Neonatal Hyperbilirubinemia

Clinical Pathway

JOHNS HOPKINS ALL CHILDREN’S HOSPITAL

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This pathway is intended as a guide for physicians, physician assistants, nurse practitioners and other healthcare providers. It should be adapted to the care of specific patient based on the patient’s individualized circumstances and the practitioner’s professional judgment.

Johns Hopkins All Children’s Hospital

Neonatal Hyperbilirubinemia Clinical Pathway

Table of Contents 1. Rationale 2. Background 3. EC Clinical Pathway 4. Inpatient Pathway 5. Evaluation

a. Initial Assessment b. Initial Evaluation c. Hour Specific Nomogram d. Phototherapy Nomogram e. Exchange Transfusion Nomogram

6. Treatment a. Administration of IVF b. Administration of Phototherapy c. IVIG d. Exchange Transfusion e. Discontinuation of Phototherapy

7. Discharge 8. Documentation Reminders 9. Outcomes 10. References 11. Team Information & Disclaimers 12. Appendix A: Phototherapy Nursing Checklist

13. Appendix B: Thermoregulation Quick Reference

Updated: July 2020

Owner: Travis Walker, MD

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Johns Hopkins All Children's Hospital Neonatal Hyperbilirubinemia Clinical Pathway for

Infants ≥ 35 Weeks Gestational Age Rationale This clinical pathway was developed by a consensus group to standardize the management of infants being evaluated and treated for neonatal hyperbilirubinemia for patients greater than or equal to 35 weeks gestational age. It addresses the following clinical questions or problems:

1. How to evaluate for neonatal hyperbilirubinemia 2. When to consider hospital admission 3. When to begin and end treatment 4. When to discharge patient

Background Neonatal hyperbilirubinemia is the most commonly encountered clinical issue in newborn babies. A number of risk factors contribute to severe hyperbilirubinemia in newborn infants with gestational age ≥ 35 weeks. Evaluation for and management of hyperbilirubinemia is variable among clinical providers despite publication of AAP clinical practice guideline (1). In some instances, phototherapy is initiated earlier than the recommended total serum bilirubin (TsB) threshold based on the risk factors and postnatal age. More importantly, significant variation exists regarding TsB value at which phototherapy is discontinued and regarding the collection of a rebound bilirubin level, leading to increased length of hospitalization, interruption in breastfeeding, family dissatisfaction, and denials by the insurance companies.

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Johns Hopkins All Children's Hospital EC Neonatal Hyperbilirubinemia Clinical Pathway

Infants ≥ 35 weeks Gestational Age

Obtain STAT Fractionated Serum Bilirubin

Assess for Hyperbilirubinemia1 & Neurotoxicity2 risk factors

Plot total serum bilirubin on Hour-Specific Nomogram3, Phototherapy Nomogram4 and Exchange Nomogram5 (www.bilitool.org or www.peditools.org)

Is infant showing

signs/symptoms of ACUTE BILIRUBIN ENCEPHALOPATHY, irrespective of bilirubin level?

or Is TsB at/above PHOTOTHERAPY THRESHOLD

or Is TsB less than 3 mg/dL below PHOTOTHERAPY THRESHOLD but with signs/symptoms of ACUTE

HEMOLYSIS?

1Hyperbilirubinemia risk factors: *TsB/TcB in high-risk zone *Jaundice in first 24 hours *ABO incompatibility with positive direct Coombs, known hemolytic disease, or elevated ETCO *Gestational age 35-36 weeks *History of prior sibling requiring phototherapy *Cephalohematoma or bruising *Exclusive breastfeeding, esp. with poor feeding or weight loss 2Neurotoxicity risk factors: *Isoimmune Hemolytic Disease *G6PD deficiency *Asphyxia *Significant lethargy *Temperature instability *Sepsis *Acidosis *Albumin < 3.0 g/dL

Admit to Hospital & refer to inpatient management pathway (For JHACH patients, contact NICU first regarding unit assignment (ie NICU vs PICU vs Pediatric Medicine) Further work up by obtaining STAT CBC, Reticulocyte Count and Neonatal Antibody Profile Consider obtaining BMP to assess for electrolyte abnormalities & hydration status, if history and physical exam findings are suggestive of dehydration / poor oral intake Consider obtaining U/A & urine culture via catheter specimen to evaluate for UTI, if hx & lab data not suggestive of dehydration/poor oral intake or hemolysis & without clear etiology for jaundice

Is TsB below PHOTOTHERAPY THRESHOLD

and meets following criteria:

1) without any risk factors for neurotoxicity, 2) demonstrating adequate oral intake /

hydration status, 3) without signs/symptoms of acute hemolysis, 4) close follow-up assured with PCP within 24

hrs of EC discharge

Discharge Home

yes

no

no

yes

Obtain history, pattern and quality of stooling and voiding, mode of feeding (mother’s own milk and/or formula), physical exam, vital signs & growth parameters (based on EC protocol)

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Johns Hopkins All Children's Hospital Inpatient Neonatal Hyperbilirubinemia Clinical Pathway

Infants ≥ 35 weeks Gestational Age

Obtain history, pattern and quality of stooling and voiding, mode of feeding (mother’s own milk and/or formula), physical exam, vital signs & growth parameters (if not already obtained)

Encourage frequent feedings & engage lacation specialist for breastfed infants. (For currently hospitalized JHACH NICU infants, continue Transcutaneous Bilirubin (TcB) every 12 hours (ie, 1 hour before 0600 labs and 1 hour before 1800 labs or per hospital protocol) up to DOL 5. Confirmatory Total Serum Bilirubin (TsB) levels should be drawn for TcB values in the High-Intermediate to High Risk zones. Once phototherapy is initiated, TcB levels should be discontinued and TsB levels should be drawn instead.)

Is infant showing signs/symptoms of

ACUTE BILIRUBIN ENCEPHALOPATHY, irrespective of bilirubin level?

or Is TsB at/above or less than 3 mg/dL below

PHOTOTHERAPY THRESHOLD but with signs/symptoms of ACUTE HEMOLYSIS?

Off Pathway Start IVF & Intensive Phototherapy STAT. Consult NICU STAT for further recommendations as infant may be candidate for IVIG and/or Exchange Transfusion.

Continue q12h TcB (if meets criteria) or q12h-qAM TsB until levels decline without intervention. Continue to follow Inpatient Pathway if levels reach threshold for intervention.

Is repeat TsB greater than 3 mg/dL below Phototherapy Threshold and remains below High-Intermediate Risk Zone?

Initiate Intensive Phototherapy (ie min of 30 µW/cm2/nm) & optimize exposed surface area. Initiate IVF if concerns for dehydration or clinically indicated. Recheck TsB within 4-6 hours of initiation of phototherapy and then every 8-12 hours after levels decline. TsB levels can be further spaced to every 12-24 hours once declining TsB levels have been well established.

Discontinue phototherapy & calculate probability of rebound prediction score: https://jscalc.io/calc/68NNiFfS7iTMZhZY (with a prediction score of <20, phototherapy can be discontinued with <4% probability of rebound)

Consider obtaining rebound TsB after discontinuation of phothotherapy if plans to discharge same day with predicition score > 20 and without established PCP follow-up within 24-48 hrs. Ideally, rebound TsB should be obtained > 12 hrs after phototherapy discontinuation.

Ensure maximization of current Intensive Phototherapy with consideration for additional phototherapy exposure & limiting time out of phototherapy.

Assess for additional etiologies (ie Isoimmune Hemolytic Disease, G6PD deficiency, RBC enzyme deficiencies, RBC membrane defects, Gilbert’s disease, Infection, etc), and consult NICU if poor response to phototherapy.

Continue to recheck TsB every 4-6 hours and then every 8-12 hours after levels decline. TsB levels can be further spaced to every 12-24 hours once declining TsB levels have been well established.

yes

yes

no

no

no

yes

Is TsB below PHOTOTHERAPY THRESHOLD and without signs/symptoms of ACUTE HEMOLYSIS?

Assess for Hyperbilirubinemia1 & Neurotoxicity2 risk factors.

Plot TsB on Hour-Specific Nomogram3, Phototherapy Nomogram4 and Exchange Nomogram5 (www.bilitool.org or www.peditools.org)

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Evaluation

o Initial Assessment a. EC Patients

o Obtain history (including prenatal, birth and post-natal), pattern and quality of stooling and voiding, mode of feeding (mother’s own milk and/or formula), physical exam (including neurologic, hydration status, and jaundice), vital signs, growth parameters (ie weight).

b. Hospitalized Patients o Assess & encourage frequent feedings. Support breastfeeding & consult

lactation for breastfeeding moms. o For currently hospitalized JHAC NICU infants, initiate Transcutaneous

Bilirubin (TcB) upon admission - TcB to be obtained every 12 hours (ie, 1 hour before 0600 labs and 1 hour before 1800 labs or per hospital protocol) up to DOL 5. Confirmatory Total Serum Bilirubin (TsB) levels should be drawn for TcB values in the High-Intermediate to High Risk zones. Once phototherapy is initiated, TcB levels should be discontinued and TsB levels should be drawn instead.

o Initial Evaluation

a. Obtain baseline laboratory tests: Fractionated Serum Bilirubin followed by CBC, Reticulocyte Count and Neonatal Antibody Profile (ie Blood Type/Rh, Direct Coomb’s, Antibody Screen) as clinically indicated and if not already obtained. If labs abnormal and/or suggestive of infection and/or infant with clinical signs/symptoms of sepsis, a full sepsis work up including CSF culture, blood culture and urine culture (via catheter specimen) should be obtained before initiation of broad spectrum antibiotics in order to assess for neonatal sepsis. Refer to NICU Sepsis and UTI pathways for additional recommendations and guidance.

b. If history and physical examination findings are suggestive of dehydration / poor oral intake, obtain BMP to assess for electrolyte abnormalities and hydration status.

c. If history and laboratory data are not suggestive of dehydration / poor oral intake, hemolysis and without clear etiology for jaundice, obtain catheter urinalysis and urine culture, as data reveals significant number of neonates with jaundice as presenting sign of UTI. Of note, if U/A is suspicious for UTI via catheter specimen, a blood culture and lumbar puncture should be obtained before initiation of broad spectrum antibiotics in order to assess for neonatal sepsis. Refer to NICU Sepsis and UTI pathways for additional recommendations and guidance. Consultation with Infectious Disease advised regarding appropriate antibiotic choice and length of treatment in cases of confirmed neonatal UTI.

d. If history and laboratory data are not suggestive of dehydration / poor oral intake and suggestive of hemolysis, and particularly if bilirubin levels do not respond to or require additional phototherapy, assess further for:

o Isoimmune Hemolytic Disease o G6PD deficiency o RBC enzymes deficiencies

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o RBC membrane defects o Gilbert disease o Infection

e. Assess hyperbilirubinemia risk factors: o TsB/TcB in high-risk zone o Jaundice in first 24 hours o ABO incompatibility with positive direct Coombs, known hemolytic

disease, or elevated ETCO o Gestational age 35-36 weeks o History of prior sibling requiring phototherapy o Cephalohematoma or bruising o Exclusive breastfeeding, esp. with poor feeding or weight loss

f. Assess neurotoxicity risk factors: o Isoimmune Hemolytic Disease o G6PD deficiency o Asphyxia o Significant lethargy o Temperature instability o Sepsis o Acidosis o Albumin < 3.0 g/dL

g. Plot total serum bilirubin on Hour-Specific Nomogram, Phototherapy Nomogram and Exchange Nomogram (www.bilitool.org or www.peditools.org).

h. Hospital Admission / EC Discharge Criteria: o Admit to Hospitalist Service. However, for JHACH patients, NICU to be

first point of contact for ALL infants that may require hospital admission, including discussions surrounding unit assignment (ie NICU vs PICU vs Pediatric Medicine) as well as need for NICU consults in cases where infants are admitted to units outside of NICU. Possible scenarios for hospital admission include:

• Infant with signs /symptoms of ACUTE BILIRUBIN ENCEPHALOPATHY, irrespective of bilirubin level

• TsB at/above PHOTOTHERAPY THRESHOLD • TsB less than 3 mg/dL below PHOTOTHERAPY THRESHOLD

and with signs/symptoms of ACUTE HEMOLYSIS? o Consider discharge to home from EC if TsB is below PHOTOTHERAPY

THRESHOLD and provided meets following criteria: • without any risk factors for neurotoxicity, • demonstrating adequate oral intake / hydration status, • without signs/symptoms of acute hemolysis, • close follow-up assured with PCP within 24 hrs of EC discharge

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3Hour-specific Nomogram for Risk Stratification http://pediatrics.aappublications.org/content/pediatrics/114/1/297/F2.large.jpg

4Phototherapy Nomogram

http://pediatrics.aappublications.org/content/pediatrics/114/1/297/F3.large.jpg

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Treatment

o Guidelines for Administration of Intravenous Fluids (IVF) a. IV fluids and/or supplemental formula is routinely NOT indicated unless clinical

signs of dehydration are suspected. It is important to underscore that enteral feeds hasten elimination of bilirubin.

b. Encourage frequent feedings every 2-3 hours and for breastfed infants, engage lactation specialist for additional breastfeeding support.

c. Consider initiating IVF based on the following clinical factors: o Weight loss disproportionate for postnatal age o Hypernatremia o Increased urine specific gravity o Poor oral intake o Decreased urine output o Signs of poor perfusion o TsB above or withine 3 mg/dL of exchange level

5Exchange Transfusion Nomogram

http://pediatrics.aappublications.org/content/pediatrics/114/1/297/F4.large.jpg

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o Guidelines for Administration of Phototherapy a. Recommend initiation of intensive phototherapy= 30 µW/cm2/nm b. Recheck TsB within 4-6 hours of initiation and then every 8-12 hours after levels

decline. TsB levels can be further spaced to every 12-24 hours once declining TsB levels have been well established

c. Measure the irradiance level with bilimeter upon initiation of phototherapy, upon addition of another phototherapy device, and at least every 12 hours.

d. Ensure maximization of current Intensive Phototherapy with consideration for additional phototherapy exposure & limiting time out of phototherapy if repeat TsB levels not responding appropriately.

o Guidelines for Intravenous Immunoglobulin (IVIG)

a. If isoimmune hemolytic disease is suspected and bilirubin levels rising despite phototherapy or are approaching exchange transfusion levels (ie within 2-3 mg/dL), consider administration of IVIG (0.5 to 1.0 gm/kg over 2 hours, repeat in 12 hours if indicated). However, as IVIG is outside the scope of this pathway, recommend NICU consult for further guidance prior to administration.

o Guidelines for Exchange Transfusion a. Serum albumin may be helpful adjunct in assessing need for exchange

transfusion, for bilirubin levels approaching threshold. b. Exchange Transfusion is outside of the scope of this pathway. Consult NICU for

further guidance.

o Discontinuation of Phototherapy a. No standards for phototherapy discontinuation, however, consider

discontinuation after TsB is greater than 3 mg/dL below Phototherapy Threshold and remains below High-Intermediate Risk Zone.

b. Calculate probability of rebound prediction score: https://jscalc.io/calc/68NNiFfS7iTMZhZY. Score = 15 (if gestational age < 38 weeks) − 7 × (age in days at phototherapy initiation) − 4 × (AAP phototherapy threshold − TSB at phototherapy termination) + 50 With a prediction score of <20, phototherapy can be discontinued with <4% probability of rebound.

c. No standards for obtaining rebound TsB’s after discontinuation of phototherapy, however, consider obtaining rebound TsB after discontinuation of phothotherapy if plans to discharge same day of discontinuation of phototherapy with prediction score > 20 and without established close PCP follow-up within 24-48 hrs. If obtained, a rebound TsB ideally should be checked no less than 12 hrs from discontinuation of phototherapy, as levels drawn sooner may not correlate well with rebound risk. If rebound TsB off of phototherapy is obtained, expected rate of rise of less should be less than 0.2 mg/dL per hour.

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Criteria for Hospital Discharge

o All other hospital discharge criteria have been met. o Close follow-up with PCP within 24-48 hrs (preferably 24 hrs) of discharge has been

assured. o Verbal and written information regarding signs/symptoms of jaundice warranting

immediate medical attention distributed to caregivers. Patient Status: All patients with neonatal indirect hyperbilirubinemia should be placed in “inpatient” status if admitted for phototherapy. Outcomes 1) Rate of readmissions for jaundice/hyperbili

2) Rate of administration of IV fluids

3) Rate of obtaining rebound bilirubin levels prior to discharge

4) Length of stay for patients in the ER

5) Total length of stay for patients in the hospital

6) Length of phototherapy (time initiated to time discontinued)

References

1. Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the Newborn infant 35 or more weeks of gestation. AAP clinical practice guideline, Pediatrics, 2004. (114): 297-316

2. Berkwitt A. The utility of inpatient rebound bilirubin levels in infants readmitted after birth hospitalization for hyperbilirubinemia. Hosp Pediatr. 2015 Feb;5(2):74-8. doi: 10.1542/hpeds.2014-0074.

3. Bhutani VK. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2011 Oct;128(4):e1046-52.

4. Chang, PW et al. A clinical prediction rule for rebound hyperbilirubinemia following inpatient phototherapy. Pediatrics, 2017 (139): 1-9

5. Mehta S, et al. A randomized controlled trial of fluid supplementation in term neonates with severe hyperbilirubinemia. J Pedaitr 2005; 147: 781-5

6. Omar, C, et al. Urinary tract infection and indirect hyperbilirubinemia in newborns. N AM J Med Sci, 2011 Dec; 3(12): 544-547

7. Varvarigou A, et al. TcB nomogram for prediction of significant hyperbilirubinemia. Pediatrics 2009; 124: 1052-1059

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Disclaimer

Clinical Pathways are intended to assist physicians, physician assistants, nurse practitioners and other health care providers in clinical decision-making by describing a range of generally acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. The ultimate judgment regarding care of a particular patient must be made by the physician in light of the individual circumstances presented by the patient.

The information and guidelines are provided "AS IS" without warranty, express or implied, and Johns Hopkins All Children’s Hospital, Inc. hereby excludes all implied warranties of merchantability and fitness for a particular use or purpose with respect to the information. Johns Hopkins All Children’s Hospital, Inc. shall not be liable for direct, indirect, special, incidental or consequential damages related to the user's decision to use the information contained herein.

Clinical Pathway Team Neonatal Hyperbilirubinemia Clinical Pathway

Johns Hopkins All Children’s Hospital Owner(s): Travis Walker, MD Also Reviewed By: Hospitalist: Catherine Major, MD; Jennifer Maniscalco, MD Critical Care Medicine: Ladonna Bingham, MD

Initial Guideline Panel:

Travis Walker, MD Sandra Brooks, MD Nicole Nghiem, MD Candice Guevarra, DO Kathy Molina, ARNP Katie Bryant, RN

Clinical Pathways Team: Joe Perno, MD; Courtney Titus, PA-C, Clinical Pathways Program Coordinator Approved by Clinical Practice Council: July 21st, 2020 Last Revised: Aug 3, 2020

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Appendix A: Neonatal Phototherapy Nursing Checklist � Phototherapy source ordered in the patient’s EMR (bili-blanket, spot,

etc.)

� Bilimeter to test irradiance level (as per phototherapy order – generally 30-35 µW/cm2/nm

� Infant should be in diaper only, no clothes � Position phototherapy device at bedside with lights set at recommended

distance from the infant. For fluorescent and LED lights, this is as close as possible to the infant’s skin, typically less than 10 cm. If using a halogen spot light, the light should be kept at the manufacturer recommended distance to avoid overheating.

� Isolette (Giraffe Omnibed) – please see attached neonatal quick

reference o Isolette is needed for most phototherapy. If infant is on bili-

blanket only, may be in open crib if swaddled

� Temperature probe and temperature probe cover for use in isolette

� Thermometer to measure axillary temperature

� Eye protection

� Bili-blanket: obtain bili-blanket cover and ensure that illuminated side is facing patient

� TsB order present with frequency listed

Further information may be found in:

MyLearning:

ACH-Giraffe Bed video

Mosby’s Nursing Skills:

Phototherapy (Maternal-Newborn)

Phototherapy Blanket (Maternal-Newborn)

NICU Education Specialists: x72116 and x72881

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Appendix B: Neonatal Thermoregulation Quick Reference

• Giraffe o Infants should remain in servo (baby) mode and their body temperature should be

maintained at 36.5C-37.5C. Keep top down as much as possible and work through portholes

o Temperature probe over the liver (not over bone) while supine or on the flank while prone When using phototherapy lights, the probe must be directly in the path of the

radiant heat of the light; do not place the probe in an area shielded from the phototherapy light

Cover probe with reflective temp probe cover Probe must be visible

o No clothing or swaddling

• Thermoregulation o Infant’s axillary temperature should be 36.5-37.5. o Keep top of isolette down whenever possible o Use “Air boost” button when working through portholes o Check axillary temperature every 3 hours

If there is more than a 0.5 degree difference between the axillary temperature and isolette temp probe temperature, the two are not correlating.

• Check temperature probe position and adjust if needed • Replace temperature probe if necessary

Select mode by tapping here:

Baby Temperature

Air Boost

Set Temperature

Air Temperature