Prenatal Metformin Not Linked to School-Entry Developmental Vulnerability

Metformin use during pregnancy was not associated with developmental vulnerability among children assessed during their first year of full-time school, according to a cohort study published in JAMA Network Open.

The investigators noted that metformin, an oral hypoglycemic agent, is increasingly prescribed during pregnancy and crosses the placenta, and that an animal study suggested in utero exposure may impair cortical development. Whether this applies to human offspring has been unclear. Prior studies were limited by small sample sizes and heterogeneous populations, and prior evidence focused on preschool ages, when delays may not yet be apparent.

The researchers linked population-level pregnancy and birth data for singleton births in Victoria, Australia, from 2009 through 2020 with the Australian Early Development Census (AEDC), a teacher-completed national assessment performed during the first year of full-time school (ages 4-6 years). Of 177,409 children with linked outcome data, 1095 (0.6%) were exposed to metformin, defined as at least 1 prescription dispensed during pregnancy. The primary outcome, developmental vulnerability, was defined as scoring below the 10th percentile in at least 2 of 5 AEDC domains. Developmental vulnerability occurred in 18.2% of exposed vs 13.9% of unexposed children (unadjusted relative risk [RR], 1.31; 95% CI, 1.16-1.49). After adjustment for confounders using inverse probability of treatment weighting with regression adjustment, no association was observed (adjusted RR, 0.97; 95% CI, 0.74-1.29).

Metformin was also not associated with vulnerability in any individual domain. Findings were similar in a sensitivity analysis restricted to women with gestational or type 2 diabetes (adjusted RR, 1.08; 95% CI, 0.86-1.35) and among children with first-trimester exposure (adjusted RR, 1.07; 95% CI, 0.77-1.48).

The authors concluded that the findings may provide reassurance for clinicians and women considering metformin use during pregnancy. They cited limitations including potential residual confounding, including by race and ethnicity, and an inability to assess medication adherence or dose. They added that further research is needed on offspring growth and cardiometabolic health.

Source: Gordon H, Hiscock RJ, Price S, et al. Metformin exposure in pregnancy and childhood developmental outcomes. JAMA Netw Open. 2026;9(9):e2637054. doi:10.1001/jamanetworkopen.2026.37054