Feto-maternal safety of statins in pregnancy: An updated systematic review and meta-analysis

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.

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).

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.

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.