Risk Factor Effects on Neurodevelopment at 2 Years in Very Preterm Children: A Systematic Review

CONTEXT Various medical and social factors are associated with adverse neurodevelopment in children born very preterm. Analyses accounting for confounders involving representative samples are essential to quantify the effects of different factors. OBJECTIVE We aimed to systematically review the effects of various risk factors on neurodevelopmental impairment (NDI) at 18 to 36 months of age in children born before 32 weeks’ gestation. DATA SOURCES Ovid MEDLINE, Embase, and PubMed were searched for articles up through April 29, 2024. STUDY SELECTION We used geographic or network population cohort studies of children born after January 1, 1990 at less than 32 completed weeks’ gestation reporting risk factors and NDI measures at 18 to 36 months old. Studies including less than 50 children, not addressing confounders in the analysis, or comprising nonrepresentative samples were excluded. DATA EXTRACTION Study characteristics, population characteristics, exposure and outcome definitions, effect sizes, and covariates were extracted. RESULTS Of 18 012 studies screened, 51 were eligible. Brain injury (intraventricular hemorrhage grade III or IV and/or periventricular leukomalacia) had the highest adjusted odds of moderate-to-severe NDI and its main contributors (moderate-to-severe cognitive or language delay and moderate-to-severe cerebral palsy), followed by neonatal seizures and retinopathy of prematurity (≥stage 3, “threshold disease” or “treated”). Small for gestational age exhibited inconsistent effects, whereas lower maternal age exhibited no effect on the outcomes included. LIMITATIONS This included an inability to meta-analyze due to factor and outcome definition heterogeneity. CONCLUSIONS This review illustrates the extent to which risk factors influence the odds of NDI in children born very preterm, finding neurologic morbidities confer the highest risk. We highlight the need for consistent factor and outcome definitions.