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Placenta as a Link between Amino Acids, Insulin-IGF Axis, and Low Birth Weight: Evidence from Twin Studies

University of Manchester, Academic Unit of Obstetrics and Gynecology, St. Mary’s Hospital for Women and Children (R.B., S.W.), Manchester, M13 OJH United Kingdom; Imperial College School of Medicine, Departments of Maternal and Fetal Medicine (S.R.S.) and Clinical Chemistry (M.H.), Chelsea and Westminster Hospital, London, SW 6 United Kingdom

Address all correspondence and requests for reprints to: Dr. Rekha Bajoria, M.D., Ph.D., St. Mary’s Hospital for Women and Children, Whitworth Park, Manchester, M13 OJH United Kingdom. E-mail: rbajoria{at}doctors.net.uk

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.

This work was supported by a grant from the Research Graduate and Support Unit, University of Manchester (Manchester, UK).

Abbreviations: AGA, Appropriate for gestational age; CI, confidence interval; DC, dichorionic; DZ, dizygotic; IGFBP, IGF-binding protein; IUGR, intrauterine growth-restricted; MZ, monozygotic.

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