with or without cleft palate) and cleft palate alone had similar predictive capability, with AUCs of 0.66 and 0.67, respectively. Secondary analyses had similar results, but the model among infants with delivery prior to 32 weeks demonstrated higher optimism-corrected predictive capability (AUC = 0.74).
Conclusions: This study provides a first step towards predicting preterm birth risk among infants with orofacial clefts. Identifying pregnancies affected by orofacial clefts at the highest risk for preterm birth may lead to new avenues for improving outcomes among these infants.
Langlois PH, et al. Outcomes up to age 36 months after congenital Zika virus infection-U.S. states. Pediatr Res. Published online September 1, 2023. doi:10.1038/s41390-023-02787-9
Abstract
Background: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure.
Methods: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively.
Results: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay.
Conclusion: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families.
Impact: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.
Jibowu M, Driesse K, May S, Wright A, Swate T, Cotter C. Notes from the field: outbreak of norovirus illness caused by consumption of oysters harvested from Galveston Bay, Texas - November-December 2022. MMWR Morb Mortal Wkly Rep. 2023 Sep 1;72(35):968-969. doi:10.15585/mmwr.mm7235a5
Abstract
On December 7, 2022, the Texas Department of State Health Services (DSHS) Public Health Region 6/5 South (PHR 6/5S) and DSHS Consumer Protection Division were notified by Galveston County Health District of 10 consumer complaints of illness after consumption of raw (nine complaints) and smoked (one) oysters at local restaurants during November 27–December 4. Signs and symptoms began within 8 hours after consumption and included diarrhea, nausea, or vomiting. Initially, no consumers sought medical care. Oyster tags from three associated restaurant inspections determined that oysters were from Oyster Harvest Area TX 1 (TX 1) in Galveston Bay, Texas.
Shumate C, et al. Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors?. Birth Defects Res. 2023 Sep 1;115(15):1438-1449. Epub 2023 Jul 13. doi:10.1002/bdr2.2224
Abstract
Background: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations.
Methods: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction.
Results: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3).
Conclusion: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors.
Babalola F, et al. Evaluation of bronchiolitis in the pediatric population in the United States of America and Canada: a ten-year review. Cureus. 2023 Aug 12;15(8):e43393. doi:10.7759/cureus.43393
Abstract
Bronchiolitis is a well-known viral infection among the pediatric population, significantly impacting hospitalization rates. The COVID-19 pandemic profoundly affected respiratory viral infections, including bronchiolitis, as various mitigation measures were implemented. In this study, we analyzed bronchiolitis cases during the pandemic and post-pandemic period, aiming to identify changes in management guidelines and their incidence and management over the last 10 years. Moreover, we explored the relationship between bronchiolitis and COVID-19, a virus that gained rapid notoriety worldwide. By analyzing data from pediatric populations in Canada and the USA, we sought to understand the role of varying seasons in the peak periods of bronchiolitis infections. The comprehensive review's results will provide valuable insights into bronchiolitis dynamics within the context of the COVID-19 pandemic. Our aim is to better comprehend the interplay between bronchiolitis, COVID-19, and seasonal variations, ultimately contributing to a deeper understanding of this respiratory viral infection and informing future management strategies. Furthermore, these findings can assist healthcare professionals in preparing for and responding to potential fluctuations in bronchiolitis cases in the post-pandemic era.
Tanksley S, et al. Evidence and recommendation for guanidinoacetate methyltransferase deficiency newborn screening. Pediatrics. 2023 Aug 1;152(2):e2023062100. doi:10.1542/peds.2023-062100
Abstract
Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine biosynthesis due to pathogenic variants in the GAMT gene that lead to cerebral creatine deficiency and neurotoxic levels of guanidinoacetate. Untreated, GAMT deficiency is associated with hypotonia, significant intellectual disability, limited speech development, recurrent seizures, behavior problems, and involuntary movements. The birth prevalence of GAMT deficiency is likely between 0.5 and 2 per million live births. On the basis of small case series and sibling data, presymptomatic treatment with oral supplements of creatine, ornithine, and sodium benzoate, and a protein-restricted diet to reduce arginine intake, appear to substantially improve health and developmental outcomes. Without newborn screening, diagnosis typically happens after the development of significant impairment, when treatment has limited utility. GAMT deficiency newborn screening can be incorporated into the tandem-mass spectrometry screening that is already routinely used for newborn screening, with about 1 per 100,000 newborns screening positive. After a positive screen, diagnosis is established by finding an elevated guanidinoacetate concentration and low creatine concentration in the blood. Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. This recommendation was accepted in January 2023.
Das T, et al. National Association of Medical Examiners Position paper: recommendations for the documentation and certification of disaster-related deaths. Am J Forensic Med Pathol. 2023;10.1097/PAF.0000000000000859. Epub 2023 Jul 31. doi:10.1097/PAF.0000000000000859
Abstract
Collecting and reporting accurate disaster mortality data are critical to informing disaster response and recovery efforts. The National Association of Medical Examiners convened an ad hoc committee to provide recommendations for the documentation and certification of disaster-related deaths. This article provides definitions for disasters and direct, indirect, and partially attributable disaster-related deaths; discusses jurisdiction for disaster-related deaths; offers recommendations for medical examiners/coroners (ME/Cs) for indicating the involvement of the disaster on the death certificate; discusses the role of the ME/C and non-ME/C in documenting and certifying disaster-related deaths; identifies existing systems for helping to identify the role of disaster on the death certificate; and describes disaster-related deaths that may require amendments of death certificates. The recommendations provided in this article seek to increase ME/C's understanding of disaster-related deaths and promote uniformity in how to document these deaths on the death certificate.
Langlois PH, Canfield MA, et al. Epidemiology of nonsyndromic, orofacial clefts in Texas: differences by cleft type and presence of additional defects. Cleft Palate Craniofac J. 2023 Jul;60(7):789-803. Epub 2022 Feb 28. doi:10.1177/10556656221080932
Abstract
To describe the current epidemiology of nonsyndromic cleft palate alone (CP) and cleft lip with or without cleft palate (CL ± P) in Texas and examine differences in the characteristics of infants with CP and CL ± P based on the presence/absence of additional defects.
We used data from the Texas Birth Defects Registry, a statewide active birth defect surveillance system, from 1815 cases with CP and 5066 with CL ± P, without a syndrome diagnosis (1999-2014 deliveries). All live births in Texas were used for comparison. Poisson regression was used to calculate crude and adjusted prevalence ratios (aPR) for each characteristic, separately for each cleft subphenotype.
The prevalence of CL ± P and CP in our study was estimated as 8.3 and 3.0 per 10 000 live births, respectively. After adjusting for several characteristics, several factors were associated with CL ± P, CP, or both, including infant sex and maternal race/ethnicity, age, smoking, and diabetes. There were several differences between infants with isolated versus nonisolated clefts. For example, maternal prepregnancy diabetes was associated with an increased prevalence of CL ± P (aPR 7.91, 95% confidence interval [CI]: 5.53, 11.30) and CP (aPR 3.24, 95% CI: 1.43, 7.36), but only when additional defects were present.
Findings from this study provide a contemporary description of the distribution of orofacial clefts in Texas accounting for differences between isolated and nonisolated clefts. They may contribute to increasing our understanding of the etiology of CP and CL ± P.
Canfield MA, et al. Scientific impact of the National Birth Defects Prevention Network multistate collaborative publications. Birth Defects Res. 2023;10.1002/bdr2.2225. Epub 2023 Jul 26. doi:10.1002/bdr2.2225
Abstract
Background: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact.
Methods: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated
Results: NBDPN publications focused on prevalence estimates (N = 17), surveillance methods (N = 11), risk factor associations (N = 10), mortality and other outcomes among affected individuals (N = 6), and descriptive epidemiology of various birth defects (N = 5). The most cited publications were those that reported on prevalence estimates for a spectrum of defects and those that assessed changes in neural tube defects (NTD) prevalence following mandatory folic acid fortification in the United States.
Conclusions: Results from multistate NBDPN publications have provided critical information not available through other sources, including US prevalence estimates of major birth defects, folic acid fortification and NTD prevention, and improved understanding of defect trends and surveillance efforts. Until a national birth defects surveillance program is established in the United States, NBDPN collaborative publications remain an important resource for investigating birth defects and informing decisions related to health services planning of secondary disabilities prevention and care.
Shumate CJ, et al. Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors? Birth Defects Res. 2023;10.1002/bdr2.2224. Epub 2023 Jul 13. doi:10.1002/bdr2.2224
Abstract
Background: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations
Methods: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction.
Results: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3).
Conclusion: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors.
Shumate CJ, et al. Sunspot activity and birth defects among Texas births (1999-2016). Birth Defects Res. 2023 Jul 1;115(12):1120-1139. Epub 2023 May 30. doi:10.1002/bdr2.2206
Abstract
Background: Building on findings that linked higher levels of sunspot (SS) activity with a range of health and adverse birth outcomes, we sought to understand how SS activity over a 17-year time period may be correlated with the occurrence of birth defects.
Methods: Data from the Texas Birth Defects Registry, vital events from the Texas Center for Health Statistics, and mean monthly numbers of sunspots from the National Oceanic and Atmospheric Administration were utilized. Poisson regression was used to calculate crude/adjusted prevalence ratios (cPRs/aPRs) and 95% confidence intervals for three quartiles (Q) of increasing SS activity (compared to a referent of low activity) and 44 birth defects (31 non-cardiac; 13 cardiac) with estimated dates of conception from 1998 to 2016.
Results: We found moderately protective aPRs (range: 0.60-0.89) in a little over half of the case groups examined in our quartiles of higher SS activity (19 non-cardiac; 6 cardiac), after adjusting for maternal age, race/ethnicity, and education. Particularly protective aPRs in the highest SS quartiles (Q3-4) were noted for: anophthalmia, cataract, gastroschisis, trisomy 18, ventricular septal defects, atrial septal defects, and pulmonary valve atresia or stenosis. Conversely, modestly elevated aPRs were noted for two defect groups (agenesis, aplasia, and hypoplasia of the lung and microcephaly [Q2-3]). Following an additional adjustment of year of conception, results remained similar although many of the estimates were attenuated.
Conclusion: The seemingly protective associations between increasing SS activity may be an artifact of increasing spontaneous abortions that occur following conception during these periods of heightened SS activity.
Shumate CJ, et al. Neighborhood-level socioeconomic position during early pregnancy and risk of gastroschisis. Epidemiology. 2023 Jul 1;34(4):576-588. Epub 2023 May 30. doi:10.1097/EDE.0000000000001621
Abstract
Background: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the understudied association between neighborhood-level socioeconomic position during early pregnancy and the risk of gastroschisis, an abdominal birth defect of increasing prevalence.
Methods: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997-2011). To characterize neighborhood-level socioeconomic position, we conducted a principal component analysis to construct two indices-Neighborhood Deprivation Index (NDI) and Neighborhood Socioeconomic Position Index (nSEPI). We created neighborhood-level indices using census socioeconomic indicators corresponding to census tracts associated with addresses where mothers lived the longest during the periconceptional period. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with multiple imputations for missing data and adjustment for maternal race-ethnicity, household income, education, birth year, and duration of residence.
Results: Mothers residing in moderate (NDI Tertile 2 aOR = 1.23; 95% CI = 1.03, 1.48 and nSEPI Tertile 2 aOR = 1.24; 95% CI = 1.04, 1.49) or low socioeconomic neighborhoods (NDI Tertile 3 aOR = 1.28; 95% CI = 1.05, 1.55 and nSEPI Tertile 3 aOR = 1.32, 95% CI = 1.09, 1.61) were more likely to deliver an infant with gastroschisis compared with mothers residing in high socioeconomic neighborhoods.
Conclusions: Our findings suggest that lower neighborhood-level socioeconomic position during early pregnancy is associated with elevated odds of gastroschisis. Additional epidemiologic studies may aid in confirming this finding and evaluating potential mechanisms linking neighborhood-level socioeconomic factors and gastroschisis.
Canfield MA, Shumate CJ, et al. Associations between birth defects with neural crest cell origins and pediatric embryonal tumors. Cancer. 2023;10.1002/cncr.34952. Epub 2023 Jul 11. doi:10.1002/cncr.34952
Abstract
Background: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.
Methods: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education.
Results: The risk of embryonal tumors among those with BDNCOs was 0.09% (co-occurring n = 105) compared to 0.03% (95% CI, 0.03%-0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5-5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3-22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3-4.2) and nephroblastoma (2.9; 95% CI, 1.9-4.4) were elevated. There was no notable HRM by the aforementioned factors.
Conclusions: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.
Bojes HK, et al. Influence of storage conditions and multiple freeze-thaw cycles on N1 SARS-CoV-2, PMMoV, and BCoV signal. Sci Total Environ. 2023;896:165098. Epub 2023 Jun 29. doi:10.1016/j.scitotenv.2023.165098
Abstract
Wastewater-based epidemiology/wastewater-based surveillance (WBE/WBS) continues to serve as an effective means of monitoring various diseases, including COVID-19 and the emergence of SARS-CoV-2 variants, at the population level. As the use of WBE expands, storage conditions of wastewater samples will play a critical role in ensuring the accuracy and reproducibility of results. In this study, the impacts of water concentration buffer (WCB), storage temperature, and freeze-thaw cycles on the detection of SARS-CoV-2 and other WBE-related gene targets were examined. Freeze-thawing of concentrated samples did not significantly affect (p > 0.05) crossing/cycle threshold (Ct) value for any of the gene targets studied (SARS-CoV-2 N1, PMMoV, and BCoV). However, use of WCB during concentration resulted in a significant (p < 0.05) decrease in Ct for all targets, and storage at -80 °C (in contrast to -20 °C) appeared preferable for wastewater storage signal stability based on decreased Ct values, although this was only significantly different (p < 0.05) for the BCoV target. Interestingly, when Ct values were converted to gene copies per influent sample, no significant differences (p > 0.05) were observed in any of the targets examined. Stability of RNA targets in concentrated wastewater against freeze-thaw degradation supports archiving of concentrated samples for use in retrospective examination of COVID-19 trends and tracing SARS-CoV-2 variants and potentially other viruses, and provides a starting point for establishing a consistent procedure for specimen collection and storage for the WBE/WBS community.
Canfield MA, et al. Associations between birth defects and childhood and adolescent germ cell tumors according to sex, histologic subtype, and site. Cancer. 2023;10.1002/cncr.34906. Epub 2023 Jun 27. doi:10.1002/cncr.34906
Abstract
Background: Studies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics.
Methods: Birth defect-GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population-based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. The odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status were estimated by using unconditional logistic regression. All defects were considered collectively and by genetic and chromosomal syndromes and nonsyndromic defects. Stratification was by sex, tumor histology (yolk sac tumor, teratoma, germinoma, and mixed/other), and location (gonadal, extragonadal, and intracranial).
Results: Birth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0% and 2.7% vs. 0.2%, respectively; both p < .001). In multivariable models, GCT risk was increased among children with birth defects (OR, 1.7; 95% CI, 1.3-2.4) and syndromic defects (OR, 10.4; 95% CI, 4.9-22.1). When stratified by tumor characteristics, birth defects were associated with yolk sac tumors (OR, 2.7; 95% CI, 1.3-5.0) and mixed/other histologies (OR, 2.1; 95% CI, 1.2-3.5) and both gonadal tumors (OR, 1.7; 95% CI, 1.0-2.7) and extragonadal tumors (OR, 3.8; 95% CI, 2.1-6.5). Nonsyndromic defects specifically were not associated with GCTs. In sex-stratified analyses, associations were observed among males but not females
Conclusions: These data suggest that males with syndromic birth defects are at an increased risk of pediatric GCTs, whereas males with nonsyndromic defects and females are not at an increased risk.
Plain language summary: We investigated whether birth defects (such as congenital heart disease or Down syndrome) are linked to childhood germ cell tumors (GCTs), cancers that mainly develop in the ovaries or testes. We studied different types of birth defects (defects that were caused by chromosome changes such as Down syndrome or Klinefelter syndrome and defects that were not) and different types of GCTs. Only chromosome changes such as Down syndrome or Klinefelter syndrome were linked to GCTs. Our study suggests that most children with birth defects are not at an increased risk of GCTs because most birth defects are not caused by chromosome changes.
White SL, Davis K, Milleron R, et al. Notes from the field: exposures to mpox among cases in children aged ≤12 years - United States, September 25-December 31, 2022. MMWR Morb Mortal Wkly Rep. 2023;72(23):633-635. Published 2023 Jun 9. doi:10.15585/mmwr.mm7223a4
During May 17–December 31, 2022, 125 probable or confirmed U.S. monkeypox (mpox) cases were reported among patients aged <18 years, including 45 (36%) in children aged ≤12 years. Eighty-three cases in persons aged <18 years diagnosed during May 17–September 24, 2022 were previously described (1); 28 (34%) of these were in children aged ≤12 years, 29% of whom did not have reported information on exposure. Among 20 (71%) of 28 patients with documented information on exposure, most were exposed by a household contact. This report updates the previous report using data collected during September 25–December 31, 2022, proposes possible mpox exposure routes in children aged ≤12 years, and describes three U.S. mpox cases in neonates. Household members or caregivers with mpox, including pregnant women and their health care providers, should be informed of the risk of transmission to persons aged <18 years, and strategies to protect persons aged <18 years at risk for exposure, including isolating household contacts with mpox, should be implemented immediately.
Canfield MA, et al. Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants. Am J Med Genet A. 2023 Jun;191(6):1546-1556. Epub 2023 Mar 21. doi:10.1002/ajmg.a.63185
Abstract
The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex.
Chapman LE, Cobb K, Hall E, Seidel S. Creating novel surveillance data products for briefing health department leadership and elected officials during the COVID-19 pandemic in Texas. J Public Health Manag Pract. 2023 May-Jun;29(3):403-410. Epub 2022 Dec 2. doi:10.1097/PHH.0000000000001675
Abstract
Beginning in March 2020, the Texas Department of State Health Services (DSHS) developed several internal surveillance tools for briefing state health department leadership and elected officials on the status of the COVID-19 pandemic in Texas. This case study describes the initial conceptualization and daily production of 3 of these internal surveillance tools: (1) a COVID-19 data book displaying daily case, fatality, hospitalization, and testing data by county; (2) graphs and data files displaying new daily COVID-19 fatalities among residents of long-term care facilities in Texas; and (3) graphs and data files comparing COVID-19 cases and hospitalizations between the 4 COVID-19 waves in Texas. In addition, this case study uses qualitative interview data to describe how DSHS leadership used these surveillance products during the pandemic. Finally, details on challenges and lessons learned around creating and maintaining these tools are provided. These surveillance products are easily replicable, and our methods and lessons learned may be helpful for researchers or health department officials working on COVID-19 or other disease surveillance teams.
Shuford JA, Pont SJ, et al. Incidence and predictors of breakthrough and severe breakthrough infections of SARS-CoV-2 after primary series vaccination in adults: a population-based survey of 22,575 participants. J Infect Dis. 2023 May 12;227(10):1164-1172. doi:10.1093/infdis/jiad020
Abstract
Background: Breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well documented. The current study estimates breakthrough incidence across pandemic waves, and evaluates predictors of breakthrough and severe breakthrough infections (defined as those requiring hospitalization).
Methods: In total, 89,762 participants underwent longitudinal antibody surveillance. Incidence rates were calculated using total person-days contributed. Bias-corrected and age-adjusted logistic regression determined multivariable predictors of breakthrough and severe breakthrough infection, respectively.
Results: The incidence was 0.45 (95% confidence interval [CI], .38-.50) during pre-Delta, 2.80 (95% CI, 2.25-3.14) during Delta, and 11.2 (95% CI, 8.80-12.95) during Omicron, per 10,000 person-days. Factors associated with elevated odds of breakthrough included Hispanic ethnicity (vs non-Hispanic white, OR = 1.243; 95% CI, 1.073-1.441), larger household size (OR = 1.251 [95% CI, 1.048-1.494] for 3-5 vs 1 and OR = 1.726 [95% CI, 1.317-2.262] for more than 5 vs 1 person), rural versus urban living (OR = 1.383; 95% CI, 1.122-1.704), receiving Pfizer or Johnson & Johnson versus Moderna, and multiple comorbidities. Of the 1700 breakthrough infections, 1665 reported on severity; 112 (6.73%) were severe. Higher body mass index, Hispanic ethnicity, vaccine type, asthma, and hypertension predicted severe breakthroughs.
Conclusions: Breakthrough infection was 4-25 times more common during the Omicron-dominant wave versus earlier waves. Higher burden of severe breakthrough infections was identified in subgroups.
Patel M, et al. Behavioral health care provider's beliefs, confidence, and knowledge in treating cigarette smoking in relation to their use of the 5A's intervention. Addict Behav Rep. 2023 May 11;17:100493. doi:10.1016/j.abrep.2023.100493
Abstract
Introduction: Evidence-based smoking cessation interventions are underused settings where behavioral health treatment is provided, contributing to smoking-related health disparities in this patient group. This study assessed the relationship of provider's beliefs about patients' smoking, perceptions of treatment capability, and knowledge of referral options and their use of the 5A's (Ask, Advise, Assess, Assist, and Arrange) intervention for smoking cessation
Methods: Surveys were collected from providers in healthcare settings in Texas where patients receive behavioral health care (N = 86; 9 federally qualified health centers, 16 Local Mental Health Authorities (LMHAs), 6 substance use treatment programs in LMHAs, and 55 stand-alone substance use treatment centers). Logistic regression analyses were used to assess the association between provider's beliefs about patients' concern and desire to quit smoking; perceptions of their confidence, skills, and effectiveness in treating smoking; their knowledge of referral options; and their use of the 5A's with patients who smoked.
Results: Providers who believed that patients were concerned about smoking and wanted to quit; who perceived themselves as confident in providing cessation care, having the required skills, and being effective in providing advice; and/or who had greater referral knowledge were more likely to use the 5A's with patients who smoked than their (respective) provider counterparts (ps < 0.05).
Conclusion: Provider-level constructs affect their 5A's provision for patients with behavioral health needs. Future work should train providers to correct misconceptions about patients' interest in quitting, bolster their confidence, and provide referral options to support tobacco provision efforts.
Fischer M, White S, Davis K, et al. Epidemiologic and clinical features of mpox-associated deaths - United States, May 10, 2022-March 7, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(15):404-410. Published 2023 Apr 14. doi:10.15585/mmwr.mm7215a5
As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States, predominantly among cisgender men who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5). Please note: This report has been corrected. An erratum has been published.
Shumate CJ, et al. Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000-2017: A report from the National Birth Defects Prevention Network. Am J Med Genet A. 2023 May;191(5):1339- 1349. Epub 2023 Mar 15. doi:10.1002/ajmg.a.63181
Abstract
The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI = 3.0-3.3, program range: 1.0-10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI = 1.8-2.1, program range: 0.2-3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR = 0.5, 95% CI = 0.4-0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation.
Shuford JA, Pont SJ, et al. SARS-CoV-2 serostatus and COVID-19 illness characteristics by variant time period in non-hospitalized children and adolescents.
Children (Basel). 2023 Apr 30;10(5):818. doi:10.3390/children10050818
Abstract
Objective: To describe COVID-19 illness characteristics, risk factors, and SARS-CoV-2 serostatus by variant time period in a large community-based pediatric sample.
Design: Data were collected prospectively over four timepoints between October 2020 and November 2022 from a population-based cohort ages 5 to 19 years old.
Setting: State of Texas, USA.
Participants: Participants ages 5 to 19 years were recruited from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural clinical practices, health insurance providers, and a social media campaign.
Exposure: SARS-CoV-2 infection.
Main outcome(s) and measure(s): SARS-CoV-2 antibody status was assessed by the Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test). Self-reported antigen or PCR COVID-19 test results and symptom status were also collected.
Results: Over half (57.2%) of the sample (N = 3911) was antibody positive. Symptomatic infection increased over time from 47.09% during the pre-Delta variant time period, to 76.95% during Delta, to 84.73% during Omicron, and to 94.79% during the Omicron BA.2. Those who were not vaccinated were more likely (OR 1.71, 95% CI 1.47, 2.00) to be infected versus those fully vaccinated.
Conclusions: Results show an increase in symptomatic COVID-19 infection among non-hospitalized children with each progressive variant over the past two years. Findings here support the public health guidance that eligible children should remain up to date with COVID-19 vaccinations.
Cantor S, Chaudhary I, et al. COVID-19 outbreaks linked to workplaces, 23 US jurisdictions, August-October 2021. Public Health Rep. 2023 Mar-Apr;138(2):333-340. Epub 2022 Dec 8. doi:10.1177/00333549221138294
Abstract
Objectives: Early in the COVID-19 pandemic, several outbreaks were linked with facilities employing essential workers, such as long-term care facilities and meat and poultry processing facilities. However, timely national data on which workplace settings were experiencing COVID-19 outbreaks were unavailable through routine surveillance systems. We estimated the number of US workplace outbreaks of COVID-19 and identified the types of workplace settings in which they occurred during August-October 2021.
Methods: The Centers for Disease Control and Prevention collected data from health departments on workplace COVID-19 outbreaks from August through October 2021: the number of workplace outbreaks, by workplace setting, and the total number of cases among workers linked to these outbreaks. Health departments also reported the number of workplaces they assisted for outbreak response, COVID-19 testing, vaccine distribution, or consultation on mitigation strategies.
Results: Twenty-three health departments reported a total of 12 660 workplace COVID-19 outbreaks. Among the 12 470 workplace types that were documented, 35.9% (n = 4474) of outbreaks occurred in health care settings, 33.4% (n = 4170) in educational settings, and 30.7% (n = 3826) in other work settings, including non-food manufacturing, correctional facilities, social services, retail trade, and food and beverage stores. Eleven health departments that reported 3859 workplace outbreaks provided information about workplace assistance: 3090 (80.1%) instances of assistance involved consultation on COVID-19 mitigation strategies, 1912 (49.5%) involved outbreak response, 436 (11.3%) involved COVID-19 testing, and 185 (4.8%) involved COVID-19
vaccine distribution.
Conclusions: These findings underscore the continued impact of COVID-19 among workers, the potential for work-related transmission, and the need to apply layered prevention strategies recommended by public health officials.
Freeland M, et al. Travel history among persons infected with SARS-CoV-2 variants of concern in the United States, December 2020-February 2021. PLOS Glob Public Health. 2023 Mar 29;3(3):e0001252. doi:10.1371/journal.pgph.0001252
Abstract
The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) lineages, were initially detected internationally. This investigation examined available travel history of coronavirus disease 2019 (COVID-19) cases reported in the U.S. in whom laboratory testing showed one of these initial VOCs. Travel history, demographics, and health outcomes for a convenience sample of persons infected with a SARS-CoV-2 VOC from December 15, 2020 through February 28, 2021 were provided by 35 state and city health departments, and proportion reporting travel was calculated. Of 1,761 confirmed VOC cases analyzed, 1,368 had available data on travel history. Of those with data on travel history, 1,168 (85%) reported no travel preceding laboratory confirmation of SARS-CoV-2 and only 105 (8%) reported international travel during the 30 days preceding a positive SARS-CoV-2 test or symptom onset. International travel was reported by 92/1,304 (7%) of persons infected with the Alpha variant, 7/55 (22%) with Beta, and 5/9 (56%) with Gamma. Of the first three SARS-CoV-2 lineages designated as VOCs in the U.S., international travel was common only among the few Gamma cases. Most persons infected with Alpha and Beta variant reported no travel history, therefore, community transmission of these VOCs was likely common in the U.S. by March 2021. These findings underscore the importance of global surveillance using whole genome sequencing to detect and inform mitigation strategies for emerging SARS-CoV-2 VOCs.
Gutiérrez Tyler C, Salinas A, Guevara A, Alva H, Ruiz M, Prot EY. Assessing 2019 Hurricane Harvey recovery in Aransas County, Texas through Community Assessment for Public Health Emergency Response (CASPER). Disaster Med Public Health Prep. 2023 Mar 23;17:e366. doi:10.1017/dmp.2023.12
Abstract
Objectives: The objective of this study was to assess recovery of Aransas County, Texas households 2 years after Category 4 Hurricane Harvey made landfall.
Methods: A 2-stage cluster sampling method used to conduct a Community Assessment for Public Health Emergency Response (CASPER) on May 3 - 4 and May 18 - 19, 2019. A household-based survey was administered through face-to-face interviews, selected through systematic random sampling using weighted analysis of the county population. Field teams collected 175 surveys (83.3% completion rate).
Results: Approximately 57% households experienced repairable damage, 23% had destroyed homes, and 19% had minimal damage. 38% stated having 'no need,' 18% needed financial assistance, 16% needed household repairs, and over 8% had behavioral health needs. 17% experiencing a behavioral health concern were seeking services. Of the 35% of households who did not seek services, 14% felt there was no need, and 4% were not aware of the resources available.
Conclusions: Households reported high levels of preparedness, but gaps remain in evacuation intention and behavioral health care access. CASPERs are effective in assessing long-term recovery of communities impacted by major disasters.
Moore KO, Stuteville HD, et al. A case of primary amebic meningoencephalitis associated with surfing at an artificial surf venue: Environmental investigation. ACS ES T Water. 2023 Mar 15;3(4):1126-1133. doi:10.1021/acsestwater.2c00592
Abstract
Naegleria fowleri is a thermophilic ameba found in freshwater that causes primary amebic meningoencephalitis (PAM) when it enters the nose and migrates to the brain. In September 2018, a 29-year-old man died of PAM after traveling to Texas. We conducted an epidemiologic and environmental investigation to identify the water exposure associated with this PAM case. The patient's most probable water exposure occurred while surfing in an artificial surf venue. The surf venue water was not filtered or recirculated; water disinfection and water quality testing were not documented. N. fowleri and thermophilic amebae were detected in recreational water and sediment samples throughout the facility. Codes and standards for treated recreational water venues open to the public could be developed to address these novel venues. Clinicians and public health officials should also consider novel recreational water venues as a potential exposure for this rare amebic infection.
Shumate CJ, Canfield MA, et al. Patterns of co-occurring birth defects in children with anotia and microtia. Am J Med Genet A. 2023 Mar;191(3):805-812. Epub 2022 Dec 21. doi:10.1002/ajmg.a.63081
Abstract
Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 infants with non-syndromic A/M, of whom 38% (N = 492) were diagnosed with co-occurring major defects. Top combinations included: hydrocephalus, ventricular septal defect, and spinal anomalies (OER 58.4); microphthalmia and anomalies of the aorta (OER 55.4); and cleft lip with or without cleft palate and rib or sternum anomalies (OER 32.8). Some combinations observed in our study may represent undiagnosed/atypical presentations of known A/M associations or syndromes, or novel syndromes yet to be described in the literature. Careful evaluation of infants with multiple birth defects including A/M is warranted to identify individuals with potential genetic or chromosomal syndromes.
Canfield MA, et al. Prevalence and mortality among children with anorectal malformation: A multi-country analysis. Birth Defects Res. 2023 Feb 1;115(3):390-404. Epub 2022 Nov 19. doi:10.1002/bdr2.2129
Abstract
We examined the total prevalence, trends in prevalence, and age-specific mortality among individuals with anorectal malformation (ARM) METHODS: We conducted a retrospective cohort study using data from 24 population- and hospital-based birth defects surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) from 18 countries and for births from 1974 to 2014. We estimated pooled and program-specific total prevalence per 10,000 total births. Poisson regression was used to assess time trends in prevalence from 2001 to 2012 when most programs contributed data. We calculated selected age-specific proportions of deaths, stratified by case status RESULTS: The pooled total prevalence of ARM was 3.26 per 10,000 total births (95% Confidence Interval = 3.19, 3.32) for birth years 1974-2014. About 60% of cases were multiple or syndromic. Prevalence of multiple, syndromic, and stillborn cases decreased from 2001 to 2012. The first week mortality proportion was 12.5%, 3.2%, 28.3%, and 18.2% among all, isolated, multiple, and syndromic cases, respectively CONCLUSIONS: ARM is relatively rare, with multiple and syndromic cases showing decreasing prevalence during the study period. Mortality is a concern during the first week of life, and especially among multiple and syndromic cases. Our descriptive epidemiological findings increase our understanding of geographic variation in the prevalence of ARM and can be used to plan needed clinical services. Exploring factors influencing prevalence and mortality among individuals with ARM could inform future studies.
Tanksley S, et al. Evidence and recommendation for mucopolysaccharidosis type II newborn screening in the United States. Genet Med. 2023 Feb;25(2):100330. Epub 2022 Nov 29. doi:10.1016/j.gim.2022.10.012
Abstract
Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision.
Canfield MA, Marengo LK, et al. Contribution of Preterm Birth to Mortality Among Neonates with Birth Defects. J Pediatr. 2023 Feb;253:270-277.e1. Epub 2022 Oct 10. doi:10.1016/j.jpeds.2022.10.002
Abstract
Objective: To estimate the proportion of neonatal mortality risk attributable to preterm delivery among neonates with birth defects.
Study design: Using a statewide cohort of live born infants from the Texas Birth Defects Registry (1999-2014 deliveries), we estimated the population attributable fraction and 95% CI of neonatal mortality (death <28 days) attributable to prematurity (birth at <37 weeks vs ≥37 weeks) for 31 specific birth defects. To better understand the overall population burden, analyses were repeated for all birth defects combined.
Results: Our analyses included 169 148 neonates with birth defects, of which 40 872 (24.2%) were delivered preterm. The estimated proportion of neonatal mortality attributable to prematurity varied by birth defect, ranging from 12.5% (95% CI: 8.7-16.1) for hypoplastic left heart syndrome to 71.9% (95% CI: 41.1-86.6) for anotia or microtia. Overall, the proportion was 51.7% (95% CI: 49.4-54.0) for all birth defects combined.
Conclusions: A large proportion of deaths among neonates with birth defects are attributable to preterm delivery. Our results highlight differences in this burden across common birth defects. Our findings may be helpful for prioritizing future work focused on better understanding the etiology of prematurity among neonates with birth defects and the mechanisms by which prematurity contributes to neonatal mortality in this population.
Pont SJ, Shuford JA, et al. Antibody duration after infection from SARS-CoV-2 in the Texas Coronavirus Antibody Response Survey. J Infect Dis. 2023 Jan 11;227(2):193-201. Epub 2022 May 6. doi:10.1093/infdis/jiac167
Abstract
Understanding the duration of antibodies to the SARS-CoV-2 virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least one nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n= 4,553) with one to three antibody tests over 11 months (10/1/2020-9/16/2021), and model fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days post-infection, and predicts individuals may remain antibody positive from natural infection beyond 500 days, depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not).
Cantu V, et al. Listeria monocytogenes illness and deaths associated with ongoing contamination of a multiregional brand of ice cream products, United States, 2010-2015. Clin Infect Dis. 2023 Jan 6;76(1):89-95. doi:10.1093/cid/ciac550
Abstract
Background: Frozen foods have rarely been linked to Listeria monocytogenes illness. We describe an outbreak investigation prompted by both hospital clustering of illnesses and product testing.
Methods: We identified outbreak-associated listeriosis cases using whole-genome sequencing (WGS), product testing results, and epidemiologic linkage to cases in the same Kansas hospital. We reviewed hospital medical and dietary records, product invoices, and molecular subtyping results. Federal and state officials tested product and environmental samples for L. monocytogenes.
Results: Kansas officials were investigating 5 cases of listeriosis at a single hospital when, simultaneously, unrelated sampling for a study in South Carolina identified L. monocytogenes in Company A ice cream products made in Texas. Isolates from 4 patients and Company A products were closely related by WGS, and the 4 patients with known exposures had consumed milkshakes made with Company A ice cream while hospitalized. Further testing identified L. monocytogenes in ice cream produced in a second Company A production facility in Oklahoma; these isolates were closely related by WGS to those from 5 patients in 3 other states. These 10 illnesses, involving 3 deaths, occurred from 2010 through 2015. Company A ultimately recalled all products.
Conclusions: In this US outbreak of listeriosis linked to a widely distributed brand of ice cream, WGS and product sampling helped link cases spanning 5 years to 2 production facilities, indicating longstanding contamination. Comprehensive sanitation controls and environmental and product testing for L. monocytogenes with regulatory oversight should be implemented for ice cream production.
Marengo LK, Archer N, Shumate C, Canfield MA, Drummond-Borg M. Survival of infants and children born with severe microcephaly, Texas, 1999-2015. Birth Defects Res. 2023 Jan 1;115(1):26-42. Epub 2022 Nov 8. doi:10.1002/bdr2.2109
Abstract
Background: Severe microcephaly is a brain reduction defect where the delivery head circumference is <3rd percentile for gestational age and sex with subsequent lifelong morbidities. Our objective was to evaluate survival among 2,704 Texas infants with severe microcephaly delivered 1999-2015.
Methods: Infants with severe microcephaly from the Texas Birth Defects Registry were linked to death certificates and the national death index. Survival estimates, hazard ratios (HR) and confidence intervals (CI) were calculated using the Kaplan-Meier method and Cox proportional hazards models stratified by presence versus absence of co-occurring defects.
Results: We identified 496 deaths by age 4 years; most (42.9%) occurred in the neonatal period, and another 39.9% died by 1 year of age. Overall infant survival was 84.8%. Lowest infant survival subgroups included those with chromosomal/syndromic conditions (66.1%), very preterm deliveries (63.9%), or co-occurring critical congenital heart defects (44.0%). Among infants with severe microcephaly and a chromosomal/syndromic co-occurring defect, the risk of death was nearly three-fold higher among those with: proportionate microcephaly (i.e., small baby overall), relative to non-proportionate (HR = 2.84, 95% CI = 2.17-3.71); low-birthweight relative to normal (HR = 2.72, 95% CI = 1.92-3.85); critical congenital heart defects (CCHD) relative to no CCHD (HR = 2.90, 95% CI = 2.20-3.80). Trisomies were a leading underlying cause of death (27.5%).
Conclusions: Overall, infants with severe microcephaly had high 4-year survival rates which varied by the presence of co-occurring defects. Infants with co-occurring chromosomal/syndromic anomalies have a higher risk of death by age one than those without any co-occurring birth defects.
Le MT, et al. Assessing associations between residential proximity to greenspace and birth defects in the National Birth Defects Prevention Study. Environ Res. 2023 Jan 1;216(Pt 3):114760. Epub 2022 Nov 7. doi:10.1016/j.envres.2022.114760
Abstract
Background: Residential proximity to greenspace is associated with various health outcomes.
Objectives: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors.
Methods: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100 m and 500 m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income.
Results: After multivariable adjustment, for the 500 m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lip ± cleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100 m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81).
Discussion: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods.
Shumate CJ, Nguyen J, Canfield MA, et al. Factors associated with nonsyndromic anotia and microtia, Texas, 1999-2014. Birth Defects Res. 2023 Jan 1;115(1):67-78. Epub 2022 Nov 17. doi:10.1002/bdr2.2130
Abstract
Background: Few risk factors have been identified for nonsyndromic anotia/microtia (A/M).
Methods: We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression.
Results: We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with less than high school education (PR: 1.3, 95% CI: 1.1-1.5), diabetes (PR: 2.0, 95% CI: 1.6-2.4), or age 30-39 versus 20-29 years (PR: 1.2, 95% CI: 1.0-1.3). The prevalence was decreased among offspring of non-Hispanic Black versus White women (PR: 0.6, 95% CI: 0.4-0.8) but increased among offspring of Hispanic women (PR: 2.9, 95% CI: 2.5-3.4) and non-Hispanic women of other races (PR: 1.7, 95% CI: 1.3-2.3). We observed similar results among cases with isolated and unilateral A/M. Sex disparities were not evident for nonisolated or bilateral phenotypes, nor did birth prevalence differ between offspring of non-Hispanic Black and non-Hispanic White women. Maternal diabetes was more strongly associated with nonisolated (PR: 4.5, 95% CI: 3.2-6.4) and bilateral A/M (PR: 5.0, 95% CI: 3.3-7.7). Crude prevalence rates increased throughout the study period (annual percent change: 1.82).
Conclusion: We identified differences in the prevalence of nonsyndromic A/M by maternal race/ethnicity, education, and age, which may be indicators of unidentified social/environmental risk factors.
Betancourt D, Canfield MA, Ethen MK, Shumate C, Drummond-Borg M, et al. Connecting children with birth defects to health and social service programs: A collaboration between the Texas Birth Defects Registry and agency social workers. Birth Defects Res. 2023 Jan 1;115(1):110-119. Epub 2022 Nov 14. doi:10.1002/bdr2.2126
Abstract
Background: Timely referral to services for children born with birth defects can improve health outcomes. Birth defects surveillance registries may be a valuable data source for connecting children to health and social service programs.
Methods: Population-based, state-wide data from the Texas Birth Defects Registry (TBDR) at the Texas Department of State Health Services (DSHS) were used to connect children 9-18 months old, born with select birth defects with DSHS social workers. The social workers reviewed developmental milestones and referred children and their families to various health and social service programs. We tabulated the proportions of children meeting milestones and referral characteristics by referral program type and type of birth defect.
Results: Social workers reached 67% (909/1,362) of identified families. Over half of children (54%, 488/909) were not meeting the developmental milestones for their age. Social workers provided over 3,000 program referrals, including referring 21% (194/909) of children to Early Childhood Intervention (ECI) and 28% (257/909) to case management.
Conclusion: Our results illustrate a method of leveraging a birth defects surveillance system for referral services. Given the large number of referrals made, our findings suggest that birth defects registries can be a valuable source of data for referring children to programs.
Marengo L, Canfield MA, et al. Evaluating the proportion of isolated cases among a spectrum of birth defects in a population-based registry. Birth Defects Res. 2023 Jan 1;10.1002/bdr2.1990. Epub 2022 Feb 26. doi:10.1002/bdr2.1990
Abstract
Introduction: Because the etiology and outcomes of birth defects may differ by the presence vs. absence of co-occurring anomalies, epidemiologic studies often attempt to classify cases into isolated versus non-isolated groupings. This report describes a computer algorithm for such classification and presents results using data from the Texas Birth Defects Registry (TBDR).
Methods: Each of the 1,041 birth defects coded by the TBDR was classified as chromosomal, syndromic, minor, or "needs review" by a group of three clinical geneticists. A SAS program applied those classifications to each birth defect in a case (child/fetus), and then hierarchically combined them to obtain one summary classification for each case, adding isolated and multiple defect categories. The program was applied to 136,121 cases delivered in 2012-2017.
Results: Of the total cases, 49% were classified by the platform as isolated (having only one major birth defect). This varied widely by birth defect; of those examined, the highest proportion classified as isolated was found in pyloric stenosis (87.6%), whereas several cardiovascular malformations had low proportions, including tricuspid valve atresia/stenosis (2.3%).
Discussion: This is one of the first and largest attempts to identify the proportion of isolated cases across a broad spectrum of birth defects, which can inform future epidemiologic and genomic studies of these phenotypes. Our approach is designed for easy modification for use with any birth defects coding system and category definitions, allowing scalability for different studies or birth defects registries, which often do not have resources for individual clinical review of all case records.
Chaudhary I, et al. Regional outbreak of multidrug-resistant Klebsiella pneumoniae carbapenemase-producing Pseudomonas Aeruginosa. Infect Control Hosp Epidemiol. 2023;44(1):96-98. Epub 2021 Oct 1. doi:10.1017/ice.2021.394
Abstract
Klebsiella pneumoniae carbapenemase-producing P. aeruginosa (KPC-CRPA) are rare in the United States. An outbreak of KPC-CRPA was investigated in Texas using molecular and epidemiologic methods and 17 cases of KPC-CRPA were identified. The isolates were genetically related and harbored the emerging P. aeruginosa multilocus sequence type 235, the first in the United States.
Canfield MA, Drummond-Borg M, et al. Identifying syndromes in studies of structural birth defects: Guidance on classification and evaluation of potential impact. Am J Med Genet A. 2023;191(1):190-204. Epub 2022 Oct 26. doi:10.1002/ajmg.a.63014
Abstract
Structural birth defects that occur in infants with syndromes may be etiologically distinct from those that occur in infants in whom there is not a recognized pattern of malformations; however, population-based registries often lack the resources to classify syndromic status via case reviews. We developed criteria to systematically identify infants with suspected syndromes, grouped by syndrome type and level of effort required for syndrome classification (e.g., text search). We applied this algorithm to the Texas Birth Defects Registry (TBDR) to describe the proportion of infants with syndromes delivered during 1999-2014. We also developed a bias analysis tool to estimate the potential percent bias resulting from including infants with syndromes in studies of risk factors. Among 207,880 cases with birth defects in the TBDR, 15% had suspected syndromes and 85% were assumed to be nonsyndromic, with a range across defect types from 28.5% (atrioventricular septal defects) to 98.9% (pyloric stenosis). Across hypothetical scenarios varying expected parameters (e.g., nonsyndromic proportion), the inclusion of syndromic cases in analyses resulted in up to 50.0% bias in prevalence ratios. In summary, we present a framework for identifying infants with syndromic conditions; implementation might harmonize syndromic classification across registries and reduce bias in association estimates.