ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Cochrane Database Syst Rev. 2018 Jul 24;7:CD010564.

This review evaluated the role of metformin in pregnant women with obesity or who are overweight, on maternal and infant outcomes, including adverse effects of treatment and costs.

Obesity and being overweight in pregnancy affect approximately 50% of women across low-income nations and is associated with a range of well recognized maternal and infant health complications. Maternal risks include gestational hypertension, pre-eclampsia and gestational diabetes; women are more likely to have their labour induced, and give to birth by caesarean section. Infants born to women with obesity or who are overweight in pregnancy have a higher risk of being of high birthweight or being large-for-gestational age, and of associated complications, including shoulder dystocia, jaundice and hypoglycaemia. It has been estimated that the costs of providing antenatal and postpartum care for women who are overweight are increased by 23% when compared with women of normal BMI, increasing further to 37% for women with obesity. Given these issues there has been considerable interest in providing antenatal dietary and lifestyle advice for women with obesity or who are overweight during pregnancy, as a strategy to limit gestational weight gain and improve maternal and infant health.

This review examined whether metformin has a role in improving health outcomes for pregnant women with obesity or who are overweight, and their babies. The review considered possible benefits, adverse effects and healthcare system costs. Three randomised controlled studies (1099 pregnant women) were found comparing metformin tablets with placebo taken by mouth from 10–20 weeks of pregnancy until birth (Chiswick C et al. ×3). The studies involved women with obesity (but not overweight). Women who were given metformin or placebo during pregnancy had a similar risk of a baby being born large-for-gestational age. Metformin probably makes little or no difference in the risk of women developing gestational diabetes. Metformin may also have little or no difference in the risk of women developing gestational hypertension or pre-eclampsia. Women who were given metformin gained slightly less weight during pregnancy, but were more likely to experience diarrhoea. There were no other important differences identified for other maternal outcomes including, caesarean birth, giving birth before 37 weeks of pregnancy, shoulder dystocia perineal trauma or heavy bleeding after the baby has been born. Babies of women who were given metformin had similar birthweight to babies of women who were given placebo. No other important differences were identified for other infant outcomes of interest: hypoglycaemia, hyperbilirubinaemia, Apgar score at five minutes or death of the baby before or after being born.

Thus, there is insufficient evidence to support the use of metformin for women with obesity in pregnancy for improving outcomes for the mother and her baby. Metformin was associated with increased risk of adverse effects, particularly diarrhoea. More research is needed to evaluate the role of metformin in pregnant women with obesity or who are overweight, as a strategy for improving maternal and infant health, either alone or as an additional intervention.

References: Chiswick C, Reynolds RM, Denison F, Drake AJ, Forbes S, Newby DE, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet. Diabetes & Endocrinology 2015;3(10):778–86.

Chiswick CA, Reynolds RM, Denison FC, Drake AJ, Forbes S, Newby DE, et al. Does metformin reduce excess birthweight in offspring of obese pregnant women? A randomised controlled trial of efficacy, exploration of mechanisms and evaluation of other pregnancy complications. Efficacy and Mechanism Evaluation 2016; Vol. 3, issue 7.

Chiswick CA, Reynolds RM, Denison FC, Whyte SA, Drake AJ, Newby DE, et al. Efficacy of metformin in pregnant obese women: a randomised controlled trial. BMJ Open 2015;5(1):e006854.