新生兒黃疸診治

新生兒黃疸診治

yaoyue28@sina.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第1頁!Paediatrics&ChildHealth1999;4(2):161-164

ReferenceNo.FN98-02RevisioninprogressMay2007Paediatrics&ChildHealth2007;12(5):1B-12B

ReferenceNo.FN07-02

Guidelinesfordetection,managementandpreventionofhyperbilirubinemiaintermandlatepretermnewborninfants

參考文獻(xiàn)新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第2頁!Hyperbilirubinemiaisverymonandusuallybenigninthetermnewborninfantandthelatepreterminfantat35to36pletedweeks.Criticalhyperbilirubinemiaisunmonbuthasthepotentialforcausinglong-termneurologicalimpairment.Earlydischargeofthehealthynewborninfant,particularlythoseinwhombreastfeedingmaynotbefullyestablished,maybeassociatedwithdelayeddiagnosisofsignificanthyperbilirubinemia.高膽紅素血癥很常見，多為良性。危險(xiǎn)的高膽紅素血癥并不常見，但是有潛在的導(dǎo)致長(zhǎng)期神經(jīng)損害的可能。新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第3頁!膽紅素水平與膽紅素腦病發(fā)生Itisestimatedthat60%oftermnewbornsdevelopjaundiceand2%reachaTSBconcentrationgreaterthan340μmol/L(19.8mg/dl).Acuteencephalopathydoesnotoccurinfull-terminfantswhosepeakTSBconcentrationremainsbelow340μmol/LandisveryrareunlessthepeakTSBconcentrationexceeds425μmol/L(24.85mg/dl).Abovethislevel,theriskfortoxicityprogressivelyincreases.Morethanthree-quartersoftheinfantsintheUnitedStateskernicterusregistry(between1992and2002)hadaTSBconcentrationof515μmol/L(30.1mg/dl)orgreater,andtwo-thirdshadaconcentrationexceeding600μmol/L(35mg/dl).Evenwithconcentrationsgreaterthan500μmol/L(29.2mg/dl),therearestillsomeinfantswhowillescapeencephalopathy.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第4頁!具有危險(xiǎn)因素人群中患者與非患者之比相當(dāng)于不具有危險(xiǎn)因素人群中患者與非患者之比的倍數(shù)

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第5頁!黃疸的發(fā)生（總體發(fā)生情況）Early(days1-2)-unmonHaemolyticjaundice(ABO,others)Normal(days3-10)-verymonUnplicatedComplicated-seebelowLate(days14+)Breastmilk-monConjugatedjaundice-unmonInheriteddeficiencyofglucuronyltransferaseenzymes-veryrare新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第6頁!Clinicalmanagementofhyperbilirubinemiaininfants

TABLE1:Laboratoryinvestigationforhyperbilirubinemiaintermnewborninfants

Indicated(ifbilirubinconcentrationsreachphototherapylevels)

Serumtotalorunconjugatedbilirubinconcentration

Serumconjugatedbilirubinconcentration

Bloodgroupwithdirectantibodytest(Coombs’test)

Hemoglobinandhematocritdeterminations

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第7頁!TimedTSBmeasurements

定時(shí)膽紅素水平監(jiān)測(cè)，適時(shí)干預(yù)UmbilicalcordbloodTSB（臍帶血膽紅素水平并無特異性）

ATSBconcentrationgreaterthan30μmol/Linumbilicalcordblood

isstatisticallycorrelatedwithapeakneonatalTSBconcentrationgreaterthan300μmol/L,butthepositivepredictivevalue（陽性預(yù)測(cè)值）isonly4.8%fortheterminfant,risingto10.9%inthelatepreterminfant,andthespecificityisverypoor．

Universalhemoglobinassessment

（常規(guī)臍帶血血紅蛋白或紅細(xì)胞比容測(cè)定并不能預(yù)測(cè)嚴(yán)重高膽紅素血癥的發(fā)生）Althoughbilirubinisderivedfromthebreakdownofhemoglobin,routineumbilicalcordbloodhemoglobinorhematocritmeasurementdoesnotaidinthepredictionofseverehyperbilirubinemia．

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第8頁!時(shí)間膽紅素水平曲線

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第9頁!Glucose-6-phosphatedehydrogenasedeficiency

（葡萄糖-6-磷酸脫氫酶缺乏癥）與嚴(yán)重膽紅素血癥相關(guān)－－Newbornswithglucose-6-phosphatedehydrogenase(G6PD)deficiencyhaveanincreasedincidenceofseverehyperbilirubinemia．G6PDdeficiencyincreasesthelikelihoodofrequiringexchangetransfusionininfantswithseverehyperbilirubinemia;therefore,atestforG6PDdeficiencyshouldbeconsideredinallinfantswithseverehyperbilirubinemia．有家族種族高危因素的都應(yīng)行此檢查－－TestingforG6PDdeficiencyinbabieswhoseethnicgrouporfamilyhistorysuggestanincreasedriskofG6PDdeficiencyisadvised.有高危因素男女孩都因檢測(cè)－－AlthoughG6PDdeficiencyisanX-linkeddisease,femaleheterozygotescanhavemorethan50%oftheirredcellsdeficientintheenzymebecauseofrandominactivationoftheXchromosome.Femaleswithgreaterproportionsoftheirredcellsaffectedhaveanincreasedriskofsevereneonatalhyperbilirubinemia；therefore,testingofbothgirlsandboyswhoareatriskisadvised．有溶血病時(shí)，G-6-PD水平會(huì)被檢測(cè)過高從而影響診斷－－Itshouldalsoberecognizedthatinthepresenceofhemolysis,G6PDlevelscanbeoverestimatedandthismayobscurethediagnosis．Femalesinparticularcanhavemisleadingresultsonthemonscreeningtests．積極進(jìn)行干預(yù)－－G6PD-deficientnewbornsmayrequireinterventionatalowerTSBconcentrationbecausetheyaremorelikelytoprogresstoseverehyperbilirubinemia.Unfortunately,inmanycentres,itcurrentlytakesseveraldaysforaG6PDdeficiencyscreeningtestresulttobeeavailable.Improvingtheturnaroundtimeforthistestwouldimprovecareofthenewborn.BecauseG6PDdeficiencyisadiseasewithlifelongimplications,testinginfantsatriskisstillofvalue.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第10頁!When?新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第11頁!Primarypreventionofseverehyperbilirubinemia

一級(jí)預(yù)防Breastfeedingsupport

對(duì)于母親的宣教Otherineffectiveinterventions

Routineuseofglycerinesuppositories（甘油栓劑）routineglycerineenemas開賽露，L-asparticacid（天冬氨酸）,whey/caseinandclofibrate（氯貝丁脂）haveallbeenstudiedinsmallrandomizedcontrolledtrials(RCTs),buttheirusehasbeenfoundtohavenoeffectonclinicallyimportantoutes.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第12頁!Preventionofseverehyperbilirubinemiaininfantswithmildormoderatehyperbilirubinemia

Phototherapy

Interruptingbreastfeeding

（停止母乳喂養(yǎng)）RCT未見明顯區(qū)別

Intravenousimmunoglobulin（靜丙）與免疫因素相關(guān)的溶血

Supplementalfluids

（補(bǔ)液）

Agar

（瓊脂）可減少腸壁對(duì)未結(jié)合膽紅素的吸收，沒有可靠的證據(jù)支持新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第13頁!HOWSHOULDSEVEREHYPERBILIRUBINEMIABETREATED?

Phototherapy

初始治療，監(jiān)測(cè)膽紅素水平，有指征時(shí)開始做換血準(zhǔn)備．補(bǔ)液，靜丙

Aninfantwhopresentswithseverehyperbilirubinemia,orwhoprogressestoseverehyperbilirubinemiadespiteinitialtreatment,shouldreceiveimmediateintensivephototherapy.Thebilirubinconcentrationshouldbecheckedwithin2hto6hofinitiationoftreatmenttoconfirmresponse.Considerationoffurthertherapyshouldmenceandpreparationsforexchangetransfusionmaybeindicated.Supplementalfluidsareindicated,andIVIGshouldbegivenifnotalreadymenced

fortheinfantwithisoimmunization.

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第14頁!Exchangetransfusion

光療失敗－－Ifphototherapyfailstocontroltherisingbilirubinconcentrations,exchangetransfusionisindicatedtolowerTSBconcentrations.沒有高危因素的健康足月兒－－Forhealthytermnewbornswithoutriskfactors,exchangetransfusionshouldbeconsideredwhentheTSBconcentrationisbetween375μmol/L(21.9mg/dL)

and425μmol/L(24.8mg/dL)(despiteadequateintensivephototherapy).在換血前采血完善相關(guān)檢查－－Becausebloodcollectedafteranexchangetransfusionisofnovalueforinvestigatingmanyoftherarercausesofseverehyperbilirubinemia,theseinvestigationsshouldbeconsideredbeforeperformingtheexchangetransfusion.Appropriateamountsofbloodshouldbetakenandstoredfortestssuchasthoseforredcellfragility,enzymedeficiency(G6PDorpyruvatekinase丙酮酸激酶deficiency)andmetabolicdisorders,aswellasforhemoglobinelectrophoresisandchromosomeanalysis.如果膽紅素水平剛達(dá)到換血指征，在換血前應(yīng)再次檢測(cè)膽紅素水平。嚴(yán)格掌握換血指征。Preparationofbloodforexchangetransfusionmaytakeseveralhours,duringwhichtimeintensivephototherapy,supplementalfluidsandIVIG(incaseofisoimmunization)shouldbeused.IfaninfantwhoseTSBconcentrationisalreadyabovetheexchangetransfusionlinepresentsformedicalcare,thenrepeatmeasurementoftheTSBconcentrationjustbeforeperformanceoftheexchangeisreasonable,aslongastherapyisnottherebydelayed.Inthisway,someexchangetransfusions,withtheirattendantrisks,maybeavoided.Exchangetransfusionisaprocedurewithsubstantialmorbiditythatshouldonlybeperformedincentreswiththeappropriateexpertiseundersupervisionofanexperiencedneonatologist.當(dāng)有急性膽紅素腦病的臨床表現(xiàn)時(shí)應(yīng)馬上換血－－Aninfantwithclinicalsignsofacutebilirubinencephalopathyshouldhaveanimmediateexchangetransfusion.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第15頁!換血指征

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第16頁!Furtherinvestigations

Theoccurrenceofseverehyperbilirubinemiamandatesaninvestigationofthecauseofhyperbilirubinemia.Investigationsshouldincludeaclinicallypertinenthistoryofthebabyandthemother,familyhistory,descriptionofthelabouranddelivery,andtheinfant

clinicalcourse.Aphysicalexaminationshouldbesupplementedbylaboratoryinvestigations(conjugatedandunconjugatedbilirubinlevels;directCoombstest;hemoglobinandhematocritlevels;andpletebloodcellcount,includingdifferentialcount,bloodsmearandredcellmorphology).Investigationsforsepsisshouldbeperformedifwarrantedbytheclinicalsituation.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第17頁!CONCLUSION嚴(yán)重的高膽紅素血癥的有發(fā)生急性膽紅素腦病及慢性后遺癥的可能．對(duì)高危因素進(jìn)行評(píng)估，輔查，在有指征時(shí)光療及換血是避免這些并發(fā)癥發(fā)生的要點(diǎn)．

Severehyperbilirubinemiainrelativelyhealthytermorlatepretermnewborns(greaterthan35weeks

gestation)continuestocarrythepotentialforplicationsfromacutebilirubinencephalopathyandchronicsequelae.Carefulassessmentoftheriskfactorsinvolved,asystematicapproachtothedetectionandfollow-upofjaundicewiththeappropriatelaboratoryinvestigations,alongwithjudiciousphototherapyandexchangetransfusionwhenindicated,areallessentialtoavoidtheseplications.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第18頁!Kernicterus（核黃疸）:thepathologicalfindingofdeep-yellowstainingofneuronsandneuronalnecrosisofthebasalganglia（基底節(jié)）andbrainstemnuclei（腦干神經(jīng)元）.Acutebilirubinencephalopathy（急性膽紅素腦病）

:aclinicalsyndrome,inthepresenceofseverehyperbilirubinemia,oflethargy（昏睡）,hypotoniaand（肌張力減低）poorsuck,whichmayprogresstohypertonia(withopisthotonos（角弓反張）andretrocollis（頸后傾）)withahigh-pitchedcryandfever,andeventuallytoseizures（發(fā)作）anda.

Chronicbilirubinencephalopathy（慢性膽紅素腦?。?/p>

:theclinicalsequelaeofacuteencephalopathywithathetoidcerebralpalsy（手足徐動(dòng)癥樣大腦麻痹）withorwithoutseizures,developmentaldelay,hearingdeficit,oculomotor（眼球運(yùn)動(dòng)異常）disturbances,dentaldysplasia（牙發(fā)育異常）andmentaldeficiency

.

Severehyperbilirubinemia（嚴(yán)重的高膽紅素血癥）

:atotalserumbilirubin(TSB)concentrationgreaterthan340μmol/Latanytimeduringthefirst28daysoflife.

Criticalhyperbilirubinemia（危險(xiǎn)的高膽紅素血癥）:aTSBconcentrationgreaterthan425μmol/Lduringthefirst28daysoflife.

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第19頁!脫水，高滲，呼吸窘迫，水腫，早產(chǎn)，酸中毒，低白蛋白血癥，缺氧，抽搐可增加急性腦病的發(fā)生率與敗血癥的關(guān)系?Allofthereasonsforthevariablesusceptibilityofinfantsarenotknown;however,dehydration,hyperosmolarity,respiratorydistress,hydrops,prematurity,acidosis,hypoalbuminemia,hypoxiaandseizuresaresaidtoincreasetheriskofacuteencephalopathyinthepresenceofseverehyperbilirubinemia,althoughreliableevidencetoconfirmtheseassociationsislacking.Inaddition,someinfantswithseverehyperbilirubinemiaarefoundtohavesepsis,butbothsepsisandhyperbilirubinemiaaremonintheneonatalperiod,andsepsisappearstobeunmoninthewell-appearinginfantwithseverehyperbilirubinemia.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第20頁!Investigations:

Measurementofbilirubin經(jīng)皮測(cè)并不準(zhǔn)確（與是否光療后，皮膚顏色及厚度都有關(guān)）．

ThereareseverallimitationstoTcBmeasurements:theybeeunreliableafterinitiationofphototherapy,andtheymaybeunreliablewithchangesinskincolourandthickness.

However,theresultsaremoreaccurateatlowerlevelsofbilirubin,andtherefore,useofTcBasascreeningdeviceisreasonable．ClinicalevaluationKramer‘sRuleRatherthanestimatingthelevelofjaundicebysimplyobservingthebaby'sskincolour,onecanutilisethecephalocaudalprogressionofjaundice.Kramerdrewattentiontotheobservationthatjaundicestartsonthehead,andextendstowardsthefeetasthelevelrises.ThisisusefulindecidingwhetherornotababyneedstohavetheSBRmeasured.Kramerdividedtheinfantinto5zones,theSBRrangeassociatedwithprogressiontothezonesisasfollows:新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第21頁!

Optional(可選擇的)

Completebloodcountincludingmanualdifferentialwhitecellcount

Bloodsmearforredcellmorphology

Reticulocytecount

Glucose-6-phosphatedehydrogenasescreen

Serumelectrolytesandalbuminorproteinconcentrations新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第22頁!BloodgroupandCoombstesting（血型及Coombs試驗(yàn)）

ABO溶血是常見原因，大部分新生兒黃疸與ABO溶血有關(guān)（bloodgroupAorBinfantsborntoamotherwithgroupOblood）

ABO溶血患兒直抗陽性者比陰性者更需光療TheneedforphototherapyisincreasedinABO-inpatibleinfantswhoaredirectantiglobulintest(DAT[directCoombstest])-positiveparedwiththosewhoareDAT-negative．對(duì)Ｏ型血母親及有高危因素的黃疸患兒進(jìn)行DAT檢測(cè)TestingallbabieswhosemothersaregroupOdoesnotimproveoutesparedwithtestingonlythosewithclinicaljaundice.Therefore,itisreasonabletoperformaDATinclinicallyjaundicedinfantsofmotherswhoaregroupOandininfantswithanelevatedriskofneedingtherapy．Theresultswilldeterminewhethertheyarelowriskorhighrisk,andmaythereforeaffectthethresholdatwhichtherapywouldbeindicated．新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第23頁!加強(qiáng)光療的指征曲線

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第24頁!建議（每項(xiàng)均有建議的等級(jí)－－與研究的可靠性相關(guān)）：孕婦ABO,Rh血型檢測(cè)及紅細(xì)胞抗體篩查－－AllmothersshouldbetestedforABOandRh(D)bloodtypesandbescreenedforredcellantibodiesduringpregnancy．臍血檢測(cè)－－Ifthemotherwasnottested,cordbloodfromtheinfantshouldbesentforevaluationofthebloodgroupandaDAT(Coombstest)母Ｏ型血的早期黃疸患兒應(yīng)做血型鑒定及DAT檢測(cè)－－BloodgroupevaluationandaDATshouldbeperformedininfantswithearlyjaundiceofmothersofbloodgroupO.

G-6-PD篩查－－Selectedat-riskinfants(Mediterranean,MiddleEastern,AfricanorSoutheastAsianorigin)shouldbescreenedforG6PDdeficiency.

嚴(yán)重的高膽紅素血癥時(shí)應(yīng)做G-6-PD檢測(cè)－－AtestforG6PDdeficiencyshouldbeconsideredinallinfantswithseverehyperbilirubinemia新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第25頁!

怎樣減少嚴(yán)重高膽紅素血癥的發(fā)生？

HOWCANTHERISKOFSEVEREHYPERBILIRUBINEMIABEREDUCED?

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第26頁!Preventionofseverehyperbilirubinemiaininfantswithhemolysis

Phenobarbitone

（苯巴比妥）

Tin-mesoporphyrin

SnMP（錫中卟啉）抑制膽紅素合成及活性，臨床使用未見明顯改變

Prophylacticphototherapy

（預(yù)防光療）是否加強(qiáng)光療見表２

新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第27頁!建議：支持母乳喂養(yǎng)－－Aprogramforbreastfeedingsupportshouldbeinstitutedineveryfacilitywherebabiesaredelivered．并不推薦給母乳喂養(yǎng)的嬰兒常規(guī)補(bǔ)充水或糖水－－Routinesupplementationofbreastfedinfantswithwaterordextrosewaterisnotremended．

靜丙的使用－－InfantswithapositiveDATwhohavepredictedseverediseasebasedonantenatalinvestigationoranelevatedriskofprogressingtoexchangetransfusionbasedonthepostnatalprogressionofTSBconcentrationshouldreceiveIVIGatadoseof1g/kg．膽紅素水平及高危因素提示可能有發(fā)生嚴(yán)重高膽紅素血癥趨勢(shì)的時(shí)候，即使出院也應(yīng)追蹤監(jiān)測(cè)膽紅素水－－ATSBconcentrationconsistentwithincreasedriskshouldleadtoenhancedsurveillancefordevelopmentofseverehyperbilirubinemia,withfollow-upwithin24hto48h,eitherinhospitalorinthemunity,andrepeatestimationofTSBorTcBconcentrationinmostcircumstances．

加強(qiáng)光療－－IntensivephototherapyshouldbegivenaccordingtotheguidelinesshowninFigure2

常規(guī)光療－－ConventionalphototherapyisanoptionatTSBconcentrations35μmol/Lto50μmol/LlowerthantheguidelinesinFigure2．光療中也應(yīng)繼續(xù)母乳喂養(yǎng)－－Breastfeedingshouldbecontinuedduringphototherapy．迅速進(jìn)展可能需要換血時(shí)，應(yīng)控制補(bǔ)液量－－Supplementalfluidsshouldbeadministered,orallyorbyintravenousinfusion,ininfantsreceivingphototherapywhoareatanelevatedriskofprogressingtoexchangetransfusion.新生兒黃疸診治共33頁，您現(xiàn)在瀏覽的是第28頁!Phototherapy

脫水－高膽紅素血癥－光療

Itisimportanttorecognizetherelationshipbetweendehydrationandhyperbilirubinemia.Dehydrationmaybeassociatedwithincreasedserumbilirubinconcentrationsandmaybeexacerbatedbyphototherapy.Alljaundicedinfantsshouldbeadequatelyhydratedbeforeandduringphototherapy.Breastfeedingisnotcontraindicatedinthepresenceofhyperbilirubinemiaandshouldbecontinued.Morefrequentbrea