Trauma Research Center, Nursing Faculty, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Midwifery, School of Nursing and Midwifery, Islamic Azad University Ahvaz Branch, Ahvaz, Iran.
Atherosclerosis. 2021 Jun;327:59-67. doi: 10.1016/j.atherosclerosis.2021.05.006. Epub 2021 May 16.
Statins are the drugs of choice for decreasing elevated low-density lipoprotein cholesterol. Based mostly on animal studies and case reports, they are forbidden to pregnant women and in the preconception period because of their possible teratogenic effects, for which causality has never been proven. The aim of this study was to systematically review the existing studies and to perform a meta-analysis on this topic.
The databases PubMed/MEDLINE, Scopus, and Web of Science were searched since the inception until May 16, 2020. The risk of bias for each clinical trial was evaluated using the Cochrane handbook criteria for systematic reviews. The National Institutes of Health (NIH) quality assessment tool was used for the evaluation of cohort and cross-sectional studies. Meta-analysis was performed on the extracted data. Heterogeneity was assessed using I measure and Cochrane's Q statistic. We calculated a pooled estimate of odds ratio (OR) and 95% confidence intervals (CI) using a random-effects model.
23 studies (nine cohort studies, six case reports, six case series, one population-based case-referent study and one clinical trial) with 1,276,973 participants were included in the systematic review and 6 of them (n = 1,267,240 participants) were included in meta-analysis. The results of the critical review did not suggest a clear-cut answer to the question whether statin treatment during pregnancy is associated with an increased rate of birth defects or not, while the results of the meta-analysis indicated that statin use does not increase birth defects [OR (95%CI): 1.48 (0.90, 2.42), p = 0.509], including cardiac anomalies [2.53 (0.81, 7.93), p = 0.112] and other congenital anomalies [1.19 (0.70, 2.03), p = 0.509)].
We observed no significant increase of birth defects after statin therapy. Thus, there is still no undoubtful evidence that statin treatment during pregnancy is teratogenic, and this issue still needs to be investigated, especially there are more and more pregnant women at high CVD risk that could have benefited from the statin therapy.
他汀类药物是降低升高的低密度脂蛋白胆固醇的首选药物。基于大多数动物研究和病例报告，由于其可能的致畸作用，他汀类药物在怀孕期间和受孕前阶段被禁用，但其因果关系从未得到证实。本研究的目的是系统地回顾现有研究，并对此主题进行荟萃分析。
自成立以来，我们在 PubMed/MEDLINE、Scopus 和 Web of Science 数据库中进行了搜索，截止到 2020 年 5 月 16 日。使用 Cochrane 系统评价手册标准评估每个临床试验的偏倚风险。使用 NIH 质量评估工具评估队列研究和横断面研究。对提取的数据进行荟萃分析。使用 I 测量和 Cochrane 的 Q 统计量评估异质性。我们使用随机效应模型计算了汇总估计的比值比（OR）和 95%置信区间（CI）。
共有 23 项研究（9 项队列研究、6 项病例报告、6 项病例系列研究、1 项基于人群的病例对照研究和 1 项临床试验），涉及 1,276,973 名参与者，我们对其进行了系统评价，其中 6 项研究（n=1,267,240 名参与者）纳入荟萃分析。批判性评论的结果并没有明确回答怀孕期间使用他汀类药物是否会增加出生缺陷的发生率的问题，而荟萃分析的结果表明，他汀类药物的使用不会增加出生缺陷的发生率[OR（95%CI）：1.48（0.90，2.42），p=0.509]，包括心脏畸形[2.53（0.81，7.93），p=0.112]和其他先天性畸形[1.19（0.70，2.03），p=0.509]）。
我们观察到他汀类药物治疗后出生缺陷没有显著增加。因此，仍然没有确凿的证据表明怀孕期间使用他汀类药物具有致畸性，这个问题仍需要进一步研究，特别是有越来越多的患有高 CVD 风险的孕妇可能受益于他汀类药物治疗。
