THE MATERNAL INSULIN-LIKE GROWTH-FACTOR (IGF) AND IGF-BINDING PROTEINRESPONSE TO TRISOMIC PREGNANCY DURING THE FIRST TRIMESTER - A POSSIBLE DIAGNOSTIC-TOOL FOR TRISOMY-18 PREGNANCIES

Many lines of evidence point to an important role for the insulinlike growth factors (IGFs) in embryonic and fetal growth in human pregnancy . The bioavailability of IGFs is modulated by IGF-binding proteins (IG FBP-1 to -6), whose permissive or inhibitory actions are regulated in part by posttranslational modification. In second and third trimester pregnancies, maternal IGFBP-1 is elevated in preeclampsia and intraute rine growth retardation. In the first trimester, trisomic pregnancies result in derangement of maternal serum levels of peptides, including hCG beta and pregnancy-associated plasma protein A. Trisomy 18 is char acterized by growth failure in the first trimester, whereas trisomy 21 is not; thus, if maternal serum levels of IGFs and IGFBPs reflect fet al growth, changes specific to trisomy 18 may be expected. We report m aternal serum levels of IGF-I, IGF-II, and IGFBP-1, -2, and -3; IGFBP- 1 phosphorylation; and IGFBP-3 proteolysis in pregnancies (n = 139) co mplicated by trisomy 18 or trisomy 21 compared with those in normal co ntrols. Maternal IGF-I, IGF-II, and IGFBP-3 showed no significant diff erence between fetuses with a normal karyotype and those with trisomy 18 or 21. The mean IGFBP-1 level was significantly higher and the mean IGFBP-2 level was lower in fetuses with trisomy 18 compared with norm al fetuses [108.8 +/- 6.1 vs. 36.7 +/- 1.9 mu g/L (P = 0.0001) and 81. 2 +/- 5.5 vs. 206.1 +/- 10.2 mu g/L (P = 0.0001), respectively]. There was no significant difference between the trisomy 21 and normal group s. The reduction in IGFBP-2 was confirmed by Western ligand and immuno blotting, and there was no evidence of variation in lower mol wt produ cts to suggest differential proteolysis. IGFBP-1 phosphoforms and IGFB P-3 proteolysis were not significantly different between groups. The f inding of altered maternal serum levels of IGFBP-1 and IGFBP-2 specifi c to pregnancies complicated by trisomy 18 suggests that these binding proteins may be important mediators of fetal growth in the first trim ester, and the clear differences in the ratio of IGFBP-1 to -2 may ser ve as an additional diagnostic marker for trisomy 18 pregnancies.