You are working in the paediatric emergency department. A 5-day old baby is brought in by their parents, having been advised to attend by the community midwife. They were concerned that the baby has lost 10% of its birthweight and also looks a bit yellow.

What additional information would you like to know? What advice would you give?

Aims

The clinical scenario outlined above will be familiar to anyone who has worked in paediatrics. There are multiple causes of jaundice in the first 2 weeks of life. The aim of this article is to help explain what these causes are and why they occur. It discusses how to focus on the history, examination and investigations in such cases. Initial management will vary depending on the clinical context; as such, this article also outlines the initial management of the most common scenarios

BackgroundWhat is jaundice?

Jaundice is a yellowish discolouration of the skin and sclera caused by an excess of the pigmented molecule bilirubin in the blood (hyperbilirubinaemia). Jaundice is common in infants under 1 month of age, affecting over 60% of term and 80% of preterm babies. In some centres, jaundice accounts for up to 15%–20% of all emergency department presentations during this period.1 2

Why does it matter?

Aside from being common, understanding jaundice in the first 2 weeks of life is important for several reasons:

Jaundice can be a source of significant anxiety for families. In the majority of cases, there is no underlying pathology and, consequently, clinical assessment can play a valuable role in providing reassurance.

In some cases, jaundice can indicate potentially serious underlying pathology (table 1).

Bilirubin is toxic to the most metabolically active parts of the infant brain. High levels can result in deposition of bilirubin in the basal ganglia and brain stem nuclei, resulting in a condition called kernicterus (derived from the German Kern meaning core and the Greek Ikteros meaning jaundiced3). This causes irreversible brain damage which may manifest as athetoid cerebral palsy, visual or hearing impairment and/or intellectual disability.4 In unconjugated hyperbilirubinaemia (the most common type in infants under 2 weeks of age) kernicterus can develop within hours. Therefore, prompt recognition and intervention are necessary to prevent this devastating but avoidable outcome.

Table 1

Common causes of jaundice in babies under 2 weeks of age

Bilirubin metabolism

The bilirubin metabolic pathway might feel like something that bears little relevance to everyday clinical practice. However, a basic understanding of normal physiology enables the healthcare practitioner to understand what to do and why to do it.

The full bilirubin metabolic pathway is shown in figure 1. Key elements include:

Bilirubin is the product of the breakdown of the haem molecule. Anything causing increased turnover or breakdown of erythrocytes increases the risk of jaundice in infants.

Bilirubin starts out in serum in its unconjugated form, which is not water-soluble and can cross the blood-brain barrier.

Unconjugated bilirubin is converted to its conjugated form inside the liver. This is water-soluble and cannot cross the blood-brain barrier.

Conjugated bilirubin is excreted from the liver, via the bile ducts, into the intestines.

Gut bacteria act on conjugated bilirubin, converting some of it into urobilinogen (which is colourless). This can be excreted by the kidneys into the urine.

Some bilirubin in the gut is deconjugated and reabsorbed, increasing serum bilirubin levels. This cycle of bilirubin being taken up, conjugated, excreted, deconjugated and reabsorbed again is called the ‘enterohepatic circulation’ and may be extensive in the newborn infant where gut transit times can be prolonged.

Stercobilinogen, one of the end products of bilirubin metabolism in the gut, is pigmented. A lack of excretion of conjugated bilirubin into the gut will mean that stercobilinogen is not produced. Therefore, stools will lack pigment and be pale (as seen in biliary atresia).

Figure 1

The simplified bilirubin metabolic pathway. GI, gastrointestinal; UDP, uridine diphosphate. Created by N. Chowdhury.

Pathophysiology

Unconjugated hyperbilirubinaemia is due to physiological or pathological processes. Over 75% of neonatal unconjugated hyperbilirubinaemia is physiological, resulting from a combination of:

increased bilirubin production;

decreased bilirubin clearance;

increased enterohepatic circulation.

These processes lead to higher serum bilirubin levels. Physiological processes can be exacerbated by pathological processes, the most common of which are outlined in table 1.

Physiological jaundice typically occurs in the first week of life, peaking around day 5 and resolving within 2 weeks.5 Jaundice requiring intervention within 24 hours of birth is considered pathological and always warrants further investigation. Hyperbilirubinaemia lasting beyond 14 days in term infants (21 days in preterm infants) is termed ‘prolonged jaundice’. This also requires investigation but is beyond the scope of this article. This fifteen-minute consultation article on liver disease in children has a useful summary.6

Conjugated hyperbilirubinaemia (>25% of the total bilirubin and/or ≥25 µmol/L)7 should be considered pathological until proven otherwise. More information about prolonged jaundiced and conjugated hyperbilirubinaemia can be found at www.childliverdisease.org.

History taking—what to ask and why

A chronological approach is logical and helps ensure nothing is missed (see table 2 for a guide). However, this list is not exhaustive and should not replace clinical judgement.

Table 2

Questions to ask when taking a history for a baby under 2 weeks of age with jaundice

Early weight loss in infants

In the initial scenario, there are concerns about weight loss in addition to jaundice. Weight loss or worries about feeding are common reasons for presentation to paediatrics,8 9 as well as a source of significant parental anxiety.

Most babies lose weight in the first few days of life due to fluid shifts and the increasing diuresis that occurs after 24 hours. A nadir in weight loss occurs 48–72 hours after birth, with loss of up to 10% of birth weight considered within normal limits. There are also small differences in weight loss related to mode of delivery and method of feeding10 11 (table 3). Most babies will return to birth weight by their second or third week of life.12

Table 3

Average weight loss as a percentage of birth weight in the first week of life according to mode of delivery and feeding method

Examination—what to look for, and why

Examining a baby always requires a thorough top-to-toe inspection. In the context of a jaundiced infant under 2 weeks of age, figure 2 outlines what features should be given particular attention.

Figure 2

When examining a jaundiced infant in the first 2 weeks of life there are several things you should pay particular attention to as they could point towards specific diagnoses. GI, gastrointestinal. Image created by N. Chowdhury.

Jaundice becomes visually apparent at serum bilirubin levels of 80–90 μmol/L13 and can easily be missed in babies with darker skin tones. In such cases, examination of the sclerae is vital.

Investigations—what to consider, and why

Several investigations are relevant when identifying potential causes of both jaundice and weight loss in babies. A simple approach guiding initial management is outlined in figure 3.

Figure 3

Flow chart to aid decision making when investigating a baby with jaundice in the first 2 weeks of life. Image created by N. Chowdhury.

It is often appropriate to just check the total serum bilirubin level. A transcutaneous bilirubinometer reading can often be used for this (although at certain levels this TCB reading will need verifying with a serum bilirubin—see table 4). If the total serum bilirubin is not high enough to require treatment or monitoring (ie, 1–50 μmol/L below the National Institute for Health and Care Excellence (NICE) treatment threshold graphs—see box 1) and there are no concerning features in the history or examination, no further investigations are necessary. If a split bilirubin is performed as standard by your laboratory, please ensure that the conjugated fraction is within normal limits or discuss with a senior colleague if there is uncertainty.

Table 4

Basic investigations to consider in infants under 2 weeks of age presenting to the paediatric emergency department with jaundice

If the bilirubin level is over the phototherapy threshold, or close enough to require monitoring, consider checking a full blood count, blood group and direct antiglobulin test. If there is significant weight loss (>10% of birth weight), a sodium and renal function may also be useful.

For infants who appear clinically unwell and/or who have a serum bilirubin level near or above the exchange transfusion threshold, consider investigating for sepsis (C reactive protein and blood culture).

Table 4 discusses the reasoning for these investigations. This list is not exhaustive. If in doubt, discuss with a senior clinician.

Management

How the above scenario is managed will depend on the outcome of the history, examination and investigations. The bilirubin may need repeating, even if the infant is discharged home. Box 2 outlines when to do this.

Box 2 When to monitor and repeat bilirubin levels in infants <14 days presenting to the paediatric emergency department with jaundiceFor babies under 24 hours of life:

If jaundice is suspected, urgently measure bilirubin levels within 2 hours.

Repeat every 6 hours until levels stable or falling.

For babies over 24 hours of life:

Babies with suspected jaundice who are >24 hours old should have their bilirubin level measured within 6 hours of the possible jaundice being noted.

If bilirubin is <50 μmol/L from treatment threshold repeat levels within 24 hours, or within 18 hours if risk factors* for neonatal jaundice.

If bilirubin is >50 μmol/L from treatment threshold in a baby who is clinically well and gestational age over 38 weeks, bilirubin levels do not need to be routinely repeated.

*Those with a sibling who had neonatal jaundice that needed phototherapy or a mother who intends to exclusively breast feed.

Adapted from the National Institute for Health and Care Excellence guideline CG98: Jaundice in newborn babies under 28 days.

Regardless, for all babies with jaundice in the first 2 weeks of life, one should:

Plot their bilirubin on a gestation-appropriate treatment threshold graph.14

Document their weight in the personal child health record (Red Book).

Directly observe feeding and discuss a feeding plan. This15 fifteen-minute consultation article is a useful guide. Use breastfeeding specialists where possible.

The majority of babies with simple physiological jaundice will not require treatment.16 However, identification of a baby with jaundice requiring treatment should be acted on without delay. The NICE guideline Jaundice in newborn babies under 28 days 14 threshold charts should be used to inform decisions about starting phototherapy and monitoring. Be aware that phototherapy is unlikely to be beneficial in cases of conjugated hyperbilirubinaemia.

Babies with significant jaundice (ie, above exchange transfusion threshold) or evidence of conjugated hyperbilirubinaemia should always be discussed with a senior. Do not delay commencement of intensive phototherapy while considering other management options such as intravenous immunoglobulin or an exchange transfusion. If the latter is necessary, consider the speed at which central access and group-specific blood need to be obtained and be aware that tertiary neonatal units should be involved in the care of these infants. More information regarding management is available in the NICE guideline CG98. Ensure that antibiotics are administered within the hour if suspected sepsis as a contributory factor. Box 3 lists the key take home messages. Box 4 identifies some common ‘red flags’ when deciding how to manage infants with jaundice in the first 2 weeks of life.

Box 3 Take home messages

Jaundice and weight loss in the first 2 weeks of life are both common reasons for paediatric presentations.

Jaundice can potentially lead to irreversible, life-long brain damage (kernicterus). It can also be associated with serious underlying pathology.

Jaundice is a sign, not a diagnosis. When assessing a baby with jaundice, it is important to consider what the level of jaundice is and what the cause of the jaundice is. However, this should not delay starting phototherapy if the jaundice is significant.

Jaundice requiring intervention within 24 hours of birth should be considered pathological until proven otherwise.

Investigations:

For infants who present with straightforward, uncomplicated jaundice not requiring treatment, a weight and bilirubin check (transcutaneous or serum) may be sufficient.

For infants who present with jaundice requiring phototherapy but who are feeding well and have no significant weight loss, relevant investigations would normally include a full blood count, blood group and direct antiglobulin test.

For infants who present with jaundice requiring treatment in addition to significant weight loss, first-line investigations would also normally include a weight, serum bilirubin, serum urea and electrolytes and a blood glucose level.

Box 4 ‘Red flags’ when assessing the neonate with jaundice in the first 2 weeks of life

Fever, poor handling or looks unwell (think infection).

Pale stools (think obstructive jaundice).

Pallor (think haemolysis).

Refractory jaundice (think enzyme deficiency).

Jaundice above the exchange transfusion line.

Conclusion

Jaundice in the newborn period is common. Understanding bilirubin metabolism and the pathophysiology of hyperbilirubinaemia in the neonate will help direct history taking, clinical examination and investigations. These will, in combination, allow healthcare practitioners to formulate differential diagnoses for the likely cause of jaundice in the baby that they are seeing, and enable the most appropriate management plan to be actioned.

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