Faculty, Staff and Student Publications
Publication Date
11-1-2023
Journal
The Journal of Pediatrics
Abstract
Objective: The objective of this study was to evaluate whether infants randomized in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Necrotizing Enterocolitis Surgery Trial differed from eligible infants and whether differences affected the generalizability of trial results.
Study design: Secondary analysis of infants enrolled in Necrotizing Enterocolitis Surgery Trial (born 2010-2017, with follow-up through 2019) at 20 US academic medical centers and an observational data set of eligible infants through 2013. Infants born ≤1000 g and diagnosed with necrotizing enterocolitis or spontaneous intestinal perforation requiring surgical intervention at ≤8 weeks were eligible. The target population included trial-eligible infants (randomized and nonrandomized) born during the first half of the study with available detailed preoperative data. Using model-based weighting methods, we estimated the effect of initial laparotomy vs peritoneal drain had the target population been randomized.
Results: The trial included 308 randomized infants. The target population included 382 (156 randomized and 226 eligible, non-randomized) infants. Compared with the target population, fewer randomized infants had necrotizing enterocolitis (31% vs 47%) or died before discharge (27% vs 41%). However, incidence of the primary composite outcome, death or neurodevelopmental impairment, was similar (69% vs 72%). Effect estimates for initial laparotomy vs drain weighted to the target population were largely unchanged from the original trial after accounting for preoperative diagnosis of necrotizing enterocolitis (adjusted relative risk [95% CI]: 0.85 [0.71-1.03] in target population vs 0.81 [0.64-1.04] in trial) or spontaneous intestinal perforation (1.02 [0.79-1.30] vs 1.11 [0.95-1.31]).
Conclusion: Despite differences between randomized and eligible infants, estimated treatment effects in the trial and target population were similar, supporting the generalizability of trial results.
Trial registration: ClinicalTrials.gov ID: NCT01029353.
Keywords
Child, Infant, Newborn, Infant, Humans, Intestinal Perforation, Enterocolitis, Necrotizing, Laparotomy, Infant, Newborn, Diseases, Infant, Premature, Diseases, generalizability, necrotizing enterocolitis, randomized clinical trials, spontaneous intestinal perforation
DOI
10.1016/j.jpeds.2023.113453
PMID
37169336
PMCID
PMC10632546
PubMedCentral® Posted Date
11-1-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes