The association between oral antihypertensive agents and perinatal outcomes in early-onset fetal growth restriction: A post-hoc analysis of the Dutch OPTICORE study

Objective: Early-onset fetal growth restriction (FGR) and hypertensive disorders of pregnancy frequently co-occur, reflecting shared underlying placental pathology. We evaluated whether the type of oral antihypertensive agent (OAA) (i.e. methyldopa, labetalol, nifedipine, or a combination) is associated with birthweight or adverse perinatal outcomes in pregnancies complicated by early-onset FGR. Study design: A post-hoc analysis of the OPtimal TIming of antenatal COrticosteroid administration in early-onset fetal growth REstriction (OPTICORE) study was performed, including women treated with methyldopa, labetalol, nifedipine, or a combination. The primary outcome was birthweight. Secondary outcomes included gestational age (GA) and adverse perinatal outcome measures as defined by the Core Outcome Set for FGR (COSGROVE). Outcomes were compared separately in monotherapy and combination therapy groups. Adjusted multilevel linear or logistic regression analyses were performed. Results: Of the 1,453 women included in the OPTICORE study, 849 (58.4%) received OAAs during pregnancy, with exposure groups ranging from 14 to 230 patients. No significant differences were found in absolute birthweight, GA, or adverse perinatal outcomes between monotherapy groups nor between combination therapy groups. Conclusion: Among early-onset FGR pregnancies, we found no differences in birthweight, GA, or adverse perinatal outcomes between the commonly used OAAs methyldopa, labetalol, and nifedipine when compared head-to-head, nor between different combination therapies. These findings suggest that OAA treatment in this context should not be guided by concerns regarding fetal growth or adverse perinatal outcomes. However, since some exposure groups included a limited number of patients and possible bias by indication, results should be interpreted with caution.