Register      Login



Volume / Issue

Online First

Related articles

VOLUME 1 , ISSUE 1 ( January-March, 2022 ) > List of Articles

Article Commentary

Current Understanding of Transfusion-associated Necrotizing Enterocolitis: Review of Clinical and Experimental Studies and a Call for More Definitive Evidence

Minesh Khashu, Christof Dame, Pascal M Lavoie, Isabelle G De Plaen, Parvesh M Garg, Venkatesh Sampath, Atul Malhotra, Michael D Caplan, Pankaj B Agrawal, Giuseppe Buonocore, Robert D Christensen, Akhil Maheshwari

Keywords : Anemia, Necrotizing enterocolitis, Preterm infants, ta-NEC, TANEC, TRAGI, Transfusion

Citation Information : Khashu M, Dame C, Lavoie PM, De Plaen IG, Garg PM, Sampath V, Malhotra A, Caplan MD, Agrawal PB, Buonocore G, Christensen RD, Maheshwari A. Current Understanding of Transfusion-associated Necrotizing Enterocolitis: Review of Clinical and Experimental Studies and a Call for More Definitive Evidence. 2022; 1 (1):201-208.

DOI: 10.5005/jp-journals-11002-0005

License: CC BY-NC 4.0

Published Online: 31-03-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Introduction: The association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC), so-called transfusion-associated NEC (ta-NEC), was first described in 1987. However, further work is needed to confirm a causal relationship, elucidate underlying mechanisms, and develop possible strategies for prevention. We performed an extensive literature search in the databases PubMed, EMBASE, and Scopus. Areas covered: Although multiple retrospective human studies have strongly suggested an association between blood transfusions and subsequent occurrence of NEC, meta-analyses of randomized controlled trials (RCTs) testing RBC transfusion thresholds or the use of recombinant erythropoiesis-stimulating growth factors did not confirm an association of anemia with ta-NEC. These conflicting data necessitated the development of an animal model to elucidate mechanisms and causal factors. Data from this recent mouse model of ta-NEC highlighted the importance of sequential exposure to severe anemia followed by transfusion for development of ta-NEC. Expert opinion: This review summarizes current human and experimental data, highlights open questions, and suggests avenues for further research aimed at preventing ta-NEC in preterm infants. Further studies are required to delineate whether there is a tipping point, in terms of the level and duration of anemia, and to develop an effective strategy for blood management and the quality of RBC transfusions.

  1. Valieva OA, Strandjord TP, Mayock DE, et al. Effects of transfusions in extremely low birth weight infants: a retrospective study. J Pediatr 2009;155(3):331–337. e1. DOI: 10.1016/j.jpeds.2009.02.026.
  2. dos Santos AM, Guinsburg R, de Almeida MF, et al. Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units. BMC Pediatr 2015;15:113. DOI: 10.1186/s12887-015-0432-6.
  3. von Lindern JS, Lopriore E. Management and prevention of neonatal anemia: current evidence and guidelines. Expert Rev Hematol 2014;7(2):195–202. DOI: 10.1586/17474086.2014.878225.
  4. Amin SC, Remon JI, Subbarao GC, et al. Association between red cell transfusions and necrotizing enterocolitis. J Matern Fetal Neonatal Med 2012;25(Suppl 5):85–89. DOI: 10.3109/14767058.2012.715465.
  5. Christensen RD, Lambert DK, Henry E, et al. Is “transfusion-associated necrotizing enterocolitis” an authentic pathogenic entity? Transfusion 2009;50(5):1106–1112. DOI: 10.1111/j.1537-2995.2009.02542.x.
  6. Mohamed A, Shah PS. Transfusion associated necrotizing enterocolitis: a meta-analysis of observational data. Pediatrics 2012;129(3):529–540. DOI: 10.1542/peds.2011-2872.
  7. Hyung N, Campwala I, Boskovic DS, et al. The relationship of red blood cell transfusion to intestinal mucosal injury in premature infants. J Pediatr Surg 2017;52(7):1152–1155. DOI: 10.1016/j.jpedsurg. 2016.10.049.
  8. Demirel G, Celik IH, Aksoy HT, et al. Transfusion-associated necrotising enterocolitis in very low birth weight premature infants. Transfus Med 2012;22(5):332–337. DOI: 10.1111/j.1365-3148.2012.01170.x.
  9. Stritzke AI, Smyth J, Synnes A, et al. Transfusion-associated necrotising enterocolitis in neonates. Arch Dis Child Fetal Neonatal Ed 2013;98(1):F10–14. DOI: 10.1136/fetalneonatal-2011-301282.
  10. Christensen RD, Lambert DK, Gordon PV, et al. Neonates presenting with bloody stools and eosinophilia can progress to two different types of necrotizing enterocolitis. J Perinatol 2012; 32(11):874–879. DOI: 10.1038/jp.2011.163.
  11. El-Dib M, Narang S, Lee E, et al. Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants. J Perinatol 2011;31(3): 183–187. DOI: 10.1038/jp.2010.157.
  12. Patel RM, Knezevic A, Shenvi N, et al. Association of red blood cell transfusion, anemia, and necrotizing enterocolitis in very low-birth-weight infants. JAMA 2016;315(9):889–897. DOI: 10.1001/jama.2016.1204.
  13. Josephson CD, Wesolowski A, Bao G, et al. Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants? J Pediatr 2010;157(6):972–978. DOI: 10.1016/j.jpeds.2010.05.054.
  14. Garg PM, Ravisankar S, Bian H, et al. Relationship between packed red blood cell transfusion and severe form of necrotizing enterocolitis: a case control study. Indian Pediatr 2015;52(12):1041–1045. DOI: 10.1007/s13312-015-0770-3.
  15. AlFaleh K, Al-Jebreen A, Baqays A, et al. Association of packed red blood cell transfusion and necrotizing enterocolitis in very low birth weight infants. J Neonatal Perinatal Med 2014;7(3):193–198. DOI: 10.3233/NPM-14814048.
  16. Baxi AC, Josephson CD, Iannucci GJ, et al. Necrotizing enterocolitis in infants with congenital heart disease: the role of red blood cell transfusions. Pediatr Cardiol 2014;35(6):1024–1029. DOI: 10.1007/s00246-014-0891-9.
  17. Derienzo C, Smith PB, Tanaka D, et al. Feeding practices and other risk factors for developing transfusion-associated necrotizing enterocolitis. Early Hum Dev 2014;90(5):237–240. DOI: 10.1016/j.earlhumdev.2014.02.003.
  18. Christensen RD, Wiedmeier SE, Baer VL, et al. Antecedents of Bell stage III necrotizing enterocolitis. J Perinatol 2010;30(1):54–57. DOI: 10.1038/jp.2009.93.
  19. Christensen RD, Baer VL, Del Vecchio A, et al. Unique risks of red blood cell transfusions in very-low-birth-weight neonates: associations between early transfusion and intraventricular hemorrhage and between late transfusion and necrotizing enterocolitis. J Matern Fetal Neonatal Med 2013;26(Suppl 2):60–63. DOI: 10.3109/14767058.2013.830495.
  20. Bak SY, Lee S, Park JH, et al. Analysis of the association between necrotizing enterocolitis and transfusion of red blood cell in very low birth weight preterm infants. Korean J Pediatr 2013;56(3):112–115. DOI: 10.3345/kjp.2013.56.3.112.
  21. Singh R, Visintainer PF, Frantz ID 3rd, et al. Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants. J Perinatol 2011;31(3):176–182. DOI: 10.1038/jp.2010.145.
  22. Elabiad MT, Harsono M, Talati AJ, et al. Effect of birth weight on the association between necrotising enterocolitis and red blood cell transfusions in <=1500 g infants. BMJ Open 2013;3(11):e003823. DOI: 10.1136/bmjopen-2013-003823.
  23. Mally P, Golombek SG, Mishra R, et al. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol 2006;23(8): 451–458. DOI: 10.1055/s-2006-951300.
  24. Marin T, Moore J, Kosmetatos N, et al. Red blood cell transfusion-related necrotizing enterocolitis in very-low-birthweight infants: a near-infrared spectroscopy investigation. Transfusion 2013;53(11):2650–2680. DOI: 10.1111/trf.12158.
  25. Paul DA, Mackley A, Novitsky A, et al. Increased odds of necrotizing enterocolitis after transfusion of red blood cells in premature infants. Pediatrics 2011;127(4):635–641. DOI: 10.1542/peds.2010-3178.
  26. Blau J, Calo JM, Dozor D, et al. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion. J Pediatr 2011;158(3):403–409. DOI: 10.1016/j.jpeds.2010.09.015.
  27. Tao HK, Tang Q, Hei MY, et al. Meta-analysis of post-transfusion necrotizing enterocolitis in neonates [Chinese]. Zhonghua Er Ke Za Zhi 2013;51(5):336–339. PMID: 23941838.
  28. Hay S, Zupancic JA, Flannery DD, et al. Should we believe in transfusion-associated enterocolitis? Applying a GRADE to the literature. Semin Perinatol 2017;41(1):80–91. DOI: 10.1053/j.semperi.2016. 09.021.
  29. Nickel RS, Josephson CD. Neonatal transfusion medicine: five major unanswered research questions for the twenty-first century. Clin Perinatol 2015;42(3):499–513. DOI: 10.1016/j.clp.2015.04.006.
  30. Bührer C, Fischer HS, Wellmann, S. Nutritional interventions to reduce rates of infection, necrotizing enterocolitis and mortality in very preterm infants. Pediatr Res 2020;87(2):371–377. DOI: 10.1038/s41390-019-0630-2.
  31. Guthmann F, Arlettaz Mieth RP, Bucher HU, et al. Short courses of dual-strain probiotics appear to be effective in reducing necrotising enterocolitis. Acta Paediatr 2016;105(3):255–259. DOI: 10.1111/apa.13280.
  32. MohanKumar K, Namachivayam K, Song T, et al. A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions. Nat Commun 2019;10(1):3494. DOI: 10.1038/s41467-019-11199-5.
  33. McGrady GA, Rettig PJ, Istre GR, et al. An outbreak of necrotizing enterocolitis: association with transfusions of packed red blood cells. Am J Epidemiol 1987;126(6):1165–1172. DOI: 10.1093/oxfordjournals.aje.a114754.
  34. Bednarek FJ, Weisberger S, Richardson DK, et al. Variations in blood transfusions among newborn intensive care units. SNAP II Study Group. J Pediatr 1998;133(5):601–607. DOI: 10.1016/S0022-3476(98)70097-6.
  35. Carter BM, Holditch-Davis D, Tanaka D, et al. Relationship of neonatal treatments with the development of necrotizing enterocolitis in preterm infants. Nurs Res 2012;61(2):96–102. DOI: 10.1097/NNR.0b013e3182410d33.
  36. Couselo M, Aguar M, Ibáñez V, et al. Relation between packed red blood cell transfusion and severity of necrotizing enterocolitis in premature infants [Chinese]. Cir Pediatr 2011;24(3):137–141.
  37. Ghirardello S, Lonati CA, Dusi E, et al. Necrotizing enterocolitis and red blood cell transfusion. J Pediatr 2011;159(2):354–355; author reply 355–356. DOI: 10.1016/j.jpeds.2011.03.027.
  38. Wan-Huen P, Bateman D, Shapiro DM, et al. Packed red blood cell transfusion is an independent risk factor for necrotizing enterocolitis in premature infants. J Perinatol 2013;33(10):786–790. DOI: 10.1038/jp.2013.60.
  39. Holder GL, Dohert DA, Patole SK. Elective red cell transfusion for anemia of prematurity and development of necrotizing enterocolitis in previously well preterm neonates: incidence and difficulties in proving a cause-effect association. J Neonat Perinat Med 2009;2(3):181–186. DOI: 10.3233/NPM-2009-0067.
  40. Stokes V, Rajai A, Mukherjee D, et al. Transfusion-associated necrotizing enterocolitis (NEC) in extremely preterm infants: experience of a tertiary neonatal center in UK. J Matern Fetal Neonatal Med 2021;20:1–6. DOI: 10.1080/14767058.2021.1874910.
  41. Lee EY, Kim SS, Park GY, et al. Effect of red blood cell transfusion on short-term outcomes in very low birth weight infants. Clin Exp Pediatr 2020;63(2):56–62. DOI: 10.3345/kjp.2019.00990.
  42. Perciaccante JV, Young, TE. Necrotizing enterocolitis associated with packed red blood cell transfusions in premature neonates. 2008. 5839.8.
  43. Harsono M, et al. Are packed red blood cell transfusions protective against late onset necrotizing enterocolitis in very low birth weight infants? in E-PAS. 2011. p. 509.
  44. Garg P, Pinotti R, Lal CV, et al. Transfusion-associated necrotizing enterocolitis in preterm infants: an updated meta-analysis of observational data. J Perinat Med 2018;46(6):677–685. DOI: 10.1515/jpm-2017-0162.
  45. Rai SE, Sidhu AK, Krishnan, RJ. Transfusion-associated necrotizing enterocolitis re-evaluated: a systematic review and meta-analysis. J Perinat Med 2018;46(6):665–676. DOI: 10.1515/jpm-2017-0048.
  46. Sharma R, Kraemer DF, Torrazza RM, et al. Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants. J Perinatol 2014;34(11):858–862. DOI: 10.1038/jp.2014.59.
  47. Kirpalani H, Whyte RK, Andersen C, et al. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr 2006;149(3):301–307. DOI: 10.1016/j.jpeds.2006.05.011.
  48. Franz AR, Engel C, Bassler D, et al. Effects of liberal vs restrictive transfusion thresholds on survival and neurocognitive outcomes in extremely low-birth-weight infants: the ETTNO randomized clinical trial. JAMA 2020;324(6):560–570. DOI: 10.1001/jama.2020. 10690.
  49. Ohlsson A, Aher SM. Early erythropoiesis-stimulating agents in preterm or low birth weight infants. Cochrane Database Syst Rev 2020;2:CD004863. DOI: 10.1002/14651858.CD004863.pub6.
  50. Wang Y, Song J, Sun H, et al. Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial. J Transl Med 2020;18(1):308. DOI: 10.1186/s12967-020-02459-w.
  51. Juul SE, Comstock BA, Wadhawan R, et al. A randomized trial of erythropoietin for neuroprotection in preterm infants. N Engl J Med 2020;382(3):233–243. DOI: 10.1056/NEJMoa1907423.
  52. Schutzman DL, Porat R. Glucose-6-phosphate dehydrogenase deficiency: another risk factor for necrotizing enterocolitis? J Pediatr 2007;151(4):435–437. DOI: 10.1016/j.jpeds.2007.06.041.
  53. Detlefsen B, Boemers TM, Schimke C. Necrotizing enterocolitis in premature twins with twin-to-twin transfusion syndrome. Eur J Pediatr Surg 2008;18(1):50–52. DOI: 10.1055/s-2007-965788.
  54. Ree IMC, de Grauw AM, Bekker V, et al. Necrotizing enterocolitis in haemolytic disease of the newborn: a retrospective cohort study. Vox Sang 2020;115(2):196–201. DOI: 10.1111/vox.12862.
  55. Huybregts RA, de Vroege R, Jansen EK, et al. The association of hemodilution and transfusion of red blood cells with biochemical markers of splanchnic and renal injury during cardiopulmonary bypass. AnesthAnalg 2009;109(2):331–339. DOI: 10.1213/ane. 0b013e3181ac52b2.
  56. Balegar VK, Jayawardhana M, Martin AJ, et al. Association of bolus feeding with splanchnic and cerebral oxygen utilization efficiency among premature infants with anemia and after blood transfusion. JAMA Netw Open 2020;3(2):e200149. DOI: 10.1001/jamanetworkopen.2020.0149.
  57. Dave V, Brion LP, Campbell DE, et al. Splanchnic tissue oxygenation, but not brain tissue oxygenation, increases after feeds in stable preterm neonates tolerating full bolus orogastric feeding. J Perinatol 2009;29(3):213–218. DOI: 10.1038/jp.2008.189.
  58. Hod EA, Zhang N, Sokol SA, et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood 2010;115(21):4284–4292. DOI: 10.1182/blood-2009-10-245001.
  59. MohanKumar K, Namachivayam K, Cheng F, et al. Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis. Pediatr Res 2016;81(1):99–112. DOI: 10.1038/pr.2016.189.
  60. Ng PC, Ang IL, Chiu RW, et al. Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants. J Clin Invest 2010;120(8):2989–3000. DOI: 10.1172/JCI40196.
  61. MohanKumar K, Killingsworth CR, McIlwain RB, et al. Intestinal epithelial apoptosis initiates gut mucosal injury during extracorporeal membrane oxygenation in the newborn piglet. Lab Invest 2014;94(2):150–160. DOI: 10.1038/labinvest.2013.149.
  62. Shiou SR, Yu Y, Chen S, et al. Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis. J Biol Chem 2011;286(14): 12123–12132. DOI: 10.1074/jbc.M110.154625.
  63. Zaynagetdinov R, Sherrill TP, Kendall PL, et al. Identification of myeloid cell subsets in murine lungs using flow cytometry. Am J Respir Cell Mol Biol 2013;49(2):180–189. DOI: 10.1165/rcmb.2012-0366MA.
  64. Zhong H, Yin H. Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biol 2015;4: 193–199. DOI: 10.1016/j.redox.2014.12.011.
  65. Gladwin MT, Kanias T, Kim-Shapiro DB. Hemolysis and cell-free hemoglobin drive an intrinsic mechanism for human disease. J Clin Invest 2012;122(4):1205–1208. DOI: 10.1172/JCI62972.
  66. Belcher JD, Chen C, Nguyen J, et al. Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood 2014;123(3):377–390. DOI: 10.1182/blood-2013-04-495887.
  67. Leaphart CL, Cavallo J, Gribar SC, et al. A critical role for tlr4 in the pathogenesis of necrotizing enterocolitis by modulating intestinal injury and repair. J Immunol 2007; 179(7):4808–4820. DOI: 10.4049/jimmunol.179.7.4808.
  68. Krimmel GA, Baker R, Yanowitz TD. Blood transfusion alters the superior mesenteric artery blood flow velocity response to feeding in premature infants. Am J Perinatol 2009;26(2):99–105. DOI: 10.1055/s-0028-1090595.
  69. Whyte R, Kirpalani H. Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants. Cochrane Database Syst Rev 2011(11):CD000512. DOI: 10.1002/14651858.CD000512. pub2.
  70. Kirpalani H, Bell EF, Hintz SR, et al. Higher or lower hemoglobin transfusion thresholds for preterm infants. N Engl J Med 2020;383(27):2639–2651. DOI: 10.1056/NEJMoa2020248.
  71. Bishara N, Ohls RK. Current controversies in the management of the anemia of prematurity. Semin Perinatol 2009;33(1):29–34. DOI: 10.1053/j.semperi.2008.10.006.
  72. Christensen RD. Identifying neonates likely to benefit from a red blood cell transfusion. Transfusion 2012;52(2):217–218. DOI: 10.1111/j.1537-2995.2011.03408.x.
  73. Henry E, Christensen RD, Sheffield MJ, et al. Why do four NICUs using identical RBC transfusion guidelines have different gestational age-adjusted RBC transfusion rates? J Perinatol 2015;35(2):132–136. DOI: 10.1038/jp.2014.171.
  74. Juul SE, Vu PT, Comstock BA, et al. Effect of high-dose erythropoietin on blood transfusions in extremely low gestational age neonates: post hoc analysis of a randomized clinical trial. JAMA Pediatr 2020;174(10):933–943. DOI: 10.1001/jamapediatrics.2020.2271.
  75. Ohls RK, Christensen RD, Kamath-Rayne BD, et al. A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants. Pediatrics 2013;132(1):e119–e127. DOI: 10.1542/peds.2013-0143.
  76. Patel S, Ohls RK. Darbepoetin administration in term and preterm neonates. Clin Perinatol 2015;42(3):557–566. DOI: 10.1016/j.clp.2015.04.016.
  77. New HV, Berryman J, Bolton-Maggs PH, et al. Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol 2016;175(5):784–828. DOI: 10.1111/bjh.14233.
  78. Patient Blood Management Guidelines: Module 6, in Neonatal and Paediatrics. 2016, National Blood Authority, Canberra, Australia.
  79. Services CB. Clinical guide to transfusion, in Chapter 13. Neonatal and Pediatric transfusion (W. Lau, ed.) 2019: Ottawa, Canada.
  80. Heeger LE, Counsilman CE, Bekker V, et al. Restrictive guideline for red blood cell transfusions in preterm neonates: effect of a protocol change. Vox Sang 2019;114(1):57–62. DOI: 10.1111/vox.12724.
  81. Whitehead HV, Vesoulis ZA, Maheshwari A, et al. Anemia and cerebral near-infrared spectroscopy: should transfusion thresholds in preterm infants be revised? J Perinatol 2018;38(8):1022–1029. DOI: 10.1038/s41372-018-0120-0.
  82. Hashem RH, Mansi YA, Almasah NS, et al. Doppler ultrasound assessment of the splanchnic circulation in preterms with neonatal sepsis at risk for necrotizing enterocolitis. J Ultrasound 2017;20(1): 59–67. DOI: 10.1007/s40477-016-0228-z.
  83. Szabo JS, Mayfield SR, Oh W, et al. Postprandial gastrointestinal blood flow and oxygen consumption: effects of hypoxemia in neonatal piglets. Pediatr Res 1987;21(1):93–98. DOI: 10.1203/00006450-198701000-00020.
  84. Fergusson D, Hutton B, Hogan DL, et al. The age of red blood cells in premature infants (ARIPI) randomized controlled trial: study design. Transfus Med Rev 2009;23(1):55–61. DOI: 10.1016/j.tmrv.2008.09.005.
  85. Gilson CR, Kraus TS, Hod EA, et al. A novel mouse model of red blood cell storage and posttransfusion in vivo survival. Transfusion 2009;49(8):1546–1553. DOI: 10.1111/j.1537-2995.2009.02173.x.
  86. Fergusson DA, Hébert P, Hogan DL, et al. Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial. JAMA 2012;308(14): 1443–1451. DOI: 10.1001/2012.jama.11953.
  87. Brown MS, Phipps RH, Dallman RH. Postnatal changes in fetal hemoglobin, oxygen affinity and 2,3-diphosphoglycerate in previously transfused preterm infants. Biol Neonate 1985;48(2):70–76. DOI: 10.1159/000242156.
  88. Cholette JM, Henrichs KF, Alfieris GM, et al. Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial. Pediatr Crit Care Med 2012;13(3):290–299. DOI: 10.1097/PCC.0b013e31822f173c.
  89. Schindler T, Yeo KT, Bolisetty S, et al. FEEding DURing red cell transfusion (FEEDUR RCT): a multi-arm randomised controlled trial. BMC Pediatr 2020;20(1):346. DOI: 10.1186/s12887-020-02233-3.
  90. Gale C, Modi N, Jawad S, et al. The WHEAT pilot trial-WithHolding Enteral feeds Around packed red cell Transfusion to prevent necrotising enterocolitis in preterm neonates: a multicentre, electronic patient record (EPR), randomised controlled point-of-care pilot trial. BMJ Open 2019;9(9):e033543. DOI: 10.1136/bmjopen-2019-033543.
  91. AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2014(4):CD005496. DOI: 10.1002/14651858.CD005496.pub4.
  92. Chang HY, Chen JH, Chang JH, et al. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: an updated meta-analysis. PLOS ONE 2017;12(2):e0171579. DOI: 10.1371/journal.pone.0171579.
  93. Warren S, Schreiber JR, Epstein MF. Necrotizing enterocolitis and hemolysis associated with Clostridium perfringens. Am J Dis Child 1984;138(7):686–688. DOI: 10.1001/archpedi.1984.02140450068021.
  94. Fustolo-Gunnink SF, Roehr CC, Lieberman L, et al. Platelet and red cell transfusions for neonates: lifesavers or Trojan horses? Expert Rev Hematol 2019;12(10):797–800. DOI: 10.1080/17474086.2019.1657824.
  95. Bayne LE. Big data in neonatal health care: big reach, big reward? Crit Care Nurs Clin North Am 2018;30(4):481–497. DOI: 10.1016/j.cnc.2018.07.005.
  96. Luo G, Stone BL, Johnson MD, et al. Automating construction of machine learning models with clinical big data: proposal rationale and methods. JMIR Res Protoc 2017;6(8):e175. DOI: 10.2196/resprot.7757.
  97. Seghatchian J. An introductory commentary on the use of artificial intelligence, machine learning and TQM, as novel computational tools in big data patterns or procedural analysis, in transfusion medicine. Transfus Apher Sci 2020;59(6):102985. DOI: 10.1016/j.transci.2020.102985.
  98. Pendry K. The use of big data in transfusion medicine. Transfus Med 2015;25(3):129–137. DOI: 10.1111/tme.12223.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.