About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks. Jaundice is caused by bilirubin deposition in the skin. Most jaundice in newborn infants is a result of increased red cell breakdown and decreased bilirubin excretion.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for unconjugated hyperbilirubinaemia in term and preterm infants? We searched Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 42 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: albumin infusion, exchange transfusion, home phototherapy, immunoglobulin, hospital phototherapy, and tin-mesoporphyrin.
About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks.
Jaundice is caused by bilirubin deposition in the skin. Most jaundice in newborn infants is a result of increased red cell breakdown and decreased bilirubin excretion.Breastfeeding, haemolysis, and some metabolic and genetic disorders also increase the risk of jaundice.Unconjugated bilirubin can be neurotoxic, causing an acute or chronic encephalopathy that may result in cerebral palsy, hearing loss, and seizures.
Phototherapy provided by conventional or fibreoptic lights in hospital reduces neonatal jaundice compared with no treatment (as assessed by serum bilirubin levels).
Low threshold compared with high threshold phototherapy reduces neurodevelopmental impairment and hearing loss and reduces serum bilirubin on day 5 in extremely low birth weight infants. However, it increases the duration of phototherapy, and there is no effect on mortality or the rate of exchange transfusion.Close phototherapy compared with distant light-source phototherapy reduces the duration of phototherapy in infants with hyperbilirubinaemia.
We don't know whether home phototherapy is more or less effective than hospital phototherapy as we found no studies comparing the two treatments.
There is consensus that exchange transfusion reduces serum bilirubin levels and prevents neurodevelopmental sequelae, although we found no studies to confirm this.
Exchange transfusion has an estimated mortality of 3 to 4 per 1000 exchanged infants, and 5% to 10% permanent sequelae in survivors.
We don't know whether albumin infusion is beneficial.
Tin-mesoporphyrin is not currently licensed for routine clinical use in the UK or US, and further long-term studies are warranted to confirm its place in clinical practice.
However, tin-mesoporphyrin reduced the need for phototherapy (as assessed by serum bilirubin levels) when given either to preterm infants on the first day, or to jaundiced term or near-term infants within the first few days of life.
Intravenous immunoglobin reduces the need for exchange transfusion in high-risk infants with haemolytic hyperbilirubinaemia, as well as reduces serum bilirubin levels, the requirement for phototherapy, and the length of hospital stay.
Benefits of immunoglobulin were observed when used either alone or in conjunction with phototherapy. No adverse effects were reported. However, we don't know whether immunoglobulin prevents neurodevelopmental sequelae.