Study: Anti-diabetes drug in pregnancy linked to restricted foetal growth

METFORMIN, a common anti-diabetes drug, if taken during pregnancy, could possibly restrict foetus growth, including a slow maturing of the kidneys, a study has found.

The drug is known to help one manage the metabolic disorder by lowering blood sugar.

Researchers, led by Baylor College of Medicine, US, said that the drug is now prescribed to pregnant women to reduce risk of complications due to diabetes-related conditions, including pre-diabetes and gestational diabetes.

However, concerns have been raised regarding the long-term effects of metformin on childhood development, even as the drug has been shown to be effective in managing blood sugar in pregnant women.

For this study, published in the American Journal of Obstetrics and Gynecology, the researchers developed an experimental primate model.

Within 30 days of conception, 13 female rhesus monkeys were initiated on twice-daily 10 milligrams per kilogram weight metformin, which is the equivalent of doses prescribed to humans, the researchers said. On the 145th day of a monkey's pregnancy, the foetus and the placenta were delivered by performing a caesarean section.

Analysing metformin levels, results showed that when given to the mother, the drug freely crossed the placenta and accumulated in the foetal kidneys, liver, intestines, placenta, amniotic fluid (in which the embryo is suspended) and urine, levels of which was similar to those found in the mother's urine.

This accumulation of metformin during pregnancy was found to be linked with a restricted growth of kidneys, liver, skeletal muscle, heart, and fat deposits known to support the abdominal organs -- all of which served to lower the foetus's body weight, the researchers said.

"Our study demonstrates fetal bioaccumulation of metformin with associated foetal growth restriction and renal dysmorphology after maternal initiation of the drug within 30 days of conception in primates," the authors wrote.

They added that while the anti-diabetes drug is not known to cause birth defects, the foetus also doesn't have a way to clear the drug.

"Many drugs undergo 'first-pass' metabolism by becoming absorbed first in the liver, which decreases the concentration before it continues through the body. However, metformin does not experience the first-pass effect; rather, it is transported across the placenta, exposing the fetus to an adult dose of the drug," co-author Jed Friedman, associate vice provost for diabetes programs at the University of Oklahoma Health Sciences, said.

The researchers also analysed the effects of feeding the pregnant primates different diets -- half were fed a conventional diet with 15 per cent calories from fat, while the other half received a high-fat diet with 36 per cent calories from fat.

Results showed metformin levels did not differ according to diet.

However, this being a small study, the researchers called for more studies to better understand the effects of metformin on the foetus, Friedman said.

(PTI)