Metformin in Pregnancy Shows No Risk to Child Neurodevelopment

Metformin in Pregnancy Poses No Child Neuro Risk, Study Shows

Infants exposed to metformin during pregnancy show no developmental delays related to the medication by age 5, according to a recent study published in JAMA Network Open and reported by Medscape. The findings address a longstanding safety concern for pregnant women with diabetes who seek an affordable, oral alternative to daily insulin injections.

“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,” explained Hannah Gordon, MD, who directed the investigation as a perinatal epidemiology researcher at Mercy Hospital for Women located in Heidelberg, Australia. “We found there was no difference in outcomes across all of the domains assessed.”

About 1 in 9 women have diabetes in the U.S., with most cases falling under type 2. Up to 9% of pregnancies face complications from gestational diabetes. Metformin serves as a preferred treatment course for many patients who oppose insulin, which carries a higher cost and requires self-administered injections up to four times daily, according to Gordon.

Analysis of 177,409 Children in Victoria, Australia

In the retrospective population study, Gordon and her research team analyzed state-level data covering 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%. Polycystic ovary syndrome accounted for 22.8% of cases, while type 2 diabetes accounted for 17.9%.

The research team compared metformin exposure against national data assessing child development during the first year of full-time school between the ages of 4 and 6. Testing occurred in 2015, 2018, or 2021, with more than three-quarters of the children assessed at age 5. Evaluations measured physical health, social competence, emotional maturity, school-based language and cognitive skills, and communication. Researchers defined developmental vulnerability as scoring 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 said.

After controlling for confounding variables including maternal age, body mass index, education, and socioeconomic status, metformin use during pregnancy showed no association with child neurodevelopment, yielding an adjusted risk ratio of 0.97 with a 95% confidence interval spanning 0.74 to 1.29. Among a subsample of 16,121 women with gestational diabetes or type 2 diabetes, 20.7% of children exposed to metformin were considered developmentally vulnerable, compared to 15.9% of unexposed children. However, researchers found no statistically significant association after adjustment, with an adjusted risk ratio of 1.08 and a 95% confidence interval of 0.86 to 1.35.

Clinical Perspectives on Long-Term Safety Data

Expectant mothers frequently voice anxiety regarding the potential long-term consequences of initiating or maintaining metformin therapy, according to Lydia Shook, MD, a maternal-fetal medicine specialist at Mass General Hospital in Boston. While smaller randomized trials and observational studies previously indicated longer-term safety for mothers and offspring, the current research expands the scope to population-level outcomes.

“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.'”

Neither Gordon nor Shook reported financial conflicts of interest. The Norman Beischer Medical Research Foundation and the Australasian Diabetes in Pregnancy Society provided grant funding for the research.

Metformin Provides Oral Alternative to Insulin Injections

Why do some pregnant women use metformin instead of insulin?

Metformin offers an oral alternative to daily insulin injections, which can require up to four self-administered shots a day and generally involve higher costs for patients managing gestational or type 2 diabetes.

What specific child development areas did researchers test?

The study evaluated physical health, social competence, emotional maturity, school-based language and cognitive skills, and communication using validated national school assessment data collected between ages 4 and 6.

What conditions prompted mothers in the study to take metformin?

Gestational diabetes was the primary indication at 39.2%, followed by polycystic ovary syndrome at 22.8% and type 2 diabetes at 17.9%.