Population screening for neonatal liver disease: potential for a community-based programme.

OBJECTIVES: To evaluate a community-based screening programme for detecting neonatal liver disease by the quantitation of conjugated bilirubin in blood. SETTINGS AND METHODS: Prospective cohort/observational study using spare plasma from routinely collected liquid neonatal screening specimens from babies born in Birmingham over a two-year period. Babies with a conjugated bilirubin above 18 mumol/l and comprising more than 20% of the total bilirubin were followed up. A total of 27654 neonates were tested in the community, with a further 2425 samples from babies hospitalised at the time of the test. RESULTS: In the community-based series, 84.7% of the specimens received were analysed, the remainder being unusable mainly because of gross haemolysis (8.6%) or insufficient sample (5.8%). In 107 neonates the results were above the cut-off limits (0.46% of the number analysed). Of these, 12 had persistently abnormal results, 11 of whom had confirmed liver disease. The liver diseases detected included neonatal hepatitis (n=6), extra-hepatic biliary atresia (n=2), hypopituitarism (n=1), alpha-1-antitrypsin deficiency (n=1) and Alagille syndrome (n=1). The sensitivity and specificity of the test for babies in the community were 100% and 99.6%, respectively. CONCLUSIONS: Conjugated bilirubin in plasma measured at 6-10 days is a reliable marker for neonatal liver disease, and a population screening programme based on this method has the potential to improve the survival and quality of life of infants born with liver disease. However, testing as part of the neonatal screening programme will prove practical only if the method can be adapted to use dried blood spots.

Population screening for neonatal liver disease: a feasibility study.

BACKGROUND: Extra-hepatic biliary atresia and several other causes of neonatal liver disease carry high mortality and morbidity rates, especially if not treated early in life. Despite professional recommendations, delayed referral of infants with prolonged jaundice continues to be a significant problem. One approach to reducing the age of referral and diagnosis is population screening to detect significant conjugated hyperbilirubinaemia as an index of liver dysfunction. METHODS: To investigate this possibility, and to provide reference data on bilirubin and its conjugated and unconjugated fractions in a normal newborn population, 1157 neonates were anonymously tested (median age 7 days, range 4-28 days) using surplus plasma from routinely collected neonatal screening specimens, using dry slide chemistry. RESULTS: Of 2310 specimens received, 50% were suitable for analysis. The remainder were either haemolysed or insufficient (10% and 40% of the total, respectively). Total bilirubin concentrations ranged from 9 to 428 micromol/l and conjugated bilirubin from 0 to 175 micromol/l, although the latter was rarely increased to more than 30 micromol/l (2.5th-97.5th percentile ranges 15-285 micromol/l and 0-18 micromol/l, respectively). The range of the percentage of conjugated bilirubin was 0-57% (2.5th-97.5th percentile; range 0-20%). CONCLUSION: An increased conjugated bilirubin, expressed as a concentration or as the percentage of the total bilirubin, could be used as a specific marker to screen for liver dysfunction in neonates. This approach has the potential to improve the age of referral and the prognosis of infants with neonatal liver disease.

Neonatal screening for phenylketonuria: evaluation of an automated enzymatic method.

An enzymatic assay for phenylalanine using phenylalanine dehydrogenase is available in kit form (Quantase) for use with dried blood spot specimens and microtitre plates. The method has been automated by use of a sample processor and its performance and suitability for neonatal screening for phenylketonuria has been evaluated by comparison with the Guthrie bacteriological inhibition assay. The enzymatic method performed well with regard to precision and accuracy. It was able to differentiate between normal and raised phenylalanine concentrations for the purpose of screening, thus greatly reducing the repeat rate for equivocal results. There were, however, some concerns about its robustness for screening and its detection limit. The Quantase assay has the potential to be used as a large-scale routine neonatal screening method, if its use can be shown to be cost-effective.