Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Center of excellence for Omics Research, National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Expert Opin Drug Saf. 2024 Mar;23(3):313-321. doi: 10.1080/14740338.2023.2251888. Epub 2023 Sep 1.
Statins, previously rated as pregnancy category X agents, were contraindicated during pregnancy due to the teratogenic effects observed in animal studies. However, it is still controversial whether statins have detrimental impact on pregnant women or not, and some studies even suggest a potential benefit of statin use against pregnancy complications. The aim of this study was to explore whether maternal exposure to statins is associated with increased rates of pregnancy-related adverse events (AEs), including abortion, abortion spontaneous, preterm birth, low birth weight, stillbirth/fetal death, and fetal complications.
Data from 1 January 2004 to 30 June 2022 were extracted through the U.S. FDA Adverse Event Reporting System (FAERS) database, to conduct disproportionality analysis and Bayesian analysis by reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms. To identify the potential risks of pregnancy-related AEs, each statin was compared to all the other drugs, all the other statins, and the reference drugs (fenofibrate and evolocumab).
A total of 477 cases involving pregnancy-related AEs associated with stains were submitted to the FAERS database by healthcare professionals. No obvious disproportionate association of abortion, abortion spontaneous, or stillbirth/fetal death was identified for all statins during gestation. In comparison with all the other drugs, lovastatin showed an increased risk of fetal complications (ROR = 2.45, 95% CI, 1.22-4.95; IC = 0.63), and pravastatin demonstrated increased risks of preterm birth (ROR = 4.89, 95% CI, 3.65-6.54; IC = 1.69) and low birth weight (ROR = 9.60, 95% CI, 5.56-16.56; IC = 1.88). Similar results were found when compared lovastatin or pravastatin with fenofibrate. Furthermore, statins were associated with higher proportion of fetal complications and preterm birth when comparing with evolocumab.
Statins did not increase the risk of pregnancy-related AEs, including abortion, abortion spontaneous, or stillbirth/fetal death. However, we did find significant disproportionality signals for preterm birth and low birth weight associated with pravastatin, and lovastatin was related to a higher proportion of fetal complications. The results in this study may provide evidence on the safety of statins during pregnancy, which need to be verified in further investigations.
他汀类药物以前被评为妊娠类别 X 药物，由于在动物研究中观察到致畸作用，因此在怀孕期间被禁用。然而，他汀类药物是否对孕妇有不良影响仍存在争议，一些研究甚至表明他汀类药物的使用可能对妊娠并发症有益。本研究旨在探讨母体暴露于他汀类药物是否与增加与妊娠相关的不良事件（AE）的发生率相关，包括流产、自然流产、早产、低出生体重、死胎/胎儿死亡和胎儿并发症。
从 2004 年 1 月 1 日至 2022 年 6 月 30 日，通过美国食品和药物管理局不良事件报告系统（FAERS）数据库提取数据，通过报告比值比（ROR）和贝叶斯置信传播神经网络（BCPNN）算法进行不相称性分析和贝叶斯分析。为了确定与妊娠相关的 AE 的潜在风险，将每种他汀类药物与所有其他药物、所有其他他汀类药物和参考药物（非诺贝特和依洛尤单抗）进行比较。
医疗保健专业人员向 FAERS 数据库提交了总共 477 例与妊娠相关的 AE 相关的他汀类药物病例。在妊娠期间，没有发现所有他汀类药物与流产、自然流产或死胎/胎儿死亡之间存在明显的不成比例的关联。与所有其他药物相比，洛伐他汀显示出胎儿并发症的风险增加（ROR=2.45，95%CI，1.22-4.95；IC=0.63），普伐他汀显示出早产（ROR=4.89，95%CI，3.65-6.54；IC=1.69）和低出生体重（ROR=9.60，95%CI，5.56-16.56；IC=1.88）的风险增加。与非诺贝特相比，洛伐他汀或普伐他汀也得到了类似的结果。此外，与依洛尤单抗相比，他汀类药物与更高比例的胎儿并发症和早产相关。
他汀类药物不会增加与妊娠相关的 AE 的风险，包括流产、自然流产或死胎/胎儿死亡。然而，我们确实发现普伐他汀与早产和低出生体重相关的显著不成比例信号，而洛伐他汀与更高比例的胎儿并发症相关。本研究的结果可能为他汀类药物在妊娠期间的安全性提供证据，但需要进一步研究证实。
