Metformin exposure in utero not linked to higher BMI for children of women with diabetes
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Children of women with type 2 diabetes who took 1,000 mg metformin twice daily during pregnancy had a similar BMI z score at age 2 years compared with those of women using placebo, according to study data.
In findings from a follow-up of the Metformin in Women with Type 2 Diabetes in Pregnancy (MiTy) trial, there were no differences between the offspring of women using metformin compared with children from mothers in the placebo group for any anthropometric measures, including BMI z score and sum of skinfold thickness, according to Denice S. Feig, MD, MSc, professor of medicine obstetrics and gynecology, and health policy, management and evaluation at the University of Toronto and head of the Diabetes in Pregnancy Program at Mount Sinai Hospital in Toronto, and colleagues. There was a greater BMI increase observed in boys of mothers in the metformin group compared with placebo from age 0 to 12 months, however.
“Given the increasing incidence of type 2 diabetes in pregnancy and the increasing use of metformin during pregnancy, we believe that these data are reassuring with regard to the use of metformin during pregnancy in women with type 2 diabetes and the long-term health of their children,” Feig and colleagues wrote in The Lancet Diabetes & Endocrinology.
In the MiTy trial, 502 pregnant women with insulin-treated type 2 diabetes were randomly assigned to 1,000 mg metformin twice daily or placebo during pregnancy. Participants in the trial were invited to take part in the MiTy Kids follow-up, in which anthropometric measurements of offspring were taken at age 6, 12 and 24 months. Demographics and neonatal baseline data were recorded. The primary outcomes were mean BMI z score and mean sum of skinfold thickness at age 24 months. BMI z score at 3, 6, 12 and 18 months and sum of skinfold thickness at 6 and 12 months were among the secondary outcomes.
BMI z scores do not differ
There were 283 trial participants who enrolled their children in the follow-up study, of whom 135 were from the metformin group and 148 were from the placebo group. At age 24 months, there were no differences in mean BMI z score or mean sum of skinfold thickness between the two groups. There were also no differences for other anthropometric measures, including weight, height, weight-for-length percentile, individual skinfold thickness measurements, BMI z scores for risk of overweight or obesity, head circumference, waist circumference or central-to-peripheral adiposity.
After stratifying by sex, boys from mothers taking metformin had a greater mean BMI increase from age 0 to 12 months compared with boys from mothers in the placebo group (mean BMI z score increase, 0.86 vs. 0.07; P = .014).
Predictors for higher BMI z score
In linear regression models, older age at measurement, previous pregnancies and a shorter duration of receiving breast milk were independently associated with higher child BMI z score at age 12 months. At age 24 months, higher maternal prepregnancy BMI, low socioeconomic status and less sleep time were associated with higher BMI z score. In a linear mixed-effects model, higher prepregnancy BMI and reduced duration of receiving breast milk were associated with higher BMI z score.
In models examining weight, length and BMI growth trajectories, boys from the metformin group reached a higher peak mean BMI at age 6 months compared placebo. The higher BMI trend continued up to 24 months, at which time the trajectories between the two groups were similar.
“Several observational studies have found that early accelerated weight gain is associated with an increase in long-term risk of obesity and noncommunicable disease,” the researchers wrote. “However, it is unclear whether this rapid weight gain is a significant contributor as some studies suggest that the rapid weight gain must occur within the first 3 to 6 months, whereas other studies show that weight gain for up to 2 years can influence later adiposity.”
Blood samples were collected at age 24 months from 31 children — 14 in the metformin group and 17 in the placebo group. The metformin group had a higher mean fasting glucose than placebo (4.8 mmol/L vs. 4.1 mmol/L; P = .009), but no other differences were observed.
The researchers concluded that more follow-up studies of the cohort are needed to determine whether trends in BMI z score or skinfold thickness change later in childhood.
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