Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations

“…They hypothesised, therefore, that perhaps the risk of congenital anomalies was due to the characteristics of the hypertensive women, rather than the antihypertensives themselves. This conclusion was similar to that made in Bateman et al 9 . The different findings may be explained by the fact that, in contrast to Walfisch et al.…”

“…Hoeltzenbein et al conducted a prospective observational trial comparing 329 women accidentally exposed to ACEIs during their first trimester of gestation and no longer than week 20 and 654 control pregnant women without a history of hypertension ( 31 ). The significantly increased rate of major birth defects in the ACEIs cohort confirmed the results of previous studies on these drugs in pregnancy ( 32 , 33 ), but they also investigated maternal hypertension impact on malformations, already demonstrated in other trials ( 34 , 35 ). Comparing patients affected by chronic hypertension exposed to ACEIs vs. patients treated with methyldopa, they concluded that malformations rate was not significantly different, also suggesting the potential role of severe hypertension per se as a risk factor for adverse fetal outcomes ( 31 ).…”

“…This review also found a significant association between cardiovascular malformations, miscarriage and stillbirth and ACEi/ARB exposure. A similar risk was observed in a cohort of 1 333 624 pregnancies [ 63 ], including 4107 (0.31%) following first trimester ACEi exposure that found an increased risk of overall malformations in the ACEi-exposed pregnancies [unadjusted relative risk (RR), 1.82; 95% CI 1.61, 2.06] and of cardiac malformations (RR 2.95; 95% CI 2.50, 3.47). On further analysis, however, restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed.…”