Dr Angela McGillivray Senior staff specialist neonatologist at Royal Prince Alfred Hospital and Sydney Children ’ s Hospitals Network , NSW .

First published online on 30 June 2023

BACKGROUND

NEONATAL jaundice or hyperbilirubinaemia

is clinically recognisable

as yellowing or icterus of the newborn ’ s skin and sclerae and is due to variable degrees of unconjugated bilirubin deposition . It is a very common neonatal condition , being clinically apparent in 50-80 % of newborns . 1 The most common aetiological type , idiopathic or ‘ physiological ’ neonatal unconjugated hyperbilirubinaemia , usually subsides within the first few weeks after birth and for most newborn babies , it is inconsequential in terms of long-term outcomes . However , brain damage and significantly impaired long-term neurodevelopment or kernicterus is an ever-present risk because of the neurotoxic potential of unconjugated bilirubin .

This How to Treat aims to provide GPs with a comprehensive guide to managing babies with jaundice who present in the community setting . This guide focuses on key aspects of clinical assessment , risk factor identification , diagnosis , investigations , treatment and management with suggested appropriate time-dependent referral pathways .

THE WORST- CASE SCENARIO : KERNICTERUS

IN the unbound or ‘ free ’ form , bilirubin

can be toxic to the newborn

brain via a complex sequence of cellular pathways . Primarily , physiological disruption occurs in the plasma membrane and mitochondria subcellular compartments of neurone and astrocyte cell types . Neurotoxic pathological mechanisms include cellular energy depletion and free radical attack . 2 Resultant damage to significant numbers of neurones and astrocytes leads to the classic neuropathological findings of bilirubin staining in nuclear regions of the brain ( see figure 1 ), the basal ganglia , hippocampus , substantia nigra , various cranial nerve nuclei ( oculomotor , vestibular , auditory and facial nerve ) and neuronal necrosis . 3-6 The likelihood of significant hyperbilirubinaemia and thus the risk of neurotoxicity developing in an individual neonate is dependent on the relative equilibria of unconjugated bilirubin levels , the availability of albumin , the bilirubin-albumin binding physiological

environment and the condition of the blood-brain barrier .

Clinically , bilirubin neurotoxicity or kernicterus spectrum disorder manifests acutely in three phases of evolving stupor , postural tonal changes , high-pitched crying and poor feeding . Early acute bilirubin encephalopathy presents as lethargy and poor feeding . The intermediate phase is typically characterised by variable muscle tone , a high-pitched cry , irritability and opisthotonus ( see figure 2 ), and the most advanced phase is depicted by a comatose baby with setting-sun eyes . The clinical features of chronic post-kernicteric bilirubin encephalopathy may subsequently develop in early childhood and are characterised by abnormal motor development , particularly choreoathetoid cerebral palsy and hearing deficit . Intellect is typically preserved , with only the minority of patients experiencing a marked cognitive deficit . 7 , 8

EPIDEMIOLOGY

AN Australian population-based surveillance study estimated the incidence of extreme neonatal

hyperbilirubinaemia to be 9.4 per 100,000 live births . 9 Reporting criteria were : birth at 34 weeks ’ gestation or older with a peak total serum bilirubin ( SBR ) of 450 µ mol / L or greater and / or clinical evidence of bilirubin encephalopathy . The main aetiologies in this cohort from most to least frequent were idiopathic ABO blood group incompatibility , glucose-6-phosphate dehydrogenase ( G6PD ) deficiency , and rhesus isoimmunisation . Seventy-eight per cent of cases were identified following discharge from hospital : 42 % by hospital-based midwives ; 27 % by community-based nurses ; 7 % by GPs and 22 % by paediatricians . There were no differences found in short-term outcomes on comparison of those cases identified during or after their initial postnatal hospital admission . Notably , cases with a haemolytic aetiology were significantly more likely to have extremely high levels of hyperbilirubinaemia ( p < 0.002 ).

The international global burden of severe neonatal hyperbilirubinaemia is estimated by Slusher et al to range from 6678 per 100,000