Practice Update: Cardiology

HYPERTENSION 13

Maternal antihypertensive use and congenital heart defects Hypertension

COMMENT By Gary D Webb MD A previous study from the National Birth Defects Prevention Study suggested that maternal anti- hypertensive use was associated with an increased frequency of congenital heart defects (CHD) in their offspring. This 2004–2011 follow-up study comes to similar conclusions. The authors observed an increased risk of four types of CHD: coarctation of the aorta, pulmo- nary valve stenosis, perimembranous VSD, and secundum ASD. Their results supported the earlier findings that anti- hypertensive medication use (including beta-blockers and angiotensin recep- tor blockers) may be associated with an increased risk of specific CHDs, although they could not completely rule out confounding factors. Interestingly, a research letter was published in JAMA Internal Medicine at about the same time. This examined beta-blocker exposure in pregnancy and the risk of fetal cardiac abnormal- ities. The authors concluded that the increased risk of CHD and offspring was due to comorbidities rather than exposure to beta-blockers specifically. These authors found that the results provided reassurance regarding the use of beta blockers for the treatment of cardiac conditions in pregnant women. Until these issues have been resolved, clinicians should use beta blockers and treat hypertension (avoiding ACE inhib- itors) in pregnant women as clinically indicated.

Until these issues have been resolved, clinicians should use beta blockers and treat hypertension (avoiding ACE inhibitors) in pregnant women as clinically indicated.

Take-home message • The authors evaluated outcomes from >20,000 pregnancies to evaluate the asso- ciation between maternal antihypertensive use in the first trimester of pregnancy and the risk of congenital heart defects (CHDs). Early pregnancy hypertensive use was reported by 1.5% of case mothers vs 0.9% of control mothers. There were four specific CHD phenotypes which appeared to be associated with antihypertensive use. These were coarctation of the aorta, pulmonary valve stenosis, perimembranous ventricular septal defect, and secundum atrial septal defect. The association between these phenotypes and both beta-blocker use or renin-angiotensin system blocker use was significant, but there was less evidence for other classes of medication. • Maternal antihypertensive use in early pregnancy may be associated with an increased risk of four specific types of CHD.

Abstract Previous NBDPS (National Birth Defects Pre- vention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers miss- ing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmal- formed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihyper- tensive use during the month before conception through the third month of pregnancy, con- trolling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking,

and NBDPS site. Overall, 164 (1.5%) case moth- ers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihyper- tensive medication class reported: coarctation of the aorta (2.50 [1.52–4.11]), pulmonary valve stenosis (2.19 [1.44–3.34]), perimembranous ventricular septal defect (1.90 [1.09–3.31]), and secundum atrial septal defect (1.94 [1.36–2.79]). The associations for these phenotypes were statistically significant for mothers who reported β-blocker use or renin-angiotensin system blocker use; estimates for other antihyperten- sive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihy- pertensive medication use may be associated with increased risk of specific CHDs, although

Dr Webb is Editor-in-Chief for the ChiP Network and the ACHD Learning Center, Consultant to the

Cincinnati Adult Congenital Heart

Program, and Emeritus Professor, University of Cincinnati, Department of Pediatrics.

we cannot completely rule out confounding by underlying disease characteristics. Maternal antihypertensive medication use and congenital heart defects: updated results from the National Birth Defects Prevention Study. Hypertension 2017 Apr 03;[EPub Ahead of Print], SC Fisher, AR Van Zutphen, MM Werler, et al.

VOL. 2 • NO. 1 • 2017