Predictors of Rebound Hyperbilirubinemia Study

## Detailed Description

Neonatal hyperbilirubinemia remains one of the leading causes of neonatal hospitalization worldwide. Phototherapy is the standard treatment for significant unconjugated hyperbilirubinemia and is highly effective in reducing serum bilirubin levels. However, a subset of neonates may develop rebound hyperbilirubinemia after discontinuation of phototherapy, occasionally requiring repeat phototherapy and prolonged hospitalization.

Current evidence regarding predictors of rebound hyperbilirubinemia remains limited, particularly in prospective NICU-based cohorts. Identification of infants at increased risk for clinically significant rebound hyperbilirubinemia may improve individualized monitoring strategies, optimize timing of discharge, and reduce unnecessary bilirubin measurements and hospital stay.

This prospective observational study will include neonates admitted to the NICU and treated with phototherapy for hyperbilirubinemia. Clinical and laboratory parameters associated with rebound hyperbilirubinemia will be evaluated. Special emphasis will be placed on delta total serum bilirubin (ΔTSB), defined as the difference between the phototherapy threshold recommended by current guidelines and the measured total serum bilirubin level at the time of phototherapy discontinuation.

Additional variables including gestational age, postnatal age at phototherapy initiation, feeding type, hemolytic risk factors, bilirubin kinetics, and phototherapy characteristics will also be analyzed. Rebound bilirubin measurements will be obtained within 24-48 hours after discontinuation of phototherapy according to unit protocol.

The primary objective is to determine predictors of clinically significant rebound hyperbilirubinemia requiring repeat phototherapy. Secondary objectives include evaluation of bilirubin rebound levels, hospitalization duration, and the association between phototherapy characteristics and rebound risk.

Inclusion criteria

• Neonates admitted to the NICU with neonatal hyperbilirubinemia
• Gestational age ≥35 weeks
• Requirement for phototherapy according to institutional protocol and current guideline-based phototherapy thresholds
• Receipt of standard and/or intensive phototherapy
• Availability of bilirubin measurements before, during, and after phototherapy
• Availability of rebound bilirubin measurement within 48 hours after phototherapy discontinuation
• Written informed consent obtained from parents or legal guardians, if required by the ethics committee

Exclusion criteria

• Major congenital anomalies
• Conjugated hyperbilirubinemia
• Neonates requiring exchange transfusion before completion of initial phototherapy
• Severe perinatal asphyxia
• Proven or suspected inborn errors of metabolism affecting bilirubin metabolism
• Significant congenital liver disease
• Neonates transferred to another center before completion of rebound bilirubin follow-up
• Missing or incomplete clinical or laboratory data
• Absence of rebound bilirubin measurement within 48 hours after phototherapy discontinuation
• Parents or legal guardians declining participation, if consent is required