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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Comparative Metabolomic Profiling of Amino Acids in Dried Blood Spots from Dichorionic and Monochorionic Twins Complicated by Selective Fetal Growth Restriction and Twin-to-Twin Transfusion Syndrome

  1. 1National Medical Research Center for Obstetrics Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia
  2. 2Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, 119991 Moscow, Russia

Abstract

Multiple pregnancy is associated with a high risk of perinatal complications, among which twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are of particular importance. These conditions are specific to monochorionic twins, yet their metabolic consequences in newborns remain poorly understood. Dried blood spots (DBSs) represent a convenient and non-invasive biomaterial for metabolomic analysis. This study included 7 twin pairs with sFGR, 10 pairs with TTTS, and 16 pairs from uncomplicated pregnancies. The amino acid profile in DBSs was determined by HPLC–MS/MS. Statistical significance of variation in normalized intra-pair difference in amino acid levels (ΔS_twins) was assessed using the Mann–Whitney U test with Benjamini–Hochberg false discovery rate correction. The dynamics of ΔS_twins between birth and the corrected full-term age were analysed. In comparing sFGR group with controls, intra-pair differences for glycine and alanine were altered at birth, and for β-alanine and leucine at the second time point. In the TTTS group, deviations from controls were observed for glutamine (at the second time point) and for alanine, α-aminobutyric acid, and aspartic acid (in terms of dynamics). Direct comparison between the two pathologies revealed differences in citrulline (TTTS vs. sFGR at birth) and in several amino acids over time (valine, leucine, ornithine). Dynamic analysis further showed that placental type significantly influenced the postnatal metabolic reorganisation of valine and alanine. These preliminary observations require independent validation and should not be considered validated clinical biomarkers.

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BibTeX
@article{chagovets2026comparative,
  title = {{Comparative Metabolomic Profiling of Amino Acids in Dried Blood Spots from Dichorionic and Monochorionic Twins Complicated by Selective Fetal Growth Restriction and Twin-to-Twin Transfusion Syndrome}},
  author = {Vitaliy V. Chagovets and Natalia A. Frankevich and Alisa O. Tokareva and Anastasia V. Novoselova and Marina N. Yushina and Fadi Hajjar and Tamara E. Karapetyan and Irina I. Ryumina and Vladimir E. Frankevich and Gennady T. Sukhikh},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219428},
  url = {https://www.mdpi.com/1422-0067/27/21/9428},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Comparative Metabolomic Profiling of Amino Acids in Dried Blood Spots from Dichorionic and Monochorionic Twins Complicated by Selective Fetal Growth Restriction and Twin-to-Twin Transfusion Syndrome
AU  - Vitaliy V. Chagovets
AU  - Natalia A. Frankevich
AU  - Alisa O. Tokareva
AU  - Anastasia V. Novoselova
AU  - Marina N. Yushina
AU  - Fadi Hajjar
AU  - Tamara E. Karapetyan
AU  - Irina I. Ryumina
AU  - Vladimir E. Frankevich
AU  - Gennady T. Sukhikh
PY  - 2026
DA  - 2026/10/22
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219428
UR  - https://www.mdpi.com/1422-0067/27/21/9428
AB  - Multiple pregnancy is associated with a high risk of perinatal complications, among which twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are of particular importance. These conditions are specific to monochorionic twins, yet their metabolic consequences in newborns remain poorly understood. Dried blood spots (DBSs) represent a convenient and non-invasive biomaterial for metabolomic analysis. This study included 7 twin pairs with sFGR, 10 pairs with TTTS, and 16 pairs from uncomplicated pregnancies. The amino acid profile in DBSs was determined by HPLC–MS/MS. Statistical significance of variation in normalized intra-pair difference in amino acid levels (ΔS_twins) was assessed using the Mann–Whitney U test with Benjamini–Hochberg false discovery rate correction. The dynamics of ΔS_twins between birth and the corrected full-term age were analysed. In comparing sFGR group with controls, intra-pair differences for glycine and alanine were altered at birth, and for β-alanine and leucine at the second time point. In the TTTS group, deviations from controls were observed for glutamine (at the second time point) and for alanine, α-aminobutyric acid, and aspartic acid (in terms of dynamics). Direct comparison between the two pathologies revealed differences in citrulline (TTTS vs. sFGR at birth) and in several amino acids over time (valine, leucine, ornithine). Dynamic analysis further showed that placental type significantly influenced the postnatal metabolic reorganisation of valine and alanine. These preliminary observations require independent validation and should not be considered validated clinical biomarkers.
SN  - 1422-0067
ER  -