The Impact of Maternal Metabolic Flexibility During Gestation on Infant Adiposity in Individuals with Obesity

Maternal metabolism adapts during pregnancy to support fetal growth, yet how variability in maternal substrate oxidation influences neonatal adiposity is not well understood. Metabolic flexibility – the ability to adapt to substrate availability – may be a critical determinant of fetal nutrient supply. Therefore, the objective of this study was to examine associations between maternal metabolic flexibility and infant adiposity. Forty-seven pregnant women (28±5 years) with obesity (35.8±5.8 kg/m 2 ) were assessed in early (14.8±0.7 weeks) and late (35.9±0.6 weeks) gestation. Maternal substrate oxidation was measured overnight in a whole-room indirect calorimeter. Metabolic flexibility was calculated as the difference in respiratory exchange ratio (RER) between peak postprandial RER following a standardized dinner and RER during sleep. Maternal body mass and composition were recorded at the same time points, and infant adiposity was measured within 10 days of birth by air displacement plethysmography. Maternal metabolic flexibility in late gestation was positively associated with infant birth weight (β=169; 95% CI: 18 to 320; P=0.03) and adiposity (β=2.4; 95% CI: 0.4 to 4.3; P=0.02) independent of gestational weight gain. Lower fasting RER was inversely associated with infant adiposity (β=-2.4; 95% CI: -4.3 to -0.4; P=0.02). Postprandial RER was not predictive. Associations with infant adiposity were attenuated when birth weight was included, suggesting maternal substrate oxidation primarily influences adiposity via fetal growth. Maternal metabolic flexibility and fasting reliance on lipid oxidation in late pregnancy are key determinants of fetal growth and adiposity, highlighting the importance of maternal metabolism on developmental programming with implications for long-term offspring health.