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  • Original Article
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Risk factors for necrotizing enterocolitis totalis: a case–control study

Abstract

Objective:

The objective of this study was to compare demographic and clinical events in three groups of preterm neonates: those with necrotizing enterocolitis totalis (NEC-T), those with NEC non-totalis (NEC non-T) and in preterm patients without NEC.

Study Design:

This retrospective case–control study was conducted at Yale New Haven Children's Hospital using patient data from January 1991 to December 2007. Study patients were less than 36 weeks of gestational age (GA) at birth, without gastrointestinal (GI) malformations. Cases (NEC-T) were diagnosed at operation or at autopsy with observation of >80% necrosis of the GI tract. Two control groups were assigned: Group 1 or NEC non-T and Group II or Non-NEC. Two to four controls per case were matched to cases by GA at birth±2 weeks. Demographic and clinical data for the day of diagnosis and retrospectively up to 7 days preceding diagnosis were recorded for those with NEC-T and NEC. Group II controls were matched for date of birth and day of life, in addition to GA at birth.

Result:

A total of 14 075 patients were admitted to the Newborn Special Care Unit during the study interval. Overall 328 patients (2.3%) developed NECBell's Stage II; 39 patients met inclusion criteria for NEC-T case status; 148 NEC non-T and 110 non-NEC controls were assigned. In the comparison of NEC T and NEC non-T neonates, use of breast milk was associated with decreased risk of NEC-T, adjusted odds ratio (OR)=0.26, 95% confidence interval (CI) of OR=0.08–0.085, P=0.03. When NEC T and non-NEC patients were compared, having reached full-enteral feeds before the date of diagnosis of the matched case (adjusted OR=28.5, 95% CI of OR=2.7–299, P=0.005) and use of breast milk (adjusted OR=0.09, 95% CI of OR=0.02–0.56, P=0.01) were significantly different between the two groups.

Conclusion:

Breast milk usage was significantly associated with decreased occurrence of NEC-T in our comparison of NEC-T, NEC non-T and non-NEC patients. Although there were some differences, the majority of demographic and clinical variables assessed were not shown to be significantly different between cases and controls. This highlights the need for more biological data in assessing risk of developing NEC-T.

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References

  1. Goulet O, Sauvet F . Short bowel syndrome and intestinal transplantation in children. Curr Opin in Clin Nutr Metab Care 2006; 9: 304–313.

    Article  Google Scholar 

  2. Hintz S, Kendrick D, Stoll B, Vohr B, Fanaroff A, Donovan E et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005; 115: 696–703.

    Article  Google Scholar 

  3. Luig M, Lui K . Epidemiology of necrotizing enterocolitis-Part I: changing regional trends in extremely preterm infants over 14 years. J Pediatr Child Health 2005; 41: 169–173.

    Article  Google Scholar 

  4. Pichler J, Horn V, MacDonald S, Hill S . Review of the diagnoses predisposing infants to intestinal failure on hospitalized parenteral nutrition. Transplant Proc 2010; 42: 22–23.

    Article  CAS  Google Scholar 

  5. Cole C, Hansen N, Higgins RD, Ziegler T, Stoll B . Very low birth weight preterm infants with surgical short bowel syndrome:incidence, morbidity and mortality, and growth outcomes at 18–22 months. Pediatrics 2008; 122 (3): e573–e582.

    Article  Google Scholar 

  6. Holman R, Stoll BJ, Clarke MJ, Glass R . The epidemiology of necrotizing enterocolitis mortality in the United States. Am J Public Health 1997; 87: 2026–2031.

    Article  CAS  Google Scholar 

  7. Panigrahi P . Necrotizing enterocolitis-a practical guide to its prevention and management. Pediatr Drugs 2006; 8 (3): 151–165.

    Article  Google Scholar 

  8. Shah P, Shah V . Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev 2007; (3): CD004339.

  9. Foster J, Cole M . Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-weight neonates (Review). Cochrane Database Syst Rev 2004; (1): CD001816.

  10. Soghier L, Brion L . Cysteine, cystine or N-acetylcysteine supplementation in parenterally fed neonates. Cochrane Database Syst Rev 2006; (4): CD004869.

  11. Grylack L, Scanlon J . Oral gentamicin therapy in the prevention of necrotizing enterocolitis. A controlled double-blind trial. Am J Dis Child 1978; 132 (12): 1192–1194.

    Article  CAS  Google Scholar 

  12. Bury R, Tudehope D . Enteral antibiotics for preventing necrotizing enterocolitis in low birth weight or preterm infants. Cochrane Database Syst Rev 2001; (1): CD000405.

  13. Siu YK, Ng PC, Fung SCK, Lee CH, Wong MY, Fok TF et al. Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birth weight infants. Arch Dis Child Fetal Neonatal Ed 1998; 79: 105–109.

    Article  Google Scholar 

  14. Voss M, Moore S, Merwe Ivd, Pieper C . Fulminant necrotising enterocolitis: outcome and prognostic factors. Pediatr Surg Int 1998; 13: 576–580.

    Article  CAS  Google Scholar 

  15. Gregory K . Clincial predictors of necrotizing enterocolitis in preterm infants. Nurs Res 2008; 57 (4): 260–270.

    Article  Google Scholar 

  16. Carter BM, Holditch-Davis D . Risk factors for necrotizing enterocolitis in preterm infants. Adv Neonatal Care 2008; 8 (5): 285–290.

    Article  Google Scholar 

  17. Moss RL, Kalish L, Duggan C, Johnston P, Brandt M, Dunn J et al. Clinical parameters alone do not adequately predict outcome in necrotizing enterocoloitis: a multi-institutional study. J Perinatol 2008; 28: 665–674.

    Article  CAS  Google Scholar 

  18. Christensen R, Wiedmeier S, Baer V, Henry E, Gerday E, Lambert D et al. Antecedents of Bell stage III necrotizing enterocolitis. J Perinatol 2010; 30: 547–557.

    Google Scholar 

  19. Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U et al. 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 Pediatr 2010; 156: 562–567.

    Article  CAS  Google Scholar 

  20. Lucas A, Cole T . Breast milk and neonatal necrotising enterocolitis. Lancet 1990; 336: 1519–1523.

    Article  CAS  Google Scholar 

  21. Updegrove K . Necrotizing enterocolitis: the evidence for use of human milk in prevention and treatment. J Human Lact 2004; 20: 335–338.

    Article  Google Scholar 

  22. Moonen R, Paulussen A, Souren N, Kessels A, Rubio-Gozalbo ME, Villamor E . Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis. Pediatr Res 2007; 2 (2): 188–190.

    Article  Google Scholar 

  23. Bhandari V, Bizzarro M, Shetty A, Zhong X, Page G, Zhang H et al. Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics 2006; 117 (6): 1901–1906.

    Article  Google Scholar 

  24. Treszl A, Tulassay T, Vasashelyi B . Genetic basis for necrotizing enterocolitis--risk factors and their relations to genetic polymorphisms. Front Biosci 2006; 11: 570–580.

    Article  CAS  Google Scholar 

  25. Treszl A, Heninger E, Kalman A, Schuler A, Tulassay T, Vasarhelyi B . Lower prevalence of IL-4 receptor α-chain gene 1902 variant in very-low-birth-weight infants with necrotizing enterocolitis. J Pediatr Surg 2003; 38: 1374–1378.

    Article  Google Scholar 

  26. Hintz S, Kendrick D, Stoll BJ, Vohr B, Fanaroff AA, Donovan E et al. Neurodevelopment and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005; 115: 696–703.

    Article  Google Scholar 

  27. Mally P, Golombek S, Mishra R, Nigam S, Mohandas K, Depalhma H 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.

    Article  Google Scholar 

  28. Christensen R, Lambert D, Henry E, Wiedmeier S, Snow G, Baer V et al. Is ‘transfusion-associated necrotizing enterocolitis’ an authentic pathogenic entity? Transfusion 2010; 50 (5): 1106–1112.

    Article  Google Scholar 

  29. Guner YS, Friedlich P, Wee CP, Dorey F, Camerini V, Upperman JS . State-based analysis of necrotizing enterocolitis outcomes. J Surf Res 2009; 157: 21–29.

    Article  Google Scholar 

  30. Henderson G, Anthony M, McGuire W . Formula milk versus maternal breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev 2007; (4): CD002972.

  31. Quigley M, Henderson G, Anthony M, McGuire W . Formula milk versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev 2007; (4): CD002971.

  32. Boyd C, Quigley M, Brocklehurst P . Donor breast milk versus infant formula for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2007; 92 (3): F169–F175.

    Article  Google Scholar 

  33. Berseth CL, Bisquera JA, Paje VU . Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2003; 111: 529–534.

    Article  Google Scholar 

  34. Bombell S, McGuire W . Early trophic feeds for very low birth weight infants (review). Cochrane Database Syst Rev 2009; (3): CD000504.

  35. Henderson G, Craig S, Brocklehurst P, McGuire W . Enteral feeding regimens and necrotising enterocolitis in preterm infants: multicentre case-control study. Arch Dis Child Fetal Neonatal Ed 2007; 10: 1–10.

    Google Scholar 

  36. Kennedy K, Tyson J . Early versus delayed intiation of progressive enteral feedings for parenterally fed low birth weight or preterm infants (Review). Cochrane Database Syst Rev 2008; (2).

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Acknowledgements

This work was supported in part by the Glaser Pediatric Research Network and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) grant no. HD07094.

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Correspondence to A Thompson.

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Thompson, A., Bizzarro, M., Yu, S. et al. Risk factors for necrotizing enterocolitis totalis: a case–control study. J Perinatol 31, 730–738 (2011). https://doi.org/10.1038/jp.2011.18

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