One of the many challenges with necrotizing enterocolitis (NEC) remains our inability to make an accurate diagnosis of NEC. The lack of a unifying cause and multiple variations in presentations lead to great uncertainty with NEC. Separating out the needs of the researcher wanting to define NEC from the clinician and patient family’s perspectives who want an accurate diagnosis for NEC is important. The need to augment and/or replace the outdated modified Bell staging criteria is crucial to improving NEC management. Emerging literature suggests that genetic susceptibility and stool microbiota signatures may help identify preterm infants at increased risk of the disease. Ongoing studies using single or multi-omic approaches may help to characterize biomarkers that will aid in the prediction or early diagnosis of NEC, as well as differentiate other causes of severe bowel injury. Bowel ultrasound shows promise in improving our diagnostic accuracy for NEC but has been slow in adoption. Patient family perspectives are key in accelerating our efforts to integrate newer diagnostic methods into practice.
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Neu, J. Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention. Pediatr. Clin. North Am. 43, 409–432 (1996).
Bell, M. J. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg. 187, 1–7 (1978).
Battersby, C., Longford, N., Costeloe, K., Modi, N. & Group UKNCNES. Development of a gestational age-specific case definition for neonatal necrotizing enterocolitis. JAMA Pediatr. 171, 256–263 (2017).
Gordon, P. V., Swanson, J. R., MacQueen, B. C. & Christensen, R. D. A critical question for NEC researchers: can we create a consensus definition of NEC that facilitates research progress? Semin. Perinatol. 41, 7–14 (2017).
Caplan, M. S. et al. Necrotizing enterocolitis: using regulatory science and drug development to improve outcomes. J. Pediatr. 212, 208.e1–215.e1 (2019).
Kliegman, R. M. & Fanaroff, A. A. Necrotizing enterocolitis. N. Engl. J. Med. 310, 1093–1103 (1984).
Berseth, C. L., Bisquera, J. A. & Paje, V. U. Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 111, 529–534 (2003).
Meinzen-Derr, J. et al. Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death. J. Perinatol. 29, 57–62 (2009).
Neu, J. & Pammi, M. Necrotizing enterocolitis: the intestinal microbiome, metabolome and inflammatory mediators. Semin. Fetal Neonatal Med. 23, 400–405 (2018).
Yee, W. H. et al. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics 129, e298–e304 (2012).
Uauy, R. D. et al. Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network. J. Pediatr. 119, 630–638 (1991).
Maayan-Metzger, A., Itzchak, A., Mazkereth, R. & Kuint, J. Necrotizing enterocolitis in full-term infants: case-control study and review of the literature. J. Perinatol. 24, 494–499 (2004).
Li, Q. Y. et al. Differences in the clinical characteristics of early- and late-onset necrotizing enterocolitis in full-term infants: a retrospective case-control study. Sci. Rep. 7, 43042 (2017).
Vongbhavit, K. & Underwood, M. A. Intestinal perforation in the premature infant. J. Neonatal Perinat. Med. 10, 281–289 (2017).
Gordon, P. V. & Attridge, J. T. Understanding clinical literature relevant to spontaneous intestinal perforations. Am. J. Perinatol. 26, 309–316 (2009).
Moorman, J. R. et al. Mortality reduction by heart rate characteristic monitoring in very low birth weight neonates: a randomized trial. J. Pediatr. 159, 900–906 e901 (2011).
Fairchild, K. D. et al. Vital signs and their cross-correlation in sepsis and NEC: a study of 1,065 very-low-birth-weight infants in two NICUs. Pediatr. Res. 81, 315–321 (2017).
Kliegman, R. M., Walker, W. A. & Yolken, R. H. Necrotizing enterocolitis: research agenda for a disease of unknown etiology and pathogenesis. Pediatr. Res. 34, 701–708 (1993).
Wang, K., Tao, G., Sun, Z. & Sylvester, K. G. Recent potential noninvasive biomarkers in necrotizing enterocolitis. Gastroenterol. Res. Pract. 2019, 8413698 (2019).
Garg, B. D., Sharma, D. & Bansal, A. Biomarkers of necrotizing enterocolitis: a review of literature. J. Matern. Fetal Neonatal Med. 31, 3051–3064 (2018).
Gephart, S. M. et al. Changing the paradigm of defining, detecting, and diagnosing NEC: perspectives on Bell’s stages and biomarkers for NEC. Semin. Pediatr. Surg. 27, 3–10 (2018).
Goldstein, G. P. & Sylvester, K. G. Biomarker discovery and utility in necrotizing enterocolitis. Clin. Perinatol. 46, 1–17 (2019).
Zani, A. & Pierro, A. Necrotizing enterocolitis: controversies and challenges. F1000Res 4, 1373 (2015).
Bhandari, V. et al. Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics 117, 1901–1906 (2006).
Cuna, A., George, L. & Sampath, V. Genetic predisposition to necrotizing enterocolitis in premature infants: current knowledge, challenges, and future directions. Semin. Fetal Neonatal Med. 23, 387–393 (2018).
Nino, D. F., Sodhi, C. P. & Hackam, D. J. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat. Rev. Gastroenterol. Hepatol. 13, 590–600 (2016).
Sampath, V. et al. SIGIRR genetic variants in premature infants with necrotizing enterocolitis. Pediatrics 135, e1530–e1534 (2015).
Hartel, C. et al. NOD2 loss-of-function mutations and risks of necrotizing enterocolitis or focal intestinal perforation in very low-birth-weight infants. Inflamm. Bowel Dis. 22, 249–256 (2016).
Kim, J. H. Role of abdominal US in diagnosis of NEC. Clin. Perinatol. 46, 119–127 (2019).
Faingold, R. et al. Necrotizing enterocolitis: assessment of bowel viability with color doppler US. Radiology 235, 587–594 (2005).
V.S. is supported by 1R01DK117296-A1 from the National Institutes of Health and a Katharine Berry Richardson Award. Publication of this article was sponsored by the Necrotizing Enterocolitis (NEC) Society, Patient-Centered Outcomes Research Institute, and National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development.
J.H.K. received grant support from Mallinckrodt and Fresenius-Kabi; received consultant or advisor fees from Evolve Bioscience, Medela, Alcresta, and Ferring; received lecture fees from Mead Johnson Nutrition and Abbott Nutrition; owns shares in Nicolette and Astarte Medical; served as expert witness; and holds a patent for a newborn heart rate device. None of these entities or funding bodies had any role in this manuscript. J.C. is the founder and Director of The NEC Society, sponsor of the supplement.
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Kim, J.H., Sampath, V. & Canvasser, J. Challenges in diagnosing necrotizing enterocolitis. Pediatr Res 88, 16–20 (2020). https://doi.org/10.1038/s41390-020-1090-4