Neonatal jaundice: a critical review of the role and practice of bilirubin analysis

Abstract

Neonatal jaundice is common, and usually harmless, because of physiological jaundice or breast-feeding. In some neonates unconjugated bilirubin concentration, coupled with other risk factors, is sufficient to allow free bilirubin to cross the bloodbrain barrier and cause kernicterus. Another subgroup of infants is jaundiced because of elevated conjugated bilirubin; a marker for a number of pathological conditions. Bilirubin measurement must identify those infants at risk. Transcutaneous bilirubin measurement is increasingly used in healthy infants, especially before early discharge or at home, to assess the need for laboratory bilirubin measurement. Transcutaneous measurements are not covered by laboratory quality assessment schemes. Guidelines on management of neonatal jaundice utilize age in hours and other risk factors to define bilirubin action thresholds, which may be as low as 100 mmol/L for sick premature infants, whereas early discharged babies may only present after bilirubin concentrations are extremely high. Hence, there is a requirement for accurate total bilirubin measurement from ,100 to .500 mmol/L, with sufficient precision to assess the rate of bilirubin change with time. Babies presenting with late jaundice always require conjugated bilirubin measurement. It is of concern that many total and direct bilirubin automated kit methods suffer from haemolysis interference, while use of in-house methods or modification of commercial methods has virtually disappeared. External quality assessment has a vital role in providing data on different methods' performance, including accuracy, precision and susceptibility to interference. Laboratories should consider whether their adult bilirubin methods are suitable for neonates.

Features and applications of bilirubin oxidases

“…The conjugated form results from the transformation of the unconjugated bilirubin in the liver by the enzyme hepatic glucuronyl transferase. The detection of unconjugated bilirubin is more specifically used in newborns where the liver is not mature enough to convert the unconjugated bilirubin to conjugated bilirubin resulting in jaundice affecting~60-80 % of newborns (Goldfinch and Maguire 1988;Kirk 2008; Table 1 Comparison between the kinetics parameters of the BOD from B. pumilus (Durand et al 2012b), B. licheniformis (Koschorreck et al 2008), Bacillus HR03 (Mohammadian et al 2010), B. subtilis (Durao et al 2008), M. verrucaria (Kataoka et al 2005b) and M. oryzae (Durand et al 2012a Mullon et al 1989;Nakamura and Lee 1977). Conjugated bilirubin is known to be a better indicator of liver function and is used in the diagnosis of jaundice and hyperbilirubinemia (Doumas et al 1987(Doumas et al , 1999Kirihigashi et al 2000;Kosaka et al 1987Kosaka et al , 1998Million et al 1988;Mullon and Langer 1987;Perry et al 1986;Soltys et al 1992).…”

Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn—a prospective randomized controlled trial

“…One of the main causes of severe hemolytic disease of the newborn (HDN) is Rh incompatibility, with a risk of acute or chronic kernicterus [16]. Many Rh-negative mothers in developing countries do not receive Rh prophylaxis when they give birth to Rh-positive baby due to inadequate care or inability to afford anti-D immunoglobulin [6].…”

Development and optimization of a noncontact optical device for online monitoring of jaundice in human subjects

“…Although the method is approved for monitoring jaundice, 4,5 it has several drawbacks. Although the method is approved for monitoring jaundice, 4,5 it has several drawbacks.…”