Research Article 2026-04-23 under-review v1

The connection between neonatal jaundice and neurodevelopment later in life: a national birth cohort study

W
Won Seok Lee CHA Ilsan Medical Center
J
Ju Hee Kim Kyung Hee University School of Medicine
B
Boeun Han CHA Bundang Medical Center
J
Jeewon Shin CHA Ilsan Medical Center
E
Eun Kyo Ha Hallym University Kangnam Sacred Heart Hospital
E
Eun Lee Chonnam National University Hospital
J
Ji Hee Kwak Kangbuk Samsung Hospital
S
Sun Kyung Lee CHA Bundang Medical Center
M
Man Yong Han CHA Bundang Medical Center

Abstract

Background Elevated serum bilirubin in neonates may serve as an early indicator of later neurodevelopment and influence gut microbiota composition after birth. This study examined the connection between neonatal jaundice requiring phototherapy and later neurodevelopment.Methods This retrospective population-based cohort included 3,203,983 children born in Korea from 2009 to 2015, tracked from birth until December 2021 in Korea. Neurodevelopmental outcomes at age six were assessed using national child health screening data. Analyses controlled for confounders including sex, birth weight, prematurity, chromosomal abnormalities, congenital malformations, income, and infant feeding type. Neurodevelopmental outcomes were evaluated in six domains (gross motor, fine motor, cognition, language, social skills, and self-help) using the Korean Developmental Screening Test (K-DST). Effect of phototherapy duration on each domain was also examined.Results A total of 1,004,385 neonates were included, of whom 121,366 (56.0% male) received phototherapy. Neonatal jaundice requiring phototherapy was significantly associated with abnormal outcomes in gross motor (adjusted odds ratio [aOR] 1.087, 95% CI 1.049–1.127, P < .0001), cognition (aOR 1.045, 95% CI 1.013–1.077, P = .0052), and language (aOR 1.049, 95% CI 1.013–1.086, P = .0072). Longer phototherapy duration (≥ 5 days) was associated with abnormal outcomes in overall assessment and gross motor, fine motor, cognition, and language domains.Conclusions Neonatal jaundice requiring phototherapy was associated with higher risk of abnormal neurodevelopment at age six, particularly in gross motor, cognition, and language domains. Prolonged phototherapy was also linked to adverse outcomes.

Citation Information

@article{wonseoklee2026,
  title={The connection between neonatal jaundice and neurodevelopment later in life: a national birth cohort study},
  author={Won Seok Lee and Ju Hee Kim and Boeun Han and Jeewon Shin and Eun Kyo Ha and Eun Lee and Ji Hee Kwak and Sun Kyung Lee and Man Yong Han},
  journal={BMC Public Health},
  year={2026},
  doi={https://doi.org/10.21203/rs.3.rs-9238959/v1}
}
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