Khalili Pantea, Zhong Zixing, Peng Yanqing
Center for Reproductive Medicine, Department of Obstetrics, Zhejiang Provincial People's Hospital, (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
Obstetrics and Gynecology Research Center, Akbar Abadi Hospital, Iran University of Medical Sciences, Tehran, Iran.
BMC Pregnancy Childbirth. 2025 Aug 12;25(1):841. doi: 10.1186/s12884-025-07967-5.
Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, characterized by angiogenic imbalance and systemic dysfunction after 20 weeks of gestation. Statins, particularly pravastatin, have showed potential in prevention due to their anti-inflammatory and endothelial-protective properties, though safety in pregnancy remains uncertain. This systematic review and meta-analysis aimed to evaluate the efficacy of statins and their association with maternal risk of preeclampsia.
Two independent reviewers systematically searched data from PubMed, Scopus, Web of Science, Cochrane, and Embase databases until December 2024 for studies evaluating statins for prevention of pre-eclampsia. Those healthy pregnant women who did not develop preeclampsia were assessed as comparators. Letters, comments, case reports, and reviews were excluded. Newcastle-Ottawa Scale (NOS) were used for assessing case-control and cohort studies. The Cochrane Risk of Bias 2.0 (RoB 2.0) were adopted for evaluating randomized trials. The primary outcome was preeclampsia. Secondary outcomes included the hypertensive disorders of pregnancy (HDP), preterm labor (PTB), neonatal birth defects, and neonatal intensive care unit (NICU) admission. The random-effects method (REM) or fixed-effects method (FEM) were employed depending on the heterogeneity. Sub-group analysis was performed to identify the source of heterogeneity. The publication bias was assessed via the funnel plot, Egger's and Begg's tests. The leave-one-out sensitivity analysis were also performed. The RevMan 5.3 and Stata 16.0 were the main software used for data extraction and analysis.
11 different studies covering 10,482 pregnant participants, with 456 diagnosed with preeclampsia. Results showed a pooled risk ratio (RR) of 0.78 (95% CI: 0.33 to 1.83, p = 0.57), indicating that statin use during pregnancy was not significantly associated with a reduced risk of preeclampsia. Heterogeneity among studies was high (I² = 94%, p < 0.05), suggesting variability in study populations, dosages, and statin types. The second outcomes also showed insignificant statistical difference. Sub-group analysis implied early initiation of statins may reduce preeclampsia risk during pregnancy. Sensitivity analysis revealed that no single study had significant impact on the overall effect.
Due to significant heterogeneity, current evidence is insufficient to establish a definitive protective role for statins in preventing preeclampsia during pregnancy. While subgroup findings suggest that early initiation may be associated with reduced risk, these observations should be interpreted with caution and require confirmation in future high-quality trials.
The study protocol was registered with PROSPERO (No. CRD42024601996).
子痫前期是孕产妇和围产期发病和死亡的主要原因，其特征是妊娠20周后血管生成失衡和全身功能障碍。他汀类药物，特别是普伐他汀，因其抗炎和内皮保护特性而显示出预防潜力，但其在孕期的安全性仍不确定。本系统评价和荟萃分析旨在评估他汀类药物的疗效及其与子痫前期孕产妇风险的关联。
两名独立 reviewers 系统检索了截至2024年12月来自 PubMed、Scopus、Web of Science、Cochrane 和 Embase 数据库的数据，以寻找评估他汀类药物预防子痫前期的研究。未发生子痫前期的健康孕妇被评估为对照。排除信件、评论、病例报告和综述。采用纽卡斯尔-渥太华量表（NOS）评估病例对照研究和队列研究。采用 Cochrane 偏倚风险2.0（RoB 2.0）评估随机试验。主要结局是子痫前期。次要结局包括妊娠高血压疾病（HDP）、早产（PTB）、新生儿出生缺陷和新生儿重症监护病房（NICU）入院。根据异质性采用随机效应方法（REM）或固定效应方法（FEM）。进行亚组分析以确定异质性来源。通过漏斗图、Egger 检验和 Begg 检验评估发表偏倚。还进行了逐一剔除敏感性分析。RevMan 5.3 和 Stata 16.0 是用于数据提取和分析的主要软件。
11项不同研究涵盖10482名孕妇参与者，其中456例被诊断为子痫前期。结果显示合并风险比（RR）为0.78（95% CI：0.33至1.83，p = 0.57），表明孕期使用他汀类药物与子痫前期风险降低无显著关联。研究间异质性较高（I² = 94%，p < 0.05），表明研究人群、剂量和他汀类型存在差异。次要结局也显示无显著统计学差异。亚组分析表明早期开始使用他汀类药物可能降低孕期子痫前期风险。敏感性分析显示没有单一研究对总体效应有显著影响。
由于显著的异质性，目前的证据不足以确定他汀类药物在预防孕期子痫前期方面的明确保护作用。虽然亚组研究结果表明早期开始使用可能与风险降低有关，但这些观察结果应谨慎解释，需要未来高质量试验予以证实。
该研究方案已在 PROSPERO 注册（编号 CRD42024601996）。
