Regulation of insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses

Objective: Our purpose was to evaluate which factors regulate insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses. Study design: We studied 76 singleton births between 25 and 36 weeks of gestation. Forty-nine pregnancies were complicated by hypertensive disease; 24 pregnancies were complicated by preterm labor or preterm rupture of membranes; and antenatal glucocorticoids were given in 49 pregnancies. Pathology reports showed infarct(s) or hematoma(s) in 31 of 69 placentas. We recorded blood gas values in umbilical artery and vein and measured glucose, C-peptide, and insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in umbilical vein. Results: Birth weight correlated with umbilical vein insulin-like growth factor-I (r = 0.68, P< .0001) and inversely with insulin-like growth factor binding protein-1 (r = −0.26, P = .02). Babies with birth weight of ≤25th percentile had lower insulin-like growth factor-I but higher insulin-like growth factor binding protein-1 levels than babies at >25th percentile. Two-factor analysis of variance showed that umbilical vein insulin-like growth factor-I was determined by gestational age (P = .0004) and birth weight percentile (P< .0001), whereas insulin-like growth factor binding protein-1 was not affected by gestational age. Umbilical vein C-peptide was highly correlated with insulin-like growth factor binding protein-1 (r = −0.55, P< .0001), but not insulin-like growth factor-I, levels. Blood gas values in umbilical artery and vein, particularly umbilical artery P 2, were correlated with umbilical vein insulin-like growth factor-I and insulin-like growth factor binding protein-1 (r = 0.51 and −0.48, respectively; P< .0001); changes in insulin-like growth factor-I and insulin-like growth factor binding protein-1 occurred at umbilical artery P 2<14.8 mm Hg. Multiple regression analysis showed that umbilical vein insulin-like growth factor-I was predicted by umbilical artery P 2, gestational age, and the presence of placental infarcts/hematomas (R2 of MODEL = 0.58, P< .0001), and umbilical vein insulin-like growth factor binding protein-1 by umbilical vein C-peptide, umbilical artery P 2, and placental infarcts/hematomas (R2 = 0.49, P< .0001). Conclusion: In the preterm fetus, circulating insulin-like growth factor-I is related to gestational age and the in utero growth potential, whereas insulin-like growth factor binding protein-1 is related only to the in utero growth potential. The P 2 is a robust determinant of both insulin-like growth factor-I and insulin-like growth factor binding protein-1 levels; hypoxia may restrain fetal growth through its effects on the insulin-like growth factor/insulin-like growth factor binding protein axis. Insulin is a powerful determinant of insulin-like growth factor binding protein-1, but not insulin-like growth factor-I, concentrations in the preterm fetus. (Am J Obstet Gynecol 2003;188:485-91.)