Dr Peter Mallett | Dr Andrew Thompson

Royal Belfast Hospital for Sick Children, Belfast, N. Ireland

‘I think they are a little bit jaundiced ‘…‘No it’s just the light we have them in’… ‘Sure they’re healthy breast-fed baby it’ll be alright won’t it?… ‘That’s a normal colour baby poo isn’t it?’

Jaundice is tricky! Whilst it is common in newborn babies (and there are many different causes) it can be challenging to identify it promptly, it may be a sign of more serious underlying disease, and if not recognised and treated properly, it can lead to irreparable damage!

Okay, now that I’ve got your attention, I can reassure you that the majority of cases are benign and often due to a physiological form of jaundice. But hang on; before you go confidently diagnosing that, perhaps it would be a good idea to have a brief overview of the physiology that contributes to jaundice, and awareness of the variety of contributing pathological causes.

In this article, I will focus on a pragmatic approach to jaundice in the newborn period (that is the first four weeks of life), breaking it down into time frame of presentation, common causes, and a basic approach to management.

After reading this you will hopefully feel a lot more confident on recognition, investigation and management of the common causes of jaundice in the neonate.

The physiology:

Okay, let’s refresh some of the physiology knowledge that is stored in the darkest realms of your med-school neurones. Red blood cells are broken down by macrophages into haem and globin. Globin is a form of protein, which is further broken down into amino acids. The haem is broken into unconjugated bilirubin and iron. Remember? Yes, of course we believe you!

Unconjugated bilirubin is a toxic substance and produces a yellow/orange colour. It is lipid-soluble and piggy-backs on albumin and is carried to the liver. There, conjugation occurs forming conjugated bilirubin. This is a water-soluble product. As a result, this form can be excreted by the liver in the bile into the small intestine. Later, in the large intestine, this conjugated bilirubin can be degraded mainly into urobilinogen and later urobilin (which is transported to the kidneys and gives urine its yellow colour) and stercobilin (giving poo its brown colour).

For a nice, brief video of bilirubin metabolism revision- check this out. Simples.

So what?!

So naturally, when things go wrong (or in some cases when a normal part of the pathway is over-worked) – either pre-hepatic, hepatic, or post-hepatic – this may lead to an accumulation of either the unconjugated or conjugated form of bilirubin with potentially serious implications such as coagulopathy, hypoglycaemia, seizure, hearing difficulties, liver failure, cerebral palsy… and death.

We need the skills to know what to recognise, when and how to investigate and who to involve… so let’s get started!

Spotting the yellow-ness…

For the language buffs out there, the term ‘jaundice’ comes from the French ‘jaunice’ meaning ‘yellowing’. It is also known as ‘icterus’, which randomly is derived from the historical notion that jaundice could be cured by looking at a yellow bird (I can’t explain that one!)

According to some literature, jaundice becomes clinically apparent when the serum bilirubin level is greater than 80μmol/L. In reality, jaundice can be difficult to identify, but is more obvious in certain areas if you know where to look –

It usually deposits in the skin, sclera (as below) and occasionally gums where the yellow discolouration is caused by our afore-mentioned friend bilirubin.

It is really important to examine the exposed child in bright natural light, and be mindful that is often more challenging to recognise in babies who are pre-term, are < 36 hours old or those who have darker skin.

One useful non-invasive way of estimating bilirubin levels is using a transcutaneous bilimeter. These are only recommended in babies over 35 weeks’ gestation and those over 24 hours of age.

They can be used by community midwives and also in hospital – potentially reducing the number of times a baby has to have a heel-prick done. Suggested practice is to take three readings of the skin bilimeter and take the highest of the three. If you think the baby looks clinically more jaundiced than the bilimeter says, then you should correlate this with a blood sample. If the reading is ever over 250μmol/L, you should take a formal serum bilirubin.

(Cue sigh…) Common things are common…

Okay, bear with me following that entirely unhelpful statement that we’ve heard too many times.

Putting things into perspective, they reckon that 3 out of 5 term babies (and 4 out of 5 pre-term babies) develop jaundice in the first week of life. That is pretty common!

Prolonged jaundice is regarded as jaundice persisting past 14 days in term babies and 21 days in pre-term babies (born > 37 weeks gestation).

Some units give term babies who are exclusively breast-fed 21 days leeway before defining this as prolonged jaundice.

It’s all in the history… well, mostly!

A really useful way of trying to group the potential causes of this newborn babies jaundice is by asking the key question:

At what day of life was the jaundice first noticed?

This vital piece of information will help you organise your thoughts as to the possible causes.

I will discuss this in three categories and touch on some of the main players in each section.

<24 hours of life

Lesson one:

Jaundice in the first 24 hours of life is always pathological and requires urgent attention

It suggests an antenatal disease process.

It is often as a result of haemolysis (causing excess release of unconjugated bilirubin) and could be due to ABO incompatibility, Rhesus disease of the newborn or haemogloninopathies such as hereditary spherocytosis. Relevant blood tests would include (aside from LFTs with total and direct bilirubin of course) Full blood count (? anaemia), blood film (?evidence of haemolysis or immature cells), reticulocyte count, Direct Coombs test, blood group of mother and baby.

Another common group of conditions responsible for jaundice presenting in the first day of life are congenital infections. This could arise from an ante-natal insult (e.g. from amniotic fluid) or a peri-natal insult (e.g. from the mothers genital tract). Sepsis must be ruled out.

Appropriate investigations include infection markers, blood cultures, and a TORCH Screen looking for:

• Toxoplasmosis
• Other
• Rubella
• Cytomegalovirus
• Hepatitis or Herpes

Onset between Day 2 – Day 14

So this isn’t as straight forward as the first group – as jaundice in this timeframe may either be physiological or pathological. Frustrating eh?!

Physiological jaundice is common, usually appears within the first week of life and gradually regresses by the end of the first week to ten days. It is probably due to several contributing factors:

• Immature neonatal liver – struggles to deal with the accumulation of bilirubin
• Quicker foetal haemoglobin breakdown leading to excessive bilirubin formation

Breast-milk jaundice generally hangs around after physiological jaundice subsides. It is

seen in term, otherwise healthy breast-fed babies. Around 1 in 10 breast-fed babies are still jaundiced at one month. The exact cause is unknown but most think that it is linked to a substance in breast milk which slows the breakdown of bilirubin. Breast milk jaundice can last for up to three months after birth – but as long as the baby is feeding well, and bilirubin levels are monitored, it rarely leads to serious problems.

Breast-feeding jaundice is a different entity and it is really important to separate these two conditions. This is related to an insufficient volume of milk received by the baby, and can often be aggravated by things like an inadequate latch, maternal anxiety, or lack of support. It is important to work out the amount of weight loss relative to the birth weight. Generally most centers allow up to ~10% weight loss for breastfed babies and expect most to have regained it by the first two- three weeks of life. Anything more than 10% – or delay in regaining birth weight – needs close attention.

As we know, ‘breast is best’, and we are obliged to ensure that mum and baby are supported to be able to breast feed successfully, if this is the parents’ choice of how to feed their baby. This can often be aided by input from breast-feeding support coordinator and community midwives. On the flip side, no mother should ever be made to feel stigmatised if she is struggling to breast feed, or has simply chosen not to breast feed for ANY reason.

Pathological causes in this 2-14 day period include important conditions such as sepsis (yep you guessed it!), haemolysis, bruising, hypothyroidism or metabolic disorders.

For sepsis – specifically focus your questions on the baby and the mum:

• Baby – Any temperatures? Warm or cold? Irritability? Poor handling? Drowsy? Poor feeding? Vomiting? Any evidence of temperature instability or disproportionate tachycardia.
• Mum– Any risk factors for sepsis- e.g. maternal temperature, prolonged rupture of membranes, chorioamniotis, and history of Group B Streptococcal (GBS) colonisation or urinary tract infections.

Appropriate tests may include FBC, CRP, blood sugar, blood culture, urinalysis and culture as well as revisiting maternal serology, vaginal swabs and urine and blood culture results.

Bruises are caused by the breakdown of red cells, and hence release of bilirubin. Consider this as a possible cause of jaundice in cases such as traumatic or instrumental

deliveries, malpresentation (e.g. face presentations) or presence of excessive bruising or cephalhaematoma. Also, ask whether the baby received Vitamin K dose post-natally (aimed to prevent haemmorhagic disease of the newborn).

Other causes in this group include the more uncommon things such as congenital hypothyroidism or metabolic conditions (such as galactosaemia). Relevant blood tests include the newborn screening test at Day 5 of life (aka the Guthrie card or checking these results if baby is older than 5 days old at presentation) and further metabolic tests such as GAL-1-PUT for galactosaemia etc. depending on the clinical situation.

Onset after Day 14

The final section is that group of babies who present with (or continue to have) jaundice after 14 days of life. Remember, in a preterm baby (born <37 weeks) it is usually considered prolonged after 21 days of life.

Again breast-milk jaundice may be responsible for persistent or late onset jaundice, as eluded to previously.

Pathological causes can be separated into those arising from in and around the liver (hepatic) and after the liver in the biliary system (post-hepatic).

Any form of neonatal hepatitis must be urgently investigated (consider in baby with unexplained coagulopathy, deranged liver function tests or encephalopathy). For a slick vodcast on this topic check this out.

Pre-term babies or those with particular GI conditions who receive total parental nutrition (TPN) are at particular risk of prolonged jaundice – but this is considered a diagnosis of exclusion and other reversible causes must be investigated and treated.

At this stage, a useful blood test is calculating total and direct bilirubin levels or a ‘split’ bilirubin. Conjugated hyperbilirubinaemia is when conjugated bilirubin levels are >20- 25% of

total bilirubin. Patients can present as green or tanned in appearance (as opposed to traditional yellow jaundice appearance) which may suggest an underlying cholestatic problem. The urine may be dark and stool pale or clay-coloured (as below in our simulated poo-nappy) or acolic due to absence of bile pigment (remember back to the bilirubin metabolism to explain why that happens).

Many healthcare organisations and countries have high-profile public health campaigns to guide parents on jaundice and specifically the colour of worrying poos (such as this ‘Beware Yellow’ campaign from NZ).

Relevant radiological investigations may include ultrasound scan of abdomen, HIDA Scan, and potentially a liver biopsy.

Biliary atresia is a rare condition in which parts of the biliary system fail to develop, leading to blockage of bile. As it occurs after the liver (post-hepatic), it leads to a conjugated hyperbilirubinaemia, and corrective surgery (Kasai procedure) is needed as soon as possible (ideally < ~8 weeks of age) to prevent long-term complications.

How do I fix it?

Firstly, just a reminder that Jaundice is a symptom and not a diagnosis in itself. Phototherapy to reduce hyperbilirubinaemia is the standard first step of management – but don’t switch your brain off until you have thought thoroughly about the possible underlying reasons that the baby is yellow!

Phototherapy needs to be started as soon as possible if the bilirubin level is above the ‘treatment line’ – use the NICE treatment graphs or the really useful ‘BiliApp’ on your smartphone.

Depending on these levels, single to quadruple phototherapy or even exchange transfusion may be required. If the levels are below the phototherapy line, then reassurance and close surveillance is needed while you optimise other aspects of care.

How does phototherapy actually work, you’re asking? When a jaundiced baby is exposed to blue or white fluorescent light of a certain wavelength, bilirubin is broken down into products which are easily excreted, in a process known as photo-oxidation. It is important that as much of the baby’s skin is exposed as possible, and that suitable eye-protection is worn. As this process interrupts the natural bonding process between parents and baby, it is crucial to carefully monitor the bilirubin levels, and when appropriate stop the phototherapy treatment when bilirubin levels fall adequately, according to your local policy.

Of course, while you are fixing the acute problem of hyperbilirubinaemia, you need to investigate the underlying cause of jaundice which may need further treatment – and you can see from the range of potential causes, the possible treatments needed are diverse (and discussing them all is beyond the scope of this article).

Follow the Yellow Brick Road…to a diagnosis!

I hope this has given you a logical step-wise approach to identifying jaundice in a newborn baby, helped distinguish some of the many different causes, and given a brief insight into management.

With a focused history, careful examination and appropriate investigations, you have the skill-set to separate the ‘normal’ yellow from the ‘worrying’ yellow… and to deliver the right treatment for your little lego-esque friend, helping them get home as soon as possible!

References:

NICE Guidelines- Neonatal Jaundice. 2010

Lissauer. Illustrated textbook of Paediatrics

Kidshealth.org.nz

Acknowledgements:

• I am very grateful to the parents of the little dude in Image 2 for consent in using this photograph for educational purposes.
• Image 3 is an image of a simulated white stool. Taken on behalf of the Simulation & Education department. Thanks to my colleagues at the RBHSC Play Therapy department for their help.

Dr Peter Mallett, Paediatric Registrar, Education & Simulation Fellow (@SimEdRBHSC) and Dr Andrew Thompson, Consultant Paediatrician