Metformin exposure during pregnancy may impact postnatal growth trajectory
medwireNews: Infants born to mothers with gestational diabetes treated with metformin have lower birthweight, but experience accelerated postnatal growth and have higher BMI in childhood, compared with those whose mothers were treated with insulin, suggest findings from a meta-analysis.
“This is a concerning finding, as previous evidence from a variety of contexts suggests that such patterns of low birth weight and postnatal catch-up growth can be associated with adverse long-term cardio-metabolic outcomes,” write the researchers in PLOS Medicine.
They explain that “[m]etformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes […] in many countries,” and “unlike insulin, metformin crosses the placenta and is present at clinically relevant concentrations in fetal and placental tissues.”
The investigators, from the University of Cambridge in the UK, analyzed data from 19 studies of neonatal growth including a total of 3723 infants, finding that babies exposed to metformin had a significant 107.7 g lower birthweight on average than those born to mothers treated with insulin.
Moreover, babies in the metformin group had a significantly lower risk for macrosomia (odds ratio [OR]=0.59) and being born large for gestational age (OR=0.78) than those in the insulin group.
In contrast to these findings, however, an analysis of two studies investigating growth in 411 infants aged 18–24 months found that metformin-exposed infants were a significant 440 g heavier on average than those born to mothers receiving insulin.
And mean BMI in mid-childhood (5–9 years of age) was a significant 0.78 kg/m2 higher among children in the metformin- versus insulin-exposed group in three studies (n=520 children), although the absolute difference in bodyweight was not significantly different among the two groups.
Jane Tarry-Adkins and colleagues note that “[l]imited evidence” from one study indicated that children born to mothers treated with metformin may have greater abdominal and visceral fat volume than those born to insulin-treated mothers, suggesting that “the higher BMI observed in children exposed to metformin in utero compared to those exposed to insulin may be the result of greater abdominal adiposity.”
And the team concludes that their findings highlight “a need for further studies examining longitudinal perinatal and childhood outcomes following intrauterine metformin exposure.”
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