Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials

• Published in: American journal of obstetrics and gynecology 2023-05, Vol.228 (5), p.535-546
• Main Authors: Liu, Yuan-hui, Zhang, Ye-shen, Chen, Jia-yi, Wang, Zhi-jian, Liu, Yao-xin, Li, Jia-qi, Xu, Xiao-ji, Xie, Nian-jin, Lye, Stephen, Tan, Ning, Duan, Chong-yang, Wei, Yan-xing, He, Peng-cheng
• Format: Article
• Language: English
• Subjects: Aspirin - therapeutic use; Bayes Theorem; Calcium; Female; Heparin, Low-Molecular-Weight - therapeutic use; Humans; Hypertension, Pregnancy-Induced - drug therapy; Network Meta-Analysis; Pre-Eclampsia - drug therapy; Pre-Eclampsia - prevention & control; preeclampsia; Pregnancy; pregnancy-induced hypertension; prevention; prophylactic strategy; Randomized Controlled Trials as Topic; Vitamin D - therapeutic use
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2022.10.014

Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42–0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45–0.95), and exercise (0.68; 95% confidence interval, 0.50–0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective pr