Newborn Jaundice
Hyperbilirubinemia & Newborn Jaundice: What NICU Nurses Need to Know (and WHY it Matters)
Jaundice is one of the most common conditions we care for in the NICU, and one of the easiest to underestimate. Most of the time it's benign and self-limited. Sometimes, it's a red flag for serious pathology. The key is knowing what you're looking at, why it's happening, and when to escalate.
Let's break it down simply then we will dive a little deeper into the physiology.
What Is Jaundice?
Jaundice is the visible yellow discoloration of the skin and sclera caused by elevated serum bilirubin. In neonates, this reflects a balance (or imbalance) between:
Bilirubin production
Hepatic uptake and conjugation
Excretion through bile and stool
Newborns (especially preemies) are uniquely vulnerable because their bilirubin load is high and their clearance systems are immature.
Why newborns are different:
Higher RBC volume per kilogram than adults
Shorter RBC lifespan (70-90 days vs. 120 days in adults)
Immature hepatic enzyme systems
Increased enterohepatic circulation
Immature blood-brain barrier (especially in preterm infants)
This combination means that even "normal" physiologic processes can quickly tip into pathologic territory if we're not vigilant.
Unconjugated vs Conjugated Bilirubin
Unconjugated (Indirect) Bilirubin
Fat-soluble
Can cross the blood–brain barrier
Responsible for bilirubin induced neurologic dysfunction (BIND) disorders like kernicterus
Most common form seen in physiologic jaundice
Why it's elevated:
Increased RBC turnover
Immature hepatic enzymes
Increased enterohepatic circulation
This is the bilirubin we are actively trying to prevent from reaching neurotoxic levels.
Clinical Pearl:Unconjugated bilirubin binds to albumin for transport to the liver. Anything that reduces albumin levels (sepsis, prematurity) or displaces bilirubin from albumin (certain medications like ceftriaxone, sulfonamides) increases the risk for neurotoxicity (even at lower total bilirubin levels).
Conjugated (Direct) Bilirubin
Water-soluble
Cannot cross the blood–brain barrier
Always pathologic when elevated
When you see an elevated direct bilirubin, think:
Cholestasis
Biliary obstruction
Liver disease
Infection (TORCH, bacterial sepsis)
Prolonged TPN exposure
Metabolic disorders (galactosemia, tyrosinemia)
🚩 Critical Point:Phototherapy does NOT treat conjugated hyperbilirubinemia and may actually causebronze baby syndrome: a grayish-brown discoloration that occurs when conjugated bilirubin and other pigments accumulate in the skin during phototherapy.
Direct bilirubin is considered elevated when it's >1 mg/dL or >20% of total bilirubin. Any infant with persistent jaundice beyond 2 weeks (term) or 3 weeks (preterm) needs a fractionated bilirubin to rule out cholestasis.
The Normal Bilirubin Pathway:
Let's walk through the normal process so you understand where things can go wrong:
Step 1: RBC Breakdown
Macrophages in the spleen, liver, and bone marrow break down hemolyzed RBCs:
Globin→ recycled as amino acids
Heme→ broken down by heme oxygenase into:
Iron(Fe²⁺) → recycled or stored
Carbon monoxide→ exhaled
Biliverdin→ green pigment
Step 2: Bilirubin Formation
Biliverdin is reduced by biliverdin reductase to formunconjugated bilirubin(UCB)—the lipophilic, potentially neurotoxic form.
Step 3: Transport to Liver
UCB binds to albumin (each albumin molecule can bind 2 bilirubin molecules) and travels through the bloodstream to the liver.
Step 4: Hepatic Uptake
At the liver sinusoids, UCB dissociates from albumin and enters hepatocytes.
Step 5: Conjugation
Inside hepatocytes, the enzymeUGT1A1(uridine diphosphate glucuronosyltransferase) conjugates bilirubin with glucuronic acid, making it water-soluble.
Why this matters:Preterm infants have significantly reduced UGT1A1 activity, which is why they develop jaundice at lower bilirubin loads and require lower treatment thresholds.
Step 6: Excretion
Conjugated bilirubin is excreted into bile → small intestine → oxidized to stercobilin → excreted in stool (gives stool its brown color).
A small amount (2%) is converted to urobilinogen, reabsorbed, and excreted in urine.
Physiologic vs Pathologic Jaundice
Physiologic Jaundice
Appearsafter 24 hours of life
Peaks day 3–5 (later in preterm infants)
Gradual rise and fall
Driven by normal newborn physiology
Total bilirubin typically <12-15 mg/dL in term infants
Use the AAP Clinical Practice Guideline for typical levels based on gestational age and age (in hours) of life
Pathologic Jaundice
Red flags every NICU nurse should recognize:
✋ Appears within the first 24 hours of life
✋ Rapid rise (>0.2–0.3 mg/dL/hr)
✋ Total bilirubin exceeding treatment thresholds
✋ Elevated direct bilirubin (>1 mg/dL or >20% of total)
✋ Associated anemia, infection, or poor feeding
✋ Jaundice persisting beyond 2 weeks (term) or 3 weeks (preterm)
Pathologic jaundice requires prompt evaluation and intervention!
Learn more about jaundice in my Certification Review Course
Why Preterm Infants Are at Higher Risk
Preterm babies are at increased risk for severe hyperbilirubinemia because they have:
Higher RBC turnover(shorter RBC lifespan)
Less albuminfor bilirubin binding (and lower binding affinity)
Immature blood–brain barrier(more permeable to bilirubin)
Reduced hepatic conjugation(less UGT1A1 enzyme activity)
Increased sensitivity to bilirubin neurotoxicity
Lower bilirubin levels can be more dangerous in preterm infants compared to term babies.
For Example:A 28-week infant with a total bilirubin of 10 mg/dL may require treatment, whereas a term infant might not need intervention until 15-17 mg/dL.Always use gestational age-specific nomograms.
Bilirubin Induced Neurologic Dysfunction and Kernicterus:
Neurologic injuries like Kernicterus occurs when unconjugated bilirubin crosses into the brain and deposits in areas like the basal ganglia, hippocampus, and brainstem nuclei.
Early signs NICU nurses may notice (Acute Bilirubin Encephalopathy):
Lethargy, poor feeding
Hypotonia ("floppy baby")
High-pitched cry
Poor Moro reflex
Temperature instability
Late findings (Chronic Bilirubin Encephalopathy):
Hypertonia, especially extensor posturing
Arching (opisthotonus)
Seizures
Permanent neurologic injury:
Choreoathetoid cerebral palsy
Auditory neuropathy/hearing loss
Upward gaze paralysis
Dental enamel dysplasia
This is why timely phototherapy, hydration, and escalation are essential neuroprotective interventions.
If you see ANY early signs of bilirubin encephalopathy, escalate immediately. Treatment may include intensive phototherapy, IV hydration, IVIG (for hemolytic disease), or emergent exchange transfusion.
Labs: Transcutaneous Bilirubin (TcB) & Total Serum Bilirubin
What is TcB?
Transcutaneous bilirubinometry measures the yellow color intensity in the skin using multi-wavelength reflectance. The device shines light into the skin and measures how much is reflected back. This estimates bilirubin levels and is typically taken from the forehead or sternum because these are areas with consistent skin thickness and minimal melanin variation.
Advantages of TcB
✅ Non-invasive - No heel stick = less pain, less stress, preserved skin integrity
✅ Quick results - Immediate reading at the bedside
✅ Trend monitoring - Easy to repeat frequently without causing distress
✅ Reduces unnecessary labs - Studies show TcB can reduce serum bilirubin testing by 20-30%
✅ Cost-effective screening - When used appropriately
✅ Useful for discharge screening - Can identify at-risk infants before leaving the hospital
Limitations of TcB
❌ Not accurate under phototherapy - Light therapy temporarily changes skin color and interferes with readings.
❌ Less accurate at higher bilirubin levels - Generally reliable up to ~15 mg/dL, but accuracy decreases as levels rise. Most guidelines recommend confirming with serum bili if TcB >12-15 mg/dL.
❌ Affected by skin pigmentation - Darker skin tones can lead to underestimation of bilirubin levels. Some studies show TcB may underestimate by 1-3 mg/dL in infants with darker skin.
❌ Interference from bruising - Cephalohematomas, bruising, or birth trauma can falsely elevate readings in that area.
❌ Gestational age limitations - Less validated in extremely preterm infants (<28 weeks). Use caution and lower threshold for confirming with serum levels.
❌ Cannot differentiate direct from indirect - TcB gives you a total bilirubin estimate only. If cholestasis is suspected, you need fractionated serum bilirubin.
❌ Variable accuracy between devices - Different brands may give slightly different readings.
Total Serum Bilirubin (TsB)
TsB is a laboratory measurement of bilirubin concentration in the blood.
Can be ordered as:
Total serum bilirubin (TsB) - Measures all bilirubin (conjugated + unconjugated)
Direct/conjugated bilirubin - Measures only the water-soluble, conjugated form
Indirect/unconjugated bilirubin - Calculated by subtracting direct from total (Total - Direct = Indirect)
Advantages of TsB
✅ Most accurate measurement - Gold standard for clinical decision-making
✅ Not affected by phototherapy - Can measure true bilirubin levels even during treatment (but turn the light off while you draw the sample!)
✅ Can fractionate bili - Gives direct/indirect breakdown, essential for diagnosing cholestasis
✅ Reliable across all skin tones - No racial or pigmentation bias
✅ Necessary for treatment decisions - Required before initiating phototherapy or considering exchange transfusion
✅ Accurate at high levels - Remains reliable even at bilirubin >20 mg/dL
Limitations of TsB
❌ Invasive - Requires blood draw
❌ Delayed results - Takes 30-90 minutes depending on lab processing
❌ More expensive - Lab processing costs more than TcB screening
❌ May cause anemia - Repeated blood draws in preemies add up (iatrogenic blood loss)
❌ Requires lab infrastructure - Not available in all settings (e.g., remote birthing centers)
Phototherapy:
When babies have elevated bilirubin levels one of our methods of treatment is phototherapy. Phototherapy works by converting unconjugated bilirubin into water-soluble isomers that can be excreted without conjugation.
Mechanism of Action:
Blue-green light (wavelength 430-490 nm) penetrates the skin and converts bilirubin through three reactions:
Configurational isomerization(4Z,15Z → 4Z,15E) - reversible
Structural isomerization(formation of lumirubin) - irreversible, most important
Photo-oxidation- breaks down bilirubin into smaller, water-soluble products
Lumirubin is the primary photoproduct excreted in bile and urine without needing hepatic conjugation.
Nursing considerations when caring for babies under phototherapy:
✅Maximize skin exposure- Remove all clothing except eye shields and diaper
✅Minimize interruptions- Cluster care, keep lights on during feeds if possible
✅Monitor temperature- Phototherapy can cause hypothermia (from radiant heat loss) or hyperthermia (from light heat)
✅Protect eyes and genitalia- Eye shields must cover the eyes completely (be sure not to obstruct the nares)
✅Watch for increased insensible water loss- May need increased fluid intake by 10-20%
✅Trend bilirubin levels- Assess rate of rise/fall, not just absolute number
✅Check for bronze baby syndrome- If direct bili is elevated
Dosing matters:Phototherapy is dose-dependent based on:
Irradiance(measured in μW/cm²/nm) - Higher is more effective
Surface area- More exposed skin = better results (use bili blankets in addition to overhead lights for intensive phototherapy)
Duration- Continuous is more effective than intermittent
Intensive phototherapy requires:
Irradiance ≥30 μW/cm²/nm at 460-490 nm wavelength
Maximum skin surface area exposure
Lights positioned close to infant (but not so close that it causes burns)
Exchange Transfusion:
Exchange transfusion is reserved for:
Severe hyperbilirubinemia unresponsive to intensive phototherapy
Signs of acute bilirubin encephalopathy
Rapidly rising bilirubin despite maximal phototherapy
Hemolytic disease with severe anemia
How it works:
Removes bilirubin-saturated blood and maternal antibodies (in hemolytic disease)
Replaces with fresh donor blood
Double volume exchange (160-180 mL/kg) removes ~85-90% of RBCs and reduces bilirubin by ~50%
This is a high-risk intervention requiring meticulous nursing preparation, monitoring, and teamwork.
Potential complications:
Electrolyte disturbances (hypocalcemia, hyperkalemia)
Thrombocytopenia
Metabolic acidosis
Infection
Cardiac arrhythmias
Necrotizing enterocolitis
Death (Rare with a 0.3-0.5% mortality risk)
Why we try to avoid it: Exchange transfusion carries significant risk, which is why aggressive phototherapy and early intervention for hemolytic disease (like IVIG) are so important.
Learn more about exchange transfusions here
NICU Nurse Takeaways (Save This Part)
✔Always clarify direct vs indirect bilirubin- They have completely different causes and treatments
✔Jaundice in the first 24 hours = pathologic until proven otherwise- Notify provider immediately
✔Preterm infants need lower treatment thresholds- Use gestational age-specific nomograms
✔Phototherapy is neuroprotection- Avoid interruptions unless absolutely necessary
✔Elevated direct bilirubin = stop and investigate- This needs a workup
✔Monitor for drugs that displace bilirubin- Ceftriaxone, sulfonamides, ibuprofen in jaundice infants bind to albumin and will displace bilirubin.
✔Trend the trend- Look at the rate of rise, what is the trend?
Every jaundiced baby deserves a systematic assessment:
When did it start?
How fast is it progressing?
Is it direct or indirect?
Are there risk factors for hemolytic disease?
Is the baby symptomatic?
As NICU nurses, we're often the first to notice subtle changes. Trust your assessment. Advocate for your patients. And remember phototherapy is a neuroprotective intervention that, when applied correctly and timely, prevents devastating outcomes.
You've got this.
Stay curious,
Amanda
© 2026 This content is for educational purposes and should complement, not replace, your unit's policies and procedures.
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Reference:
Kemper, A. R., Newman, T. B., Slaughter, J. L., Maisels, M. J., Watchko, J. F., Downs, S. M., Bundy, D. G., Stark, A. R., Bogen, D. L., Holmes, A. V., Feldman-Winter, L. B., Bhutani, V. K., Brown, S. R., Maradiaga Panayotti, G. M., Okechukwu, K., Rappo, P. D., & Russell, T. L. (2022).Clinical practice guideline revision: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics, 150(3), e2022058859.https://doi.org/10.1542/peds.2022-058859
Falke, M. (2025).The basics of neonatal hyperbilirubinemia. Neonatal Network, 44(1), 61–66.https://doi.org/10.1891/NN-2024-0051
Jnah, A. J., & O’Mara, K. (2023). The Hematopoietic System in Fetal and Neonatal Physiology for the Advanced Practice Nurse. Springer Publishing Company.
