What is the step‑by‑step approach to assess and manage a newborn with suspected hyperbilirubinemia, including when to obtain total serum bilirubin, phototherapy thresholds, and indications for exchange transfusion?

Neonatal Hyperbilirubinemia: Approach and Management

Initial Assessment and Monitoring

All newborns require systematic jaundice assessment at least every 8–12 hours during hospitalization, with protocols allowing nursing staff to obtain transcutaneous bilirubin (TcB) or order total serum bilirubin (TSB) measurements when jaundice is detected. 1

• Measure TSB or TcB immediately if jaundice appears within the first 24 hours of life—this is always pathologic and requires urgent evaluation. 1, 2
• Visual estimation of jaundice severity is unreliable, particularly in darkly pigmented infants, and should never guide treatment decisions. 1, 2
• Jaundice typically progresses cephalocaudally (face → trunk → extremities), but the degree of skin discoloration does not correlate reliably with bilirubin levels. 1

Laboratory Evaluation

Immediate Testing

• Obtain TSB (not just TcB) for any infant with visible jaundice in the first 24 hours or when jaundice appears excessive for the infant's age. 1, 2
• If maternal blood is group O Rh-positive, test cord blood or infant blood for ABO/Rh type and Direct Antiglobulin Test (DAT/Coombs'). 1, 3

When to Investigate Underlying Causes

• Evaluate the cause of hyperbilirubinemia in any infant requiring phototherapy. 1

• Obtain complete blood count with peripheral smear, reticulocyte count, blood type, DAT, and G6PD enzyme activity if:

  • TSB rises despite intensive phototherapy 1
  • TSB rises suddenly or after an initial decline 1
  • Jaundice persists at or beyond 3 weeks of age 1
  • Escalation of care is required 1

• For infants jaundiced beyond 3 weeks, measure total and direct/conjugated bilirubin to identify cholestasis, and verify newborn thyroid and galactosemia screening results. 1, 2

Interpreting Bilirubin Levels

All bilirubin measurements must be plotted on hour-specific nomograms according to the infant's exact age in hours (not days), gestational age, and presence of neurotoxicity risk factors. 1

Risk Stratification

Lower treatment thresholds apply to infants with:

• Gestational age 35–37 weeks 1, 2
• Isoimmune hemolytic disease (positive DAT) 1
• G6PD deficiency 1, 2
• Sepsis or acidosis 2
• Albumin <3.0 g/dL 2

Phototherapy Indications and Implementation

When to Start Phototherapy

• Use the 2024 AAP hour-specific phototherapy nomograms that incorporate gestational age, neurotoxicity risk factors, and infant age in hours. 1
• The 2024 guidelines raised phototherapy thresholds compared to 2004, reducing overtreatment. 4

Phototherapy Technique

• Maximize skin exposure and use blue-green spectrum light (special blue fluorescent tubes or LED devices) with spectral irradiance >30 μW/cm²/nm for intensive phototherapy. 1
• Combined phototherapy (overhead plus fiberoptic pad) achieves lower bilirubin levels, shorter treatment duration, and fewer exchange transfusions than single-source phototherapy. 5
• Continue breastfeeding during phototherapy; increase feeding frequency to 8–12 times per 24 hours to enhance bilirubin excretion. 3

Monitoring During Phototherapy

• Measure TSB to verify efficacy after starting phototherapy; timing depends on the TSB trajectory (rate of rise in mg/dL per hour) and infant age. 1
• For non-hemolytic hyperbilirubinemia in late preterm and term infants, TSB monitoring frequency can be reduced during phototherapy because TSB does not exceed exchange transfusion thresholds once phototherapy is established. 6
• TcB measurements are inaccurate during and immediately after phototherapy because light "bleaches" the skin; use TSB instead unless ≥24 hours have elapsed since phototherapy stopped. 1, 2

Discontinuing Phototherapy

• Stop phototherapy when TSB has declined 2–4 mg/dL below the hour-specific threshold at which phototherapy was initiated. 1
• Consider the cause of hyperbilirubinemia, the difference between current TSB and the phototherapy threshold, and the risk of rebound when deciding to discontinue. 1

Post-Phototherapy Follow-Up

High-risk infants (phototherapy started <48 hours of age, gestational age <38 weeks, positive DAT, or suspected hemolytic disease) require:

• TSB measurement 8–12 hours after phototherapy discontinuation 1
• Repeat TSB the following day 1

All other infants require TSB within 1–2 days after stopping phototherapy. 1

Escalation of Care and Exchange Transfusion

Escalation Threshold

Escalate care immediately when TSB reaches or exceeds the exchange transfusion threshold, or falls within 0–2 mg/dL below it (the "escalation of care" level). 1

Immediate Interventions

• Initiate intravenous hydration and emergent intensive phototherapy as soon as the escalation threshold is reached. 1
• Measure TSB at least every 2 hours from the start of escalation until the escalation period ends. 1
• If TSB continues rising despite intensive phototherapy and IV hydration, consult neonatology for NICU transfer. 1

Exchange Transfusion Indications

• Proceed to exchange transfusion if TSB continues rising or fails to decline despite optimized intensive phototherapy, or if any signs of acute bilirubin encephalopathy appear (lethargy, hypotonia, high-pitched cry, retrocollis, opisthotonos). 3
• The bilirubin-to-albumin ratio (B/A, in mg/dL : g/dL) can be used as an additional factor—but not in lieu of TSB—when determining exchange transfusion need. 1

Evidence on Forgoing Exchange Transfusion

• Recent data demonstrate that intensive phototherapy can successfully lower TSB even when levels reach exchange transfusion range, preventing neurological complications in many cases. 7
• However, this approach requires close monitoring, rapid TSB decline, and absence of acute bilirubin encephalopathy signs. 7

Home Phototherapy Option

For infants already discharged who develop TSB above the phototherapy threshold, home LED-based phototherapy is an option if the infant meets specific criteria (clinically well, feeding adequately, reliable family, close follow-up arranged). 1

Critical Pitfalls to Avoid

• Never subtract direct bilirubin from total bilirubin when making phototherapy or exchange transfusion decisions—always use the total bilirubin value. 2, 8
• Do not obtain a venous sample solely to "confirm" an elevated capillary TSB; this delays treatment without providing useful information. 2, 8
• Do not rely on TcB measurements during phototherapy or within 24 hours of stopping phototherapy; phototherapy "bleaches" the skin, rendering both visual assessment and TcB unreliable. 1, 2
• Recognize that G6PD levels can be falsely elevated during active hemolysis; a normal result does not exclude deficiency, and repeat testing at 3 months is necessary if clinical suspicion remains high. 2, 8
• Do not treat 35–37 week infants as term infants; they require closer monitoring and have lower phototherapy thresholds. 2

Pre-Discharge Risk Assessment and Follow-Up

• Ensure appropriate surveillance, risk assessment, and follow-up are arranged before discharge. 1
• Infants discharged before 24 hours must be seen by 72 hours of age; those discharged between 24–48 hours must be seen by 96 hours; those discharged between 48–72 hours must be seen by 120 hours. 2
• Provide written and verbal parent education instructing immediate return if jaundice worsens, feeding decreases, or the infant becomes lethargic. 2