Metformin Exposure in Pregnancy and Childhood Developmental Outcomes
- 1Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia
- 2Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia
- 3The Royal Women’s Hospital, Parkville, Victoria, Australia
Abstract
Importance: Metformin is an oral hypoglycemic agent increasingly prescribed during pregnancy. In animal models, metformin influences embryonic cortical development, and it is uncertain whether this translates to clinical implications for humans.
Objective: To examine whether metformin prescription in pregnancy is associated with a risk of developmental vulnerability among offspring at school entry.
Design, Setting, and Participants: This cohort study used population-level pregnancy and birth data from January 1, 2009, to December 31, 2020, linked with the Australian Early Development Census (AEDC), a standardized national assessment of childhood development completed every 3 years during the first year of full-time school (age 4-6 years). The data analysis was performed between March 14, 2025, and January 30, 2026.
Exposure: Metformin prescription dispensation during pregnancy.
Main Outcome and Measures: The association of developmental vulnerability, defined as scoring below the 10th percentile in at least 2 of the 5 assessed domains of the AEDC (physical health and well-being, social competence, emotional maturity, school-based language and cognitive skills, and communication skills and general knowledge), was estimated using inverse probability of treatment weighting combined with regression adjustment.
Results: From 871 627 singleton births in Victoria between 2009 and 2020, 177 409 children with linked developmental outcome data were identified, of whom 1095 (0.6%) were exposed to metformin antenatally (43 [3.9%] aged ≤5 years 0 months, 860 [78.5%] aged 5 years 1 month to 6 years 0 months, and 192 [17.5%] aged ≥6 years 1 month at assessment; 557 male [50.9%]). Developmental vulnerability was observed in 199 children (18.2%) exposed to metformin compared with 24 379 children (13.9%) not exposed. After adjustment for confounders, metformin was not associated with developmental vulnerability among children exposed to metformin (adjusted relative risk, 0.97 [95% CI, 0.74-1.29]) or across any of the individual developmental domains.
Conclusions and Relevance: This cohort study found that metformin use in pregnancy was not associated with an altered risk of developmental vulnerability among children aged 4 to 6 years and may provide reassurance to clinicians and women considering metformin use during pregnancy.
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BibTeX
@article{gordon2026metformin,
title = {{Metformin Exposure in Pregnancy and Childhood Developmental Outcomes}},
author = {Hannah Gordon and Richard J. Hiscock and Sarah Price and Alexis Shub and Alexandra Roddy Mitchell and Jessica Atkinson and Susan Walker and Anna Forsythe and Stephen Tong and Anthea Lindquist and Roxanne Hastie},
journal = {JAMA Network Open},
year = {2026},
month = sep,
doi = {10.1001/jamanetworkopen.2026.37054},
url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854644},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metformin Exposure in Pregnancy and Childhood Developmental Outcomes
AU - Hannah Gordon
AU - Richard J. Hiscock
AU - Sarah Price
AU - Alexis Shub
AU - Alexandra Roddy Mitchell
AU - Jessica Atkinson
AU - Susan Walker
AU - Anna Forsythe
AU - Stephen Tong
AU - Anthea Lindquist
AU - Roxanne Hastie
PY - 2026
DA - 2026/09/30
JO - JAMA Network Open
DO - 10.1001/jamanetworkopen.2026.37054
UR - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854644
AB - Importance: Metformin is an oral hypoglycemic agent increasingly prescribed during pregnancy. In animal models, metformin influences embryonic cortical development, and it is uncertain whether this translates to clinical implications for humans. Objective: To examine whether metformin prescription in pregnancy is associated with a risk of developmental vulnerability among offspring at school entry. Design, Setting, and Participants: This cohort study used population-level pregnancy and birth data from January 1, 2009, to December 31, 2020, linked with the Australian Early Development Census (AEDC), a standardized national assessment of childhood development completed every 3 years during the first year of full-time school (age 4-6 years). The data analysis was performed between March 14, 2025, and January 30, 2026. Exposure: Metformin prescription dispensation during pregnancy. Main Outcome and Measures: The association of developmental vulnerability, defined as scoring below the 10th percentile in at least 2 of the 5 assessed domains of the AEDC (physical health and well-being, social competence, emotional maturity, school-based language and cognitive skills, and communication skills and general knowledge), was estimated using inverse probability of treatment weighting combined with regression adjustment. Results: From 871 627 singleton births in Victoria between 2009 and 2020, 177 409 children with linked developmental outcome data were identified, of whom 1095 (0.6%) were exposed to metformin antenatally (43 [3.9%] aged ≤5 years 0 months, 860 [78.5%] aged 5 years 1 month to 6 years 0 months, and 192 [17.5%] aged ≥6 years 1 month at assessment; 557 male [50.9%]). Developmental vulnerability was observed in 199 children (18.2%) exposed to metformin compared with 24 379 children (13.9%) not exposed. After adjustment for confounders, metformin was not associated with developmental vulnerability among children exposed to metformin (adjusted relative risk, 0.97 [95% CI, 0.74-1.29]) or across any of the individual developmental domains. Conclusions and Relevance: This cohort study found that metformin use in pregnancy was not associated with an altered risk of developmental vulnerability among children aged 4 to 6 years and may provide reassurance to clinicians and women considering metformin use during pregnancy.
SN - 2574-3805
ER -