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Metformin During Gestational Diabetes Increases Risk of Childhood Obesity

Mar 10, 2018
 

Long-term impact of intrauterine exposure to medication on the offspring remains unclear.

A growing number of pregnant women are taking metformin to treat gestational diabetes or a condition called polycystic ovary syndrome (PCOS). PCOS is a common cause of infertility and can put women at risk of developing diabetes and other metabolic health problems. PCOS affects an estimated 7 percent to 10 percent of women of childbearing age, according to the Hormone Health Network.

Children born to women who take a commonly used diabetes medication during pregnancy may have an increased risk of being overweight or having obesity, according to new data from two Norwegian studies.

The study’s first author, Liv Guro Engen Hanem, M.D., of the Norwegian University of Science and Technology in Trondheim, Norway stated that, according to two Norwegian studies, women with polycystic ovary syndrome (PCOS), gestational diabetes, type 2 diabetes, and even obesity are increasingly prescribed metformin during pregnancy, with studies indicating that the drug reduces the risk of PCOS-related complications.

Even though we know that metformin crosses the placenta, the long-term impact of such intrauterine exposure on the offspring remains unclear, with previous investigations yielding conflicting results. So a follow-up of two randomized controlled trials were done. It was expected that children exposed to metformin in utero may have a higher average weight at 4 years old, then children who have not been exposed to metformin.

The studies also showed that the data from 182 children whose mothers used metformin during their pregnancy were more than double the chances of being overweight or having obesity than those on placebo. The effect begins appearing at the age of 6 months.

Primary endpoints were height, weight, body mass index (BMI), and having excessive weight/obesity at 4 years of age, for which complete data were available for 161 children, and head circumference at 1 year, for which complete data were available for 154 children. At four years of age, the children whose mothers were randomized to metformin during pregnancy tended to weigh more than the children whose mothers took the placebo. Although metformin did not appear to affect birth weight, the trend became apparent when children reached six months of age. At the age of four years, the children in the metformin group had higher BMI scores and were more likely to meet the criteria for obesity or overweight than children in the placebo group.

There were no significant differences in baseline characteristics between the metformin and placebo groups, including maternal characteristics at inclusion, mode of contraception, pregnancy complications, maternal weight gain during pregnancy, placenta weight, and duration of breastfeeding.

There was no significant difference in birth weight between infants exposed vs not exposed to metformin, but between age 6 months to 4 years it became apparent that those exposed to metformin were significantly heavier (P = .015).

Although the authors note the current analysis is the largest follow-up study to date of metformin exposure in utero, they acknowledge the findings may not be applicable to mothers without PCOS and a potential limitation is the low participation rate.

They nevertheless hypothesize that metformin may increase offspring weight via two primary mechanisms: maternal metabolic alterations that affect the intrauterine environment, and the direct effect of metformin on the offspring, potentially by inhibition of the mitochondria respiratory chain.

Hanem also added that, “Few studies have examined the long-term health of children born to women with PCOS who took metformin….Our findings indicate more research is needed to determine its effects on children who were exposed in the womb.”

Practice Pearls:

  • PCOS affects an estimated 7 percent to 10 percent of women of childbearing age.
  • Metformin crosses the placenta, the long-term impact of such intrauterine exposure on the offspring remains unclear.
  • Metformin can increase offspring weight via two primary mechanisms: maternal metabolic alterations that affect the intrauterine environment, and the direct effect of metformin on the offspring, potentially by inhibition of the mitochondria respiratory chain.

Published online February 27 in the Journal of Clinical Endocrinology & Metabolism.