2024/9/111新生儿黄疸诊治新生儿黄疸诊治 Paediatrics & Child Health1999;4(2):161-164ReferenceNo.FN98-02RevisioninprogressMay2007Paediatrics & Child Health2007;12(5):1B-12BReferenceNo.FN07-02Guidelinesfordetection,managementandpreventionofhyperbilirubinemiaintermandlatepretermnewborninfants参考文献Hyperbilirubinemiaisverycommonandusuallybenigninthetermnewborninfantandthelatepreterminfantat35to36completedweeks.Criticalhyperbilirubinemiaisuncommonbuthasthepotentialforcausinglong-termneurologicalimpairment.Earlydischargeofthehealthynewborninfant,particularlythoseinwhombreastfeedingmaynotbefullyestablished,maybeassociatedwithdelayeddiagnosisofsignificanthyperbilirubinemia.高胆红素血症很常见，多为良性。危险的高胆红素血症并不常见，但是有潜在的导致长期神经损害的可能。胆红素水平与胆红素脑病发生胆红素水平与胆红素脑病发生Itisestimatedthat60%oftermnewbornsdevelopjaundiceand2%reachaTSBconcentrationgreaterthan340mol/L(19.8mg/dl).Acuteencephalopathydoesnotoccurinfull-terminfantswhosepeakTSBconcentrationremainsbelow340mol/LandisveryrareunlessthepeakTSBconcentrationexceeds425mol/L(24.85mg/dl).Abovethislevel,theriskfortoxicityprogressivelyincreases.Morethanthree-quartersoftheinfantsintheUnitedStateskernicterusregistry(between1992and2002)hadaTSBconcentrationof515mol/L(30.1mg/dl)orgreater,andtwo-thirdshadaconcentrationexceeding600mol/L(35mg/dl).Evenwithconcentrationsgreaterthan500mol/L(29.2mg/dl),therearestillsomeinfantswhowillescapeencephalopathy.Kernicterus（核黄疸核黄疸）:thepathologicalfindingofdeep-yellowstainingofneuronsandneuronalnecrosisofthebasalganglia（基底节）andbrainstemnuclei（脑干神经元）.Acutebilirubinencephalopathy（急性胆红素脑病）（急性胆红素脑病）:aclinicalsyndrome,inthepresenceofseverehyperbilirubinemia,oflethargy（昏睡）,hypotoniaand（肌张力减低）poorsuck,whichmayprogresstohypertonia(withopisthotonos（角弓反张）andretrocollis（颈后倾）)withahigh-pitchedcryandfever,andeventuallytoseizures（发作）andcoma.Chronicbilirubinencephalopathy（慢性胆红素脑病）（慢性胆红素脑病）:theclinicalsequelaeofacuteencephalopathywithathetoidcerebralpalsy（手足徐动症样大脑麻痹）withorwithoutseizures,developmentaldelay,hearingdeficit,oculomotor（眼球运动异常）disturbances,dentaldysplasia（牙发育异常）andmentaldeficiency.Severehyperbilirubinemia（严重的高胆红素血症）（严重的高胆红素血症）:atotalserumbilirubin(TSB)concentrationgreaterthan340mol/Latanytimeduringthefirst28daysoflife.Criticalhyperbilirubinemia（危险的高胆红素血症）（危险的高胆红素血症）:aTSBconcentrationgreaterthan425mol/Lduringthefirst28daysoflife.具有危险因素人群中患者与非患者之比相当于不具有危险因素人群中患者与非患者之比的倍数具有危险因素人群中患者与非患者之比相当于不具有危险因素人群中患者与非患者之比的倍数脱水，高渗，呼吸窘迫，水肿，早产，酸中毒，低白蛋白血症，缺氧，抽搐可增加急性脑病的发生率与败血症的关系?Allofthereasonsforthevariablesusceptibilityofinfantsarenotknown;however,dehydration,hyperosmolarity,respiratorydistress,hydrops,prematurity,acidosis,hypoalbuminemia,hypoxiaandseizuresaresaidtoincreasetheriskofacuteencephalopathyinthepresenceofseverehyperbilirubinemia,althoughreliableevidencetoconfirmtheseassociationsislacking.Inaddition,someinfantswithseverehyperbilirubinemiaarefoundtohavesepsis,butbothsepsisandhyperbilirubinemiaarecommonintheneonatalperiod,andsepsisappearstobeuncommoninthewell-appearinginfantwithseverehyperbilirubinemia.黄疸的发生（总体发生情况）Early(days1-2)-uncommonHaemolyticjaundice(ABO,others)Normal(days3-10)-verycommonUncomplicatedComplicated-seebelowLate(days14+)Breastmilk-commonConjugatedjaundice-uncommonInheriteddeficiencyofglucuronyltransferaseenzymes-veryrareInvestigations:Measurementofbilirubin经皮测并不准确（与是否光疗后，皮肤颜色及厚度都有关）经皮测并不准确（与是否光疗后，皮肤颜色及厚度都有关）ThereareseverallimitationstoTcBmeasurements:theybecomeunreliableafterinitiationofphototherapy,andtheymaybeunreliablewithchangesinskincolourandthickness.However,theresultsaremoreaccurateatlowerlevelsofbilirubin,andtherefore,useofTcBasascreeningdeviceisreasonableClinicalevaluationKramersRuleRatherthanestimatingthelevelofjaundicebysimplyobservingthebabysskincolour,onecanutilisethecephalocaudalprogressionofjaundice.Kramerdrewattentiontotheobservationthatjaundicestartsonthehead,andextendstowardsthefeetasthelevelrises.ThisisusefulindecidingwhetherornotababyneedstohavetheSBRmeasured.Kramerdividedtheinfantinto5zones,theSBRrangeassociatedwithprogressiontothezonesisasfollows:ClinicalmanagementofhyperbilirubinemiaininfantsTABLE1:LaboratoryinvestigationforhyperbilirubinemiaintermnewborninfantsIndicated(ifbilirubinconcentrationsreachphototherapylevels)SerumtotalorunconjugatedbilirubinconcentrationSerumconjugatedbilirubinconcentrationBloodgroupwithdirectantibodytest(Coombstest)HemoglobinandhematocritdeterminationsOptional(可选择的)CompletebloodcountincludingmanualdifferentialwhitecellcountBloodsmearforredcellmorphologyReticulocytecountGlucose-6-phosphatedehydrogenasescreenSerumelectrolytesandalbuminorproteinconcentrationsTimedTSBmeasurements定时胆红素水平监测，适时干预UmbilicalcordbloodTSB（脐带血胆红素水平并无特异性）（脐带血胆红素水平并无特异性）ATSBconcentrationgreaterthan30mol/LinumbilicalcordbloodisstatisticallycorrelatedwithapeakneonatalTSBconcentrationgreaterthan300mol/L,butthepositivepredictivevalue（阳性预测值）isonly4.8%fortheterminfant,risingto10.9%inthelatepreterminfant,andthespecificityisverypoorUniversalhemoglobinassessment（常规脐带血血红蛋白或红（常规脐带血血红蛋白或红细胞比容测定并不能预测严重高胆红素血症的发生）细胞比容测定并不能预测严重高胆红素血症的发生）Althoughbilirubinisderivedfromthebreakdownofhemoglobin,routineumbilicalcordbloodhemoglobinorhematocritmeasurementdoesnotaidinthepredictionofseverehyperbilirubinemiaBloodgroupandCoombstesting（血型及（血型及Coombs试试验）验）ABO溶血是常见原因，大部分新生儿黄疸与ABO溶血有关（bloodgroupAorBinfantsborntoamotherwithgroupOblood）ABO溶血患儿直抗阳性者比阴性者更需光疗TheneedforphototherapyisincreasedinABO-incompatibleinfantswhoaredirectantiglobulintest(DATdirectCoombstest)-positivecomparedwiththosewhoareDAT-negative对型血母亲及有高危因素的黄疸患儿进行DAT检测TestingallbabieswhosemothersaregroupOdoesnotimproveoutcomescomparedwithtestingonlythosewithclinicaljaundice.Therefore,itisreasonabletoperformaDATinclinicallyjaundicedinfantsofmotherswhoaregroupOandininfantswithanelevatedriskofneedingtherapyTheresultswilldeterminewhethertheyarelowriskorhighrisk,andmaythereforeaffectthethresholdatwhichtherapywouldbeindicated时间胆红素水平曲线时间胆红素水平曲线加强光疗的指征曲线Glucose-6-phosphatedehydrogenasedeficiency（葡萄糖（葡萄糖-6-磷酸脱氢酶缺乏症磷酸脱氢酶缺乏症）与严重胆红素血症相关Newbornswithglucose-6-phosphatedehydrogenase(G6PD)deficiencyhaveanincreasedincidenceofseverehyperbilirubinemiaG6PDdeficiencyincreasesthelikelihoodofrequiringexchangetransfusionininfantswithseverehyperbilirubinemia;therefore,atestforG6PDdeficiencyshouldbeconsideredinallinfantswithseverehyperbilirubinemia有家族种族高危因素的都应行此检查TestingforG6PDdeficiencyinbabieswhoseethnicgrouporfamilyhistorysuggestanincreasedriskofG6PDdeficiencyisadvised.有高危因素男女孩都因检测AlthoughG6PDdeficiencyisanX-linkeddisease,femaleheterozygotescanhavemorethan50%oftheirredcellsdeficientintheenzymebecauseofrandominactivationoftheXchromosome.Femaleswithgreaterproportionsoftheirredcellsaffectedhaveanincreasedriskofsevereneonatalhyperbilirubinemia；therefore,testingofbothgirlsandboyswhoareatriskisadvised有溶血病时，G-6-PD水平会被检测过高从而影响诊断Itshouldalsoberecognizedthatinthepresenceofhemolysis,G6PDlevelscanbeoverestimatedandthismayobscurethediagnosisFemalesinparticularcanhavemisleadingresultsonthecommonscreeningtests积极进行干预G6PD-deficientnewbornsmayrequireinterventionatalowerTSBconcentrationbecausetheyaremorelikelytoprogresstoseverehyperbilirubinemia.Unfortunately,inmanycentres,itcurrentlytakesseveraldaysforaG6PDdeficiencyscreeningtestresulttobecomeavailable.Improvingtheturnaroundtimeforthistestwouldimprovecareofthenewborn.BecauseG6PDdeficiencyisadiseasewithlifelongimplications,testinginfantsatriskisstillofvalue.建议建议（每项均有建议的等级与研究的可靠性相关）：孕妇ABO,Rh血型检测及红细胞抗体筛查AllmothersshouldbetestedforABOandRh(D)bloodtypesandbescreenedforredcellantibodiesduringpregnancy脐血检测Ifthemotherwasnottested,cordbloodfromtheinfantshouldbesentforevaluationofthebloodgroupandaDAT(Coombstest)母型血的早期黄疸患儿应做血型鉴定及DAT检测BloodgroupevaluationandaDATshouldbeperformedininfantswithearlyjaundiceofmothersofbloodgroupO.G-6-PD筛查Selectedat-riskinfants(Mediterranean,MiddleEastern,AfricanorSoutheastAsianorigin)shouldbescreenedforG6PDdeficiency.严重的高胆红素血症时应做G-6-PD检测AtestforG6PDdeficiencyshouldbeconsideredinallinfantswithseverehyperbilirubinemiaWhen?怎样减少严重高胆红素血症的发生？怎样减少严重高胆红素血症的发生？HOW CAN THE RISK OF SEVERE HYPERBILIRUBINEMIA BE REDUCED? Primarypreventionofseverehyperbilirubinemia一级预防一级预防Breastfeedingsupport对于母亲的宣教OtherineffectiveinterventionsRoutineuseofglycerinesuppositories（甘油栓剂）routineglycerineenemas开赛露，L-asparticacid（天冬氨酸）,whey/caseinandclofibrate（氯贝丁脂）haveallbeenstudiedinsmallrandomizedcontrolledtrials(RCTs),buttheirusehasbeenfoundtohavenoeffectonclinicallyimportantoutcomes.PreventionofseverehyperbilirubinemiaininfantswithhemolysisPhenobarbitone（苯巴比妥）Tin-mesoporphyrinSnMP（锡中卟啉）抑制胆红素合成及活性，临床使用未见明显改变Prophylacticphototherapy（预防光疗）是否加强光疗见表PreventionofseverehyperbilirubinemiaininfantswithmildormoderatehyperbilirubinemiaPhototherapyInterruptingbreastfeeding（停止母乳喂养）RCT未见明显区别Intravenousimmunoglobulin（静丙）与免疫因素相关的溶血Supplementalfluids（补液）Agar（琼脂）可减少肠壁对未结合胆红素的吸收，没有可靠的证据支持建议：支持母乳喂养支持母乳喂养Aprogramforbreastfeedingsupportshouldbeinstitutedineveryfacilitywherebabiesaredelivered并不推荐给母乳喂养的婴儿常规补充水或糖水并不推荐给母乳喂养的婴儿常规补充水或糖水Routinesupplementationofbreastfedinfantswithwaterordextrosewaterisnotrecommended静丙的使用静丙的使用InfantswithapositiveDATwhohavepredictedseverediseasebasedonantenatalinvestigationoranelevatedriskofprogressingtoexchangetransfusionbasedonthepostnatalprogressionofTSBconcentrationshouldreceiveIVIGatadoseof1g/kg胆红素水平及高危因素提示可能有发生严重高胆红素血症趋势的时候，即使出院也应追踪胆红素水平及高危因素提示可能有发生严重高胆红素血症趋势的时候，即使出院也应追踪监测胆红素水监测胆红素水ATSBconcentrationconsistentwithincreasedriskshouldleadtoenhancedsurveillancefordevelopmentofseverehyperbilirubinemia,withfollow-upwithin24hto48h,eitherinhospitalorinthecommunity,andrepeatestimationofTSBorTcBconcentrationinmostcircumstances加强光疗加强光疗IntensivephototherapyshouldbegivenaccordingtotheguidelinesshowninFigure2常规光疗常规光疗ConventionalphototherapyisanoptionatTSBconcentrations35mol/Lto50mol/LlowerthantheguidelinesinFigure2光疗中也应继续母乳喂养光疗中也应继续母乳喂养Breastfeedingshouldbecontinuedduringphototherapy迅速进展可能需要换血时，应控制补液量迅速进展可能需要换血时，应控制补液量Supplementalfluidsshouldbeadministered,orallyorbyintravenousinfusion,ininfantsreceivingphototherapywhoareatanelevatedriskofprogressingtoexchangetransfusion.HOWSHOULDSEVEREHYPERBILIRUBINEMIABETREATED?Phototherapy初始治疗，监测胆红素水平，有指征时开始做换血准备补液，静丙Aninfantwhopresentswithseverehyperbilirubinemia,orwhoprogressestoseverehyperbilirubinemiadespiteinitialtreatment,shouldreceiveimmediateintensivephototherapy.Thebilirubinconcentrationshouldbecheckedwithin2hto6hofinitiationoftreatmenttoconfirmresponse.Considerationoffurthertherapyshouldcommenceandpreparationsforexchangetransfusionmaybeindicated.Supplementalfluidsareindicated,andIVIGshouldbegivenifnotalreadycommencedfortheinfantwithisoimmunization.Phototherapy脱水高胆红素血症光疗脱水高胆红素血症光疗Itisimportanttorecognizetherelationshipbetweendehydrationandhyperbilirubinemia.Dehydrationmaybeassociatedwithincreasedserumbilirubinconcentrationsandmaybeexacerbatedbyphototherapy.Alljaundicedinfantsshouldbeadequatelyhydratedbeforeandduringphototherapy.Breastfeedingisnotcontraindicatedinthepresenceofhyperbilirubinemiaandshouldbecontinued.Morefrequentbreastfeedingsmaybebeneficial.Exchangetransfusion光疗失败Ifphototherapyfailstocontroltherisingbilirubinconcentrations,exchangetransfusionisindicatedtolowerTSBconcentrations.没有高危因素的健康足月儿Forhealthytermnewbornswithoutriskfactors,exchangetransfusionshouldbeconsideredwhentheTSBconcentrationisbetween375mol/L(21.9mg/dL)and425mol/L(24.8mg/dL)(despiteadequateintensivephototherapy).在换血前采血完善相关检查Becausebloodcollectedafteranexchangetransfusionisofnovalueforinvestigatingmanyoftherarercausesofseverehyperbilirubinemia,theseinvestigationsshouldbeconsideredbeforeperformingtheexchangetransfusion.Appropriateamountsofbloodshouldbetakenandstoredfortestssuchasthoseforredcellfragility,enzymedeficiency(G6PDorpyruvatekinase丙酮酸激酶deficiency)andmetabolicdisorders,aswellasforhemoglobinelectrophoresisandchromosomeanalysis.如果胆红素水平刚达到换血指征，在换血前应再次检测胆红素水平。严格掌握换血指征。Preparationofbloodforexchangetransfusionmaytakeseveralhours,duringwhichtimeintensivephototherapy,supplementalfluidsandIVIG(incaseofisoimmunization)shouldbeused.IfaninfantwhoseTSBconcentrationisalreadyabovetheexchangetransfusionlinepresentsformedicalcare,thenrepeatmeasurementoftheTSBconcentrationjustbeforeperformanceoftheexchangeisreasonable,aslongastherapyisnottherebydelayed.Inthisway,someexchangetransfusions,withtheirattendantrisks,maybeavoided.Exchangetransfusionisaprocedurewithsubstantialmorbiditythatshouldonlybeperformedincentreswiththeappropriateexpertiseundersupervisionofanexperiencedneonatologist.当有急性胆红素脑病的临床表现时应马上换血Aninfantwithclinicalsignsofacutebilirubinencephalopathyshouldhaveanimmediateexchangetransfusion.建议：InfantswithaTSBconcentrationabovethethresholdsshownonFigure3shouldhaveimmediateintensivephototherapy,andshouldbereferredforfurtherinvestigationandpreparationforexchangetransfusion.Aninfantwithclinicalsignsofacutebilirubinencephalopathyshouldhaveanimmediateexchangetransfusion.换血指征Follow-up随访：随访：Routinenewbornsurveillance,whetherinhospitalorafterdischarge,shouldincludeassessmentofbreastfeedingandjaundiceevery24hto48huntilfeedingisestablished(usuallyonthethirdorfourthdayoflife).Alljaundicedinfants,especiallyhigh-riskinfantsandthosewhoareexclusivelybreastfed,shouldcontinuetobecloselymonitoreduntilfeedingandweightgainareestablishedandtheTSBconcentrationstartstofall.CommunityservicesshouldincludebreastfeedingsupportandaccesstoTSBorTcBtesting.Infantswithisoimmunizationareatriskforsevereanemiaafterseveralweeks;itissuggestedthatarepeathemoglobinmeasurementbeperformedattwoweeksifitwaslowatdischargeandatfourweeksifitwasnormal.Infantsrequiringexchangetransfusionorthosewhoexhibitneurologicalabnormalitiesshouldbereferredtoregionalmultidisciplinaryfollow-upprograms.Neurosensoryhearinglossisofparticularimportanceininfantswithseverehyperbilirubinemia,andtheirhearingscreenshouldincludebrainstemauditoryevokedpotentials.FurtherinvestigationsTheoccurrenceofseverehyperbilirubinemiamandatesaninvestigationofthecauseofhyperbilirubinemia.Investigationsshouldincludeaclinicallypertinenthistoryofthebabyandthemother,familyhistory,descriptionofthelabouranddelivery,andtheinfantclinicalcourse.Aphysicalexaminationshouldbesupplementedbylaboratoryinvestigations(conjugatedandunconjugatedbilirubinlevels;directCoombstest;hemoglobinandhematocritlevels;andcompletebloodcellcount,includingdifferentialcount,bloodsmearandredcellmorphology).Investigationsforsepsisshouldbeperformedifwarrantedbytheclinicalsituation.建议：每个黄疸的患儿均应随访Adequatefollow-upshouldbeensuredforallinfantswhoarejaundiced.加强光疗的患儿应完善相关检查，以了解黄疸病因Infantsrequiringintensivephototherapyshouldbeinvestigatedfordeterminationofthecauseofjaundice.CONCLUSION严重的高胆红素血症的有发生急性胆红素脑病及慢性后遗症的可能严重的高胆红素血症的有发生急性胆红素脑病及慢性后遗症的可能对高危因素进行评估，辅查，在有指征时光疗及换血是避免这些并发对高危因素进行评估，辅查，在有指征时光疗及换血是避免这些并发症发生的要点症发生的要点Severehyperbilirubinemiainrelativelyhealthytermorlatepretermnewborns(greaterthan35weeksgestation)continuestocarrythepotentialforcomplicationsfromacutebilirubinencephalopathyandchronicsequelae.Carefulassessmentoftheriskfactorsinvolved,asystematicapproachtothedetectionandfollow-upofjaundicewiththeappropriatelaboratoryinvestigations,alongwithjudiciousphototherapyandexchangetransfusionwhenindicated,areallessentialtoavoidthesecomplications.Thank you!