The ‘72-Hour Divergence’ in severe hyperbilirubinemia: sepsis is associated with altered renal and hematologic adaptation in a 10-year exchange transfusion cohort

To investigate the association between concurrent sepsis and physiological recovery trajectories in neonates undergoing exchange transfusion (ET) for severe hyperbilirubinemia. A 10-year longitudinal cohort study (2010–2020) of 54 neonates requiring double-volume ET. Patients were stratified into Sepsis (n = 26) and No-Sepsis (n = 28) groups. Renal and hematologic adaptation markers were analyzed over the first 72 h post-procedure. The initial severity of hyperbilirubinemia was comparable between the groups (admission TSB: 23.8 vs. 23.1 mg/dL; p = 0.42). Sepsis, predominantly driven by Klebsiella and E. coli, was identified in 48.1% of the cohort. While ET effectively lowered bilirubin in all infants, concurrent sepsis was associated with a “72-Hour Divergence” an altered physiological state characterized by severe thrombocytopenia (85 vs. 240 × 10³/µL; p < 0.001) and persistent creatinine elevation (1.1 vs. 0.4 mg/dL; p < 0.001) at 72 h. Furthermore, sepsis was linked to a prolonged hospitalization of 7.8 days (p < 0.001), independent of admission bilirubin levels. Sepsis is associated with altered renal and hematologic adaptation in neonates undergoing ET. The “72-Hour Divergence” represents a distinct high-risk phenotype requiring clinical vigilance beyond isolated bilirubin clearance.