Amino acid exchange as an integral part of the growth of preterm babies (literature review)




prematurely born, amino acids, growth


An important factor influencing the occurrence of metabolic disorders is premature birth. Compared to full-term children, prematurely born children are a special group of children in whom the morphology of organs and their physiological functions are not yet fully formed, and the activity of enzymes associated with protein metabolism is insufficient, which leads to disorders, including blocking the metabolism of certain amino acids. Thesis has been formed that certain factors will influence screening indicators of metabolic status in prematurely born children.

The transition from the intrauterine environment, leading to a change from a state of complete dependence on the mother to an independent extrauterine environment, is perhaps the most dramatic physiological and metabolic event in life. Birth and early adaptation provoke the formation of significant changes in protein and energy metabolism.

Amino acid concentrations are biomarkers of protein metabolism, and studying their patterns and levels in preterm infants may reveal metabolic changes associated with contributing factors. To date, standard values for the concentration of amino acids in the plasma of adults, infants and older children have been established.

Since amino acids are important components of a large number of vital compounds, disruption of the physiological metabolism of the protein component can lead to growth retardation in a child born prematurely. Thesis has been formed that certain factors can influence screening indicators of metabolic status in prematurely born children. The purpose of the study was to summarize the literature data, understand the characteristics of the metabolism of individual amino acids in prematurely born children, and also systematize data on changes in amino acid levels against the background of perinatal pathology.

Understanding and interpreting metabolic status provides a scientific basis and at the same time provides real-world guidance for improving the metabolic quality of care for preterm infants.

No conflict of interests was declared by the authors.


Adnan M, Puranik S. (2023, Jan). Hypertyrosinemia. [Updated 2022 Nov 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. URL:

Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D et al. (2010). Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. Am J Clin Nutr. 2010a; 92: 1080-1088.; PMid:20844073

Badurdeen S, Mulongo M, Berkley J. (2015). Arginine depletion increases susceptibility to serious infections in preterm newborns. Pediatr Res. 77: 290-297.; PMid:25360828 PMCid:PMC4335378

Beaufrère B. (1994). Protein turnover in low-birth-weight (LBW) infants. Acta paediatrica (Oslo, Norway : 1992). Acta Paediatrica. Supplement. 405: 86-92.; PMid:7734798

Bennet WM, Connacher AA, Scrimgeour CM, Jung RT, Rennie MJ. (1990). Euglycemic hyperinsulinemia augments amino acid uptake by human leg tissues during hyperaminoacidemia. Am J Physiol Endocrinol Metab. 259: E185-E194.; PMid:2166435

Bennet WM, Connacher AA, Scrimgeour RT, Smith K, Rennie MJ. (1989). Increase in anterior tibialis muscle protein synthesis in healthy man during mixed amino acid infusion: studies of incorporation of [1-13C] leucine. Clin Sci (Lond). 76: 447-454.; PMid:2714054

Bonnar K, Fraser D. (2019). Extrauterine growth restriction in low birth weight infants. Neonatal Netw. 38: 27-33.; PMid:30679253

Chesney RW, Helms RA, Christensen M, Budreau AM, Han X, Sturman JA. (1998). The role of taurine in infant nutrition. Advances in experimental medicine and biology. 442: 463-476.; PMid:9635063

Chien HC, Chen CH, Wang TM, Hsu YC, Lin MC. (2018). Neurodevelopmental outcomes of infants with very low birth weights are associated with the severity of their extra-uterine growth retardation. Pediatr Neonatol. 59: 168-175.; PMid:28866004

Chinsky JM, Singh R, Ficicioglu C, van Karnebeek CDM, Grompe M, Mitchell G et al. (2017). Diagnosis and treatment of tyrosinemia type I: A US and Canadian consensus group review and recommendations. Genet. Med. 19: 1380-1395.; PMid:28771246 PMCid:PMC5729346

Cleal JK, Lewis RM. (2008). The mechanisms and regulation of placental amino acid transport to the human foetus. Journal of neuroendocrinology. 20(4): 419-426.; PMid:18266945

Columbus DA, Fiorotto ML, Davis TA. (2015). Leucine is a major regulator of muscle protein synthesis in neonates. Amino acids. 47(2): 259-270.; PMid:25408462 PMCid:PMC4304911

Cormack BE, Bloomfield FH. (2013). Increased protein intake decreases postnatal growth faltering in ELBW babies. Arch Dis Child Fetal Neonatal Ed. 98: F399-404.; PMid:23487551

Denne SC, Poindexter BB. (2007). Evidence supporting early nutritional support with parenteral amino acid infusion. Semin Perinatol. 31: 56-60.; PMid:17462489

Denne SC, Rossi EM, Kalhan SC. (1991). Leucine kinetics during feeding in normal newborns. Pediatr Res. 30: 23-27.; PMid:1891278

Dessì A, Murgia A, Agostino R, Pattumelli MG, Schirru A, Scano P et al. (2016). Exploring the role of different neonatal nutrition regimens during the first week of life by urinary GC-MS metabolomics. Int J Mol Sci. 17: 265.; PMid:26907266 PMCid:PMC4783994

Dixon M, MacDonald A, White F, Stafford J. (2015). Disorders of amino acid metabolism, organic acidaemias and urea cycle disorders. In Clinical Paediatric Dietetics. 4th ed. Shaw V., Ed.; Wiley: Chichester, UK: 381-525.; PMid:25211207

Forny P, Hörster F, Ballhausen D, Chakrapani A, Chapman KA, Dionisi-Vici C et al. (2021). Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision. J. Inherit. Metab. Dis. 44: 566-592.; PMid:16702340

Graham GG, MacLean WC, Jr Brown KH, Morales E, Lembcke J, Gastañaduy A. (1996). Protein requirements of infants and children: growth during recovery from malnutrition. Pediatrics. 97(4): 499-505.; PMid:8632935

Häberle J, Burlina A, Chakrapani A, Dixon M, Karall D, Lindner M et al. (2019). Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision. J. Inherit. Metab. Dis. 42: 1192-1230.; PMid:30982989

Hicks SD, Confair A, Warren K, Chandran D. (2022). Levels of Breast Milk MicroRNAs and Other Non-Coding RNAs Are Impacted by Milk Maturity and Maternal Diet. Front. Immunol. 12: 785217.; PMid:35095859 PMCid:PMC8796169

Hoffmann B, Helbling C, Schadewaldt P et al. (2006). Impact of Longitudinal Plasma Leucine Levels on the Intellectual Outcome in Patients with Classic MSUD. Pediatr Res. 59: 17-20.; PMid:16326996

Hogewind-Schoonenboom JE, Zhu L, Zhu L, Ackermans EC, Mulders R, Te Boekhorst B et al. (2015). Potreby u fenilalanini u donoshenykh i nedonoshenykh novonarodzhenykh, yaki kharchuiutsia enteralno. Amerykanskyi zhurnal klinichnoho kharchuvannia. 1016: 1155-1162.; PMid:25926506

Huang L, Hogewind-Schoonenboom JE, van Dongen MJ, de Groof F, Voortman GJ, Schierbeek H et al. (2012). Methionine requirement of the enterally fed term infant in the first month of life in the presence of cysteine. The American journal of clinical nutrition. 95(5): 1048-1054.; PMid:22492372

Kalhan SC, Bier DM. (2008). Protein and amino acid metabolism in the human newborn. Annual review of nutrition. 28: 389-410.; PMid:18393660

Kasinski A, Doering CB, Danner DJ. (2004). Leucine toxicity in a neuronal cell model with inhibited branched chain amino acid catabolism. Brain Res Mol Brain Res. 122: 180-187.; PMid:15010210

Kryvosheieva VV, Vorobiova OV, Samoilenko IH. (2021). Stan problemy tranzytornykh porushen obminu rechovyn u novonarodzhenykh. Mizhnarodnyi zhurnal pediatrii, akusherstva ta hinekolohii. Lypen veresen. 14; 1: 63-64.

Lauinger L, Kaiser P. (2021). Sensing and Signaling of Methionine Metabolism. Metabolites. 11(2): 83.; PMid:33572567 PMCid:PMC7912243

Lin CJ, Geng GX, Peng ZR, Huang XT, Wu LL, Xu YQ et al. (2022). Characteristics of amino acid metabolism in preterm infants in Guangxi, China. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 24(2): 162-168.

Liu Q, Wu J, Shen W, Wei R, Jiang J, Liang J et al. (2017). Analysis of amino acids and acyl carnitine profiles in low birth weight, preterm, and small for gestational age neonates. The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 30(22): 2697-2704.; PMid:27844490

Malloy MH, Gaull GE. (1979). Enteral protein and amino acid nutrition in preterm infants. Seminars in perinatology. 3(4): 315-320.

Micheli JL, Schutz Y. (1987). Protein metabolism and postnatal growth in very low birthweight infants. Biology of the neonate. 52; Suppl 1: 25-40.; PMid:3327531

Morton DH, Strauss KA, Robinson DL, Puffenberger EG, Kelley RI. (2002). Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics. 109: 999-1008.; PMid:12042535

Pages AS, Tandonnet O, Renesme L. (2017). Evaluation of a modification of the nutrition policy on the frequency of extrauterine growth retardation in premature newborns between 2012 and 2014. Arch Pediatr. 24: 925-933.; PMid:28927927

Parimi PS, Kalhan SC. (2007). Glutamine supplementation in the newborn infant,Seminars in Fetal and Neonatal Medicine. Seminars in Fetal and Neonatal Medicine. 12; 1: 19-25. ISSN 1744-165X.; PMid:17142118

Parkhitko AA, Jouandin P, Mohr SE, Perrimon N. (2019). Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species. Aging cell. 18(6): e13034.; PMid:31460700 PMCid:PMC6826121

Riedijk MA, van Goudoever JB. (2007). Splanchnic metabolism of ingested amino acids in neonates. Current opinion in clinical nutrition and metabolic care. 10(1): 58-62.; PMid:17143056

Robinson JL, Bertolo RF. (2016). The Pediatric Methionine Requirement Should Incorporate Remethylation Potential and Transmethylation Demands. Advances in nutrition (Bethesda, Md.). 7(3): 523-534.; PMid:27184279 PMCid:PMC4863267

Tan JBC, Boskovic DS, Angeles DM. (2018). The Energy Costs of Prematurity and the Neonatal Intensive Care Unit (NICU) Experience. Antioxidants (Basel, Switzerland). 7(3): 37.; PMid:29498645 PMCid:PMC5874523

Techakittiroj C, Cunningham A, Hooper PF, Andersson HC, Thoene J. (2005). High protein diet mimics hypertyrosinemia in newborn infants. The Journal of Pediatrics. 146; 2: 281-282. ISSN 0022-3476.; PMid:15689925

Van den Akker CH, Van Goudoever JB. (2010). Recent advances in our understanding of protein and amino acid metabolism in the human fetus. Current opinion in clinical nutrition and metabolic care. 13(1): 75-80.; PMid:19904202

Van der Schoor S, Schierbeek H, Bet P et al. (2010). Majority of Dietary Glutamine Is Utilized in First Pass in Preterm Infants. Pediatr Res. 67: 194-199.; PMid:19809373

Van Goudoever JB, van der Schoor SR, Stoll B, Burrin DG, Wattimena D, Schierbeek H et al. (2006). Intestinal amino acid metabolism in neonates. Nestle Nutrition workshop series. Paediatric programme. 58: 95-108.; PMid:16902328

Verner A, Craig S, McGuire W. (2007). Effect of taurine supplementation on growth and development in preterm or low birth weight infants. The Cochrane database of systematic reviews. 4: CD006072.; PMid:17943882 PMCid:PMC8912912

Waisman HA, Kerr GR. (1965). Amino acid and protein metabolism in the developing fetus and the newborn infant. Pediatric clinics of North America. 12: 551-572.; PMid:14312825

Waisman HA, Kerr GR. (1965). Amino Acid and Protein Metabolism in the Developing Fetus and the Newborn Infant. Pediatric Clinics of North America. 12; 3: 551-572. ISSN 0031-3955. URL:; PMid:14312825

Wu S, Ren L, Li J, Shen X, Zhou Q, Miao Z et al. (2023). Breastfeeding might partially contribute to gut microbiota construction and stabilization of propionate metabolism in cesarean-section infants. Eur. J. Nutr. 62: 615-631.

Yilmaz O, Cochrane B, Wildgoose J, Pinto A, Evans S, Daly A et al. (2023). Phenylalanine free infant formula in the dietary management of phenylketonuria. Orphanet J. Rare Dis. 18: 16.; PMid:36698214 PMCid:PMC9878783

Zello GA, Menendez CE, Rafii M, Clarke R, Wykes LJ, Ball RO, Pencharz PB. (2003). Minimum protein intake for the preterm neonate determined by protein and amino acid kinetics. Pediatric research. 53(2): 338-344.; PMid:12538796

Zuvadelli J, Paci S, Salvatici E, Giorgetti F, Cefalo G, Re Dionigi A et al. (2022). Breastfeeding in Phenylketonuria: Changing Modalities, Changing Perspectives. Nutrients. 14: 4138.; PMid:36235790 PMCid:PMC9572443