The prevalence of obesity is increasing in both developed and developing countries. It is estimated that one-fifth of pregnant women in the UK and one-third in the USA are obese. Obesity in pregnancy is associated with increased risk of adverse short and long term consequences for both mother and baby. Intervention studies in obese pregnant women, such as diet and exersice, have shown no evidence of benefit.
An alternative strategy is the use of metformin. This drug reduces insulin resistance and has been extensively used in the treatment of gestational diabetes mellitus and polycystic ovarian disease with no evidence of increase in birth defects or other pregnancy complications Hyperglycemia and increased insulin resistance are inter-correlated with obesity and this may be the reason for the association between obesity and fetal macrosomia as well as other pregnancy complications.
The MOP trial was designed to test the hypothesis that metformin, compared to placebo, would reduce birthweight and pregnancy complications in non-diabetic pregnant women with a BMI >35 kg/m2. The trial was conducted in three NHS maternity hospitals in the United Kingdom (King’s College Hospital, London; Medway Maritime Hospital, Gillingham; Epsom & St Helier University Hospitals NHS Trust, London). Eligible women were randomized in a 1:1 ratio to either metformin or placebo, using computer generated random numbers.
Results of the study
Syngelaki A, Nicolaides KH, Balani J, Hyer S, Akolekar R, Kotecha R, Pastides A, Shehata H. Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus. N Engl J Med 2016;374:434-43.
In total 400 women participated in the study. There was no significant between-group difference in the median neonatal birth-weight z score (0.05 in the metformin group [interquartile range, -0.71 to 0.92] and 0.17 in the placebo group [interquartile range, -0.62 to 0.89], P=0.66). The median maternal gestational weight gain was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], P<0.001), as was the incidence of preeclampsia (3.0% vs. 11.3%; odds ratio, 0.24; 95% confidence interval, 0.10 to 0.61; P=0.001). The incidence of side effects was higher in the metformin group than in the placebo group. There were no significant between-group differences in the incidence of gestational diabetes, large-for-gestational-age neonates, or adverse neonatal outcomes.
It was concluded that among women without diabetes who have a BMI of more than 35, the antenatal administration of metformin reduces maternal weight gain but not neonatal birth weight.