Introduction
Hypertensive disorders affect 5-10% of pregnancies,1increasing the risk of fetal growth restriction, stillbirth and other adverse outcomes.2-5 About 160,000 pregnant women take antihypertensive medications annually in the US,2 yet it is unclear which medication results in the best outcomes for women and infants. Current US and UK guidelines favor labetalol and nifedipine over methyldopa, while acknowledging uncertainty.6,7 The International Society for the Study of Hypertension in Pregnancy has stated that both methyldopa and nifedipine are acceptable.8
Randomized clinical trials (RCTs) have not provided definitive evidence because they have had small sample sizes and heterogeneous methods. A 2018 Cochrane meta-analysis9 found no evidence that any antihypertensive medication was superior to others in pregnancy, except that β-blockers and calcium channel blockers appeared more effective than methyldopa at preventing severe hypertension.9 A recent RCT reported that methyldopa was associated with significantly lower risk of small for gestational age (SGA) and NICU admission compared to labetalol, with ORs on the order of 0.40, and that the two medications were associated with similar risk of severe maternal hypertension or preeclampsia.10 The Control of Hypertension in Pregnancy Study, which randomized pregnant women to tight vs. less tight blood pressure control rather than to specific medications,11 observed better pregnancy outcomes with methyldopa than labetalol,12 but other antihypertensive medications were not examined. Many observational studies have compared women treated with an antihypertensive medication to unexposed women from the general pregnant population,3,5,13-16 making it difficult to distinguish the risks of treatment from those of hypertension itself.
Because additional evidence is needed, we sought to compare the risk of important maternal and infant outcomes with use of different antihypertensive medications using electronic health records (EHR) data for a large, diverse US population.