Metformin Use During Pregnancy Not Linked to Developmental Vulnerability in Children: JAMA
Australia: A cohort study found that metformin use during pregnancy was not associated with an increased risk of developmental vulnerability in children aged 4 to 6 years. The findings provide reassurance regarding the developmental safety of metformin during pregnancy for clinicians and women who require the medication.
Published in JAMA Network Open, the study examined whether exposure to metformin before birth was associated with developmental difficulties when children reached the first year of full-time school. The research was conducted by Hannah Gordon of the Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Australia, and colleagues.
Metformin is an oral glucose-lowering medication increasingly used during pregnancy. Although its use has expanded, concerns remain regarding its potential effects on fetal development. Experimental studies in animals have suggested that metformin may influence development of the embryonic cortex, raising questions about whether similar effects could occur in humans.
Researchers conducted a population-based cohort study using pregnancy and birth records for singleton children born in Victoria, Australia, between January 2009 and December 2020. These records were linked to the Australian Early Development Census (AEDC), a standardized national assessment conducted during the first year of full-time school, generally between 4 and 6 years of age.
The analysis included 177,409 children with available developmental assessment data, including 1,095 children (0.6%) who had been exposed to metformin during pregnancy. Development was assessed across five domains: physical health and well-being, social competence, emotional maturity, school-based language and cognitive skills, and communication skills and general knowledge.
Developmental vulnerability was defined as scoring at or below the 10th percentile in at least two of these five domains. Statistical analyses used inverse probability of treatment weighting together with regression adjustment to account for potential confounding factors.
The findings showed:
- Developmental vulnerability was identified in 199 metformin-exposed children (18.2%), compared with 24,379 children (13.9%) who were not exposed.
- After adjustment for confounding factors, metformin exposure was not associated with developmental vulnerability, with an adjusted relative risk of 0.97.
- No significant association was observed between antenatal metformin exposure and vulnerability in any of the individual developmental domains assessed.
- The results remained reassuring despite the higher unadjusted proportion of developmental vulnerability among children exposed to metformin.
The study was limited by potential residual confounding, unavailable race and ethnicity data, inability to confirm medication adherence or dose, and small numbers for some treatment-pattern analyses.
Overall, metformin use during pregnancy was not associated with developmental vulnerability in children aged 4 to 6 years. Further research is needed to assess its longer-term effects on offspring growth and cardiometabolic health.
Reference:
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
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