Interrogation of the association between leptin, insulin resistance and fetal growth may provide a biological link for the fetal programming of later metabolic health. Our aim was to clarify the relationship between maternal and fetal leptin, insulin resistance and fetal growth. Maternal leptin, glucose and insulin were measured in early pregnancy and at 28weeks and the HOMA index calculated. At 34weeks, ultrasound scan assessed fetal weight and adiposity (abdominal wall width). At delivery birthweight was recorded and cord blood analyzed for fetal c-peptide and leptin. Analysis was performed using a multivariate linear regression model. 574 non-diabetic pregnant women. Fetal growth and maternal and fetal insulin resistance. On multivariate analysis a relationship was identified between maternal and fetal leptin concentrations at each time point and maternal body mass index. Maternal leptin was related to insulin resistance in early pregnancy (β=0.15, p=0.02) and at 28week gestation (β=0.27, p<0.001). Fetal insulin resistance correlated with maternal leptin in early pregnancy (β=0.17, p=0.004); at 28weeks (β=0.12, p=0.05), and with leptin in cord blood (r=0.28, p<0.001). Fetal weight at 34weeks was related to maternal leptin in early pregnancy (β=0.16, p=0.02). Both maternal and fetal leptin correlated with infant size at birth (β=0.12, p=0.07 in early pregnancy, β=0.21, p=0.004 in cord blood), independent of all other outcome measures. Our findings have confirmed that in a non-diabetic cohort there is a link between maternal and fetal leptin and insulin resistance. We also established a link between maternal leptin in early pregnancy and both fetal and neonatal size. These results add to the growing body of evidence suggesting a role for leptin in the fetal programming of childhood obesity and metabolic dysfunction.
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