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Birth Defects Risk Factor Series

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Conotruncal heart defects are also known as outflow tract defects. Common types of conotruncal heart defects are truncus arteriosus, transposition of the great arteries, double outlet of the right ventricle, and tetralogy of Fallot. In truncus arteriosus, also known as common truncus, there is a single outflow tract instead of a separate aorta and pulmonary artery. Transposition of the great arteries consists of the great arteries being switched so that the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta originate from the right ventricle. Tetralogy of Fallot involves a ventricular septal defect, right ventricular outflow tract obstruction such as pulmonary atresia or stenosis, aorta overriding the ventricular septum, and right ventricular hypertrophy. Common truncus often occurs with interrupted aortic arch (Pradat 2003). Other types of conotruncal defects include pulmonary atresia with ventricular septal defect and aortopulmonary window.


A portion of conotruncal heart defects are associated with chromosomal abnormalities such as trisomy 21, trisomy 13, and trisomy 18 (Harris 2003, Boldt 2002, Garne 1999, Tennstedt1999, Torfs 1998, Ferencz 1997, Kallen 1996, O’Malley 1996, Pradat 1992, Ferencz 1989). About 6% of patients with conotruncal defects have 22q11 microdeletion syndrome (Beauchesne 2005). In particular, truncus arteriosus and tetralogy of Fallot may occur with the chromosome 22q microdeletion linked to DiGeorge syndrome and velocardiofacial syndrome (Boudjemline 2002, Kessler-Icekson 2002, Boudjemline 2001, Cuneo 2001, Driscoll 2001, Marino 2001, Maeda 2000, Borgmann 1999, Lu 1999, Trost 1999, Goldmuntz 1998, Ferencz 1997, Ryan 1997, Webber 1996, Takahashi 1995). Cases of tetralogy of Fallot associated with severe pulmonary artery anomalies, extracardiac anomalies, increased nuchal translucency, polyhydramnios, intrauterine growth retardation were more likely to have 22q11 deletion (Boudjemline 2002). In addition, hypoparathyroidism with 22q11 deletion has been associated with extended regression of the 4th aortic arch, but not outflow tract malformations (Koch 2002).

Approximately 4% of nonsyndromic cases of tetralogy of Fallot may have mutations in the transcription factor NKX2.5 (Goldmuntz 2001). Two mutations in the CFC1 gene have also be found in patients with transposition of the great arteries and double outlet right ventricle (Goldmuntz 2002), and mutations in the F2, F7, NPPA, and ITGB3 genes carry a higher risk for offspring with conotruncal defects (combined). (Shaw 2005).

Over the last several decades, ultrasonography and fetal echocardiography have allowed conotruncal defects to be identified in utero (Boudjemline 2001, Hafner 1998, Kirk 1997, Stoll 1997). In regions where elective termination is allowed, prenatal diagnosis and elective termination may reduce the birth prevalence of conotruncal defects (Boldt 2002, Garne 2001, Riley 1998, Stoll 1995, Stoll 1993, Stoll 1992).


Investigations into the relationship between conotruncal defects and race/ethnicity have been mixed. Various studies found higher rates among whites and Hispanics than African-Americans for transposition of the great arteries, tetralogy of Fallot, and truncus arteriosus (Botto 2001a, O’Malley 1996, Fixler 1993, Correa-Villasenor 1991), although in one study the difference was influenced by socioeconomic status (Correa-Villasenor 1991). Native Americans have higher rates of transposition of the great arteries and double outlet of the right ventricle than whites (O’Malley 1996). One investigation reported transposition of the great arteries to occur more frequently among whites than among non-whites (Adams 1989) or non-Hispanic whites compared to Hispanics (Pradat 2003). Pradat et al. (2003) also demonstrated higher rates of tetralogy of Fallot compared among blacks when with Hispanics, yet other studies reported no relationship between race/ethnicity and tetralogy of Fallot and truncus arteriosus (Shaw 2002, Storch 1992, Adams 1989) and conotruncal defects (Ferencz 1997).

Several studies have reported secular trends for conotruncal defects, with increasing rates over time for tetralogy of Fallot and double outlet right ventricle (Botto 2001a), conotruncal defects with normally related great arteries (Ferencz 1997), tetralogy of Fallot (Adams 1989), and transposition of the great arteries and tetralogy of Fallot (Grech 1998, Francannet 1993). However, in one study the increase was possibly due to increased ascertainment (Grech 1998) and in another the increase was only observed in several birth defects registries (Francannet 1993). Still another study reported little variation in rates of transposition of the great arteries and tetralogy of Fallot and greater variation in truncus arteriosus rates over time (Wren et al., 2000). One investigation observed seasonal variation, with higher rates of conotruncal defects among July-December deliveries (Ferencz 1997), while other studies identified no seasonal variation in rates of transposition of the great arteries or conotruncal defects as a group (Tikkanen 1991, Tikkanen 1990, Bound 1989). A study in Czechoslovakia reported seasonal differences in rates of transposition of the great arteries and tetralogy of Fallot (Samanek 1991a).

One study identified no relationship between geographic variation and transposition of the great arteries, while conotruncal defects with normally positioned great arteries (tetralogy of Fallot, truncus arteriosus, and some types of double outlet of the right ventricle) were more common in urban areas (Ferencz 1997). Another investigation found no geographic differences between conotruncal defect cases and controls (Tikkanen 1992a). A study in Czechoslovakia reported regional differences in rates of transposition of the great arteries, tetralogy of Fallot, and truncus arteriosus (Samanek 1991b).

Maternal age does not appear to influence risk of conotruncal defects, particularly transposition of the great arteries and tetralogy of Fallot (O’Malley 1996, Francannet 1993, Tikkanen 1992a, Tikkanen 1990, Baird 1991). However, one investigation observed increased risk of transposition of the great arteries with increasing maternal age (Rothman 1976). One study observed that risk of conotruncal defects was higher with paternal age greater than 30 years (O’Malley 1996). Several investigations noted increasing parity to increase risk of transposition of the great arteries, tetralogy of Fallot, and hypoplastic left heart syndrome taken as a group (Francannet 1993, Rothman 1976), and Pradat et al. (2003) found higher risk for mothers with 2 or more children for transposition of the great arteries and lower risk for tetralogy of Fallot. Other studies found no association between conotruncal defects and parity (O’Malley 1996, Adams 1989). Rates of transposition of the great arteries and tetralogy of Fallot have been found to be lower with maternal birthplace in Mexico than when the mother was born in the United States (O’Malley 1996).

With respect to sex, transposition of the great arteries, double outlet of the right ventricle, and tetralogy of Fallot are more common among males than females, while truncus arteriosus is more common among females or demonstrates no differences between the sexes (Pradat 2003, Lary 2001, Grech 2000, Garne 1999, Riley 1998, Ferencz 1997, O’Malley 1996, Samanek 1994, Sampayo 1994, Francannet 1993, Pradat 1992, Storch 1992, Fyler 1980, Rothman 1976).

Lower birth weight and gestational age is associated with increased risk of tetralogy of Fallot, double outlet of the right ventricle, and truncus arteriosus, although the relationship between birth weight and gestational age and transposition of the great arteries is less clear (Rasmussen 2001, Riley 1998, Ferencz 1997, Francannet 1993, Mili 1991, Rosenthal 1991). There is no relationship between conotruncal defects and macrosomia (Lapunzina 2002, Waller 2001). Transposition of the great arteries, tetralogy of Fallot, and truncus arteriosus have been associated with intrauterine growth retardation (Khoury 1988).

Several studies failed to identify any association between plurality and conotruncal defects (Ferencz 1997, O’Malley 1996, Doyle 1991). However, other studies reported increased rates of particular types of conotruncal defects among multiple gestations (Mastroiacovo 1999, Riley 1998, O’Malley 1996, Francannet 1993, Layde 1980).

Consanguinity has not been found to influence risk of conotruncal defects (Becker 2001, Rittler 2001).


The effects of socio-economic status (SES) and risk for conotruncal defects are variable; one study found that women of lower SES were more likely to have babies with transposition of the great arteries, but less likely for their offspring to have tetralogy of Fallot (Carmichael 2003).

Maternal occupation in clerical, sales, or factory fields increases risk of conotruncal defects with normally related great arteries (Ferencz 1997, Adams 1989) and paternal occupation of policeman or guard associated with transposition of the great arteries (Chia 2002). An investigation noted that maternal psychosocial or emotional stress (death, job loss, relationship breakup) may increase risk of conotruncal defects (Carmichael 2000, Adams 1989).

One study failed to identify any relationship between paternal exposures and conotruncal defects (Correa-Villasenor 1993). In contrast, another investigation identified associations between paternal X-rays and general anesthesia and tetralogy of Fallot and between marijuana and cocaine and transposition of the great arteries with intact ventricular septum (Ferencz 1997).

Increased risk of conotruncal defects has been reported with maternal exposure to dyes, lacquers, or paints at work, but not with organic solvents, disinfectants, pesticides, wood preservatives, anesthetic gases, glues, plastic raw materials, dust, video display terminals, or microwave ovens (Tikkanen 1992a, Tikkanen 1992b, Tikkanen 1990). However, another investigation found no association between conotruncal defects and parental pesticide exposure with the exception of maternal gardening pesticide exposure and insect repellent use (Shaw 1999). An additional study reported increased risk of transposition of the great arteries with maternal exposure to herbicides and rodenticides but not insecticides; other conotruncal defects were not associated with pesticides (Loffredo 2001a).

One study that examined the relationship between ambient air pollution and conotruncal defects found risk of the cardiac defects increased with second-month ozone exposure (Ritz 2002). No association was found with carbon monoxide, nitrogen dioxide, and PM10. Another investigation reported no relationship between the trihalomethanes, which are water disinfection byproducts, and conotruncal defects (Shaw 1991).

Association between between maternal alcohol use and conotruncal defects is none (Tikkanen 1992, Tikkanen 1990, Adams 1989) to moderate (Carmichael 2003). Higher rates of transposition of the great arteries have been reported with maternal smoking (Kallen 1999, Ferencz 1997), and higher rates were found among mothers with a variant of the NOS3 gene and perinatal cigarette smoking for conotruncal defects combined (Shaw 2005). However, other investigations noted that maternal smoking, coffee, tea, cocoa, and marijuana or hashish did not affect risk of conotruncal defects (Wasserman 1996, Tikkanen 1992, Adams 1989). One study reported higher rates of transposition of the great arteries and conotruncal defects when both parents smoked tobacco (Wasserman 1996).

Several studies had identified aspirin to increase risk of transposition of the great arteries (Zierler 1985, Heinonen 1977); however, a subsequent investigation failed to verify this association (Werler 1989). Bendectin has not been linked to conotruncal defects, while tetracycline has been reported to increase risk of transposition of the great arteries and codeine to increase risk of double outlet of the right ventricle (Adams 1989, Zierler 1985). An investigation reported increased risk of transposition of the great arteries with maternal anticonvulsant use, although exposure was reported for only one case (Correy 1991). Analyses have reported associations between benzodiazepines (Valium, Librium, Serax) and conotruncal defects (Ferencz 1997, Adams 1989) and ibuprofen and transposition of the great arteries, progesterone and transposition of the great arteries and truncus arteriosus, solvents and transposition of the great arteries and double outlet of the right ventricle, and ionizing radiation and transposition of the great arteries (Ferencz 1997). General anesthesia, tranquilizers, contraceptives, and Clomid do not appear to influence conotruncal defect rates ( Adams 1989). Maternal use of ampicillin during pregnancy does not appear to be associated with risk of truncus arteriosus, transposition of the great arteries, or tetralogy of Fallot (Czeizel 2001).

Maternal diabetes elevates risk of conotruncal defects (Loffredo 2001b, Ferencz 1997, Ramos-Arroyo 1992, Becerra 1990, Ferencz 1990, Adams 1989), although one study failed to find that association (Harris 2003). Associations between maternal influenza, thyroid disease (hyperthyroidism, hypothyroidism), and urinary tract or kidney infection and conotruncal defects have been inconsistent (Ferencz 1997, Adams 1989, Khoury 1989). One investigation found no statistically significant association between maternal febrile illness during early pregnancy and transposition of the great arteries or tetralogy of Fallot (Botto 2001b). Untreated maternal phenylkentonuria does not appear to increase risk of conotruncal defects (Levy 2001). One investigation reported no relationship between conotruncal defects and such long-term maternal illnesses as asthma, fever, nonrheumatoid heart disease, and epilepsy ( Adams 1989). Maternal upper respiratory infection has been associated with increased conotruncal defect risk (Tikkanen 1992, Tikkanen 1991, Tikkanen 1990). Obesity has been found to increase risk of defects of the great vessels (Waller 1994).

Various studies have reported a reduction in conotruncal defect rates with maternal multivitamin use (Botto 2000, Botto 1996, Shaw 1995, Czeizel 1993). One study observed increased risk of cardiac outflow trace defects and maternal fever and no multivitamin use; however, risk was reduced with multivitamin use (Botto 2002). In addition, there is evidence that certain mutations of a folate-related gene (MTHFR) in infants increases their likelihood of having omphalocele (van Beynum 2006). However, several studies failed to identify a reduction in conotruncal defect risk and multivitamins or folic acid (Werler 1999, Scanlon 1998), or heart defects in general (Bower 2006), nor did it reduce the risk of conotruncal defects among children with Down syndrome (Meijer 2006). One investigation reported increased risk of transposition of the great arteries with maternal supplementation of 10,000 IU or more of vitamin A (Botto 2001c). Another study noted no increased risk of transposition of the great arteries if the infant had the 677TT genotype of the methylenetetrahydrofolate reductase (MTHFR) gene (Junker 2001).


Prevalence of conotruncal heart defects per 10,000 live births


Texas (95% Confidence Interval) (Texas Department of State Health Services 2006)

United States (95% Confidence Interval) (Canfield 2006)

Common Truncus

0.89 (0.75-1.02)

0.82 (0.71-0.93)

Transposition of the Great Arteries

4.87 (4.55-5.19)

4.73 (4.46-5.00)

Tetralogy of Fallot

3.35 (3.09-3.62)

3.92 (3.67-4.17)

Double Outlet Right Ventricle



(Botto 2001a, O’Malley 1996, Ferencz 1985, Fyler 1980)


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Please Note: The primary purpose of this report is to provide background necessary for conducting cluster investigations. It summarizes literature about risk factors associated with this defect. The strengths and limitations of each reference were not critically examined prior to inclusion in this report. Consumers and professionals using this information are advised to consult the references given for more in-depth information. 

This report is for information purposes only and is not intended to diagnose, cure, mitigate, treat, or prevent disease or other conditions and is not intended to provide a determination or assessment of the state of health. Individuals affected by this condition should consult their physician and when appropriate, seek genetic counseling.

For more information:

Birth Defects Epidemiology and Surveillance
Texas Department of State Health Services
1100 W. 49th Street, Austin, Texas 78756
512-776-7232 Fax 512-776-7330

Document E58-10957                      Revised August 2007

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Last updated February 10, 2012