Insulin-like growth factors, their binding proteins, and fetal macrosomia in offspring of nondiabetic pregnant women

The Objective of this paper is to determine the relation between fetal macrosomia in offspring of nondiabetic women, and the levels of insulin-like growth factors (IGF-I, IGF-II), insulin growth factor binding protein-3 (IGFBP-3) and insulin, in maternal and neonatal compartments. Serum samples were obtained from normal pregnant women (n = 60) and their neonates (n = 60) between 37-41 weeks' gestation (mean 39 ± 9). Neonates were categorized as appropriate for gestational age (AGA; 10th-90th percentile; n = 20), and large for gestational age (LGA; >90th percentile; n = 40). Maternal and neonatal serum samples were analyzed for levels of IGF-I, IGFII, IGFBP-3 and insulin, by specific radioimmunoassays (RIAs). Serum levels were correlated with birth weight. The mean birth weight of the AGA group was 3296 ± 500 g versus 4201 ± 300 g for the LGA group (p <0.0001). Cord blood IGF-I was statistically higher in LGA group than in the AGA infants, (139 ± 67 ng/mL and 80 ± 32 ng/mL, respectively; p <0.0001). There was no correlation between maternal IGF-I serum levels and birth weight (363 ± 131 in the AGA vs. 308 ± 158 in the LGA group). IGF-II in maternal and cord blood did not correlate with fetal weight. Cord blood IGFBP-3 was significantly higher in the LGA group (1.1 ± 0.07 μg/mL) than in the AGA group (0.96 ± 0.05 μg/mL; p <0.05). Maternal insulin levels were similar between the two groups. Neonatal insulin levels were higher in the LGA group (18 ± μU/mL) as compared to the AGA group (16 ± μU/mL), however, this difference did not reach statistical significance. Fetal cord blood levels of IGF-I and IGFBP-3 are directly correlated with the birth weight of large for gestational age fetuses. These data suggest that the somatotropic axis plays a role in fetal growth. Additionally, insulin growth factor-1 appears to be an in utero growth promoter in the development of fetal macrosomia in infants of nondiabetic women.