Paternal Use Of Metformin Linked To Birth Defects In Babies

Metformin, one of the world’s most widely prescribed type 2 diabetes drugs, has been linked to major birth defects in children when taken before conception, suggests a new study published this week in the Annals of Internal Medicine. The even more surprising part: the result was found not in the female parents, but the male.

Now, for a very long time, the general idea was that when it came to growing babies there was really only one party that needed to make any lifestyle sacrifices. If your body was the one that had the fetus, you were the one who had to give up alcohol, coffee, cigarettes – basically all your vices; if your body was fetus-free, then fill your boots.

Recently, though, that idea is being challenged. Studies have emerged showing that using cannabis can affect the expression of certain genes in sperm cells, for instance, leading researchers to recommend abstinence from the drug for nearly 11 weeks before getting somebody pregnant.

This new study suggests that even drugs of the physician-prescribed variety might not be as safe as we thought for your future progeny. By looking at data from more than a million births in Denmark between 1997 and 2016, the researchers compared the incidence of major birth defects based on paternal exposure to various diabetes medications. The study included any child whose prospective paternal parent had filled a prescription in the three months before conception for any of the drugs being studied – metformin, insulin, and sulfonylurea. If both parents were taking diabetes medication, the children were excluded.

Out of the 1,116,779 offspring included in the study, 3.3 percent were found to have one or more major birth defects. In cases with paternal exposure to metformin, however, that number was more than half as high again, at 5.2 percent. There was a particular increase in genital defects, but only for boys.

What’s more, these higher odds of birth defects were not seen in babies exposed to the other medications, and their unexposed siblings were not affected. The inclusion of insulin prescriptions meant that the researchers were also able to discount the diabetes diagnosis itself as a confounding variable, CNN reports.

“If patients would like to switch to an alternative [to metformin], they should contact their doctor,” study co-author Maarten Wensink told Reuters. However, diet and exercise remain the best interventions for type 2 diabetes, and so the study “could be an extra reason to put more priority on paternal health,” he added.

As with all studies of this nature, it’s important to be aware of the limitations involved. The researchers included the children of parents who filled a prescription – that’s all. They didn’t have information on whether those prescriptions were taken properly, or how well their diabetes was kept under control. The team also noted that parents taking metformin were older and of a lower socioeconomic status than the typical study participant, both of which could have played a part in the result.

Nevertheless, there is a potential explanation for the increased risk of birth defects. In an editorial accompanying the paper, reproductive and perinatal epidemiologist Germain Buck Louis, who was not involved in the research, noted that metformin works by altering testosterone levels in those who take it.

That “may be an underlying mechanism raising concern about the antiandrogenic activity of oral diabetes pharmacologic agents, including metformin,” Louis wrote. “Clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.”

But Channa Jayasena, head of andrology at Imperial College London, who was not involved in the work, cautioned against reading too much into the study. The results are “thought-provoking but inconclusive,” he told Reuters.

“Men with diabetes should not be dissuaded from taking metformin,” he said, “but this is worth looking at more closely.”

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