Jaundice describes the condition of abnormally high levels of bilirubin in the blood. Red blood cells contain unconjugated bilirubin. When red blood cells break down, they 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.
Physiological Jaundice
There is a high concentration of red blood cells in the fetus and neonate. These red blood cells are more fragile than normal red blood cells. The fetus and neonate also have less developed liver function.
Fetal red blood cells break down more rapidly than normal red blood cells, releasing lots of bilirubin. Normally this bilirubin is excreted via the placenta, however at birth the foetus no longer has access to a placenta to excrete bilirubin. This leads to a normal rise in bilirubin shortly after birth, causing a mild yellowing of skin and sclera from 2 – 7 days of age. This usually resolves completely by 10 days. Most babies remain otherwise healthy and well.
Causes of Neonatal Jaundice
The causes of neonatal jaundice can be split into increased production or decreased clearance.
Increased production of bilirubin:
- Haemolytic disease of the newborn
- ABO incompatibility
- Haemorrhage
- Intraventricular haemorrhage
- Cephalo-haematoma
- Polycythaemia
- Sepsis and disseminated intravascular coagulation
- G6PD deficiency
Decreased clearance of bilirubin:
- Prematurity
- Breast milk jaundice
- Neonatal cholestasis
- Extrahepatic biliary atresia
- Endocrine disorders (hypothyroid and hypopituitary)
- Gilbert syndrome
TOM TIP: Jaundice in the first 24 hours of life is pathological. This needs urgent investigations and management. Neonatal sepsis is a common cause. Babies with jaundice within 24 hours of birth need treatment for sepsis if they have any other clinical features or risk factors.
Jaundice in Premature Neonates
In premature babies, the process of physiological jaundice is exaggerated due to the immature liver. This increases the risk of complications, particularly kernicterus. Kernicterus is brain damage due to high bilirubin levels. Bilirubin levels need to be carefully monitored in premature babies, as they may require treatment.
Breast Milk Jaundice
Babies that are breastfed are more likely to have neonatal jaundice. There are several potential reasons for this. Components of breast milk inhibit the ability of the liver to process the bilirubin. Breastfed babies are more likely to become dehydrated if not feeding adequately. Inadequate breastfeeding may lead to slow passage of stools, increasing absorption of bilirubin in the intestines.
Breastfeeding should still be encouraged, as the benefits of breastfeeding outweigh the risks of breast milk jaundice. Mothers may need extra support and advice to ensure adequate breastfeeding.
Haemolytic Disease of the Newborn
Haemolytic disease of the newborn is 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. The rhesus antigens on the red blood cells vary between individual. This is different to the ABO blood group system.
Within the rhesus group, there are many different types of antigens that can be present or absent depending on the persons blood type. The most important antigen within the rhesus blood group system is the rhesus D antigen.
When a woman that is rhesus D negative (does not have the rhesus D antigen) becomes pregnant, we have to consider the possibility that her child will be rhesus D positive (has the rhesus D antigen). It is likely at some point in the pregnancy the blood from the baby will find a way into her bloodstream. When this happens, the baby’s red blood cells display the rhesus D antigen. The mother’s immune system will recognise this rhesus D antigen as foreign and produce antibodies to the rhesus D antigen. The mother has then become sensitised to rhesus D antigens.
Usually, this sensitisation process does not cause problems during the first pregnancy (unless the sensitisation happens early on, such as during antepartum haemorrhage). 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. This leads to haemolysis, causing anaemia and high bilirubin levels. This leads to a condition called haemolytic disease of the newborn.
Prolonged Jaundice
Jaundice is “prolonged” when it lasts longer than would be expected in physiological jaundice. This is:
- More than 14 days in full term babies
- More than 21 days in premature babies
Prolonged jaundice should prompt further investigation to look for an underlying cause. These are particularly looking for conditions that will cause jaundice to persist after the initial neonatal period, such as biliary atresia, hypothyroidism and G6PD deficiency.
Investigations
- Full blood count and blood film for polycythaemia or anaemia
- Conjugated bilirubin: elevated levels indicate a hepatobiliary cause
- Blood type testing of mother and baby for ABO or rhesus incompatibility
- Direct Coombs Test (direct antiglobulin test) for haemolysis
- Thyroid function, particularly for hypothyroid
- Blood and urine cultures if infection is suspected. Suspected sepsis needs treatment with antibiotics.
- Glucose-6-phosphate-dehydrogenase (G6PD) levels for G6PD deficiency
Management
In jaundiced neonates, total bilirubin levels are monitored and plotted on treatment threshold charts. These charts are specific for the gestational age of the baby at birth. The age of the baby is plotted on the x-axis and the total bilirubin level on the y-axis. If the total bilirubin reaches the threshold on the chart, they need to be commenced on treatment to lower their bilirubin level.
TOM TIP: It is worth familiarising yourself with treatment threshold charts for neonatal jaundice, as you may be asked to plot or interpret one in your exams. Take care to note the time the baby is born and count in hours. This will be a common task if you ever work in paediatrics.
Phototherapy is usually adequate to correct neonatal jaundice. Extremely high levels may require an exchange transfusion. Exchange transfusions involve removing blood from the neonate and replacing it with donor blood.
Phototherapy
Phototherapy converts unconjugated bilirubin into isomers that can be excreted in the bile and urine without requiring conjugation in the liver. Phototherapy involves removing clothing down to the nappy to expose the skin and eye patches to protect the eyes. Blue light is the best at breaking down bilirubin. A light-box shines blue light on the baby’s skin. Little or no UV light is used. Double phototherapy involves two light-boxes. Bilirubin is closely monitored during treatment. Once phototherapy is complete, a rebound bilirubin should be measured 12 – 18 hours after stopping to ensure the levels do not rise about the treatment threshold again.
Kernicterus
Kernicterus is a type of brain damage caused by excessive bilirubin levels. It is the main reason we treat neonatal jaundice to keep bilirubin levels below certain thresholds.
Bilirubin can cross the blood-brain barrier. Excessive bilirubin causes direct damage to the central nervous system. Kernicterus presents with a less responsive, floppy, drowsy baby with poor feeding. The damage to the nervous system is permeant, causing cerebral palsy, learning disability and deafness. Kernicterus is now rare due to effective treatment of jaundice.
Last updated January 2020