NCNC Jaundice Guideline



Consensus Guidelines for Screening & Management of Hyperbilirubinemia in Neonates UCSF (NC)2 (Northern CA Neonatology Consortium)Executive summaryObjectivesStandardize the approach to screening and management of hyperbilirubinemia in neonates ≥ 35 weeks gestational age (GA) across the consortium hospitals using current practice standards and best available evidenceImprove quality and safety of care for neonates ≥ 35 weeks GA with hyperbilirubinemia; specifically:Improve recognition and efficient management of infants at high risk for complications of hyperbilirubinemiaDecrease unnecessary testingDeliver safe, effective, and appropriate phototherapyDecrease unnecessary hospital daysRecommendationsPromote & support successful breastfeedingPerform a systematic assessment before newborn discharge for risk of severe hyperbilirubinemiaTreat newborns with phototherapy or exchange transfusion when indicated to prevent the development of severe hyperbilirubinemia and kernicterusRevisions to 2004 AAP Guidelines: Provide customized thresholds based on gestational age, neurotoxicity risk factors, and hours of life for each infantIncrease the threshold for phototherapy and exchange transfusion for most infants based on recent evidence given the extremely low rates of kernicterus and the possible risk of phototherapy causing adverse outcomesMethodsThis guideline was developed through local consensus based on published evidence and expert opinion as part of the UCSF Northern California Neonatal Consortium.Metrics PlanMonitoring of frequency of phototherapy use during the birth admission and readmissions for phototherapy.Consensus Guidelines for Screening & Management of Hyperbilirubinemia in NeonatesUCSF (NC)2 (Northern CA Neonatology Consortium)PART I: IntroductionJaundice / hyperbilirubinemia is common in newbornsMost jaundice is benign, but bilirubin can be toxic at very high levelsSevere hyperbilirubinemia can lead to acute bilirubin encephalopathy or kernicterus in rare casesGoal of developing standardized clinical practices is to reduce incidence of severe hyperbilirubinemia and kernicterus while minimizing risks of unintended harm (family anxiety, decreased breastfeeding, unnecessary costs or treatment, potential risk of phototherapy)AAP 2004 Clinical Practice Guideline (for newborns ≥35 weeks gestational age)[1]Outline of 2004 recommendations:Promote & support successful breastfeedingPerform a systematic assessment before newborn discharge for risk of severe hyperbilirubinemiaProvide early & focused follow-up based on risk assessmentTreat newborns with phototherapy or exchange transfusion when indicated to prevent the development of severe hyperbilirubinemia and kernicterusProduct = nomogram guidelines for phototherapy & exchange transfusion thresholds Concerns:2004 guidelines for phototherapy & exchange transfusion are based on limited evidence, insufficient to make specific recommendations No population-based studies of kernicterus incidenceNo studies to allow estimation of number needed to treat (NNT)2004 guideline recommends abrupt change in treatment thresholds at 38 weeks gestationResearch since 2004 suggests guideline leads to overtreatment with phototherapy and should be changedRarity of kernicterus ADDIN EN.CITE <EndNote><Cite><Author>Brooks</Author><Year>2011</Year><RecNum>10</RecNum><DisplayText>[2]</DisplayText><record><rec-number>10</rec-number><foreign-keys><key app="EN" db-id="zvsswrav8t2apbep2dbpv25ufvpprfe9rpex" timestamp="0">10</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brooks, J. C.</author><author>Fisher-Owens, S. A.</author><author>Wu, Y. W.</author><author>Strauss, D. J.</author><author>Newman, T. B.</author></authors></contributors><auth-address>Life Expectancy Project, San Francisco, California, USA. brooks@</auth-address><titles><title>Evidence suggests there was not a &quot;resurgence&quot; of kernicterus in the 1990s</title><secondary-title>Pediatrics</secondary-title></titles><periodical><full-title>Pediatrics</full-title></periodical><pages>672-9</pages><volume>127</volume><number>4</number><edition>2011/03/30</edition><dates><year>2011</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1098-4275 (Electronic)&#xD;0031-4005 (Linking)</isbn><accession-num>21444599</accession-num><urls><related-urls><url> [pii]&#xD;10.1542/peds.2010-2476</electronic-resource-num><language>eng</language></record></Cite></EndNote>[2], especially in term babies without hemolysisPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYW1hbGVsZGluPC9BdXRob3I+PFllYXI+MjAxMTwvWWVh

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ADDIN EN.CITE.DATA [7, 8]Internal inconsistency of guideline and high NNT ADDIN EN.CITE <EndNote><Cite><Author>Newman</Author><Year>2009</Year><RecNum>40</RecNum><DisplayText>[9]</DisplayText><record><rec-number>40</rec-number><foreign-keys><key app="EN" db-id="zvsswrav8t2apbep2dbpv25ufvpprfe9rpex" timestamp="0">40</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Newman, T. B.</author><author>Kuzniewicz, M. W.</author><author>Liljestrand, P.</author><author>Wi, S.</author><author>McCulloch, C.</author><author>Escobar, G. J.</author></authors></contributors><auth-address>Department of Epidemiology and Biostatistics, UCSF Box 0560, San Francisco, CA 94143, USA. newman@epi.ucsf.edu</auth-address><titles><title>Numbers needed to treat with phototherapy according to American Academy of Pediatrics guidelines</title><secondary-title>Pediatrics</secondary-title></titles><periodical><full-title>Pediatrics</full-title></periodical><pages>1352-9</pages><volume>123</volume><number>5</number><edition>2009/05/01</edition><keywords><keyword>Bilirubin/blood</keyword><keyword>Exchange Transfusion, Whole Blood</keyword><keyword>Female</keyword><keyword>Guidelines as Topic/*standards</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Jaundice, Neonatal/*therapy</keyword><keyword>Logistic Models</keyword><keyword>Male</keyword><keyword>Phototherapy/*standards/statistics &amp; numerical data</keyword><keyword>Risk Assessment</keyword></keywords><dates><year>2009</year><pub-dates><date>May</date></pub-dates></dates><isbn>1098-4275 (Electronic)</isbn><accession-num>19403502</accession-num><urls><related-urls><url> [pii]&#xD;10.1542/peds.2008-1635</electronic-resource-num><language>eng</language></record></Cite></EndNote>[9]Potential associations between phototherapy and childhood cancer PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DbmF0dGluZ2l1czwvQXV0aG9yPjxZZWFyPjE5OTU8L1ll

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ADDIN EN.CITE.DATA [13, 14]UCSF NC2 Consensus Guidelines goalsUpdate hyperbilirubinemia clinical practice recommendations based on recent researchDraw on Kaiser Permanente Northern California (KPNC) experience with updated practice guidelines [NOTE: Parts II-IV apply to neonates ≥ 35 weeks gestational age (GA)]PART II: Jaundice & bilirubin screening Blood TypingNewborn cord blood should be sent to blood bank on all newborns, with testing in the following circumstances:Rh neg mother Rh type + direct antiglobulin test (DAT)O pos mother DAT onlyNOTE: ABO group unnecessary, does not change management (e.g. neonate is low risk if DAT negative, regardless of ABO group) OPTION: send cord blood to blood bank to hold on infants born to O pos mothers; order DAT (and other studies) only IF clinical jaundice is notedMaternal antibody screen positive DAT Consider: cord blood bilirubin levelMaternal blood type and antibody screen unknown DATNOTE: Blood bank can hold cord blood / peripheral blood specimen for further testing if requestedIf cord blood was not sent to the blood bank initially, OK to wait for jaundice or other clinical indication for blood type/group/DAT except in Rh-negative mothersTranscutaneous Bilirubin (TcB) Screening24-48hrs of life in all neonates and/or prior to dischargeAnytime jaundice is detectedEarlier + more frequent screening if DAT positiveFrequent re-assessment if TcB close to phototherapy threshold or rapidly risingTotal Serum Bilirubin (TsB) TestingTcB within 3 mg/dL of phototherapy threshold Consider if TcB >12-13 (TcB less accurate above this range)Follow TsB if TcB >13 or if TsB has been >15 until declining PART III: TreatmentMedical ManagementGeneral recommendationsLactation support; oral hydration if dehydratedAGGRESSIVE MEDICAL THERAPY: for babies within two mg/dL of NCNC exchange transfusion threshold, or rapidly rising (>7 mg/dL in 24hrs or > 0.3mg/dL per hour)Aggressive IV + PO hydrationIntensive phototherapyMonitor TsB every 2-4 hours depending on previous rate of riseConsult with neonatologist re: additional therapies (e.g. IVIG)Phototherapy Thresholds1 Basic recommendations:Identify neurotoxicity risk factors:Isoimmune hemolytic disease, G6PD deficiency,?or other hemolytic diseaseSepsis?or suspected sepsis (sufficient to be currently on antibiotics)Acidosis (BE ≤ ??8 meq/L?or pCO2 >50 mmHg within the last 24 hr)Albumin <3.0 mg/dLAny clinical instability?TsB within 1-2 mg/dL below NCNC phototherapy threshold = CONSIDER PHOTOTHERAPYOptimize feeding (breastfeeding support, supplement, formula, etc)Repeat TsB @ 4-24hrs (prior to discharge if during birth admission)Consider phototherapy (including home phototherapy if available)NOTE: NCNC threshold to initiate phototherapy is lower for younger gestational ages, rapid rate of rise, or neurotoxicity risk factors (i.e. “medium risk” or “higher risk” infants)TsB ≥ NCNC threshold = PERFORM PHOTOTHERAPYStart phototherapy Optimize feeding (as above)If there is suspicion for hemolysis or other underlying causes of hyperbilirubinemia (G6PD, sepsis, etc), it is appropriate to start phototherapy at the threshold for newborns with neurotoxicity risk factors and proceed with an appropriate work up for those causes. For example, for a 38 0/7-week formula-fed African American male at 96 hours of age, if the TSB were 19.0 mg/dL, it would be appropriate to start phototherapy (and check the G6PD activity) even though the threshold used if neurotoxicity risk factors are absent would be 20.4. This is because the threshold would be 18.2 if neurotoxicity risk factor were present and the clinical picture suggests G6PD deficiency, a neurotoxicity risk factor for which confirmation is often not immediately available.? ? ?CONSIDER: Higher threshold for readmission for phototherapy if infant at home (≥ 2-3 days of life) versus the threshold for phototherapy during the birth admission “Customized thresholds”: Individualized thresholds based on exact gestational age, neurotoxicity risk factors, and hours of life: Figure 1: New Phototherapy Thresholds for babies with no neurotoxicity risk factors (NT RF)Figure 2: New Phototherapy Thresholds for babies with neurotoxicity risk factors (NT RF)See website for calculator: Guideline soon to be housed at: Transfusion Thresholds2Basic Recommendations:Consultation with neonatologist when infants have bilirubin within 2 mg/dL of NCNC exchange transfusion threshold or rapidly rising (>7 mg/dL in 24 hours or >0.3mg/dL/hr), particularly in first 48 hours of lifeINITIAL bilirubin (e.g. no prior bilirubin measurement or intervention)> 2 mg/dL above NCNC Exchange Transfusion threshold = PREPARE FOR IMMEDIATE EXCHANGE TRANSFUSIONPerform aggressive medical therapy as above while preparing for exchange transfusion OR initiating transfer to institution capable of performing exchange transfusion0-2 mg/dL above NCNC threshold = CONSIDER EXCHANGE TRANSFUSIONAggressive medical therapy as aboveStrongly consider transfer to institution capable of performing exchange transfusion0-2 mg/dL below NCNC Threshold Aggressive medical therapy as aboveSee flow chart for full recommendationsFigure 3: Exchange Transfusion Recommendations Near NCNC Exchange Transfusion Threshold “Customized thresholds”: Individualized thresholds based on exact gestational age, neurotoxicity risk factors, and hours of life:Figure 4: New Exchange Transfusion Thresholds for Babies WITHOUT Neurotoxicity Risk Factors Figure 5: New Exchange Transfusion Thresholds for Babies WITH Neurotoxicity Risk Factors (NT RF)IVIG: for isoimmune hemolytic anemia ONLYIVIG 1g/kg?IV over 2 hours if the Total Serum Bilirubin is rising despite intensive phototherapy. May repeat x1 after 12 hours of first dose. (With an acceptable range of 0.5g/kg to 1g/kg – round to vial size)For hemolytic jaundice that is NOT isoimmune, consult Neonatologist or HematologistBilirubin monitoringPrior to initiation of phototherapy:NOTE: For infants readmitted for phototherapy, if last TsB was >4-6 hours prior, repeat TsBDuring phototherapy:For all infants, check TsB within 12 hours of initiation of phototherapyTsB ~ q12 hours:No hemolytic disease or rapid rate of riseTsB within 6-8 hours:Evidence or suspicion of hemolytic disease Rapid rate of rise (>7 mg/dL/24 hours or >0.3mg/dL/hr)Other neurotoxicity risk factors (i.e. sepis or acidosis)TsB q2-4 hours: Bilirubin within 1-2 mg/dL of NCNC threshold for exchange transfusion NOTE: all bilirubin monitoring during phototherapy should be done via serum bilirubin levels; transcutaneous bilirubin is not accurate Discontinuation of PhototherapyDiscontinue phototherapy when TsB is at least 2-3 mg/dL below the phototherapy initiation thresholdIndications for longer course of phototherapy:Ongoing feeding difficultyPrematurity (< 37 weeks GA)Slow rate of decrease while on phototherapyHemolytic jaundiceHydration and nutrition considerations:Support breastfeedingConsider enteral supplementation with expressed breast milk, formula, etcConsider IV fluids only if close to exchange transfusion or if other indications for IV fluidsRebound bilirubin measurement:Indications for ordering rebound TsB:Hemolytic jaundice Prematurity (<37 weeks GA)If phototherapy is discontinued sooner than 2-3 mg/dL below the phototherapy initiation threshold If phototherapy was started prior to 48 hoursTiming: 6-24 hoursTcB may be inaccurate following phototherapy. Use TsB in this setting.PART IV: Discharge & Follow-upDischarge CriteriaOff phototherapy and otherwise wellFeeding adequatelyFollow-up arranged for 24-48hrsExpectation that additional phototherapy will not be necessaryFootnotesMethodology for determining new phototherapy thresholds/calculator: The starting point for the new thresholds were the 2004 AAP guidelines. On examination of new data, the evidence since 2004 suggested raising thresholds, given the extremely low rates of kernicterus and the possible risk of phototherapy causing adverse outcomes. Therefore, for babies with no NT risk factors we added 2 mg/dL to the 2004 AAP low risk threshold for 40-week babies and 1 mg/dL to the AAP MRT for 35-week babies, then adjusted for individualized gestational age. For babies with NT risk factors we added 1 mg/dL for infants ≥ 38 weeks and nothing for 35 week infants, then adjusted for individualized gestational age.Methodology for determining new exchange transfusion thresholds/calculator: The starting point for the new thresholds were the 2004 AAP guidelines. On examination of new data, the evidence since 2004 suggested raising thresholds, given the extremely low rates of kernicterus. Therefore, for babies with no NT risk factors we added 0 to the AAP low-risk threshold at birth and 5 mg/dL to the 2004 AAP low risk threshold at 96 hours for 40 week babies and 0 at birth and 3 mg/dL at 96 hours to the threshold for 35-week then adjusted for individualized age (if < 96 hours) and gestational age. For babies with NT risk factors we added 0 to the AAP medium risk threshold for 40 week babies at birth and 3 mg/dL to the AAP medium risk threshold for 40-week babies at 96 hours; the changes from the AAP guidelines increase from 0 at birth to 3 mg/dL at 96 hours. We added nothing to the AAP high-risk threshold for 35-week babies. We then adjusted for individualized age (if < 96 hours) and gestational age. ADDIN EN.REFLIST REFERENCES1.Maisels, M.J., et al., Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics, 2004. 114(1): p. 297-316.2.Brooks, J.C., et al., Evidence suggests there was not a "resurgence" of kernicterus in the 1990s. Pediatrics, 2011. 127(4): p. 672-9.3.Gamaleldin, R., et al., Risk factors for neurotoxicity in newborns with severe neonatal hyperbilirubinemia. Pediatrics, 2011. 128(4): p. e925-31.4.Kuzniewicz, M.W., et al., Incidence, Etiology, and Outcomes of Hazardous Hyperbilirubinemia in Newborns. Pediatrics, 2014: p. peds.2014-0987.5.Wu, Y.W., et al., Risk for cerebral palsy in infants with total serum bilirubin levels at or above the exchange transfusion threshold: a population-based study. JAMA Pediatr, 2015. 169(3): p. 239-46.6.Ebbesen, F., J.V. Bjerre, and P.K. Vandborg, Relation between serum bilirubin levels >/=450 mumol/L and bilirubin encephalopathy; a Danish population-based study. Acta Paediatr, 2012. 101(4): p. 384-9.7.Vandborg, P.K., et al., Follow-up of extreme neonatal hyperbilirubinemia in 5- to 10- year old children: a Danish population-based study. Developmental Medicine and Child Neurology, 2014.8.Newman, T.B., et al., Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more. N Engl J Med, 2006. 354(18): p. 1889-900.9.Newman, T.B., et al., Numbers needed to treat with phototherapy according to American Academy of Pediatrics guidelines. Pediatrics, 2009. 123(5): p. 1352-9.attingius, S., et al., Prenatal and neonatal risk factors for childhood myeloid leukemia. Cancer Epidemiol Biomarkers Prev, 1995. 4(5): p. 441-5.11.Newman, T.B., et al., Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California. Pediatrics, 2016. 137(6).12.Frazier, A.L., M. Krailo, and J. Poynter, Can Big Data Shed Light on the Origins of Pediatric Cancer? Pediatrics, 2016. 137(6).13.Maimburg, R.D., J. Olsen, and Y. Sun, Neonatal hyperbilirubinemia and the risk of febrile seizures and childhood epilepsy. Epilepsy Res, 2016. 124: p. 67-72.14.Newman, T.B., et al., Phototherapy and risk of subsequent seizures. Work in progress, Pending. ................
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