Effect of Maternal Metformin Treatment in Pregnancy on Neonatal Metabolism: Evidence From Newborn Metabolic Screening
Research Design and Methods: Retrospective case-control study. NBS results of infants born to mothers treated with metformin for hyperglycaemia during pregnancy were compared with diet-treated diabetes and matched normal controls. Exclusions: maternal type 1 diabetes, major fetal anomalies, incomplete infant data. Inclusions: maternal hyperglycemia in pregnancy treated with diet alone or diet plus metformin. Results from the New South Wales NBSP (dried infant bloodspot sample, 24-72 hours after birth) for 25 routinely studied analytes, were measured using mass spectrometry. Data from metformin-exposed and control infants were compared using non-parametric methods and multiples of the median for each analyte.
Results: 574 cases were compared with 952 diet-treated diabetes cases and 979 controls. Metformin-exposed infants had shorter gestational age (266 days ±7 vs 272±10±34vs 274 ±9 ) (p= <0.001) and lower birth weights (3.28 kg ±0.51vs 3.29±0.49 ±0.52 vs 3.33±0.43) (p=0.008). Short, medium and one long-chain acylcarntine (tetradecanoylcarnitine; C14) concentrations were higher in the metformin exposed group compared to normal controls. Comparison with diet-treated diabetes controls (to eliminate confounding by hyperglycemia) continued to show raised butyrylcarntine (C4), isovalerylcarnitine (C5), glutarylcarnitine (C5D) in the metformin-exposed group. There was no evidence of vitamin B12 deficiency (low methionine, elevated propionylcarnitine; C3) in metformin-exposed infants. All results were within normal population limits.
Conclusions: We have identified subtle (non-pathological) changes in neonatal metabolism which represents a signature effect of fetal metformin exposure.
