Genes or placenta as modulator of fetal growth: evidence from the insulin-like growth factor axis in twins with discordant growth

To determine whether fetal growth is regulated by placental and/or fetal fa ctors, we measured maternal and fetal concentrations of insulin-like growth factor-I (IGF-I), IGF-II and insulin-like growth factor binding protein-1 (IGFBP-1) (total and non-phosphorylated) in dichorionic (DC) and monochorio nic (MC) twins with (DC, n = 13; MC, n = 12) or without (DC, n = 13; MC, n = 12) discordant birth weight. In the discordant MC pregnancy, growth-restr icted (IUGR) twins had lower IGF-II concentrations (P < 0.001) but similar IGF-I concentrations compared to the appropriate for gestational age (AGA) co-twin. The differences in IGF-II concentrations showed a positive associa tion with percentage birth weight discordance (r = 0.60; P < 0.05) in MC tw ins, In contrast, IUGR DC twins had lower IGF-I concentrations (P < 0.05) b ut similar IGF-II concentrations compared to the AGA co-twins. There was a positive correlation between IGF-I concentrations and birth weight (r = 0.4 7; P < 0.05) in DC twins. Total IGFBP-1 concentrations were higher in both MC and DC IUGR twins (P < 0.05) compared to AGA twins. A negative associati on was found between total IGFBP-1 concentrations and birth weight of both MC (r = 0.47; P < 0.05) and DC (r = 0.58; P < 0.01) twins. No such differen ces in IGF concentrations were found between concordant MC and DC twin pair s. The maternal IGF concentrations were comparable between the MC and DC gr oups. These data suggest that growth discordances of twins exposed to the s ame maternal environment may be due to variations in either IGF-I or IGF-II /IGFBP-1, depending upon the functioning of the placenta.