Placental regulation of insulin-like growth factor axis in monochorionic twins with chronic twin-twin transfusion syndrome

To test the hypothesis that severe growth restriction (intrauterine growth retardation) in donor twins with chronic twin-twin transfusion syndrome (TT TS), a common complication of monochorionic twin pregnancy, is due to an ab erration in the insulin-like growth factor (IGF) axis, Ne studied 25 sets o f monochorionic twins with (n = 13) and without (n = 12) TTTS. Maternal and cord blood samples were collected at birth and analyzed for IGF-I, IGF-H, IGF-binding protein-1 (IGFBP-1), and IGFBP-1 phosphorylation status. Fetal IGF-II levels in the recipient twins with TTTS were higher than those in the donor twins (829 +/- 45 us. 543 +/- 60 ng/mL; P < 0.001), but were comparable with those in the non-TTTS twin pairs. IGF-I levels in recipient and donor twin pairs were similar,The total IGFBP-1 concentration was high er in the donor twins than in the recipients (1153 +/- 296 vs. 419 +/- 108 ng/mL; P < 0.001) and npn-TTTS twin pairs (P < 0.01). The percent less phos phorylated IGFBP-1 was higher in the recipients than in the donor twins (P < 0.05). There were no differences in IGF-I, IGF-II, and IGFBP-1 levels bet ween non; TTTS twin pairs. Maternal levels of IGFs were comparable in the t wo groups. In the TTTS group, fetal birth weight gave a positive correlatio n with serum IGF-II levels (y = 0.25x + 361.1; r = 0.47; P < 0.05) and a ne gative association with IGFBP-1 levels (y = -0.72x + 1593.6; r = 0.58; P < 0.01). Our data argue against intertwin transfusion as the cause of intrauterine g rowth retardation in the donor twin and provide evidence that the placenta is the key regulator of the fetal IGF ards, especially when fetal genotype and maternal environments are similar.