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.