Using metformin during the first trimester of pregnancy does not increase the risk for nongenetic congenital abnormalities, according to a study published in BMJ.

Joanna E. Given, research associate, of the Administrative Data Research Centre Northern Ireland at Ulster University in Belfast, and associates conducted a population-based exploratory case-control study to elucidate whether a relationship exists between metformin exposure during pregnancy and risk for certain congenital abnormalities.

The investigators assessed 29 specific subcategories of nongenetic anomalies as well as all nongenetic anomalies combined with malformed controls; 11 surveys including information from 1,892,482 births between 2006 and 2013 were used for the study.

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The primary outcome measure was the odds ratio adjusted for maternal age, maternal diabetes status, registry, and multiple births.

A total of 50,167 infants with congenital abnormalities (41,242 nongenetic, 8925 genetic) were included in the study. Live births, fetal fatalities from 20 weeks’ gestation, and fetal anomaly-related pregnancy terminations were included; 168 of these infants were exposed to metformin in utero (141 with nongenetic congenital anomalies, 27 with genetic congenital anomalies).

When comparing infants with all nongenetic abnormalities to genetic controls, the researchers did not find significant correlations for higher rates of metformin exposure during the first trimester (adjusted odds ratio, 0.84). The only significant value was for pulmonary valve atresia (adjusted odds ratio, 3.54), which the authors speculate might have been a chance finding.

“No evidence was found for an increased risk of all non-genetic congenital anomalies combined following exposure to metformin during the first trimester, and the one significant association was no more than would be expected by chance,” the authors wrote. “Further surveillance is needed to increase sample size and follow up the cardiac signal, but these findings are reassuring give the increasing use of metformin in pregnancy.”


Given JE, Loane M, Garne E, et al. Metformin exposure in first trimester of pregnancy and risk of all or specific congenital anomalies: exploratory case-control study. BMJ. 2018;361:k2477.