{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:08:11Z","timestamp":1790784491396,"version":"4.1.0"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine whether metformin prescription in pregnancy is associated with a risk of developmental vulnerability among offspring at school entry.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Metformin prescription dispensation during pregnancy.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n From 871\u202f627 singleton births in Victoria between 2009 and 2020, 177\u202f409 children with linked developmental outcome data were identified, of whom 1095 (0.6%) were exposed to metformin antenatally (43 [3.9%] aged \u22645 years 0 months, 860 [78.5%] aged 5 years 1 month to 6 years 0 months, and 192 [17.5%] aged \u22656 years 1 month at assessment; 557 male [50.9%]). Developmental vulnerability was observed in 199 children (18.2%) exposed to metformin compared with 24\u202f379 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.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.37054","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:32:05Z","timestamp":1790782325000},"page":"e2637054","source":"Crossref","is-referenced-by-count":0,"title":["Metformin Exposure in Pregnancy and Childhood Developmental 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Victoria, Australia"},{"name":"The Royal Women\u2019s Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Shub","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Roddy Mitchell","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Walker","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Forsythe","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Tong","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthea","family":"Lindquist","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanne","family":"Hastie","sequence":"additional","affiliation":[{"name":"Perinatal Epidemiology Group, Department of Obstetrics, Gynaecology and Newborn Health, University of 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