Eligibility Criteria and Representativeness of Randomized Clinical Trials That Include Infants Born Extremely Premature: A Systematic Review

Abstract

To assess the eligibility criteria and trial characteristics among contemporary (2010-2019) randomized clinical trials (RCTs) that included infants born extremely preterm (<28weeks of gestation) and to evaluate whether eligibility criteria result in underrepresentation of high-risk subgroups (eg, infants born at <24weeks of gestation). PubMed and Scopus were searched January 1, 2010, to December 31, 2019, with no language restrictions. RCTs with mean or median gestational ages at birth of <28weeks of gestation were included. The study followed the PRISMA guidelines; outcomes were registered prospectively. Data extraction was performed independently by multiple observers. Study quality was evaluated using a modified Jadad scale. Among RCTs (n=201), 32 552 infants were included. Study participant characteristics, interventions, and outcomes were highly variable. A total of 1603 eligibility criteria were identified; rationales were provided for 18.8% (n=301) of criteria. Fifty-five RCTs (27.4%) included infants <24weeks of gestation; 454 (1.4%) infants were identified as <24weeks of gestation. The present study identifies sources of variability across RCTs that included infants born extremelypreterm and reinforces the critical need for consistent and transparent policies governing eligibility criteria.