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live births ( 95 % CI 6034 to 7385 )
in Africa , the range is from 3.5 ( 2.0-6.0 ) per 100,000 live births in Europe . 10 The estimated incidence of kernicterus in Australia is 0.35 per 100,000 live births based on follow-up of the aforementioned surveillance study cohort . 9 This compares with international estimates of 0.4 to 2.7 per 100,000 live births . 11-33 Extrapolated to the Australian population , this would infer an estimate of between one and seven cases of kernicterus a year nationally .
Major pathophysiological causes or associations with severe hyperbilirubinaemia include ABO and other blood group incompatibility , G6PD deficiency , infection and haemolysis of other causes including spherocytosis . Other factors associated with poor outcomes included prematurity , male gender , ethnicity , breastfeeding and early hospital discharge . 34
How does neonatal jaundice evolve ?
Clinical neonatal jaundice occurs
when there is an imbalance in bilirubin production , conjugation and elimination . Unconjugated bilirubin is a catabolic product of the haem porphyrin ring that predominantly results from the destruction of red blood cell haemoglobin within the reticuloendothelial system . Unconjugated bilirubin binds to albumin and is transported to the liver where it is converted to conjugated bilirubin . Conjugated bilirubin is water-soluble and can thus be excreted via urine and fae-
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US Department of Health , Education and Welfare / bit . ly / 40EgPDC |
US Department of Health , Education and Welfare / bit . ly / 3KgBgRw |
Figure 1 . Bilirubin staining in the brain .
Figure 2 . Opisthotonus .
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Box 2 . Risk factors for severe unconjugated neonatal jaundice
• Maternal red cell antibodies ( rhesus or other ).
• Infants with a positive direct antiglobulin test .
• Infants with accumulation of extravascular blood ( cephalohaematoma , see figure 7 , bruising ).
• Prematurity .
• Unwell infants ( sepsis / viral infections / metabolic disease ).
• Elevated haemoglobin and haematocrit .
• Dehydration .
• Poor feeding .
• Breastfeeding .
• Bowel obstruction , including delayed passage of meconium .
• Family history of previous sibling with haemolytic disease of the newborn , sickle cell anaemia , G6PD deficiency .
• Low Apgar score .
• Asphyxia .
• Low albumin .
• Maternal diabetes .
• Macrosomia .
• Asian or Mediterranean ethnicity .
INVESTIGATIONS
ONE approach healthcare providers have taken to reduce the incidence and risk of severe neonatal jaundice and kernicterus is universal newborn bilirubin level screening . Currently , universal screening for neonatal jaundice is not consistently mandated or recommended
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ces ( see figure 3 ). |
in Australia , although it is prac- |
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Unconjugated neonatal hyperbilirubinaemia is often clinically |
Box 1 . Classification of neonatal jaundice |
factors frequently cited in local unitbased guidelines include those listed |
tised in some individual neonatal ICUs . In the US , the American |
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categorised according to the timing of presentation and severity . Such categorisation of the aetiology of neonatal jaundice is only possible retrospectively ; therefore , promptly and thoroughly manage any neonates presenting with jaundice and proactively investigate . Unconjugated neonatal jaundice is readily treatable with phototherapy and , in most circumstances , will be the only treatment required .
Box 1 offers a classification of neonatal jaundice .
Breastfeeding
Despite the many benefits of breastfeeding , there is an association with an increased risk of neonatal jaundice . 35 Postulated mechanisms are complex and include the inhibition of hepatic excretion of bilirubin by breastmilk , increased intestinal absorption of bilirubin facilitated by
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• Early onset : — The first 24-48 hours after birth and / or rapidly rising or high levels of unconjugated hyperbilirubinaemia are concerning and require swift treatment and investigation for underlying pathological causes .
— ‘ Pathological jaundice ’ includes neonatal jaundice due to blood group incompatibility ( ABO or rhesus blood group incompatibility ) and other causes such as sepsis , bruising , metabolic disorders or obstruction .
• Idiopathic or physiological jaundice : — This typically presents later postnatally , at around day three and peaks on days 5-7 .
— Newborn term babies in this context commonly have bilirubin levels exceeding the typical upper limit of normal for an adult in the first week after birth and this may persist for 10 days before subsiding .
• Prolonged unconjugated jaundice :
— This is more common in breastfed neonates beyond 14 days of age in a term neonate , but exclude other important causes ( such as obstructive jaundice , biliary atresia , endocrine or metabolic dysfunction and / or infection ) before making the diagnosis of ‘ breastmilk jaundice ’. 35
is unusual and warrants timely and thorough assessment and investigation , particularly to exclude biliary atresia ( see figures 4 and 5 ). 36 ‘ Obstructed ’ or conjugated jaun-
UNCONJUGATED NEONATAL JAUNDICE
THE risk of severe neonatal hyperbilirubinaemia
relates to the baby ’ s
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in box 2 .
CLINICAL ASSESSMENT
ASSESSMENT of a jaundiced baby
includes an initial evaluation of the systemic wellness or otherwise of the neonate . ‘ Red flags ’ include any worrying vital signs or abnormal behaviour , jaundice within the first 48 hours after birth and / or dark urine and pale stools . Urgently refer these infants to the local acute paediatric service . A detailed history , including the identification of factors associated with increased risk of neonatal jaundice , will influence planned investigations and the phototherapy treatment threshold . Relevant history includes family history , maternal blood group , antibodies and infection serology , birth history ( mode of delivery , the use of instruments or a history of trauma ), age of onset
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Academy of Pediatrics recommends universal screening as do the Canadian Paediatric Society and the Swedish Paediatric Society . 43-45 The UK ’ s National Institute for Health and Care Excellence ( NICE ) guidelines specifically do not recommend universal screening for neonatal hyperbilirubinaemia . 46
Serum bilirubin
The gold standard method for
quantification of hyperbilirubinaemia is direct measurement of bilirubin in blood . SBR is most commonly measured in the laboratory using methods based on the ‘ diazo reaction ’ which utilises diazotised sulfanilic acid . 47 , 48 This test is readily available in most pathology laboratories . The process of blood-taking from babies to acquire samples for SBR measurement involves either venepuncture or heel-prick sampling . Clinicians
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raised levels of beta-glucuronidase and reduced fluid and energy intake |
dice results from the failure of clearance of the bilirubin that has |
levels of unbound unconjugated bilirubin and relative individual suscep- |
of jaundice , feeding in terms of breastmilk or formula , and weight |
typically interpret the significance of the SBR measurement based on |
with associated delayed gut transit |
already been conjugated in the liver |
tibility to neurotoxicity because of |
gain or loss since birth . |
hour-specific nomograms and indi- |
compared with formula fed infants . |
with glucuronic acid , and gener- |
an array of clinical and physiological |
Complete a routine detailed neo- |
vidual infant risk factors . There are |
The relationship between jaundice |
ally implies biliary tree obstruction . |
risk factors . Consistently , the strong- |
natal systems examination . Take |
a number of commonly used pop- |
and breastfeeding is further complicated by the negative effect of hyperbilirubinaemia on an infant ’ s |
The jaundiced infant may present with associated dark urine and pale stools . Excess levels of conjugated |
est predictors of severe hyperbilirubinaemia are early jaundice , blood group incompatibility , lower gesta- |
particular note of the child ’ s level of alertness and responsiveness to handling , tone and reflexes . Assess |
ulation-based nomograms widely used internationally . 49 A conjugated bilirubin level should be |
wakefulness and feeding ability , |
bilirubin must be urgently inves- |
tional age , family history , bruising |
the hydration status , for exam- |
checked at least once in all jaun- |
and thus the cycle of poor feed- |
tigated to establish the pathologi- |
and ineffective exclusive breastfeed- |
ple , looking for excessive weight |
diced infants . |
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ing and deepening jaundice may self-perpetuate . 34
CONJUGATED HYPERBILI- RUBINAEMIA
CONJUGATED hyperbilirubinaemia
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cal underlying cause , particularly because the diagnosis and treatment of biliary atresia is time-critical in an infant . Other causes of neonatal conjugated hyperbilirubinaemia include hepatitis , metabolic conditions and other causes of |
ing and weight loss . 8 , 37-41
These risk factors tend to be relatively common in many newborn populations and therefore independently are of low attributable risk . However , in combination with timed bilirubin measurement their
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loss , reduced urine output , tachycardia and sunken anterior fontanelle . Inspection of the nappy for urine and stool output , colour and consistency can be useful . Exclude liver and / or splenic enlargement on abdominal palpation and check |
Visual inspection
With increasing bilirubin levels ,
neonatal jaundice spreads from the face to the trunk and extremities in a so-called ‘ cephalocaudal pattern ’. In 1969 , Kramer correlated
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( greater than 10 % of total bilirubin ) in a newborn at any timepoint |
extrahepatic obstruction such as a choledochal cyst ( see figure 6 ). |
clinical application can be useful . 42 The clinical and physiological risk |
for any signs or bruising and / or cephalohaematoma . |
evolving skin zones of jaundice with SBR measurements . 50 PAGE 30 |