Potential of intestinal fatty acid-binding protein in assessing enteral tolerance in neonates of different gestational ages: A cross-sectional cohort study
https://doi.org/10.25207/1608-6228-2025-32-1-39-51
Abstract
Background. Functional gastrointestinal disorders are highly prevalent among young children and pose a significant burden on outpatient healthcare services. Functional disorders of the gastrointestinal tract may be caused by increased intestinal permeability. Markers characterizing the transcellular pathway are currently being studied. Intestinal fatty acid-binding protein (I-FABP) serves as a marker of intestinal mucosal integrity, represents a cytosolic protein that plays a crucial role in intracellular transport and metabolism of fatty acids in enterocytes, and is released upon their death.
Objectives. To evaluate the diagnostic value of the intestinal fatty acid-binding protein as a marker for enteral tolerance in neonates with gestational ages ranging from 33 to 41 weeks.
Methods. A cross-sectional cohort study involved 115 newborns admitted to the second-stage care units of Voronezh Regional Children’s Clinical Hospital No. 1 from maternity facilities in Voronezh Oblast between March 2023 and May 2024. The cohort included boys n = 72, 62.6%; girls n = 43, 37.4%. The participants were divided into two groups: Group 1 consisted of term neonates (gestational age 37–41 weeks, n = 80), while Group 2 included preterm neonates (gestational age 33–36 weeks, n = 35). The age of term patients accounted for 5.0 [4.0; 7.0] days, while the age of preterm neonates was 7.0 [4.0; 8.0] days. I-FABP concentration was measured once using the Human IFABP/FABP2 ELISA kit on a Multiskan Go analyzer. Based on the presence of symptoms indicating impaired enteral tolerance during the neonatal period, the groups were further subdivided into Subgroups 1A (n = 39) and 2A (n = 10) without symptoms of reduced enteral tolerance, 1B (n = 41) and 2B (n = 25) with symptoms of reduced enteral tolerance. Statistical analysis was performed using StatTech v. 4.3.2 (Stattech, Russia). The differences were considered statistically significant at p <0.05.
Results. The circulating intestinal fatty acid-binding protein level in term neonates accounted for 1.130 [0.796–1.911] ng/ml, while in preterm neonates, it was 1.134 [1.050–1.614] ng/ml, showing no dependence on the type of feeding (p > 0.05). In term newborns without gastroenterological symptoms in the neonatal period, the concentration of I-FABP amounted to 0.920 [0.695–1.160] ng/ml, compared to 1.900 [0.965–2.564] ng/ml in those with gastrointestinal symptoms, (p < 0.001). A similar tendency was observed in preterm neonates: those without clinical signs of reduced enteral tolerance had an I-FABP concentration of 1.002 [0.867 to 1.073] ng/mL versus 1.312 [1.102 to 1.972] ng/mL in neonates with gastroenterological symptoms (p = 0.002). The level of intestinal fatty acid-binding protein was associated with the degree of enteral tolerance: the highest values were noted in newborns with all three symptoms, measuring 2.802 [1,641–3.402] ng/ml.
Conclusion. Circulating intestinal fatty acid-binding protein during the neonatal period is independent of gestational age and feeding type but increases in neonates with gastrointestinal symptoms, suggesting that intestinal fatty acid-binding protein may serve as a biomarker for assessing enteral tolerance in neonates. Further investigation of intestinal fatty acid-binding protein may contribute to the development of decision-making tools for complex clinical situations, including the initiation and expansion of enteral nutrition in extremely preterm neonates or following an enteral pause, as well as in the differential diagnosis of early stages of surgical gastrointestinal pathology in newborns.
About the Authors
I. A. BavykinaRussian Federation
Irina A. Bavykina — Dr. Sci. (Med.), Assoc. Prof., Department of Faculty and Palliative Pediatrics
Studencheskaya str., 10, Voronezh, 394036
A. A. Berdnikov
Russian Federation
Andrey A. Berdnikov — Assistant, Department of Faculty and Palliative Pediatrics; Deputy Chief Physician for Clinical and Expert Work
Studencheskaya str., 10, Voronezh, 394036
Lomonosova str., 114, Voronezh, 394087
A. A. Zvyagin
Russian Federation
Aleksandr A. Zvyagin — Dr. Sci. (Med.), Prof., Department of Propaedeutics of Children’s Diseases and Outpatient Pediatrics
Studencheskaya str., 10, Voronezh, 394036
A. V. Kubyshkina
Russian Federation
Anastasiya V. Kubyshkina — Cand. Sci. (Med.), Deputy Head of the Center for the Training of Scientific and Scientific-Pedagogical Personnel; Intensivist, Resuscitation and Intensive Care Department
Studencheskaya str., 10, Voronezh, 394036
Moskovsky Prospect, 151, Voronezh, 394066
S. V. Barannikov
Russian Federation
Sergey V. Barannikov — Cand. Sci. (Med.), Assoc. Prof., Department of Urgent and Faculty Surgery
Studencheskaya str., 10, Voronezh, 394036
References
1. Eisfeld H, Glimm AM, Burmester GR, Ohrndorf S, Backhaus M. Pregnancy outcome in women with different rheumatic diseases: a retrospective analysis. Scand J Rheumatol. 2021;50(4):299–306. https://doi.org/10.1080/03009742.2020.1849788
2. Malaza N, Masete M, Adam S, Dias S, Nyawo T, Pheiffer C. A Systematic Review to Compare Adverse Pregnancy Outcomes in Women with Pregestational Diabetes and Gestational Diabetes. Int J Environ Res Public Health. 2022;19(17):10846. https://doi.org/10.3390/ijerph191710846
3. Huang X, Xiang H, Bao J, Zhu J, Chen J, Zhou P, Zhou T, Xu Z. The effects of intrauterine growth on physical and intellectual development of one-year-old infants: a study on monochorionic twins with selective intrauterine growth restriction. J Obstet Gynaecol. 2023;43(1):2125300. https://doi.org/10.1080/01443615.2022.2125300
4. Kim SY, Kim EK, Song H, Cheon JE, Kim BN, Kim HS, Shin SH. Association of Brain Microstructure and Functional Connectivity With Cognitive Outcomes and Postnatal Growth Among Early School-Aged Children Born With Extremely Low Birth Weight. JAMA Netw Open. 2023;6(3):e230198. https://doi.org/10.1001/jamanetworkopen.2023.0198
5. Bavykina IA, Berdnikov AA, Zvyagin AA, Kubyshkina AV, Antakova .N. Dynamics of Claudin-2 tight junction protein levels in enterocytes of infants during the first months of life. Russian Bulletin of Perinatology and Pediatrics. 2024;69(6):59–65 (In Russ.). https://doi.org/10.21508/1027-4065-2024-69-6-59-65
6. Robin SG, Keller C, Zwiener R, Hyman PE, Nurko S, Saps M, Di Lorenzo C, Shulman RJ, Hyams JS, Palsson O, van Tilburg MAL. Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria. J Pediatr. 2018;195:134–139. https://doi.org/10.1016/j.jpeds.2017.12.012
7. Vandenplas Y, Benninga M, Broekaert I, Falconer J, Gottrand F, Guarino A, Lifschitz C, Lionetti P, Orel R, Papadopoulou A, Ribes-Koninckx C, Ruemmele FM, Salvatore S, Shamir R, Schäppi M, Staiano A, Szajewska H, Thapar N, Wilschanski M. Functional gastro-intestinal disorder algorithms focus on early recognition, parental reassurance and nutritional strategies. Acta Paediatr. 2016;105(3):244–252. https://doi.org/10.1111/apa.13270
8. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016:S0016-5085(16)00223-7. https://doi.org/10.1053/j.gastro.2016.02.032
9. Vandenplas Y, Abkari A, Bellaiche M, Benninga M, Chouraqui JP, Çokura F, Harb T, Hegar B, Lifschitz C, Ludwig T, Miqdady M, de Morais MB, Osatakul S, Salvatore S, Shamir R, Staiano A, Szajewska H, Thapar N. Prevalence and Health Outcomes of Functional Gastrointestinal Symptoms in Infants From Birth to 12 Months of Age. J Pediatr Gastroenterol Nutr. 2015;61(5):531–537. https://doi.org/10.1097/MPG.0000000000000949
10. Belmer SV, Volynets GV, Gorelov AV, Gurova MM, Zvyagin AA, Kornienko EA, Novikova VP, Pechkurov DV, Privorotskiy VF, Tyazheva AA, Faizullina RA, Khavkin AI, Erdes SI. Functional digestive disorders in children. Guidelines of Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists. Part 1. Ros Vestn Perinatol i Pediatr. 2020; 65:(4): 150–161 (In Russ). https://doi.org/10.21508/1027–4065–2020–65–4–150–161
11. Giorgio V, Margiotta G, Stella G, Di Cicco F, Leoni C, Proli F, Zampino G, Gasbarrini A, Onesimo R. Intestinal Permeability in Children with Functional Gastrointestinal Disorders: The Effects of Diet. Nutrients. 2022;14(8):1578. https://doi.org/10.3390/nu14081578
12. Schoultz I, Keita ÅV. The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability. Cells. 2020;9(8):1909. https://doi.org/10.3390/cells9081909
13. Khavkin AI, Novikova VP, Shapovalova NS. Perspective non-invasive biomarkers: intestinal proteins in the diagnosis for diagnosis and control of intestinal mucosal damage. Experimental and Clinical Gastroenterology. 2021;188(4):155–160 (In Russ.). https://doi.org/10.31146/1682-8658-ecg-188-4-155-160
14. Zvyagin AA, Bavykina IA, Nastausheva TL, Bavykin DV. Intestinal Fatty Acid Binding Protein as a promising marker of small intestine permeability. Ros Vestn Perinatol i Pediatr. 2020;65:(6):29–33 (In Russ). https://doi.org/10.21508/1027–4065–2020–65–6–29–33
15. Voth M, Duchene M, Auner B, Lustenberger T, Relja B, Marzi I. I-FABP is a Novel Marker for the Detection of Intestinal Injury in Severely Injured Trauma Patients. World J Surg. 2017;41(12):3120–3127. https://doi.org/10.1007/s00268-017-4124-2
16. Sun DL, Cen YY, Li SM, Li WM, Lu QP, Xu PY. Accuracy of the serum intestinal fatty-acid-binding protein for diagnosis of acute intestinal ischemia: a meta-analysis. Sci Rep. 2016;6(1):34371. https://doi.org/10.1038/srep34371
17. Yang G, Wang Y, Jiang X. Diagnostic Value of Intestinal Fatty-Acid-Binding Protein in Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis. Indian J Pediatr. 2016;83(12–13):1410–1419. https://doi.org/10.1007/s12098-016-2144-9
18. Kim LV, Zhelev VA, Slizovsky GV. Diagnostic value of fatty acidbinding protein in newborns with necrotizing enterocolitis. Clinical Practice in Pediatrics. 2022;17(4):13–16 (In Russ.). https://doi.org/10.20953/1817-7646-2022-4-13-16
19. Coufal S, Kokesova A, Tlaskalova-Hogenova H, Frybova B, Snajdauf J, Rygl M, Kverka M. Urinary I-FABP, L-FABP, TFF-3, and SAA Can Diagnose and Predict the Disease Course in Necrotizing Enterocolitis at the Early Stage of Disease. J Immunol Res. 2020;2020:3074313. https:// doi.org/10.1155/2020/3074313
20. Prikhodchenko NG, Shumatova TA, Nee AN, Zernova ES. Clinical and diagnostic significance of the intestinal fraction of fatty acid binding protein in children with protein-induced enteropathy. Russian Bulletin of Perinatology and Pediatrics. 2021;66(4):58–63 (In Russ.). https://doi.org/10.21508/1027-4065-2021-66-4-58-63
21. Walker LS, Sherman AL, Bruehl S, Garber J, Smith CA. Functional abdominal pain patient subtypes in childhood predict functional gastrointestinal disorders with chronic pain and psychiatric comorbidities in adolescence and adulthood. Pain. 2012;153(9):1798–1806. https://doi.org/10.1016/j.pain.2012.03.026
22. Horst S, Shelby G, Anderson J, Acra S, Polk DB, Saville BR, Garber J, Walker LS. Predicting persistence of functional abdominal pain from childhood into young adulthood. Clin Gastroenterol Hepatol. 2014;12(12):2026–2032. https://doi.org/10.1016/j.cgh.2014.03.034
23. Pavlova M, Noel M, Orr SL, Walker A, Madigan S, McDonald SW, Tough SC, Birnie KA. Early childhood risk factors for later onset of pediatric chronic pain: a multi-method longitudinal study. BMC Pediatr. 2024;24(1):508. https://doi.org/10.1186/s12887-024-04951-4
24. Boronat AC, Ferreira-Maia AP, Matijasevich A, Wang YP. Epidemiology of functional gastrointestinal disorders in children and adolescents: A systematic review. World J Gastroenterol. 2017;23(21):3915–3927. https://doi.org/10.3748/wjg.v23.i21.3915
25. Shores DR, Fundora J, Go M, Shakeel F, Brooks S, Alaish SM, Yang J, Sodhi CP, Hackam DJ, Everett A. Normative values for circulating intestinal fatty acid binding protein and calprotectin across gestational ages. BMC Pediatr. 2020;20(1):250. https://doi.org/10.1186/s12887-020-02142-5
Supplementary files
Review
For citations:
Bavykina I.A., Berdnikov A.A., Zvyagin A.A., Kubyshkina A.V., Barannikov S.V. Potential of intestinal fatty acid-binding protein in assessing enteral tolerance in neonates of different gestational ages: A cross-sectional cohort study. Kuban Scientific Medical Bulletin. 2025;32(1):39-51. (In Russ.) https://doi.org/10.25207/1608-6228-2025-32-1-39-51