Understanding Newborn Jaundice
A new and exciting study1 raises the possibility that newborn jaundice is not merely an undesired side effect of the body getting used to life outside the womb, but an advantageous mechanism, that from an evolutionary perspective protects newborns from the hazards of their new surroundings. Before diving into the details of this new concept, here is a short description of what newborn jaundice is and how it is commonly treated.
What is newborn jaundice
Newborn jaundice is caused by the accumulation in the body of bilirubin, a yellow pigment produced during breakdown of red blood cells. Before birth, the removal of bilirubin from baby’s body is handled by the mother. In the newborn, the liver takes over, converting circulating bilirubin into a water-soluble form, which is then excreted in both faeces and urine. However, newborn’s still-developing liver may not be mature enough and may take longer to clear bilirubin from the body. In addition, newborns have a higher turnover of red blood cells, resulting in more bilirubin produced during their breakdown. Also, the process of moving substances through the intestines is slower in newborns, causing bilirubin to remain in the intestines longer. When the bilirubin remains in the intestines for a long period, it is reabsorbed by the intestinal cells and sent back to baby’s liver. All these reasons may contribute to raised bilirubin levels in the newborn’s body, leading to jaundice - yellow coloration of the baby’s skin and eyes.
Jaundice is usually noticeable on the baby’s face first, then spreads downward toward the chest, abdomen, arms, and legs. It is possible to check for jaundice by gently pressing one finger on the baby’s nose or forehead. If the skin is jaundiced, the area will have a yellowish appearance when the finger is removed from the skin.
Jaundice is one of the most common conditions needing medical attention in newborn babies. Approximately 60% of term and 80% of preterm babies develop jaundice in the first week of life2. For most babies, jaundice is not an indication of an underlying disease, and this early jaundice (termed 'physiological jaundice') is usually harmless.
In most cases, jaundice becomes visibly apparent on day 3, peaks at day 5 - 7 and resolves by 2 - 3 weeks2. Jaundice that persists longer is usually harmless but in some cases may indicate an underlying condition such as internal bleeding, liver disease, an infection, a particular enzyme deficiency, an abnormality in the baby’s red blood cells, or incompatibility in blood type between mother and baby.
Breastfed babies are more likely than bottle-fed babies to develop physiological jaundice within the first week of life. Often it is related to limited fluid intake as breast milk supply is established.
Prolonged jaundice – that is, jaundice persisting beyond the first 2 weeks – is also seen more commonly in breastfed babies. About 10% of breastfed babies are still jaundiced at 4 weeks2.
When is treatment needed, treatment options, and risks
As unconjugated bilirubin (the form of bilirubin that has not been treated by the liver and cannot be excreted from the body) is fat-soluble, it can penetrate the blood-brain barrier (a highly selective membrane barrier that separates the circulating blood from the brain), bind with neural tissue, and cause brain damage. Therefore severe jaundice, regardless of the cause, carries the risk of temporary (Acute bilirubin encephalopathy) or permanent brain damage (Kernicterus), including hearing loss, vision problems, intellectual disabilities, seizures, coma, and even death. These sequelae are very rare among infants, but exact incidences are difficult to estimate3. In addition, some underlying causes of high bilirubin are serious or even life-threatening illnesses that require urgent treatment. The need to treat also depends on the overall state of the infant, where symptoms such as poor feeding, lethargy, irritability and high-pitched crying can indicate increased urgency.
Treatment for newborn jaundice is usually unnecessary, unless the baby has very high bilirubin levels or is unwell. Treatment depends on the cause, but phototherapy is usually the primary treatment. In very severe cases a blood transfusion may be needed.
Phototherapy is performed by placing the baby in a warm incubator under blue-green lights. This exposure transforms the bilirubin in the baby’s skin into water-soluble byproducts that are less likely to cross the blood-brain barrier and can be easily filtered by the liver and excreted in the usual pathways. To maximise skin exposure, the baby is undressed, wearing only a nappy and eye protection. Treatment usually lasts one or two days, with brief breaks throughout for breastfeeds, cuddles and parent-baby interaction. During phototherapy, bilirubin level is usually monitored closely, ensuring the baby feeds well to prevent dehydration and increase bilirubin excretion.
Phototherapy is usually safe and effective, but still carries the risk of complications: overheating, overcooling, diarrhoea, dehydration, skin rashes and retinal damage. Another rare adverse effect of phototherapy is the “Bronze baby syndrome” - a brown or bronze discoloration of the skin that may persist for many months. Phototherapy also involves separation of mother and baby, which may interfere with maternal-infant bonding, hinder skin-to-skin contact, and interrupt breastfeeding. Frequent blood draws and in some cases, prolonged hospitalization can add to baby and parent distress. Furthermore, studies suggest that phototherapy may slightly increase the risk of cancer in infancy, although the absolute risk increase is small4,5.
A newer alternative to the standard phototherapy is a ‘biliblanket’ - a pad placed directly against the baby that bathes the baby in light. This is a portable phototherapy device, offering treatment to some degrees of jaundice at home as long as the baby is otherwise healthy. The biliblanket is less effective than traditional phototherapy but avoids prolonged hospitalization, separation from the parents, and isolation in a box with eyes covered. Further, it allows the baby to be held and nursed during treatment, although the baby remains connected to the machine with a stiff pad between the baby and parent.
Phototherapy is the primary treatment for newborn jaundice due to its ease and associated low risks. However, exchange transfusion is used as an effective and quick method to remove bilirubin from the infant’s blood stream in cases where bilirubin level remains very high despite intensive phototherapy; when signs of bilirubin encephalopathy are seen; or with some underlying conditions (usually an immune reaction between mum’s and baby’s blood groups).
In exchange transfusion, the blood of a jaundiced newborn is replaced with donor blood containing normal bilirubin levels. It is performed by inserting a plastic tube called a catheter through the umbilical vein of the baby (a vein in the belly button). In cycles lasting a few minutes each, the baby’s blood is slowly withdrawn, and fresh, pre-warmed blood is put into the body, so that the circulating blood volume is constantly maintained. The exchange usually takes 1 to 2 hours. It may need to be done more than once.
The success of this technique is marred by the many risks associated with it, some of which are life-threatening: Infection (either at the transfusion site, or from an undetected
pathogen in the donor’s blood), blood vessel problems such as a blood clot, air embolism (bubble), or spasm in an artery (all of which may limit blood flow and hurt organs and tissues), bleeding outside of a blood vessel, decreased platelet count (which increases the risk of bleeding), chemical imbalances in the blood and tissues, temperature problems (hypo or hyperthermia), necrotizing enterocolitis (a bowel disease), heart and respiratory problems including cardiac arrest and irregular heart beating, and shock. Given the many associated risks, exchange transfusion is usually suggested only in cases in which other possible treatments have been unsuccessful or have little chance of success.
Can newborn jaundice be beneficial
The new study1 takes a different perspective to the high bilirubin levels often observed in sick or premature newborns. The authors raise an alternative hypothesis, suggesting that high bilirubin in the early neonatal period may give an advantage to the baby by inhibiting bacteria and hence improving the infant’s chances of surviving sepsis. It is based on the idea that the biggest threat to a newborn’s life after surviving delivery is sepsis in the first few days – bacterial infection which can overwhelm the immune system, potentially leading to severe inflammation, organ failure and death. The most common bacteria involved in newborn sepsis are Streptococcus agalactiae, commonly called Group B Streptococcus (GBS). In this study, GBS isolates were taken from septic newborns and grown with different concentrations of bilirubin in plates and in liquid cultures, which are supposed to better reflect the situation in the infant’s blood. Bilirubin was found to have antibacterial properties against GBS, such that even modest concentrations of bilirubin reduced substantially the growth of GBS in both plates and liquid cultures. In response to the presence of bilirubin, there were also changes in gene expression and protein regulation by the bacteria - possibly a defence mechanism, destined to cope with the exposure to bilirubin.
However, this study is still very preliminary, as the work has been done in vitro (bacterial isolates grown in the lab, outside the very complex context of the human body), using a small number of isolates taken from just a few infants. The impact of bilirubin on other bacteria that are linked with sepsis or even other GBS strains has not been investigated. Still, this study supports the hypothesis that bilirubin may have an important yet under-recognised antibacterial role in newborn sepsis. Further evidence is needed before this new hypothesis can be taken into account in clinical practice.
About this project
Reaching into Research - simply written, brief articles on scientific studies to encourage the general public to reach into research for themselves, rather than relying on other peoples' opinions. These articles will point out the pitfalls that can lurk when interpreting data, to help families gain confidence in coming to their own best decisions for their care."