Deep Dutta, Kunal Mahajan, Sweekruti Jena, A B M Kamrul-Hasan, Meha Sharma, Saptarshi Bhattacharya
Statin exposure in pregnancy was not associated with increased congenital malformation risk. Potential LBW and cesarean signals, largely confined to non-pravastatin use for dyslipidaemia, warrant individualized risk-benefit assessment rather than routine use.
BACKGROUND: Statins were historically contraindicated in pregnancy over teratogenicity concerns, but accumulating human evidence prompted the FDA to remove the Category X designation in 2021. This updated systematic review and meta-analysis assessed the feto-maternal safety of statin use in pregnancy, incorporating data published since the last review in 2022.
METHODS: Following Cochrane and PRISMA guidance (PROSPERO CRD420251139343), Cochrane, ISI Web of Science, PubMed, Scopus were searched through 31 August 2025. RCTs and controlled observational studies comparing statin-exposed and unexposed pregnancies were included. Cohort data were analyzed after propensity-score matching for confounders. The primary outcome was any congenital malformation; secondary outcomes included low birth weight (LBW), stillbirth, neonatal respiratory distress, Apgar score, NICU admission, organ-specific malformations, preterm birth, gestational diabetes, and cesarean delivery. Random-effects models generated pooled odds ratios (OR).
RESULTS: Twenty-one studies (6 RCTs, 14 cohorts, 1 case-control) were analyzed, comprising 9016 exposed and 3,112,561 unexposed women. Statin-exposed women were older with higher rates of diabetes, hypertension, smoking, and cardiovascular disease. Statin exposure was not associated with congenital malformations (OR 1.05, 95%CI 0.92-1.21), including organ-specific anomalies, nor with stillbirth, neonatal respiratory distress, low Apgar, preterm birth, or gestational diabetes. LBW was increased in cohort studies and with non-pravastatin statins used for dyslipidaemia. Cesarean section appeared higher and NICU admission lower, but both lost significance on prediction interval.
CONCLUSION: Statin exposure in pregnancy was not associated with increased congenital malformation risk. Potential LBW and cesarean signals, largely confined to non-pravastatin use for dyslipidaemia, warrant individualized risk-benefit assessment rather than routine use.