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Impact of concomitant necrotizing enterocolitis on mortality in very low birth weight infants with intraventricular hemorrhage

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Abstract

Objective

To evaluate the impact of necrotizing enterocolitis (NEC) on mortality in very low birth weight (VLBW) infants with intraventricular hemorrhage (IVH).

Study design

Data were collected on VLBW infants born 2014–2018 at Vermont Oxford Network (VON) centers. NEC and IVH were categorized by severity. Adjusted risk ratios (ARR) for in-hospital mortality were calculated.

Results

This study included 187 187 VLBW infants. Both medical and surgical NEC increased mortality risk compared to those without NEC. Stratification by IVH severity modified this effect (no IVH: ARR 3.04 (95%CI 2.74–3.38) for medical NEC and 4.17 (3.84–4.52) for surgical NEC; mild IVH: ARR 2.14 (1.88–2.44) for medical NEC and 2.49 (2.24–2.78) for surgical NEC; severe IVH: ARR 1.14 (1.03–1.26) for medical NEC and 1.10 (1.02–1.18) for surgical NEC).

Conclusion

The relative impact of NEC on mortality decreased as IVH severity increased. Given the frequent coexistence of NEC and IVH, these data inform multidisciplinary management of these complex patients.

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Fig. 1: Incidence of medical and surgical necrotizing enterocolitis among infants with intraventricular hemorrhage.
Fig. 2: Unadjusted in-hospital mortality in infants with IVH and NEC.
Fig. 3: Forest plot of adjusted risk ratios for in-hospital mortality in infants with IVH and NEC.

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Data availability

The code used for this analysis can be made available upon request.

References

  1. Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH. Necrotizing enterocolitis among neonates in the United States. J Perinatol. 2003;23:278–85.

    Article  Google Scholar 

  2. Christian EA, Jin DL, Attenello F, Wen T, Cen S, Mack WJ, et al. Trends in hospitalization of preterm infants with intraventricular hemorrhage and hydrocephalus in the United States, 2000-2010. J Neurosurg Pediatr. 2016;17:260–9.

    Article  Google Scholar 

  3. Knell J, Han SM, Jaksic T, Modi BP. Current status of necrotizing enterocolitis. Curr Probl Surg. 2019;56:11–38.

    Article  Google Scholar 

  4. Han SM, Hong CR, Knell J, Edwards EM, Morrow KA, Soll RF, et al. Trends in incidence and outcomes of necrotizing enterocolitis over the last 12 years: A multicenter cohort analysis. J Pediatr Surg. 2020;55:998–1001.

    Article  Google Scholar 

  5. Hull MA, Fisher JG, Gutierrez IM, Jones BA, Kang KH, Kenny M, et al. Mortality and management of surgical necrotizing enterocolitis in very low birth weight neonates: A prospective cohort study. J Am Coll Surg. 2014;218:1148–55.

    Article  Google Scholar 

  6. Poryo M, Boeckh JC, Gortner L, Zemlin M, Duppré P, Ebrahimi-Fakhari D, et al. Ante-, peri- and postnatal factors associated with intraventricular hemorrhage in very premature infants. Early Hum Dev. 2018;116:1–8.

    Article  Google Scholar 

  7. Heuchan AM, Evans N, Henderson Smart DJ, Simpson JM. Perinatal risk factors for major intraventricular haemorrhage in the Australian and New Zealand Neonatal Network, 1995-97. Arch Dis Child Fetal Neonatal Ed. 2002;86:86–90.

    Article  Google Scholar 

  8. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.

    Article  CAS  Google Scholar 

  9. Ellenbogen JR, Waqar M, Pettorini B. Management of post-haemorrhagic hydrocephalus in premature infants. J Clin Neurosci. 2016;31:30–34.

    Article  Google Scholar 

  10. Koutsouras GW, Koustov T, Zyck S, Krishnamurthy S. Pathophysiologic mechanisms and strategies for the treatment of post-hemorrhagic hydrocephalus of prematurity. Child’s Nerv Syst. 2022;38:511–20.

    Article  Google Scholar 

  11. Flanders TM, Kimmel AC, Lang SS, Bellah R, Chuo J, Wellons JC, et al. Standardizing treatment of preterm infants with post-hemorrhagic hydrocephalus at a single institution with a multidisciplinary team. Child’s Nerv Syst. 2020;36:1737–44.

    Article  Google Scholar 

  12. Fullerton BS, Hong CR, Velazco CS, Mercier CE, Morrow KA, Edwards EM, et al. Severe neurodevelopmental disability and healthcare needs among survivors of medical and surgical necrotizing enterocolitis: A prospective cohort study. J Pediatr Surg. 2018;53:101–7.

    Article  Google Scholar 

  13. Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005;115:696–703.

    Article  Google Scholar 

  14. Jen HC, Graber JJ, Hill JL, Alaish SM, Voigt RW, Strauch ED. Surgical necrotizing enterocolitis and intraventricular hemorrhage in premature infants below 1000 g. J Pediatr Surg. 2006;41:1425–30.

    Article  Google Scholar 

  15. Vermont Oxford Network Manual of Operations: Part 2. Data Definitions and Infant Data Forms. 2019 http://www.vtoxford.org/tools/ManualofOperationsPart2.pdf.%0A.

  16. Siffel C, Kistler KD, Sarda SP. Global incidence of intraventricular hemorrhage among extremely preterm infants: A systematic literature review. J Perinat Med. 2021;49:1017–26.

    Article  Google Scholar 

  17. Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR, et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol. 2007;196:147.e1–147.e8.

    Article  Google Scholar 

  18. Rolnitsky A, Lee SK, Piedbouf B, Harrison A, Shah PS. Prophylactic interventions in neonatology: how do they fare in real life? Am J Perinatol. 2015;32:1098–104.

    Article  Google Scholar 

  19. Wei JC, Catalano R, Profit J, Gould JB, Lee HC. Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants. J Perinatol. 2016;36:352–6.

    Article  CAS  Google Scholar 

  20. Walsh MC, Bell EF, Kandefer S, Saha S, Carlo WA, D’angio CT, et al. Neonatal outcomes of moderately preterm infants compared to extremely preterm infants. Pediatr Res. 2017;82:297–304.

    Article  Google Scholar 

  21. Yee WH, Soraisham AS, Shah VS, Aziz K, Yoon W, Lee SK et al. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics. 2012;129. https://doi.org/10.1542/peds.2011-2022.

  22. Ellsbury DL, Clark RH, Ursprung R, Handler DL, Dodd ED, Spitzer AR. A multifaceted approach to improving outcomes in the NICU: The pediatrix 100 000 babies campaign. Pediatrics. 2016;137. https://doi.org/10.1542/peds.2015-0389.

  23. Levene MI, Fawer CL, Lamont RF. Risk factors in the development of intraventricular haemorrhage in the preterm neonate. Arch Dis Child. 1982;57:410–7.

    Article  CAS  Google Scholar 

  24. Lang J, Hickey L, King S, Curley A. OC58 Morbidity and mortality of medical and surgical necrotising enterocolitis. Arch Dis Child. 2019;104:A24.2–A24.

  25. Youn YA, Kim EK, Kim SY. Necrotizing enterocolitis among very-low-birth-weight infants in Korea. J Korean Med Sci. 2015;30:S75–S80.

    Article  Google Scholar 

  26. Enzmann D, Murphy-Irwin K, Stevenson D, Ariagno R, Barton J, Sunshine P. The natural history of subependymal germinal matrix hemorrhage. Am J Perinatol. 1985;2:123–33.

    Article  CAS  Google Scholar 

  27. Andrew M, Castle V, Saigal S, Carter C, Kelton JG. Clinical impact of neonatal thrombocytopenia. J Pediatr. 1987;110:457–64.

    Article  CAS  Google Scholar 

  28. Hall NJ, Hiorns M, Tighe RNH, Peters M, Khoo AK, Eaton S, et al. Is necrotizing enterocolitis associated with development or progression of intraventricular hemorrhage? Am J Perinatol. 2009;26:139–44.

    Article  Google Scholar 

  29. Lampe R, Rieger-Fackeldey E, Sidorenko I, Turova V, Botkin N, Eckardt L, et al. Assessing key clinical parameters before and after intraventricular hemorrhage in very preterm infants. Eur J Pediatr. 2020;179:929–37.

    Article  CAS  Google Scholar 

  30. Fisher JG, Jones BA, Gutierrez IM, Hull MA, Kang KH, Kenny M, et al. Mortality associated with laparotomy-confirmed neonatal spontaneous intestinal perforation: A prospective 5-year multicenter analysis. J Pediatr Surg. 2014;49:1215–9.

    Article  Google Scholar 

  31. Pet GC, McAdams RM, Melzer L, Oron AP, Horslen SP, Goldin A, et al. Attitudes surrounding the management of neonates with severe necrotizing enterocolitis. J Pediatr. 2018;199:186–.e3.

    Article  Google Scholar 

  32. Cheong JLY, Olsen JE, Lee KJ, Spittle AJ, Opie GF, Clark M, et al. Temporal trends in neurodevelopmental outcomes to 2 years after extremely preterm birth. JAMA Pediatr. 2021;175:1035–42.

    Article  Google Scholar 

  33. Younge N, Goldstein RF, Bann CM, Hintz SR, Patel RM, Smith PB, et al. Survival and neurodevelopmental outcomes among periviable infants. N. Engl J Med. 2017;376:617–28.

    Article  Google Scholar 

  34. Bolisetty S, Dhawan A, Abdel-Latif M, Bajuk B, Stack J, Lui K. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics. 2014;133:55–62.

    Article  Google Scholar 

  35. Calisici E, Eras Z, Oncel MY, Oguz SS, Gokce IK, Dilmen U. Neurodevelopmental outcomes of premature infants with severe intraventricular hemorrhage. J Matern Neonatal Med. 2015;28:2115–20.

    Article  Google Scholar 

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Acknowledgements

We thank our colleagues who submit data to VON on behalf of infants and their families. Participating centers are listed in Supplementary Table 1.

Funding

Dr. Horbar, Dr. Soll and Ms. Morrow are employees of the Vermont Oxford Network. Dr. Edwards receives salary support from Vermont Oxford Network. The remaining authors do not have financial relationships to disclose.

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Authors and Affiliations

Authors

Contributions

KC was involved in analysis, interpretation of data, drafting of the manuscript, and critical revision of the manuscript. JK, TJ, and BPM were involved in study conception and design, analysis, interpretation of data, and critical revision of the manuscript. GK, EN, and SMH were involved in analysis, interpretation of data, and critical revision of the manuscript. EME and KAM were involved in designing the data collection instruments, the acquisition of the data, interpretation of data, and critical revision of the manuscript. RFS and JDH were involved in coordinating data collection, interpretation of the data, and critical revision of the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Biren P. Modi.

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The authors declare no competing interests.

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Culbreath, K., Knell, J., Keefe, G. et al. Impact of concomitant necrotizing enterocolitis on mortality in very low birth weight infants with intraventricular hemorrhage. J Perinatol 43, 91–96 (2023). https://doi.org/10.1038/s41372-022-01434-1

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  • DOI: https://doi.org/10.1038/s41372-022-01434-1

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