Increased rate of birth defects after first trimester use of angiotensin converting enzyme inhibitors – Treatment or hypertension related? An observational cohort study

Maternal and Fetal Outcomes of Pregnancy in Nephrotic Syndrome Due to Primary Glomerulonephritis

“…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).…”

“…Their teratogen effect on the cardiovascular, urinary, skeletal, and central nervous systems makes them contraindicated in pregnancy particularly during the second trimester of gestation, so general advice is to have them immediately discontinued at the beginning of pregnancy ( 28 – 30 ). 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 ).…”

Adverse pregnancy outcomes associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers: A systematic review and meta‐analysis

“…A total of 19 articles, published between 1992 and 2018, were included for data extraction, with 18 articles that enabled quantitative analysis (Figure 1). Characteristics of 19 studies are presented in Table 1 32‐50 : 15 are observational cohort studies, three are case‐control studies, and one is a randomized‐controlled trial, all of which were classified as ‘sufficient quality’ or ‘low risk of bias’ studies (Table S1). Relevant studies were conducted in North America (n = 9), Europe (n = 9), or Australia (n = 2).…”

Hypertension Canada’s 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children

“…The risk for major birth defects was significantly increased for women who received ACE inhibitors with hypertension compared with nonhypertensive women (adjusted hazard ratio, 2.41; 95% CI, 1.07-5.43). 104 When women with hypertension who were receiving ACE inhibitors were compared with those receiving methyldopa, the risks were similar (adjusted hazard ratio, 1.47; 95% CI, 0.51-4.23). In a systematic review of population-based studies, Li et al also reported similar risk associations for ACE inhibitors compared with other antihypertensive medications.…”