Oral antihypertensive agents in pregnancy and fetal growth restriction – a population-based cohort study
Summary
Introduction: Currently, there is no consensus on whether methyldopa, labetalol, or nifedipine is the preferred treatment for hypertension in pregnancy. These agents might have varying effects on fetal growth and the risk for small for gestational age (SGA) birth. Randomised controlled trials lack sufficient power to determine if one of the three agents poses an increased risk regarding this outcome.
Methods: In this population-based cohort study, automated pharmacy dispensing data (PHARMO) was linked to the Netherlands Perinatal Registry (Perined) for outcomes of pregnancies between 2000-2019. Using multivariate logistic regression analysis, we retrospectively assessed the effect of methyldopa, labetalol and nifedipine on the outcome SGA.
Results: The risk of SGA birth was not significantly different for pregnancies exposed to labetalol compared to methyldopa (adjusted odds ratio (aOR) = 0.94, 95% confidence interval (CI): 0.81-1.10, p=0.47). Due to the inclusion of pregnancies where nifedipine was used as a tocolytic agent for threatened preterm delivery, this treatment could only be validly compared with the other two agents in the chronic hypertension subgroup analysis (start of treatment < 20 weeks gestational age). In this subgroup, the risk of SGA birth for nifedipine was comparable to that of methyldopa (aOR=1.11, 95% CI: 0.71–1.68, p=0.22) and labetalol (aOR=1.01, 95% CI: 0.63–1.59, p=0.93).
Conclusion: Our findings suggest that there is no difference in the risk of SGA birth between methyldopa, labetalol and nifedipine. Large-scale observational studies using other data sources with more elaborate data on covariates and treatment indication are needed for confirmation.