Paediatrics chapters
Neonatal jaundice
Why newborns become yellow, how to separate physiological from pathological jaundice, Rh and ABO haemolytic disease, breast milk jaundice, kernicterus, and when to use phototherapy or exchange transfusion.
- Most newborn jaundice is physiological: unconjugated, appears after 24 hours, peaks on days 3-5 and settles within 1 week (term) or 2 weeks (preterm).
- Jaundice is pathological if it appears in the first 24 hours, rises more than 5 mg/dL a day, exceeds the age-specific threshold, has a direct fraction above 2 mg/dL, or lasts beyond 2 weeks; the commonest serious causes are Rh and ABO haemolysis, G6PD deficiency and sepsis.
- High unconjugated bilirubin can cause kernicterus; prevent it with phototherapy (blue light) and double-volume exchange transfusion when levels reach the treatment lines.
On this page
Overview
Jaundice is the commonest problem of the first week. About 60% of term and 80% of preterm babies become visibly yellow, with bilirubin above 5 mg/dL, in the first week. Most cases are harmless, but high unconjugated bilirubin can enter the brain and cause kernicterus, and conjugated jaundice may signal liver disease such as biliary atresia.
The task is to find the few babies who need investigation and treatment.
Bilirubin metabolism in the newborn
- Red cells break down; haem becomes biliverdin and then unconjugated (indirect) bilirubin. Each gram of haemoglobin yields about 34 mg of bilirubin.
- Unconjugated bilirubin is fat-soluble and travels bound to albumin. Bound bilirubin does not enter the brain; unbound bilirubin can.
- The liver takes it up and glucuronyl transferase conjugates it into water-soluble (direct) bilirubin, which is excreted in bile.
- In the gut, bacteria convert it to urobilinogen and stercobilinogen. Some is deconjugated and reabsorbed (enterohepatic circulation).
Why newborns are jaundiced
- More bilirubin: high haemoglobin (about 18-22 g/dL), mostly fetal haemoglobin with a shorter red cell life (60-70 days).
- Less conjugation: immature glucuronyl transferase, poor liver uptake.
- More reabsorption: increased enterohepatic circulation (sterile gut, slow feeding).
Drugs that displace bilirubin from albumin (sulphonamides, ceftriaxone, high-dose vitamin K) and acidosis, hypoxia, sepsis and hypoalbuminaemia raise the risk of kernicterus at a lower bilirubin level.
Classification
| Type | Features |
|---|---|
| Unconjugated (indirect) | Physiological or pathological; the type that causes kernicterus |
| Conjugated (direct) | Direct bilirubin above 2 mg/dL or more than 20% of total; always pathological; sign of hepatobiliary disease |
Physiological versus pathological jaundice
| Feature | Physiological | Pathological |
|---|---|---|
| Onset | After 24 hours | Within the first 24 hours |
| Rise | Less than 5 mg/dL a day | More than 5 mg/dL a day (Nelson: more than 0.5 mg/dL per hour) |
| Peak | Term: about day 3, no more than about 12-13 mg/dL; preterm: about day 5, up to about 15 mg/dL | Term peak above 13 mg/dL (Nelson) or above the treatment line |
| Type | Unconjugated | Direct fraction above 2 mg/dL at any time (Nelson uses above 1.5 mg/dL) |
| Duration | Gone by 1 week (term), 2 weeks (preterm) | Persists beyond 14 days |
| Baby | Well | Unwell: pallor, hepatosplenomegaly, poor feeding, vomiting, lethargy, apnoea, pale stools, dark urine |
Physiological jaundice is a diagnosis of exclusion.
Jaundice in the first 24 hours is always pathological; the usual cause is haemolysis (Rh or ABO incompatibility, G6PD deficiency) or congenital infection.
For time of onset think "Day 1 haemolysis, Days 2-5 physiological, after 2 weeks look for the liver, thyroid and breast milk."
Causes by time of onset
| Onset | Main causes |
|---|---|
| First 24 hours | Rh or ABO haemolytic disease, G6PD deficiency, spherocytosis, congenital (TORCH) infection |
| Days 2-7 | Physiological, breastfeeding jaundice, sepsis, haemolysis, cephalhaematoma and bruising, polycythaemia, infant of diabetic mother, prematurity |
| After 2 weeks (prolonged) | Breast milk jaundice, hypothyroidism, galactosaemia, sepsis and UTI, prematurity, biliary atresia, neonatal hepatitis, Crigler-Najjar syndrome, pyloric stenosis |
Causes by mechanism (unconjugated)
- Overproduction (haemolysis): Rh, ABO and minor group incompatibility; G6PD deficiency (common in Pakistan; drugs given to the mother such as sulphonamides, antimalarials and nitrofurantoin can trigger it); spherocytosis; pyruvate kinase deficiency; sepsis.
- Extravasated blood: cephalhaematoma, bruising, intracranial bleeding.
- Polycythaemia (venous haematocrit above 65%): IDM, SGA, delayed cord clamping, twin-to-twin transfusion.
- Increased enterohepatic circulation: poor feeding, bowel obstruction, pyloric stenosis.
- Reduced conjugation: Crigler-Najjar (types I and II), Gilbert syndrome, hypothyroidism, breast milk jaundice.
Blood-group interactions
Rh haemolytic disease
- Mother Rh-negative, baby Rh-positive.
- Fetal cells enter the mother's blood (at delivery, miscarriage, abortion, bleeding, procedures) and sensitise her. The first response produces mainly IgM, which does not cross the placenta.
- In a later pregnancy with an Rh-positive baby, IgG anti-D crosses the placenta and destroys fetal red cells.
- So Rh disease is rare in the first pregnancy and gets worse with each pregnancy.
- Severity spectrum: mild anaemia and jaundice, through severe jaundice in the first day, to hydrops fetalis (severe anaemia, heart failure, generalised oedema, ascites) and stillbirth.
- Direct Coombs test strongly positive.
ABO haemolytic disease
- Mother group O, baby group A or B (O mothers more often make IgG anti-A and anti-B).
- ABO incompatibility occurs in 20-25% of pregnancies, but haemolytic disease in only about 1 in 10 of these.
- Usually milder than Rh disease because most natural anti-A/anti-B is IgM, fetal A and B antigens are weak, and soluble A and B substances in tissues absorb the antibody.
- Can occur in the first-born baby, because the antibodies are naturally present.
- Direct Coombs test is weakly positive or even negative; spherocytes on the film.
ABO incompatibility with the mother protects against Rh sensitisation: fetal cells that enter her blood are destroyed by her anti-A or anti-B before they can sensitise her.
| Feature | Rh disease | ABO disease |
|---|---|---|
| Mother | Rh-negative | Group O |
| First pregnancy | Rarely affected | Can be affected |
| Severity | Often severe; hydrops possible | Usually mild |
| Coombs test | Strongly positive | Weak or negative |
| Prevention | Anti-D to the mother | None |
Prevention of Rh disease
Give anti-D immunoglobulin to the Rh-negative unsensitised mother within 72 hours of delivering an Rh-positive baby (and after miscarriage, abortion and other sensitising events).
Anti-D is useless once the mother is already sensitised; it must be given before she makes her own antibody.
Breast milk and breastfeeding jaundice
| Feature | Breastfeeding jaundice | Breast milk jaundice |
|---|---|---|
| Cause | Too little milk (dehydration, slow stooling, more enterohepatic circulation) | A factor in the milk that inhibits conjugation |
| Onset | First week | Late: rises from the end of the first week, peaks at 2-3 weeks |
| How common | About 13% of breastfed babies | About 2% of breastfed term babies |
| Clues | Weight loss over 10%, few wet nappies, few stools | Well, thriving baby |
| Management | Feed more often (more than 10 times a day), support breastfeeding | Continue breastfeeding; phototherapy if very high |
- If breastfeeding is stopped for a short time in breast milk jaundice, bilirubin falls quickly within 48 hours and does not rise to the same level on restarting. This is rarely needed.
- Kernicterus is rare with breast milk jaundice.
In ABO disease the direct Coombs test can be negative; a group O mother, a group A or B baby, spherocytes and a high reticulocyte count still make the diagnosis.
Assessment
- Look in daylight; press the skin lightly to see the yellow colour. Jaundice spreads from the face downwards to the trunk and limbs as levels rise; it becomes visible at about 5-7 mg/dL (Nelson: 5-10 mg/dL, compared with 2-3 mg/dL in adults).
- Yellow palms and soles mean severe jaundice (IMNCI: refer urgently).
- Check stool and urine colour: pale stools and dark urine mean conjugated jaundice.
- Look for pallor, bruising, cephalhaematoma, hepatosplenomegaly, signs of sepsis, plethora, microcephaly and chorioretinitis (TORCH).
Investigations
| First-line | What it shows |
|---|---|
| Total and direct bilirubin | Level and type |
| Blood groups of mother and baby | Rh or ABO incompatibility |
| Direct Coombs test on the baby | Positive in immune haemolysis |
| Haemoglobin, reticulocytes, blood film | Haemolysis (low Hb, high retics, spherocytes, nucleated red cells); polycythaemia |
Second-line: G6PD assay, blood and urine cultures, thyroid function, urine reducing substances (galactosaemia), TORCH serology, liver function, abdominal ultrasound, HIDA scan, liver biopsy.
Management of unconjugated jaundice
Plot the total serum bilirubin against the baby's age in hours on a gestation-specific treatment chart (Akbar refers to the NICE graphs), which give separate phototherapy and exchange transfusion lines. Sick, preterm and haemolysing babies are treated at lower levels.
Rule-of-thumb thresholds (Nelson)
| Treatment | Level of indirect bilirubin |
|---|---|
| Phototherapy, term baby | Start at about 16-18 mg/dL; lower in preterm babies |
| Exchange, haemolysis, baby over 2000 g | About 20 mg/dL |
| Exchange, well term baby with physiological or breast milk jaundice | Only above about 25 mg/dL |
| Exchange, other babies | Birth weight in grams ÷ 100 (for example 15 mg/dL at 1500 g) |
| Exchange, baby under 1000 g | Rarely needed below about 10 mg/dL |
Birth weight 1800 g
Estimated exchange level = 1800 ÷ 100 = 18 mg/dL indirect bilirubin
Phototherapy
Mechanism: blue light (420-470 nm in Akbar; Nelson 425-475 nm) is absorbed by bilirubin in the skin and converts it into water-soluble isomers (photoisomers and lumirubin) that are excreted in bile and urine without needing conjugation.
Practice:
- Expose as much skin as possible; cover the eyes; turn the baby regularly.
- Continue feeding; give extra fluid with older units (they increase water loss).
- Check bilirubin every 12-24 hours (more often in haemolysis).
- Stop when bilirubin is about 3 mg/dL below the phototherapy line and risk factors have settled; in haemolytic disease check again about 24 hours later for rebound.
- Phototherapy has failed if bilirubin does not fall by 1-2 mg/dL within 4-6 hours of intensive treatment.
Side effects: overheating or hypothermia, dehydration, loose green stools, skin rash, eye damage if not shielded, separation from the mother, and bronze baby syndrome (grey-brown skin when phototherapy is given to a baby with conjugated jaundice).
Phototherapy treats unconjugated bilirubin only. In conjugated jaundice it is not useful and causes bronze baby syndrome.
Exchange transfusion
Aims: remove bilirubin, remove antibody-coated red cells and circulating antibody, and correct anaemia.
Indications:
- Bilirubin at or above the exchange line for age and gestation.
- Bilirubin rising more than 1 mg/dL per hour despite phototherapy, or phototherapy failing.
- Signs of acute bilirubin encephalopathy at any level.
- At birth in haemolytic disease (Akbar): Hb below 12 g/dL, bilirubin above 5 mg/dL, positive Coombs test, reticulocytes above 10%.
- Worsening anaemia despite control of bilirubin.
- Previous sibling who needed exchange or died of kernicterus.
In exam questions a level of about 20 mg/dL in a term baby with haemolysis is the usual exchange answer; in preterm babies it is much lower (Akbar: 10-15 mg/dL).
Technique: a double-volume exchange (2 × 80 mL/kg = 160 mL/kg) through the umbilical vein, in aliquots of 10-20 mL, using fresh blood (less than 5 days old).
Choice of blood:
- Rh disease: group O Rh-negative blood (or the baby's ABO group with Rh-negative blood), cross-matched against the mother.
- ABO disease: group O red cells (Rh-compatible) suspended in AB plasma, so no anti-A or anti-B is given.
Baby weight 3.0 kg; blood volume about 80 mL/kg
Double-volume exchange = 2 × 80 × 3.0 = 480 mL
Complications: hypocalcaemia, hyperkalaemia (old blood), hypoglycaemia, volume overload, arrhythmias and cardiac arrest, air embolism, portal vein thrombosis, NEC, infection, thrombocytopenia, hypothermia.
Other treatments
- Intravenous immunoglobulin (IVIG) for immune (ABO or Rh) haemolysis, and albumin infusion for low albumin, may help (Akbar).
- Phenobarbitone induces glucuronyl transferase (used in Crigler-Najjar type II and to promote bile flow in cholestasis).
- Adequate feeding; treat sepsis, hypothyroidism and other causes.
Kernicterus (bilirubin encephalopathy)
Definition: brain damage from deposition of unconjugated bilirubin in the basal ganglia, brainstem nuclei (including the oculomotor and auditory nuclei) and hippocampus.
- In term babies kernicterus is uncommon below about 20-25 mg/dL and becomes more frequent above 25 mg/dL (Nelson); Akbar notes about 30% of babies with levels of 25-30 mg/dL develop it. It occurs at lower levels in preterm (Nelson: below 10 mg/dL in babies under 1000 g), acidotic, hypoxic, hypothermic, hypoglycaemic or septic babies and with bilirubin-displacing drugs.
| Phase | Features |
|---|---|
| Acute (early) | Deep jaundice, lethargy, poor feeding, poor Moro, hypotonia; usually after day 4 |
| Acute (advanced) | High-pitched cry, hypertonia with opisthotonus and retrocollis, fever, seizures, apnoea; many die |
| Chronic | Choreoathetoid cerebral palsy, high-frequency sensorineural deafness, upward gaze palsy, dental enamel defects, learning difficulty |
Kernicterus is irreversible; it is prevented, not treated, by timely phototherapy and exchange transfusion. Survivors need hearing tests.
Conjugated and prolonged jaundice
Prolonged jaundice is jaundice lasting more than 2 weeks. Always check the direct bilirubin, stool colour and thyroid function.
Causes of conjugated jaundice:
- Obstruction: biliary atresia, choledochal cyst, inspissated bile.
- Liver cell injury: neonatal hepatitis, sepsis, TORCH, hepatitis B; metabolic (galactosaemia, alpha-1 antitrypsin deficiency); TPN cholestasis.
Biliary atresia:
- Jaundice with pale (acholic) stools, dark urine and a firm liver; the baby often looks well at first.
- Ultrasound: absent or small gallbladder; HIDA scan shows no excretion into the gut; liver biopsy shows bile duct proliferation with bile plugs.
- Kasai portoenterostomy before 6-8 weeks gives the best result; later cases may need liver transplantation.
A thriving, breastfed baby with prolonged jaundice still needs a split bilirubin and a stool colour check. Missing biliary atresia beyond 8 weeks worsens the outcome.
Expect: physiological jaundice after 24 hours peaking on days 3-5 and gone by 1 or 2 weeks; jaundice in the first day as pathological; rise of more than 5 mg/dL a day and direct bilirubin above 2 mg/dL; Rh disease in later pregnancies versus ABO disease in a group O mother that can affect the first-born; Coombs test strength; anti-D within 72 hours; breast milk versus breastfeeding jaundice; phototherapy mechanism with blue light and bronze baby syndrome; exchange transfusion indications and double-volume technique; choice of blood; kernicterus in the basal ganglia with choreoathetosis and deafness; prolonged jaundice with pale stools pointing to biliary atresia and the Kasai operation.
Quick revision
- Visible jaundice at 5-7 mg/dL; spreads face to feet.
- Physiological: after 24 h, under 5 mg/dL/day rise, peak days 3-5, gone by 1 week (term) or 2 weeks (preterm).
- Pathological: day 1, fast rise, high peak, direct above 2 mg/dL, beyond 14 days.
- Day 1: haemolysis (Rh, ABO, G6PD).
- Rh: Rh-negative mother, later pregnancies, strong Coombs, hydrops; anti-D within 72 h.
- ABO: group O mother, first-born possible, mild, weak Coombs.
- Phototherapy 420-470 nm; eyes covered; bronze baby if conjugated.
- Exchange: 160 mL/kg via umbilical vein; O Rh-negative for Rh disease; O cells with AB plasma for ABO disease.
- Kernicterus: basal ganglia; choreoathetosis, deafness, upward gaze palsy.
- Pale stools + prolonged jaundice: biliary atresia; Kasai before 6-8 weeks.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why is Rh disease rare in a first pregnancy?
The mother is usually sensitised only at the first delivery, and the IgG antibodies that cross the placenta are made in later pregnancies.
Why can ABO disease affect a first baby?
Group O mothers already have anti-A and anti-B antibodies, some of them IgG, without needing prior sensitisation.
How does phototherapy work?
Blue light converts unconjugated bilirubin in the skin into water-soluble forms that are excreted in bile and urine without conjugation by the liver.
What is the difference between breast milk and breastfeeding jaundice?
Breastfeeding jaundice comes from too little milk in the first week, while breast milk jaundice comes from a factor in the milk and peaks at 2-3 weeks in a thriving baby.
Which test should be done first in a baby jaundiced beyond two weeks?
A split (direct and indirect) bilirubin with a look at the stool colour, plus thyroid function, to pick up conjugated causes such as biliary atresia.