TY - JOUR
T1 - The association between serum bilirubin and kernicterus spectrum disorder
T2 - A systematic review and meta-analysis
AU - Lai, Nai Ming
AU - Gerard, Joanna Priya
AU - Ngim, Chin Fang
AU - Kamar, Azanna Ahmad
AU - Chen, Kee-Hsin
N1 - Funding Information:
Nine studies received funding from government-linked institutions, 2 from universities, 6 received no funding, and the remaining provided no information.
Publisher Copyright:
© 2021
PY - 2021/12
Y1 - 2021/12
N2 - Background: 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.
AB - Background: 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.
KW - Kernicterus spectrum disorder
KW - Neonatal hyperbilirubinemia
KW - Serum bilirubin
UR - https://www.scopus.com/pages/publications/85119400160
U2 - 10.1159/000519497
DO - 10.1159/000519497
M3 - Review Article
C2 - 34731859
AN - SCOPUS:85119400160
SN - 1661-7800
VL - 118
SP - 654
EP - 664
JO - Neonatology
JF - Neonatology
IS - 6
ER -