Episode 133: Neonatal Jaundice

Episode 133: Neonatal Jaundice

Jennifer explained the pathophysiology of neonatal jaundice and how to treat it and described why screening for hyperbilirubinemia is important.    

Written by Jennifer Lai, MS3, College of Osteopathic Medicine of the Pacific Western University of Health Sciences. Comments by Hector Arreaza, MD.  

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What is neonatal jaundice? 

Jenni: Infant jaundice, also known as hyperbilirubinemia, is when there is a high level of serum bilirubin causing yellow discoloration of the newborn's skin and eyes. Bilirubin is a red-orange byproduct of hemoglobin catabolism that gives yellow pigment to skin and mucosa membranes. 

Arreaza: When we see jaundice on the eyes, it is actually the conjunctiva color we are seeing. So, the term “scleral icterus” should be changed to “conjunctival icterus,” but you may get corrected by unaware clinicians. Bilirubin actually binds elastin.

What’s the pathophysiology/ big picture?

Jenni: The key problem is the accumulation of high levels of bilirubin in serum and if left untreated, it can bind to tissues and cause toxicity. There are multiple reasons why there might be too much bilirubin in the serum. Excess bilirubin can be due to a benign normal condition, but it can also be due to a pathologic reason. It is important to differentiate between these two because the management and treatment can differ significantly. 

Arreaza: Highly bilirubin means that it is being either overproduced or under-eliminated. 

Physiologic jaundice 

Most of the time, hyperbilirubinemia is benign and physiologic, with yellowing typically occurring between 2-4 days. 

Normally, there is a period of transition caused by the turnover of the fetal red blood cells and the immaturity of the newborn’s liver to efficiently metabolize bilirubin and increased enterohepatic circulation. The most common reason is that the liver isn't mature enough to get rid of the bilirubin in the bloodstream or because the baby’s gut is sterile, so it does not have the bacteria to convert the bilirubin to get it out of the body. In general, newborns have a higher level of total serum or plasma bilirubin levels compared to adults for the following reasons: 

• Newborns have more red blood cells (hematocrit between 50-60), and fetal red blood cells have a shorter life span (85 days vs. 120 days) than those of adults. After birth, there is an increased turnover of fetal red blood cells, so there is more bilirubin.
• Bilirubin clearance (conjugation and excretion) is decreased in newborns, mainly because of a deficiency of the hepatic enzyme UGT.
• Increase in the enterohepatic circulation of bilirubin as the amount of unconjugated bilirubin increases due to the limited bacterial conversion of conjugated bilirubin to urobilin.

Pathologic Jaundice

Pathologic jaundice includes severe neonatal hyperbilirubinemia, extreme neonatal hyperbilirubinemia, and bilirubin-induced neurologic disorders. We determine the severity of the jaundice using the total serum bilirubin (TSB). It is defined as a TSB >25 (severe) and TSB >30 (extreme). Other concerning signs include a TSB over the 95% percentile, a greater than 5mg/dL/day or 0.2mg/dL/hour, or jaundice that lasts for more than 2-3 weeks. 

Potential pathologic causes include but are not limited to: 

1. Increased bilirubin production from increased hemolysis which is when the red blood cells in the baby are being destroyed faster than normal, this can be due to blood group incompatibilities where the mom’s immune system starts to attack the baby’s red blood cells (such as Rh incompatibility) or from RBC membrane defects (spherocytosis).
2. Birth Trauma when the head gets bruised after a vacuum or forceps is used to remove the baby from the vaginal canal
3. Infection which prevents the bilirubin from being metabolized and excreted
4. Problems with bilirubin clearance either from enzyme deficiencies such as Crigler-Najjar or Gilbert syndrome
5. Obstructed biliary systems causing bile to get stuck in the liver

Arreaza: Indirect bilirubin is the one elevated in newborns, but if you see direct hyperbilirubinemia, then you have to think of an obstruction.

Jenni: Severe hyperbilirubinemia can cause brain damage. The amount of bilirubin and the duration of bilirubin ultimately determine the severity of the brain damage. This is because the bilirubin blocks some mitochondrial enzymes from being able to function properly, also it inhibits DNA synthesis/protein synthesis, and can cause DNA damage. This can ultimately lead to acute bilirubin encephalopathy which is described as 3 different phases: Phase 1 with poor feeding, lethargy, hypotonia, and seizures, Phase 2 with increased tone in extensor muscles causing neck contractions (retrocollis and opisthotonos), and Phase 3 with generalized increased tone. If the bilirubin encephalopathy persists it can also ultimately cause cerebral palsy, sensorineural hearing loss, and gaze abnormalities.  

How and when do we treat? 

No phototherapy:

The goal of treating jaundice is to safely decrease the amount of bilirubin in the body. Oftentimes babies with mild hyperbilirubinemia don't get any treatment and we just watch and wait. In premature babies, there is an increased risk for brain toxicity because a lower amount of bilirubin can result in brain toxicity. For these babies, it is important to ensure there is adequate breast milk to both prevent and treat jaundice because it helps the baby get rid of bilirubin through the stool and urine. 

Arreaza: Indirect sunlight exposure of the baby.

Phototherapy:

Other babies get phototherapy or more commonly known as light therapy. Phototherapy light treatment is when the baby’s skin is exposed to a special blue light which will help break down bilirubin and help with the excretion in stool and urine. The phototherapy should be continuous and placed on as much skin as possible and the treatment should be administered until bilirubin levels drop to a safe level based on the baby’s hour-specific thresholds. 

Arreaza: Home phototherapy is an option (UV blanket) available for rent or purchase.

Phototherapy is very safe, however, with any treatment, there are risks and potential side effects. Some of these include skin rashes, loose stools, overheating, and dehydration. Occasionally, babies turn a dark gray-brown color in their skin and urine, but this is temporary and usually resolves on its own. While the baby is receiving phototherapy, it is important to continue breastfeeding to ensure appropriate fluid hydration, but in babies that cannot get enough breast milk, they may need to supplement with formula or even potentially start IV fluids. 

Benefits of screening

It is therefore essential for universal bilirubin screening for all newborns prior to discharge to identify newborns who are at risk for developing severe hyperbilirubinemia. Hyperbilirubinemia is extremely common in newborns, with nearly all neonates having a higher total serum bilirubin than adults. The reason we screen is that this reduces the risk of developing severe hyperbilirubinemia and ultimately brain damage. This universal screening also then decreases hospital readmissions for neonatal hyperbilirubinemia. 

Arreaza: So, we check at 12-24 hours in a typical pediatric unit. We use a bilimeter (transcutaneous) and if we suspect it is not accurate, we do a serum bili. Be aware of the accuracy of bilimeters.

How do we screen? 

We do this prior to newborn discharge through a transcutaneous bilirubin device (TcB) or lab total serum bilirubin (TSB). The bilirubin level is used with the assessment of risk for the development of severe hyperbilirubinemia. Newborn bilirubin screening guidelines include TSB or TcB within 24-48 hours after birth or before discharge. TcB is the noninvasive test, but TSB is the gold standard for assessing neonatal bilirubin. Newborns with visible jaundice in the first 24 hours should be concerned for severe hyperbilirubinemia. These babies should be screened earlier because of the risk of pathologic causes of jaundice. 

In addition to the bilirubin test, physicians will clinically assess by examining the skin under ambient or daylight to assess whether there is a yellow discoloration of the buccal, gingival, or conjunctival mucosa. Additionally, if a baby presents with scleral icterus, pallor, bruising, hepatosplenomegaly, or cephalohematoma (enclosed hemorrhage), these can be clinical presentations of neonatal jaundice. 

Follow up:

After screening, we recommend that babies be closely monitored if jaundice does occur as it can be well managed with early treatment. A quick way to assess this at home is to press gently on the baby’s forehead and if the skin looks yellow where you press, it’s probably jaundice. If your baby doesn’t have jaundice, then the place where you pressed it should look lighter than normal. 

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Conclusion: Now we conclude episode number 133, “Neonatal Jaundice.” Jennifer explained the pathophysiology behind the increased levels of bilirubin in babies. She reminded us that it is a physiologic process, but when the level of bilirubin is too high, then we need to start treatment. Treatments include indirect sunlight exposure of the baby, breastfeeding, and in some cases phototherapy, IV fluids, and even antibiotics and exchange transfusion in some cases. Dr. Arreaza reminded us of the importance of screening and monitoring “bili babies” in the clinic. 

This week we thank Hector Arreaza and Jennifer Lai. Audio editing by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! 

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Links:

1. Episode 17: Why does bilirubin deposit in the eyes? – The Curious Clinicians, https://curiousclinicians.com/2021/01/20/episode-17-why-does-bilirubin-deposit-in-the-eyes/.
2. Ansong-Assoku B, Shah SD, Adnan M, et al. Neonatal Jaundice. [Updated 2022 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532930/.
3. Mayo Clinic. “Infant Jaundice – Symptoms and Causes.” Mayo Clinic, 2018, www.mayoclinic.org/disease-conditions/infant-jaundice/symptoms-causes/syc-20373865.
4. “Newborn Jaundice.” Nhs.uk, 19 Oct. 2017, www.nhs.uk/conditions/jaundice-newborn/#:~:text=Jaundcie%20in%20newborn%20babies%20is.
5. Preud’Homme D., “Neonatal Jaundice.” American College of Gastroenterology, Dec 2012, https://gi.org/topics/neonatal-jaundice/.
6. Wong R., et al. “Risk factors, Clinical Manifestations, and Neurologic Complications of Neonatal Uncomplicated Hyperbilirubinemia.” Up to Date, Last Updated: Jan 5, 2023, https://www.uptodate.com/contents/risk-factors-clinical-manifestations-and-neurologic-complications-of-neonatal-unconjugated-hyperbilirubinemia
7. Royalty-free music used for this episode: “Gushito - Burn Flow." Downloaded on October 13, 2022, from https://www.videvo.net/