Metformin Use During Pregnancy May Alter Babies' Growth Patterns

By Reuters Staff

August 19, 2019

NEW YORK (Reuters Health) - Metformin use during pregnancy may alter the trajectory of fetal, infant and childhood growth, a new systematic review and meta-analysis suggest.

The study found that children exposed to metformin in the womb were born at significantly lower birth weights compared to babies whose mother's took insulin during pregnancy, but then grew faster in infancy and were significantly heavier in childhood.

"It is known that children who are born small and then undergo 'catch-up growth' after birth are at increased risk of developing cardiovascular disease and type 2 diabetes later in life," the U.K.-based research team writes in PLOS Medicine, online August 6. "It is important to understand whether this increased risk applies to children whose mothers were treated with metformin during pregnancy."

Dr. Susan Ozanne from the Wellcome Trust-Medical Research Council Institute of Metabolic Science at the University of Cambridge and colleagues found 28 studies that included nearly 4,000 mothers who were randomized to metformin or insulin for treatment of gestational diabetes mellitus (GDM).

Compared with babies of insulin-treated mothers, babies of metformin-treated mothers weighed on average 108 g less at birth and had a lower risk of macrosomia and being born large for gestational age.

In addition, metformin-exposed babies were 0.44 kg heavier by 18 to 24 months than insulin-exposed babies. And metformin-exposed children had higher BMI (by 0.8 kg/m2) by age 5 to 9 years than insulin-exposed children.

"We don't know enough yet about the long-term risks to the health of these children, so it's important that there are more studies to explore this in depth and to help fine-tune treatments. We know that metformin crosses the placenta, while insulin doesn't, so it is likely that the drug acts on the placenta or fetal tissue," Dr. Ozanne said in a news release.

In their paper, the researchers caution that the ability to draw definitive conclusions from this analysis is limited by both the quantity and quality of the studies available.

"In particular, longitudinal follow-up data into mid-childhood from trials of GDM treatment are sparse in comparison to earlier time points (110–301 children from 3 studies). Where follow-up data are available, the original studies may be subject to recall bias and power issues with respect to childhood outcomes. The majority of clinical trials in this area are powered only for primary outcomes at the time of birth," they point out.

"Our findings highlight a need for further longitudinal studies of growth and body composition following intrauterine metformin exposure," they conclude.

The study had no commercial funding and the authors have declared no relevant conflicts of interest.


PLOS Med 2019.