Antenatal metformin exposure not linked to adverse neurodevelopment

Antenatal metformin exposure not linked to adverse neurodevelopment | Image Credit: © BGStock72 - © BGStock72 - stock.adobe.com.

There is no association between in utero exposure to metformin and adverse neurodevelopmental outcomes in children aged up to 14 years, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Since the 1970s, metformin has been prescribed to pregnant patients for diabetes management and to reduce the risk of pregnancy complications in women with polycystic ovary syndrome. However, data has indicated metformin may not be more effective than insulin alone among women with preexisting diabetes.

Prior studies have shown a lack of association between metformin use during pregnancy and adverse birth outcomes.² This included a risk ratio (RR) of 1.02 for nonlive births and 0.72 for congenital malformations.

While data has indicated improved safety outcomes from metformin vs insulin among pregnant patients with diabetes, long-term safety data is lacking.¹ Data is needed to determine the impact of antenatal metformin exposure on childhood neurodevelopment.

To evaluate the association between metformin exposure during pregnancy and neurodevelopmental outcomes in offspring, investigators conducted a systematic review and meta-analysis. The Embase, Medline, and Web of Science databases were assessed using terms such as metformin, insulin, childhood, adolescence, development, cognition, and intelligence.

Studies including women who received metformin during pregnancy with follow-up results for neurodevelopmental outcomes were eligible for the analysis. Exclusion criteria included not being written in English, not having a control group, and being a case study, review article, editorial, or guideline.

Neurodevelopmental outcomes included intelligence based on assessments of intelligence quotient and motor, cognitive, and verbal outcomes defined using validated tools. Title and abstract assessment and full text screening were performed by 2 reviewers, with a third consulted during discrepancies.

Two reviewers independently performed data extractions, resolving discrepancies through discussion. A modified version of the Newcastle-Ottawa Scale and the Risk of Bias 2 tool were used to assess risk of bias.

There were 7 studies included in the final analysis, encompassing 14,042 children. Of these, 7641 were exposed to metformin during pregnancy. Five of the studies were follow-up studies of randomized controlled trials while 2 were observational cohort studies.

Neurodevelopmental outcomes in infants aged under 2 years were assessed in 3 studies, which reported an RR of 1.09 for global neurodevelopmental delay in infants with antenatal metformin exposure vs unexposed infants. This indicated no increased risk, and similar results were reported in children aged 3 to 5 years, with an RR of 0.90.

When evaluating motor function, mean scores in children aged 2 to 5 years were similar between those exposed to metformin and those unexposed, with a mean difference of 0.30. Similarly, the mean difference for cognitive function in children aged up to 14 years was -0.45, indicating no significant variation based on antenatal metformin exposure.

Finally, a single study evaluated behavioral development in children before school commencement, and found mean scores on the Strength and Difficulties Questionnaire did not differ in children who received insulin vs those who did not. Overall, the included studies had a low risk of bias.

These results indicated no association between metformin use during pregnancy and offspring neurodevelopmental outcomes. Investigators concluded these findings can reassure clinicians and patients considering metformin.

Reference

1. Gordon HG, Atkinson JA, Tong S, et al. Metformin in pregnancy and childhood neurodevelopmental outcomes: a systematic review and meta-analysis. The American Journal of Obstetrics & Gynecology. 2024;231(3):208-314. doi:10.1016/j.ajog.2024.02.316
2. Kunzmann K. Metformin during pregnancy not linked to adverse birth outcomes. June 21, 2024. September 5, 2024. https://www.contemporaryobgyn.net/view/metformin-during-pregnancy-not-linked-to-adverse-birth-outcomes