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Patent ductus arteriosus (PDA), also called persistent ductus arteriosus, occurs as a result of persistence after birth of the normal fetal vessel (ductus arteriosus) that connects the left pulmonary artery to the aorta. The ductus normally closes in a two-phase process. First, smooth muscle constricture of the ductus results in a functional closure hours after birth; this initial closure is likely caused by increased pressure in the vessels (Ravishankar 2003). Following this action, smooth muscle loss and migration cause an anatomical closure hours or days after birth (Ravishankar 2003, Buyse 1990). In order for the second phase of closure to occur, the first phase must take place. The ductus arteriosus generally closes shortly after birth in normal infants; persistence of the ductus is considered normal in preterm infants and will close spontaneously (Buyse 1990)

PDA accounts for 2%-15% of all congenital heart defects (Becker 2001, Botto 2001, Borgmann 1999, Samanek 1999, Jaiyesimi 1993, Kidd 1993, Fixler 1990, Stoll 1989, Grabitz 1988, Ferencz 1985). Approximately 10 to 70% of premature infants manifest this defect (Van Overmeire 2005, De Felice 2004, Ravishankar 2003); the majority of these infants require some sort of intervention in order to close the defect. Both drug therapy (indomethancin and ibuprofen) and surgical intervention can be utilized to correct the defect (Van Overmeire 2005, Shah 2005, Keady 2005). Vitamin A therapy has also been used to close the defect; however, this method has not been as successful as the other drug therapies (Ravishankar 2003).


Between 28%-88% of PDA cases have other cardiac and non-cardiac birth defects (Ferencz 1997, Stoll 1993, Castilla 1990), and 8%-11% of cases with PDA also have a chromosomal abnormality (Ferencz 1997, Stoll 1989). PDA is associated with trisomy 21, where PDA can account for 4% of all associated congenital heart defects (Kallen 1996). PDA has also been found with trisomy 18, trisomy 13, Char syndrome, Noonan syndrome, Holt-Oram syndrome, Meckel-Gruber syndrome, and congenital rubella syndrome (Goldmuntz 2001, Torfs 1998, Webster 1998, Ferencz 1997). PDA occurs among people with 22q11 deletion linked to DiGeorge syndrome, velo-cardio-facial syndrome, and several other syndromes (Borgmann 1999).

One study indicated that there might be some evidence for recessive inheritance of this defect. In an Iranian population with high consanguinity, the rates for PDA were higher than those in the United States. When infants were heterozygous (having two copies of a particular gene) for the 12q24 gene, they were more likely to manifest the PDA defect However, the 12q24 gene was only significant in non-syndromic PDA cases (Mani 2002).

Patent ductus arteriosus is associated with Char syndrome. This syndrome is characterized by skeletal anomalies of the hand, facial dismorphism, and PDA. One gene, TFAP2B, has been positively associated with this syndrome (Mani 2005).


PDA may be identified by prenatal ultrasound and fetal echocardiography. However, the ductus arteriosus is a normal condition among fetuses. PDA is only a defect if it persists after birth.


The mortality rate associated with PDA has declined in the United States during 1979-1997 (Boneva 2001, Lee 2001). One study noted that 4% of infants with isolated PDA expired within the first year of life (Ferencz 1997). There are several therapies available to correct this defect, including drug therapy and surgical intervention (see above) (Van Overmeire 2005).



Studies of risk of PDA by race/ethnicity have been inconsistent. While some studies have reported higher rates of PDA among African Americans than among whites (Botto 2001, Ferencz 1997, Chavez 1988), other investigations found no such difference (Fixler 1993, Correa-Villansenor 1991). PDA rates among Hispanics tend to be lower than among whites and African Americans (Fixler 1993, Chavez 1988).

Secular and Seasonal Trends

PDA rates have increased over the last several decades (Botto 2001a, Ferencz 1997, Anderson 1978). Generally this increase has been attributed to increased use of echocardiography.

Investigation of PDA and seasonality have produced mixed results. One study found no seasonal variation in PDA rates (Tikkanen 1991) while other studies did report seasonal variation (Samanek 1991, Bound 1989). Another investigation observed rates for isolated PDA to be lowest in January-March and highest in October-December (Ferencz 1997).


One study noted isolated PDA to be more common in urban areas (Ferencz 1997). PDA risk increases with high altitudes (Olley 1987, Alzamora-Castro 1960).


PDA is more common among females than among males (Ferencz 1997, Samanek 1994, Sampayo 1994, Fyler 1980, Rothman 1976), although one investigation reported 53% of the PDA cases to be among males (Lary 2001).


One study noted isolated PDA not to be associated with the mother’s number of previous pregnancies (Ferencz 1997). Another study reported PDA risk to decrease with increasing birth order (Rothman 1976).


Several investigations reported increased risk of PDA among twins (Doyle 1991, Layde 1980) while a more recent study found no association between isolated PDA risk and twins (Ferencz 1997).

Gestational Age and Birth Weight

As noted previously, PDA is associated with preterm delivery, where PDA generally is not considered to be a birth defect. However, among term births isolated PDA risk is associated with lower birth weight (Jacobs 2003, Ferencz 1997). PDA risk is associated with small for gestational age (intrauterine growth retardation) (Ferencz 1997, Khoury 1988). One study indicated that there was an association between PDA and hypothyroidism in the newborn. The defect corrected itself after thyroid replacement therapy in most cases (Allegaert 2004).


One investigation reported no increased risk of PDA among the offspring born to first cousins (Becker 2001). However, another study indicated that within an Iranian population with a high level of consanguinity the rates of PDA were higher than when compared to the United States population (15% vs. 2-7%) (Mani 2004).

Parental Age

Several studies observed decreased risk of PDA with increasing maternal age (Baird 1991, Rothman 1976). However, another study noted no association between isolated PDA and maternal or paternal age (Ferencz 1997).


Socioeconomic Status (SES)

An investigation noted increased risk of isolated PDA with low maternal and paternal education. However, annual household income was not related to isolated PDA risk (Ferencz 1997). Another investigation found that low SES was a risk factor for all non-chromosomal birth defects (Vrijheid 2000).

Maternal Illnesses and Conditions

PDA risk increases with maternal diabetes (Vaaramaki 2002, Loffredo 2001, Ferencz 1997, Becerra 1990). PDA has been reported among the offspring of mothers with phenylketonuria (Levy 2001). There is no association between PDA and maternal hypothyroidism orhyperthyroidism (Khoury 1989), or influenza (Ferencz 1997).

In a study that examined the relationship between PDA and maternal hyperthermia, PDA risk was associated with fever and upper respiratory infection but not with workplace temperature or sauna bathing (Tikkanen 1991).

Maternal Exposures

PDA has not been associated with maternal ampicillin use (Czeizel 2001). Maternal alcohol use does not appear to increase risk of isolated PDA (Ferencz 1997). Although one investigation reported increased risk of PDA with maternal smoking (Kallen 1999), several other studies found no such association (Ferencz 1997, Van Den Eeden 1990).

One study indicated that exposure to busulfan, lithium, retinoids, thalidomide, and thrimethadion are detrimental to the developing cardiovascular system. Cocaine use has also been linked to fetal cardiac defects, as has alcohol (Mone 2004). Maternal use of folic acid and multivitamins generally reduced the risk of birth defects, however, the effect of these substances on cardiac defects is unclear (Botto 2004, Botto 2001).

Other Exposures

One study observed increased risk of isolated PDA with paternal occupation of clerical/sales (Ferencz 1997). A recent review article reported increased risk of PDA with paternal occupations of painter, plywood mill worker, and sheet and other metal worker (Chia 2002). Exposure to solid waste facilities or incinerators is not a risk factor for PDA (Cordier 2004, Harrison 2003). The use of calcium channel blockers (Sorensen 2001), coritcosteroids (Park-Wyllie 2000), marijuana (Fried 2000), fluoxetine (Prozac™) (Chambers 1996), chemotherapy (Cardonick 2004), antihistamine drugs (Kallen 2002), or anticonvulsant drugs (Holmes 2001) are risk factors for PDA.


The reported prevalence for PDA has shown wide variation between studies, ranging between 0.9 and 20.6 per 10,000 births. There are various potential reasons for the differences in prevalence. For example, infants with PDA may be asymptomatic. One study observed that 26% of infants undergoing echocardiography solely because of heart murmur had a PDA (Rein 2000). Another study found that 60% of infants with innocent heart murmurs and 12% of infants without heart murmurs had a PDA (Arlettaz 1998).

Differences in prevalence may also be due to differences in case inclusion criteria or the use of echocardiography among the study populations. Studies may differ in their definitions of preterm, i.e., use different gestational age limits, or base the limit on birth weight; some investigations may not exclude preterm infants at all. It should be noted that the ductus arteriosus is not supposed to close until after birth, therefore, the criteria for PDA diagnosed in preterm infants varies (Hoffman 2002).


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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:

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Document E58-10957J                    Revised November 2005

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Last updated February 10, 2012