Jaundice

• Jaundice <24hr:

  • Always pathological
  • Haemolytic disorders:
  • Rh incompatibility
  • ABO incompatibility
  • G6PD deficiency
  • Spherocytosis
  • Thalassaemia
  • Pyruvate kinase deficiency
  • Sepsis - congenital infection - CMV, congenital rubella, GBS
• Jaundice 24hr-2wks:

  • Physiological jaundice - increased risk if preterm, breastfed or significant bruising
  • Infection/sepsis
  • Hepatitis
  • Haemolytic disease
  • Crigler-Najjar syndrome
• Jaundice >2wks:

  • Unconjugated:
  • Physiological
  • Sepsis
  • Hypothyroidism
  • Haemolytic disease
  • Gilbert's syndrome
  • High GI obstruction e.g. pyloric stenosis
  • Conjugated:
  • Bile duct obstruction e.g. biliary atresia
  • Neonatal hepatitis
  • Cystic fibrosis
  • Galactosaemia/inborn errors of metabolism
• Jaundice is “prolonged” when it lasts longer than would be expected in physiological jaundice. This is:

  • More than 14 days in full term babies
  • More than 21 days in premature babies
• Overview:

  • Yellow discolouration of the sclerae and skin due to excess bilirubin
  • Neonatal jaundice is extremely common - 60% of term babies and 80% of preterm babies will develop jaundice
  • Most cases are not caused by an underlying pathology
  • Can indicate serious disease and may result in long-term morbidity and even mortality if left untreated
• Physiology of bilirubin metabolism:

  • Bilirubin produced from the breakdown of RBCs - most unconjugated bilirubin circulates bound to albumin but some is free - lipid soluble and can cross BBB
  • Liver UGT converts to conjugated bilirubin - water soluble so cannot cross BBB
  • Conjugated bilirubin transported to small intestines - some converted back to unconjugated bilirubin
  • Remaining conjugated bilirubin is metabolised by intestinal bacteria to produce urobilinogen and stercobilinogen
  • Urobilinogen oxidised to urobilin - yellow urine
  • Stercobilinogen oxidised to stercobilin - brown faeces
• Physiological jaundice:

  • There is a high concentration of RBC in the foetus and neonate - they are more fragile
  • Foetus and neonate also have less developed liver function
  • Foetal RBC break down more rapidly - releasing large amounts of bilirubin - normally excreted by placenta
  • Leads to normal rise in bilirubin shortly after birth, causing mild jaundice from 2-7 days of age
  • Usually resolves completely by 10 days
  • Most babies remain otherwise healthy and well
• Some neonates are more prone to physiological jaundice:

  • Preterm - tend to have higher bilirubin levels and more prolonged jaundice
  • Breastfed - components inhibit ability of liver to process bilirubin, more likely to become dehydrated leading to slow passage of stools and increased intestinal absorption of bilirubin - encourage to still breastfeed
  • Significant bruising or cephalohaematoma (blood collection between scalp and skull)
• Unconjugated jaundice causes:

  • Haemolytic
  • Endocrine or metabolic
  • Neonatal sepsis
• Unconjugated jaundice haemolytic causes:

  • Haemolytic disease of the newborn - Rh or ABO incompatibility
  • Hereditary spherocytosis - inherited disease causing RBCs to be spherical with reduced lifespan
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency - X linked recessive condition where lack of G6PD makes RBCs susceptible to oxidative damage and haemolysis - can cause severe jaundice
• Unconjugated jaundice endocrine/metabolic causes:

  • Gilbert's syndrome - autosomal recessive disorder with reduced UGT enzyme activity - mild episodes of jaundice throughout life
  • Crigler-Najjar syndrome - rare autosomal recessive disorder - no functioning UGT - severe, prolonged jaundice that often results in neurological damage and death within 1 year
  • Congenital hypothyroidism
  • Galactosaemia and other inborn errors of metabolism (may also cause conjugated jaundice)
• Conjugated jaundice causes:

  • Usually presents after 2 weeks
  • Biliary atresia
  • Neonatal hepatitis e.g. cytomegalovirus, hepatitis B, rubella, HSV
  • Galactosaemia and other inborn errors of metabolism
• Risk factors for significant hyperbilirubinaemia requiring treatment:

  • Gestational age <38 weeks
  • Previous sibling with neonatal jaundice requiring phototherapy
  • Mother's intention to breastfeed exclusively
  • Jaundice within first 24 hours of life
• Important areas to cover in history:

  • Family history - inherited disease (e.g. G6PD deficiency, liver disease), previous sibling with jaundice (suggests higher change of haemolytic disease of newborn)
  • Pregnancy history - congenital infections, diabetes (increases risk of jaundice), maternal drugs (sulfonamides interfere with bilirubin-albumin binding), blood group and any known antibodies
  • L+D - birth trauma
  • Feeding history - breast or formula feeding, intake (poor intake increases bilirubin), vomiting (sign of sepsis or galactosaemia)
• Clinical exam:

  • Thorough systems exam
  • Should be naked and examined in bright, natural light
  • Jaundice most obvious in sclerae and gums - skin can be lightly pressed which may reveal jaundice on blanched skin
  • Assess if baby if clinically well and whether there are any signs of infection or bilirubin encephalopathy
  • Inspect nappy for stools and urine - pale, chalky stools and dark urine suggest conjugated jaundice
• Jaundice in the first 24 hours of life and conjugated jaundice are always pathological and require urgent investigation for an underlying cause.
• Measuring bilirubin:

  • Transcutaneous bilirubinometry - evaluated light absorption through skin over forehead or sternum - not as accurate but non-invasive
  • Serum bilirubin - if visibly jaundiced <24hrs of life, gestational age <35 weeks, to confirm high transcutaneous level, monitoring levels during treatment - can request split bilirubin to get ratio of conjugated/unconjugated
• Investigations for babies who require treatment for jaundice:

  • Blood packed cell volume (PCV) - degree of anaemia or polycythaemia
  • Blood group of mother and baby
  • Direct antiglobulin test (DAT, Coombs) - positive DAT suggests autoimmune (haemolytic disease of newborn), negative suggests non immune haemolysis (spherocytosis, G6PD deficiency)
• Other laboratory investigations to consider include:

  • Full blood count and blood film: to assess the morphology of the RBCs (e.g. in hereditary spherocytosis)
  • G6PD levels: especially if there is a positive family history or in Mediterranean, Asian or African ethnicity
  • Blood, urine and/or cerebrospinal fluid cultures: if there are signs of infection
• More specialist tests may be needed to diagnose certain diseases, these include:

  • Liver ultrasound or percutaneous biopsy: biliary atresia
  • Genetic testing: Gilbert’s syndrome or Crigler-Najjar syndrome
  • Urinary reducing substances: galactosaemia
• When to treat:

  • Based on treatment threshold graphs - different graphs for different gestations and preterm babies have a lower threshold for starting treatment
  • Age of the baby is plotted on the x-axis and total bilirubin level on the y-axis, if total bilirubin reaches the threshold on the chart, they need to commence treatment
  • Different treatment thresholds for phototherapy and exchange transfusion (higher threshold)
• Management:

  • Phototherapy - placed under blue-green light which converts neurotoxic unconjugated bilirubin to lumirubin (water soluble isomer) - readily excreted in bile and urine
  • Phototherapy can be given via overhead light or blanket that wraps around the baby
  • Exchange transfusion - small volume of baby's blood is removed as donor blood is injected, repeated many times. Lowers bilirubin but also removes antibodies (haemolytic disease of newborn)
  • Exchange transfusions have high rate of complications - reserved for severe cases
• Bilirubin encephalopathy (kernicterus)

  • Complication of high levels of unconjugated bilirubin (neurotoxic) - lipid soluble so crosses BBB
  • Initially presents with lethargy, hypotonia and poor suck reflex
  • Progresses to hypertonia, opisthotonus (abnormal position, arching of back), fever, seizures and a high-pitched cry
  • Early damage can be reversed
  • If raised bilirubin pronounced or prolonged it can lead to cerebral palsy, sensorineural hearing loss or cognitive impairment