Comparison of bilirubin albumin ratio and total serum bilirubin for predicting neurological dysfunction in newborns: A meta-analysis.

Abstract

Background: Bilirubin-induced neurologic dysfunction (BIND) remains a serious complication of severe neonatal hyperbilirubinemia, especially in resource-limited settings. While total serum bilirubin (TSB) is widely used for risk stratification, the bilirubin/albumin (B/A) ratio has been proposed as a surrogate for free bilirubin, the neurotoxic fraction.

Aim: To compare the diagnostic accuracy of the B/A ratio vs TSB for predicting acute BIND in neonates.

Methods: We conducted a systematic review and meta-analysis of observational studies evaluating the B/A ratio and TSB for predicting BIND in neonates (≥ 35 weeks' gestational age). Data sources included PubMed, EMBASE, Cochrane Central, and Google Scholar. Pooled standardized mean difference (SMD), sensitivity, specificity, and heterogeneity (I ²) were calculated using a bivariate random-effects model. Meta-regression was used to assess whether biomarker type (B/A vs TSB) explained performance differences. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results: Five studies involving a total of 1022 neonates were included, with a male-to-female ratio of approximately 57:40. The SMD for B/A ratio was 1.71 (95%CI: 1.00-2.41, P < 0.0001), and for TSB it was 1.68, both showing strong associations with BIND. Meta-regression revealed no significant difference in predictive value between the two biomarkers (P = 0.96).

Conclusion: Both TSB and the B/A ratio are comparably effective in predicting BIND. While the B/A ratio may provide incremental value in specific clinical contexts, current evidence supports continued reliance on TSB for routine risk stratification.