2015加拿大早产儿喂养指南.ppt

2015加拿大早产儿喂养指南GuidelinesforFeedingVeryLowBirthWeightInfants,Nutrients2015,7,423-442,主要内容,1.达到全胃肠内喂养的时间2.非营养性喂养、营养性喂养3.乳品选择4.无创通气极低体重儿的喂养5.喂养耐受性的评估6.胃潴留、胃食管返流的诊治7.母乳强化剂,Contents,1.TimetoReachFullFeeds2.TrophicFeeds、NutritionalFeeds3.TypeofMilkforStartingFeeds4.FeedingBabiesonNon-InvasiveVentilation5.AssessmentofFeedTolerance6.ManagementofResiduals、Gastro-EsophagealReflux(GER)7.HumanMilkFortification,引言,极低体重儿喂养的首要目标是在最短时间内达到全肠内营养，维持最好的生长和营养状态，并避免喂养速度过快导致的不良并发症。,Introduction,Adequatenutritionisessentialfortheoptimalgrowthandhealthofverylowbirthweight(VLBW)infants.Enteralnutritionispreferredtototalparenteralnutrition(TPN)becausetheformeravoidscomplicationsrelatedtovascularcatheterization,sepsis,adverseeffectsofTPN,andfasting.,按照循证医学中心的标准标注出了证据级别（LOE），证据级别分类如下：,1a随机对照研究（RCT）的系统评价1b置信区间较窄的单个随机对照研究2a队列研究的系统评价2b单个的队列研究或低质量的随机对照研究3a病例对照研究的系统评价3b单个的病例对照研究4病例系列报道，低质量的队列研究或病例对照研究5专家意见,Whereverpossible,wehavestatedthelevelofevidence(LOE)aspertheCentreforEvidence-basedMedicine,UnitedKingdom.TheoutlineoftheLOEfortherapytrialsisasfollows:,1aSystematicreview(withhomogeneity)ofrandomizedcontrolledtrials(RCT)1bIndividualRCTwithnarrowconfidenceinterval(CI)2aSystematicreview(withhomogeneity)ofcohortstudies2bIndividualcohortstudiesandlow-qualityRCTs3aSystematicreview(withhomogeneity)ofcase-controlstudies3bIndividualcase-controlstudies4Caseseries,poor-qualitycohortandpoor-qualitycase-controlstudies5Expertopinionwithoutexplicitcriticalappraisal,达到全胃肠内喂养的时间,建议：出生体重1000g的早产儿喂养目标是生后2周内达到全胃肠内喂养（150-180ml/kg/d），1000-1500g早产儿目标是生后1周内达到全胃肠内喂养。个别早产儿特别是1000g以下早产儿不能耐受大量肠内喂养，因此本目标需要个体化评估。依据较快达到全胃肠内喂养可以尽快拔除血管内置管、减少败血症发生、减少其他导管相关的并发症（LOE2b）。标准化喂养方案可以改善极低出生体重儿预后。生后1周内达到全胃肠内喂养是完全可以做到的，在一项随机对照研究中，喂养量达到170ml/kg/d的中位时间是生后7天，而且并不增加呼吸暂停、喂养不耐受的发生率。,TimetoReachFullFeedsSuggestionAimtoreachfullenteralfeeding(150180mL/kg/day)byabouttwoweeksinbabiesweighing1000gatbirthandbyaboutoneweekinbabiesweighing10001500gbyimplementingevidence-basedfeedingprotocols.Itmaybenotedthatsomebabies,especiallythoselessthan1000grams,willnottoleratelargervolumesoffeedings(suchas180mL/kg/dayormore)andthusmayneedindividualization.RationaleReachingfullenteralfeedingfasterresultsinearlierremovalofvascularcatheters,andlesssepsisandothercatheter-relatedcomplications(LOE2b).StandardizedfeedingprotocolsimproveoutcomesinVLBWI.ReachingfullfeedswithinaweekisachievableinanRCTonVLBWI,themediantimetoreach170mL/kg/daywas7daysafterfastadvancementofenteralfeeding,withnoincreaseinapneas,feedinterruptions,andintolerance.,喂奶频次,建议：建议1250g以上早产儿每3小时喂奶一次。1250g以下早产儿尚无足够证据决定选择每隔3小时喂奶还是每隔2小时喂奶。依据：在一项随机对照研究中，92名出生体重1250g.Thereisnotenoughevidencetochoosebetweentwo-hourlyversusthree-hourlyfeedsforbabiesweighing1250g.RationaleInanRCT,92neonatesweighing1750gwereallocatedtoeitherthree-ortwo-hourlyfeeds.Theincidenceoffeedintolerance,apnea,hypoglycemia,andnecrotizingenterocolitis(NEC)didnotsignificantlydiffer,andnursingtimespentonfeedingwassignificantlylessinthethree-hourlygroup(LOE2b).Tworetrospectivestudiesonthisissuewerecontradictory.Inonethatcompared2-hand3-henteralfeedinginELBWbabies,thetimetofullenteralfeeding,enteralmorbidity,hospitalstay,andgrowthparametersweresimilarinthetwogroups(LOE4).Inanother,VLBWI(meanbirthweight1200g)fedtwicehourlyreachedfullfeedsfaster,receivedlessprolongedTPN,andwerelesslikelytohavefeedsheld,comparedtothosefedthreetimeshourly(LOE4).,非营养性喂养：开始时间、喂养量、持续时间,建议：非营养性喂养定义为最小喂养量（10-15ml/kg/d）。建议生后24小时内开始非营养性喂养，超早产儿、超低出生体重儿及生长发育受限早产儿可适当谨慎处理。若生后24-48小时仍无母乳或捐赠母乳，可考虑代乳品喂养。尚无足够证据对营养性喂养前的非营养性喂养持续时间做出建议。依据一项囊括了9项研究、754名极低出生体重儿的系统性综述中，非营养性喂养量为10-25ml/kg/d不等，开始喂养时间从生后一天开始。与禁食相比，尽早开始非营养性喂养并不能更早地达到全胃肠内喂养，NEC发生率无差异（LOE1a-），需要进行更多研究以找到适合于极早产儿、超低出生体重儿和生长发育受限早产儿的临床建议。另一项系统性评价对开始营养性喂养的时间与预防NEC的关系进行综述，认为早期进行肠胃内喂养（生后1-2天）并不增加NEC、喂养不耐受的风险和死亡率（LOE1a）。,TrophicFeeds:TimeofStarting,Volume,DurationSuggestion：Trophicfeedsaredefinedasminimalvolumesofmilkfeeds(1015mL/kg/day).Starttrophicfeedspreferablywithin24hoflife.Exercisecautioninextremelypreterm,extremelylowbirthweight(ELBW),orgrowth-restrictedinfants.If,by2448h,nomaternalordonormilkisavailable,considerformulamilk.Thereisnotenoughevidencetorecommendthemaximumdurationoftrophicfeedingbeforestartingnutritionalfeeds.Rationale：Inasystematicreview(ninetrials,754VLBWI),theactualvolumeoftrophicfeedsrangedfrom10to25mL/kg/day;andonsetfromdayoneoflifeonwards.Earlyintroductionoftrophicfeedscomparedtofastinghadanon-significanttrendtowardsreachingfullfeedsearlier(meandifference1.05days(95%CI2.61,0.51)andnodifferenceinNEC(LOE1a).Moredataisrequiredbeforeonecangeneralizethesefindingstoextremelypreterm,ELBW,orgrowth-restrictedinfants.Inasystematicreview(seventrials,964VLBWI)ontimingofintroductionofnutritionalenteralfeedingtopreventNEC,earlyintroductionofprogressiveenteralfeeding(1to2daysofage)didnotincreasetheriskofNEC(typicalrelativerisk(RR)0.92(95%CI0.64,1.34),mortality(typicalRR1.26(95%CI0.78,2.01),orfeedintolerance(LOE1a).,非营养性喂养的禁忌症,建议肠梗阻或会出现肠梗阻的情况时停止喂养。窒息、呼吸窘迫、败血症、低血压、血糖代谢紊乱、机械通气、脐血管置管不是非营养性喂养的禁忌症。依据一项荟萃分析指出伴有窒息、呼吸窘迫、败血症、低血压、糖代谢紊乱、机械通气、脐血管置管的极低出生体重儿未发现不良反应增加（LOE1a-）。,ContraindicationsforTrophicFeedsSuggestionWithholdtrophicfeedsinintestinalobstructionorasettingforintestinalobstructionorileus.Asphyxia,respiratorydistress,sepsis,hypotension,glucosedisturbances,ventilation,andumbilicallinesarenotcontraindicationsfortrophicfeeds.RationaleThestudiesincludedinaCochranereviewincludedVLBWIwithasphyxia,respiratorydistress,sepsis,hypotension,glucosedisturbances,ventilation,andumbilicallines,withoutanyexcessadverseeffectsbeingreported(LOE1a).,营养性喂养：开始时机、喂养量、频次、增加速度,建议：出生体重1000g早产儿自30ml/kg/d开始营养性喂养，每天加奶30ml/kg/d。依据：荟萃分析结果发现，快速加奶（30-35ml/kg/d）并不比慢速加奶（15-20ml/kg/d）增加NEC风险、喂养中断和死亡率（LOE1a），并且可以帮助早产儿更快恢复出生体重（LOE1b）、更快达到全胃肠内喂养（LOE2b）。暂时没有关于超低出生体重儿亚组的研究，我们建议超低出生体重儿从较小量开始喂养（15-20ml/kg/d）。,NutritionalFeeds:DayofStarting,Volume,Frequency,IncreaseSuggestionInbabiesweighing1kgatbirth,startnutritionalfeedsat1520mL/kg/dayandincreaseby1520mL/kg/day.Ifthefeedsaretoleratedforaround23days,considerincreasingfaster.Forbabiesweighing1kgatbirth,startnutritionalfeedsat30mL/kg/dayandincreaseby30mL/kg/day.RationaleACochranereviewindividuallyreportedthatthefastdailyincrementgroupregainedbirthweightandreachedfullfeedsfaster(LOE1band2b).AstherewasnosubgroupanalysisofELBWbabies,wesuggeststartingwithalowerfeedvolumeinELBWbabiesasinthecontrolarm(1520mL/kg/day)untilmorestudiesareavailable.,开始喂养时乳品选择,建议：首选母亲挤出的母乳或初乳，次选捐赠母乳，若均无可选早产儿专用奶粉。依据：新鲜挤出的母乳对早产儿有诸多益处。虽然没有对比新鲜母乳和冷冻母乳的直接证据，但考虑到冷冻过程中共生物、免疫细胞、免疫因子消耗和酶活性下降，推荐使用新鲜母乳。母乳喂养（母亲母乳或捐赠母乳加母乳来源的增强剂）的新生儿比早产儿奶粉喂养或人乳加牛乳来源增强剂喂养组NEC发病率更低（LOE1b）。一项成本效益分析研究表明，纯人乳品喂养降低NEC发病率，从而可以缩短住院时间，节省医疗费用（平均每个极早产儿节省8167美元）。,TypeofMilkforStartingFeedsSuggestionThefirstchoiceisownmothersexpressedbreastmilkorcolostrum.Secondchoice:donorhumanmilk.Thirdchoice:pretermformula.RationaleFreshlyexpressedhumanmilkhasnumerousbenefitsforpretermbabies.Althoughthereisnodirectevidencecomparingfreshversusfrozenmothersmilk,theuseoffreshmilkmakessensebecauseofthedepletionofcommensals,immunecells,immunefactors,andenzymeactivitythatoccurswithfreezing.Neonateswhoreceiveanexclusivelyhumanmilk-baseddiet(mothersmilkordonorhumanmilkwithhumanmilk-basedfortifier)havesignificantlylowerratesofNECcomparedtothosewhoreceivepretermformulaorhumanmilkwithabovinemilk-basedfortifier(LOE1b).however,acost-effectivenessanalysisshowedthatuseofexclusivelyhumanmilk-basedproductsresultedinshorterdurationofhospitalization(lessbyanaverageof3.9daysinneonatalintensivecareunit(NICU)andsavingsof$8167perextremelyprematureinfant(p0.0001)becauseofthereductioninNEC.,伴不伴脐动脉舒张末期无血流或反流的小于胎龄儿（SGA）的喂养,建议：如果腹部查体未见异常，可以生后24小时内开始喂养，但加奶时谨慎，采取每日加奶量的最低值。29周小于胎龄儿伴脐动脉舒张末期无血流或反流者，生后10天内极其缓慢加奶。尽最大努力选择母乳，特别是脐动脉舒张末期无血流或反流、29周的小于胎龄儿。依据：Mihatsch等研究124例极低出生体重儿（其中35例伴有宫内生长发育受限），宫内生长发育受限组与无生长发育受限组达到全量喂养的时间无显著性差异。多元回归分析表明，脐动脉阻力、脑保护反射、Apgar评分、脐动脉血pH、宫内生长发育受限等对达到全量喂养的时间无预测作用。一项关于产前脐血流异常的SGA早产儿的RCT研究中，早期喂养组和延迟喂养组NEC和喂养不耐受发生率无显著性差异（LOE2b）。,FeedingSmallforGestationalAge(SGA)Babieswith/withoutHistoryofAbsent/ReversedEndDiastolicUmbilicalFlow(AREDF)SuggestionIftheabdominalexaminationisnormal,startfeedingwithin24hoflife,butadvanceslowlywithvolumesatthelowestendoftherange.Advancefeedsextremelyslowlyinthefirst10daysamongpretermSGAbabieswithgestation29weeksandAREDF.Makeeveryefforttofeedhumanmilk,especiallyinSGAbabieswithAREDFandgestation29weeks.RationaleMihatschetal.fed124VLBWI(35hadintra-uterinegrowthretardation(IUGR)withastandardizedprotocol(LOE2b).TherewasnostatisticaldifferenceintheagetoreachfullfeedsintheIUGRandnon-IUGRgroups(p=0.6).Inamultipleregressionmodel,increasedumbilicalarteryresistance,brainsparing,Apgarscores,umbilicalarterypH,andIUGRdidnotpredicttheagetoreachfullfeeds.InanRCTonSGApretermbabies(gestationof2734weeks)whohadabnormalantenatalumbilicalDopplerflows,theincidenceofNECandfeedingintolerancewasnotsignificantlydifferent(p=0.35andp=0.53,respectively)betweentheearlyfeeders(n=42;medianage2days)anddelayedfeeders(n=42;7days)(LOE2b).,依据：另一项SGA早产儿的RCT研究对比了微量胃肠内喂养和禁食五天，NEC发病率无显著性差异，而且微量胃肠内喂养组有缩短NICU住院时间的倾向（LOE2b）。一项名为“ADEPT”的RCT研究中，伴有脐动脉舒张末期无血流或反流和脑血流重新分布的402例SGA早产儿分为早期肠内喂养组（第2天）和晚期肠内喂养组（第6天），早期肠内喂养组更早达到全量喂养，NEC总发病率和II-III期NEC发病率均无显著性差异，早期喂养组全肠外营养时间短，重症监护时间短，胆汁淤积症发生率低（LOE1b）。,InanRCTonpretermSGAinfants,comparingminimalenteralfeedingandnoenteralfeedingforfivedays,therewasnodifferenceintherateofNEC(p=0.76)andtherewasatrendtowardsshorterNICUstayintheenteralfeedinggroup(p=0.2)(LOE2b).IntheAbnormalDopplerEnteralPrescriptionTrial(ADEPT)RCT,402pretermSGAinfants(35weeksgestation,birthweight10thcentile)withabsentorreversedenddiastolicumbilicalbloodflowandcerebralredistributionwereallocatedtoearlyorlateonsetofenteralfeeding(Day2or6,respectively)(LOE1b).Theearlyfeedinggroupreachedfullenteralfeedsfasterthanthelatefeedinggroup(median(IQR)days:18(1524)versus21(1927),respectively;p=0.003).Therewasnodifferenceintheincidenceofall-stageNEC(18%versus15%,respectively;p=0.42)andstageIIIIINEC.,无创通气极低体重儿的喂养,建议谨慎加奶。不能把腹胀作为喂养不耐受的征象，在1000g早产儿尤其如此。依据无创通气可以导致腹胀，经鼻持续气道正压通气（nCPAP）降低早产儿的餐前餐后肠血流量（LOE4）。Jaile等人的研究对比25例nCPAP早产儿和29例无CPAP的早产儿，1000g和1000g早产儿中分别有83%和14%因CPAP导致肠胀气，本研究中无NEC病例，但本研究样本量太小不能对NEC发病率做出结论。,FeedingBabiesonNon-InvasiveVentilationSuggestionIncreasefeedscautiously.Donotrelyonabdominaldistensionasasignoffeedingintolerance,especiallyinbabiesweighing1000g.RationaleNon-invasiveventilationcancauseabdominaldistension,andnasalcontinuouspositiveairwaypressure(nCPAP)decreasespre-andpost-prandialintestinalbloodflowinpreterminfants(LOE4).Jpared25prematureinfantsonnCPAPwith29prematureinfantsnotonCPAP(LOE2b).GaseousboweldistensionduetoCPAPdevelopedin83%ofinfantsbelow1000gversus14%ofthoseweighing1000g.NocasesofNECwerereportedinthestudy;however,thesamplesizewastoosmalltodrawconclusionsaboutNEC.,伴低血压的极低体重儿的喂养,建议暂无足够证据提出某项建议。依据尚无系统性低血压极低体重儿喂养策略的相关文献。,FeedingBabieswithSystemicArterialHypotensionSuggestionThereisnotenoughevidencetomakeasuggestion.RationaleThereisnopublishedliteratureonfeedingpoliciesduringsystemicarterialhypotension.,采用吲哚美辛布洛芬治疗者的喂养,建议如果已经开始微量喂养，继续进行非营养性喂养，吲哚美辛疗程结束后才进行营养性喂养。如果是禁食的早产儿，以母乳进行非营养性喂养。目前没有随机对照实验对比研究吲哚美辛治疗和布洛芬治疗时的喂养情况，只有间接证据支持布洛芬可能更安全。依据一项临床研究研究对象是每日喂养量60ml/kg/d、需要药物治疗关闭动脉导管的117例新生儿，随机分为继续微量喂养组和药物治疗期间禁食组，微量喂养组在更短时间内达到喂养量120ml/kg/d。布洛芬不会减少肠系膜血流量，因此比吲哚美辛安全。一项包括19个研究的荟萃分析发现，布洛芬组NEC发病率较低（LOE1a）。,FeedingBabiesonIndomethacinorIbuprofenSuggestionIftheneonateisalreadyonminimalfeeds,continuetogivetrophicfeedsuntiltheindomethacincoursefinishes.Iftheneonateisfasting,introducetrophicfeedswithhumanmilkasperSection3.WhiletherearenoRCTscomparingfeedingduringindomethacintherapyversusibuprofen,indirectevidencesuggestsibuprofenmaybethesaferofthetwo.RationaleIntheDuctusArteriosusFeedorFastwithIndomethacinorIbuprofen(DAFFII)trial,117infants(26.31.9weeks)whowereon60mL/kg/dayfeedsandrequiredtreatmentforpatentductusarteriosus(PDA)(75%to80%receivedindomethacin)wererandomizedat6.53.9daystoreceivetrophicfeedsornofeedsduringthedrugadministrationperiod.Infantsrandomizedtothetrophicfeedingsubsequentlyrequiredfewerdaystoreach120mL/kg/day(10.36.6daysvs.13.17.8days,p0.05).Ibuprofenissaferthanindomethacinasitdoesnotreducemesentericbloodflow.Inameta-analysisof19studies(956infants),NECrateswerelowerintheIbuprofengroup(typicalRR0.68(95%CI0.47,0.99)(LOE1a).,喂养耐受性的评估,建议不必常规检查胃内潴留物。只在达到每餐最小喂养量时检查餐前胃内潴留量，我们建议这个每餐最小喂养量是：1000g早产儿:5ml。不必常规测量腹围。单纯的绿色或黄色胃潴留物并不重要。呕吐胆汁样物提示可能存在肠梗阻。有血性胃潴留物时需要禁食。,AssessmentofFeedToleranceSuggestionDonotcheckgastricresidualsroutinely.Checkpre-feedgastricresidualvolume(GRV)onlyafteraminimumfeedvolume(perfeed)isattained.Wesuggestthefollowingthresholds:1000g:5mL.Donotcheckabdominalgirthroutinely.Isolatedgreenoryellowresidualsareunimportant.Vomitingbilemayindicateanintestinalobstructionorileus.Withholdfeedsincaseofhemorrhagicresiduals,ashemorrhagicresidualsaresignificant.,喂养耐受性的评估,依据胃内潴留并不像以前认为的是NEC的重要预测因素，在一定的喂养量范围内，没有必要检查胃内潴留量。全肠外营养早产儿的胃内潴留量大约是4ml（LOE4）。Mihatsch等认为50%ofthepreviousfeedvolume,pushbacktheGRVupto50%ofthefeedvolumeanddonotgivethecurrentfeed.Ifthishappensagain,considerslowbolusfeedsorwithholdingfeeds,dependingontheclinicalcondition.Iftheproblemofresidualvolumespersistsdespiteslowbolusfeeds,considerdecreasingthefeedvolumetothelastwell-toleratedfeedvolume.Usethesmallestvolumesyringeforcheckingresiduals.Takecaretoaspirategently.Afterafeed,nursethebabyinthepronepositionforhalfanhour.,依据胃潴留量的50%在以前研究中证实是与截断值相近的标准。把部分胃内抽吸物注回胃内可以减少胃酸和消化酶的丢失。关于减慢喂奶速度目前的研究资料不是很多。某研究对比持续120min缓慢喂奶和快速注奶，前者胃排空速度更快，胃储留量少，十二指肠蠕动更频繁（LOE2b）。,RationaleTherationalefor5mL/kgiscoveredinSection11.Thecriterionof50%isaroundfigureapproximatelyequaltothecutofffromthestudybyCobbetal.Pushingbackpartiallydigestedgastricaspiratesmayreplenishacidandenzymesthataidinthedigestiveprocess.Thereisapaucityofdataregardingtheroleofslowbolusfeeding.Inaphysiologicstudyonpre-termscomparinga120-mininfusionoffeedscomparedtobolusfeeds,theformerwasassociatedwithfastergastricemptying,lowerGRV,andmorefrequentduodenalmotorresponses(LOE2b).Whetherthesetheoreticaladvantagesofslowbolustranslateintoclinicalbenefitsisunclear,butthereisaphysiologicalbasisfortrying.,胃食管反流（GER）的临床诊断,建议：不能依靠呼吸暂停、血氧饱和度下降、心动过缓、咳嗽、作呕、易激惹等作为诊断早产儿胃食管反流的证据。依据：GER与心血管及呼吸系统事件的关系尚存在争议。MII-pH（多通道腔内阻抗pH监测）研究中71例早产儿发生了12957次心血管呼吸系统事件和4164次GER发作，所有的心血管呼吸系统事件只有3%发生之前有GER发作（LOE2b）。另一项研究中，反流发生20s内呼吸暂停发作的频率和无反流发作期间无显著性差异（LOE2b）。,ClinicalDiagnosisofGastro-EsophagealReflux(GER)SuggestionDonotrelyonapnea,desaturation,orbradycardia;orbehavioralsigns,suchasgagging,coughing,arching,andirritability,RationaleTherelationshipbetweenGERandcardio-respiratoryeventsiscontroversial.EarlystudieseitherusedapHprobe,whichisunabletodetectnon-acidreflux;orusedonlythemulti-channelintraluminalimpedance(MII)probe,whichunderestimatesacidGERevents.ThemodalityofchoiceiscombinedMII-pHmonitoring.InMII-pHstudieson71preterminfants(meanbirthweight1319g)therewere12,957cardiorespiratoryeventsand4164GERepisodes,butGERprecededlessthan3%ofallcardiorespiratoryevents(LOE2b).InanotherMIIstudyon19preterminfants,thefrequencyofapneasoccurringwithin20sofrefluxepisodeswasnotsignificantlydifferentfromthatduringreflux-freeperiods(LOE2b).,胃食管反流的体位治疗,建议喂奶后置新生儿于左侧卧位，半小时后改仰卧位。头部抬高30。家庭护理中，婴儿睡觉时采取俯卧位。依据22例反流病早产儿在四种不同体位下进行24小时多通道腔内阻抗pH监测，餐后早期采取左侧卧位食道内酸性暴露最少，餐后晚期取仰卧位食道酸性暴露最少（LOE2b）。睡觉采取俯卧位的建议不适用于早产儿，因为早产儿俯卧位会增加婴儿猝死综合征的风险。,BodyPositionforTreatmentofGERSuggestionPlacethebabyintheleftlateralpositionafterafeedandturnovertothepronepositionabouthalfanhourlater.Elevatetheheadendto30.Placetheinfantsupineforsleepingathome.RationaleAmong22preterminfantswithregurgitationwhounderwent24-hrecordingofpH-MIIinfourbodypositions,theleftlateralpositionshowedthelowestesophagealacidexposureintheearlypost-prandialperiodandthepronepositioninthelatepost-prandialperiod(LOE2b)56.Preterminfantsarenotanexceptiontothesupinesleeprecommendationforhomecare,becauseoftheincreasedriskofsuddeninfantdeathsyndrome(SIDS)amongpreterminfants57,58.,胃食管反流的药物治疗,建议：不建议使用多潘力酮、H2受体阻滞剂、质子泵抑制剂作为GER的治疗药物。依据仅有的一项评价多潘力酮的研究中，13例疑诊GER多潘力酮治疗组与13例未治疗对照组比较，多潘力酮治疗组GER发作更频繁。另一项研究显示甲氧氯普胺治疗组和安慰剂组疗效相似。多潘力酮与32周以上早产儿QT间期延长相关，需要更多资料证实其安全性。雷尼替丁与早产儿晚发性败血症（LOE4）和NEC（LOE3b）有关。研究发现极低出生体重儿使用雷尼替丁可使败血症发生的相对危险度增加5.5倍，发生NEC的相对危险度增加6.6倍（LOE2b），接受雷尼替丁治疗的新生儿死亡率也增加。双盲安慰剂对照研究显示，奥美拉唑可以降低胃内酸度但并不能减少反流症状（LOE2b）。另一项研究也显示，早产儿艾美拉唑治疗与安慰剂组间GER相关症状体征改善程度、反流发作次数无显著性差异。GER与心血管呼吸系统事件是否有相关性尚存疑问。唯一一项证实两者相关的研究也只是认为心血管呼吸系统事件与非酸性反流相关。,MedicationsforTreatmentofGERSuggestionDonotusedomperidone,H2-blockers,orproton-pumpinhibitorsforthetreatmentofGER.RationaleIntheonlystudyevaluatingdomperidone,13infantswithsuspectedGERtreatedwithdomperidonewerecomparedto13untreatedcontrolswithsuspectedGER(LOE2b).On24-hpH-MIImonitoring,thefrequencyofGERepisodeswashigherinthedomperidonegroup(p=0.001).Acrossovertrialon18infantscomparingmetoclopramidewithaplacebohadsimilarfindings.DomperidoneisassociatedwithprolongationofQTcintervalinneonatesabove32weeksofgestation.QTcprolongationhasnotbeendemonstratedinmoreprematureinfants(n=40);however,weneedadditionaldatatodeclaredomperidoneassafe.Ranitidineisassociatedwithahigherincidenceoflateonsetsepsis(LOE4)andNECinpretermneonates(LOE3b).InastudyonVLBWIcomparingn=91whohadreceivedranitidinewithn=183whohadnot,theoddsofdevelopingsepsisintheranitidinegroupwas5.5-foldhigherandofNEC6.6-foldhigher(LOE2b).Mortalitywasalsohigherinneonatesreceivingranitidine(p=0.003).Inadouble-blindplacebo-controlledcrossoverstudyinpretermneonates,omeprazolereducedintra-gastricaciditybutnotthefrequencyofrefluxsymp