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The age of necrotizing enterocolitis onset: an application of Sartwell's incubation period model

Journal of Perinatology volume 31, pages 519–523 (2011)Cite this article

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Abstract

Objective:

Model age of necrotizing enterocolitis (NEC) onset applying Sartwell's model of incubation periods, and examine its relationship to gestational age (GA).

Study Design:

Retrospective chart review of St Louis Children's Hospital neonates diagnosed with NEC (⩾Bell's stage II) from 2004 to 2008, inclusive.

Result:

The relationship between age of NEC (N=84 cases) onset and GA best fits a non-linear model, with infants ⩽28 weeks having a disproportionately longer time to onset than older GA groups and explained 50.3% of the variability in age of NEC onset. Additional clinical variables provided no improvement in explaining age of NEC onset. Application of Sartwell's model to age of NEC onset proved a good fit, when birth is used as the common exposure episode, and age is equivalent of the incubation period.

Conclusion:

The relationship between day of NEC diagnosis and GA is non-linear, with lower GA infants having disproportionately longer time to onset. Despite these GA differences, the fit to Sartwell's model for incubation periods model is consistent with NEC being a consequence of an event that occurs at or soon after birth.

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References

  1. Holman RC, Stoll BJ, Curns AT, Yorita KL, Steiner CA, Schonberger LB . Necrotising enterocolitis hospitalisations among neonates in the United States. Paediatr Perinat Epidemiol 2006; 20 (6): 498–506.

    Article  Google Scholar 

  2. 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 (1 Pt 1): 143–151.

    Article  Google Scholar 

  3. Sankaran K, Puckett B, Lee DS, Seshia M, Boulton J, Qiu Z et al. Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units. J Pediatr Gastroenterol Nutr 2004; 39 (4): 366–372.

    Article  Google Scholar 

  4. Lin PW, Stoll BJ . Necrotising enterocolitis. Lancet 2006; 368 (9543): 1271–1283.

    Article  Google Scholar 

  5. Luig M, Lui K . Epidemiology of necrotizing enterocolitis—Part II: risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health 2005; 41 (4): 174–179.

    Article  Google Scholar 

  6. Blakely ML, Lally KP, McDonald S, Brown RL, Barnhart DC, Ricketts RR et al. Postoperative outcomes of extremely low birth-weight infants with necrotizing enterocolitis or isolated intestinal perforation: a prospective cohort study by the NICHD Neonatal Research Network. Ann Surg 2005; 241 (6): 984–989; discussion 9–94.

    Article  Google Scholar 

  7. Sartwell PE . The distribution of incubation periods of infectious disease. Am J Hyg 1950; 51 (3): 310–318.

    CAS  PubMed  Google Scholar 

  8. Sartwell PE . The incubation period of poliomyelitis. Am J Public Health Nations Health 1952; 42 (11): 1403–1408.

    Article  CAS  Google Scholar 

  9. Armenian HK, Lilienfeld AM . The distribution of incubation periods of neoplastic diseases. Am J Epidemiol 1974; 99 (2): 92–100.

    Article  CAS  Google Scholar 

  10. Armenian HK, Khoury MJ . Age at onset of genetic diseases: an application for Sartwell's model of the distribution of incubation periods. Am J Epidemiol 1981; 113 (5): 596–605.

    Article  CAS  Google Scholar 

  11. Armenian HK, Lilienfeld AM . Incubation period of disease. Epidemiol Rev 1983; 5: 1–15.

    Article  CAS  Google Scholar 

  12. Armenian HK . Incubation periods of cancer: old and new. J Chronic Dis 1987; 40 (Suppl 2): 9S–15S.

    Article  Google Scholar 

  13. Philippe P . Competing stochastic models of the incubation period: an investigation of age-at-diagnosis of familial and sporadic retinoblastoma. Am J Med Genet 1993; 46 (2): 113–122.

    Article  CAS  Google Scholar 

  14. Alcabes P, Munoz A, Vlahov D, Friedland GH . Incubation period of human immunodeficiency virus. Epidemiol Rev 1993; 15 (2): 303–318.

    Article  CAS  Google Scholar 

  15. Wilkening DA . Modeling the incubation period of inhalational anthrax. Med Decis Making 2008; 28 (4): 593–605.

    Article  Google Scholar 

  16. Sartwell PE . The distribution of incubation periods of infectious disease. 1949. Am J Epidemiol 1995; 141 (5): 386–394; discussion 5.

    Article  CAS  Google Scholar 

  17. Walsh MC, Kliegman RM . Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986; 33 (1): 179–201.

    Article  CAS  Google Scholar 

  18. Gordon PV, Swanson JR, Attridge JT, Clark R . Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's criteria? J Perinatol 2007; 27 (11): 661–671.

    Article  CAS  Google Scholar 

  19. Sartwell PE . The incubation period and the dynamics of infectious disease. Am J Epidemiol 1966; 83 (2): 204–206.

    Article  CAS  Google Scholar 

  20. Claud EC, Walker WA . Bacterial colonization, probiotics, and necrotizing enterocolitis. J Clin Gastroenterol 2008; 42 (Suppl 2): S46–S52.

    Article  Google Scholar 

  21. Claud EC, Walker WA . Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 2001; 15 (8): 1398–1403.

    Article  CAS  Google Scholar 

  22. Lin PW, Nasr TR, Stoll BJ . Necrotizing enterocolitis: recent scientific advances in pathophysiology and prevention. Semin Perinatol 2008; 32 (2): 70–82.

    Article  Google Scholar 

  23. Mackie RI, Sghir A, Gaskins HR . Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 1999; 69 (5): 1035S–1045S.

    Article  CAS  Google Scholar 

  24. Fanaro S, Chierici R, Guerrini P, Vigi V . Intestinal microflora in early infancy: composition and development. Acta Paediatr Suppl 2003; 91 (441): 48–55.

    CAS  PubMed  Google Scholar 

  25. Ostlie DJ, Spilde TL, St Peter SD, Sexton N, Miller KA, Sharp RJ et al. Necrotizing enterocolitis in full-term infants. J Pediatr Surg 2003; 38 (7): 1039–1042.

    Article  Google Scholar 

  26. Beeby PJ, Jeffery H . Risk factors for necrotising enterocolitis: the influence of gestational age. Arch Dis Child 1992; 67 (4 Spec No): 432–435.

    Article  CAS  Google Scholar 

  27. Sharma R, Hudak ML, Tepas III JJ, Wludyka PS, Marvin WJ, Bradshaw JA et al. Impact of gestational age on the clinical presentation and surgical outcome of necrotizing enterocolitis. J Perinatol 2006; 26 (6): 342–347.

    Article  CAS  Google Scholar 

  28. Yaseen H, Kamaledin K, Al Umran K, Al Arfaj A, Darwich M, Awary B . Epidemiology and outcome of ‘early-onset’ vs ‘late-onset’ necrotizing enterocolitis. Indian J Pediatr 2002; 69 (6): 481–484.

    Article  Google Scholar 

  29. Scheiner AP, Sexton ME . Prediction of developmental outcome using a perinatal risk inventory. Pediatrics 1991; 88 (6): 1135–1143.

    CAS  PubMed  Google Scholar 

  30. Zaramella P, Freato F, Milan A, Grisafi D, Vianello A, Chiandetti L . Comparison between the perinatal risk inventory and the nursery neurobiological risk score for predicting development in high-risk newborn infants. Early Hum Dev 2008; 84 (5): 311–317.

    Article  Google Scholar 

  31. Guillet R, Stoll BJ, Cotten CM, Gantz M, McDonald S, Poole WK et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2006; 117 (2): e137–e142.

    Article  Google Scholar 

  32. Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH . Necrotizing enterocolitis among neonates in the United States. J Perinatol 2003; 23 (4): 278–285.

    Article  Google Scholar 

  33. Moss RL, Dimmitt RA, Barnhart DC, Sylvester KG, Brown RL, Powell DM et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation. N Engl J Med 2006; 354 (21): 2225–2234.

    Article  CAS  Google Scholar 

  34. Stoll BJ . Epidemiology of necrotizing enterocolitis. Clin Perinatol 1994; 21 (2): 205–218.

    Article  CAS  Google Scholar 

  35. Llanos AR, Moss ME, Pinzon MC, Dye T, Sinkin RA, Kendig JW . Epidemiology of neonatal necrotising enterocolitis: a population-based study. Paediatr Perinat Epidemiol 2002; 16 (4): 342–349.

    Article  Google Scholar 

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Acknowledgements

We wish to thank the late Dr David Alling for his insight and wisdom regarding incubation period distributions, and Beth Wolf, Gina Meyers, Amy Distler and Christine Musser for assistance with manuscript preparation. Ms González-Rivera was supported by the Doris Duke Clinical Research Foundation. Dr Warner received support from the Children's Discovery Institute MD II-2009-201. Drs Tarr and Warner were partially supported by UH2 AI083265 and DDRCC grant 5P30 DK052574 to Washington University Digestive Diseases Research Core Center. Drs Warner and Hamvas received support from the Washington University Institute for Clinical and Translational Studies (UL1 RR024992). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH. Dr Culverhouse is partially supported by the National Institute of General Medical Sciences (K25 GM69590).

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO, USA

    R González-Rivera & P I Tarr

  2. Department of Internal Medicine, Division of General Medical Sciences, Washington University School of Medicine, St Louis, MO, USA

    R C Culverhouse

  3. Division of Newborn Medicine, Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO, USA

    A Hamvas & B B Warner

  4. University of Puerto Rico, School of Medicine, San Juan, Puerto Rico

    R González-Rivera

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Correspondence to B B Warner.

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González-Rivera, R., Culverhouse, R., Hamvas, A. et al. The age of necrotizing enterocolitis onset: an application of Sartwell's incubation period model. J Perinatol 31, 519–523 (2011). https://doi.org/10.1038/jp.2010.193

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