Physiological jaundice is common in the first week of life, occurring in around 60% of term and 80% of preterm infants (Ng and How, 2015; Mitra and Rennie, 2017). It is the result of rising levels of bilirubin, which eventually binds to tissues such as the skin and sclera, producing clinically recognisable jaundice around day 3 or 4 (Mitra and Rennie, 2017; Rankin, 2017). Bilirubin is produced during the breakdown of red blood cells, and in newborn infants there is a transitional imbalance between its production and elimination, resulting in an excess of bilirubin. This normal imbalance that produces physiological jaundice can, however, be exacerbated by factors that result in pathological jaundice, which can result in neurological damage, dysfunction, and death (Ng and How, 2015).
Most bilirubin is produced during the breakdown of senescent red blood cells, with bilirubin being produced as a result of the breakdown of the haem component of haemoglobin (Figure 1). This occurs in phagocytic monocytes and macrophages in various tissues of the body (Mitra and Rennie, 2017), and first results in a form of bilirubin called unconjugated bilirubin. This is lipid-rather than water-soluble, so is transported to the liver for metabolism bound to albumin (Blackburn, 2017). In the liver it undergoes conjugation (it is combined with glucuronic acid by the enzyme glucuronyl transferase) to produce conjugated bilirubin, which is more water-soluble and can thus be excreted in urine and bile (Mitra and Rennie, 2017; Rankin, 2017). Mutations in this enzyme that reduce its function can result in Gilbert and Crigler-Najjar syndromes, which are characterised by hyperbilirubinaemia due to reduced functioning of the liver's bilirubin-conjugating ability and the resulting build-up of unconjugated bilirubin (Wong and Stevenson, 2015; Chang et al, 2017). As the liver conjugating system also requires oxygen and glucose to function efficiently, hypoxia and hypoglycaemia may also slow down this process and increase the risk of hyperbilirubinaemia (Blackburn, 2017; Rankin, 2017).