(B-268) Comparative Effectiveness of Nifedipine versus Labetalol in Pregnancy for Risk of Pregnancy Loss and Preterm Birth

Background: U.S. guidelines recommend pharmacologic management for mild or severe chronic hypertension in pregnancy. However, minimal data exist to support choice between the two first-line antihypertensives.

Objectives: To estimate the effect of initiating nifedipine versus labetalol prior to 23 weeks of gestation on the risk of pregnancy loss (miscarriage, stillbirth) and preterm birth ( < 37 weeks’ gestation).

Methods: We constructed a cohort of pregnancies in Merative’s MarketScan insurance claims data with estimated last menstrual periods between July 1, 2016 and February 1, 2022 using a prospective approach. We identified indexing prenatal claims (i.e., 1st claim with ≥1 pregnancy-related diagnosis/procedure code) and looked forward for pregnancy outcomes, if observed. We restricted to pregnancies with a fill for nifedipine or labetalol between the indexing prenatal claim and 23 weeks’ gestation and no antihypertensive use ≥270 days prior. Pregnancies were followed until the pregnancy outcome, end of the risk period, or last prenatal claim if no outcome was observed. We estimated the standardized mortality ratio and inverse probability of censoring weighted risks and risk ratios (RRs) using the Aalen-Johansen estimator. We conducted a sensitivity analysis of bias due to outcomes missing not at random (MNAR) (e.g., missing due to loss). Specifically, we repeated the analysis assuming that pregnancies with an unknown outcome in each of the following groups actually experienced the event of interest: 1) all, 2) none, 3) only nifedipine-treated, and 4) only labetalol-treated pregnancies.

Results: We identified 987 nifedipine and 4,570 labetalol initiators, of which 13% in each group had unknown outcomes. The weighted risk of pregnancy loss was 7.0% for nifedipine and 6.0% for labetalol initiators, resulting in a RR of 1.18 (95% confidence interval [CI]: 0.88, 1.58). The corresponding risks of preterm birth were 29.3% for nifedipine and 22.1% for labetalol initiators, with a RR of 1.33 (95% CI: 1.13, 1.55). We derived similar estimates in a complete case analysis: for pregnancy loss, the RR was 1.11 (95% CI: 0.81, 1.51), and for preterm birth, the RR was 1.31 (95% CI: 1.13, 1.51). In sensitivity analyses, RRs ranged from 1.09 to 1.17 for pregnancy loss and 1.21 to 1.30 for preterm birth when censoring was assumed non-differential by treatment, and 0.37 to 3.46 for loss and 0.80 to 1.97 for preterm when censoring was assumed differential by treatment.

Conclusions: Initiators of nifedipine versus labetalol prior to 23 weeks’ gestation had a higher risk of preterm birth but similar risk of pregnancy loss. Findings were robust to bias due to MNAR outcomes when censoring was assumed to be non-differential by treatment.