Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants

Abstract

Objective:

To determine association of anemia and red blood cell (RBC) transfusions with necrotizing enterocolitis (NEC) in preterm infants.

Study Design:

A total of 111 preterm infants with NEC stage 2a were compared with 222 matched controls. In all, 28 clinical variables, including hematocrit (Hct) and RBC transfusions were recorded. Propensity scores and multivariate logistic regression models were created to examine effects on the risk of NEC.

Result:

Controlling for other factors, lower Hct was associated with increased odds of NEC (odds ratio (OR)=1.10, P=0.01). RBC transfusion has a temporal relationship with NEC onset. Transfusion within 24 h (OR=7.60, P=0.001) and 48 h (OR=5.55, P=0.001) has a higher odds of developing NEC but this association is not significant by 96 h (OR=2.13, P=0.07), post-transfusion.

Conclusion:

Anemia may increase the risk of developing NEC in preterm infants. RBC transfusions are temporally related to NEC. Prospective studies are needed to better evaluate the potential influence of transfusions on the development of NEC.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Stoll BJ . Epidemiology of necrotizing enterocolitis. Clin Perinatol 1994; 21 (2): 205.

    Article  CAS  Google Scholar 

  2. Luig M, Lui K . Epidemiology of necrotizing enterocolitis-part II: risk and susceptibility of premature infants during the surfactant era: regional study. J Paediatr Child Health 2005; 41 (4): 174–179.

    Article  Google Scholar 

  3. Holman RC, Stoll BJ, Clarke MJ, Glass RI . The epidemiology of necrotizing enterocolitis infant mortality in the United States. Am J Public Health 1997; 87 (12): 2026–2031.

    Article  CAS  Google Scholar 

  4. Kafetzis DA, Skevaki C, Costalos C . Neonatal necrotizing enterocolitis: an overview. Curr Opinions Infect Disease 2003; 16 (4): 349–355.

    Article  CAS  Google Scholar 

  5. Kennedy KA, Tyson JE, Chamnanvanakij S . Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed low-birth-weight infants. Cochrane Database Syst Rev 2000; (2): CD001241.

  6. Lucas A, Cole TJ . Breast milk and neonatal necrotizing enterocolitis. Lancet 1990; 336 (8730): 1519–1523.

    Article  CAS  Google Scholar 

  7. McKeown RE, Marsh TD, Amarnath U, Garrison CZ, Addy CL, Thompson SJ et al. Role of delayed feeding and of feeding increments in necrotizing enterocolitis. J Pediatr 1992; 121 (5 part 1): 764–770.

    Article  CAS  Google Scholar 

  8. Rayyis SF, Ambalavanan N, Wright L, Carlo WA . Randomized trial of ‘slow’ versus ‘fast’ feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants. J Pediatr 1999; 134 (3): 293–297.

    Article  CAS  Google Scholar 

  9. Stark AR, Carlo WA, Tyson JE, Papile LA, Wright LL, Shankaran S et al. Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 2001; 344 (2): 95–101.

    Article  CAS  Google Scholar 

  10. Agwu JC, Narchi H . In a preterm infant, does blood transfusion increase the risk of necrotizing enterocolitis? Arch Dis Child 2005; 90: 102–103.

    Article  CAS  Google Scholar 

  11. Andrew S, Andrew G, Munir A . Necrotizing enterocolitis following blood transfusion electronic letter to the editor. Arch Dis Child 2005.

  12. Mally P, Golombek SG, Mishra R, La Gamma EF, Nigam S, Mohandas K et al. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in premature neonates. Am J Perinatol 2006; 23 (8): 451–458.

    Article  Google Scholar 

  13. Blau J, Calo J, Dozor D, La Gamma E . Transfusion related acute gut injury (TRAGI): necrotizing enterocolitis (NEC) in VLBW neonates following PRBC transfusion. The Eastern Society of Pediatric Research Annual Meeting. 2009, Abstract 30.

  14. McGrady GA, Rettig PJ, Istre GR, Jason JM, Holman RC, Evatt BL et al. An outbreak of necrotizing enterocolitis. Association with transfusion of packed red blood cells. Am J Epidemiol 1987; 126 (6): 1165–1172.

    Article  CAS  Google Scholar 

  15. Reber KM, Nankervis CA . Nowicki PT newborn intestinal circulation. Physiol Pathophysiol Clin Perinatol 2002; 29 (1): 23–29.

    Google Scholar 

  16. Kleigman RM, Walsh MC . Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of disease. Curr Probl Pediatr 1987; 17: 213.

    Google Scholar 

  17. Gomella TL, Cunnigham MD, Eyal FG, Zenk KE . Handbook of neonatology 4th edn, 1999; 316.

  18. Dempsey EM, Barrington KJ . Evaluation and treatment of hypotension in the preterm infant. Clin Perinatol 2009; 36: 75–85.

    Article  CAS  Google Scholar 

  19. Kaempf JW, Campbell B, Brown A, Bowers K, Gallegos, Goldsmith JP . PCO2 and room air saturation values in premature infants at risk for bronchopulmonary dysplasia. J Perinatol 2008; 28: 48–54.

    Article  CAS  Google Scholar 

  20. Papile LA, Burstein J, Burstein R, Koffler H . Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birthweights less than 1500g. J Pediatr 1978; 92: 529–534.

    Article  CAS  Google Scholar 

  21. Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005; 123 (7): 991–999.

    Article  Google Scholar 

  22. Hirano K, Imbens GW . The propensity score with continuous treatments. In: Gelman A, Meng X (eds). Applied Bayesian Modeling and Causal Inference from Incomplete-Data Perspectives. John Wiley & Sons: New York, 2004; 73–84.

    Google Scholar 

  23. D'Agostino Jr RB . Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 1998; 17 (19): 2265–2281.

    Article  Google Scholar 

  24. Horbar JD, Badger GJ, Carpenter JH, Fanaroff AA, Kilpatrick S, LaCorte M et al. Trends in mortality and morbidity for very low birth weight infants, 1991–1999. Pediatrics 2002; 110: 143–151.

    Article  Google Scholar 

  25. Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA, Stoll BJ et al. Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics 2001; 107: E1.

    Article  CAS  Google Scholar 

  26. Caplan MS, Simon D, Jilling T . The role of PAF, TLR, and the inflammatory response in neonatal necrotizing enterocolitis. Semin Pediatr Surg 2005; 14 (3): 145–151.

    Article  Google Scholar 

  27. Ceylan H, Yuncu M, Gurel A, Armutçu F, Gergerlioğlu HS, Bağci C et al. Effects of whole-body hypoxic preconditioning on hypoxia/reoxygenation-induced intestinal injury in newborn rats. Eur J Pediatr Surg 2005; 15 (5): 325–332.

    Article  CAS  Google Scholar 

  28. Peter CS, Feuerhahn M, Bohnhorst B, Schlaud M, Ziesing S, von der Hardt H et al. Necrotizing enterocolitis: is there a relationship to specific pathogens? Eur J Pediatr 1999; 158: 67–70.

    Article  CAS  Google Scholar 

  29. Caplan MS, Jilling T . New concepts in necrotizing enterocolitis. Current Opinion Pediatr 2001; 13 (2): 111–115.

    Article  CAS  Google Scholar 

  30. Caplan MS, Jilling T . The pathophysiology of necrotizing enterocolitis. Neo Rev 2001; 2: 103–109.

    Google Scholar 

  31. Ledbetter DJ, Juul SE . Erythropoietin and the incidence of necrotizing enterocolitis in infants with very low birth weight. J Pediatr Surg 2000; 35: 178–182.

    Article  CAS  Google Scholar 

  32. Ohls RK . Erythropoietin to prevent and treat the anemia of prematurity. Curr Opin Pediatr 1999; 11: 108–114.

    Article  CAS  Google Scholar 

  33. Kohorn IV, Ehrenkranz . Anemia in the preterm infant. Erythropoietin versus erythrocyte transfusion–It's not that simple. Clin Perinatol 2009; 36 (1): 111–123.

    Article  Google Scholar 

  34. Bednarek FJ, Weisberger S, Richardson DK, Frantz ID, Shah BL, Rubin LP et al. Variations in blood transfusions among newborn intensive care units. II SNAP study group. J Pediatr 1998; 133 (5): 601–607.

    Article  CAS  Google Scholar 

  35. Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA et al. A randomized controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants, the PINT study. J Pediatr 2006; 149: 301–307.

    Article  Google Scholar 

  36. Bell EF, Strauss RG, Widness JA, Mahoney LT, Mock DM, Seward VJ et al. Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics 2005; 115: 1685–1691.

    Article  Google Scholar 

  37. Bell EF . Transfusion thresholds for preterm infants: how low should we go? J Pediatr 2006; 149 (3): 287–289.

    Article  Google Scholar 

  38. Christensen RD, Wiedmeier SE, Baer VL, Henry E, Gerday E, Lambert DK et al. Antecedents of bell stage III necrotizing enterocolitis. J Perinatol 2010; 30: 54–57.

    Article  CAS  Google Scholar 

  39. Stockman JA . Anemia of prematurity. Current concepts in the issue of when to transfuse. Ped Clin N Amer 1986; 33 (1): 111–128.

    Article  Google Scholar 

  40. Widness JA . Pathophysiology, diagnosis, and prevention of neonatal anemia. Neo Rev 2000; 1 (4): e61–e68.

    Google Scholar 

  41. Murray NA, Howarth LJ, McCloy MP, Letsky EA, Roberts IA . Platelet transfusion in the management of severe thrombocytopenia in neonatal intensive care unit patients. Transfus Med 2002; 12: 35–41.

    Article  CAS  Google Scholar 

  42. Alkalay AL, Galvis S, Ferry DA, Simmons CF, Krueger RC . Hemodynamic changes in anemic premature infants: are we allowing the hematocrits to fall too low? Pediatrics 2003; 112: 838–845.

    Article  Google Scholar 

  43. Alverson DC . The physiologic impact of anemia in the neonate. Clin Perinatol 1995; 22: 609–625.

    Article  CAS  Google Scholar 

  44. Boralessa H, Modi N, Cockburn H, Malde R, Edwards M, Roberts I et al. RBC T activation and haemolysis in a neonatal intensive care population: implications for transfusion practice. Transfusion 2002; 42 (11): 1428–1434.

    Article  CAS  Google Scholar 

  45. Lucas A, Cole TJ . Breast milk and neonatal necrotizing enterocolitis. Lancet 1990; 336 (8730): 1519–1523.

    Article  CAS  Google Scholar 

  46. Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Lucas A . An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Peds 2009; 156 (4): 562–567.

    Article  Google Scholar 

  47. 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.

    Article  Google Scholar 

  48. Satar M, Turhan E, Yapicioglu H, Narli N, Narli N, Ozgunen FT et al. Cord blood cytokine levels in neonates born to mothers with prolonged premature rupture of membranes and its relationship with morbidity and mortality. Eur Cytokine Netw 2008; 19: 37–41.

    CAS  PubMed  Google Scholar 

  49. Manogura AC, Turan O, Kush ML, Berg C, Bhide A, Turan S et al. Predictors of necrotizing enterocolitis in preterm growth- restricted neonates. Am J Obstet Gynecol 2008; 198 (6): 638. e1-5.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported in part by Grant number 3U10HD053119-04S1 from the National Institute of Child Health and Human Development, Grant number UL1 RR025752 from the National Institutes of Health and by institutional/departmental funds.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R Singh.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Singh, R., Visintainer, P., Frantz, I. et al. Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants. J Perinatol 31, 176–182 (2011). https://doi.org/10.1038/jp.2010.145

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2010.145

Keywords

This article is cited by

Search

Quick links