Infants exposed to metformin during pregnancy show no developmental delays related to the medication by age 5, according to a study published in JAMA Network Open and reported by Medscape. The findings address long-standing safety concerns for pregnant women with diabetes who seek an affordable, oral alternative to daily insulin injections.
Victoria Australia Population Study Data
Hannah Gordon, a perinatal epidemiology researcher at Mercy Hospital for Women in Heidelberg, Australia, led a retrospective population study analyzing state-level data of 177,409 children born in Victoria, Australia, between 2009 and 2020. Among 1,095 children with in utero metformin exposure, the primary indication for maternal use was gestational diabetes at 39.2 percent. Polycystic ovary syndrome accounted for 22.8 percent of cases, while type 2 diabetes accounted for 17.9 percent.
“There’s a bit of hesitancy using metformin in pregnancy because we know that it crosses the placenta, and the long-term impacts for the child have been less well described in the past,” Gordon stated. “We found there was no difference in outcomes across all of the domains assessed.”
Child Development Assessments at Age Five
To analyze the impact of metformin exposure, the researchers utilized national data that evaluated the development of children between 4 and 6 years old during their initial year of full-time schooling. Children were tested in 2015, 2018, or 2021, with more than three-quarters of the cohort evaluated at age 5. Evaluators tested physical health, social competence, emotional maturity, school-based language and cognitive skills, and communication. Researchers defined developmental vulnerability as a score below the 10th percentile in two or more areas.
“Ages 4 to 6 is a sweet spot in that we’ve got high-quality data that is validated, but is also predictive of future educational outcomes,” Gordon explained.
Study finds no link between metformin and neurodevelopmental risk
Metformin use during pregnancy was not linked to children’s neurodevelopment after adjusting for confounding factors including socioeconomic status, education, body mass index, and maternal age, resulting in an adjusted risk ratio of 0.97 (95 percent confidence interval: 0.74 to 1.29). Researchers also examined a subsample of women with gestational diabetes or type 2 diabetes totaling 16,121 participants. In this group, 20.7 percent of children exposed to metformin were considered developmentally vulnerable, compared to 15.9 percent of unexposed children. However, no statistically significant association emerged after adjustment, showing an adjusted risk ratio of 1.08 and a 95 percent confidence interval between 0.86 and 1.35.
Lydia Shook, a maternal-fetal medicine specialist at Mass General Hospital in Boston, noted that many pregnant patients worry about the long-term effects of starting or continuing the medication. Smaller randomized trials and observational studies previously demonstrated longer-term safety for offspring and mothers, and the current research adds population-level outcomes to that clinical picture. “Now we have long-term safety data to support its use,” Shook said. “It’s helpful to have a large, population-based study to say, ‘We don’t think there’s a signal towards harm.'”
Common Questions Regarding Metformin Exposure
Why did clinical hesitancy exist regarding metformin during pregnancy?
Because metformin crosses the placenta, lingering questions about its long-term impact on offspring created clinical hesitation among providers and patients, even though the American College of Obstetricians and Gynecologists lists it as a reasonable alternative to insulin.
What financial and logistical factors drive interest in metformin over insulin?
Insulin is generally more expensive and requires self-administered injections up to four times a day, making the oral alternative preferred by many patients.
What specific health conditions prompted mothers to take metformin in the study?
Gestational diabetes accounted for 39.2 percent of maternal metformin use in the study, polycystic ovary syndrome accounted for 22.8 percent, and type 2 diabetes accounted for 17.9 percent.
Who funded the research published in JAMA Network Open?
The research received grant funding from the Norman Beischer Medical Research Foundation and the Australasian Diabetes in Pregnancy Society, with authors Gordon and Shook reporting no financial conflicts of interest.
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