Skin residual bilirubin volume: a physiologically informed framework for transcutaneous bilirubin interpretation in...

Transcutaneous bilirubinometry (TcB) is increasingly relied upon for neonatal jaundice management in settings without access to laboratory-based total serum bilirubin (TSB) testing. However, inconsistent agreement between transcutaneous bilirubin levels (TBL) and TSB limits its reliability as a standalone clinical tool.

To propose and evaluate skin residual bilirubin volume (SRBV) as a physiological explanation for TcB-TSB discordance and to assess its impact on TcB interpretation during diagnosis, treatment, and recovery.

This observational, multicentre study was conducted in resource-limited neonatal care settings. TcB readings were calibrated against laboratory TSB in non-jaundiced neonates (TSB <3 mg/dL). Neonates undergoing phototherapy were monitored using paired TcB measurements obtained immediately after treatment interruption (TBL-out) and prior to treatment resumption (TBL-return). TSB was measured before treatment, during treatment, and prior to discharge where feasible. Patterns of TcB-TSB disparity and the "Recovery Value Flip (RVP)" phenomenon were analysed.

TBL consistently equalled or exceeded TSB in cases with paired measurements. Early in treatment at higher bilirubin levels, TBL-return exceeded TBL-out, indicating persistent cutaneous bilirubin. A reproducible RVP was observed, after which TBL-return became lower than TBL-out, coinciding with sustained bilirubin decline. SRBV contribution varied with bilirubin level and treatment phase.

SRBV provides a biologically plausible explanation for TcB-TSB discordance and dynamic TcB behaviour. Incorporating SRBV into TcB interpretation enables physiologically informed monitoring, improving safety and reliability in laboratory-limited neonatal settings.