Metformin pregnancy exposure appears developmentally safe

Metformin use in pregnancy was not associated with school-entry developmental vulnerability.
*Population-based cohort study; Level 2b (OCEBM).

Citation

Gordon H, Hiscock RJ, Price S, et al. Metformin Exposure in Pregnancy and Childhood Developmental Outcomes. JAMA Network Open. 2026;9(9):e2637054. doi:10.1001/jamanetworkopen.2026.37054

Background

Metformin is increasingly used during pregnancy and crosses the placenta. Animal data raised concern about brain development, but human long-term developmental data have been limited.

Patients

177,409 singleton children born in Victoria, Australia, from 2009 to 2020 with linked school-entry developmental data. Exclusions included congenital anomalies, uncertain diabetes diagnoses, and insulin use without recorded diabetes.

Intervention

At least 1 dispensed metformin prescription during pregnancy.

Control

No metformin dispensed during pregnancy.

Outcome

Developmental vulnerability on the Australian Early Development Census: below the 10th percentile in at least 2 of 5 developmental domains.

Follow-up Period

First year of full-time school, age 4 to 6 years.

Results

Group Children Developmentally vulnerable
Metformin exposed 1,095 199 (18.2%)
Not exposed 176,314 24,379 (13.9%)

After adjustment, metformin was not associated with developmental vulnerability: adjusted relative risk 0.97 (95% CI 0.74 to 1.29). No individual developmental domain showed a significant association.

In the subgroup with gestational or type 2 diabetes, results were similar: adjusted relative risk 1.08 (95% CI 0.86 to 1.35). First-trimester exposure also was not associated with vulnerability: adjusted relative risk 1.07 (95% CI 0.77 to 1.48).

Domain-specific analyses did not suggest that one domain drove the overall result.

Limitations

Observational design limits causal certainty. Residual confounding is possible. Prescription dispensing does not prove medication use, and dose was unavailable. Metformin indication was not directly recorded. Only children with linked school census data were included.

Funding

Australian nonprofit/government grants; funders had no role.

Clinical Application

These data support reassuring counseling when metformin is clinically indicated during pregnancy, without changing current indications for use.