Amino acid profile of umbilical cord blood plasma of premature newborns in early diagnosis of necrotizing enterocolitis: a pilot study
- Authors: Sinitskii A.I.1, Vinel P.K.1, Shatrova Y.M.1, Tsareva V.V.1,2, Grunin A.V.1, Gusarova E.O.3
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Affiliations:
- South-Ural State Medical University
- Chelyabinsk Regional Children’s Clinical Hospital
- Regional perinatal center
- Issue: Vol 69, No 7 (2024)
- Pages: 91-100
- Section: Original Study Articles
- Published: 27.08.2024
- URL: https://kld-journal.fedlab.ru/0869-2084/article/view/633797
- DOI: https://doi.org/10.17816/cld633797
- ID: 633797
Cite item
Abstract
BACKGROUND: Necrotizing enterocolitis is a common emergency condition in premature infants, which is characterized by high rates of mortality and disability. Its diagnosis is complex and often ineffective, thus, the search for biomarkers for prognosis and early diagnosis of the disease is underway.
AIM: To identify changes in the amino acid spectrum of umbilical cord blood plasma that precede the development of necrotizing enterocolitis in extremely premature infants.
MATERIALS AND METHODS: The study was conducted from June 2023 to May 2024. Umbilical cord blood was obtained from physiological and operative deliveries of extremely preterm newborns of ≤32 weeks gestational age, considering the informed consent obtained from the mother, absence of standard contraindications, and exclusion criteria. The children were observed from birth to discharge. Necrotizing enterocolitis was diagnosed by identifying laboratory signs of a systemic inflammatory response in combination with clinical and instrumental data. Amino acid levels in cord blood plasma were determined by capillary electrophoresis. Based on the results of monitoring patients, two groups were retrospectively formed: the comparison group including 10 extremely premature newborns who did not develop necrotizing enterocolitis during the entire observation period, and the main group consisting of 5 patients with necrotizing enterocolitis. The study participants were comparable in body weight and Apgar and Ballard scores at birth. In the main group, necrotizing enterocolitis of stages I–III was diagnosed within 2 weeks of birth.
RESULTS: The development of necrotizing enterocolitis is preceded by a decrease in proteinogenic amino acid level in the umbilical cord blood plasma by 13.9% (p=0.019). This includes the levels of arginine and proline (by 36.2 and 32.8%, p=0.008 and p=0.028, respectively), leucine and isoleucine (41.8 and 36.9%, p=0.030 and p=0.005, respectively), and tryptophan (by 35.5%, p=0.019). A decrease in the levels of methionine (by 28.0%, p=0.028), serine (by 24.1%, p=0.013), and phenylalanine (by 15.8%, p=0.040) was less pronounced, but statistically significant.
CONCLUSION: Comparing the data obtained to the results of other studies, disturbances in the biosynthesis and/or transplacental transfer of amino acids (primarily arginine and amino acids with branched hydrocarbon radicals) can be considered as crucial links in the pathogenesis of necrotizing enterocolitis. The present study used umbilical cord blood obtained at the birth of a child, hence, the identified changes should be considered not as a consequence of intestinal damage but as specific changes in the pool of free amino acids, against which necrotizing enterocolitis is highly possible to develop.
Full Text
About the authors
Anton I. Sinitskii
South-Ural State Medical University
Author for correspondence.
Email: sinitskiyai@yandex.ru
ORCID iD: 0000-0001-5687-3976
SPIN-code: 3681-1816
Scopus Author ID: 24781343800
ResearcherId: D-6010-2014
MD, Dr. Sci. (Medicine), Assistant Professor
Russian Federation, 64 Vorovskogo Str., 454092 ChelyabinskPolina K. Vinel
South-Ural State Medical University
Email: vinelpolina@icloud.com
ORCID iD: 0000-0002-3745-3690
SPIN-code: 6298-8131
Postgraduate student of the Department of Biochemistry named after R.I. Lifshitz
Russian Federation, 64 Vorovskogo Str., 454092 ChelyabinskYulia M. Shatrova
South-Ural State Medical University
Email: shatr20@yandex.ru
ORCID iD: 0000-0002-8865-6412
SPIN-code: 6365-0061
Cand. Sci. (Biology)
Russian Federation, 64 Vorovskogo Str., 454092 ChelyabinskValentina V. Tsareva
South-Ural State Medical University; Chelyabinsk Regional Children’s Clinical Hospital
Email: semenovatsareva@mail.ru
ORCID iD: 0000-0002-6695-7388
SPIN-code: 7966-9068
MD, Cand. Sci. (Medicine)
Russian Federation, 64 Vorovskogo Str., 454092 Chelyabinsk; ChelyabinskAlexandr V. Grunin
South-Ural State Medical University
Email: sasha_grunin@mail.ru
ORCID iD: 0009-0007-9327-7779
SPIN-code: 2209-4645
Russian Federation, 64 Vorovskogo Str., 454092 Chelyabinsk
Eugenia O. Gusarova
Regional perinatal center
Email: Evgeniyagusarova89@yandex.ru
ORCID iD: 0009-0002-8483-0265
SPIN-code: 3279-5957
Russian Federation, Chelyabinsk
References
- Agakidou E, Agakidis C, Gika H, Sarafidis K. Emerging biomarkers for prediction and early diagnosis of necrotizing enterocolitis in the era of metabolomics and proteomics. Frontiers in Pediatrics. 2020,8:602255. doi: 10.3389/fped.2020.602255
- Hu X, Liang H, Li F, et al. Necrotizing enterocolitis: current understanding of the prevention and management. Pediatric Surgery International. 2024,40(1):32. doi: 10.1007/s00383-023-05619-3
- Klerk DH, van Varsseveld OC, Offringa M, et al. Core Outcome Set for Necrotizing Enterocolitis Treatment Trials. Pediatrics. 2024,153(6):e2023065619. doi: 10.1542/peds.2023-065619
- Vinel PK, Tsareva VV, Sinitskii AI, et al. Biomarkers of necrotizing enterocolitis through the prism of etiopathogenesis. Medical News of North Caucasus. 2023,18(2):211–218. doi: 10.14300/mnnc.2023.18051
- Kaplina AV, Kayumova EE, Vasil’eva EYu, et al. Biomarkers and predictors of postoperative necrotizing enterocolitis in neonates with duct-dependent congenital heart defects undergoing cardiac surgery: a cohort study. Experimental and Clinical Gastroenterology. 2023,215(11):81–101. EDN: QBGZFP doi: 10.31146/1682-8658-ecg-219-11-81-101
- Kosterina EE, Balashova EN, Krasnyi AM, et al. Fecal cytokine profile in preterm infants in the diagnosis of necrotizing enterocolitis: pilot study results. Pediatric Hematology/Oncology and Immunopathology. 2024,23(1):119–126. EDN: NBGDCZ doi: 10.24287/1726-1708-2024-23-1-119-126
- Sinclair TJ, Ye C, Chen Y, et al. Progressive metabolic dysfunction and nutritional variability precedes necrotizing enterocolitis. Nutrients. 2020,12(5):1275. doi: 10.3390/nu12051275
- Putra RA. Analysis of Risk Factors for Necrotizing Enterocolitis (NEC) in Newborns: A Systematic Literature Review. Scientific Journal of Pediatrics. 2024,2(1):52–58. doi: 10.59345/sjped.v2i1.97
- Bosco A, Piu C, Picciau ME, et al. Metabolomics in NEC: An Updated Review. Metabolites. 2024,14(1):14. doi: 10.3390/metabo14010014
- Deianova N, el Hassani SM, Struijs EA, et al. Fecal amine metabolite analysis before onset of severe necrotizing enterocolitis in preterm infants: a prospective case–control study. Scientific reports. 2022,12(1):12310. doi: 10.1038/s41598-022-16351-8
- Mackay S, Frazer LC, Bailey GK, et al. Improving Diagnostic Precision: Urine Proteomics Identifies Promising Biomarkers for Necrotizing Enterocolitis. medRxiv. 2024,2024.03:21.24304374. doi: 10.1101/2024.03.21.24304374
- Guo T, Hu S, Xu W, et al. Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis. iScience. 2023,26(6). doi: 10.1016/j.isci.2023.106882
- Obayashi M, Iwata S, Okuda T, et al. Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants. Nutrients. 2024,16(4):476. doi: 10.3390/nu16040476
- Nasef M, Turkia HB, Ali AMH, Mahdawi E, Nair A. To What Extent Does Arginine Reduce the Risk of Developing Necrotizing Enterocolitis? Cureus. 2023,15(9):e45813. doi: 10.7759/cureus.45813
- Zamora SA, Amin HJ, McMillan DD, et al. Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis. J. Pediatr. 1997,131(2):226–232. doi: 10.1016/S0022-3476(97)70158-6
- Amin HJ, Zamora SA, McMillan DD, et al. Arginine supplementation prevents necrotizing enterocolitis in the premature infant. The Journal of pediatrics. 2002,140(4):425–431. doi: 10.1067/mpd.2002.123289
- Bahr TM, Carroll PD. Cord blood sampling for neonatal admission laboratory testing–an evidence-based blood conservation strategy. Seminars in Perinatology. 2023,47(5):151786. doi: 10.1016/j.semperi.2023.151786
- Rumyantsev AG, Rumyantsev SA. Umbilical blood as a source of information about fetus condition. Pediatriya. Zhurnal im G.N. Speranskogo. 2012,91(3):43–52. EDN: OZMAWB
- Dorofeyeva EI, Podurovskaya YuL, Burov AA, et al. Diagnosis and conservative treatment of necrotizing enterocolitis in newborn (project of clinical practice guidelines). Neonatology: news, views, education. 2014,(2(4)):84–92. EDN: SZWJHX
- Walsh MC, Kliegman RM. Necrotizing enterocolitis: Treatment based on staging criteria. Pediatr. Clin. North Am. 1986,33(1):179–201. doi: 10.1016/s0031-3955(16)34975-6
- Poinsot V, Ong-Meang V, Gavard P, Couderc F. Recent advances in amino acid analysis using capillary electromigration methods, 2013–2015. Electrophoresis. 2016,37(1):142–161. doi: 10.1002/elps.201500302
- Monirujjaman MD, Ferdouse A. Metabolic and physiological roles of branched-chain amino acids. Advances in Molecular Biology. 2014,2014(1):364976. doi: 10.1155/2014/364976
- Menichini D, Feliciello L, Neri I, Facchinetti F. L-Arginine supplementation in pregnancy: a systematic review of maternal and fetal outcomes. The Journal of Maternal-Fetal & Neonatal Medicine. 2023,36(1):2217465. doi: 10.1080/14767058.2023.2217465
- Manta-Vogli PD, Schulpis KH, Dotsikas Y, Loukas YL. The significant role of amino acids during pregnancy: nutritional support. The Journal of Maternal-Fetal & Neonatal Medicine. 2020,33(2):334–340. doi: 10.1080/14767058.2018.1489795