Discordant Amino Acid Profiles in Monochorionic Twins with Twin-Twin Transfusion Syndrome

Abstract

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n ϭ 12) and without (n ϭ 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p Ͻ 0.001), leucine (p Ͻ 0.001), iso-leucine (p Ͻ 0.05), histidine (p Ͻ 0.001) and L-arginine (p Ͻ 0.001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p Ͻ 0.001), serine (p Ͻ 0.01), glycine (p Ͻ 0.001) and tyrosine (p Ͻ 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 Ϯ 64 versus 396 Ϯ 23 M; p Ͻ 0.001) and the non-TTTS twin pairs (p Ͻ 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism. Abbreviations MC, monochorionic F/M, feto-maternal ratio IUGR, intrauterine growth restriction TTTS, twin, twin transfusion syndrome AGA, appropriate for gestational age DC, dichorionic Perinatal death and postnatal handicap are more common in monochorionic (MC) than dichorionic (DC) twins (1). The high perinatal mortality in MC twins has been attributed to the presence of vascular anastomoses in the placenta, which may lead to twin-twin transfusion syndrome (TTTS) (2).Twin-twin transfusion syndrome is a chronic condition that presents in the early mid trimester of pregnancy, with characteristic discordance in fetal growth and amniotic fluid volume (1). Severe polyhydramnios develops in the larger "recipient" twin's sac, while oligohydramnios ensues in the growth restricted "donor" twin's sac. As pregnancy progresses, both fetuses are at a substantial risk of perinatal mortality and morbidity. The donor twin is at risk of the well described complications of severe intrauterine growth retardation, while the recipient twin may develop hydrops, cardiac dilatation, myocardial hypertrophy, tricuspid regurgitation, right ventricular outflow obstruction, and renal failure (3).Despite recent advances in the diagnostic and therapeutic modalities in fetal medicine, the treatment of chronic TTTS remains far from satisfactory (4, 5). This is attributed to the poor understanding of the patho-physiology of this enigmatic condition. Recent vascular anast...

Growth Restriction: Etiology, Maternal and Neonatal Outcome. A Review

“…In TTTS pregnancies leptin levels in recipient twins were three times higher than in IUGR donor twins, whereas in twin pregnancies with one IUGR twin, but without TTTS, the leptin differences were only 2-fold [144]. Concentrations of certain amino acids have been lower in IUGR twins than in normal co-twins, probably as a result of impaired placental amino acid transport [142,[144][145][146][147].…”

“…Monochorial twin pregnancies with intra-placental anastomoses may permit twin to twin transfusion [142,143] and thus lead to a twin-twin transfusion syndrome (TTTS). The donor twin develops IUGR, oligohydramnios and a small or non-visible urinary bladder whereas the recipient twin polyhydramnios, a large urinary bladder, cardiac hypertrophy with tricuspidal regurgitation and hydrops fetalis [143].…”

Fetal Leptin Influences Birth Weight in Twins with Discordant Growth

“…Additional factors, such as impaired placental transfermediated fetal undernutrition, may be responsible for the association between fetal growth and leptin. To this end, our recent work also suggests that fetal plasma concentrations of certain essential amino acids in growth-restricted MC twins are markedly reduced (42).…”

Multiple Pregnancies

“…They are secondary phenomena, however, not primary features of the TTTS. It might here also be mentioned that Bajoria et al ( 2000 ) , fi nding signi fi cantly different amino acid concentrations in the two twins, believed that this is an indication that the severe growth restriction of the donor may not be due primarily to the anastomotic loss of blood but that it is the possible result of impaired transplacental transport of amino acids. We differ with this interpretation.…”