Insulin-Like Growth Factors, Their Binding Proteins, and Fetal Macrosomia in Offspring of Nondiabetic Pregnant Women

Abstract

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, IGF-II, 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 microg/mL) than in the AGA group (0.96 +/- 0.05 microg/mL; p < 0.05). Maternal insulin levels were similar between the two groups. Neonatal insulin levels were higher in the LGA group (18 +/- microU/mL) as compared to the AGA group (16 +/- microU/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.

Placental Growth Hormone (GH), GH-Binding Protein, and Insulin-Like Growth Factor Axis in Normal, Growth-Retarded, and Diabetic Pregnancies: Correlations with Fetal Growth*

“…Our finding is consistent with a number of studies (5,8,22) that showed decreased maternal serum IGF-I in IUGR, but differs from the results of Witznitzer et al (35). The latter group did not find a correlation between maternal serum IGF-I and birth weight after week 37, but their study did not include cases of IUGR.…”

Maternal anthropometric and metabolic factors in the first half of pregnancy and risk of neonatal macrosomia in term pregnancies. A prospective study

“…This does not exclude the possibility that leptin may be an important mediator of the obesityinduced fetal macrosomia. Maternal serum levels of IGF-I have previously been shown not to be directly related to birth weight (29). IGF-I was, however, included in the present study because it is related to maternal weight and because we specifically wanted to study the risk of delivering a baby with weight in the upper percentiles (28).…”

Longitudinal Data for Intrauterine Levels of Fetal IGF-I and IGF-II

“…The aim of several recent publications [2, 3, 4, 5, 6, 7]was to relate specific hormone alteration including IGF-I and/or IGF-II to human fetal growth. Results were conflicting, some describing a positive correlation [2, 3], while others could show this only for IGF-I, but not for IGF-II [1, 5].…”

“…IGF-I (but not IGF-II) levels in fetuses with IUGR were significantly lower than those in normal fetuses of the same age [5, 6]. The same could be shown for large-for-gestational-age fetuses, in whom IGF-I and IGFBP-3 were directly correlated with birth weight [7, 8]. These findings suggest that IGF-I (but not IGF-II) is involved in the control of fetal size during the second half of gestation.…”