Kay Hee Yeon, Jang Ha Young, Kim In-Wha, Oh Jung Mi
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
College of Pharmacy, Gachon University, Incheon, 21936, Republic of Korea.
Eur J Pediatr. 2025 May 14;184(6):340. doi: 10.1007/s00431-025-06119-3.
Statin use during pregnancy remains controversial, leading to frequent therapy discontinuation in women with dyslipidemia. This study assessed the association between first-trimester statin exposure and neonatal outcomes, with a focus on long-term developmental effects up to 9 years. Using a nationwide cohort from Korea (2012-2021), we analyzed live births in women with dyslipidemia. Outcomes included congenital malformations and neurodevelopmental disorders. Among 752,351 live births, 218,296 pregnancies met the inclusion criteria after applying exclusions. Of these, 2466 were exposed to statins during the first trimester. Consistent with previous studies, no significant difference in congenital malformations was observed after adjustment (OR 1.00, 95% CI 0.83-1.20). However, subgroup analysis revealed that high-intensity statins were associated with an increased malformation risk (OR 1.47, 95% CI 1.12-1.93). Neurodevelopmental disorders initially appeared more common in the statin-exposed group, but no significant differences were found after adjustment (OR 1.13, 95% CI 0.92-1.41). This finding underscores the long-term associations of statin use during pregnancy in terms of neurodevelopmental outcomes up to 9 years of age.
This large-scale nationwide cohort study found that statin exposure during early pregnancy did not affect the long-term risk of mental and behavioral disorders in offspring. However, exposure to high-intensity statins was associated with increased risk of congenital malformations. While these findings suggest a potential risk, due to the observational nature of this study, additional studies are required to establish causality.
• Statins, widely used for reducing the risk of atherosclerotic cardiovascular disease, are contraindicated during pregnancy due to concerns about fetal development and potential teratogenic effects. • While early animal studies and some case reports suggested teratogenic risks, recent cohort studies and meta-analyses have not found a significant association between first-trimester statin use and major congenital malformations.
• This study, using a large nationwide cohort, found no significant increase in overall congenital malformations after first-trimester statin exposure, but high-intensity statin use was associated with an increased risk. • Long-term neurodevelopmental outcomes up to 9 years showed no significant differences after adjustment, providing novel insights into the safety of statin exposure during pregnancy.
孕期使用他汀类药物仍存在争议，这导致血脂异常的女性频繁中断治疗。本研究评估了孕早期他汀类药物暴露与新生儿结局之间的关联，重点关注长达9年的长期发育影响。我们利用韩国的一个全国性队列（2012 - 2021年），分析了血脂异常女性的活产情况。结局包括先天性畸形和神经发育障碍。在752351例活产中，排除不符合标准的情况后，有218296例妊娠符合纳入标准。其中，2466例在孕早期暴露于他汀类药物。与先前研究一致，调整后未观察到先天性畸形有显著差异（比值比1.00，95%置信区间0.83 - 1.20）。然而，亚组分析显示，高强度他汀类药物与畸形风险增加相关（比值比1.47，95%置信区间1.12 - 1.93）。神经发育障碍最初在他汀类药物暴露组似乎更常见，但调整后未发现显著差异（比值比1.13，95%置信区间0.92 - 1.41）。这一发现强调了孕期使用他汀类药物在9岁前神经发育结局方面的长期关联。
这项大规模全国性队列研究发现，孕早期他汀类药物暴露并未影响后代患精神和行为障碍的长期风险。然而，暴露于高强度他汀类药物与先天性畸形风险增加相关。虽然这些发现提示了潜在风险，但由于本研究的观察性质，需要进一步研究来确定因果关系。
• 他汀类药物广泛用于降低动脉粥样硬化性心血管疾病风险，由于担心胎儿发育和潜在致畸作用，孕期禁用。• 虽然早期动物研究和一些病例报告提示有致畸风险，但近期队列研究和荟萃分析未发现孕早期使用他汀类药物与主要先天性畸形之间存在显著关联。
• 本研究利用大规模全国性队列，发现孕早期他汀类药物暴露后总体先天性畸形无显著增加，但使用高强度他汀类药物与风险增加相关。• 长达9年的长期神经发育结局调整后无显著差异，为孕期他汀类药物暴露的安全性提供了新见解。
