Performing a split bilirubin test to identify liver disease in any infant who remains jaundiced beyond 2 weeks of age has been recognised as good clinical practice. The Leeds Community Midwifery Team performed this test, following an agreed protocol, from December 2000. By February 2008, 882 infants had been tested. Three infants were identified as having significant liver disease, including one with biliary atresia. Examining the liver unit database, a further 38 infants with Leeds post codes presented with neonatal liver disease during the study period. Five infants were identified appropriately by the midwives but not reported via the study protocol, 29 were referred from secondary care, (1) by a general practitioner at 9 days of age and (2) who did not become jaundiced before 3 months, leaving one infant who was ‘missed’ by the midwives. No infant whose conjugated bilirubin was below the authors' threshold later presented with liver disease. This is an effective protocol for identifying neonatal liver disease but requires ongoing education to maintain compliance.
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Neonatal liver disease is rare, and late diagnosis is still frequent despite numerous campaigns to increase awareness among healthcare professionals. Biliary atresia, which occurs in 1:16 700 live births in the UK,1 is the most common cause of neonatal liver disease, and the outcome following surgery for this condition is improved if it is performed in infants before 8 weeks of age. Any form of neonatal liver disease leads to malabsorption of fat-soluble vitamins, especially vitamin K. Early diagnosis and instigation of fat-soluble vitamin supplements can prevent these children presenting at 3–8 weeks of age with an intracranial haemorrhage.2 These are compelling arguments for early diagnosis, but jaundice in newborn babies is common, and there is currently no universal screening test for neonatal liver disease.
Performing a split bilirubin test (measuring total and conjugated bilirubin) in any infant who remains jaundiced, beyond 2 weeks of age, has been recognised as good clinical practice since the 1990s and is championed by the ‘Yellow Alert’ campaign of the Children's Liver Disease Foundation.2 This report describes the assessment of a protocol to help midwives identify neonatal liver disease in Leeds.
From December 2000, the Leeds Community Midwifery Team agreed to perform a split bilirubin test on all infants who remained jaundiced beyond 2 weeks of age. Follow-up was according to an agreed protocol (figure 1), and special request forms were printed to aid the laboratory in fast-tracking results to the midwifery office. All infants with a conjugated hyperbilirubinaemia, defined as a conjugated fraction of ≥20% of total bilirubin and >18 µmol/l,3 were referred for investigation of liver disease. The Liver Unit database was also examined to find infants with liver disease, with a Leeds postcode, who had not been referred by the midwives. Their notes were scrutinised to identify why they had not been picked up by the protocol. Finally, birth statistics were obtained from Leeds City Council for the period of the study.
From the biochemistry database a total of 1154 samples were referred from the community using the protocol request forms between December 2000 and February 2008. Two hundred and seventy-two were excluded: over 6 months of age (n=6), no date of birth available (n=8), no total bilirubin level available (n=38), no conjugated bilirubin level available (n=87) and repeat referrals (n=133). Eight hundred and eighty-two referrals were therefore reviewed. The median age of referral was 21 days (range 0–51 day; 820 infants ≤28 days of life, 72 infants under 14 days of life). Five infants fulfilled the criteria for conjugated hyperbilirubinaemia. Three were found to have significant pathology; biliary atresia (referred at 25 days of life), Niemann–Pick Type C (referred at 33 days of life) and idiopathic neonatal hepatitis (referred at 23 days of life). Two further infants had a borderline conjugated fraction which resolved on retesting, and they were classified as false positives. None of the 877 infants who had a conjugated bilirubin below our threshold value later developed liver disease.
Examining the Liver Unit database revealed a further 38 infants with a Leeds postcode seen with neonatal liver disease between December 2000 and February 2008 (table 1). Reviewing the clinical history from the notes: five infants were identified appropriately by the midwives but not reported via the study protocol; hence they were not highlighted on the biochemistry database. Twenty-nine were referred from secondary care, usually inpatients and predominantly from neonatologists. General practitioners referred one infant, with galactosaemia, at 9 days of age and one infant, with Alagille syndrome, who did not become jaundiced until over 3 months of age. His sister was identified with Alagille syndrome on day 446 of life while attending the clinic with her brother. We would not have expected the protocol to pick up these infants. However, on scrutinising the notes, we could not identify any reason why the final infant, who presented with idiopathic neonatal hepatitis on day 41, was not picked up earlier by the protocol.
Over the study period, 59 238 infants were born in Leeds. The cumulative referral rate was therefore only 1.5% of the newborn population (1:70 live births). However, the referral rate did increase year on year from 8 per 1000 live births, in 2001, to 22 per 1000 live births, in 2007. All 41 of the infants referred to the Liver Unit (38 in notes review, three picked up by protocol) with liver disease had Leeds postcodes, and therefore the incidence of liver disease in our local population is 1:1500 live births (including those infants on the neonatal unit).
From this study the use of a split bilirubin measurement to identify children with neonatal liver disease is clearly accurate at identifying conjugated hyperbilirubinaemia with a sensitivity of 100% (ie, all screened children who had liver disease were identified) and has a negative predictive value of 100% (ie, all infants with a negative test did not have liver disease). The midwives correctly identified eight infants with liver disease (three via the protocol request forms and five via standard request forms). From our scrutiny of the hospital notes of children subsequently referred to the Liver Unit, with Leeds postcodes, we could only identify one child with no explanation why the midwives did not pick him up earlier using the protocol. It is encouraging that the number of infants screened is increasing each year and that 93% of the screened infants were tested before 4 weeks of age. However, there is always room for improvement and ongoing education about this protocol.
In a previous population study in Birmingham, 23 214 newborns were screened by split bilirubin using liquid blood collected for the routine neonatal screening programme at 6–10 days of age. The sensitivity and specificity of this test for liver disease for babies in the community were 100% and 99.6% respectively, and none of the infants with a negative test were later diagnosed as having liver disease. However, most neonatal screening is now carried out on dried blood spots, and a method for using these to screen for neonatal conjugated hyperbilirubinaemia has not yet been achieved.3 An earlier attempt at screening using mass spectrum analysis of bile acids in dried blood spots did not adequately identify those with neonatal liver disease.4
In Taiwan, where the incidence of biliary atresia is higher (approximately 1:5000 live births), an infant stool colour card has been integrated into the Child Health Booklet, and a recent paper reports that 97.1% of babies with biliary atresia were correctly identified.5 This is impressive, but clearly it is only useful in identifying infants with severe obstructive jaundice. Many infants with neonatal liver disease due to other causes may not have pale stools, although they can still be at risk of coagulopathy.
In our experience there is still confusion among many healthcare professional about the significance of different types of infant jaundice. The National Institute for Health and Clinical Excellence Guidelines for Neonatal Jaundice have been published and hopefully will help, although they are primarily directed at preventing kernicterus. For infants with prolonged jaundice, we will continue to implement our protocol with feedback to midwives when a child with liver disease is identified and provide ongoing regional multiprofessional educational sessions.
The overall incidence of neonatal liver disease is uncertain in the UK. This audit has found an incidence of 1:1500 live births in the Leeds population. Two previous community-based studies gave an incidence of 1:2500 live births in the South East of England in 1970s6 and 1:2000 live births in Birmingham in the 1990s.3 Whether this represents a true difference in incidence with era or region is unclear, as there is some variability in case definition.
The authors thank the community midwives for their involvement.
Funding No funding, performed as departmental audit.
Competing interests None.
Ethics This audit is registered with the Leeds Teaching Hospitals NHS Trust audit department. The chairman of the Local Research Ethics Committee (LREC) advised that REC approval was not appropriate.
Provenance and peer review Not commissioned; externally peer reviewed.
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