Neonatal Jaundice

Question 1

Define

Answer 1

> 50% new-borns become visibly jaundiced due to…

• Physiological Hb release from RBC (high [Hb] at birth)
• Breast milk jaundice (only >24hrs)
• RBC lifespan of 70 days rather than 120 days in adults
• Hepatic billirubin metabolism less efficient in 1st few days of life

Unconjugated bilirubin can be deposited in the brain, particularly in the basal ganglia, causing kernicterus.

NOTE: babies become clinically jaundiced when the bilirubin level reached about 80mM/L

1. Unconjugated jaundice- resolves spontaneously
2. Conjugated jaundice- indicates liver disease

Question 2

Jaundice in a neonate <24hrs
Signs and Symptoms

Answer 2

May be a sign of disorder (haemolytic anaemia, infection/sepsis, inborn error of metabolism, liver disease)

uBR -> deposit in basal ganglia -> kernicterus (a form of encephalopathy)
* Once albumin saturated and free uBR circulates (fat-soluble) -> crosses BBB and accumulates
* Causes spectrum from severe damage -> death;

Signs & symptoms:

1. Lethargy, poor feeding
2. Irritability
3. Increased muscle tone (arched back)
4. Seizures and coma

• May develop into cerebral palsy (dyskinetic), learning difficulties and sensorineural deafness
• Was a major problem with Rhesus disease of the newborn (not so much now with anti-D prophylaxis)
• Prevented with phototherapy ± IVIG, and exchange transfusion if required

Visible jaundice seen at 80umol/L:
- uBR (fat soluble) -> kernicterus
- cBR (water soluble) -> dark urine, pale stools

N.B. phototherapy only works on uBR (converts uBR to lumirubin and photobilirubin) and not cBR. If you give phototherapy and ‘bronzing’ occurs, then the child has cBR and not uBR and the phototherapy should be stopped.

Question 3

Risk factors

Answer 3

Gestational age < 38 weeks

Previous sibling with neonatal jaundice requiring phototherapy

Exclusive breastfeeding

Visible jaundice within 24 hours of life

Question 4

Kernicterus

Answer 4

DEFINITION: encephalopathy resulting from the deposited unconjugated bilirubin in the basal ganglia and brainstem nuclei

It may occur when the level of unconjugated bilirubin EXCEEDS the albumin-binding capacity of bilirubin of the blood.

As the free bilirubin is fat soluble, it can cross the BBB.

The neurotoxic effects vary in severity, from transient disturbance to severe damage and death

Acute manifestations include lethargy and poor feeding.

In severe cases, infants will show:
* Irritability
* Increased muscle tone causing the baby to lie with an arched back (opisthotonos)
* Seizures
* Coma

Infants who survive may develop:
* Choreoathetoid cerebral palsy (due to damage to the basal ganglia)
* Learning difficulties
* Deafness

Kernicterus (cerebral palsy + deafness) used to be an important cause of brain damage in infants with severe rhesus haemolytic disease. However, it has become rare since the introduction of prophylactic anti-D immunoglobulin for rhesus-negative mothers

Prevented with phototherapy ± IVIG, and exchange transfusion if required

Question 5

Causes for <24 h

Answer 5

< 24 hours of age

Always pathological, usually due to haemolysis

Haemolytic disorders

**Rhesus Haemolytic Disease **
* Infants affected are usually identified antenatally
* Severely affected infants will have anaemia, hydrops and hepatosplenomegaly with rapidly developing severe jaundice
* Antibodies may develop due to rhesus antigens other than D (e.g. Kell and Duffy)

**ABO incompatibility **

• Most ABO antibodies are IgM and DO NOT cross the placenta
• However, some group O women have some IgG anti-A haemolysin in the blood which can cross the placenta and haemolyse the red cells of a group A infant.
• NOTE: occasionally, group B infants are affected by anti-B haemolysin
• The jaundice occurring is usually less severe than Rhesus disease and hepatosplenomegaly is ABSENT.
• Infant’s haemoglobin is usually NORMAL OR only slightly reduced
• The direct antibody test (Coomb’s test) will be positive- demonstrates the antibody to the surface of RBCs.
• Jaundice usually peaks between 12-72 hours

G6PD deficiency

• Mainly affects male infants but some females develop significant jaundice
• Parents of affected infants should be given a list of drugs to avoid as they may precipitate haemolysis

Hereditary spherocytosis
* Often a family history (but not always)
* Spherocytes found on blood film

PK deficiency

Bruising
* Breakdown of haemoglobin with bruising

Metabolic disorders : Gilbert’s, Crigler-Najjar, Dubin-Johnson

Congenital Infection
* Bilirubin is conjugated and infants will have other abnormal clinical signs:

Growth restriction

Hepatosplenomegaly

Thrombocytopenic purpura

Question 6

Causes 2 days to 2 weeks

Answer 6

Physiological Jaundice

• Most babies will become mildly-moderately jaundiced and have no underlying cause
• Bilirubin has risen as the infant is adapting to transition from foetal life

Breast Milk Jaundice

• Jaundice is more common and prolonged in breast-fed infants
• Hyperbilirubinaemia is unconjugated
• Multifactorial cause but may involve increased enterohepatic circulation of bilirubin

Dehydration

• Jaundice is exacerbated if milk intake is poor and infant becomes dehydrated (> 10% weight loss from birthweight)
• Breastfeeding should continue but sometimes supplemental feeding is needed to reverse dehydration
• In some infants, IV fluids may be needed

Infection

• A baby with an infection may develop an unconjugated hyperbilirubinaemia from poor fluid intake, haemolysis, reduced hepatic function and an increase in enterohepatic circulation

Other causes

Bruising and polycythaemia can exacerbate jaundice

Crigler-Najjar syndrome (deficient or absent glucuronyl transference (UGT))- very rare but results in extremely high bilirubin levels

Gilbert’s syndrome

Dubin-Johnson

Haemolysis - G6PDD, PK def, HS

Congenital hypothyroidism

Question 7

> 2 weeks

Answer 7

Jaundice in babies > 2 weeks old (or 3 weeks if preterm) is called persistent or prolonged neonatal jaundice

Unconjugated hyperbilirubinaemia (MOST COMMON):

• Breast milk jaundice is the MOST COMMON cause- affecting up to 15% of infants
• Infection- especially of the urinary tract should be considered
• A urinary tract infection (UTI) is a common serious cause of jaundice in the newborn, and can often present with vague symptoms of lethargy or difficulty feeding. UTI in a newborn is particularly serious as it can rapidly progress to sepsis

Congenital hypothyroidism- may cause prolonged jaundice before clinical features of coarse facial features, dry skin, hypotonia and constipation become evident.

Pyloric stenosis - presents 2-4 wks of age

Conjugated hyperbilirubinaemia- (>25mmol/L) will cause pale stools and dark urine

It may also cause hepatomegaly and poor weight gain

Causes include:
* Neonatal hepatitis syndrome
* Biliary atresia! – IMPORTANT (where ≥ 1 bile ducts are abnormally marrow, blocked or absent)
* Inherited metabolic conditions (Gal-1-PUT deficiency, A1AT deficiency, Tyrosinaemia type 1, Peroxisomal disease)
* Ascending cholangitis (if on TPN, the lipids can cause an ascending cholangitis)
* CF
* Idiopathic

Clinical Features and Severity of Jaundice

Jaundice can be observed most easily by blanching the skin with a finger

Jaundice tends to start on the head and face and then spreads down the trunk and limbs.

Question 8

Investigations

Answer 8

Transcutaneous bilirubin meter OR blood sample – check bilirubin levels

• IMPORTANT: Transcutaneous bilirubin CANNOT be used if newborn is < 24 hours
• Non-invasive – uses spectroscopy to measure light reflection from the skin
• If the result is >250 μmol/L, check the result by measuring serum bilirubin

It is recommended in the UK that all babies should be checked clinically for jaundice in the first 72 hours of life, and if clinically jaundiced, a transcutaneous measurement should be made

Serial measurements and plot bilirubin levels on a chart- the rate at which bilirubin rises tends to be linear until it plateaus- used to anticipate the need for treatment

Drugs that displace bilirubin from albumin e.g. sulphonamides and diazepam, should be avoided in newborn infants

Question 9

Management

Answer 9

Transcutaneous bilirubin meter OR blood sample – check bilirubin levels

IMPORTANT: Transcutaneous bilirubin CANNOT be used if newborn is < 24 hours

Non-invasive – uses spectroscopy to measure light reflection from the skin

If the result is >250 μmol/L, check the result by measuring serum bilirubin

It is recommended in the UK that all babies should be checked clinically for jaundice in the first 72 hours of life, and if clinically jaundiced, a transcutaneous measurement should be made

Serial measurements and plot bilirubin levels on a chart- the rate at which bilirubin rises tends to be linear until it plateaus- used to anticipate the need for treatment

Drugs that displace bilirubin from albumin e.g. sulphonamides and diazepam, should be avoided in newborn infants

Question 10

PACES

Answer 10

Explain that neonatal jaundice is common and usually harmless:

If <1 day, >14 days or >7 days of first presentation of jaundice explain you will investigate the cause

If physiological explain why it happens

Explain treatment (light therapy)

Reassure that the light therapy is not harmful (but eyes will be protected, and blood samples will need to be taken quite regularly).

Encourage frequent breastfeeding (e.g. every 3 hours) and to wake the baby up to feed

Explain need to stay in after phototherapy has stopped to check rebound hyperbilirubinaemia

Resources:

NHS Choices Neonatal Jaundice Factsheet

The Breastfeeding Network (information and support for breastfeeding mothers)

Bliss (for premature and sick babies)