Jaundice describes raised bilirubin, leading to yellowing of the skin and sclera (whites of the eyes).
Kernicterus is a type of brain damage caused by excessive bilirubin levels. Bilirubin can cross the blood-brain barrier and cause direct and permanent damage to the central nervous system, potentially leading to cerebral palsy, learning disabilities, and deafness.
Unconjugated and Conjugated Bilirubin
Red blood cells contain unconjugated bilirubin. When they 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
- Via the urine
Physiological Jaundice
The fetus and neonate have a high concentration of red blood cells, which 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, after birth, the newborn can no longer excrete bilirubin via the placenta, leading to a rise in bilirubin from 2-7 days of age. This usually resolves within 10 days.
In premature babies, an immature liver can exaggerate the physiological jaundice, increasing the risk of complications, particularly kernicterus. Bilirubin levels need to be carefully monitored in premature babies.
Causes of Neonatal Jaundice
The causes of neonatal jaundice can be split into increased production and decreased clearance.
Causes of increased production of bilirubin include:
- Haemolytic disease of the newborn
- ABO incompatibility
- Haemorrhage
- Intraventricular haemorrhage
- Cephalo-haematoma
- Polycythaemia
- Sepsis and disseminated intravascular coagulation
- G6PD deficiency
Causes of decreased clearance of bilirubin include:
- 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 and requires urgent investigations and management. Neonatal sepsis is a common cause.
Breast Milk Jaundice
Breastfed newborns are more likely to have neonatal jaundice. There are several potential reasons for this. Components of breast milk inhibit the liver’s ability 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 the 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 help feeding go well.
Haemolytic Disease of the Newborn
Haemolytic disease of the newborn causes 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.
Many different types of rhesus antigens can vary between individuals. The most important antigen within the rhesus blood group system is the rhesus D antigen.
A problem arises when the mother is rhesus D-negative (she does not have the rhesus D antigen) and the baby is rhesus D-positive. It is likely that at some point in the pregnancy, the baby’s red blood cells will find a way into her bloodstream. When this happens, the mother’s immune system recognises the rhesus D antigen as foreign and produces antibodies to it. The mother has then become sensitised to rhesus D antigens.
Usually, this sensitisation process does not cause problems during the first pregnancy (unless it happens early on, such as during antepartum haemorrhage). During subsequent pregnancies, the mother’s anti-D antibodies can cross the placenta to the fetus. If that fetus is rhesus positive, these antibodies cause the immune system to attack the red blood cells, leading to haemolysis, anaemia, and raised bilirubin.
Prolonged Jaundice
Jaundice is “prolonged” when it lasts longer than expected in physiological jaundice. This is:
- More than 14 days in term infants
- More than 21 days in premature infants
Prolonged jaundice should prompt further investigation to look for an underlying cause:
- Full blood count and blood film for polycythaemia or anaemia
- Conjugated bilirubin: elevated levels indicate a hepatobiliary cause (biliary atresia)
- Blood type testing of mother and baby for ABO or rhesus incompatibility
- Direct Coombs test (direct antiglobulin test) for haemolytic disease of the newborn
- Thyroid function, particularly for hypothyroidism
- Blood and urine cultures if infection is suspected
- Glucose-6-phosphate-dehydrogenase (G6PD) levels for G6PD deficiency
Management
Total bilirubin levels are monitored and plotted on treatment threshold charts. These charts are specific to the gestational age of the baby. The age in hours is plotted on the x-axis, and the total bilirubin level is plotted on the y-axis. When the bilirubin reaches the treatment threshold, treatment to lower it is needed.
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.
Phototherapy is usually adequate to correct neonatal jaundice. Extremely high levels may require an exchange transfusion. Exchange transfusions involve removing and replacing blood from the neonate 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.
The baby wears a nappy and eye patches, exposing the remainder of their skin. 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, rebound bilirubin should be measured 12 – 18 hours after stopping to ensure the levels do not rise above the treatment threshold again.
Last updated May 2025
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