Preconception Paternal Metformin Linked to Major Birth Defects

Genital birth defects, all in boys, more common among metformin-exposed offspring

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WEDNESDAY, March 30, 2022 (HealthDay News) -- Preconception paternal metformin treatment is associated with an increased risk for major birth defects, according to a study published online March 29 in the Annals of Internal Medicine.

Maarten J. Wensink, M.D., Ph.D., from the University of Southern Denmark in Odense, and colleagues conducted a nationwide prospective registry-based study in Denmark from 1997 to 2016 to examine whether the risk for birth defects in offspring varies with preconception pharmacologic treatment of fathers with diabetes.

The researchers found that 3.3 percent of the 1,116,779 offspring included had one or more major birth defects. There was no increase in birth defect frequency for insulin-exposed offspring (5,298 individuals; adjusted odds ratio, 0.98; 95 percent confidence interval, 0.85 to 1.14). The frequency of birth defects was elevated for metformin-exposed offspring (1,451 individuals; adjusted odds ratio, 1.40; 95 percent confidence interval, 1.08 to 1.82). Birth defect frequencies were not increased for offspring whose fathers filled a metformin prescription in the year before (1,751 individuals) or after (2,484 individuals) sperm development, or for unexposed siblings of exposed offspring. Genital birth defects, all in boys, were more common among metformin-exposed offspring (adjusted odds ratio, 3.39; 95 percent confidence interval, 1.82 to 6.30).

"The sheer size of the diabetes pandemic suggests that treatment of prospective fathers with diabetes, including pharmacologic management and counseling on diet, physical exercise, and weight loss, should be subject to further study," the authors write.

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