Oral antihypertensive treatment during pregnancy: a systematic review and network meta-analysis

Considering safety and effectiveness of oral antihypertensive agents when treating hypertensive disorders of pregnancy, no preference can be stated between the 3 agents currently available. Therefore, this systematic review and network meta-analysis aims to determine the effects of antenatal treatment with methyldopa, labetalol, or nifedipine for hypertensive disorders of pregnancy regarding maternal or fetal/neonatal morbidity and mortality.

On August 25, 2023, an electronic search in PubMed/Medline, Embase, and CENTRAL was performed.

Randomized controlled trials reporting on perinatal outcomes in hypertensive pregnancies treated with oral antihypertensive agents of interest (methyldopa, labetalol, or nifedipine) or placebo/no treatment were identified.

Quality assessment was performed using the Cochrane Risk of Bias tool for randomized controlled trials and trustworthiness was assessed with the Trustworthiness in RAndomised Controlled Trials Checklist. Data on our predefined outcomes were extracted and relative risks were calculated in network estimates if possible.

Twenty three trials (3989 women) were included in our network meta-analysis with an overall low-to-moderate quality. Compared to placebo/no treatment, labetalol and methyldopa significantly reduced the incidence of severe hypertension (including 8 studies, relative risk 0.20 [95% confidence interval 0.09-0.48] and 0.44 [0.20-0.99], respectively). In the network meta-analysis, labetalol vs nifedipine was associated with a reduction in preeclampsia (relative risk, 0.50 [0.28-0.87]; 15 studies) and preterm birth (relative risk, 0.68 [0.52-0.90]; 14 studies). No significant differences could be detected for any of the other outcomes of interest.

When comparing the oral antihypertensive agents currently available head-to-head, no significant differences in the primary outcome, severe hypertension, could be detected as well as on most of the secondary outcomes of interest. Considering the preference of labetalol over nifedipine regarding the outcomes preeclampsia and preterm birth, a modest favor for labetalol could be stated. Included studies however were of low overall quality warranting caution when interpreting results.