Hyperbilirubinemia in the Newborn: New Guidelines

Educational Objectives

The goal of this program is to improve management of hyperbilirubinemia in newborns. After hearing and assimilating this program, the clinician will be better able to:

1. Identify infants at increased risk for significant hyperbilirubinemia.
2. Recognize infants with jaundice who require phototherapy.
3. Use diagnostic tests to guide escalation of care in newborns with hyperbilirubinemia.

Summary

Introduction: the American Academy of Pediatrics (AAP) published new neonatal hyperbilirubinemia (NHB) guidelines in September 2022; the guidelines are for newborns born at >35 wk gestation in the United States and were formulated to prevent kernicterus (ie, bilirubin encephalopathy caused by deposition of unconjugated bilirubin in the basal ganglia and brainstem nuclei)

Types of hyperbilirubinemia: unconjugated hyperbilirubinemia (UHB) is the most common type seen in the first 2 wk of life; may be physiologic or pathologic; conjugated hyperbilirubinemia (CHB), defined as a level ≥2 mg/dL or >20% of total bilirubin, is always pathologic; most often seen after the first 2 wk of life; measurement of direct bilirubin (DB) is used to estimate conjugated bilirubin (CB) in the body; guidelines suggest checking DB if a formula-fed newborn is still jaundiced at 2 wk or a breastfed newborn is still jaundiced at 3 to 4 wk of life, and in cases of clinical suspicion for pathologies that cause CHB

Differential Diagnosis of UHB

Physiologic jaundice (PJ): newborns are predisposed to jaundice because they are born with relatively higher hematocrit and an immature hepatic system; PJ occurs after the first 24 hr of life and may last for ≤1 wk; peak levels are not dangerous to newborns

Hemolysis: 3 main causes; isoantibodies — maternal antibodies against paternal red blood cells (RBC) antigens present on the RBCs of the newborn; 95% of cases involve Rh or ABO antibodies; enzyme defects — glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common; causes increased breakdown of RBCs; structural RBC defects — eg, spherocytosis, elliptocytosis

G6PD deficiency: 13% of African-American males and 4% of African-American females have G6PD deficiency; screening in newborns is mandatory; cases of elevated bilirubin with no apparent cause should provoke extra caution; checking the enzyme level when the newborn is hemolyzing may not produce an accurate result; testing should be done 3 mo after birth

Differential diagnosis of CHB: 40% of cases are biliary atresia; diagnosis is time sensitive and requires imaging and subspecialist care

Risk factors for significant HB: include parental or sibling history of phototherapy or exchange transfusion, inherited RBC disorders (eg, G6PD deficiency), gestational age <40 wk, macrosomia in infants of diabetic mothers, trisomy 21, scalp hematoma or significant bruising, signs of hemolysis (often indicated by an elevated rate of rise of total serum bilirubin [TSB]), exclusive breastfeeding with suboptimal intake, pre-discharge bilirubin level close to phototherapy threshold level, or if phototherapy is required before discharge from the nursery; breastfeeding support should be provided to mothers of breastfed babies with difficulties in nursing; frequent feedings are recommended with close monitoring of urination, stooling, and weight; oral supplementation with water or dextrose water should be avoided because of the risk for hyponatremia, and its ineffectiveness in preventing HB

Risk factors for neurotoxicity: include newborns with gestational age <38 wk, presence of a hemolytic condition, low albumin level, sepsis, and major clinical instability

Guideline for identification of newborns at risk for immune-mediated hemolysis: first determine if the mother tested positive for antibodies (ideally screened during the first trimester or upon obstetric care admission); blood typing and direct antiglobulin test (DAT) should be done in infants with mothers who screened positive; negative results allow adherence to standard protocols; criteria- exclusive anti-Rh(D) positivity, maternal Rh immunoglobulin (RhoGAM) receipt during pregnancy, and maternal anti-Rh(D) negativity confirmation should be evaluated before RhoGAM administration in infants who are DAT positive; a true positive may be assumed if all 3 conditions are not established; appropriate management should follow

Infant is DAT positive: total serum bilirubin (TSB) should be immediately checked, and cord blood in most cases; guidelines recommend checking TSB every 4-hr × 2 and then spacing it out to every 12-hr × 3; use TSB as the definitive test to guide phototherapy or escalation-of-care decisions

Infants not at risk for hemolysis: visually assess for jaundice at least once every 12 hr; bilirubin should be immediately checked with a TSB or transcutaneous bilirubin (T_cB) in infants with signs of jaundice; bilirubin should be measured at least once between 24 to 48 hr of age prior to being discharged in infants never jaundiced

T_cB measurement devices: easy to use, but estimates bilirubin levels through the skin and are error prone; T_cB levels may fluctuate within 3 mg/dL of the actual TSB level when TSB levels are <15 mg/dL; melanin levels in the skin affect accuracy; guidelines recommend checking TSB if the T_cB level is within 3 units of the phototherapy threshold because of potential errors associated with transcutaneous devices

Follow-up: bilirubin level of newborns prior to discharge influences their follow-up; phototherapy should be considered if TSB is within 2 mg/dL of the phototherapy threshold; when T_cB is >3.5 mg/dL below the phototherapy threshold, follow ups can be planned with more flexibility; all follow-up should be done within 3 days

Phototherapy: used to prevent further increase of bilirubin levels and avoid escalation of care; narrow spectrum LED light (460 to 490 nm) is used; the eyes of newborns must be shielded with protective eyewear and overhead lights should be positioned 15 to 20 cm away; a fiberoptic phototherapy blanket may be positioned underneath; efficacy equals intensity times surface area; only a diaper should be worn; phototherapy results in expedited removal of bilirubin without conjugation (eg, lumirubin can be excreted via the kidneys); complications include loose stools, erythematous macular rash, bronze baby syndrome (associated with CHB, and should trigger DB check); sunlight exposure is discouraged; phototherapy thresholds are gestational-age-specific and ≈0.5 units higher than in the 2004 guidelines

Monitoring TSB: AAP guidelines define an elevated rate of rise as a rate of rise ≥0.3 mg/dL/hr in the first 24 hr of life and ≥0.2 mg/dL/hr after the first 24 hr; DAT should be checked in patients with elevated rate of bilirubin rise to screen for hemolysis

Indications for phototherapy at home: include availability of a suitable fiberoptic blanket, newborns ≥38 wk gestation and ≥48 hr old, clinical wellness with adequate feeding, absence of neurotoxicity risk factors, and no prior phototherapy history; total bilirubin level must not exceed 1 mg/dL above the phototherapy threshold, and daily TSB measurement must be feasible

Monitoring of newborns on phototherapy: TSB levels should be monitored for the first 12 hr of phototherapy to ensure its efficacy; hemoglobin and hematocrit should be tested for anemia and to establish a baseline; DAT should be checked if the mother's blood type is O

Stopping phototherapy: discontinuing phototherapy should occur when TSB is ≥2 mg/dL below the initiation threshold; guidelines suggest a sooner rebound check for high-risk newborns, particularly if phototherapy starts within the first 48 hr of life or due to a hemolytic process (typically within 6 to 12 hr); rebound may be checked the following day in lower-risk cases; T_cB devices should not be used for 12 hr after phototherapy; accurate readings are required in high-risk situations

Escalation of care: crucial when TSB levels are rising but have not reached the exchange threshold yet (typically within 2 units of the level); immediate consultation with a neonatologist is necessary to assess if exchange transfusion is needed and if the newborn is in the appropriate care facility; essential labs at this stage include DB, complete blood count, and albumin levels (to address neurotoxicity risks associated with low albumin); check serum chemistries, type and cross match, and notify the blood bank; monitor TSB levels every 2 hr, especially if there is a delay in transferring the newborn to intensive care

Acute bilirubin encephalopathy: urgent exchange transfusion is indicated; signs include hypertonia, retrocollis, high pitch cry, seizures, apnea

Discharge: educate families on neonatal jaundice both verbally and in writing; provide a detailed follow-up plan including the specifics of the next appointment; advise parents to monitor their baby's eye sclerae for any color changes; ensure families are able to contact medical providers if they observe jaundice signs before the follow-up appointment

Readings

Arnold C, Pedroza C, Tyson JE. Phototherapy in ELBW newborns: does it work? Is it safe? The evidence from randomized clinical trials. Semin Perinatol. 2014 Nov;38(7):452-64. doi: 10.1053/j.semperi.2014.08.008; Bezerra JA, Wells RG, Mack CL, et al. Biliary Atresia: clinical and research challenges for the twenty-first century. Hepatology. 2018 Sep;68(3):1163-1173. doi: 10.1002/hep.29905; Brahee DD, Lampl BS. Neonatal diagnosis of biliary atresia: a practical review and update. Pediatr Radiol. 2022 Apr;52(4):685-692. doi: 10.1007/s00247-021-05148-y; Hulzebos CV, Dijk PH. Bilirubin-albumin binding, bilirubin/albumin ratios, and free bilirubin levels: where do we stand?. Semin Perinatol. 2014;38(7):412-421. doi:10.1053/j.semperi.2014.08.004; Ling DXH, Bolisetty S, Krishnan U. Cholestatic jaundice in neonates: How common is biliary atresia? Experience at an Australian tertiary centre. J Paediatr Child Health. 2021 Jan;57(1):87-95. doi: 10.1111/jpc.15131; Kaplan M, Wong RJ, Stevenson DK. Hemolysis and glucose-6-phosphate dehydrogenase deficiency-related neonatal hyperbilirubinemia. Neonatology. 2018;114(3):223-225. doi:10.1159/000489820; Par EJ, Hughes CA, DeRico P. Neonatal hyperbilirubinemia: evaluation and treatment. Am Fam Physician. 2023 May;107(5):525-534. PMID: 37192079; Vidavalur R, Devapatla S. Trends in hospitalizations of newborns with hyperbilirubinemia and kernicterus in United States: an epidemiological study. J Matern Fetal Neonatal Med. 2022 Dec;35(25):7701-7706. doi: 10.1080/14767058.2021.1960970.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Kinlaw was recorded at the Jon B. Tingelstand Conference: Practical Pediatrics, held May 25-26, 2023, in Greenville, NC, and presented by the Brody School of Medicine at East Carolina University. For information on upcoming CME activities from this presenter, please visit https://cme.ecu.edu. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

PD701801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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