Neonates: Neonatal Jaundice Flashcards
How common is neonatal jaundice?
Around 60% of term babies and 80% of preterm babies will develop jaundice in the first week of life.
Although most cases are not caused by an underlying pathology, jaundice can indicate serious disease and may result in long-term morbidity and even mortality if untreated.
When is neonatal jaundice ALWAYS pathological?
In the first 24 hours
Give 4 causes of jaundice in the first 24 hours?
Haemolytic disease:
1) rhesus haemolytic disease
2) ABO haemolytic disease
3) hereditary spherocytosis
4) glucose-6-phosphodehydrogenase
What is jaundice?
Describes the condition of abnormally high bilirubin in the blood.
RBCs contain unconjugated bilirubin.
When RBCs break down, the release unconjugated bilirubin into the blood.
Unconjugated bilirubin is conjugated in the liver.
Conjugated bilirubin is excreted in two ways: via the biliary system into the gastrointestinal tract and via the urine.
Where is bilirubin conjugated?
Liver
Jaundice in a healthy baby, born at term.
What are the 2 reasons behind physiological neonatal jaundice?
1) Increased RBC breakdown
2) Immature liver not able to process high bilirubin concentrations
3) A relatively high concentration of β-glucuronidase in the small intestine
Why is there increased RBC breakdown in neonates?
In utero the foetus has a high concentration of Hb (to maximise oxygen exchange and delivery to the fetus).
These RBCs are more fragile than normal RBCs and break down, releasing bilirubin as high Hb is no longer needed.
Normally this bilirubin is excreted via the placenta, however at birth the foetus no longer has access to a placenta to excrete bilirubin.
When is physiological neonatal jaundice most common?
From 2-10 days
What type of babies is physiological jaundice more commonly seen in?
Breastfed babies
Interventions in neonatal jaundice?
None
When would neonatal jaundice caused by haemolytic disease present?
In the first 24 hours
What is bilirubin produced from?
Breakdown of RBCs
What happens to circulating unconjugated bilirubin?
Most binds to albumin but some circulates as ‘free’ bilirubin –> this is lipid-soluble and can cross the blood-brain barrier.
What enzyme converts unconjugated bilirubin to conjugated bilirubin in the liver?
UDP-glucuronosyltransferase (UGT)
Pathway of bilirubin metabolism:
1) Bilirubin is produced from the breakdown of RBCs
2) UDP-glucuronosyltransferase (UGT), converts unconjugated bilirubin to conjugated bilirubin in the liver
3) Conjugated bilirubin is transported to the small intestines via the biliary system and some is converted back to unconjugated bilirubin by the enzyme β-glucuronidase.
4) This unconjugated bilirubin re-enters the circulating pool of bilirubin via the enterohepatic circulation.
5) The remaining conjugated bilirubin is metabolised by intestinal bacteria to produce urobilinogen and stercobilinogen
6) Urobilinogen is oxidised to urobilin, which gives urine its yellow colour.
7) Stercobilinogen is oxidised to stercobilin, which gives faeces its brown colour.
Can unconjugated bilirubin cross the BBB?
Yes - is lipid soluble
Can conjugated bilirubin cross the BBB?
No - is water soluble but lipid insoluble
What are the 2 metabolites of conujgated bilirubin?
1) Urobilinogen
2) Stercobilinogen
What gives urine its yellow colour?
Urobilin
What is urobilinogen oxidised to?
Urobilin
What is stercobilinogen oxidised to?
Stercobilin
What gives faeces its brown colour?
Stercobilin
Which neonates are more prone to jaundice?
1) Preterm babies: tend to have higher bilirubin levels and more prolonged jaundice than term infants.
2) Breastfed babies: experience more marked and prolonged jaundice than formula-fed infants
3) Babies with significant bruising or cephalohaematoma: occurs in difficult deliveries
Is physiological jaundice conjugated or unconjugated?
Unconjugated
Give some haemolytic causes of neonatal jaundice
1) Haemolytic disease of the newborn: caused by maternal Rhesus or ABO antibodies against the baby’s RBCs
2) Hereditary spherocytosis: an inherited disease where defects in RBC skeletal proteins cause RBCs to assume a spherical shape with a reduced lifespan
3) G6PD deficiency: an X-linked recessive condition where lack of G6PD makes RBCs susceptible to oxidative damage and haemolysis. It can cause severe neonatal jaundice.
Give 4 endocine or metabolic causes of unconjugated neonatal jaundice
1) Gilbert’s syndrome
2) Crigler-Najjar syndrome
3) Congenital hypothyroidism
4) Galactosaemia and other inborn errors of metabolism (these may also cause conjugated jaundice)
What is Gilbert’s syndrome?
An autosomal recessive disorder with reduced UGT enzyme activity in the liver. This causes reduced ability to conjugate bilirubin, resulting in mild episodes of jaundice throughout life in response to certain triggers.
What enzyme has reduced activity in Gilbert’s syndrome?
UGT enzyme - enzyme in liver responsible for conjugating bilirubin.
What is Crigler-Najjar syndrome?
A rare autosomal recessive disorder where no functioning UGT is produced in the liver. It presents with severe, prolonged jaundice that often results in neurological damage and death within one year of life.
What are 3 causes of conjugated neonatal jaundice?
1) Biliary atresia
2) Neonatal hepatitis (e.g. CMV, hepatitis B, rubella or herpes simplex virus)
3) Galactosaemia and other inborn errors of metabolism
What is a common cause of neonatal jaundice within the first 24 hours?
Neonatal sepsis
Why is physiological jaundice exaggerated in premature neonates?
Due to the immature liver.
What is haemolytic disease of the newborn (HDN)?
A cause of haemolysis (red blood cells breaking down) and jaundice in the neonate.
It is caused by incompatibility between the rhesus antigens on the surface of the red blood cells of the mother and fetus.
What must you consider when a woman that is rhesus D negative (does not have the rhesus D antigen) becomes pregnant?
Must consider the possibility that her child will be rhesus D positive (has the rhesus D antigen).
1) It is likely at some point in the pregnancy the blood from the baby will find a way into her bloodstream.
2) When this happens, the baby’s red blood cells display the rhesus D antigen.
3) The mother’s immune system will recognise this rhesus D antigen as foreign and produce antibodies to the rhesus D antigen.
4) The mother has then become sensitised to rhesus D antigens –> normally not a problem during 1st pregnancy
5) During subsequent pregnancies, the mother’s anti-D antibodies can cross the placenta into the fetus. If that fetus is rhesus positive, these antibodies attach themselves to the red blood cells of the fetus and causes the immune system of the fetus to attack their own red blood cells.
6) This leads to haemolysis, causing anaemia and high bilirubin levels (haemolytic disease of the newborn)
When can the sensitisation process in a rhesus D negative mother be a problem in their first pregnancy?
If the sensitisation happens early on, such as during antepartum haemorrhage
Risk factors for pathological hyperbilirubinaemia?
1) Prematurity, low birth weight, small for dates
2) Previous sibling required phototherapy
3) Exclusively breast fed
4) Jaundice <24 hours
5) Infant of diabetic mother
What is biliary atresia?
A congenital inflammatory disease of unknown cause.
It results in complete obliteration of the extra-hepatic bile ducts after birth.
If untreated, it progresses to liver cirrhosis and death.
How does biliary atresia present?
1) Prolonged conjugated jaundice
2) Pale stools
3) Dark urine
What defines prolonged neonatal jaundice?
More than 14 days in full term babies.
More than 21 days in premature babies.
What is the gold standard diagnostic method for biliary atresia?
A percutaneous biopsy
Management of biliary atresia?
1) portoenterostomy (Kasai procedure)
or
2) liver transplant
What investigations are required in prolonged neonatal jaundice?
1) conjugated and unconjugated bilirubin levels
2) direct antiglobulin test (Coombs’ test): for haemolysis
3) TFTs
4) FBC and blood film: for polycythaemia or anaemia
5) urine for MC&S and reducing sugars
6) U&Es and LFTs
7) G6PD levels for G6PD deficiency
Causes of prolonged neonatal jaundice?
1) biliary atresia
2) hypothyroidism
3) galactosaemia
4) UTI
5) breast milk jaundice
6) prematurity
7) congenital infections e.g. CMV, toxoplasmosis
Clinical features of neonatal jaundice?
1) Colour
- baby should be naked and examined in bright, natural light
- jaundice is often most obvious in the sclerae and gums
- blanche the skin
2) Drowsy: difficult to rouse, not waking for feeds, very short feeds
3) Neuro:
- altered muscle tone
- seizures-needs immediate attention
4) Pale, chalky stools (conjugated jaundice)
5) Dark urine (conjugated jaundice)
Which neonates require routine bilirubin checking?
All babies who are visibly jaundiced
What are 2 options for measuring bilirubin levels in neonates?
1) Transcutaneous bilirubinometry
2) Serum bilirubin
What is transcutaneous bilirubinometry?
A bedside test that evaluates light absorption through the skin over the forehead or sternum.
It is not as accurate as serum bilirubin but is non-invasive.
When would transcutaneous bilirubinometry be used to over serum bilirubin and vice versa?
Transcutaneous bilirubinometer:
- >35 weeks gestation
- >24 hours old
- Can be used for all subsequent measurements, providing the level remains <250 µmol/L and the child has not required treatment
Serum bilirubin:
- Babies who are visibly jaundiced <24 hours of life
- Gestational age <35 weeks
- Monitoring bilirubin after starting treatment.
Which investigation is used to monitor bilirubin levels AFTER starting treatmnet?
Serum bilirubin
Which investigation is used to monitor bilirubin levels in jaundiced neonates with a gestational age <35 weeks?
Serum bilirubin
Which investigation is used to monitor bilirubin levels in neonates that are jaundiced <24 hours of life?
Serum bilirubin
What investigations are required for babies who require TREATMENT for jaundice?
1) Blood packed cell volume (PCV)
2) Blood group of the mother and baby
3) Direct antiglobulin test (DAT, aka Coombs’ test)
Also consider:
- FBC and blood film
- G6PD levels
- Blood, urine and/or cerebrospinal fluid cultures: if signs of infection
Purpose of a blood packed cell volume (PCV) in neonatal jaundice?
To assess the degree of anaemia or polycythaemia
Purpose of investigating blood group of the mother and baby in neonatal jaundice?
To assess for incompatibility (i.e. haemolytic disease of the newborn)
What does a positive Coombs test indicate?
Suggests immune-mediated haemolysis (i.e. haemolytic disease of the newborn).
What does a negative Coombs test indicate?
suggests non-immune-mediated haemolysis (e.g. hereditary spherocytosis or G6PD deficiency)
What are the 2 main methods to treating neonatal jaundice?
1) phototherapy
2) exchange transfusion
Note - most babies will respond well to phototherapy and exchange transfusions are rarely used.
What is the decision to begin treatment in neonatal jaundice based on?
Treatment threshold graphs.
There are different graphs for different gestations and preterm babies have a lower threshold for starting treatment.
What happens in phototherapy in the management of neonatal jaundice?
The baby is placed under blue-green light.
The light converts the neurotoxic unconjugated bilirubin to a harmless, water-soluble isomer called lumirubin, which is readily excreted in the bile and urine.
What is unconjugated bilirubin converted to during phototherapy?
lumirubin
How do exchange transfusions work in neonatal jaundice?
Exchange transfusions reduce bilirubin levels by swapping the baby’s blood with donor blood. A small volume of the baby’s blood is removed as donor blood is injected.
This may be required for dangerously high levels of bilirubin.
As well as lowering serum bilirubin levels, exchange transfusions can also remove a significant proportion of the antibodies responsible for haemolytic disease of the newborn.
Who are exchange transfusions reserved for in neonatal jaundice?
Exchange transfusions have a high rate of complications, so they are reserved for the most severe cases of neonatal jaundice which are not responding to intense phototherapy or where babies are showing signs of acute bilirubin encephalopathy.
What is found on a treatment threshold charts for neonatal jaundice?
Age of the baby - plotted on x-axis
Total bilirubin level - plotted on y-axis
If the total bilirubin reaches the threshold on the chart, they need to be commenced on treatment to lower their bilirubin level.
When is treatment for neonatal jaundice initiated according to treatment graph?
1) If level is on or above the phototherapy line
2) If level is below phototherapy line:
a) >50µmol/L below, clinically well with no risk factors for neonatal jaundice do not routinely repeat level
b) <50µmol/L below, clinically well repeat level within 18 hours (risk factors present) to 24 hours (no risk factors present)
How often should bilirubin levels be monitored during treatment for neonatal jaundice?
Repeat bilirubin 4-6 hours post initiation to ensure not still rising, 6-12 hourly once level is stable or reducing.
When can phototherapy for neonatal jaundice be stopped?
Stop phototherapy once level >50µmol/L below treatment line on the threshold graphs.
Check for rebound of hyperbilirubinaemia 12-18 hours after stopping phototherapy.
What can be used as adjunct to intensified phototherapy in rhesus haemolytic disease or ABO haemolytic disease?
IV Immunglobulin
What is the key complication of neonatal jaundice?
Bilirubin encephalopathy (kernicterus).
This occurs with high levels of unconjugated bilirubin.
What is Kernicterus?
A type of brain damage caused by excessive bilirubin levels.
Unconjugated bilirubin is lipid-soluble and can cross the BBB. It accumulates in the brainstem nuclei, basal ganglia, hippocampus and cerebellum and is neurotoxic.
How does bilirubin encephalopathy (kernicterus) present?
- lethargy
- hypotonia
- poor suck reflex
This progresses to:
- hypertonia
- opisthotonos
- fever
- seizures
- a high-pitched cry
Prognosis of kernicterus?
Early damage to the brain can be reversible.
If hyperbilirubinemia is pronounced or prolonged then it can lead to cerebral palsy, sensorineural hearing loss or cognitive impairment.
1st line investigation in suspected pathological neonatal jaundice?
Coombs test
+ve when mothers Abs attack baby’s RBC (due to ABO or Rh incompatibility).
When are doses of anti D given?
1) 28 weeks gestation
2) Within 24 hours of birth
What is the most common scenario of ABO incompatibility causing HDN?
Mother has O blood group and baby has A or B blood type.
Typically there are already anti-A and anti-B antibodies present in the mother’s circulation (even without any sensitisation from a prior pregnancy).
This is because A and B antigens are similar to common enivornmental antigens (e.g. bacteria, dust or pollen).
Exposure to these antigens results in the generation of anti-A and anti-B antibodies –> these Abs cross the placenta and cause haemolysis in the 1st pregnancy.
If the Coombs test is negative in neonatal jaundice, what is the next step?
Check Hb level.
If low –> may be a blood collection outside vessels e.g. cephalohaematoma due to trauma during delivery.
If high –> increased load of RBCs is slowly getting broken down –> common in babies of diabetic mothers, twin-twin transfusion syndrome, delayed cord clamping.
How can a cephalohaematoma cause neonatal jaundice?
Blood collection outside vessels breaks down and gets absorbed as bilirubin.
If Hb is normal in neonatal jaundice, what is next step?
Check reticulocyte count, LDH & haptoglobin.
Then consider blood film.
Possible investigations in neonatal jaundice?
1) Coombs test
2) Hb level
3) Reticulocyte count, LDH & haptoglobin
4) Blood film
5) Enzyme levels e.g. G6PD
6) Hb electrophoresis –> haemoglobinopathies e.g. sickle cell, thalassaemia
