Medications for preventing hypertensive disorders in high-risk pregnant women: a systematic review and network meta-analysis

Abstract

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

Barriers to progress in pregnancy research: How can we break through?

“…For pre-eclampsia prevention, repurposed basic drugs are in current clinical use including calcium and low-dose aspirin (<300 mg) (14). Although evidence from clinical trials suggests that aspirin is effective in reducing the risk of pre-eclampsia by ~60% in selected women, whose risk of preterm pre-eclampsia was >1:100 using a biomarker and risk-factor based screening algorithm (15), there is no clarity on the underlying mechanism of action.…”

Maternal‐neonatal events resulting from medications for preventing hypertensive disorders in high‐risk pregnant women: A systematic review and network meta‐analysis

“…[7][8][9] A PubMed search conducted in October 2022 found four network meta-analyses focusing on the medications used for PE prophylaxis, which confirmed the benefits of certain medications for preventing PE and gestational hypertension (GHT). [10][11][12][13] Among these, three supported the effects of calcium supplementation [10][11][12] and one considered five medication groups, namely antiplatelet agents, anticoagulants, antioxidants, nitric oxide, and calcium. 13 To date, the effects of these preventive medications on placental abruption and maternal and neonatal hemorrhage from the evidence of systematic reviews and meta-analyses are still uncertain.…”

“…[10][11][12][13] Among these, three supported the effects of calcium supplementation [10][11][12] and one considered five medication groups, namely antiplatelet agents, anticoagulants, antioxidants, nitric oxide, and calcium. 13 To date, the effects of these preventive medications on placental abruption and maternal and neonatal hemorrhage from the evidence of systematic reviews and meta-analyses are still uncertain. 2,12,14…”

Results of a Five-Year Experience in First Trimester Preeclampsia Screening

“…Current guidelines from the Italian Association of Preeclampsia (AIPE) for the early identification of women with a higher risk of developing preeclampsia (PE) are mainly based on maternal personal, medical, and family history [ 1 ]. Among these risk factors, the main role is played by [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]: Nulliparity; Afro-Caribbean ethnicity; Maternal age < 20 or >35 years; Maternal body mass index (BMI) > 30; Chronic maternal hypertension; Diabetes, renal pathologies, and autoimmune diseases such as scleroderma, rheumatoid arthritis, and systemic lupus erythematosus; Positive obstetric history of PE; Positive familiar history of PE. …”