Understanding neonatal jaundice

Around 60% of babies born at term and around 80% of premature babies exhibit signs of jaundice within the first week of life (Koura et al, 2009). Jaundice is caused by high levels of bilirubin in the blood (hyperbilirubinaemia) and presents with yellowing of the skin and eyes (Wong and Bhutani, 2017; NICE, 2016a). Prolonged jaundice is defined as jaundice persisting beyond two weeks of age in a baby born after 37 weeks’ gestation or three weeks in a premature infant (NICE, 2016a).

Jaundice presents a challenge for healthcare professionals. Neonatal jaundice can be either physiological or pathological. Physiological jaundice is extremely common, and in most cases requires no treatment. However, pathological jaundice, resulting from an underlying serious health condition, presents a serious problem. The consequences of failing to recognise, monitor, and treat this can be devastating for a child (Erlichman and Loomes, 2020; Rennie et al, 2019).

Physiological jaundice presents frequently in babies; in comparison with adults, they have relatively large numbers of red blood cells, which are rapidly broken down. The immature livers of infants are not able to easily process and excrete the raised levels of bilirubin, which builds up in the body and presents jaundice as mild yellowing of the skin (Green et al, 2014).

NICE guidelines (2016b) state that assessing a baby for neonatal jaundice should include assessing the sclera and gums, alongside pressing lightly on the skin to assess for yellowing in blanched skin. Martin et al (2012) report that practitioners tend to rely solely on the appearance of the skin rather than observing the sclera when diagnosing persistent neonatal jaundice. This puts darker-skinned babies at higher risk of not having their jaundice identified in a timely manner, delaying any necessary treatment options (Ives, 2011). In a retrospective cohort study, Martin et al (2012) identified that non-white babies were referred later for surgery for biliary atresia, further evidencing the need for healthcare professionals to be alert to effective examination protocols for neonatal jaundice.

Breastfed babies may present with prolonged breastmilk jaundice, which continues for weeks or even months. This presents with good weight gain, normal stools and urine and causes them no harm; however, underlying pathologies must be excluded before a diagnosis of breastmilk jaundice is made to avoid any problems with the liver being missed (Children’s Liver Disease Foundation, 2019).

Jaundice can be an indicator of serious liver diseases – for example, kernicterus and biliary atresia – with an initial symptom presenting as prolonged jaundice (Erlichman and Loomes, 2020). Breastmilk jaundice is a benign condition that gradually eases over time; it is distinct from breastfeeding jaundice, which occurs within the first week and is associated with weight loss, fewer than five dirty nappies a day and low urine output. Breastfeeding jaundice is generally caused by inadequate oral intake (Flaherman and Maisels, 2017).

NICE (2016a) guidelines state that mothers of breastfed babies should be supported and encouraged to breastfeed regularly, including waking the baby to feed if needed. The support should include guidance on feeding and lactation, including being encouraged to engage in skin-to-skin contact alongside a full breastfeeding assessment by a qualified practitioner; support, education and advice is particularly important when babies are experiencing breastfeeding jaundice (Flaherman and Maisels, 2017).

Breastmilk jaundice is a benign condition that gradually eases over time; it is distinct from breastfeeding jaundice

Biliary atresia and kernicterus

Babies presenting with very early signs of liver disease may appear well and be feeding well (Children’s Liver Disease Foundation, 2019). Biliary atresia is a liver disease that involves a blockage in the extrahepatic biliary tree (bile ducts). This stops bile being excreted from the liver and requires surgical correction. It can occur in utero due to malformation of the bile ducts or shortly after birth due to inflammation or occlusion (Children’s Liver Disease Foundation, 2020).

Although biliary atresia is a rare condition, with an incidence of around 0.58 per 100,000 live births in England and Wales (UK National Screening Committee, 2017), around 70% of infants with biliary atresia will need a liver transplant – without surgery, the condition will be fatal (Erlichman and Loomes, 2020).

While some countries screen babies for biliary atresia, this is not currently recommended in the UK (UK National Screening Committee, 2017). This means that it is imperative that healthcare professionals can identify babies with prolonged jaundice to ensure that those who may be at risk of harm from biliary atresia receive prompt treatment (NICE, 2016a).

Kernicterus is a rare but serious complication of neonatal jaundice and is caused by excessive bilirubin in the blood. The bilirubin can cross the tissue that separates the brain from the blood and cause brain damage to the infant (NORD, 2021). Kernicterus occurs in six or seven babies in the UK every year (NICE, 2014).

Healthcare professionals need to make a thorough assessment of the infant if any incidences of jaundice are evident. Assessment should not focus on skin jaundice alone. This helps separate any pathological jaundice from physiological jaundice and ensures prompt instigation of support and treatment actions. The urine of newborn babies should be colourless: yellow urine in a young baby may be a sign of conjugated bilirubin being excreted in the urine, which could indicate a problem with the liver. The stools of a neonate should be yellow or greenish in colour; chalky stools are a red flag for inflammation or blockage in the liver preventing bile from draining from the liver into the digestive tract (Children’s Liver Disease Foundation, 2019). Healthcare professionals should refer babies who present with jaundice in the first 24 hours of life for urgent medical review (NICE, 2016a). Babies with prolonged jaundice should have a blood test for split bilirubin.

Treatment for neonatal jaundice

NICE (2016a) advises that professionals should be directed by the algorithm for monitoring and treatment of neonatal jaundice. Neonates who have prolonged jaundice should always be investigated and any pathological cause eliminated (Abbey et al, 2019).

Jaundice can be a direct result of severe liver disease in neonates, with success rates of treatment being determined by timely interventions (Fawaz et al, 2017). The goal of any treatment or intervention for neonatal jaundice is primarily to reduce the amount of circulating bilirubin.

The primary decision for monitoring or intervention should be based on the split bilirubin level and determined by age of the infant in hours, postpartum age and presence of any risk factors (NICE, 2016a; Maisels and McDonagh, 2008). The first step in assessing prolonged neonatal jaundice should be a split bilirubin blood test.

This blood test should be performed regardless of feeding status, and breastmilk jaundice should not be presumed until blood analysis rules out the need for treatment or further intervention.

Step 1. Phototherapy (not sunlight)

Phototherapy reduces bilirubin by using energy from fluorescent light tubes to change the shape and structure of the bilirubin particle, converting them into molecules that can easily be excreted (Maisels and McDonagh, 2008). The rate at which bilirubin changes and is broken down is dependent on the intensity and penetration of the light used. Light wavelengths that penetrate the tissue increase absorption of bilirubin and the phototherapeutic effect (Lightner and McDonagh, 1984).

Babies are managed in hospital units in cribs or cots with fluorescent lighting, and are encouraged to have breaks for breastfeeding, nappy changes and cuddles. Breastmilk is the feed of choice for all babies. Where there is a need for intense phototherapy, feeding and changing occurs without breaks. Parenteral feeds of breastmilk where possible are encouraged using bottles or nasogastric feed tubes until bilirubin levels indicate that intense phototherapy can discontinue, and breastfeeding can resume as normal with support.

Step 2. Exchange transfusion

This is the final step in the NICE (2016a) management plan for neonatal jaundice. Infants who do not show a positive outcome following an exchange of blood will require significant medical intervention. This procedure is now rarely used in most developed countries due to advances in phototherapy, prenatal monitoring and detection of rhesus risk as well as more increasingly widespread use of immunoglobulin (Murki and Kumar, 2011; Steiner et al, 2007). Reductions in poor outcomes related to exchange transfusion and in mortality of effected infants is seen as a positive move in the management of neonatal jaundice (Steiner et al, 2007). However, NICE (2016a) continues to recommend exchange transfusion as a procedure to be considered following unsuccessful attempts to reduce bilirubin through phototherapy. Exchange transfusion remains to be recommended as a procedure that can prevent brain injury as a result of bilirubin entering the cerebral space in infants with hyperbilirubinemia (Murki and Kumar, 2011; Dennery et al, 2001).

Exchange transfusion is a procedure that removes the infant’s blood in small incremental amounts and replaces this with donor blood, with the aim of removing the antibodies in the baby’s blood that are unable to breakdown bilirubin. The donor blood provides enhanced albumin binding sites for bilirubin breakdown (Murki and Kumar, 2011).

Step 3. Intravenous immunoglobulin

Where phototherapy and exchange transfusion have not reduced bilirubin levels within safe limits and continue to indicate a need for treatment, NICE (2016a) advises that the next stage would be to administer intravenous immunoglobulin (IVIG). Zweirs et al (2018) report that the risks involved with IVIG are significantly lower than those of exchange transfusion. Their study suggests that IVIG therapy is a safer and effective treatment option. However the authors report that IVIG use only moderately reduced the likelihood of a need for exchange transfusion and therefore use for all patients was not recommended.

Immunoglobulin is a protein that helps the rapid breakdown of antibodies in red blood cells. Administration of IVIG for babies with neonatal jaundice intends to target maternal antibodies in the infant’s blood and aid the disintegration and removal of bilirubin from the blood (Koura et al, 2009).

However, a review by Ives (2011) analysed the use of IVIG within the treatment protocol for managing neonatal jaundice prior to an exchange blood transfusion. Results were undetermined and the authors concluded insufficient evidence to advocate that IVIG would reduce the risk of needing an exchange transfusion. Within the UK, the treatment algorithm advocates IVIG as an option following suboptimal exchange transfusion.

Summary

• Jaundice in neonates is not an unusual occurrence and can occur due to physiological causes that generally self-resolve without needing medical management.
• Pathological causes are often serious and always require prompt medical intervention.
• Without urgent and effective assessment of neonatal jaundice, health outcomes are significantly reduced.
• Health professionals who are aware of the full assessment for neonatal jaundice will ensure that timely and effective monitoring and management is available for the infant.
• Support for parents and carers is paramount in all incidences of neonatal jaundice. Education and advice can help families remain informed, and able to seek advice should they become alert to any changes in their child’s health at the outset.

Surgical intervention

Biliary atresia is the most common cause of liver disease in infants and requires surgery to repair the affected bile ducts. In biliary atresia, the bile ducts outside the liver become diminished with scar tissue. This scar tissue impedes mobility in the bile duct and reduces the ability to excrete bile and bilirubin into the digestive tract (Hartley et al, 2010). Major surgery to relieve this obstruction is known as a Kasai portoenterostomy. Without this procedure, infants would not survive beyond one or two years of life.

Kasai portoenterostomy has a success rate of 60% if performed in the first two months of life. However, this decreases rapidly to below 30% if surgery is delayed beyond three months of age. Where this surgical intervention is unsuccessful, infants will require a liver transplant as their only treatment option to prolong life (Cartledge and McClean, 2009).

Elaine Robinson is a senior lecturer at Northumbria University, and Nicci Jones-Anderson is a medical student at Newcastle University.

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