Objective: Necrotizing enterocolitis (NEC) remains a major cause of neonatal morbidity and mortality. Some infants recover uneventfully with medical therapy whereas others develop severe disease (that is, NEC requiring surgery or resulting in death). Repeated attempts to identify clinical parameters that would reliably identify infants with NEC most likely to progress to severe disease have been unsuccessful. We hypothesized that comprehensive prospective data collection at multiple centers would allow us to develop a model which would identify those babies at risk for progressive NEC.
Study Design: This prospective, observational study was conducted at six university children's hospitals. Study subjects were neonates with suspected or confirmed NEC. Comprehensive maternal and newborn histories were collected at the time of enrollment, and newborn clinical data were collected prospectively, thereafter. Multivariate logistic regression analysis was used to develop a predictive model of risk factors for progression.
Result: Of 455 neonates analyzed, 192 (42%) progressed to severe disease, and 263 (58%) advanced to full feedings without operation. The vast majority of the variables studied proved not to be associated with progression to severe disease. A total of 12 independent predictors for progression were identified, including only 3 not previously described: having a teenaged mother (odds ratio, OR, 3.14; 95% confidence interval, CI, 1.45 to 6.96), receiving cardiac compressions and/or resuscitative drugs at birth (OR, 2.51; 95% CI, 1.17 to 5.48), and having never received enteral feeding before diagnosis (OR, 2.41; 95% CI, 1.08 to 5.52).
Conclusion: Our hypothesis proved false. Rigorous prospective data collection of a sufficient number of patients did not allow us to create a model sufficiently predictive of progressive NEC to be clinically useful. It appears increasingly likely that further analysis of clinical parameters alone will not lead to a significant improvement in our understanding of NEC. We believe that future studies must focus on advanced biologic parameters in conjunction with clinical findings.
Journal of Perinatology (2008) 28, 665-674; doi:10.1038/jp.2008.119; published online 11 September 2008
Keywords: necrotizing enterocolitis; clinical risk factors; progression to severe disease; multicenter study; enteral feeding; prematurity
Necrotizing enterocolitis (NEC) is the most common serious gastrointestinal disease among neonates and a leading cause of morbidity and death in neonatal intensive care units (NICUs). The only consistently demonstrable risk factor for NEC is prematurity. Approximately one-half of infants with NEC will recover fully with bowel rest and antibiotics whereas the other half will develop severe disease requiring urgent surgical intervention. (1,2) Up to one-half of the patients with serious disease will die and a significant proportion of the survivors will suffer long-term growth, gastrointestinal and neurodevelopmental consequences. (3-5)
The ability to understand why certain infants are at risk for severe disease would enhance our understanding of NEC and open doors for prevention and treatment. Multiple previous investigations have attempted to develop prediction models based upon clinical parameters. Most of these efforts involved retrospective case series reviews at single institutions and were, therefore, limited by their retrospective nature and inability to achieve desired power. We aimed to bring the strength...