Comparative Effectiveness of Antihypertensive Agents vs. Control in the Prevention and Management of Preeclampsia: A Network Meta-Analysis
Abstract
Hypertensive disorders of pregnancy, particularly preeclampsia, are a leading cause of maternal and perinatal morbidity. While antihypertensive therapy is recommended, clinical uncertainty persists regarding the optimal agent to maximize maternal safety while minimizing adverse neonatal outcomes such as neonatal intensive care unit (NICU) admission. This review aimed to evaluate the comparative effectiveness and safety of pharmacological antihypertensive agents versus standard care or placebo in the management of hypertensive disorders of pregnancy through a network meta-analysis (NMA). A systematic review and frequentist random-effects NMA of randomized controlled trials (RCTs) was conducted. Major databases were searched for RCTs comparing antihypertensive agents (labetalol, nifedipine, methyldopa, hydralazine, prazosin) and controls. The primary neonatal outcome evaluated in this network was NICU admission. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Twenty-five RCTs were included in the qualitative and quantitative synthesis. The network geometry was anchored by labetalol and nifedipine. In the NMA, no individual antihypertensive agent demonstrated a statistically significant reduction in the risk of NICU admission compared to labetalol. However, probabilistic ranking (P-scores) identified methyldopa (P-score = 0.859) and hydralazine (0.791) as the most favourable interventions for minimizing NICU admissions. Nifedipine showed a slightly elevated, though non-significant, risk profile compared to labetalol (RR 1.09, 95% CI 0.80-1.49). The placebo and standard care ranked lowest. The overall certainty of evidence ranged from moderate to very low due to imprecision and indirectness. Active pharmacological management of hypertension in pregnancy is superior to placebo or standard care. While labetalol and nifedipine remain mainstays for acute blood pressure control, methyldopa and hydralazine probabilistically rank higher for minimizing NICU admissions. These findings support individualized antihypertensive selection based on clinical acuity and maternal-fetal hemodynamics.