Aren’t all babies a little jaundiced anyways? What’s up with those phototherapy lights? Come for the answers, stay for this de-light of a conversation with pediatrician Dr. Alison Holmes and neonatologist Dr. Tom Shimotake, both of whom have extensive experience with commonly used guidelines for neonatal hyperbilirubinemia. We will cover common and rarer etiologies of neonatal hyperbilirubinemia, the whens and hows of working up and screening, and the ins and outs of treatment.
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Risk factors for unconjugated hyperbilirubinemia, resulting in a high indirect bilirubin, are varied and fall into several categories.
Expert pearl: Obtain a thorough set of labs from birthing parent’s prenatal care from your obstetric and family medicine colleagues, including the minor blood group antigens which are often responsible for an antibody setup.
Expert pearl: Although G6PD deficiency is classically taught to occur more often in darker-skinned populations, it is in fact a global concern and can happen in many populations that ethnic categorizations are not adequate for. Because a large percentage of kernicterus cases can be attributed to G6PD deficiency (up to 30%), it is important not to let bias determine screening and workup, especially as hemolysis from G6PD deficiency may not occur in the first few days of life.
Finally, a common risk factor is any feeding difficulty, through which an infant does not receive enough nutrition. The pathophysiology of this starvation jaundice is unclear. Expert practice: Although sometimes termed “breastfeeding jaundice”, this term is inaccurate since this type of hyperbilirubinemia can occur with failure to feed either with breastmilk or formula.
Conjugated hyperbilirubinemia results from cholestasis and an impaired ability to form or excrete bile. The conjugated, or direct, bilirubin should be less than 20% of the total bilirubin measurement; anything more is considered elevated. Causes include:
Expert opinion: Consider obtaining a TcB meter in your outpatient practice (Kilmarten et al, 2020).
Use an algorithm (and the bilirubin rate of rise) to determine whether the bilirubin level needs intervention, e.g. phototherapy or exchange transfusion. Existing algorithms are:
Since the advent of Rhogam to prevent hemolytic disease of the newborn, rates of exchange transfusion have dropped, while rates of phototherapy have risen.
Phototherapy utilizes specific wavelengths of light on the skin to convert bilirubin into an excretable water-soluble compound. In principle, should administer as much blue wavelength light to as much surface area as possible, thereby limiting time spent under lights. Sometimes this can be achieved with multiple banks of light with a “bili blanket” underneath to provide extra sources of light. Sometimes, phototherapy can also be done with a home machine. Stress to parents that phototherapy uses non-UV light. Although sunlight has been shown to decrease bilirubin, the risks of hyperthermia and the variability in sunlight for now do not outweigh the benefits and needs more research (Horn et al., 2020) – thus, parents should not expose their infants to sunlight for hyperbilirubinemia.
While on phototherapy, continue to feed patients at regular intervals to prevent further starvation jaundice, check bilirubin levels up to every 4 hours (via serum bilirubin – transcutaneous bilirubin is not a reliable measurement until approximately 24 hours after phototherapy cessation), and examine patients for clinical signs of bilirubin encephalopathy.
Important note: Phototherapy cannot be used for conjugated/direct hyperbilirubinemia! This will result in hyperpigmentation of the skin known as “bronze baby” and will not resolve the underlying pathology.
Phototherapy is not a wholly benign intervention, and thus should only be used when indicated by the “lightable” threshold, as opposed to prophylactically to prevent bilirubin from reaching threshold. Phototherapy has been associated with increased risk for childhood seizures (excluding febrile seizures). Other multifactorial risks of phototherapy are controversial, with research evolving over time. Some data have shown that families of infants who received phototherapy were more likely to worry that their infant was sick and display high healthcare utilization; other data have shown no change or even slight increase in breastfeeding. A previous correlation of phototherapy with different kinds of childhood cancer has been disproved with recent data.
In premature infants, and extremely low birth weight infants, phototherapy should be used with even more caution given their under-developed skin. Discuss the use of cycled phototherapy for these ELBW infants. Arnold et al. found that cycling phototherapy (15 minutes on for every hour) reduced duration of therapy by over half, with minimal changes in peak bilirubin level.
Exchange transfusion is reserved for more severe cases of hyperbilirubinemia. Expert pearl: After the advent of Rhogam, it is now much more rare, perhaps a few times a year, to initiate exchange transfusion in the NICU. Exchange transfusion replaces patient with donor blood to remove bilirubin, offending antibodies, and replenish red blood cell stores; it is usually performed until the patient’s total blood volume is replaced twice.
If unconjugated bilirubin paradoxically stays constant or continues to rise during intervention, this may suggest ongoing hemolysis and requires further work-up.
If the bilirubin is dropping as expected, intervention can be discontinued once bilirubin levels are below threshold. Depending on the bilirubin level at time of phototherapy cessation, the likelihood of a rebound hyperbilirubinemia can be calculated using gestational age and “starting threshold-ending TSB” difference. Because the risk for rebound hyperbilirubinemia is relatively low (Chang and Newman found that when phototherapy is stopped at a bilirubin of 2 mg/dL below the starting threshold, the rebound probability was 2.5%), there is often no need to stay inpatient to monitor rebound hyperbilirubinemia, as long as there is a robust outpatient follow-up plan. Considering health equity is paramount to mitigate barriers to outpatient follow-up.
Preparing for discharge should include a follow-up plan for assessing jaundice and hyperbilirubinemia based on infant risk nomograms and predischarge bilirubin risk zone nomogram. Because the two nomograms of infant and bilirubin risk can be confusing, new research may result in a composite nomogram using a Δ-TSB value (difference between the last pre-discharge serum bilirubin and the AAP phototherapy threshold) and a simpler prediction value.
Listeners will explain the basic pathophysiology, diagnosis, and management of neonatal hyperbilirubinemia to improve both inpatient care and outpatient follow-up.
After listening to this episode listeners will be able to…
Dr. Holmes and Dr. Shimotake report no relevant financial disclosures. The Cribsiders report no relevant financial disclosures.
Zhang AY, Holmes A, Shimotake T, Cruz M, Masur S, Chiu C, Berk J. “#45: Neonatal Hyperbilirubinemia – Their Future’s So Bright, They Gotta Wear Shades!”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ March 2, 2022.
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