Bilirubin pathway: red blood cells break down → heme becomes unconjugated (indirect) bilirubin, which is fat-soluble and travels bound to albumin → the liver conjugates it (enzyme UGT1A1) into conjugated (direct) bilirubin, which is water-soluble → excreted in bile to the intestine → most leaves in stool. Some is deconjugated in the gut and reabsorbed (enterohepatic circulation).

Why newborns become jaundiced: high red cell mass with a shorter red cell lifespan, immature hepatic conjugation, and increased enterohepatic circulation (sterile gut, delayed stooling). Jaundice becomes visible at a total serum bilirubin (TSB) of roughly 5 mg/dL (86 µmol/L) and progresses head to toe (cephalocaudal).

Danger: unconjugated bilirubin not bound to albumin can cross the blood–brain barrier and injure the basal ganglia, brainstem auditory nuclei, and cerebellum → acute bilirubin encephalopathy and, if permanent, kernicterus.

Types of jaundice

Hemolytic disease of the fetus and newborn (HDFN)

• Rh(D) incompatibility: Rh-negative mother previously sensitized to Rh-positive fetal cells makes anti-D IgG that crosses the placenta and destroys fetal red cells. Usually affects second and later pregnancies. Severe cases cause fetal anemia, hydrops fetalis (generalized edema, heart failure), and rapid postnatal jaundice.
• ABO incompatibility: typically a type O mother with a type A or B infant; naturally occurring anti-A/anti-B IgG. Can occur in the first pregnancy, is usually milder than Rh disease, and cannot be predicted reliably before birth.
• G6PD deficiency: an inherited red cell enzyme deficiency (X-linked; mostly males) causing hemolysis that may be sudden and severe; triggers include infection and oxidant exposures.
• Other causes: hereditary spherocytosis, cephalohematoma or bruising, polycythemia, infant of diabetic mother, sepsis.

• Yellow skin and sclerae; press the skin to blanch it and look in good natural light. Visual estimates are unreliable, especially in darker skin — confirm with a measurement
• Feeding: frequency, latch, swallowing, wet diapers and stools, weight loss from birth weight
• Hemolysis clues: jaundice in the first 24 hours, pallor, hepatosplenomegaly, edema (hydrops)
• Stool and urine color: pale (acholic) stools and dark urine point to conjugated hyperbilirubinemia

Acute bilirubin encephalopathy — progression

Kernicterus (chronic, permanent): athetoid cerebral palsy, sensorineural hearing loss / auditory neuropathy, impaired upward gaze, dental enamel dysplasia, intellectual disability.

AAP 2022 guideline (infants 35 weeks or more) — principles

• Measure TcB or TSB in every infant who looks jaundiced in the first 24 hours; measure bilirubin in all infants before discharge (or at 24–48 hours).
• Phototherapy and exchange-transfusion thresholds are hour-specific: the TSB is plotted against the infant's age in hours on curves chosen by gestational age and by whether neurotoxicity risk factors are present. The thresholds were raised modestly compared with 2004 to reduce unnecessary phototherapy.
• Neurotoxicity risk factors (these lower the thresholds): gestational age under 38 weeks, albumin below 3.0 g/dL (30 g/L), isoimmune hemolytic disease, G6PD deficiency or other hemolytic condition, sepsis, and significant clinical instability in the previous 24 hours.
• A separate hyperbilirubinemia risk assessment (e.g., younger gestational age, jaundice in the first 24 hours, a sibling who needed phototherapy, exclusive breastfeeding with suboptimal intake) guides follow-up timing.
• Escalation of care begins when TSB reaches 2 mg/dL (34 µmol/L) below the exchange-transfusion threshold: urgent NICU-level care, intensive phototherapy, frequent TSB checks, and preparation for exchange.
• Rapidly rising TSB (for example, faster than about 0.3 mg/dL per hour in the first day) suggests hemolysis.

Phototherapy

• Blue-green light (about 460–490 nm) converts bilirubin in the skin into water-soluble isomers excreted in bile and urine without conjugation.
• Intensive phototherapy uses high irradiance to the maximum body surface.
• Discontinue when TSB is at least 2 mg/dL (34 µmol/L) below the hour-specific threshold at which phototherapy was started; check for rebound after stopping (sooner for infants started early or with hemolysis).
• Home phototherapy is limited to well infants meeting strict criteria (e.g., 38 weeks or more, older than 48 hours, no neurotoxicity risk factors, no prior phototherapy).
• Adverse effects: insensible water loss, temperature instability, loose green stools, transient rash, separation from parents. Bronze baby syndrome occurs if phototherapy is used with conjugated hyperbilirubinemia.

Feeding: continue breastfeeding (at least 8–12 feeds in 24 hours). Routine water or dextrose water supplementation is not recommended. Supplement with expressed milk or formula when intake is inadequate or weight loss is excessive; give IV fluids only if dehydrated or during escalation of care.

Intravenous immune globulin (IVIG): for isoimmune hemolytic disease when TSB reaches or exceeds the escalation-of-care threshold; it reduces hemolysis. Adverse effects: allergic reactions/anaphylaxis, fluid overload, hemolysis; an association with necrotizing enterocolitis has been reported — monitor abdomen and vital signs.

Exchange transfusion: double-volume exchange through umbilical catheters removes bilirubin and maternal antibody-coated cells and corrects anemia. Given slowly in small aliquots with continuous cardiorespiratory monitoring. Complications: hypocalcemia (citrate), hypoglycemia, hyperkalemia, thrombocytopenia, dysrhythmias, infection, thrombosis, NEC, air embolism.

Prevention of Rh disease: give Rh(D) immune globulin (RhIG) IM to the Rh-negative, unsensitized mother at about 28 weeks, within 72 hours after birth of an Rh-positive infant, and after sensitizing events (bleeding, trauma, amniocentesis, miscarriage, ectopic pregnancy; for pregnancy loss before 12 weeks, current ACOG guidance allows omitting RhIG). The postpartum dose may be adjusted by a fetal-cell quantification test. RhIG is never given to the infant and is useless once the mother is already sensitized. Adverse effects are mainly injection-site pain and rare allergy; it is a blood product (obtain consent, verify identity).

Listed in priority order.

1. Recognize neurologic danger — any lethargy, poor suck, hypotonia, high-pitched cry, arching, or fever in a jaundiced infant is an emergency; notify the provider immediately
2. Early detection
   • Measure bilirubin (TcB/TSB) at once if jaundice appears in the first 24 hours
   • Plot every value by age in hours on the correct AAP curve; know the infant's risk factors
3. Phototherapy care
   • Maximize exposed skin: infant naked or with a minimal diaper; reposition as ordered
   • Opaque eye protection — check placement often; remove during feeding and skin-to-skin to assess eyes (discharge, irritation) and allow interaction
   • Lights at the manufacturer-recommended distance; no lotions or oils (burn risk)
   • Monitor temperature (overheating and cooling), and hydration: urine output (wet diapers), daily weight, stools
   • Turn lights off briefly when drawing blood for TSB; do not rely on TcB during treatment
   • Continue feeding on schedule; interruptions for breastfeeding are acceptable unless TSB is near the escalation zone
4. Exchange transfusion support — baseline and ongoing vital signs, glucose, calcium, strict aseptic line care, emergency equipment, accurate recording of volumes in and out
5. Feeding support — lactation help, assess latch and milk transfer, supplementation as ordered
6. Family support — explain treatment and that the green loose stools are expected

• Feed often: 8–12 times per day; expect increasing wet diapers and yellow stools by day 4–5
• Before discharge, know the follow-up appointment date and time — bilirubin often peaks after discharge
• Call promptly if jaundice spreads to the legs, the baby is hard to wake, feeds poorly, has a high-pitched cry or arching, or has pale stools or dark urine
• Sunlight exposure is not a safe treatment for jaundice
• G6PD deficiency: avoid naphthalene mothballs, fava beans once solids start, and specific oxidant medicines; check before giving any new medicine or herbal product, and tell every health worker about the diagnosis
• Rh-negative mothers: explain why RhIG is given and keep a record of doses

• Jaundice in the first 24 hours = pathologic until proven otherwise (think hemolysis) — measure bilirubin immediately
• Jaundice progresses head to toe; visual assessment is unreliable — use TcB/TSB
• AAP 2022: thresholds are hour-specific, based on gestational age and neurotoxicity risk factors
• Escalation of care at 2 mg/dL below the exchange threshold; stop phototherapy when TSB is 2 mg/dL below the starting threshold
• Phototherapy: maximize skin exposure, eye shields, monitor temperature and hydration, no lotions; loose green stools are expected
• Breastfeeding jaundice → feed more, do not give water or dextrose water
• ABO: mother O, infant A or B, can occur in the first pregnancy, usually mild
• Rh: mother Rh-negative and sensitized, worsens in later pregnancies; RhIG at 28 weeks and within 72 hours postpartum
• Early encephalopathy: lethargy, hypotonia, poor suck; late: hypertonia, opisthotonos
• Exchange transfusion removes bilirubin and antibodies; watch for hypocalcemia
• Pale stools and dark urine → check direct bilirubin (biliary atresia)