NEONATAL NEWS Here s Some More Good Poop

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1 NEONATALNEWS Here ssomemoregoodpoop WINTEREDITION2010 THISNEWSLETTERISPUBLISHEDPERIODICALLYBYTHENEONATOLOGISTSOF ASSOCIATESINNEWBORNMEDICINETOCONVEYNEWANDUPDATEDPOLICIES ANDGUIDELINESANDPROVIDEGENERALEDUCATIONTONICUCARETAKERSAT CHILDREN SHOSPITALSANDCLINICSOFMINNESOTA ST.PAUL.ALLCONTENT HASBEENREVIEWEDANDAPPROVEDBYTHENEONATOLOGYSTAFF.ANY REVISIONSORUPDATESWILLBEEXPRESSEDINSUBSEQUENTISSUES. Inthisissue: RevisionofELBWprotocoland hydrocortisoneuse page2 Updatesoncurrentandfuture researchprotocolsinourunit page 3 GOODQUESTION:Cancerriskinthe formernicupatient page9 AssociatesinNewbornMedicine s newwebsite page10 Alookback:Dr.Virginia Apgar page12 1

2 PoliciesandProceduresUpdate:Hydrocortisone Recently,wereviewedtheimpactthatourroutineuseofhydrocortisonehashadon preservingorimprovingthehealthoftheelbwpatient,alongwithcurrentopinions andevidenceintheliterature.asaresult,theroutineuseofhydrocortisonefor treatmentofadrenalinsufficiencywillnolongerbearoutinepartofourelbw protocol,butwillbeconsideredintheseinfantswhereastrongsuspicionofmaternal chorioamnionitisisheld.hydrocortisonewillremainatoolforthetreatmentof hypotension,however,asitremainsaveryusefuladjunctivetherapywithvasopressors andinotropes.thefollowingsummaryhighlightsthedatainsupportofthispractice change. Earlyhydrocortisoneuseininfants 1000gmbirthweight. MarkCMammel,MD ResultsofthePROPHETstudy(1),andits18 22monthfollow upresults(2), showedearlyreductionsinmortalityandimprovedsurvivalwithoutbpdininfants withhistologicchorioamnionitiswithevidenceofimprovedneurodevelopmental outcomesintreatedinfantsatfollowup.becauseofthesefindings,wehaveused earlyphysiologichydrocortisone(hc)inthisgroupofinfants.allbabiesunder 1000gramsrequiringmechanicalventilationhavebeenstartedon1mg/kg/don thedayofbirth;acortisollevelwasobtainedbeforedosing,andthosewithlow levels,lessthan15mcg/dl,werecontinuedforthefull2weekprotocolusedinthe originalstudy.afterreviewoftheseandsubsequentstudiesandcommentaries(3 6),wewillnolongeraddthistherapyroutinelytoourmanagementoftheELBW infant.anumberofreasonsareimportantinthisdecision.first,thoughthe greatestpotentialbenefitappearstobeininfantswithpathologically diagnosed chorioamnionitis,wearecurrentlyunabletoestablishthisdiagnosisinatimely enoughfashiontoaidintreatmentdecisions.second,furtherevaluationofthe PROPHETstudydatabasehasshownthatlowearlycortisollevelsarenotpredictive ofvasopressorrequirement,increasedmorbidity,mortality,oradverselong term outcomes;high( 18.1mcg/dl)levelswerepredictiveofincreasedsevereIVHand PVL(4,6).Finally,becauseoftheinteractionbetweenindomethacin(and presumablyibuprofen)andhc,weareactuallyunabletousehctherapyintheway itwasstudied,asthedosingisinterruptedforuptoaweekinmanybabiesinthis weightgroupwhentheirpdasaretreated.itseemsthatmoredataareneededto targettheinfantsmostlikelytobenefitfromthistherapy,andtobetterdetermine optimaldosingduringtheperiodwhenmanybabieswillbetreatedwithibuprufin orindomethacin. UseofearlyphysiologicHCmaystillbebeneficialforsomepatients.Those withobviouschorioamnionitismaybenefit.similarly,asuseofhcatthisdose improvesbloodpressurestability,infantsrequiringvasopressortherapyinthefirst fewdaysoflifemaybenefitfrom1mg/kg/dofhcdividedq12hours.finally,we haveseenaclinicalpictureofincreasingoxygenrequirement,decreasedurine output,andlowbloodpressureduringthefirst2 4weeksoflifeinthispatient 2

3 group,ofteninbabieswhohavecompletedtheirinitialhccourse1 3daysbefore, thatrespondsto1 2mg/kg/dofHC. References 1. Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, Couser RJ, Garland JS, Rozycki HJ, Leach CL, Backstrom C, Shaffer ML. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: A multicenter trial. Pediatrics 2004; 114: Watterberg KL, Shaffer ML, Mishefske MJ, Leach CL, Mammel MC, Couser RJ, Abassi S, Cole CH, Aucott SW, Thilo EH, Rozycki HJ, Lacy CB. Growth and neurodevelopmental outcomes after early low-dose hydrocortosone treatment in extremely low birth weight infants. Pediatrics 2007; 120: Watterberg KL, Shaffer ML, Garland JS, Thilo EH, Mammel MC, Couser RJ, Aucott SW, Leach CL, Cole CH, Gerdes JS, Rozycki HJ, Backstrom C. Effect of dose on response o adrenocorticotropin in extremely low birth weight infants. J Clin Endol and Metab 2005; 90: Aucott SW, Watterberg KL, Shaffer ML, Donohue PK; PROPHET Study Group. Do cortisol concentrations predict short-term outcomes in extremely low birth weight infants? Pediatrics 2008;122: Fernandez EF, Watterberg KL. Relative adrenal insufficiency in preterm and term infants. J perinatol 2009;29:S44-S Aucott SW, Watterberg KL, Shaffer ML, Donohue PK, PROPHET Study Group. Early cortisol values and long-term outcomes in extremely low birth weight infants. J Perinatol epub ahead of print 12/10/2009. ResearchStudiesComingSoontoOurUnit 1. TOLSURFSTUDY:TobegininMarch/April Summary Premature infants are at risk for both respiratory distress syndrome (RDS) and bronchopulmonarydysplasia(bpd),definedasacontinuingrequirementforventilatorysupport and/orsupplementaloxygenat36wkpostmenstrualage.bpdaffectsmorethan70%ofinfants whoarebornatlessthan30weeksgestationandwhorequiremechanicalventilatorysupport after 7 days of age. Severe forms of BPD are associated with long term pulmonary disability, neurodevelopmentalabnormalitiesanddeath.itisestimatedthatthereareupto15,000new casesofbpdannuallyintheunitedstates. Most very premature newborn infants are deficient in pulmonary surfactant at birth, and currentclinicalstandardofcareincludessurfactantreplacementtherapyinintubatedinfantsto reduce the incidence and severity of RDS. Despite surfactant treatment at birth, premature infantsoftenneedmechanicalventilationand/orsupplementaloxygenduringthefirstweekof life. Many of these premature infants have a continuing requirement for respiratory support beyond the first week of life, often requiring continued mechanical ventilation with increased support or repeat intubation due to failure when the endotracheal tube is removed. Most of 3

4 these infants experience respiratory deteriorations that are associated with dysfunctional surfactant.althoughinhalednitricoxide(ino)startedbetween7and14dofagesignificantly improves outcomes in this group of infants, these infants still have episodes of surfactant dysfunction. We propose that episodes of surfactant dysfunction in chronically ventilated infants contribute to development of BPD by increasing lung inflammation and injury secondary to greaterexposuretooxygenandventilatorinducedlunginjury,andbyrestrictingdistributionof ino secondary to atelectasis. Based on these observations, we hope to participate in a multicenter,randomized,controlledtrialofsurfactanttreatmentfor500infantsbornat<30weeks gestationandreceivinginoforlungdiseaserequiringmechanicalventilationbeyond7daysof age.itisourhypothesisthatadministrationofadditional late surfactantinconjunctionwith inoinventilatedprematureinfantsbetween7and14daysofagewillimprovetheinfants lung functionandrespiratorystatus.wealsoanticipateanincreasedbenefitfromtheinowhenlate surfactantisadded,andexpecttoseeimprovedsurvivalwithoutbpdinthetreatedpopulation. Webelievethatthisinterventionwillbesafeandwelltolerated. SpecificAim1:AssesstheeffectoflatedosesofsurfactantininfantsreceivinginhalediNO onsurvivalwithoutbpdinventilatedextremelylowgestationalagenewborn(elgans)infants. Specific Aim 2: Assess effects of late surfactant treatment on surfactant status and lung inflammatory biomarkers, and establish a DNA repository for genomic studies of the pathogenesisofbpd. 4

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6 2.Observationalcrossoverstudycomparingoxygenationand ventilationusingsipapversuscpaptotreatrespiratory distressinlowbirthweightinfants. To Begin Late Feb. Andrea Lampland MD: principal investigator; Mark Mammel MD: co-investigator; Brenda Plumm RCP: study coordinator; Pat Meyers RCP: research assistant; Cathy Worwa RCP: research assistant Background/Significance In the face of exogenous surfactant and use of antenatal steroids, respiratory distress syndrome (RDS) remains a leading cause of morbidity and mortality in premature infants (1). RDS is the result of a series of complex, interrelated events, including atelectasis, ventilation-perfusion mismatching, and lung inflammation/injury (2). The cascade of events which typifies RDS and its long-term counterpart, chronic lung disease (CLD), is rooted in the intrinsic deficits of the premature lung as well as exacerbated by mechanical ventilation, a mainstay of therapy. For this reason, scientists and clinicians alike continue to search for treatment modalities that will not only treat RDS but also decrease the incidence of chronic lung disease. The use of non-invasive ventilatory strategies, such as nasal continuous positive airway pressure (NCPAP), in the treatment of RDS are thought to provide constant positive distending pressure while minimizing lung inflammation and injury associated with mechanical ventilation (3). Avoidance of intubation and increased use of NCPAP to treat respiratory distress syndrome has been shown to decrease the incidence of chronic lung disease (4,5). In those babies that require intubation and mechanical ventilation, use of NCPAP at the time of extubation has been shown to decrease extubation failure (6). Investigation is ongoing into the various forms of non-invasive ventilation available to treat respiratory distress in premature infants. Recently, studies have documented that the use of non-invasive nasal intermittent mechanical ventilation (NIPPV), with short inspiratory times and adequate ventilation rates, can adequately treat hypoventilation, apnea of prematurity, and decrease extubation failure when compared to the use of CPAP (7). This being said, only a select few ventilators can provide synchronized NIPPV and our current ventilators used in the Children s Hospitals and Clinics Minnesota NICU do not provide this mode of non-invasive ventilation. Our respiratory therapy department, however, has recently acquired the Viasys CPAP delivery system that can provide both conventional nasal CPAP, at a constant pressure delivery, as well as SiPAP, a newer bi-level pressure delivery system. Unlike the constant airway pressure delivered by CPAP, SiPAP systems cycle the positive airway pressure between two levels and allow patients to breathe throughout the respiratory cycle, with the potential to improve both oxygenation and ventilation during this cycling of pressures. There has been only one study to date looking at the ability of SiPAP to improve ventilation and oxygenation in the premature infant as compared to the standard use of nasal CPAP (8). Standard nasal CPAP delivers a constant distending pressure to promote oxygenation and recruitment of the lung. With this, it has little effect on ventilation, as 6

7 there are no mechanical changes in pressure delivery to promote movement of a tidal volume of air. SiPAP has the potential to improve both ventilation and oxygenation, as it changes the mean airway pressure delivery over time to promote tidal volume movement (ventilation) as well as recruitment of atelectatic lung tissue (oxygenation). This study will provide new findings regarding the oxygenation and ventilatory capacity of SiPAP in the low birth weight population. The ability to use SiPAP as a noninvasive ventilatory tool in the LBW population would have significant clinical impact because this population is highly prone to requiring intubation and invasive mechanical ventilation if failing conventional nasal CPAP due to suboptimal ventilation and persistent hypercarbia. Similarly, it has the potential to extend information already demonstrated in the NIPPV literature showing that a noninvasive ventilatory strategy can often times keep these low birth weight infants from experiencing the deleterious effects of intubation and mechanical ventilation. Lastly, the results of our study have the potential for impacting our respiratory care strategies in the NICU as currently, without the ability to provide NIPPV, we have no noninvasive ventilatory strategy to avoid intubation and Subjects 20lowbirthweightinfantswhoareinpatientintheNICUatChildren shospitals andclinics St.PaulandbeingtreatedwithCPAP. Enrollment EligibilitywillinitiallybedeterminedbybirthweightnotedontheNICUcensus.Ifa patient sbirthweightis<2500grams,thenfurtherreviewofthemedicalchartwill ensuetoseeifallinclusioncriteriaaremet/exclusioncriteriaarenotmet.oncethe patientisdeemedapotentialstudycandidate,aninvestigatorwillapproachthe parent(s)regardingstudyenrollmentandwillobtaininformedconsent. Inclusion Criteria 1. LBW infant (birth weight <2500 grams) 2. Currently on nasal CPAP 3. Use of nasal CPAP for >24 hours prior to study initiation 4. If history of intubation with mechanical ventilation, patient will be extubated >24 hours prior to study initiation 5. FiO2 requirement of 25-50% Exclusion Criteria 1. FiO2 requirement > Congenital defects/deformities of the head, pulmonary or cardiovascular systems 3. Chromosomal abnormalities/genetic syndromes 4. Active medical treatment for symptomatic PDA 5. Active medical treatment for culture proven sepsis 6. Within 24 hours of invasive surgical procedure 7

8 ResearchQuestion Inlowbirthweightinfantswithrespiratorydistress,whataretheeffectson oxygenationandventilationwhenusingsipapversuscpap? Study Procedures Afterparentalconsentisobtained,thepatientswillberandomizedbysealedenvelopeshuffletoastartingmodeofCPAPorSiPAP.Theinfanthospitalchartwill bereviewedforprenatalhistoryandcurrentmedicalhistoryatthetimeof enrollment.thepatientswillthenenterthe4 hourstudyconsistingofone hour blocksalternatingbetweencpapandsipap. Baselinevitalsignswillbeobtainedpriortostartingthestudy.A transcutaneousco2monitoraswellaspneumogramimpedencebandwillbeplaced onthetrunkforcontinuousrespiratorydataacquisition.physiologicdatawillbe obtainedfromcontinuousbedsidecardiorespiratoryandpulseoximetrymonitors usedroutinelyonallpatientsinthenicu.a3 channelpneumogram(heartrate, oximetry,thoracicimpedence)willbeperformedthroughoutthestudytoquantify centralapneicevents.supplementaloxygenwillbeprovidedtoattainagoaloxygen saturationof88 90%,withinthestandardNICUguidelines. References 1.Stevens,T.P.,M.Blennow,andR.F.Soll.Earlysurfactantadministrationwith briefventilationvs.selectivesurfactantandcontinuedmechanicalventilationfor preterminfantswithoratriskforrespiratorydistresssyndrome.cochrane DatabaseSystRev(3)2004;CD A.FanaroffandJ.Martin.Neonatal PerinatalMedicine,7 th ed.2001.mosby Year Book,Inc.St.Louis,MO.Ch.42,pg JobeAH,KramerBW,MossTJ,etal.Decreasedindicatorsoflunginjurywith continuouspositiveexpiratorypressureinpretermlambs.pediatricres2002; 52: LinderW,VossbeckS,HummlerH,PohlandtF.Deliveryroommanagementof extremelylowbirthweightinfants:spontaneousbreathingorintubation?pediatrics 1999;103: GittermannGK,FuschC,GittermannAR,etal.Earlynasalcontinuouspositive airwaypressuretreatmentreducestheneedforintubationinverylowbirthweight infants.eurjpediatr1997;156: DavisPG,Henderson SmartDJ.Nasalcontinuouspositiveairwaypressure immediatelyafterextubationforpreventingmorbidityinpreterminfants.cochrane DatabaseSystRev2003;2:CD

9 7.DavisPG,LemyreB,dePaoliAG.Nasalintermittentpositivepressureventilation (NIPPV)versusnasalcontinuouspositiveairwaypressure(NCPAP)forpreterm neonatesafterextubation.cochranedatabasesystrev2001;3:cd MiglioriC,MottaM,AngeliA,etal.Nasalbilevelvs.continuouspositiveairway pressureinpreterminfants.pediatrpulmonol2005;40: GoodQuestion:CancerRiskforFormerPreemies Afterreadingthe"NeonatalPoop"wewerediscussingtheincreasedincidenceof cancerandchildhoodleukemiasafterbeingexposedto100%o2evenfor abriefperiodoftime.thenotesrefertothis"atbirth".isthisalsotrueduringthe courseofapreemiestimeintheunit,ie:gettingblow byforaspell?hasthisevenbeen studied?thisisreallyscary. Thisisaveryinterestingtopic,andtimely,givenourfocusonlimitingoxygen exposureonpreemiestoreducebpdandroprisk.arecentliteraturefoundstill verylittleonlong termcancerriskfornicugraduates.thebestofwhatisoutthere isbylocalauthorsfromtheuniversityofminnesota(includingformerneonatology fellowfromourprogram,dr.michaelgeorgieff).a2005articlepublishedinjournal ofpediatricslookedat48casesofchildhoodcancersin54,795childrenborninthe U.S.between1959and1966whowerefollowedinastudyuntilage8(1).This studyfoundalowbutstatisticallysignificantincreaseintherateofchildhood cancer(e.g.leukemia,cnstumors,neuroblastomas,andothers)diagnosedduring thesefirst8yearsoflifeamongchildrenexposedto3ormoreminutesofoxygenat birth.however,theauthorscautionedthatthemagnitudeofassociationwassolow thattheriskcouldeasilybeduetosomeotherfactorforwhichoxygenisaproxy. Similarly,aone minuteapgarof<7hadanincreasedriskofcancers,butatavery lowmagnitude.thisstudydidnotspecificallylookattherisksassociatedwith prematurityorlowbirthweight.toanswerthis,theleadauthorfromthe previouslymentionedstudypublishedastudyin2009inpediatrics(2)lookingat 16,672childhoodcancercasesinseveralstatesincludingMinnesotaandfoundno associationbetweenmostcancersandverylowbirthweight,withanexceptiontoa lowbutincreasedriskoftherarelivertumorhepatoblastomainpreterminfants firstdescribedin1998(3)aswellasamoderateincreasedriskofgliomasand retinoblastomawarrantingfurtherstudy.theauthors conclusionsshouldbe reassuringtofamiliesandprovidersinthenicu:theoveralllongtermriskof childhoodcancersfornicugraduatesisvery,verylow. References: 1. SpectorLG.KlebanoffMA.FeusnerJH.GeorgieffMK.RossJA.Childhood cancerfollowingneonataloxygensupplementation.j.peds.2005;147(1):

10 2. SpectorLG.PuumalaSE.CarozzaSE.ChowEJ.FoxEE.HorelS.JohnsonKJ. McLaughlinCC.ReynoldsP.BehrenJV.MuellerBA.Cancerriskamong childrenwithverylowbirthweights.pediatrics.2009;124(1): TanimuraM,MatusiI,AbeJ,etal.Increasedriskofhepatoblastomaamong immaturechildrenwithalowerbirthweight.cancerres.1998;58(14): Ifyouhaveaburningquestionyou dlikeansweredhere,sendittomarkbergeron atxxxxxandwe llgetitansweredhere! IntroducingOurNewWebsite! AssociatesinNewbornMedicinehasgeneratedanew websitefornicustaffaswellasfamilies.ithasbiosof theneonatologists,linkstothenurseriesweserve, clinicalresources,andpatient/familyinformationand 10

11 more.thesiteisgrowingwithlinksandinfoalmost daily,socheckbackoften.ifyouhavesuggestions, commentsorquestions, markbergeronatxxxx. ALookBack: Virginia Apgar ( ) If we neonatologists ever get a patron saint of our own, it will probably be Virginia Apgar. We are reminded of Dr. Apgar's dedication, wisdom, wit, tenacity, and many contributions to infant care every time we are called to the delivery room to evaluate a baby. Dr. Apgar originally intended to become a surgeon, but to our great good fortune, ended up in anesthesia instead, where she soon turned her attention to the care of mothers and the assessment and resuscitation of newborns. Her elegant paper of 1952 established the scoring system that now bears her name, but she was also famous for her work in the March of Dimes, her love of cars and fast driving, and her construction of her owned stringed instruments -- among other things. For more information, see the Apgar family web site. EDITORIALNOTEFROMMICHAELCOLEMAN: Pleasebringtomyattentionanyerrorsormissionsinthisdocument.Guidelinesarewrittentoprovidedirectionandconsistencyandarenot intendedtoreplaceclinicaldecision makingonrounds. 11