Long-Term Impact on Offspring (5 to 11 Years of Age) of Metformin Use in Pregnancy in Mothers With Diabetes: A Systematic Review and Meta-Analysis

Abstract

Objective

Data are scant on the impact of metformin use in gestational diabetes mellitus/diabetes in pregnancy on long-term outcomes in children and mothers beyond 5 years of childbirth. This systematic review and meta-analysis aimed to evaluate the long-term impact of metformin use in pregnancy on children and their mothers.

Methods

Electronic databases were searched for studies evaluating metformin compared with insulin for managing gestational diabetes mellitus/diabetes in pregnancy. The primary outcome was the change in body mass index (BMI) in children at the ages of 5 to 11 years. The secondary outcomes were alterations in other anthropometric measures, obesity, and changes in the levels of lipids and adipocytokines in children and mothers.

Results

Children at the age of 9 years born to mothers who were treated with metformin during pregnancy had similar BMI (mean difference [MD], 1.09 kg/m² [95% confidence interval {CI}, −0.44 to 2.62]; P = .16; I² = 16%), waist circumference-to-height ratio (MD, 0.13 [95% CI, −0.05 to 0.30]; P = .16; I² = 94%), dual-energy X-ray absorptiometry (DXA) total fat mass (MD, 0.68 kg [95% CI, −2.39 to 3.79]; P = .66; I² = 70%), DXA total fat percent (MD, 0.04% [95% CI, −3.44 to 3.51]; P = .98; I² = 56%), DXA total fat-free mass (MD, 0.81 kg [95% CI, −0.96 to 2.58]; P = .37; I² = 55%), magnetic resonance imaging visceral adipose tissue volume (MD, 80.97 cm³ [95% CI, −136.47 to 298.41]; P = .47; I² = 78%), and magnetic resonance spectroscopy liver fat percentage (MD, 0.27% [95% CI, −1.26 to 1.79]; P = .73; I² = 0%) to those born to mothers who were treated with insulin. Serum adiponectin, leptin, alanine aminotransferase, and ferritin were comparable among groups. In children between the ages of 9 and 11 years, the occurrence of obesity, diabetes, or challenges in motor and social development were comparable between the 2 groups. After 9 years of childbirth, BMI and the risk of developing diabetes were similar between the 2 groups of women.

Conclusion

Metformin use in pregnancy did not show any adverse effects compared with insulin on long-term outcomes in children and their mothers.