Elevated Bilirubin Levels in Infants: Screening and Management

Introduction

For our 32nd podcast episode, we reviewed hyperbilirubinemia and why it is so common in newborns. If you have not already listened, I strongly recommend that you go back and listen to: Elevated Bilirubin Levels in Infants: Why Does it Occur?

For our 33rd podcast, I review the recommendations for screening and managing hyperbilirubinemia. The American Academy of Pediatrics (AAP) recommends universal screening of bilirubin levels in newborns. I review how screenings can be done, when it should occur, and when it should be repeated. I also review the risk factors that make certain infants more susceptible to elevated bilirubin levels and how those risk factors contribute to guidelines for the treatment plan.

I discuss the nomograms commonly used that guide the care of identifying infants at risk as well as when they should be treated. And finally, I discuss phototherapy, the primary treatment method used to treat hyperbilirubinemia. I discuss how phototherapy works to lower bilirubin levels and review additional considerations to follow when caring for infants undergoing treatment for hyperbilirubinemia.  

Whether you are a neonatal clinician or a parent, this review on management of hyperbilirubinemia will be beneficial. Hyperbilirubinemia is incredibly common in neonates. Clinicians who care for infants whether they are a term newborn in the nursery or an infant in the NICU, will screen for and manage infants with elevated bilirubin levels. And parents of either term, healthy infants, or those critically ill in the NICU will hear about their infant’s bilirubin levels. So it is crucial that you understand why it is so essential to screen for and manage elevated bilirubin levels.

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Episode 33

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Hyperbilirubinemia

Elevated Bilirubin Levels: What causes it?

Before we dive into the management of hyperbilirubinemia in infants, I am going to briefly review why infants are so prone to developing elevated bilirubin levels. 

Jaundice or yellowing of the skin is caused by elevated levels of bilirubin in the bloodstream. We as humans constantly form bilirubin and it is formed in our bodies once our red blood cells are broken down. For us to effectively remove bilirubin once it is formed in our bodies, it has to be changed into a form that the body can get excrete and this is done through a process called conjugation. Conjugation occurs in the liver and must be done so the bilirubin can be converted into water-soluble bilirubin pigments. Once the conversion occurs, the bilirubin can be naturally excreted through our stool and to a lesser degree filtered through the kidneys and excreted in urine. 

Elevated bilirubin levels, otherwise known as hyperbilirubinemia, occurs when bilirubin is made faster than it is removed due to either decreased conjugation or a reduction in the elimination. Bilirubin that is not conjugated or otherwise called unconjugated can cross the blood brain barrier and cause damage to the brain. 

Hyperbilirubinemia is more predominant in newborns due to their higher blood volume as well as their shortened lifespan of red blood cells. The red blood cell lifespan for infants is 70-90 days on average as opposed to the typical 120 days of an adult. The typical bilirubin load of a newborn is 2-3 times that of an adult. So the larger volume of red blood cells coupled with the shorter lifespan of them results in a large amount of red blood cell breakdown and an overproduction of bilirubin. 

Toxic Bilirubin Levels

If bilirubin levels are not closely monitored and treated in infants, toxic levels of bilirubin can progress to silent or symptomatic behavioral and neurological impairments. Unconjugated bilirubin gets reabsorbed and deposited into the brain tissue which leads to encephalopathy, brain damage, and hearing loss. 

Acute bilirubin encephalopathy (ABE) is acute, progressive, and can be reversible if treated with aggressive interventions. If the elevated bilirubin levels are not treated once the infant develops ABE, it can lead to what was previously known as kernicterus, but is now referred to as chronic bilirubin encephalopathy (CBE). Infants with chronic bilirubin encephalopathy suffer from irreversible or chronic brain damage that leads to permanent impairments. 

Importance of Screening for Hyperbilirubinemia

Now, bearing that in mind, it will hopefully help you to understand why we as neonatal providers assess, screen, and monitor infants so closely for signs of jaundice and elevated levels of bilirubin in the first few days and weeks of their life. Bilirubin levels in overall healthy term infants progressively increase during the first 96-120 hours after birth then they gradually decline over the first week of life. The rate of decline is dependent upon the maturation of the infant’s liver, initiation of feedings, the motility of the gastrointestinal tract, and the ability of the infant to clear its bilirubin load, especially in preterm infants. For those infants with an uncomplicated clinical course the decline typically commences by the 7th day of life. 

As we discussed in the last episode, there are some additional risk factors that place certain infants at an increased risk for developing elevated bilirubin levels including, but not limited to blood group incompatibilities like Rh hemolytic disease, ABO incompatibility, G6PD, infants with polycythemia, excessive bruising, and those born prematurely. 

Infants with hyperbilirubinemia that are screened, monitored, and treated appropriately and in a timely manner, even those with risk factors, almost all have benign outcomes and do not develop adverse neurological effects. 

But due to the potential risk for elevated bilirubin levels to cause irreversible brain damage if it goes undetected or untreated, all term and late preterm infants should be physically assessed and evaluated for hyperbilirubinemia. 

Evaluating for jaundiced skin

To properly assess an infant for jaundice, the clinician should assess the infant in a well-lit area. Next, gently blanch the skin with your finger to reveal the color of the skin and subcutaneous tissue. Although, we must remember that the changes in skin color may be more difficult to appreciate in children with darker skin. With this in mind, it is one of the main reasons that a physical assessment alone is a suboptimal screening tool to evaluate for jaundice. So all term newborns should be evaluated for hyperbilirubinemia with a transcutaneous measurement or a bilirubin serum value.  

Hospitalized Screening for Hyperbilirubinemia

Each institution has a systematic approach in place to identify and treat infants that are at risk for elevated bilirubin levels, but the timing of when that occurs may vary. The American Academy of Pediatrics (AAP) has outlined clinical guidelines to assist clinicians in identifying infants at risk for developing severe hyperbilirubinemia. 

Many hospitals screen newborns at 24 hours of age and at least daily thereafter. Screening should be completed earlier than 24 hours if an infant begins to appear jaundiced prior to 24 hours of age or if they have a positive direct antibody test (DAT) or a positive Coombs test. Additionally, an infant that is feeding poorly or displays a lack of energy, may also warrant an earlier evaluation for elevated bilirubin levels.

Risk Factors for Hyperbilirubinemia

The American Academy of Pediatrics (AAP) has also identified important risk factors that may place an infant at an increased risk for hyperbilirubinemia including a gestational age less than 38 weeks, infants that are exclusively breastfeeding, particularly if nursing is inadequate and weight loss is excessive, a previous sibling with a history of being significantly jaundiced, a cephalohematoma and/or severe bruising, those that are of East Asian descent, and as I previously mentioned if there is hemolytic disease, or noticeably jaundiced skin in tashe first 24 hours. The final risk factor is a predischarge total serum bili or transcutaneous bili in the high risk or high-intermediate risk, which I’ll explain what exactly that means now! 

Nomogram for designation of risk

Now the high or high-intermediate risk, as mentioned above, comes from a nomogram that was developed and published back in 1999 by Bhutani, Johnson, and Sivieri. They published an hour-specific bilirubin nomogram in attempts to predict the severity of subsequent bilirubin levels. It was this particular nomogram that led to the development of the 2004 and the 2009 American Academy of Pediatrics (AAP) clinical guidelines for managing hyperbilirubinemia in infants > 35 weeks’ gestation. 

To grab your document with the nomograms mentioned during the podcast episode, go HERE.

Now the 1999 Bhutani nomogram (Figure 1 from the images we provided) is still widely used today and guides practices across the country. The nomogram allows clinicians to plot the infant’s transcutaneous or total serum bilirubin value based on their hours of age. Once the value is plotted, the clinician is able to identify if the infant is in the low risk, low-intermediate risk, high-intermediate risk, or high risk category. By using the nonogram, “the risk” refers to the risk that the infant’s subsequent bilirubin level will be > 95th percentile. 

With the 1999 Bhutani nomogram, not only are there lines to identify the infant’s risk from low to high, but there are also percentages. I mention these because at times, the percentages are mentioned rather than the risk to guide practice. Infant’s within the high risk zone are also referred to as the > 95th percentile, high-intermediate > 75th percentile, and low-intermediate > 40th percentile. 

The Bhutani nomogram is still widely used today throughout institutions, but there was a recent study in 2021 by Bahr et al., that reviewed the Bhutani nomogram and attempted to fill in some gaps in knowledge with some new data and research. With their 2021 study, they developed a modified nomogram that includes the ability to plot infants less than 12 hours of age, which the Bhutani nomogram does not allow for, and after collecting additional data from participants, they created a new nomogram. The authors from this study are currently using the new nomogram in their Utah hospitals, but it has not been fully adapted elsewhere nor is it currently endorsed by the American Academy of Pediatrics. So for today, the recommendations I will be discussing are based on the most recent recommendations from the American Academy of Pediatrics from 2009.  

Transcutaneous Bilirubin Measurement (TcB)

Now, many centers are actively using Transcutaneous Bilirubin (TcB) measurements as a screening tool. Transcutaneous spectrophotometric measurement is a technique for estimating serum bilirubin that is noninvasive, fast, and relatively inexpensive. When used properly, transcutaneous bilirubin measurement (TcB) is a reliable identifier of hyperbilirubinemia in newborns from a variety of ethical backgrounds. A 2016 study by Taylor et al., found that transcutaneous bilirubin measurements can be used effectively to screen newborns for jaundice during their hospitalization after birth. 

Transcutaneous bilirubinometry works by emitting a beam of light into the skin and measuring the intensity of the wavelength of light that is reflected. It is based on optical spectroscopy, which relates the amount of light absorption by bilirubin to the concentration of bilirubin in the skin. 

To obtain the measurement with transcutaneous bilirubinometry, the handheld meter is gently pressed against the sternum or forehead of the infant. It provides an immediate bilirubin level result. By using the transcutaneous bilirubin screening tool, it saves time, reduces cost, and minimizes the pain and trauma associated with obtaining a serum value. 

Once the value is obtained, it is plotted on the nomogram based on the infant’s age in hours. Now, although transcutaneous bilirubin measurements have been shown to provide a reasonably accurate estimate of the total serum bilirubin, it is just a screening tool to help providers identify infants at risk for developing hyperbilirubinemia. 

Total Serum Bilirubin (TSB)

If the transcutaneous bilirubin value is beyond the threshold for either the institution’s guidelines or the individual provider, a total serum bilirubin (TSB) will be drawn. The total serum bilirubin (TSB), which is the total amount of bilirubin in the blood, is the gold standard bilirubin measurement and it is done by a lab draw, typically from a heel stick. Some institutions have specific guidelines for the clinicians to follow, to direct them when a serum bilirubin level should be drawn based on the TcB value and where it falls on the nomogram. 

When referring to bilirubin levels, we will be speaking of the total bilirubin level. If you ever hear the term direct bilirubin, it is referring to conjugated bilirubin which is followed and if elevated, indicative of cholestasis, which is beyond the scope of this particular episode. 

Currently, it is recommended to send a total serum bilirubin level if the transcutaneous value is at 70% of the total serum bilirubin level recommended for phototherapy, if the transcutaneous bilirubin is above the 75th percentile on the Bhutani nomogram or if the transcutaneous value is greater than 13 mg/dL at the infant’s follow-up post discharge. 

Phototherapy

Now to determine if an infant needs to be treated with phototherapy, the American Academy of Pediatrics recommends using the Guidelines for phototherapy nomogram, which is Figure 2 in your document. With the guidelines for phototherapy nomogram, it again allows the clinician to plot the value based on how many hours old the infant is at the time of the bilirubin lab draw. This particular nomogram factors in hyperbilirubinemia neurotoxicity risk factors including Isoimmune hemolytic disease, G6PD, Asphyxia, Sepsis, Acidosis, and an Albumin level < 3.0 mg/dL. The neurotoxicity risk factors encompass those that might increase the risk of brain damage in an infant who has severe hyperbilirubinemia. The risk factors help guide the clinician when they are making the decision whether or not to initiate phototherapy or consider an exchange transfusion.

With the neurotoxicity risk factors in mind, the nomogram is broken down into Infants at a lower risk or those > 38 weeks’ gestation and well, Infants at medium risk or those greater than or equal to 38 weeks with risk factors, or 35-37 6/7 weeks and well, and finally those infants at higher risk or 35-37 6/7 weeks with risk factors. 

Many of the electronic medical records in hospitals today have a tab for us clinicians that automatically plots the bilirubin value with the infant’s hours of life. Additionally, there is an online bili tool that is convenient if the tab is not available. 

When infants are in the hospital, providers need to evaluate the bilirubin level and decide if or when it needs to be repeated. Once there are 2 values obtained, it is helpful to plot the data on the nomogram to assess the rate of rise. The American Academy of Pediatrics also developed some algorithms to help guide the provider whether or not the infant needs to have a bilirubin level repeated, how soon, or if they should consider treatment with phototherapy. 

Benefits of Phototherapy

Phototherapy is the most commonly used treatment for elevated bilirubin levels. It is convenient, non-invasive, and most importantly, effective in reducing bilirubin levels. Phototherapy is the use of visible light, specifically blue wavelengths that irreversibly converts bilirubin in the body to a water soluble isomer through several mechanisms. Once it is converted to a water-soluble substance, it is then able to be excreted by the baby’s body without the need of further metabolism by the liver. 

The goal of phototherapy is to blunt the rise of the serum bilirubin and prevent its toxic accumulation in the body and brain. The photoisomerization of bilirubin begins almost immediately once the infant is exposed to the phototherapy light. There is an incredibly strong relationship between the dose of the phototherapy and the rate of decline in serum bilirubin levels. The dose of phototherapy is determined by the wavelength range and peak, the irradiance or intensity, the distance between the light and the infant’s skin, and the body surface area exposed. 

The distance between the light and the infant should be 15 to 20 cm and the goal is to expose the greatest amount of surface area, so the newborn should be naked except for a diaper and an opaque eye shield. It is important to ensure that the eye shield does not cover the nose or slide off the orbits of the eyes. The eye shield protects the infant’s eyes from retinal damage and should be used with all phototherapy devices including bili blankets. 

There are several phototherapy devices that are used commercially including overhead or spotlight phototherapy lights meaning they are above the infant or a bilirubin blanket that is under the infant. Blue LED lights are preferred and phototherapy lights do not emit UV light. 

It is common when speaking of phototherapy treatment to refer to it as “single,” “double,” and/or “triple” or “intensive.” The terms refer to how many pieces of equipment are used to deliver phototherapy. Obviously, the more light that is on the infant, the more intense the treatment. And although you may be thinking, then why not automatically put each infant on 3 lights, but phototherapy should be treated just like a medication and only the necessary amount needed should be used. 

Phototherapy Side Effects

Phototherapy is safe, but there are some potential side effects including skin rashes, hypocalcemia, and it does interfere with mother-infant interaction. Loose stools are also common and this is attributed to the increased excretion of the unconjugated bilirubin from the intestine, which is what we want, but we need to closely monitor the infant’s skin and hydration status. There is also the potential for the infant to overheat and/or become dehydrated if the infant is not receiving enough breast milk or formula. 

Some infants may develop a dark, grayish brown discoloration of the skin and urine known as “bronze baby” syndrome. It is not harmful and will resolve without treatment after a few weeks. 

Clinical Considerations

While caring for the infant who is being treated with phototherapy, it is important for clinicians to closely monitor the infant’s temperature. It is recommended to use the skin control mode while treating an infant with phototherapy to ensure normothermia. Although the more advanced phototherapy devices are not supposed to produce additional heat, it is still possible. 

With the likelihood of loose stools, it is important to monitor the infant’s weight, as well as their intake and output. Excessive fluid loss via the skin is common with all newborns, especially in smaller infants, but the addition of phototherapy can exacerbate it.  

Term infants should continue to breastfeed while being treated with phototherapy at least 8-12 times per day according to the AAPs recommendations. If there is concern for dehydration, the infant may need to be supplemented with expressed maternal breast milk and/or donor breast milk if it’s available or formula. The nutritional aspect is incredibly important for infants with hyperbilirubinemia because poor caloric intake and/or dehydration associated with suboptimal breastfeeding can contribute to the development of hyperbilirubinemia. Routine supplementation with IV fluids is not recommended. 

It is typically up to the provider and based on the severity of the hyperbilirubinemia whether or not the infant can be removed from all of the phototherapy lights during breastfeeding to encourage parent-infant attachment. But, at the very least, the eye shields should be removed during breastfeeding when possible to promote mother-infant attachment and with each assessment to properly evaluate the infant’s eyes and clean them as needed.  

It is key to ensure that the largest skin surface area of the infant’s body is positioned in the center of the light where the irradiance is the highest. Although exposure to sunlight is known to lower bilirubin levels, direct exposure to sunlight is not recommended for infants due to the risk of sunburn, the exposure to UV radiation, and risk of overheating. 

The provider will continue to monitor the infant’s bilirubin levels during phototherapy treatment to monitor its effectiveness, but it is important to remember to turn off all of the phototherapy lights during the lab draw because the light will act on the bilirubin pigments in the samples giving erroneous data. 

Additional labs to consider while treating hyperbilirubinemia

Your infant’s provider may also order additional labs especially if the infant does not respond as quickly to the phototherapy as expected. If not done so already, the infant’s blood type should be tested along with a Direct Antibody Test (DAT) or a Coombs test. This is always done for any infant whose mother has type O blood or one who is Rh negative to monitor for any potential incompatibilities. As we spoke about in our previous podcast episode, any infant who is Coombs positive or has a positive Direct Antibody Test (DAT), are much more likely to develop hyperbilirubinemia due to their hemolysis and they may require extensive, prolonged phototherapy as well as the potential for rebound hyperbilirubinemia.   

A complete blood count (CBC) is often drawn to evaluate for anemia or polycythemia which may both contribute to hyperbilirubinemia as well as a reticulocyte count. If the retic count is elevated, it is indicative of hemolysis which helps to explain at least a significant part of the rationale for the hyperbilirubinemia.

A G6PD test may also be helpful especially in infants of African, East Asian, Mediterranean, or Middle Eastern descent, or if the total bilirubin level is elevated. The G6PD results may take 24-48 hours in some centers, so it should be drawn early if there is a high level of suspicion. It is also recommended once bilirubin levels become elevated to draw a total and direct bilirubin to monitor for other potential diagnoses.  

Phototherapy, when used effectively, results in a decline of the total bilirubin level of at least 2 to 3 mg/dL within four to six hours and a 25 to 40% decrease after 24 hours of treatment. 

Rebound Hyperbilirubinemia

Once the bilirubin levels have gone down to an acceptable level and phototherapy is discontinued, they may experience rebound hyperbilirubinemia. It is due to the rise in the rate of bilirubin production that exceeds its elimination, but is typically an elevation of no more than 1-2 mg/dL.  With that said, it is important for the provider to follow the total serum bilirubin levels after the phototherapy has been discontinued. Follow-up total bilirubin measurements after phototherapy has been commenced is recommended to be done 18 to 24 hours later. It is reasonable for providers to follow this value as an outpatient, but will vary with each infant. 

IVIG

Additional treatments used for the treatment of hyperbilirubinemia if the levels continue to rise despite intensive phototherapy, include the use of IVIG. Intravenous immunoglobulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease. 

Exchange Transfusion

And finally, I am going to briefly touch on exchange transfusions. Luckily, exchange transfusions are not needed as often as they once were to treat hyperbilirubinemia. Between early identification of infants at risk for hyperbilirubinemia and improved treatment methods like phototherapy and IVIG, it is rarely needed. Exchange transfusions are an emergent, life-saving procedure that replaces an infant’s blood with donated blood to quickly lower the bilirubin level. It is an expensive, time-consuming procedure that can only be done in a high level NICU, but essential if an infant’s bilirubin levels are nearing toxic levels. 

Hyperbilirubinemia in Preterm Infants

Now, what I just reviewed applies to term infants, or those born >35 weeks’ gestation. Hyperbilirubinemia in preterm infants is more common, more severe, and typically lasts longer. Preterm infants are more vulnerable to hyperbilirubinemia because brain toxicity occurs at lower levels than it does in term infants. With this in mind, the threshold range of when to initiate phototherapy is lower when compared with term infants. There have been some studies that have led to guidance for clinicians to assist with their management of hyperbilirubinemia in premature infants, but may vary between institutions. The same principles, though, do apply to preterm infants in regards to monitoring bilirubin levels and treatment with phototherapy.  

Follow-up after discharge

In general, universal screening before a term infant is discharged home is recommended by the American Academy of Pediatrics. Additionally, appropriate follow-up after discharge is essential. The bilirubin levels will continue to rise over the first few days and many mother-infant couplets are being discharged just 24 hours after delivery when bilirubin levels have not reached their peak. So screening infants and ensuring they have proper follow-up post discharge is essential for the safety of all newborns. Occasionally infants may have a delay in their discharge to ensure proper bilirubin follow-up, especially if it occurs on or around the weekend. Term infants discharged from the hospital should have appropriate follow-up within 1-2 days based on the provider’s recommendations. 

Parents should also be given education on signs or symptoms to monitor for once their infant is discharged home. And parents, please notify your Pediatrician or head to the emergency department if your infant appears jaundiced, will not wake up for feedings, and/or if they are lethargic and not acting well. 

Using a systematic approach with universal screening in combination with the clinical factors, specifically gestational age and exclusive breastfeeding, is essential in identifying infants at risk for hyperbilirubinemia. Once the transcutaneous bilirubin measurement or the total serum bilirubin have been collected, the hour specific nomogram provides the clinician with an immediate mechanism for evaluating the degree of hyperbilirubinemia and the need for additional surveillance and testing while in the hospital. All of this coupled with targeted follow-up will prevent the risk of infants developing bilirubin encephalopathy or any brain damage. 

 

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Closing

I hope this review on screening and management of hyperbilirubinemia in infants has been helpful. Whether you are a neonatal clinician or a parent, it is important to understand the importance of screening infants for elevated bilirubin levels. With the recommendations provided by the American Academy of Pediatrics, it helps to guide providers with use of a systematic approach as well as guidelines to treat our specialized neonatal population. 

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References

Bahr, T., Henry, E., Christensen, R., Minton, S., & Bhutan, V. (2021). A New Hour-Specific Serum Bilirubin Nomogram for Neonates >35 Weeks of Gestation. The Journal of Pediatrics, 236, 28-33. 

Bhutani, V., Wong, R., & Stevenson, D. (2016). Hyperbilirubinemia in Preterm Neonates. Clinical Perinatology, 43(2), 215-232.

Hynes, S., Moore, Z., Patton, D., O’Connor, T., & Nugent, L. (2020). Accuracy of Transcutaneous Bilirubin Versus Serum Bilirubin Measurement in Preterm Infants Receiving Phototherapy. Advances in Neonatal Care, 20(6), E118-E126. 

Eichenwald, E., Hansen, A., Martin, C., & Stark, A. (2017). Cloherty and Stark’s Manual of Neonatal Care, 8^th edition. Wolters Kluwer. 

Maisels, M., Bhutani, V., Bogen, D., Newman, T., Stark, A., & Watchko, J. (2009). Hyperbilirubinemia in the Newborn Infant >35 Weeks’ Gestation: An Update with Clarifications. American Academy of Pediatrics, 124(4), 1193-1198.

Maisels, MJ., Watchko, JF., Bhutani, VK., & Stevenson, DK. (2012). An Approach to the Management of Hyperbilirubinemia in the Preterm Infant Less Than 35 Weeks of Gestation. Journal of Perinatology, 32, 660-664. 

Okwundu, C., Uthman, O., Suresh, G., Smith, J., Wiysonge, C., & Bhutani, V. (2017). Transcutaneous Biliurubinometry Versus Total Serum Bilirubin Measurement for Newborns. Cochrane Database, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481485/pdf/CD012660.pdf

Porter, M. & Dennis, B. (2002). Hyperbilirubinemia in the Term Newborn. American Family Physician, 65 (4), 599-606.

Stokowski, L. (2011). Fundamentals of Phototherapy for Neonatal Jaundice. Advances in Neonatal Care, 11(5S), S10-S21.

Subcommittee on Hyperbilirubinemia. (2004). Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics, 114(1), 297-316.

Taylor, J., Burgos, A., Flaherman, V., Chung, E., Simpson, E., Goyal, N., Von Kohorn, I., & Dhepyasuwan, N. (2016). Utility of Decision Rules for Transcutaneous Bilirubin Measurements. Pediatrics, https://doi.org/10.1542/peds.2015-3032

Wang, J., Guo, G., Li, A., Cai, W., & Wang, X. (2020). Challenges of Phototherapy for Neonatal Hyperbilirubinemia (Review). Experimental and Therapeutic Medicine, https://doi.org/10.3892/etm.2021.9662

Wong, R. & Bhutani, V. (2022). Patient education: Jaundice in newborn infants (Beyond the Basics). UpToDate. https://www.uptodate.com/contents/jaundice-in-newborn-infants-beyond-the-basics?search=iaundice-in-newborn-infants-beyond-the-basics&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Wong, R. & Bhutani, V. (2021). Unconjugated Hyperbilirubinemia in the Newborn: Interventions. UpToDate. https://www.uptodate.com/contents/unconjugated-hyperbilirubinemia-in-the-newborn-interventions#:~:text=The%20three%20interventions%20used%20to,%2C%20phototherapy%2C%20and%20exchange%20transfusion

Wong, R. & Bhutani, V. (2021). Unconjugated Hyperbilirubinemia in Term and Late Preterm Infants: Management. UpToDate. https://www.uptodate.com/contents/unconjugated-hyperbilirubinemia-in-term-and-late-preterm-infants-management?source=related_link

Wong, R. & Bhutani, V. (2021). Unconjugated Hyperbilirubinemia in Term and Late Preterm Infants: Screening. UpToDate. https://www.uptodate.com/contents/unconjugated-hyperbilirubinemia-in-term-and-late-preterm-infants-screening

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