The relation between human fetal growth and fetal blood levels of insulin-like growth factors I and II, their binding proteins, and receptors

Abstract

Objective: To determine the relation between normal human fetal growth and the levels of insulin-like growth factors (IGF-I, IGF-II), their receptors, and IGF binding protein-3 (IGFBP-3) in both the maternal and fetal compartments.

Methods: Serum samples were obtained from normal pregnant women (n = 52) and their fetuses (n = 32) via funipuncture at 21-34 weeks' gestation (mean 29 +/- 4.3) and from term neonates (n = 20) between 38-41 weeks (mean 39 +/- 0.9). Neonates were divided into two groups: the "large" group, whose weights were above the mean for gestational age, and the "small" group, whose weights were below the mean. Aliquots of amniotic fluid (AF) and serum samples were analyzed for levels of IGF-I, IGF-II, and IGFBP-3. Type 1 IGF receptors were assayed from placental extracts of first-trimester elective abortions and from term deliveries.

Results: Fetal IGF-I serum levels remained stable throughout most of pregnancy until 34 weeks' gestation (56 +/- 30 ng/mL). Thereafter, IGF-I increased significantly until term (79 +/- 8 ng/mL) (P < .05). Fetal IGF-II levels were relatively unchanged from 23 weeks to term except for a significant increase at 34 weeks. Fetal serum levels of IGFBP-3 averaged 0.8 +/- 0.05 microgram/mL up to 30 weeks' gestation and then increased slightly toward term, at 0.96 +/- 0.05 micrograms/mL. At term, the levels of IGF-I and IGF-II in the AF were not different from the levels in the neonatal serum, but were lower (P < .005) than those in maternal blood. All placental tissue obtained from first-trimester terminations of pregnancy assayed positive for IGF type 1 receptors. There was a direct correlation between neonatal weight and the levels of IGF-I (P < .02), but not with the levels of IGF-II. There were no significant correlations between newborn weights and IGFBP-3, or maternal serum levels of IGF-I and IGF-II. Amniotic fluid IGF-I and IGF-II levels were almost similar to fetal serum levels.

Conclusion: These data demonstrate the presence of type 1 receptors and the bioavailability of IGF-I, IGF-II, and IGFBP-3 throughout pregnancy. Insulin-like growth factor-I is shown to be adjunctively and directly associated with fetal size in normal pregnancies. The precise role that IGFs play in deviant fetal growth or whether IGFs can be used to treat reduced fetal growth remains unknown and awaits further investigation.