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Population screening for neonatal liver disease: a feasibility study
S Keffler1, D A Kelly, J E Powell
1Department of Clinical Chemistry, Birmingham Children's Hospital NHS Trust, United Kingdom.
Insights
Screening for neonatal liver disease can be improved by measuring conjugated bilirubin levels. This approach may lead to earlier diagnosis and better outcomes for infants with prolonged jaundice.
Area of Science:
- Neonatal Medicine
- Clinical Chemistry
- Pediatric Gastroenterology
Background:
- Neonatal liver diseases, such as extra-hepatic biliary atresia, have high mortality rates if not treated early.
- Delayed referral of jaundiced infants is a persistent issue despite recommendations.
- Population screening for conjugated hyperbilirubinemia can aid early detection of liver dysfunction.
Purpose of the Study:
- To investigate the utility of conjugated bilirubin as a screening marker for neonatal liver dysfunction.
- To establish reference ranges for bilirubin fractions in a normal newborn population.
Main Methods:
- Anonymously tested 1157 neonates (median age 7 days) using surplus plasma from routine screening specimens.
- Utilized dry slide chemistry for bilirubin and its conjugated/unconjugated fractions analysis.
- Assessed specimen suitability, with 50% being adequate for analysis.
Main Results:
- Total bilirubin ranged from 9-428 micromol/l; conjugated bilirubin ranged from 0-175 micromol/l.
- Conjugated bilirubin rarely exceeded 30 micromol/l (2.5th-97.5th percentile: 0-18 micromol/l).
- Percentage of conjugated bilirubin ranged from 0-57% (2.5th-97.5th percentile: 0-20%).
Conclusions:
- Elevated conjugated bilirubin concentration or percentage can serve as a specific marker for neonatal liver dysfunction.
- This screening method has the potential to reduce referral age and improve prognosis for affected infants.
- Early identification of liver dysfunction through bilirubin screening can significantly impact infant health outcomes.
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.