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07-04-2018 | Metformin | Highlight | News

First trimester metformin exposure unlikely to raise congenital anomaly risk

medwireNews: A European-wide case–control study finds little evidence for risk to the developing fetus if a mother is taking metformin.

“Given the rise in exposure to metformin during pregnancy” – because of the increasing prevalence of type 2 and gestational diabetes – “our findings are particularly timely,” say Joanne Given (Ulster University, Belfast, UK) and co-workers.

They note that in utero metformin exposure was still rare during their study period of 2006 to 2013, despite the number of exposures being more than fivefold larger than previously reported numbers, but they stress that current exposure is likely to be higher.

Of the total 50,167 babies with congenital anomalies (41,242 nongenetic and 8925 genetic), just 168 were exposed to metformin during the first trimester, giving a rate of 3.3 per 1000 affected babies. From this, the researchers estimate that 6245 pregnancies of the total 1,892,482 in the registry were exposed to metformin.

The researchers identified the affected babies in the EUROmediCAT database, which is part of the European Surveillance of Congenital Anomalies (EUROCAT) network. They included fetal deaths from 20 weeks’ gestation and pregnancy terminations because of fetal anomaly, as well as live births.

Metformin exposure among babies with congenital anomalies varied widely by region, from 0.8 per 1000 babies in Tuscany to 17.9 per 1000 babies in Malta.

Overall, there was no association between nongenetic congenital anomalies and exposure to metformin, Given and team report in The BMJ. “Teratogens, however, tend to increase the risk of specific, rather than all, congenital anomalies, so focusing on specific congenital anomalies is important,” they note.

They did find an association between metformin exposure and the risk for pulmonary valve atresia. However, the team stresses that “[a]ny investigation of the risk of congenital anomaly associated with metformin is complicated by the fact that pregestational diabetes increases the risk of major congenital anomaly two to threefold.”

Pulmonary valve atresia has previously been linked to maternal diabetes, leading the researchers to suspect the association with metformin “may suggest some residual confounding by indication.”

They add that it could have been a chance finding, because of the number of associations tested. The odds ratio for pulmonary valve atresia in metformin exposed pregnancies was 3.54, with a confidence interval of 1.05–12.00 and p value of 0.04 after adjusting for maternal age, registry, multiple birth, and maternal pre-existing or gestational diabetes.

There were no associations with any other specific anomalies. When looking at nongenetic anomalies, babies with genetic anomalies were used as controls, and vice versa.

The team describes the overall findings as “reassuring,” but advises further study of the possible pulmonary valve atresia association.

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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