Pregnancy Outcome After First‐Trimester Exposure to Statins: Study Results Based on the Embryotox Cohort

PURPOSE: This observational cohort study aimed to assess the risk of adverse pregnancy and neonatal outcomes in pregnancies exposed to statins during the first trimester, given that the use of statins during pregnancy remains controversial. The primary study endpoints were the rates of spontaneous abortion and major birth defects. METHODS: In total, 188 pregnancies exposed to statins in the first trimester were compared with a cohort of 564 pregnancies without the study medication, which were recorded at the Embryotox Centre between January 2000 and June 2021. The effect of statin exposure on pregnancy outcome was estimated using Cox proportional hazards regression models. Log-binomial regression was used to evaluate the risk of major birth defects. RESULTS: Major birth defects were observed in 10 of 135 (7.4%) infants in the statin cohort and in 12 of 501 (2.4%) infants in the comparison cohort (RR 3.09, 95% CI 1.37-7.00). After adjustment for relevant baseline covariates and additional maternal disease factors, the difference substantially attenuated (RRadj 2.16; 95% CI 0.88-5.31). The cumulative incidence of spontaneous abortion was 26.8% in the statin-exposed versus 15.0% in the comparison cohort (HR 1.86, 95% CI 1.13-3.04; HRadj 1.66, 95% CI 0.99-2.78). CONCLUSIONS: Current evidence suggests that statins are not major teratogens. The observed associations between statin exposure and birth defects, as well as unfavourable pregnancy outcomes, are presumably influenced by confounding factors such as underlying maternal disease. Our study results lend support to this assumption. However, they should be interpreted cautiously due to the limited cohort size.