ArticlePediatric research2025
Unbound bilirubin and risk of severe neurodevelopmental impairment in extremely low birthweight newborns.
Article in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Parenteral Lipid Dose and Bilirubin Neurotoxicity in Extremely Preterm Infants: A Factorial Randomized Trial.The Journal of pediatrics · 2026Trial
- Unbound bilirubin: a call to reframe neonatal care and clinical decision-making.Pediatric research · 2026Article
- Determinants of unbound bilirubin and clinical utility of the total bilirubin/albumin ratio in neonates.Pediatric research · 2026Article
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Authors and funding
5 authors.
Funding
Abstract
backgroundUnbound bilirubin (UB) was measured on day 5 ± 1 in 1101 ELBW newborns in the Aggressive vs Conservative Phototherapy randomized controlled trial. We accessed this dataset to quantify the UB-mediated risk of severe neurodevelopmental impairment (sNDI) in extremely low birthweight (ELBW) newborns.
methodsUB levels were standardized within laboratories as z-score percentiles. A dichotomous UB exposure variable was based on sharply increased risk of sNDI at the 85th percentile (UBz>85th). Targeted maximum likelihood estimation with ensemble machine learning (TMLE + ML) and logistic regression (LR) were used to estimate sNDI risk attributable to UBz>85th.
resultsUB - total bilirubin correlation was poor: R
conclusionsExposure to UBz>85th was associated with a large increase in risk of sNDI in ELBW newborns. IMPACT: Accessing the only large dataset with measures of unbound bilirubin (UB) and neurodevelopmental outcomes in extremely low birthweight (ELBW) newborns we found poor correlation between UB and total bilirubin (TB). The risk of severe neurodevelopmental impairment (sNDI) associated with UB rose non-linearly with an inflection point at UB z-score 85th percentile (UBz>85th), increasing the risk of sNDI by an estimated 14% (number need to harm: 7). The current incidence of exposure to harmful UB levels in very premature newborns is unlikely to be rare. TB levels provide a false sense of security to clinicians caring for very premature newborns.
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