Occasional review
Neonatal hyperbilirubinaemia

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Abstract

Neonatal hyperbilirubinaemia is an extremely common condition which continues to be a significant cause of readmission of neonates to hospitals. The aim of early recognition and appropriate treatment is to prevent bilirubin encephalopathy which can cause severe neurodisability. This article reviews the national guidelines issued by various organizations like American Academy of Paediatrics in USA and National Institute of Clinical Excellence in the UK which have attempted to standardize approaches to diagnosis and management. This review highlights how early detection with measurement of bilirubin as opposed to visual estimation and appropriate use of high intensity phototherapy based on recommended treatment threshold charts reduces the incidence of severe jaundice requiring exchange transfusion and how evaluation and support of new mothers and their babies in the community by trained nurses with access to transcutaneous bilirubinometers can reduce hospital referrals while providing safe care at home.

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Incidence

Neonatal jaundice affects 60% of term babies and 80% of preterm infants. Only a small proportion of these need treatment. Estimation during a quality improvement project undertaken by the ABMU Health Board in Wales in 2014 over a 6 month period looking at all births in the area showed 1046 (19%) of babies reviewed by community midwives required testing with transcutaneous bilirubinometers for visible neonatal jaundice. 63 babies (1%) required referral to hospital. 69% of babies referred needed

Bilirubin metabolism

Bilirubin is produced by the catabolism of haem in the reticuloendothelial system. Haem is mainly produced from breakdown of red blood corpuscles (RBC). Myoglobin and cytochrome also release haem when broken down. Haem in presence of haem oxygenase and biliverdin reductase is converted to bilirubin. Carbon monoxide and iron is released during this process. Bilirubin is transported to liver bound to albumin. It is then conjugated in liver with glucuronic acid in the presence of the enzyme

Bilirubin encephalopathy or kernicterus

Unconjugated bilirubin is lipid soluble and therefore can cross blood–brain barrier. Here it can deposit in areas of the brain. There is a predilection for deposition to occur in the basal ganglia, auditory pathways, and oculomotor nucleus. This deposition and accompanying damage result in the classical symptoms associated with kernicterus. Hypoxia, acidosis, prematurity, and genetic predispositions all increase the risk for kernicterus. Some medicines e.g. ceftriaxone and high dose lipid

Diagnosis and management of hyperbilirubinaemia

The best approaches to diagnosis for neonatal hyperbilirubinaemia facilitate early detection and management of treatable conditions. Most cases of unconjugated hyperbilirubinaemia are due to haemolysis, immaturity of liver, or infection. The majority of these respond to treatment with appropriate hydration and phototherapy. Occasionally riskier interventions including intravenous immunoglobulin and exchange transfusions are required (see below). Antibiotics are indicated for infections and

Conjugated hyperbilirubinaemia

Conjugated hyperbilirubinaemia should be suspected in babies presenting with prolonged jaundice with conjugated bilirubin levels more than 25 μmol/litre or 20% of the total bilirubin if the total bilirubin is more than 85 μmol/litre. Management will be based on the underlying diagnosis suspected. The commonest causes are breast milk jaundice and jaundice associated with use of TPN in preterm babies and post surgical babies. These mostly resolve spontaneously with supportive care. Stopping

Transcutaneous bilirubinometry

TcB are point of care devices used for non-invasive estimation of serum bilirubin in neonates. In general they are reliable in babies who are more than 35 weeks in gestation, less than 14 days of age, and are not exposed to phototherapy or exchange transfusion. Levels are not reliable in the first 24 hours when bilirubin thresholds tend to be lower and when bilirubin levels exceed 250 μmol/litre. The error rate within this acceptable range is approximately 50 μmol/litre and varies between

Clinical experience with TcB

Bilirubinometer use in post-natal wards in Singleton Hospital, ABMU Health Board in Wales reduced invasive blood sampling by five fold. The device had high satisfaction ratings from both staff and parents. Evaluation during a quality improvement project in ABMU Health Board where bilirubinometers were used by all community midwifes found the TcB to be 100% specific in predicting need for hospital admission (95% CI 78%–100%) and need for phototherapy (95% CI 84.4–100%). Use of TcB in the

Phototherapy

Phototherapy remains the main treatment for neonatal jaundice. The main mechanism is photo-oxidation of lipid soluble bilirubin to more water soluble lumirubin. This is eliminated in urine and stool. Light of around 460 nm (blue light) is best suited for phototherapy. A mix of blue and white light is generally used. A spectral irradiance of 25–30 μW/cm2/nm is required to provide adequate phototherapy. Intensive phototherapy should have a spectral irradiance of more than 30 μW/cm2/nm. The

Phototherapy in clinical settings

Phototherapy should be initiated and maintained as per the recommendations in the NICE neonatal jaundice guidelines and recommended phototherapy charts. Charts vary based on gestation and takes into account the bilirubin levels and age of the baby. Risk of kernicterus progressively increases when bilirubin rises above 340 μmol/litre in term babies and 250 μmol/litre in preterm babies. The intention is to try and limit exposure to these levels.

During single unit phototherapy it is important to

Exchange transfusion

A double volume exchange transfusion (2 x 80 ml x weight in kg) is indicated when bilirubin levels continue to rise in spite of adequate hydration and multiple high intensity phototherapy. The total bilirubin threshold for term babies more than 96 hours old and is 450 μmol/litre. Prior to this age and in preterm babies it is recommended to use guidance from the NICE treatment charts. A rapidly rising bilirubin (8.5 μmol/litre/hour), especially in the presence of haemolysis and other risk

Intravenous immunoglobulin (IVIG)

NICE guidelines on neonatal jaundice recommend the use of IVIG in babies whose bilirubin levels remain above the threshold for exchange transfusion, have signs of kernicterus, or have rapidly rising bilirubin levels despite phototherapy. The recommended dose is 500 mg/kg over 4 hours in babies while preparing for exchange transfusion. A systematic survey of IVIG use in babies with Rh or ABO incompatibility in 2003 showed a significant reduction in the need for exchange transfusion [Relative

Pharmacological agents

Agents such as tin protoporphyrin or phenobarbitone are not recommended as effective treatments.

Recent advances

Spectroradiometers can be used to measure the spectral irradiance of the phototherapy units at several sites on the infant's body surface. The recommended spectral irradiance for intensive phototherapy is 30 μW/cm2/nm. Ideally 80% of the body surface of the infant should receive this amount of phototherapy. Anticipated decreases in serum total bilirubin are 34 μmol/litre/hour (2 mg/dL/hour). Home phototherapy could reduce the need for hospital admissions. More research into the safety and

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