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

Abstract

To test the hypothesis that severe growth restriction (intrauterine growth retardation) in donor twins with chronic twin-twin transfusion syndrome (TTTS), a common complication of monochorionic twin pregnancy, is due to an aberration in the insulin-like growth factor (IGF) axis, we studied 25 sets of 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-II, 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 vs. 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 higher in the donor twins than in the recipients (1153 +/- 296 vs. 419 +/- 108 ng/mL; P < 0.001) and non-TTTS twin pairs (P < 0.01). The percent less phosphorylated 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 between non-TTTS twin pairs. Maternal levels of IGFs were comparable in the two groups. In the TTTS group, fetal birth weight gave a positive correlation with serum IGF-II levels (y = 0.25x + 361.1; r = 0.47; P < 0.05), and a negative 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 growth retardation in the donor twin and provide evidence that the placenta is the key regulator of the fetal IGF axis, especially when fetal genotype and maternal environments are similar.