OfficialreprintfromUpToDate

www.uptodate.com2016UpToDate

Managementofasthmaduringpregnancy
Authors: MichaelSchatz,MD,MS,StevenEWeinberger,MD
SectionEditors: BruceSBochner,MD,CharlesJLockwood,MD,MHCM
DeputyEditor: HelenHollingsworth,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Oct2016.|Thistopiclastupdated:Sep19,2016.
INTRODUCTIONAsthmaisoneofthemostcommonmedicalconditionsencounteredduringpregnancy,
occurringin3to8percentofpregnantwomen[13].Pregnancymaybeassociatedwithchangesinthecourseof
asthma,andasthmamayaffecttheoutcomeofpregnancy.Whenconsideringtheuseofasthmamedicationsina
pregnantwoman,thepotentialriskofadrugmustbebalancedagainsttheeffectsofuntreatedasthma.
Themanagementofasthmainpregnancy,includingthesafetydataforspecificasthmamedications,general
management,andrecommendedpharmacotherapyforacuteandchronicasthmainpregnancy,isreviewedhere.
Anoverviewofasthmamanagementandthephysiologyandclinicalcourseofasthmainpregnancyare
discussedseparately.(See"Anoverviewofasthmamanagement"and"Physiologyandclinicalcourseofasthma
inpregnancy".)
ASSESSINGDRUGSAFETYINPREGNANCYInformationaboutpotentialadverseeffectsmustbe
interpretedwithanunderstandingthatthebaselinefrequencyofcomplicationsinpregnancyisrelativelyhigh,
evenintheabsenceofasthmaorotherdisorders.IntheUnitedStates,majorcongenitalanomaliesoccurin2to
4percentofliveborninfants.Anoverviewofcongenitalmalformationsandadiscussionofgeneticand
environmentalcausesareprovidedseparately.(See"Approachtocongenitalmalformations".)
Thereisasmallbutsignificantincreaseincomplicationsofpregnancyinasthmaticwomen[4].Alarge
representativestudysuggeststhatasthmaticpatients,onaverage,havea15to20percentincreasedriskof
perinatalmortality,preeclampsia,pretermdelivery,orlowbirthweightinfantscomparedwithnonasthmatic
women,andthatpatientswithmoresevereasthmahavea30to100percentincreasedrisk(table1)[4].
Formanyyears,theUSFoodandDrugAdministration(FDA)hasusedfivecategories(A,B,C,D,andX)to
describeadrug'spotentialforcausingadverseeffectsduringpregnancy(table2)[5].Thecategoriesarebased
upontheresultsofanimalstudies,humandata,andconsiderationofwhetherthebenefitofthedrug'suseduring
pregnancyoutweighstherisk.TheFDAhasbegunthephaseoutofpregnancyriskcategoriesfromprescription
druglabelingandnowrequiresinformationfromavailablehumanandanimalstudiesabout(1)knownorpotential
maternalorfetalrisks,(2)doseadjustmentsneededduringpregnancyandthepostpartumperiod,and(3)
benefit/riskconsiderations[6].Whilenewmedicationsincludethisinformation,theprocessofupdatingexisting
medicationswilllikelytakeseveralyears.Intheinterim,itisusefultohaveanunderstandingofthevarious
categories.
NoneofthecurrentlyavailableasthmamedicationsmeetstherequirementsforcategoryA(controlledstudiesin
pregnantwomenshownorisk).MostcategoryBdrugsarelabeledassuchbecauseofreassuringanimalstudies
without"adequateandcontrolled"humandata.OnemaywishtochooseaclassBversusaclassCdrug(risk
cannotberuledout)amongequallyeffectivealternativesduetothereassuringanimalstudies.Amongcommonly
usedasthmamedications,budesonide(inhaledandintranasal)[7],cromolynsodium,andomalizumabare
assignedcategoryB.CategoryDprovidesastrongrelativecontraindicationtouseinpregnancy,andcategoryX

drugsshouldnotbeused.Ofnote,adrugthathasastrongrelativecontraindicationtouseinthefirsttrimester
mayhaveagoodsafetyprofilewhenusedlaterinpregnancywhenorganogenesishasbeencompleted(eg,
palatehasclosed).
Inadditiontothesafetyofthemedicationitself,atopical(inhaled)medicationwouldappeartobepreferabletoa
systemiconeduetoreducedlikelihoodofsystemiccirculationandtransplacentaltransfertothefetus.Anolder
medicationwitha"trackrecord"maybepreferabletoanewerone.Finally,absoluteandrelativeefficacymust
alsobeconsideredinthechoiceofamedicationforuseduringpregnancy.
MAINTAININGASTHMACONTROLAsthmamayimprove,worsen,orremainunchangedinseverityduring
pregnancy[8].Thepotentialmechanismsinvolvedandclinicalimplicationsofthesefindingsarediscussed
separately.(See"Physiologyandclinicalcourseofasthmainpregnancy".)
Thetwoprimarygoalsofasthmamanagement,ie,preventionofacuteexacerbationsandoptimizationofongoing
asthmacontrol,areunchangedinthesettingofpregnancyandshouldservetomaximizebothmaternalandfetal
health[9].Whileuseofanymedicationduringpregnancyraisesconcernsaboutpotentialadverseeffectsonthe
motherorfetus,thebenefitofactivetreatmenttomaintainasthmacontrolandpreventexacerbationsoutweighs
thepotentialrisksofroutinelyusedasthmamedications.
AdjustmentstopharmacologictherapyinpregnancyThegeneralprinciplesofpharmacologictherapyfor
asthmaduringpregnancyaresimilartothoseinnonpregnantpatientsandinvolveastepwiseapproachto
achieveandmaintainasthmacontrol,asrecommendedbynationalandinternationalguidelines(figure1and
table3andtable4)[10,11].Thedetailsofthisapproacharediscussedseparately.(See"Anoverviewofasthma
management".)
Currentguidelinesemphasizethefollowingpoints[1012]:
Albuterolisrecommendedastheshortactingbetaagonistofchoice.
Forpatientswithmildpersistentormoresevereasthma,inhaledglucocorticoidsreduceexacerbationsduring
pregnancyandcessationofinhaledglucocorticoidsduringpregnancyincreasestheriskofanexacerbation.
Budesonideisthepreferredinhaledglucocorticoidforuseduringpregnancy,asmorepublishedgestational
humandataareavailableforthatmedication[7,13].However,otherinhaledglucocorticoidscouldbe
continuedifthepatientwaswellcontrolledononeofthesemedicationspriortopregnancy,anddatafor
fluticasonehavebeenreassuringregardinglowbirthweight(<2500grams),smallforgestationalage(<10
percentofexpectedforgestationalage),pretermbirth(<37weeks)[14],andmajorcongenitalmalformations
[15].
SalmeterolhasbeenrecommendedastheinhaledlongactingbetaagonistofchoiceintheUnitedStates
duetothelongerdurationofclinicalexperiencewiththisagentcomparedwithformoterol.However,
retrospectivecohortstudiesprovidereassuringdataforbothsalmeterolandformoterol[14,16].
MontelukastorzafirlukastcouldbeconsideredasalternativebutNOTpreferredtherapyformildpersistent
asthmaorasaddontherapytoinhaledglucocorticoids,especiallyforpatientswhohaveshownauniquely
favorableresponsepriortopregnancy.Morepregnancydataareavailableformontelukastthanzafirlukast.
(See'Leukotrienemodifiers'below.)
SafetyofspecificmedicationsExperiencewithmanyofthemedicationsusedtotreatasthmasuggests
minimalornoknownadverseeffectsfortheiruseduringpregnancy[7,12,1726].Mostdrugsusedinthe
treatmentofasthmafallintocategoriesBorC.Additionalinformationandlinkstonationaldatabasesfor
reproductiveteratologyareprovidedseparately.(See"Approachtocongenitalmalformations".)

Thefollowingsectionsreviewthesafetyinformationthatisavailableforeachofthemajordrugclassesusedin
thetreatmentofasthma.Additionalinformationonthefetalandneonatalrisksofmaternaldrugingestionduring
pregnancyandlactationisavailablefromthefollowingresources:
Perinatology:Drugsinpregnancyandbreastfeeding
Reprotox
MotherToBaby:Medicationsandmoreduringpregnancyandbreastfeeding
MOTHERISK:Drugsinpregnancy
InhaledbetaadrenergicagonistsThemajorityofreportsprovidereassuranceregardingtheuseof
inhaledbetaagonistsduringpregnancy[18,19,27,28].Clinicalexperienceisgreaterwiththeolderagents(eg,
albuterol)thanwiththenewerones(eg,formoterol,salmeterol).
ShortactingbetaadrenergicagonistsTheshortacting,selectivebeta2adrenergicbronchodilators
(SABAs)areusedtoprovidequickreliefofasthmasymptomsandappeartoberelativelysafeduring
pregnancy.However,somecasecontrolstudieshavesuggestedaslightincreaseinriskofcertaininfant
abnormalities,asnotedbythefollowingreports:
Inacasecontrolstudy,asmallincreasedriskofgastroschisiswasreportedamonginfantsexposedin
uterotobronchodilators[29].
InacasecontrolstudyusingEuropeanregistrydata,gastroschisis(oddsratio[OR]1.89,95%CI1.12
3.20)andcleftpalate(OR1.63,95%CI1.052.52)wereassociatedwithagreaterlikelihoodoffirst
trimesterbetaagonistexposure[30].
Anassociationwithcardiacdefectswasnotedinacohortstudythatexaminedtheeffectofexposureto
bronchodilatortherapyduringpregnancy[31].
Acasecontrolstudyreporteda30percentincreasedrisk(OR1.3,95%CI1.11.5)ofautismspectrum
disorderinchildrenexposedtomaternalbeta2adrenergicreceptoragonistdrugsduringgestation[32].
Oneproblemwithassessingtheconsequencesofbronchodilatoruseinpregnancyisconfoundingintroduced
byindicationSABAuseisamarkerforpoorlycontrolledasthmaandmorefrequentexacerbations,which
mayindependentlycontributetothedevelopmentofcongenitalanomalies[33].Furthermore,somestudies
onlyhaveaccesstodataaboutprescriptionsfilledandnotthefrequencyofactualuse[30].Evenifthe
statisticalassociationsforrelativeriskarevalid,theanomaliesmentionedaboveareinfrequent.Therefore,
theabsoluteincreaseinriskisverysmalland,asnotedearlier,lessthantheriskofpoorlycontrolled
maternalasthma.
LongactingbetaadrenergicagentsClinicalexperiencewithinhalationofthelongacting,selective
beta2adrenergicbronchodilators(LABAs)duringpregnancyislessextensivethanwiththeSABAs(table
5).Salmeterolisnotexpectedtoincreasetheriskofcongenitalanomalies,basedondatafromanimal
studiesandlimitedhumanexperience[34].Animalstudiesarealsoreassuringforformoterol,althoughdata
fromhumanpregnanciesarelimited[35,36].Aretrospectivedatabasestudyshowedthatsalmeteroland
formoteroldonotincreasetheriskofdeliveringlowbirthweight,smallforgestationalage,orpreterminfants
[14,16].Giventhesefindings,continuationofaLABAduringpregnancyisreasonableifaLABAhasbeen
needed(incombinationwithaninhaledglucocorticoid)toachieveasthmacontrolbeforepregnancy[37,38].
HumansafetydatafornewerLABAs,suchasindacaterol,olodaterol,andvilanterolarelacking.Some
adverseeffectswerenotedinanimalstudiesofolodaterol,butarenotreportedwithindacaterolorvilanterol.
Oftheseagents,theonlyonethatisavailableinaninhaledglucocorticoidcombinationinhalerisvilanterol,
whichisavailablewithfluticasone.

WhencomparingacombinationLABAplusinhaledglucocorticoidversusmonotherapywithahigherdoseof
theinhaledglucocorticoid,theriskofcongenitalmalformationsappearssimilar.Inastudyof1302pregnant
womenwithasthma,theoddsratioforamajorcongenitalmalformationwasnotincreased(OR1.1,95%CI
0.61.9)whenaLABApluslowdoseinhaledglucocorticoidwascomparedwithamediumdoseinhaled
glucocorticoidorwhenaLABAplusmediumdoseinhaledglucocorticoidwascomparedwithahighdose
inhaledglucocorticoid(OR1.2,95%CI0.52.7)[39].
TheindicationsforLABAtherapyinasthma,theimportanceofcombiningLABAtherapywithaninhaled
glucocorticoid,andthecontroversyregardingthesafetyofLABAtherapyarediscussedseparately.(See
"Treatmentofmoderatepersistentasthmainadolescentsandadults",sectionon'MediumdoseinhaledGCs
plusaLABA'and"Treatmentofsevereasthmainadolescentsandadults",sectionon'Combinationinhaled
GC/LABA'and"Betaagonistsinasthma:Controversyregardingchronicuse",sectionon'Longactingbeta
agonists'.)
Oral/SystemicglucocorticoidsSystemicglucocorticoidshavebeenusedfairlyextensivelyduring
pregnancytotreatasthmaexacerbationsandrarelyforcontrolofsevereasthma.Foreachpregnantwoman,the
potentialrisksofgestationaloralglucocorticoidsmustbebalancedagainsttheriskstothemotherorinfantof
inadequatelytreatedasthma.Astherisksofsevereuncontrolledasthmaincludematernalorfetalmortality,these
risksareconsideredtobegreaterthanthepotentialriskofsystemicglucocorticoids.Thus,oralglucocorticoids
shouldbeusedduringpregnancywhenindicatedforthemanagementofsevereasthma[12,21].
Severalpotentialareasofconcernhavebeenraisedwithsystemicglucocorticoids:congenitalmalformations
(primarilycleftpalate),preeclampsia,gestationaldiabetes,lowbirthweight,andneonataladrenalinsufficiency.
Amongthestudiesinwhichsystemicglucocorticoidswereusedforthemanagementofasthmaduringpregnancy
[18,19,4043],someshowedaslightlyincreasedriskofprematurityandaslightlyhigherriskoflowbirthweight
(<2500grams)[18,19,42].
CongenitalmalformationsDatafromanimalstudiesinseveralspeciessuggestthathighdosesystemic
glucocorticoidsmayleadtocleftpalate.Palatalclosureisusuallycompletebythe12thweekofpregnancy,
sopotentialriskwouldbelimitedtoadministrationduringthefirsttrimester.Humanstudiesareless
concerningbutapossibleeffectcannotbedismissed.Theriskofcleftlip/palatewithsystemicglucocorticoid
useisdiscussedseparately.(See"Etiology,prenataldiagnosis,obstetricalmanagement,andrecurrenceof
orofacialclefts",sectionon'Medications'.)
PretermbirthandlowbirthweightAlarge,prospective,cohortstudyof2123pregnantwomenwith
asthmarecruitedfrom16centersintheUnitedStatesintheperiodfromDecember1994toFebruary2000
foundthatoralglucocorticoidusewassignificantlyassociatedwithpretermbirth(before37weeksof
gestation,OR1.54,95%CI1.022.33)andlowbirthweight(<2500grams,OR1.80,95%CI1.132.88)[18].
Increasedprematurityand/orlowerbirthweightshavebeennotedinotherstudiesaswell[19,41,42,4448].
Theauthorsdidnotevaluatetherelationshipbetweentheseeffectsandthedoseordurationoftherapy.
OtheradverseoutcomesPreeclampsiahasbeenattributedtooralglucocorticoiduseinseveralstudies
[40,49,50].Neonataladrenalinsufficiencyfollowingmaternaladministrationofglucocorticoidsisdistinctly
unusual,probablybecausethenonhalogenatedglucocorticoidsarelargelymetabolizedtoinactive
metabolitesbytheplacenta[51].Gestationaldiabetesandhypertensionareadditionalpotentialmaternal
complicationsofsystemicglucocorticoidadministration[46].
However,itremainspossiblethattheconsequencesofsevereuncontrolledasthmacausedtheseadverseeffects,
giventhatasthmasymptomsweresevereenoughtorequireoralglucocorticoids.

InhaledglucocorticoidsIncontrasttooral/systemicglucocorticoids,thesafetydataoninhaled
glucocorticoidsarereassuring[2,7,18,20,27,40,41,50,5261].
Examplesofstudiesassessingthesafetyofinhaledglucocorticoidsincludethefollowingpopulationbased
studies:
Inametaanalysisofdataon519,242pregnanciesfromthreecohortstudies,inhaledglucocorticoidswere
associatedwithanoddsratioforanalatresiaof3.4(99%CI1.1510.04)[26].However,analatresiaisrare
andtheabsoluteriskremainslow.
Useofinhaledbudesonideduringearlypregnancywasassessedinaregistrybasedcohortstudyof2014
Swedishwomen[7].Therateofcongenitalmalformationswasnotdifferentfromthatofthegeneral
population(3.8versus3.5percent).AdditionaldatafromtheSwedishMedicalBirthRegistryreportedno
clinicallysignificanteffectsofinhaledbudesonideonfetalmortality,gestationalage,orfetalgrowth[52].
Basedlargelyuponthesefindings,budesonideiscurrentlytheonlyinhaledglucocorticoidwithapregnancy
categoryBrating[12].
InapopulationbasedstudyusingtheUnitedKingdom'sClinicalPracticeResearchDatalink,theriskofmajor
congenitalmalformation(MCM)wasassessedamong5362pregnancieswithinhaledglucocorticoid
exposureduringthefirsttrimesterandknownfetaloutcomesatoneyearofage[15].EightynineMCMs
wereidentifiedfollowingexposuretononfluticasoneinhaledglucocorticoids,and42followingexposureto
fluticasonepropionate(overall2.4percent).Whenfluticasonewascomparedwithotherinhaled
glucocorticoids,theadjustedoddsratioforMCMwas1.1(95%CI0.52.3),suggestingnoincreaseinrisk
withfluticasone.
Inaddition,aseparatestudyof13,280pregnanciesinwomenwithasthmaconfirmedthatlowtomoderate
dosesofinhaledglucocorticoidswereNOTassociatedwithanincreasedriskofcongenitalmalformations.
However,theuseofhighdoses(>1000mcg/day)duringthefirsttrimesterwasassociatedwitha63percent
increaseinriskofallcongenitalmalformations[58].Thestrengthofthisobservationislimitedbecausethe
studywasunderpoweredtoassesstheriskofspecificmalformations,suchascleftpalate,whichhasbeen
associatedwithmaternaluseofsystemicglucocorticoids.Inaddition,theauthorscouldnotexcludethe
possibilitythatgreaterasthmaseveritycontributedtotheoverallincreasedriskofmalformations.Benefitrisk
considerationsfavortheuseofhighdoseinhaledglucocorticoidsoveralowerdosewhenneededforasthma
controltoavoidtheuseofsystemicoralglucocorticoids,withthepotentialriskslistedabove.(See
'Oral/Systemicglucocorticoids'above.)
Tworandomizedtrialssupporttheefficacyandsafetyofinhaledglucocorticoidsduringpregnancy.Onestudy
assessed84pregnantwomenwhoweremanagedwithorwithoutinhaledbeclomethasoneafterdischarge
followinganasthmahospitalizationduringpregnancy[62].Useofthismedicationsignificantlydecreasedtherate
ofreadmissionforasthma(12versus33percent),andnoadverseeventsoroutcomeswerereported.A
subsequentstudycomparedinhaledbeclomethasonetotheophyllineinthemanagementofmoderateasthma
duringpregnancy[55].Althoughexacerbationratesweresimilarinthetwogroups,pulmonaryfunctionwasbetter
inthebeclomethasonegroupandfewerpatientsinthebeclomethasonegroupdiscontinuedtherapyduetoside
effects.
AnticholinergicagentsAnticholinergicagents(alsoknownasantimuscarinicagents),suchas
ipratropium,glycopyrrolate,andtiotropium,arenotgenerallyusedasaprimaryformoftherapyforasthma.
However,questionsmayariseabouttheirsafetyduringpregnancy.
Fetaltachycardiacanoccurwiththesystemicadministrationofatropinetothemotherhowever,theminimal
chronotropiceffectofinhaledipratropiuminthemothersuggeststhattheinhaledpreparationshouldhave

negligiblechronotropiceffectsonthefetus.Gestationalanimalstudiesarealsoreassuringforipratropium[51].
Consequently,inhaledipratropium,themostcommonlyuseddruginthiscategory,isfelttobesafeduring
pregnancy[12,63].
Theinhaledlongactingmuscarinicantagonist(LAMA),tiotropium,isapprovedbytheUSFoodandDrug
Administration(FDA)foruseinasthma,althoughitisreasonabletoassumethattheotherLAMAswouldhave
similareffects(table5).LAMAsareusuallyreservedforpatientswithmoderatetosevereasthmathatisnot
controlledwithaLABAinhaledglucocorticoidcombination.Thesafetyofinhaledtiotropium,aclidinium,
glycopyrrolate,andumeclidiniumduringpregnancyisuncertainasadverseeffectswerereportedinanimal
studiesandhumanfetaloutcomeshavenotbeenreported.
LeukotrienemodifiersZafirlukastandmontelukast(leukotrienereceptorantagonists)andzileuton(a5
lipoxygenaseinhibitor)areagentsthataffectleukotrienesynthesisoraction.Wesuggestuseofmontelukastor
zafirlukast,inpreferencetozileuton,andwouldreservetheseagentsforaddontherapytoinhaled
glucocorticoids,especiallyinpatientswhohadagoodresponsetothismedicationpriortopregnancy[12].(See
"Agentsaffectingthe5lipoxygenasepathwayinthetreatmentofasthma".)
Accumulatingevidenceformontelukastandzafirlukastisreassuring,althoughlimited.
Thefirstprospective,controlledstudyoftheuseofleukotrienereceptorantagonistsinpregnancyfollowed96
womentakingthesemedications,122womentakingSABAsonly,and346womenwithoutasthma.No
increaseinmajorbirthdefectsoradverseoutcomeswasdetectedintheoffspringofpatientsreceivingthese
medications[64].Asubsequentstudywithsimilardesigndescribed180montelukastexposedpregnancies
comparedto180diseasematchedcontrolsand180pregnanciesinnonasthmaticwomen.Inthisstudy,
montelukastdidnotappeartoincreasethebaselinerateofmajormalformations,althoughlowerbirth
weightswereseeninbothasthmaticgroups[65].Largerstudiesareneededtodetectsmallincreasesin
adversepregnancyoutcomesorrarebirthdefects.
Alargeretrospectiveinsuranceclaimscohortanalysiscomparedtheincidencesofselectedcongenital
malformationsininfantsofmothersexposedtomontelukast(n=1535),inhaledcorticosteroids(n=3918),
otherasthmamedications(n=8834),andcontrolswithnoasthmamedicationsorasthmadiagnoses(n=
38,828)[66].Nosignificantdifferencesbetweengroupswereobserved.
Noteratogenicitywasobservedwithmontelukastgiventoratsorrabbitsatdosesgreaterthan300timesthe
maximumhumandailyoraldoseonanmg/m2basis[67].
Animaldataonzafirlukasthaveshownnoteratogenicityatoraldosesupto160timesthemaximumhuman
dailyoraldoseonamg/m2basis[68].Humanstudiesarereassuring,althoughthenumbersofpregnant
womenincludedaresmall[64].
Incontrast,adverseeventswerenotedinanimalreproductionstudiesofzileuton,andadequateandstudies
ofzileutoninpregnantwomenarelacking[69].
ImmunotherapyforallergicasthmaTheinitiationofsubcutaneousorsublingualallergenimmunotherapy
isnotrecommendedduringpregnancyduetothepotentialharmtothefetusshouldasystemicallergicreaction
occur[18,70].However,patientswhoaretoleratingmaintenanceimmunotherapy(oratleastasubstantial
dosage)andderivingbenefitmaycontinueit.Immunotherapyduringpregnancyisdiscussedinmoredetail
separately.(See"Recognitionandmanagementofallergicdiseaseduringpregnancy",sectionon'Allergen
immunotherapy'and"Sublingualimmunotherapyforallergicrhinoconjunctivitisandasthma",sectionon'Usein
pregnancy'.)

AntiimmunoglobulinEOmalizumabisahumanized,recombinantIgG1,monoclonalantiimmunoglobulin
Eantibodyapprovedforaddontherapyinpatientswithmoderatetosevereasthmathatisinadequately
controlleddespiteappropriateuseofinhaledglucocorticoids.Studiesofthesafetyofomalizumabinpregnancy
arelimited,althoughavailabledataarereassuring.ImmunoglobulinGmolecules,suchasomalizumab,are
knowntocrosstheplacenta.
Aprospectiveobservationalregistrystudyreportedpregnancyoutcomesof191pregnantwomenexposedto
omalizumab[71].Theincidencesofprematurity(14.5percent),smallforgestationalage(10.9percent),lowbirth
weight(3.2percent),andmajorcongenitalmalformationswerenotsubstantiallydifferentfromoutcomesreported
inotherstudiesofwomenwithmoresevereasthma.Theinitiationofomalizumabduringpregnancyisnot
recommended,althoughifawomanbecomespregnantwhilereceivingomalizumab,itissuggestedthattherapy
canbecontinuedifthebenefitsareestimatedtooutweighthepotentialharms.(See"AntiIgEtherapy"and"Anti
IgEtherapy",sectionon'Safetyinpregnancyandlactation'.)
Antiinterleukin5Theantiinterleukin(IL)5antibodypreparations,mepolizumabandreslizumab,are
approvedbytheFDAforaddonmaintenancetherapyinpatientswithsevereeosinophilicasthma.Theuseof
theseagentsinsevereasthmaisdiscussedseparately.(See"Treatmentofsevereasthmainadolescentsand
adults",sectionon'AntiIL5therapy'.)
Monoclonalantibodies,includingmepolizumabandreslizumab,arelikelytocrosstheplacentainincreasing
amountsaspregnancyprogresses[72,73].
Noevidenceoffetalharmwasnotedinmonkeystreatedwithintravenousmepolizumabindosesupto30
timesthehumandose,butstudiesinhumanpregnancyarelacking[74].Informationaboutapregnancy
exposureregistryisprovidedinthepackageinsert[73].
Adverseeventswerenotnotedwithreslizumabinanimalstudies(miceandrabbits),buthumanstudiesare
notavailable[72].
RarelyusedmedicationsMethylxanthinesandcromoglycatesarerarelyusedinthemanagementof
asthmaduetotheavailabilityofalternativeagentswithgreatereffectivenessandeaseofuse.
MethylxanthinesTheclinicaluseofmethylxanthines(theophylline,aminophylline)duringpregnancyis
limitedbecauseofthepotentialforalteredmetabolismduringpregnancy,theneedfordruglevelmonitoring,
andthepotentialforfetaltachycardiaandirritabilityatthetimeofdelivery.Moreover,inhaledglucocorticoids
havebeenshowntobemoreeffectivethantheophyllineforpersistentasthmainnonpregnantpatientsand
atleastaseffectiveastheophyllinewithfewersideeffects[12,55].Extensiveclinicalexperiencesuggests
thattheophyllinedoesnotincreasetheriskoffetalanomalies[3,23].
Methylxanthinebindingtoalbuminandhepaticclearancearealteredduringpregnancy,necessitatingcareful
assessmentofserumlevelsandadjustmentstodosingoverthecourseofpregnancy.(See"Theophylline
useinasthma".)
Likethebeta2adrenergicagonists,theophyllinecaninhibituterinemusclecontractioninvitro,butthiseffect
hasnotbeenshowntobeclinicallyimportant.Methylxanthinesaretransferredacrosstheplacenta,leading
totheophyllineconcentrationsinneonatalandcordbloodthataresimilartothoseinmaternalblood[75].
Transienttachycardiaandirritabilityhavebeenreportedinsomeneonatesofmothersreceiving
methylxanthines.
CromoglycatesTheavailabilityofthecromolynsodiumandnedocromilislimitedandvariesfromone
countrytoanother.(See"Theuseofchromones(cromoglycates)inthetreatmentofasthma",sectionon
'Limitationsonavailability'.)

Animalandlimitedhumandataonuseduringpregnancy(n=318)havenotdemonstratedanincreasein
fetalmalformationsorotheradverseeffectswithcromolynsodium[40,63].Theonestudythatreportedan
increaseinmusculoskeletalabnormalitieswithmaternaluseofchromoneshadaverysmallnumberof
exposures(n=5),limitingthestrengthoftheobservation[17].(See"Theuseofchromones(cromoglycates)
inthetreatmentofasthma".)
NonpharmacologictreatmentsThemainnonpharmacologicinterventionstomaintainasthmacontrolduring
pregnancyarepatienteducation,avoidanceofirritant(eg,cigarettesmoke)andcontrolofallergenictriggersof
asthma.
PatienteducationTheprinciplesofpatienteducationaregenerallysimilarforthepregnantand
nonpregnantpatientwithasthma.Importantissuesincludeearlyrecognitionofsignsandsymptomsofan
asthmaexacerbation,avoidanceofprecipitatingfactors,correctuseofmedications,anddevelopmentofa
treatmentplanforacuteexacerbations.(See"Whatdopatientsneedtoknowabouttheirasthma?"and
"Patienteducation:Asthmaandpregnancy(BeyondtheBasics)".)
Theprimaryissuesthatarespecificforpregnancyareeducationabouttheinterrelationshipsbetween
asthmaandpregnancyandthesafetyofasthmamedicationsduringpregnancy.Theclinicianshouldclearly
explainthatitissaferforpregnantwomenwithasthmatotakeasthmamedicationsthantohaveongoing
symptomsorexacerbationsofasthma[33,76,77].Womenshouldbereassuredthatsafeandadequate
asthmatreatmentispossibleduringpregnancyandthatgoodasthmacontrolcanhelptominimizetheriskof
complications[3].
SmokingcessationItiscriticalforthepregnantasthmaticmothertodiscontinuesmokingduring
pregnancy[78].First,smokingmaypredisposethepatienttoasthmaexacerbations,bronchitisorsinusitis,
andthereforenecessitateanincreasedneedformedication[79].Second,cigarettesmokingisassociated
withnumerousadversepregnancyoutcomes,includingspontaneouspregnancyloss,placentalabruption,
pretermprematureruptureofmembranes(PPROM),placentaprevia,pretermlaboranddelivery,lowbirth
weight,andectopicpregnancy.Therisksassociatedwithmaternalsmokingduringpregnancyandmethods
toenablesmokingcessationarediscussedseparately.(See"Cigarettesmoking:Impactonpregnancyand
theneonate",sectionon'Adverseoutcomes'.)
ControlofenvironmentaltriggersControlofenvironmentaltriggersisaparticularlyimportant
componentofthemanagementofasthmaduringpregnancyasithelpstoreducetheneedfor
pharmacologicintervention.Thisincludesavoidingexposuretoallergensandtononspecificairwayirritants,
suchastobaccosmoke,dust,andenvironmentalpollutants.Particularallergensofconcernaredanderfrom
petsandantigensfromhouseholddustmites.(See"Allergenavoidanceinthetreatmentofasthmaand
allergicrhinitis"and"Triggercontroltoenhanceasthmamanagement".)
MonitoringCarefulfollowupbycliniciansexperiencedinmanagingasthmaisessential.Theoptimal
frequencyofasthmaevaluationsisnotknowngenerally,thefrequencyisdeterminedbasedontheprepregnancy
degreeofasthmacontrol.Inanobservationalstudy,visitseveryfourweeksimprovedadherencetocontroller
medicationandasthmacontrol[80].Allpregnantpatientsshouldhavereadyaccesstotheirclinicianshouldtheir
symptomschangeorincrease.Itisalsoimportantthateffectivecommunicationexistsamongtheclinician
managingtheasthma,thepatient,andtheobstetrician.
Asthmaticsymptomsareoftengreatestatnight,leadingtonocturnalawakening,orsymptomswhenwakingupin
themorning.Functionalassessmentbythepatientduringtimesofworseningsymptomsmayprovideamore
accuratereflectionofthepatient'sconditionthanspirometricmeasurementsattheclinician'soffice.

Diminishedpulmonaryfunctionduringpregnancyisassociatedwithadverseperinataloutcomes[76,81]itis
thereforeimportanttomonitorpulmonaryfunctioninpatientswithasthma.Normalpregnancyrelatedchangesin
pulmonaryfunctionarediscussedseparately.(See"Respiratorytractchangesduringpregnancy".)
Althoughmonitoringpulmonaryfunctionusingspirometrycanbeuseful,measurementofpeakexpiratoryflow
(PEF)orforcedexpiratoryvolumeinonesecond(FEV1)usingaportabledeviceofferstheadvantagesofless
expenseandgreatereaseofserialmeasurementsathome.Thefrequencyofmeasurementshouldbe
individualizedpatientswithmoresevereasthmamayneedtomeasuretheirPEFtwiceaday:uponawakening
andapproximately12hourslater.(See"Peakexpiratoryflowratemonitoringinasthma".)
Anadditionalissueforpregnantwomenwithasthmaisthedifficultydifferentiatingsymptomsduetoan
exacerbationofasthmafromthenormalsensationofdyspneaexperiencedduringpregnancy.Thepresenceof
coughandwheezingsuggestsasthma.ObjectiveinformationcanalsobeobtainedbymeasurementofthePEF
orFEV1reductionsineithersuggestanasthmaexacerbation.(See"Dyspneaduringpregnancy"and"Diagnosis
ofasthmainadolescentsandadults",sectionon'Pulmonaryfunctiontesting'.)
ACUTEEXACERBATIONSAcuteasthmaexacerbationsarecommonduringpregnancyandincreasetherisk
ofpreeclampsia,gestationaldiabetes,placentalabruptionandplacentaprevia[82].Therecommended
pharmacotherapyofacuteasthmaduringpregnancydoesnotdiffersubstantiallyfromthemanagementinnon
pregnantpatients(table6)[83].Intensivemonitoringofbothmotherandfetusisessential.(See"Overviewof
antepartumfetalsurveillance".)
MaternalandfetalmonitoringForacuteasthmaexacerbationsthatrequireemergencydepartment
managementorhospitalization,fetalmonitoringmaybeindicatedinadditiontoroutinemonitoringforasthma.
Earlyconsultationwiththeobstetricsserviceforcomanagementisappropriate.
MaternalmonitoringContinuousmeasurementofoxygensaturationbypulseoximetry(SpO2)isprudent,
aimingforaSpO295percent.Measurementofexpiratoryairflowwithapeakflowmeter(orspirometer)is
thebestmethodforobjectiveassessmentoftheseverityofanasthmaattack.Peakflowmeasurementscan
alsobeusedtomonitorapatient'sresponsetotreatmentandasapredictivemarkerforthepossibilityof
hypercapnia.Normalvaluesforpeakexpiratoryflowarenotsignificantlyalteredbypregnancy.
Thechangesinbloodgasesthatoccursecondarytoacuteasthmaduringpregnancyaresuperimposedon
the"normal"respiratoryalkalosisofpregnancy.Thus,anarterialcarbondioxidetension(PaCO2)>35mmHg
oranarterialoxygentension(PaO2)<70mmHgassociatedwithacuteasthmarepresentmoresevere
compromiseduringpregnancythaninthenongravidstate.(See"Physiologyandclinicalcourseofasthma
inpregnancy".)
Achestradiographisnotindicatedforthemajorityofasthmaexacerbationsandisreservedforpatientswith
suspectedpneumonia,pneumothorax,orimpendingoractualrespiratoryfailure.
FetalmonitoringFetalheartratemonitoringisthebestavailablemethodfordeterminingwhetherthe
fetusisadequatelyoxygenated.After23to24weeksofgestation,noninvasivefetalheartratemonitoringis
appropriateduringasthmaexacerbationsrequiringemergencydepartmenttreatmentorhospitalization.The
fetalheartratetracingshouldbeevaluatedbyaclinicianexperiencedinfetalheartrateassessment.(See
"Nonstresstestandcontractionstresstest".)
Supportivecare
MaternalpositioningIngeneral,pregnantpatientswithacuteasthmashouldrestinaseatedorlateral
position,ratherthansupine,particularlyinthethirdtrimester,toavoidaortocavalcompressionbythegravid
uterus.

 HydrationIntravenousfluidsarenotnecessaryunlessthepatientisunabletomaintainoralhydration.
SupplementaloxygenSupplementaloxygen(initially3to4L/minbynasalcannula)shouldbeadministered,
adjustingthefractionofinspiredoxygen(FiO2)tomaintainaPaO2ofatleast70mmHgand/oroxygensaturation
bypulseoximetryof95percentorgreater[12].
MedicationsTherecommendedagentsformanagementofacuteasthmaexacerbationsinpregnantpatients
arethesameasforasthmaexacerbationsinnonpregnantadultsandadolescents.Theseagentsincludeinhaled
shortactingbetaagonists,inhaledanticholinergicagents,oralorintravenousglucocorticoids,and,ifappropriate,
intravenousmagnesiumsulfate(table6).(See'Safetyofspecificmedications'aboveand"Treatmentofacute
exacerbationsofasthmainadults".)
Additionalpointsregardingpharmacotherapyincludethefollowing:
SystemicglucocorticoidsTheindicationsforsystemicglucocorticoidsarethesameforpregnant
patientsexperiencinganasthmaexacerbation,asfornonpregnantpatients.Patientsshouldbereassured
thatthebenefitsoforalglucocorticoidsinpreventingexacerbationsfrombecominglifethreateningasthma
outweighanyrisktothemotherorfetus[11,84].Dosagesofsystemicglucocorticoidsforacuteasthma
exacerbationsinpregnancyarenotdifferentthanthoserecommendedfornonpregnantpatients,as
glucocorticoidbioavailabilitydoesnotappeartobeaffectedbypregnancy[85].(See'Oral/Systemic
glucocorticoids'aboveand"Treatmentofacuteexacerbationsofasthmainadults",sectionon'Systemic
glucocorticoids'.)
IpratropiumIpratropiumisoftenusedtotreatsevereacuteasthmaexacerbations.Asnotedabove,inhaled
ipratropiumisfelttobesafeduringpregnancy[12,63].(See'Anticholinergicagents'above.)
IntravenousmagnesiumsulfateIntravenousmagnesiumsulfatemaybebeneficialinacutesevereasthma
asanadjuncttoinhaledbetaagonistsandintravenousglucocorticoids[85].Magnesiumsulfateisamongthe
mostextensivelystudiedmedicationsinpregnancy.Itisroutinelygiventopreventeclampticseizuresand
appearstohaveneuroprotectiveeffectsfortheneonateifadministeredpriortopretermbirth.Italsomay
decreasethefrequencyofuterinecontractions.(See"Treatmentofacuteexacerbationsofasthmainadults",
sectionon'Magnesiumsulfate'and"Neuroprotectiveeffectsofinuteroexposuretomagnesiumsulfate".)
ParenteralbetaagonistsParenteralbetaagonistsarerarelyneededforasthmaexacerbations.Dueto
theoreticconcernsthatthealphaadrenergiceffectsofepinephrinemightcausevasoconstrictioninthe
uteroplacentalcirculation,theWorkingGrouponPregnancyandAsthmarecommendedthatepinephrine
generallybeavoidedduringpregnancyexceptinthesettingofanaphylaxis[12].Fortherarepatientwho
requiresuseofasystemicbetaagonisttotreatasthma,subcutaneousadministrationofterbutalineisa
reasonablechoice(table6).
Thesafetyofterbutalineissuggestedbyitsuseasatocolyticagent(ie,asinhibitorsofuterinecontraction)in
thesettingofprematurelabor.Whengivenfortocolysis,themajormaternaladverseeffectsare
hyperglycemia,hypokalemia,and,lesscommonly,noncardiogenicpulmonaryedema.Prenatallyexposed
neonateshavebeenfoundtohavetachycardia,hypoglycemia,andtremor.However,theseeffectsinthe
neonatearetreatable,reversible,andnotconsideredacontraindicationtouse.(See"Inhibitionofacute
pretermlabor",sectionon'Betaagonists'.)
Intravenousaminophylline/theophyllineisNOTgenerallyrecommendedforuseintheemergency
managementofacutegestationalasthmabecauseaminophylline/theophyllineprovidesnoadditionalbenefit
tooptimalinhaledbetaagonistandintravenousglucocorticoidtherapy[12,62].Inaddition,whenusedin
combinationwithintensiveinhaledbetaagonisttherapy,intravenousaminophyllinecausesincreased
adversesideeffects[12].

Amoredetaileddiscussionofthetreatmentofacuteexacerbationsofasthma,includingstatusasthmaticus,is
providedseparately.(See"Treatmentofacuteexacerbationsofasthmainadults".)
RespiratoryinfectionsMostrespiratoryinfectionsthattriggeranexacerbationofasthmaareviralratherthan
bacterialanddonotrequireantibiotictherapy[10].However,testingforandtreatmentofinfluenzamaybe
appropriate,dependingonthetimeofyearandsymptompattern.Thetreatmentofrespiratoryinfectionsduring
pregnancyisdiscussedseparately.(See"Treatmentofrespiratoryinfectionsinpregnantwomen".)
PERIPARTUMCAREAfewissuesarerelevanttotheperipartummanagementoftheasthmaticpatientand
herbaby[12]:
Oxytocinisthedrugofchoiceforinductionoflaborandcontrolofpostpartumhemorrhage[86].(See
"Managementofpostpartumhemorrhageatvaginaldelivery",sectionon'Uterotonicdrugs'and
"Managementofpostpartumhemorrhageatcesareandelivery",sectionon'Initialmanagement'and
"Inductionoflabor",sectionon'Guidelines'.)
AnalogsofprostaglandinF2alphacancausebronchoconstriction[87,88]andshouldnotbeusedfor
terminationofpregnancy,cervicalripening,inductionoflabor,orcontrolofuterinehemorrhage.
ProstaglandinE2(ingelorsuppositoryform)andprostaglandinE1(misoprostol)havenotbeenreportedto
causebronchoconstrictionandaresaferanalogsifprostaglandintreatmentisrequired[89].
Forperipartumpaincontrol,morphineandmeperidineshouldbeavoided,ifpossible,sincetheycaninduce
histaminerelease,especiallyfromskinmastcells,however,evidenceofacutebronchoconstrictioncausedby
theseagentsislacking.Butorphanolorfentanylmaybeappropriatealternatives.
Epiduralanesthesiaispreferredfortheasthmaticpatientwhooptsforpaincontrolduringlaborbecauseit
reducesoxygenconsumptionandminuteventilationinthefirstandsecondstageoflaborandusuallycan
provideadequateanesthesiaifcesareandeliverybecomesnecessary.
Ifgeneralanesthesiaisrequired,ketamineandhalogenatedanestheticsarepreferred,becausetheymay
haveabronchodilatoryeffect.(See"Anesthesiaforadultpatientswithasthma".)
Useofergotderivativesforpostpartumbleedingorheadacheshouldbeavoidedbecauseoftheirpotentialto
causebronchoconstriction.
IfhighdosesofSABAhavebeengivenduringlaboranddelivery,bloodglucoselevelsshouldbemonitored
inthebaby(especiallyifpreterm)forthefirst24hours.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandare
comfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopics(see"Patienteducation:Asthmaandpregnancy(TheBasics)")

 BeyondtheBasicstopics(see"Patienteducation:Asthmatreatmentinadolescentsandadults(Beyondthe
Basics)"and"Patienteducation:Asthmaandpregnancy(BeyondtheBasics)"and"Patienteducation:
Triggeravoidanceinasthma(BeyondtheBasics)"and"Patienteducation:Howtouseapeakflowmeter
(BeyondtheBasics)"and"Patienteducation:Asthmainhalertechniquesinadults(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Asthmamayimprove,worsen,orremainunchangedinseverityduringpregnancy.Thepotentialmechanisms
involvedandclinicalimplicationsofthesefindingsarediscussedseparately.(See"Physiologyandclinical
courseofasthmainpregnancy".)
Thetwoprimarygoalsofasthmatherapyduringpregnancyarethepreventionofacuteexacerbationsand
optimizationofongoingpulmonaryfunction.(See'Nonpharmacologictreatments'above.)
Thefourimportantcomponentsofeffectiveasthmatherapyduringpregnancyare:
Objectivemonitoringofmaternallungfunctionandfetalwellbeingasaguidetotherapy(see"An
overviewofasthmamanagement",sectionon'Monitoringpatientswithasthma'and"Overviewof
antepartumfetalsurveillance")
Propercontrolofenvironmentalandothertriggersforasthma(eg,cigarettesmoking,animalallergen
exposure)(see'Nonpharmacologictreatments'aboveand"Triggercontroltoenhanceasthma
management")
Patienteducation(see"Whatdopatientsneedtoknowabouttheirasthma?")
Pharmacologictherapy(see'Adjustmentstopharmacologictherapyinpregnancy'above)
Studiesarereassuringregardingtherarityofadverseeffectsonhumanpregnancyoutcomeswithalbuterol
andinhaledglucocorticoids(especiallybudesonideandfluticasone).Reassuringanimalstudieshavebeen
reportedwith,ipratropium,nedocromil,zafirlukast,montelukast,andomalizumab,butpublishedexperience
inhumanpregnancywiththeseagentsismorelimited.Somereassuringhumangestationaldataexistfor
formoterolandsalmeterol.(See'Safetyofspecificmedications'above.)
Thegeneralprinciplesofpharmacologictherapyforasthmaduringpregnancyaresimilartothosein
nonpregnantpatientsandinvolveastepwiseapproach,asrecommendedbynationalandinternational
guidelines(figure1andtable3andtable4andtable7).(See'Maintainingasthmacontrol'aboveand"An
overviewofasthmamanagement".)
Afewmedicationpreferenceshavebeenidentifiedforasthmamanagementduringpregnancybasedon
greaterexperienceintreatingpatientswiththesemedications(see'Adjustmentstopharmacologictherapyin
pregnancy'above):
Forreliefofacuteasthmasymptoms,wesuggestusingtheshortactingbetaagonist(SABA)albuterol,
ratherthanotherSABAs(Grade2C).
Forpatientswhorequirealongtermcontrollerforasthma,wesuggestusingbudesonideasthe
preferredinhaledglucocorticoid(Grade2C).However,otherinhaledglucocorticoidscanbecontinuedif
thepatientwaswellcontrolledononeofthesemedicationspriortopregnancy.
Fortheinitialmanagementofmoderatepersistentasthma,wesuggestusingmediumdoseinhaled
glucocorticoids,duetothegreaterexperiencewithinhaledglucocorticoidsthanLABAsduring
pregnancy,ratherthanthecombinationoflowdoseinhaledglucocorticoidsplusalongactingbeta

agonist(LABA)(Grade2C).(See'Adjustmentstopharmacologictherapyinpregnancy'aboveand
"Treatmentofmoderatepersistentasthmainadolescentsandadults",sectionon'Preferredoptions'.)
Themanagementofacuteasthmaexacerbationsduringpregnancydoesnotdiffersubstantiallyfromthatof
nonpregnantpatientsandincludesinhaledshortactingbetaagonistalbuterol,inhaledipratropium,oralor
intravenousglucocorticoids,and,ifnecessary,intravenousmagnesiumsulfate(table6).Intensivemonitoring
ofbothmotherandfetusisessential.(See'Acuteexacerbations'above.)
Potentialareasofconcernhavebeenraisedwiththeuseofsystemicglucocorticoids,includingslightly
increasedrisksofcongenitalmalformations(primarilycleftpalate),preeclampsia,lowbirthweight,and
neonataladrenalinsufficiency.However,thesepotentialrisksofsystemicglucocorticoidsaresmallcompared
withthesubstantialrisktothemotherandfetusofsevere,uncontrolledasthma.Dosagesofglucocorticoids
fortreatmentofacuteasthmaexacerbationsinpregnancyarenotdifferentthanthosefornonpregnant
patients.(See'Oral/Systemicglucocorticoids'above.)
Fortherarepatientwhorequiresuseofasystemicbetaagonisttotreatasthma,wesuggestsubcutaneous
administrationofterbutalineratherthanepinephrine(table6)(Grade2C).Thisisbasedonaconcernabout
potentialuterinearteryvasoconstrictionwithsystemicadministrationofepinephrine(table6).(See
'Medications'above.)
Werecommendnotinitiatingallergenimmunotherapyduringpregnancy(Grade1B).However,allergen
immunotherapycanbecontinuedduringpregnancyinpatientsalreadyreceivingitwhoappeartobederiving
benefit,whoarenotpronetosystemicreactions,andwhoarereceivingamaintenanceconcentrationorat
leastasubstantialdosage.(See'Immunotherapyforallergicasthma'above.)
Forpharmacologicinductionoflaborandcontrolofpostpartumhemorrhageinpatientswithasthma,oxytocin
appearstobesafeinpregnancy.(See'Peripartumcare'aboveand"Managementofpostpartum
hemorrhageatvaginaldelivery",sectionon'Uterotonicdrugs'and"Inductionoflabor",sectionon'Oxytocin'.)
Forpatientswithasthmawhorequireprostaglandintreatmentforterminationofpregnancy,cervicalripening,
inductionoflabor,orcontrolofuterinehemorrhage,werecommendusingprostaglandinE1orE2,rather
thananalogsofprostaglandinF2alpha(Grade1B).Thisrecommendationisbasedontheriskof
bronchoconstrictionassociatedwiththelatteragent.(See'Peripartumcare'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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60.HodylNA,StarkMJ,OseiKumahA,etal.Fetalglucocorticoidregulatedpathwaysarenotaffectedby
inhaledcorticosteroiduseforasthmaduringpregnancy.AmJRespirCritCareMed2011183:716.
61.TegethoffM,GreeneN,OlsenJ,etal.Inhaledglucocorticoidsduringpregnancyandoffspringpediatric
diseases:anationalcohortstudy.AmJRespirCritCareMed2012185:557.
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study.AmJObstetGynecol1996175:150.
63.NationalAsthmaEducationandPreventionProgramExpertPanelExecutiveSummaryReport:Guidelines
fortheDiagnosisandManagementofAsthmaUpdateonSelectedTopics2002.NationalInstitutesof
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65.SarkarM,KorenG,KalraS,etal.Montelukastuseduringpregnancy:amulticentre,prospective,
comparativestudyofinfantoutcomes.EurJClinPharmacol200965:1259.

66.NelsenLM,ShieldsKE,CunninghamML,etal.Congenitalmalformationsamonginfantsborntowomen
receivingmontelukast,inhaledcorticosteroids,andotherasthmamedications.JAllergyClinImmunol2012
129:251.
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Topic554Version24.0

GRAPHICS
Oddsratios(95percentCI)foroutcomesofpregnancyinasthmaticvscontrol
womeninalargepopulationbasedstudy
Outcome

Allsubjects,n=36,985

Asthmamostsevere,n=1,396

Perinatalmortality

1.21(1.081.35)

1.28(0.762.17)

Preeclampsia

1.15(1.081.23)

1.42(1.091.86)

Pretermbirth(<37weeks)

1.15(1.091.21)

1.56(1.271.90)

Lowbirthweight(<2500gm)

1.21(1.141.29)

1.98(1.522.59)

Congenitalmalformations

1.05(0.991.10)

1.08(0.831.40)

FromKallen,B,Rydhstroem,H,Aberg,A.Asthmaduringpregnancyapopulationbasedstudy.EurJEpidem2000
16:167.
Graphic59809Version1.0

Drugratingsinpregnancy(USFoodandDrugAdministration)
Category
A

Interpretation
Controlledhumanstudiesshownorisk
Controlledstudiesinpregnantwomenfailtodemonstratearisktothefetusinthefirsttrimesterwith
noevidenceofriskinlatertrimesters.Thepossibilityoffetalharmappearsremote.

Noevidenceofriskinstudies
Eitheranimalreproductionstudieshavenotdemonstratedafetalriskbuttherearenocontrolled
studiesinpregnantwomenoranimalreproductionstudieshaveshownanadverseeffect(otherthan
adecreaseinfertility)thatwasnotconfirmedincontrolledstudiesinwomeninthefirsttrimesterand
thereisnoevidenceofariskinlatertrimesters.

Riskcannotberuledout
Eitherstudiesinanimalshaverevealedadverseeffectsonthefetus(teratogenicorembryocidal
effectsorother)andtherearenocontrolledstudiesinwomenorstudiesinwomenandanimalsare
notavailable.Drugsshouldbegivenonlyifthepotentialbenefitsjustifythepotentialrisktothefetus.

Positiveevidenceofrisk
Thereispositiveevidenceofhumanfetalrisk,butthebenefitsfromuseinpregnantwomenmaybe
acceptabledespitetherisk(eg,ifthedrugisneededinalifethreateningsituationorforaserious
diseaseforwhichsaferdrugscannotbeusedorareineffective).

Contraindicatedinpregnancy
Studiesinanimalsorhumanbeingshavedemonstratedfetalabnormalitiesorthereisevidenceoffetal
riskbasedonhumanexperience,orboth,andtheriskoftheuseofthedruginpregnantwomen
clearlyoutweighsanypossiblebenefit.Thedrugiscontraindicatedinwomenwhoareormaybecome
pregnant.

In2015,theUSFoodandDrugAdministration(FDA)beganoverseeingthephaseoutofpregnancyriskcategories(A,
B,C,D,andX)fromprescriptiondruglabelingandbeganrequiringinformationfromavailablehumanandanimal
studiesof(1)knownorpotentialmaternalorfetaladversereactionsand(2)doseadjustmentsneededduring
pregnancyandthepostpartumperiod.AdditionalinformationisavailableattheFDAwebsite:PregnancyandLactation
LabelingFinalRule.
Reproducedwithpermissionfrom:LexicompOnline.Copyright19782016Lexicomp,Inc.AllRightsReserved.
Graphic50021Version25.0

Stepwiseapproachformanagingasthmainyouths12yearsofageand
adults

Thestepwiseapproachismeanttoassist,notreplace,theclinicaldecisionmakingrequiredtomeet
individualpatientneeds.Ifalternativetreatmentisusedandresponseisinadequate,discontinueitanduse
thepreferredtreatmentbeforesteppingup.Zileutonisalessdesirablealternativeduetolimitedstudiesas
adjunctivetherapyandtheneedtomonitorliverfunction.Theophyllinerequiresmonitoringofserum
concentrationlevels.Instep6,beforeoralsystemicglucocorticoidsareintroduced,atrialofhighdoseICS
+LABA+eitherLTRA,theophylline,orzileutonmaybeconsidered,althoughthisapproachhasnotbeen
studiedinclinicaltrials.Step1,2,and3preferredtherapiesarebasedonevidenceAstep3alternative
therapyisbasedonevidenceAforLTRA,evidenceBfortheophylline,andevidenceDforzileuton.Step4
preferredtherapyisbasedonevidenceB,andalternativetherapyisbasedonevidenceBforLTRAand
theophyllineandevidenceDforzileuton.Step5preferredtherapyisbasedonevidenceB.Step6preferred
therapyisbasedon(EPR21997)andevidenceBforomalizumab.Immunotherapyforsteps2to4isbased
onevidenceBforhousedustmites,animaldanders,andpollensevidenceisweakorlackingformoldsand
cockroaches.Evidenceisstrongestforimmunotherapywithsingleallergens.Theroleofallergyinasthmais
greaterinchildrenthaninadults.Clinicianswhoadministerimmunotherapyoromalizumabshouldbe
preparedandequippedtoidentifyandtreatanaphylaxisthatmayoccur.
Alphabeticalorderisusedwhenmorethanonetreatmentoptionislistedwithineitherpreferred
oralternativetherapy.

SABA:inhaledshortactingbeta 2 agonistPRN:"asneeded"LTRA:leukotrienereceptorantagonistLABA:long
actinginhaledbeta 2 agonistEIB:exerciseinducedbronchospasm.
*Cromolynhaslimitedavailability.
Updatedandreproducedfrom:NationalHeart,Blood,andLungInstituteExpertPanelReport3(EPR3):
GuidelinesfortheDiagnosisandManagementofAsthma.NIHPublicationno.084051,2007.
Graphic56729Version7.0

Classifyingasthmaseverityandinitiatingtreatmentinyouthsgreaterthanor
equalto12yearsofageandadults
Classificationofasthmaseverity(12yearsofage)
Componentsofseverity

Persistent

Intermittent
Mild

Impairment
Normal
FEV 1 /FVC:
8to19years85
percent
20to39years80
percent
40to59years75
percent
60to80years70
percent

Severe

Symptoms

2days/week

>2days/weekbut
notdaily

Daily

Throughoutthe
day

Nighttime
awakenings

2x/month

3to4x/month

>1x/weekbutnot
nightly

Often7x/week

Shortacting
beta 2 agonist
useforsymptom
control(not
preventionof
EIB)

2days/week

>2days/weekbut
notdaily,andnot
morethan1xon
anyday

Daily

Severaltimesper
day

Interferencewith
normalactivity

None

Minorlimitation

Somelimitation

Extremelylimited

Lungfunction

NormalFEV 1
between
exacerbations

FEV 1 80
percentpredicted

FEV 1 >60but
<80percent
predicted

FEV 1 <60
percentpredicted

FEV 1 >80
percentpredicted

FEV 1 /FVC
normal

FEV 1 /FVC
normal
Risk

Moderate

Exacerbations
requiringoral
systemic
glucocorticoids

0to1/year(see
footnote)

FEV 1 /FVC
reduced5
percent

FEV 1 /FVC
reduced>5
percent

2/year(seefootnote)

Considerseverityandintervalsincelastexacerbation
Frequencyandseveritymayfluctuateovertimeforpatientsinany
severitycategory
RelativeannualriskofexacerbationsmayberelatedtoFEV 1

Recommendedstepforinitiating
treatment

Step1

Step2

Step3

Step4or5

Andconsidershortcourseoforal
systemicglucocorticoids
Intwotosixweeks,evaluatelevelofasthmacontrolthatisachievedand
adjusttherapyaccordingly.

Assessingseverityandinitiatingtreatmentforpatientswhoarenotcurrentlytakinglongtermcontrol
medications.Thestepwiseapproachismeanttoassist,notreplace,theclinicaldecisionmakingrequiredtomeet
individualpatientneeds.Levelofseverityisdeterminedbyassessmentofbothimpairmentandrisk.Assess
impairmentdomainbypatient's/caregiver'srecallofprevioustwotofourweeksandspirometry.Assignseveritytothe
mostseverecategoryinwhichanyfeatureoccurs.Atpresent,dataareinadequatetocorrelatefrequenciesof
exacerbationswithdifferentlevelsofasthmaseverity.Ingeneral,morefrequentandintenseexacerbations(eg,
requiringurgent,unscheduledcare,hospitalization,orICUadmission)indicategreaterunderlyingdiseaseseverity.For
treatmentpurposes,patientswhohad2exacerbationsrequiringoralsystemicglucocorticoidsinthepastyearmay
beconsideredthesameaspatientswhohavepersistentasthma,evenintheabsenceofimpairmentlevelsconsistent
withpersistentasthma.
FEV 1 :forcedexpiratoryvolumeinonesecondFVC:forcedvitalcapacityICU:intensivecareunit.
Reproducedfrom:NationalHeart,Blood,andLungInstituteExpertPanelReport3(EPR3):GuidelinesfortheDiagnosisand
ManagementofAsthma.NIHPublicationno.084051,2007.

Graphic58247Version3.0

Assessingasthmacontrolandadjustingtherapyinyouthsgreaterthanorequalto
12yearsofageandadults
Classificationofasthmacontrol(12yearsofage)
Componentsofcontrol
Wellcontrolled
Impairment

Verypoorly
controlled

Notwellcontrolled

Symptoms

2days/week

>2days/week

Throughouttheday

Nighttimeawakenings

2x/month

1to3x/week

4x/week

Interferencewith
normalactivity

None

Somelimitation

Extremelylimited

Shortactingbeta 2
agonistusefor
symptomcontrol(not
preventionofEIB)

2days/week

>2days/week

Severaltimesperday

FEV 1 orpeakflow

>80percent
predicted/personal
best

60to80percent
predicted/personal
best

<60percent
predicted/personal
best

ATAQ

1to2

3to4

ACQ

0.75*

1.5

N/A

ACT

20

1619

15

Exacerbations
requiringoral
systemic
glucocorticoids

0to1/year

2/year(seefootnote)

Progressivelossof
lungfunction

Evaluationrequireslongtermfollowupcare

Treatmentrelated
adverseeffects

Medicationsideeffectscanvaryinintensityfromnonetovery
troublesomeandworrisome.Thelevelofintensitydoesnotcorrelate
tospecificlevelsofcontrolbutshouldbeconsideredintheoverall
assessmentofrisk.

Validatedquestionnaires

Risk

Recommendedactionfortreatment

Considerseverityandintervalsincelastexacerbation

Maintaincurrent
step
Regularfollowups
everyonetosix
monthstomaintain
control
Considerstepdown
ifwellcontrolledfor
atleastthreemonths

Stepup1stepand
Reevaluateintwoto
sixweeks
Forsideeffects,
consideralternative
treatmentoptions

Considershort
courseoforal
systemic
glucocorticoids,
Stepup1to2
steps,and
Reevaluateintwo
weeks
Forsideeffects,
consideralternative
treatmentoptions

Thestepwiseapproachismeanttoassist,notreplace,theclinicaldecisionmakingrequiredtomeetindividualpatient
needs.Thelevelofcontrolisbasedonthemostsevereimpairmentorriskcategory.Assessimpairmentdomainby
patient'srecallofprevioustwotofourweeksandbyspirometry/orpeakflowmeasures.Symptomassessmentfor
longerperiodsshouldreflectaglobalassessment,suchasinquiringwhetherthepatient'sasthmaisbetterorworse
sincethelastvisit.Atpresent,dataareinadequatetocorrelatefrequenciesofexacerbationswithdifferentlevelsof
asthmacontrol.Ingeneral,morefrequentandintenseexacerbations(eg,requiringurgent,unscheduledcare,
hospitalization,orICUadmission)indicatepoorerdiseasecontrol.Fortreatmentpurposes,patientswhohad>2
exacerbationsrequiringoralsystemicglucocorticoidsinthepastyearmaybeconsideredthesameaspatientswho
havenotwellcontrolledasthmaevenintheabsenceofimpairmentlevelsconsistentwithnotwellcontrolledasthma.

Validatedquestionnairesfortheimpairmentdomain(thequestionnairesdonotassesslungfunctionor
theriskdomain):
ATAQ:AsthmaTherapyAssessmentQuestionnaire
ACQ:AsthmaControlQuestionnaire(userpackagemaybeobtainedatwww.qoltech.co.ukorjuniper@qoltech.co.uk)
ACT:AsthmaControlTest
Minimalimportantdifference:1.0fortheATAQ0.5fortheACQnotdeterminedfortheACT.
Beforestepupintherapy:
Reviewadherencetomedication,inhalertechnique,environmentalcontrol,andcomorbidconditions.
Ifanalternativetreatmentoptionwasusedinastep,discontinueandusethepreferredtreatmentforthatstep.
EIB:exerciseinducedbronchospasmFEV 1 :forcedexpiratoryvolumeinonesecondICU:intensivecareunitN/A:not
applicable.
*ACQvaluesof0.76to1.4areindeterminateregardingwellcontrolledasthma.
Reproducedfrom:NationalHeart,Blood,andLungInstituteExpertPanelReport3(EPR3):GuidelinesfortheDiagnosisand
ManagementofAsthma.NIHPublicationno.084051,2007.
Graphic53233Version5.0

Longactingbronchodilators:Implicationsforpregnancyandlactation

Agent

Adverseevents
inanimal
studies

Humandata

Crosses
placenta

Excretedin
humanmilk

Longactingbetaagonists*
Salmeterol

Limiteddatasuggest
safety

Observedinsome
studies

Unknown

Formoterol

Limiteddatasuggest
safety

Observedinsome
studies

Unknown

Indacaterol

No

Unknown

Olodaterol

Yes

Unknown,butlikely

Vilanterol

No

Unknown

Longactinganticholinergicagents
Aclidinium

Yes

Notknown

Probable

Glycopyrrolate

Yes

Smallamounts

Yes

Tiotropium

Yes

Notknown

Notknown

Umeclidinium

Negligiblesystemic
absorptionfollowing
oralinhalation

Notknown

Dataobtainedfrompackageinserts.RefertotheUpToDatetopiconthemanagementofasthmainpregnancyfor
additionalinformation.
*Longactingbetaagonists(LABAs)shouldbeusedforasthmaincombinationwithinhaledglucocorticoids,andnotas
monotherapy.LABAshavethepotentialtodecreaseuterinecontractility,ifadministeredduringlabor.LABAsarenot
consideredacontraindicationtobreastfeeding,whennecessarytocontrolasthma.
NotapprovedbytheUSFoodandDrugAdministrationforuseinasthma.
Approvedforuseinasthmainthecombinationpreparationfluticasonevilanterol.
Graphic109891Version1.0

Pharmacologicmanagementofacuteasthmaexacerbationsduringpregnancy
1.Beta 2 agonistbronchodilator(nebulizedormetereddoseinhaler)
AlbuterolbyMDI4to8puffsevery20minutesupto1hour,thenevery1to4hours,asneeded
Albuterolbynebulizer0.083percent(2.5mg/3mL),2.5to5mgevery20minutesfor3dosesandthen2.5to5mgevery1to4
hours,asneeded
Albuterolbycontinuousnebulization,administering10to15mgperhour

2.Ipratropium
Bynebulizer,500mcgevery20minutesfor3doses,thenasneeded.Canbegivensimultaneouslywithbeta 2 agonist.
ByMDI,4to8inhalationsevery20minutesfor3doses,thenasneeded

3.Systemicglucocorticoids(forthosewithapoorresponsetotreatmentafteronehour,orwithinitialtherapyfor
patientsonchronicoralglucocorticoids)
Forpatientswhocanbemanagedathome:prednisone40to60mgperdayinasingleordivideddose
Forpatientswhorequirehospitalization:prednisone40to80mgdailyinasingleordivideddose(ortheequivalentdoseof
methylprednisolone*intravenously)untilpeakflowreaches70percentofpredictedorpersonalbest,andthentaperaspatient
improves
Forpatientswhohavealifethreateningexacerbation,ahigherinitialdoseofmethylprednisolone*,60to80mgevery6to12
hours,maybegivenintravenously,andthentaperedasthepatientimproves,asabove

4.Forpatientsnotrespondingtoabovetherapies,consideradjuncttherapies
Intravenousmagnesiumsulfate2ginfusedover20minutes,inabsenceofrenalinsufficiency
Subcutaneousterbutaline0.25mgevery20minutesforupto3doses

MDI:metereddoseinhaler.
*AconversioncalculatorisavailableinUpToDate.Refertothecalculatoroncorticosteroidmedicationdosingconversions
(glucocorticoideffect).
Forpatientswithrenalinsufficiency,abaselineserummagnesiumlevelisassessed.Thedecisiontouseintravenous
magnesiumrequiresconsiderationofthepotentialbenefitintermsofasthmaandtheanticipatedriskofhypermagnesemia
basedonthedegreeofrenalinsufficiencyandbaselineserummagnesiumlevel.
Adaptedfrom:NationalAsthmaEducationandPreventionProgram:ExpertpanelreportIII:Guidelinesforthediagnosisand
managementofasthma.Bethesda,MD:NationalHeart,Lung,andBloodInstitute,2007.(NIHpublicationno.084051)
www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm(AccessedonMay12,2011).
Graphic67529Version9.0

Preferredpharmacologicsteptherapyofasthmaduringpregnancy:NAEPPupdate
2004
Category

Steptherapy

Mildintermittent

Inhaledshortactingbeta2agonist*asneeded(forallcategories)

Mildpersistent

Lowdoseinhaledglucocorticoid

Moderatepersistent

Mediumdoseinhaledglucocorticoid
OR
Lowdoseinhaledglucocorticoid pluslongactingbetaagonist
OR
Mediumdoseinhaledglucocorticoid pluslongactingbetaagonist ,ifneeded

Severepersistent

Highdoseinhaledglucocorticoid pluslongactingbetaagonist
Prednisoneifneeded

*Albuterolispreferredinhaledshortactingbeta2agonistduringpregnancy.
Budesonideispreferredinhaledcorticosteroidduringpregnancy.
Salmeterolispreferredlongactingbetaagonistduringpregnancy.
Basedondatafrom:QuickReference.NAEPPExpertPanelReportManagingAsthmaDuringPregnancy:Recommendations
forPharmacologicTreatmentUpdate2004.USDeptofHealthandHumanServices,Bethesda,MD.NIHPublicationNo.04
5246,March,2004.
Graphic55513Version6.0

ContributorDisclosures
MichaelSchatz,MD,MS Grant/Research/ClinicalTrialSupport:AstraZeneca[Asthma,rhinitis(Budesonide)]
Merck[Asthma(Montelukast)]GlaxoSmithKline[Asthma,rhinitis(Salmeterol,fluticasone)].Consultant/Advisory
Boards:Amgen[Asthma]BostonScientific[Asthma(Bronchialthermoplasty)]. StevenEWeinberger,
MD Nothingtodisclose BruceSBochner,MD Grant/Research/ClinicalTrialSupport:NIAIDNHLBIDixon
award(internalNorthwesternUniversitySchoolofMedicinegrant)[Siglec8,Siglec9,asthma,COPD,
anaphylaxis,imaging,eosinophilicgranulomatosiswithpolyangiitismastocytosis(Mepolizumab)].
Consultant/AdvisoryBoards:AstraZenecaTEVAAllakos[Eosinophilassociateddisease(Reslizumab,
benralizumab)].PatentHolder:Siglec8anditsligandantiSiglec8antibodies[Eosinophilandmastcell
associateddisease(AK001andAK002[inclinicaltrialsnotyetFDAapproved])].Employment:Northwestern
UniversityFeinbergSchoolofMedicine[AllergyandImmunology].EquityOwnership/StockOptions:
GlycoMimeticsAllakos[Eosinophilandmastcellassociateddiseases(AK001andAK002[inclinicaltrialsnot
yetFDAapproved])].OtherFinancialInterest:Elsevier[Publicationroyalties(AllergyandImmunology)]. Charles
JLockwood,MD,MHCM Consultant/AdvisoryBoards:Celula[Aneuploidyscreening(Nocurrentproductsor
drugsintheUS)]. HelenHollingsworth,MD Nothingtodisclose
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconformto
UpToDatestandardsofevidence.
Conflictofinterestpolicy