Higher Cord C-Peptide Concentrations Are Associated With Slower Growth Rate in the 1st Year of Life in Girls but Not in Boys

OBJECTIVE: To understand the relationships between maternal glycemia during pregnancy and prenatal and early postnatal growth by evaluating cord C-peptide and IGF-I as mediating biomarkers in boys and girls separately. RESEARCH DESIGN AND METHODS: We evaluated 342 neonates within the EDEN mother-child cohort study born to mothers without diabetes diagnosis before pregnancy. We measured maternal glycemia at 24–28 weeks of gestation and neonates’ cord blood C-peptide (used as a proxy for fetal insulin) and IGF-I at birth. Reported maternal prepregnancy BMI and all measured infant weights and lengths in the 1st year were recorded. Growth modeling was used to obtain an individual growth curve for each infant in the 1st year. Path models, a type of structural equation modeling, were used for statistical analysis. Path analysis is a multivariate method associated with a graphical display that allows evaluation of mediating factors and distinguishes direct, indirect, and total effects. RESULTS: Cord C-peptide at birth was positively correlated with maternal prepregnancy BMI and maternal glycemia and was higher in girls. In a path model that represented prenatal growth, there was no significant direct effect of maternal glycemia on birth weight, but the effect of maternal glycemia on birth weight was mediated by fetal insulin and IGF-I in both girls and boys. However, in girls only, higher concentrations of cord C-peptide (but not cord IGF-I or maternal glucose) were associated with slower weight growth in the first 3 months of life. CONCLUSIONS: Our study underlines the role of the fetal insulin–IGF-I axis in the relationship between maternal glycemia during pregnancy and birth weight. We also show for the first time that high insulin concentration in female fetuses is associated with slower early postnatal growth. This slow, early growth pattern may be programmed by fetal hyperinsulinemia, and girls may be more susceptible than boys to its consequences.