(284) Oral Antihypertensives in Hypertensive Pregnancy and the Association with Fetal Growth: a Population-Based Cohort Study

Background: Hypertensive disorders of pregnancy complicate up to 10% of pregnancies. Currently, three oral antihypertensive agents (methyldopa, labetalol, nifedipine) are frequently prescribed. In the Netherlands, only methyldopa is registered as safe during pregnancy. This is due to insufficient data on nifedipine use in pregnancy to report safety. Moreover, previous studies report an association between labetalol use and fetal growth restriction.

Objectives: Our aim was to determine if exposure to oral methyldopa, labetalol or nifedipine affects fetal growth.

Methods: In this retrospective population-based cohort study, linked pharmacy dispensing and pregnancy records from the PHARMO Perinatal Research Network (PPRN) were used, including pregnancies from 2000-2019. Pregnancies were considered exposed when an antihypertensive was prescribed for at least seven days of pregnancy . Pregnancies using polytherapy were excluded from analysis. Our primary outcome of interest was small for gestational age (SGA), defined as birth weight less than 10th percentile, corrected for gestational age and sex . Using multivariate logistic regression analysis, we computed adjusted odds ratios (aOR) to assess the association between the three oral antihypertensives and SGA. For our primary outcome SGA, pregnancies using nifedipine were analyzed in the subgroup chronic hypertension because above 20 weeks gestational age nifedipine could be used as tocolytic agent in risk for premature delivery.

Results: A total of 10.614 pregnancies were identified with dispensing data, of which 7.986 pregnancies were considered exposed to methyldopa (N=5900), labetalol (N=1391) or nifedipine (N=695). Maternal age was 32.2 (4.7) for methyldopa, 32.6 (4.7) for labetalol and 30.7 (5.4) for nifedipine group (mean(SD)). Gestational age and birth weight was 38+0 (2+3) weeks and 3057 (736) grams for methyldopa, 38+3 (2+2) weeks and 3134 (695) grams for labetalol and 37+3 (2+4) weeks and 2922 (707) grams for nifedipine (mean(SD)). No significant difference in risk for SGA birth was observed for labetalol versus methyldopa (aOR = 0.94, 95% CI: 0.81-1.10). No significant difference in risk for SGA birth was observed for nifedipine versus methyldopa (aOR = 1.11, 95% CI: 0.71-1.68) and nifedipine versus labetalol (aOR 1.01, 95% CI: 0.63-1.59).

Conclusions: Our results do not suggest a difference in risk of SGA between methyldopa, labetalol and nifedipine . Cumulative dose will be analyzed to support these findings. Large-scale observational studies using Electronic Patient Files with elaborate data (e.g. treatment indication) will be helpful to study other maternal and fetal outcomes.