Maternal body mass index is related to fetal uptake of glucose and oxygen via fetal insulin resistance rather than fetal glucose levels

Maternal obesity significantly impacts fetal growth and is linked to adverse pregnancy outcomes. However, the specific influence of maternal metabolic status on fetal metabolism and growth in healthy pregnancies is poorly understood. This study investigates the hypothesis that pre-pregnancy maternal body mass index (BMI) correlates with increased fetal insulin resistance, subsequently affecting fetal glucose and oxygen uptake-key determinants of growth. We examined 32 participants with healthy pregnancies, assessing pre-pregnancy BMI alongside blood gas analyses, umbilical glucose, insulin, lactate levels and Doppler blood flow in the umbilical vein. Our findings reveal a positive correlation between maternal BMI and fetal insulin resistance, indicated by the homeostatic model assessment for insulin resistance (HOMA-IR) (<i>ρ</i> = 0.39, <i>p</i> = 0.03, <i>n</i> = 31) and fetal insulin levels (<i>ρ</i> = 0.43, <i>p</i> = 0.02, <i>n</i> = 31). Both fetal HOMA-IR and insulin levels demonstrated significant relationships with birthweight (<i>ρ</i> = 0.39, <i>p</i> = 0.03; <i>ρ</i> = 0.49, <i>p</i> = 0.005). Notably, fetal glucose levels did not correlate with birthweight. Enhanced insulin resistance was positively correlated with increased fetal oxygen and glucose uptake per kilogram of birthweight. These results suggest pre-pregnancy BMI influences fetal growth via insulin resistance rather than direct effects on glucose levels.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.