Insulin-like growth factors and their binding proteins in normal and abnormal human fetal growth

There is now a well recognized series of findings which suggests that the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may play an important role in both normal and abnormal human fetal growth: (1) IGFs are detectable in many fetal tissues from the first trimester onwards; (2) the levels of the IGFs in the fetal circulation increase during pregnancy, and at term the levels of IGF-I are directly related to birthweight; (3) in mice, disruption of the IGF gene leads to severe growth retardation; (4) in the first trimester the levels of IGFBP-1 are higher in the coelomic fluid than in amniotic fluid or maternal serum; (5) at 9-12 weeks there is a striking increase in IGFBP-1 and IGFBP-2 levels in amniotic fluid; (6) the major binding proteins in the human fetus are IGFBP-1 and IGFBP-2; (7) from as early as 16 weeks there is an inverse correlation between fetal levels of IGFBP-1 and birthweight; (8) in the mother, circulating levels of IGF-I and IGFBP-1 increase during pregnancy; (10) maternal levels of IGFBP-1 are elevated in severe pre-eclampsia and intrauterine growth retardation; (11) fetal levels of IGFBP-1 are elevated in cases of intrauterine growth retardation, especially those associated with specific evidence of reduced uteroplacental bloodflow; and (12) fetal levels of IGFBP-1 are elevated in labour, especially if there is evidence of fetal hypoxia. In conclusion, levels of IGFBP-1 appear to be a sensitive indicator of fetal nutrition, and of the short- or long-term response to reduced fetal nutrition.