[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.161.155.6. Please contact the publisher to request reinstatement.
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
Views 465
Citations 0
Original Investigation
January 03, 2017

Development of a Gestational Age–Specific Case Definition for Neonatal Necrotizing Enterocolitis

Cheryl Battersby, MRCPCH1; Nick Longford, PhD1; Kate Costeloe, MD2; et al Neena Modi, MD1; for the UK Neonatal Collaborative Necrotising Enterocolitis Study Group
Author Affiliations
  • 1Neonatal Data Analysis Unit, Imperial College London, London, England
  • 2Barts and the London School of Medicine and Dentistry, London, England
JAMA Pediatr. Published online January 3, 2017. doi:10.1001/jamapediatrics.2016.3633
Key Points

Question  Is it possible to develop a case definition for necrotizing enterocolitis (NEC) that discriminates between infants with and without the disease?

Findings  In this population study using data from 3866 infants, we developed a simple NEC score associated with the probability of NEC and identified gestational age–specific cutoff points. Less mature infants are less likely to present with pneumatosis or blood or mucus in their stool and more likely to present with gasless abdominal radiography findings.

Meaning  Consistent application of a gestational age–specific case definition offers an opportunity to strengthen global efforts to reduce the burden of neonatal NEC.

Abstract

Importance  Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality. Preventive and therapeutic research, surveillance, and quality improvement initiatives are hindered by variations in case definitions.

Objective  To develop a gestational age (GA)–specific case definition for NEC.

Design, Setting, and Participants  We conducted a prospective 34-month population study using clinician-recorded findings from the UK National Neonatal Research Database between December 2011 and September 2014 across all 163 neonatal units in England. We split study data into model development and validation data sets and categorized GA into groups (group 1, less than 26 weeks’ GA; group 2, 26 to less than 30 weeks’ GA; group 3, 30 to less than 37 weeks’ GA; group 4, 37 or more weeks’ GA). We entered GA, birth weight z score, and clinical and abdominal radiography findings as candidate variables in a logistic regression model, performed model fitting 1000 times, averaged the predictions, and used estimates from the fitted model to develop an ordinal NEC score and cut points to develop a dichotomous case definition based on the highest area under the receiver operating characteristic curves [AUCs] and positive predictive values [PPVs].

Exposures  Abdominal radiography performed to investigate clinical concerns.

Main Outcomes and Measures  Ordinal NEC likelihood score, dichotomous case definition, and GA-specific probability plots.

Results  Of the 3866 infants, the mean (SD) birth weight was 2049.1 (1941.7) g and mean (SD) GA was 32 (5) weeks; 2032 of 3663 (55.5%) were male. The total included 2978 infants (77.0%) without NEC and 888 (23.0%) with NEC. Infants with NEC in group 1 were less likely to present with pneumatosis (31.1% vs 47.2%; P = .01), blood in stool (11.8% vs 29.6%; P < .001), or mucus in stool (2.1% vs 5.6%; P = .048) but more likely to present with gasless abdominal radiography findings (6.3% vs 0.9%; P = .009) compared with infants with NEC in group 3. In the ordinal NEC score analysis, we allocated 3 points to pneumatosis, 2 points to blood in stool, and 1 point each to abdominal tenderness and abdominal discoloration; 1 point was assigned if 1 or more of pneumoperitoneum, fixed loop, and portal venous gas were present, and 1 point was assigned if both increased and/or bilious aspirates and abdominal distension were present. The cutoff scores for the dichotomous GA-specific case definition were 2 or greater for infants in groups 1 and 2, 3 or greater for infants in group 3, and 4 or greater for infants in group 4. The ordinal NEC score and dichotomous case definition discriminated well between infants with (AUC, 87%) and without (AUC, 80%) NEC. The case definition has a sensitivity of 66.2% (95% CI, 63.0-69.4), a specificity of 94.4% (95% CI, 93.2-95.4), an AUC of 80.0% (95% CI, 79-82), and a PPV of 85.5% (95% CI, 82.6-88.1). Applying the cut points to the 431 infants who underwent a laparotomy yielded a sensitivity of 76.5% (95% CI, 70.0-82.1), a specificity of 74.4% (95% CI, 68.3-80.0), an AUC of 75.0% (95% CI, 71.0- 80.0), and a PPV of 72.9% (95% CI, 66.4-78.7).

Conclusions and Relevance  The risk of NEC and clinical presentation are associated with GA. Adoption of a consistent GA-specific case definition would strengthen global efforts to reduce the population burden of this devastating neonatal disease.

×