Comparative effectiveness of initiating nifedipine versus labetalol in early gestation for chronic hypertension in pregnancy

Background: Limited data exist on the comparative effectiveness and safety of first-line medications to treat chronic hypertension in pregnancy. We compared nifedipine versus labetalol initiation before 23 weeks gestation for risk of pregnancy loss (miscarriage or stillbirth) and preterm birth (<37 weeks). Methods: We identified pregnancies in Merative's MarketScan commercial claims data with estimated last menstrual periods between July 1, 2016 and February 1, 2022. We included those with a new nifedipine or labetalol fill before 23 weeks gestation. We estimated risks, risk differences (RDs) per 100 pregnancies, and risk ratios (RRs) among nifedipine versus labetalol initiators using a weighted Aalen-Johansen estimator to account for confounding and informative censoring. We also conducted a post hoc analysis to estimate the comparative effect of nifedipine versus labetalol on risk of preeclampsia. Results: We identified 987 nifedipine and 4,570 labetalol initiators during the study period. The weighted risk of pregnancy loss was 7.0% among nifedipine and 6.0% among labetalol initiators (RD=1.1 [-0.7, 2.8]; RR=1.18 [0.87, 1.59]). Weighted risks of preterm birth were 29.4% versus 22.2%, respectively (RD=7.2 [3.9, 10.5], RR=1.32 [1.13, 1.55]). In post hoc analyses, the weighted risks of preeclampsia were 38.6% versus 33.9%, respectively (RD=4.7 [0.7, 8.7], RR=1.14 [1.01, 1.28]). Findings were consistent across various sensitivity analyses. Conclusions: Compared to labetalol initiators, nifedipine initiators experienced an increased risk of preterm birth but not pregnancy loss. The elevated risk of preterm birth may be explained by an increased risk of preeclampsia among nifedipine initiators, resulting in medically indicated preterm birth.