Antihypertensive Use In Pregnancy Linked With Congenital Heart Defects

Research reported in Hypertension confirmed an association between the use of antihypertensive medication during pregnancy and the risk for congenital heart defects.¹

Although maternal hypertension has been linked with an increased risk for congenital heart defects, it is unclear whether there is also a connection between congenital heart defect risk and antihypertensive use in early pregnancy.²

A previous study by the current investigators, which analyzed data from the National Birth Defects Prevention Study (NBDPS) found positive associations between the following antihypertensives and congenital heart defects: beta-blockers and pulmonary valve stenosis and secundum atrial septal defects (ASD2); centrally acting antiadrenergic agents and Ebstein malformation; and diuretics and ASD2.³

At that time, the NBDPS data set included births that occurred from 1997 to 2003; it now includes births through 2011. To expand on those earlier findings, the researchers conducted a new analysis of 10,625 cases of congenital heart defect and 11,137 controls from the updated dataset. Participants represented 10 US states and had estimated delivery dates between 1997 and 2011. Antihypertensive use in early pregnancy was reported by 1.5% of cases and 0.9% of controls.

After controlling for maternal age, race/ethnicity, body mass index, cigarette smoking during the first trimester, and study site, the results show that an increased risk of the following congenital heart defects was associated with antihypertensive use in the month prior to conception through the third month of pregnancy:

• Coarctation of the aorta (odds ratio [OR]: 2.50; 95% CI, 1.52-4.11)
• Pulmonary valve stenosis (OR: 2.19; 95% CI, 1.44-3.34)
• Perimembranous ventricular septal defect (OR: 1.90; 95% CI, 1.09-3.31)
• Secundum atrial septal defect (OR: 1.94, 95% CI, 1.36-2.79)

The strongest associations with these congenital heart defects were observed with the use of beta-blockers or renin-angiotensin system blockers, with risk estimates ranging from 2.35 to 6.58. Mothers with untreated hypertension showed a lower risk for congenital heart defects compared with mothers taking antihypertensives.  

These 4 particular congenital heart defects “have been hypothesized to stem from abnormal intracardiac blood flow. The increased blood pressure variability that characterizes hypertension may lead to this type of abnormal blood flow, as may antihypertensives acting directly on the fetus,” the investigators wrote.

“Many antihypertensives — including beta-blockers and angiotensin-converting enzyme inhibitors — cross the placenta, potentially inducing fetal hypotension, which may affect fetal heart development.”^4,5

These findings are in line with previous results, although further research is needed to explore whether elevated congenital heart defect risk may be accounted for by underlying disease characteristics rather than antihypertensive use.

References

1. Fisher SC, Van Zutphen AR, Werler MM, et al;  the National Birth Defects Prevention Study. Maternal antihypertensive medication use and congenital heart defects: updated results from the National Birth Defects Prevention Study. Hypertension. 2017;69(5):798-805. doi:10.1161/HYPERTENSIONAHA.116.08773
2. Bateman BT, Huybrechts KF, Fischer MA, et al. Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study. Am J Obstet Gynecol. 2015;212(3):337.e1-14. doi:10.1016/j.ajog.2014.09.031
3. Caton AR, Bell EM, Druschel CM, et al; National Birth Defects Prevention Study. Antihypertensive medication use during pregnancy and the risk of cardiovascular malformations. Hypertension. 2009;54(1):63-70. doi:10.1161/HYPERTENSIONAHA.109.129098
4. Reisenberger K, Egarter C, Sternberger B, Eckenberger P, Eberle E, Weissenbacher ER. Placental passage of angiotensin-converting enzyme inhibitors. Am J Obstet Gynecol. 1996;174(5):1450-1455.
5. Schneider H, Proegler M. Placental transfer of beta-adrenergic antagonists studied in an in vitro perfusion system of human placental tissue. Am J Obstet Gynecol. 1988;159(1):42-47.