Objectives: To determine the relative effectiveness of medications for preventing hypertensive disorders in high-risk pregnant women and to provide a ranking of medications using network meta-analysis.

Methods: All randomized controlled trials comparing the most commonly used medications to prevent hypertensive disorders in high-risk pregnant women that are nulliparity and pregnant women having family history of preeclampsia, history of pregnancy-induced hypertension in previous pregnancy, obstetric risks, or underlying medical diseases. We received the search results from the Cochrane Pregnancy and Childbirth's Specialised Register of Controlled Trials, searched on 31st July 2020. At least two review authors independently selected the included studies and extracted the data and the methodological quality. The comparative risk ratios (RR) and 95% confidence intervals (CI) were analyzed using pairwise and network meta-analyses, and treatment rankings were estimated by the surface under the cumulative ranking curve for preventing preeclampsia (PE), gestational hypertension (GHT), and superimposed preeclampsia (SPE). Safety of the medications is also important for decision-making along with effectiveness which will be reported in a separate review.

Results: This network meta-analysis included 83 randomized studies, involving 93,864 women across global regions. Three medications, either alone or in combination, probably prevented PE in high-risk pregnant women when compared with a placebo or no treatment from network analysis: antiplatelet agents with calcium (RR 0.19, 95% CI 0.04 to 0.86; 1 study; low-quality evidence), calcium (RR 0.61, 95% CI 0.47 to 0.80; 13 studies; moderate-quality evidence), antiplatelet agents (RR 0.69, 95% CI 0.57 to 0.82; 31 studies; moderate-quality evidence), and antioxidants (RR 0.77, 95% CI 0.63 to 0.93; 25 studies; moderate-quality evidence). Calcium probably prevented PE (RR 0.63, 95% CI 0.46 to 0.86; 11 studies; moderate-quality evidence) and GHT (RR 0.89, 95% CI 0.84 to 0.95; 8 studies; high-quality evidence) in nulliparous/primigravida women. Few included studies for the outcome of superimposed preeclampsia were found.

Conclusion: Antiplatelet agents, calcium, and their combinations were most effective medications for preventing hypertensive disorders in high-risk pregnant women when compared with a placebo or no treatment. Any high-risk characteristics for women are important in deciding the best medications. The qualities of evidence were mostly rated to be moderate.

Systematic review registration: PROSPERO CRD42018096276.