The Association between serum bilirubin and kernicterus spectrum disorder: A systematic review and meta-analysis

Lai, Nai Ming and Gerard, Joanna Priya and Ngim, Chin Fang and Kamar, Azanna Ahmad and Chen, Kee-Hsin (2021) The Association between serum bilirubin and kernicterus spectrum disorder: A systematic review and meta-analysis. Neonatology, 118 (6). pp. 654-664. ISSN 1661-7800, DOI

Full text not available from this repository.
Official URL:


Total serum bilirubin (TSB) is used in managing neonates with jaundice, but clear evidence on its association with major outcomes is lacking. Objectives: We evaluated the association between TSB and kernicterus spectrum disorder (KSD). Methods: We searched PubMed, EMBASE, and CENTRAL till July 2021. Two authors independently selected relevant cohort studies, extracted data (CHARMS checklist), assessed risk of bias (RoB) (QUIPS tool), and rated certainty-of-evidence (Grades of Recommendation, Assessment, Development, and Evaluation). We pooled adjusted odds ratio (aOR) (random-effect) via generic inverse variance methods. Results: From 2,826 records retrieved, we included 37 studies (n = 648,979). Fifteen studies had low, 16 moderate, and 6 high RoB, with majority having concerns on confounder adjustment and statistical analysis. Twenty-two studies contributed meta-analysis data, and 15 were summarized narratively. TSB appears associated with KSD in infants with certain risk factors (aOR 1.10, 95 CI: 1.07-1.13; 5 studies n = 4,484). However, TSB (aOR 1.10, 95% CI: 0.98-1.23; 1 study n = 34,533) or hyperbilirubinemia (aOR 1.00, 95% CI: 0.51-1.95; 2 studies n = 56,578) have no clear association with kernicterus or neurological diagnosis in overall neonatal population (moderate-certainty-evidence). One study shows that infants with hyperbilirubinemia appear likelier to develop attention-deficit disorder (aOR 1.90, 95% CI: 1.10-3.28) and autistic spectrum disorder (aOR 1.60, 95% CI: 1.03-2.49, n = 56,019) (low-certainty-evidence). Certain clinical factors appear associated with KSD, although very few studies contributed to the analyses. Conclusions: Despite the importance of this question, there is insufficient high-quality evidence on the independent prognostic value of TSB for adverse neurodevelopmental outcomes in most neonatal populations. Future studies should incorporate all known risk factors alongside TSB in a multivariable analysis to improve certainty-of-evidence. © 2021

Item Type: Article
Uncontrolled Keywords: Neonatal hyperbilirubinemia;Serum bilirubin;Kernicterus spectrum disorder
Subjects: R Medicine
R Medicine > RJ Pediatrics
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 18 Oct 2022 07:50
Last Modified: 18 Oct 2022 07:50

Actions (login required)

View Item View Item