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 (IGF BPs) may play an important role in both normal and abnormal human feta l growth: (1) IGFs are detectable in many fetal tissues from the first trimester onwards; (2) the levels of the IGFs in the fetal circulatio n increase during pregnancy, and at term the levels of IGF-I are direc tly related to birthweight; (3) in mice, disruption of the IGF gene le ads to severe growth retardation; (4) in the first trimester the level s of IGFBP-1 are higher in the coelomic fluid than in amniotic fluid o r maternal serum; (5) at 9-12 weeks there is a striking increase in IG FBP-1 and IGFBP-2 levels in amniotic fluid; (6) the major binding prot eins 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 ar e elevated in severe pre-eclampsia and intrauterine growth retardation ; (11) fetal levels of IGFBP-1 are elevated in cases of intrauterine g rowth 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 hypox ia. In conclusion, levels of IGFBP-1 appear to be a sensitive indicato r of fetal nutrition, and of the short- or long-term response to reduc ed fetal nutrition.