Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012–13: a whole-population surveillance study

Abstract

Word count: Abstract (300 /300w) Background: Necrotising enterocolitis (NEC), a feared neonatal gastrointestinal inflammatory disease with high mortality and morbidity, is growing in global relevance as birth rates and early survival of low gestational age (GA) infants increases. Population data are scant and pathogenesis is incompletely understood but enteral feed exposures are believed to influence risk. Methods:We conducted a two-year national surveillance study to quantify the total population burden of severe NEC (confirmed at laparotomy and/or leading to death) in England, and a propensity score analysis of the impact of early feeds of maternal milk (MM), and avoidance of bovine-origin formula (BOF) and milk fortifier (BMF), on NEC risk in very preterm infants. Findings:During the study period 118,073 infants (14,678 <32w GA) were admitted to 163 neonatal units across 23 networks; 531 (462 <32w GA) developed severe NEC; 247 died, 139 following laparotomy. Among infants <32w GA the adjusted network incidence ranged from 2·51% to 3·85% with no evidence of unusual variation in relation to the national incidence of 3·13% (95%CI 2·85, 3·42) despite variation in feeding practices. Also among infants <32w GA, commencing any MM within seven postnatal days resulted in an Absolute Risk Difference (ARD) of -0·88% (95% CI -1·15, -0·61), Relative Risk (RR) 0·69 (95% CI 0·60, 0·78), and Number Needed to Treat (NNT) 114 (95% CI 87, 136); equivalent figures for infants receiving no, compared to any bovine-origin products within 14 postnatal days were ARD -0·65% (95% CI -1·01, -0·29), RR 0·61 (95% CI 0·39, 0·83), NNT 154 (95% CI 94, 345). Interpretation:Commencing MM early and avoiding bovine-origin products may reduce NEC but absolute risk reductions appear small. The rarity of severe NEC requires national and international collaboration for adequately powered preventive trials.Funding: This study represents independent research funded by the National Institute for Health Research (NIHR). Research in contextEvidence before this study Necrotising enterocolitis (NEC) is a feared, acute neonatal gastrointestinal inflammatory disease with high mortality and morbidity. Reliable population incidence data are necessary for designing preventive and treatment studies. Enteral feeding stratagems are widely believed to influence NEC risk. When maternal milk (MM) is insufficient or unavailable some clinicians prefer pasteurised human donor milk (HDM) over bovine-origin formula (BOF) in the hope that avoidance of bovine-origin products will be protective and/or pasteurised HDM will retain some of the protective properties of MM. Others prefer BOF to HDM as the composition of the former is consistent, nutrient density is higher, and costs are lower. Other uncertainties relate to the timing of introduction of milk feeds in very preterm infants, and use of bovineorigin fortifier (BMF) (additional vitamins, minerals, and nutrients added to human milk).We conducted a systematic search of studies from the 34 countries in the Organisation fo...

Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis

“…Until recently, data from the UK have been limited to a survey of 158 neonatal intensive care units [8], but following the UK National Confidential Enquiry into Patient Outcome and Death report, in which gaps in our knowledge about NEC in the UK were highlighted [9], 2 national prospective studies were initiated, 1 focused on neonatal aspects and the other on surgical aspects. In the neonatal study, data were prospectively acquired from 163 English neonatal units over 2 years; this included 118,073 infants, of whom 531 (0.4%) developed severe NEC with a mortality of 48% [10]. Interestingly, given the well-known protective effect of breast milk, in these infants the absolute risk reduction from human milk compared with bovine products was modest.…”

“…Interestingly, the protective effect of breast milk appears to be dose related [38], although, as discussed in the epidemiology section above, the absolute risk reduction may be modest [10]. A huge array of protective factors present in breast milk has been suggested and some of these have been proposed as potential preventative measures or treatments (see below).…”

eNewborn: The Information Technology Revolution and Challenges for Neonatal Networks

“…The information is collected from a multipurpose health service database created from regular extractions of data from contemporaneous point-of-care, clinician-entered electronic patient records [19]. Using the NNRD, Battersby et al [20,21] described the population prevalence of necrotizing enterocolitis by gestational age and drew inferences about the influence of feeding practices in this devastating disease. The NNRD is also very helpful in determining the incidence of diseases and the sample size needed to conduct a trial [22].…”

Searching for Causes of Necrotising Enterocolitis. An Application of Propensity Matching

“…The results of this study are presented and their implications discussed by Battersby et al (2017b) for a clinical (medical) audience. This paper focuses on the statistical and computational aspects.…”