There’s a connection between a commonly prescribed drug for diabetes and a higher risk for birth defects if a father uses it within three months of conceiving a baby, a new study has found.
The drug metformin, one of the top treatments for type 2 diabetes, is linked to this heightened risk, according to researchers from Stanford University and Denmark. The drug helps control high blood sugar, according to WebMD.
Specifically, there’s as much as a 40% greater chance of babies being born with birth defects, including genital, digestive, urinary, heart, chromosomal and limb defects if a father uses it within the certain time frame, according to the work published March 29 in the journal Annals of Internal Medicine.
A higher risk of developing genital birth defects was found only in baby boys, the study found.
While many health risk factors for women conceiving children are understood, there’s a “limited but growing understanding of how paternal factors can affect” a child’s health, a Stanford Medicine news release on the research said.
“Given that men contribute half the DNA to a child, it makes sense that there could be some effects that travel through paternal pathways as well,” Dr. Michael Eisenberg, Stanford urology professor and a senior author of the study, said in a statement.
“It wasn’t just taking metformin at any time in a man’s life; it really has to do with taking it in that window when the sperm that is going to become the child is being developed.”
The study was based on health-registry data from Denmark on more than 1 million births between 1997 and 2016.
“When I saw the paper … I thought: ‘Yup, this is gonna go viral,’” Dr. Germaine Buck Louis, a reproductive and perinatal epidemiologist at George Mason University, told Science about the work.
Metformin is often the “first medication prescribed for type 2 diabetes,” according to Mayo Clinic.
In the U.S., type 2 diabetes affects roughly 90-95% of people with diabetes, typically adults, while type 1 diabetes affects about 5% of those with the condition, typically first diagnosed in kids and teens, according to Johns Hopkins University.
More on the research
An analysis of 1,116,779 birth records revealed 36,585 babies born in Denmark between 1997 and 2016, or 3.3%, had “1 or more major birth defects,” according to the study. Additionally, 51.4% of these babies were male.
The median ages of the mothers and fathers were 30 and 33, researchers noted. Babies born to women who had diabetes or hypertension weren’t included in the study, according to the news release.
Of this group, 1,451 babies born to fathers who used metformin within three months of conception were identified. It was found that 5.2% of these children had birth defects.
Offspring of fathers who filled a metformin prescription “during the 3 months before conception,” also known as the time when sperm develop, “were considered exposed,” according to the work.
“These rates mean that, in Denmark, where today approximately 120 babies per year are exposed through their fathers, metformin use may account for two additional babies born with birth defects every year,” the news release notes.
Of the 1,451 metformin-exposed babies, genital birth defects were more common and only seen in male offspring, but fewer boys were born overall, according to the research.
Researchers compared metformin-exposed babies with those who were insulin-exposed, with unexposed siblings and with babies whose fathers took metformin before or after sperm development. They didn’t find “elevated birth defect frequencies” in those groups unlike the children exposed to metformin during sperm development.
Ultimately, it’s not exactly clear why a father’s metformin use while sperm is maturing is linked to birth defects in offspring, the news release said. However, prior studies in mice “have shown that the drug can cause reproductive harm.”
Birth defects are responsible for roughly 20% of infant deaths in the U.S., according to Buck Louis, who wrote an editorial on the study.
“Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.”
Buck Louis said the research calls for a “more conclusive study of the potential risks for paternal use of diabetes drugs to offspring.”
When asked whether men planning to become fathers should avoid metformin, Eisenberg said in a statement, “I think that it’s a single study, so it’s hard to change clinical practice based on that.”
“But for somebody considering fatherhood, this study emphasizes the importance of a father’s health on the health of a child.”
One study limitation included how “information on underlying disease status was limited,” according to the research.
The work received funding from the National Institutes of Health.
More on metformin
Metformin was approved in 1995 as a type 2 diabetes treatment by the Food and Drug Administration.
“[Metformin] is widely used even by young men because of the obesity issue that we have. So that is potentially a huge source of exposure for the next generation,” Buck Louis told Science.
Also, “doctors have long prescribed (metformin) off-label — that is, to treat conditions outside its approved use” for diabetes, according to Harvard University.
The drug is known for cardiovascular benefits and has been prescribed for prediabetes, gestational diabetes, polycystic ovary syndrome and antipsychotic medicine-induced weight gain, the university points out.
It’s also being investigated for its potential to decrease the risk breast, colon and prostate cancer for those living with type 2 diabetes, according to Harvard. Additionally, researchers are looking into whether it can lower dementia and stroke risks, as well as slow down aging and prolong life-expectancy.
“When we think about reproduction, we still mostly think about maternal factors, so this study brings further awareness that paternal factors can make a difference,” Eisenberg said in the news release.
“Don’t forget the father.”
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