Higher Cord C-Peptide Concentrations Are Associated With Slower Growth Rate in the 1st Year of Life in Girls but Not in Boys
- Nolwenn Regnault1,2⇓,
- Jérémie Botton1,2,3,
- Barbara Heude1,2,
- Anne Forhan1,2,
- Régis Hankard4,5,
- Bernard Foliguet6,
- Teresa A. Hillier7,
- Jean-Claude Souberbielle8,
- Patricia Dargent-Molina9,10,
- Marie-Aline Charles1,2 and
- the EDEN Mother-Child Cohort Study Group*
- 1INSERM, U1018, Center for Research in Epidemiology and Population Health, Lifelong Epidemiology of Diabetes, Obesity, and Chronic Kidney Disease, Villejuif, France
- 2University Paris–Sud, Faculty of Medicine, Kremlin-Bicêtre, France
- 3University Paris–Sud, Faculty of Pharmacy, Chatenay-Malabry, France
- 4University Hospital, INSERM Clinical Investigation Center 802, Poitiers, France
- 5University of Poitiers, Faculty of Medicine and Pharmacy, Poitiers, France
- 6Regional University Maternity, Laboratory of Reproduction and Development, University Nancy- Lorraine, Nancy, France
- 7Kaiser Permanente Center for Health Research Northwest/Hawaii Division, Portland, Oregon
- 8INSERM, U845, Necker Hospital, Paris, France
- 9INSERM, UMR 953, Epidemiological Research in Perinatal Health and Women’s and Child Health, Villejuif, France
- 10University Pierre and Marie Curie, UMR S953, Paris, France
- Corresponding author: Nolwenn Regnault, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db10-1189/-/DC1.
*A complete list of the members of the EDEN Mother-Child Cohort Study Group can be found in the appendix.
- Received August 20, 2010.
- Accepted May 8, 2011.
- © 2011 by the American Diabetes Association.
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