Placenta as a link between amino acids, insulin-IGF axis, and low birth weight: Evidence from twin studies

Current evidence suggests that reduced placental transport of amino acids regulates fetal growth. We determined the association between fetal nutrition and the insulin-IGF axis by measuring the plasma concentrations of amino acids, insulin, IGF-I and IGF-binding protein-1 (IGFBP-1) in maternal and cord blood from gestational age-matched dichorionic (DC) twins with (n = 10) and without discordant birth weights (n = 10). In the growth-restricted (IUGR) twins, fetal concentrations of total essential (P < 0.01), nonessential (P < 0.01), and branched chain amino acids (P < 0.01) were lower than those in the appropriate for gestational age co-twins and concordant twin pairs. The IUGR twins had lower fetal concentrations of insulin (P < 0.001) and IGF-I (P < 0.05) and higher concentrations of IGFBP-1 (P < 0.01) than their appropriate for gestational age co-twins. In the discordant group, fetal IGFBP-1 had a negative association with fetal insulin (r = 0.71; P < 0.001), total essential amino acids (r = 0.78; P < 0.001), and branched chain amino acids (r = 0.64; P < 0.01). There was a positive correlation between total essential amino acids (r = 0.63; P < 0.001) and branched chain amino acids (r = 0.58; P < 0.01) and plasma insulin. However, there were no associations among fetal insulin, IGFBP-1 and nonessential amino acids. These data demonstrate the link between the reduction in certain essential and nonessential amino acids and alterations in fetal circulating levels of insulin and IGFBP-1, in growth-restricted twins.