Association between red blood cell transfusion and the development of necrotizing enterocolitis in neonates: Contribution to achieving Sustainable Development Goal 3
DOI:
https://doi.org/10.37800/RM.2.2026.710Keywords:
necrotizing enterocolitis , preterm neonates, red blood cell transfusion, thrombocytopenia, risk factors, neonatal intensive careAbstract
Relevance: Sustainable Development Goal 3 aims to reduce preventable neonatal mortality and improve the quality of medical care. Necrotizing enterocolitis (NEC) remains one of the most severe conditions in preterm neonates and is associated with high mortality and adverse long-term outcomes. Preterm infants frequently require red blood cell transfusions; however, the contribution of transfusions to the development of NEC remains controversial.
The study aimed to evaluate the association between red blood cell transfusion and the development of necrotizing enterocolitis in preterm neonates and to identify independent clinical predictors of the disease.
Materials and Methods: A retrospective single-center cohort study was conducted in the neonatal intensive care unit in Almaty. Medical records of 479 preterm neonates treated between 2023 and 2025 were analyzed. Patients were divided into groups with (n = 38) and without (n = 441) NEC. Standard statistical methods were applied, including the Mann-Whitney U test, χ² test, and Fisher’s exact test. Multivariable logistic regression was used to identify independent risk factors.
Results: NEC was diagnosed in 7.9% of neonates. Patients with the disease more frequently received red blood cell transfusions and had higher rates of thrombocytopenia and sepsis, as well as lower gestational age, birth weight, and hemoglobin levels. In the multivariable model, independent associations with NEC were identified for red blood cell transfusion (OR 12.70; 95% CI 1.43-112.99), thrombocytopenia (OR 3.58; 95% CI 1.46-8.75), and lower birth weight (OR 0.997 per 1 g; 95% CI 0.995-0.999). Gestational age, hemoglobin level, and sepsis were not independently associated.
Conclusion: Red blood cell transfusion, thrombocytopenia, and low birth weight were independently associated with the development of NEC in preterm neonates. These findings confirm the multifactorial nature of disease risk and highlight the need for a rational, individualized approach to transfusion therapy to improve the quality and safety of neonatal care, in line with the priorities of Sustainable Development Goal 3.
References
1. United Nations. Transforming our world: the 2030 Agenda for Sustainable Development. Resolution adopted by the General Assembly on 25 September 2015 [Internet]. New York: United Nations; 2015 [cited 2026 Feb 27]. Available from:
https://docs.un.org/en/A/RES/70/1
2. De Bernardo G, Vecchione C, Langella C, Ziello C, Parisi G, Giordano M, Buonocore G, Perrone S. Necrotizing enterocolitis: a current understanding and challenges for the future. Curr Pediatr Rev. 2025;21(3):207-212.
https://doi.org/10.2174/0115733963318619240923062033
3. Blum L. Immunological aspects of necrotizing enterocolitis models: a review. Front Immunol. 2024;15:1434281.
https://doi.org/10.3389/fimmu.2024.1434281
4. Sha C, Sander WR, Bass K, Hsieh H, Bialkowska AB. Necrotizing enterocolitis: what’s new and what’s next? Int J Mol Sci. 2025;26(19):9660.
https://doi.org/10.3390/ijms26199660
5. Ishiyama A, Jang HS, Dintaman JM, Duess JW, Tragesser C, Sodhi CP. Necrotizing enterocolitis: a comprehensive review on Toll-like receptor 4-mediated pathophysiology, clinical, and therapeutic insights. Biomedicines. 2025;13(9):2288.
https://doi.org/10.3390/biomedicines13092288
6. Garg PM, Paschal JL, Ansari MAY, Block D, Inagaki K, Weitkamp JH. Clinical impact of NEC-associated sepsis on outcomes in preterm infants. Pediatr Res. 2022;92(6):1705-1715.
https://doi.org/10.1038/s41390-022-02034-7
7. ten Barge JA, Vermeulen MJ, Keyzer-Dekker CMG, Bouw N, de Vos CC, Reiss IKM, Simons SHP, van den Bosch GE. Long-term impact of necrotizing enterocolitis on somatosensory function in preterm born children. Pediatr Res. 2025 Aug 26. Epub ahead of print.
https://doi.org/10.1038/s41390-025-04348-8
8. Lamireau N, Greiner E, Hascoët JM. Risk factors associated with necrotizing enterocolitis in preterm infants: a case-control study. Arch Pediatr. 2023;30(7):477-482.
https://doi.org/10.1016/j.arcped.2023.07.003
9. Ibrohim IS, Pratama HA, Fauzi AR. Association between prognostic factors and the clinical deterioration of preterm neonates with necrotizing enterocolitis. Sci Rep. 2022;12:13911.
https://doi.org/10.1038/s41598-022-17846-0
10. Kirpalani H, Bell EF, Hintz SR, Tan S, Schmidt B, Chaudhary AS. Higher or lower hemoglobin transfusion thresholds for preterm infants. N Engl J Med. 2020;383(27):2639-2651.
https://doi.org/10.1056/NEJMoa2020248
11. Whyte RK, Kirpalani H. Low versus high hemoglobin concentration for blood transfusion for preventing morbidity and mortality in very low birth weight infants. Cochrane Database Syst Rev. 2011;(11):CD000512.
https://doi.org/10.1002/14651858.CD000512.pub2
12. Божбанбаева Н., Танирберген С., Муздубаева У. Трансфузия пуповинной крови недоношенным детям: обзор литературы. Репрод Мед (Центр Азия). 2025;3:564.
Bozhbanbaeva N, Tangirbergen S, Muzdubaeva U. Umbilical cord blood transfusion for preterm neonates: A literature review. Reprod Med (Centr Asia). 2025;3:564.
https://doi.org/10.37800/RM.3.2025.564
13. Mohamed A, Shah PS. Transfusion-associated necrotizing enterocolitis: a meta-analysis of observational data. Pediatrics. 2012;129(3):529-540.
https://doi.org/10.1542/peds.2011-2872
14. Maheshwari A, Patel RM, Christensen RD. Anemia, red blood cell transfusions, and necrotizing enterocolitis. Semin Pediatr Surg. 2018;27(1):47-51.
https://doi.org/10.1053/j.sempedsurg.2017.11.009
15. Jasani B, Rao S, Patole S. Withholding feeds and transfusion-associated necrotizing enterocolitis in preterm infants: a systematic review. Adv Nutr. 2017;8(5):764-769.
https://doi.org/10.3945/an.117.015818
16. Bell EF, Strauss RG, Widness JA, Mahoney LT, Mock DM, Seward VJ, Cress GA, Johnson KJ, Kromer IJ, Zimmerman MB. Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics. 2005;115(6):1685-1691.
https://doi.org/10.1542/peds.2004-1884
17. Deschmann E, Dame C, Sola-Visner MC. Clinical practice guideline for red blood cell transfusion thresholds in very preterm neonates. JAMA Netw Open. 2024;7(6):e2417431.
https://doi.org/10.1001/jamanetworkopen.2024.17431
18. Patel RM, Knezevic A, Shenvi N, Hinkes M, Keene S, Roback JD, Easley KA, Josephson CD. Association of red blood cell transfusion, anemia, and necrotizing enterocolitis in very low-birth-weight infants. JAMA. 2016;315(9):889-897.
https://doi.org/10.1001/jama.2016.1204
19. Dang D, Liu A, Huyen VN, Vu CT, Nguyen MH, Nguyen BT, Nguyen KT, Tran TL, Nguyen DH, Phan NT, Le TTH, Hoang DH. Red blood cell transfusion and necrotizing enterocolitis in very preterm infants. Sci Rep. 2024;14:64923.
https://doi.org/10.1038/s41598-024-64923-7
20. Ghirardello S, Dusi E, Cortinovis I, Villa S, Fumagalli M, Agosti M. Effects of red blood cell transfusions on short-term outcomes in very low birth weight infants. Am J Perinatol. 2017;34(8):791-798.
https://doi.org/10.1055/s-0036-1593992
21. Salas AA, Carlo WA, Ambalavanan N, Bell EF, Das A, Laptook AR, Walsh MC, Shankaran S, Higgins RD, Tyson JE. Timing of red blood cell transfusions and occurrence of necrotizing enterocolitis in very preterm infants. JAMA Netw Open. 2024;7(2):e240123.
https://doi.org/10.1001/jamanetworkopen.2024.0123
22. Guo J, Chen Y, Li J, Zhang Y, Wang L, Liu X. Thrombocytopenia as an early predictor of severity and outcomes in neonatal necrotizing enterocolitis. BMC Pediatr. 2021;21:259.
https://doi.org/10.1186/s12887-021-02721-5
23. Zani A, Pierro A. Necrotizing enterocolitis: controversies and challenges. F1000Res. 2015;4:F1000 Faculty Rev-1373.
https://doi.org/10.12688/f1000research.6888.1
24. Alganabi M, Lee C, Bindi E, Li B, Pierro A. Recent advances in understanding necrotizing enterocolitis. F1000Res. 2019;8:107.
https://doi.org/10.12688/f1000research.17228.1
25. Su Y, Chen H, Liu W, Liu J, Chen H, Wang L. Risk factors for necrotizing enterocolitis in neonates: a meta-analysis. Medicine (Baltimore). 2023;102(1):e32701.
https://doi.org/10.1097/MD.0000000000032701
26. Zhao S, Li Y, Zhang Y. Factors influencing necrotizing enterocolitis in premature infants: a retrospective study. BMC Pediatr. 2024;24.
https://doi.org/10.1186/s12887-024-04607-3
27. Liu K, Guo J, Zhu Y, Yang J, Su Y. Analysis of risk factors and establishment of predictive models for neonatal necrotizing enterocolitis: a retrospective study. Ital J Pediatr. 2025;51(1):80.
https://doi.org/10.1186/s13052-025-01930-y
28. Zhao S, Jiang H, Miao Y. Factors influencing necrotizing enterocolitis in premature infants in China: a systematic review and meta-analysis. BMC Pediatr. 2024;24:148.
https://doi.org/10.1186/s12887-024-04607-3
29. Salas AA, Gunn E, Carlo WA, Bell EF, Das A, Josephson CD, Patel RM, Tan S, Kirpalani H. Timing of red blood cell transfusions and occurrence of necrotizing enterocolitis: a secondary analysis of a randomized clinical trial. JAMA Netw Open. 2024;7(5):e249643.
https://doi.org/10.1001/jamanetworkopen.2024.9643
30. Vyas D, Reddy M, Garg PM. Association of anemia and necrotizing enterocolitis in neonates: systematic review and meta-analysis of transfusion thresholds, erythropoietin trials, and observational studies. J Neonatal Perinatal Med. 2026 Jan 13:19345798261416362. Epub ahead of print.
https://doi.org/10.1177/19345798261416362
31. Battersby C, Longford N, Mandalia S, Costeloe K, Modi N. Incidence and risk factors for necrotising enterocolitis in preterm infants: a UK population-based study. PLoS One. 2018;13(2):e0192101.
https://doi.org/10.1371/journal.pone.0192101
32. Hällström M, Koivisto AM, Janas M, Tammela O, Andersson S. Risk factors for necrotizing enterocolitis in extremely preterm infants: a population-based cohort study. Pediatr Res. 2021;89(6):1541-1547.
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Copyright (c) 2026 Н. Журавлев, Д. Надирханова, А. Куанышбек, В. Балан , К. Коновалова, Ж. Акрамий, Ж. Сабырдильда, Н. Божбанбаева, А. Абикулова
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