Use of antihypertensive medications in pregnancy and the risk of adverse perinatal outcomes: McMaster Outcome Study of Hypertension In Pregnancy 2 (MOS HIP 2).

backgroundUncertainty remains about the potential harmful effects of antihypertensive therapy on the developing fetus, especially for beta-blockers (betab).

methodsWe prospectively enrolled all singleton women with a blood pressure >/= 140/90 mm Hg during pregnancy. The main analysis included 1948 women with all forms of hypertension and compared the use of betab drugs, non-betab drugs or a combination of both, to no treatment. The primary study outcome was a composite of the diseases of prematurity, need for assisted ventilation for greater than 1 day, or perinatal death. A sub-group analysis evaluated the four treatment options among 583 singleton women with chronic hypertension before 20 weeks gestation.

resultsIn the main analysis, no association was observed between betab use and the primary composite outcome [adjusted odds ratio (OR) 1.4, 95% CI 0.9-2.2], while an association was seen with non-betab therapy (OR 5.0, 95% CI 2.6-9.6) and combination therapy (OR 2.9, 95% CI 1.8-4.7). In the sub-group of 583 women with hypertension before 20 weeks, use of a non-betab drug (OR 4.9, 95% CI 1.7-14.2) or combination therapy (OR 2.9. 95% CI 1.1-7.7) was significantly associated with the primary composite outcome, while betab monotherapy was not (OR 1.4, 95% CI 0.6-3.4).

conclusionsMaternal use of antihypertensive medications other than betabs was associated with both major perinatal morbidity and mortality, while betab monotherapy was not. The combined use of betab and non-betab medications demonstrated the strongest association. Before definitive conclusions can be drawn, a large multicentre randomized controlled trial is needed to address the issues of both maternal efficacy and fetal safety with the use of one or more antihypertensive agents in pregnancy.