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. Conclusion: 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. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> What Is Known: • 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. </entry> </row> <row> <entry align="left" nameend="c2" namest="c1"> What Is New: • 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. </entry> </row> </tbody> </tgroup> </Table>

Pregnancy and neonatal outcomes after fetal exposure to statins among women with dyslipidemia: a nationwide cohort

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2025年5月14日

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Hee Yeon Kay,
Ha Young Jang,
In-Wha Kim,
Jung Mi Oh

摘要

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. Conclusion: 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.

What Is Known:

• 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.

What Is New:

• 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.