Hypertension Linked to First-Trimester Birth Defects

From Medscape Medical News Ricki Lewis, PhD October 18, 2011 — Pregnant women with treated or untreated hypertension are at higher risk of carrying fetuses with congenital anomalies than are normotensive women. The finding points to elevated blood pressure as the teratogen, rather than the drugs used to treat it, according to a report published online October 18 in the British Medical Journal. Angiotensin-converting enzyme (ACE) inhibitors are known to be teratogenic during the second and third trimesters. A 2006 study using data from the Tennessee Medicaid population associated first-trimester ACE inhibitor exposure with neural tube defects and cardiac malformations, but did not find association with other antihypertensives. Two subsequent studies implicated other drugs. The new investigation disentangles the effects of antihypertensive drugs from those of the condition they treat. De-Kun Li, MD, PhD, MPH, and colleagues at the Kaiser Foundation Research Institute in Oakland, California, conducted a population-based retrospective cohort study that evaluated 465,754 mother-infant pairs from northern California in the Kaiser Permanente database, from 1995 to 2008. This included electronic medical records of fetal malformations, maternal drug exposures, and potential confounding factors such as preexisting diabetes and overweight during pregnancy. The researchers compared 4 groups of pregnant women: those with hypertension who took ACE inhibitors during the first trimester, those with hypertension who took other antihypertensives during the first trimester, those with hypertension who took no antihypertensives during the first trimester, and pregnant women who did not have hypertension and did not receive antihypertensives for other indications. The offspring of women taking antihypertensives had elevated rates of cardiac anomalies and birth defects overall, but not of neural tube defects, compared with women not taking the drugs. However, the elevation was not seen when rates were compared with the cohort of women with untreated hypertension, implicating the underlying hypertension. Use of ACE inhibitors in women with hypertension was associated with increased risk for congenital heart defects compared with normal control participants (those with neither hypertension nor use of antihypertensives), at 15 of 381 (3.9%) v 6232 of 400,021 (1.6%) patients, with an odds ratio of 1.54 (95% confidence interval [CI], 0.90 - 2.62). Similar associations were found for other antihypertensives. However, compared with the 2.4% (708/29,735) of pairs with untreated hypertension that had congenital heart defects, the use of ACE inhibitors or other antihypertensives in the first trimester was not associated with increased risk (odds ratios, 1.14 [95% CI, 0.65 - 1.98] and 1.12 [95% CI, 0.76 - 1.64]). "Compared with the hypertension controls, there was no increased risk of malformation associated with use of either ACE inhibitors or other antihypertensive drugs," the investigators conclude. Limitations of the study include not controlling for influences of diet and exposures to other medications and not delineating more specific types of birth defects. In an editorial, Allen Mitchell, MD, from the Slone Epidemiology Center at Boston University, Massachusetts, supports the findings, adding that we still have much more to learn about the precise effects of elevated maternal blood pressure on the fetus. The study was funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration. The authors have disclosed no relevant financial relationships. BMJ. Published online October 18, 2011.