GUIAS HEMORRAGIA POSPARTO

WHO recommendations for the prevention and treatment of postpartum haemorrhage

For more information, please contact:

Department of Reproductive Health and Research World Health Organization Avenue Appia 20, CH-1211 Geneva 27 Switzerland Fax: +41 22 791 4171 E-mail: [email protected] www.who.int/reproductivehealth

Maternal, Newborn, Child and Adolescent HealthE-mail: [email protected]/maternal_child_adolescent

WHO Library Cataloguing-in-Publication Data

WHO recommendations for the prevention and treatment of postpartum haemorrhage.

1.Postpartum hemorrhage prevention and control. 2.Postpartum hemorrhage therapy. 3.Obstetric labor complications. 4.Guideline. I.World Health Organization.

ISBN9789241548502 (NLMclassification:WQ330)

World Health Organization 2012

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Contents

Acknowledgements 1

Abbreviations 2

Executive summary 3

BoxA: RecommendationsforthepreventionofPPH 5

BoxB: RecommendationsforthetreatmentofPPH 6

BoxC: Recommendationsonorganizationofcare 7

1. Background 8

2. Methods 9

3. Results 12

Box1: RecommendationsforthepreventionofPPHuterotonics 15

Box2: RecommendationsforthepreventionofPPHcordmanagement anduterinemassage 16

Table1:Recommendationstatusoftheindividualcomponentsof theactivemanagementofthethirdstageoflabour,basedonwho delivers the intervention 18

Box3: RecommendationsforthepreventionofPPHincaesareansections 18

Box4: RecommendationsforthetreatmentofPPHuterotonics 19

Box5: RecommendationsforthetreatmentofPPHfluidresuscitation andtranexamicacid 19

Box6: RecommendationsforthetreatmentofPPHmanoeuvresand other procedures 20

Box7: Recommendationsforthetreatmentofretainedplacenta 21

Box8: HealthSystemsandOrganizationofCarerecommendations 22

Box9: Statementsrelatedtotopicsforwhichthereisinsufficient evidence to issue a recommendation 23

4. Research implications 24

5. Dissemination and implementation of the guideline 25

6. Applicability issues 26

7. Updating the guideline 27

References 27

Annex 1. External experts, WHO staff involved in the preparation of the guideline, and summary of declarations of interest 29

Annex 2. Critical outcomes for decision making 33

Annex 3: Summary of the considerations related to the strength of the recom-mendations (Balance Worksheets) 34

Box1. Summaryofconsiderationsrelatedtothestrengthof therecommendations(Recommendations15) 34

Thestandardizedcriteriausedingradingtheevidence,thenarrativesummariesofevidence and GRADE tables are not included in this document. This material has been published in a separate document entitled WHO recommendations for postpartum haemorrhage: evidence baseandcanbeaccessedonlineat:www.who.int/reproductivehealth/publications/maternal_perinatal_health/9789241548502/en/







Box8. Templateforthesummaryofconsiderationsrelatedto thestrengthoftherecommendationswithexplanationsfor completing the template 41


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AcknowledgementsWorkonthisguidelinewasinitiatedbyA.MetinGlmezogluandJooPauloSouza,oftheWHODepartmentofReproductiveHealthandResearch,andbyMatthewsMathai,oftheWHODepartmentofMaternal,Newborn,ChildandAdolescentHealth.JooPauloSouzacoordinatedthedevelopmentofthepresentguidelineanddraftedthisdocument.EdgardoAbalosandVirginiaDiaz,oftheCentroRosarinodeEstudiosPerinatales(CREP),Rosario,Argentina,reviewedthescientificevidencerelatedtothepreventionandtreatmentofPostpartumHaemorrhage(PPH)andproducedtheGRADEtablesusedinthisguideline.NatashaHezelgrave,oftheAcademicWomensHealthCentre,KingsCollegeLondon(KCL),UnitedKingdom(UK),draftedthenar-rativesummariesofevidence.TheGRADEtablesweredouble-checkedbyKanokwa-roonWatananirun(Fon)oftheUniversityofBangkok,Thailand.A.MetinGlmezo-glu,MatthewsMathaiandEdgardoAbaloscommentedonthedraftdocumentbeforeit was reviewed by Natasha Hezelgrave and participants at the WHO Technical ConsultationonthePreventionandTreatmentofPPH(seeAnnex1).

ThankstoZahidaQureshi,oftheUniversityofNairobi,Kenya,forservingastheChairpersonoftheTechnicalConsultation.Weacknowledgegratefullythevaluablefeedbackgivenbyalargenumberofinternationalstakeholdersduringtheonlineconsultationwhichtookplaceaspartofthisprocess.

WHOisgratefulforthecontinuedsupportoftheUnitedStatesAgencyforInter-nationalDevelopment(USAID)inthisareaofwork.SpecialthanksarealsoduetoGynuityHealthProjectsforprovidingadditionalfinancialsupportforthisguidelinework.WHOalsowishestothanktheauthorsofthesystematicreviewsusedinthisguideline for their assistance and collaboration in updating them. WHO is also grate-fultotheCochranePregnancyandChildbirthGroup,especiallythestaffattheirLiverpoolofficeintheUnitedKingdom,fortheirsupportinupdatingtheCochranereviews.


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AbbreviationsAGREE Appraisal of Guidelines Research and Evaluation

AMTSL Active Management of the Third Stage of Labour

CCT Controlled Cord Traction

CI ConfidenceInterval

GREAT Guidelinedevelopment,Researchpriorities,Evidencesynthesis, Applicabilityofevidence,Transferofknowledge(aWHOproject)

GDG Guideline Development Group

GRADE GradingofRecommendationsAssessment,DevelopmentandEvaluation

HIV Humanimmunodeficiencyvirus

IM Intramuscular

IU InternationalUnit

IV Intravenous

MCA Maternal,ChildandAdolescentDepartment

g Microgram

MMR Maternal Mortality Ratio

PICO Population,Interventions,Comparisons,andOutcomes

PO PerOs(orally)

PPH Postpartum Haemorrhage

RCT Randomized Controlled Trial

RevMan ReviewManager(software)

RR RelativeRisk

OR Odds Ratio

USAID UnitedStatesAgencyforInternationalDevelopment


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Executive summaryIntroductionPostpartumHaemorrhage(PPH)iscommonlydefinedasabloodlossof500mlormore within 24 hours after birth. PPH is the leading cause of maternal mortality in low-income countries and the primary cause of nearly one quarter of all maternal deathsglobally.MostdeathsresultingfromPPHoccurduringthefirst24hoursafterbirth:themajorityofthesecouldbeavoidedthroughtheuseofprophylacticutero-tonics during the third stage of labour and by timely and appropriate management.

Improving health care for women during childbirth in order to prevent and treat PPH is an essential step towards the achievement of the Millennium Development Goals. The primary objective of this guideline therefore is to provide a foundation for the strategic policy and programme development needed to ensure the sustainable implementation of effective interventions for reducing the global burden of PPH.

Guideline development methodsThe procedures used in the development of this guideline are outlined in the WHO handbook for guideline development1.Briefly,theseproceduresare:(i)theidenti-ficationofquestionsrelatedtoclinicalpracticeandhealthpolicyforwhichanswersareneeded,(ii)theretrievalofup-to-dateresearch-basedevidence,(iii)theas-sessmentandsynthesisofevidence,(iv)theformulationofrecommendationsusinginputfromawiderangeofstakeholders,and(v)theformulationofplansforthedissemination,implementation,impactevaluationandupdatingoftheguideline.

ThescientificevidencefortherecommendationswassynthesizedusingtheGradingofRecommendationsAssessment,DevelopmentandEvaluation(GRADE)methodol-ogy.ForeachofthepreviousWHOrecommendationsonPPH(2007and2009)andforallthenewly-addedquestions,evidenceprofileswerepreparedbasedon22up-to-date systematic reviews. The revised and new recommendations were devel-opedandadoptedbyaninternationalgroupofexpertswhoparticipatedintheWHOTechnicalConsultationonthePreventionandTreatmentofPPH,heldinMontreux,Switzerland,68March2012.

The WHO Technical Consultation adopted 32 recommendations and these are shown inBoxesA,BandC.Foreachrecommendation,thequalityofthesupportingevi-denceisgradedasverylow,low,moderateorhigh.Thecontributingstake-holdersqualifiedthestrengthoftheserecommendationsbytakingthequalityoftheevidence and other factors into account (including the values and preferences of stakeholders,themagnitudeofeffect,thebalanceofbenefitsversusdisadvantages,resourceusage,andthefeasibilityofeachrecommendation).Toensurethateachrecommendationiscorrectlyunderstoodandusedinpractice,additionalremarkshavealsobeenincluded,andthesearenotedinthefulldocumentbelowtherecom-mendations.Readersshouldrefertotheseremarksinthefullversionoftheguide-line if they are in any doubt about the meaning of each recommendation.

1 WHO handbook for guideline development.Geneva,WorldHealthOrganization,2012.


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Recommendations for PPH preventionThe intrinsic contribution of each component of the active management of the thirdstageoflabourwasexaminedinlightofnewavailableevidence,andrelevantrecommendations were made. All women giving birth should be offered uterotonics duringthethirdstageoflabourforthepreventionofPPH;oxytocin(IM/IV,10IU)is recommended as the uterotonic drug of choice. Other injectable uterotonics and misoprostol are recommended as alternatives for the prevention of PPH in settings whereoxytocinisunavailable.Theimportanceofcontrolledcordtraction(CCT)wasrevisited because of new evidence. This intervention is now regarded as optional insettingswhereskilledbirthattendantsareavailable,andiscontraindicatedinsettingswhereskilledattendantsdonotassistwithbirths.Earlycordclampingisgenerally contraindicated. Continuous uterine massage is not recommended as an interventiontopreventPPHinwomenwhohavereceivedprophylacticoxytocin,asitmaycausematernaldiscomfort,requireadedicatedhealthprofessional,andmaynotleadtoareductionofbloodloss.However,surveillanceofuterinetonusthroughabdominalpalpationisrecommendedinallwomenforearlyidentificationofpostpartumuterineatony.Insummary,theGuidelineDevelopmentGroup(GDG)considered the use of uterotonics as the main intervention within the active man-agementofthirdstageoflabourpackage.Inthiscontext,theuseofmisoprostolforthepreventionofPPHbycommunityhealthcareworkersandlayhealthworkersissupportedinsettingswhereskilledbirthattendantsarenotpresent.

The GDG also issued recommendations for reducing blood loss during the third stage oflabourincaesareansections.Oxytocinistherecommendeduterotonicdrugforthe prevention of PPH in caesarean sections. Cord traction is recommended in pref-erence to manual removal when assisting placental delivery in caesarean sections.

Recommendations for PPH treatmentTheuseofuterotonics(oxytocinaloneasthefirstchoice)playsacentralroleinthetreatmentofPPH.UterinemassageisrecommendedforthetreatmentofPPHassoonasitisdiagnosed,andinitialfluidresuscitationwithisotoniccrystalloidsisrecommended.Theuseoftranexamicacidisadvisedincasesofrefractoryatonicbleeding or persistent trauma-related bleeding. The use of intrauterine balloon tamponade is recommended for refractory bleeding or if uterotonics are unavail-able.Bimanualuterinecompression,externalaorticcompression,andtheuseofnon-pneumaticanti-shockgarmentsarerecommendedastemporizingmeasuresuntilsubstantive care is available. If there is persistent bleeding and the relevant re-sourcesareavailable,uterinearteryembolizationshouldbeconsidered.Ifbleedingpersists,despitetreatmentwithuterotonicdrugsandotherconservativeinterven-tions,surgicalinterventionshouldbeusedwithoutfurtherdelay.

Ifthethirdstageoflabourlastsmorethan30minutes,CCTandIV/IMoxytocin(10IU)shouldbeusedtomanagetheretainedplacenta.Iftheplacentaisretainedandbleedingoccurs,themanualremovaloftheplacentashouldbeexpedited.Wheneverthemanualremovaloftheplacentaisundertaken,asingledoseofpro-phylactic antibiotics is recommended.

The GDG also issued recommendations related to the organization of PPH care. Health facilities delivering maternity services should adopt formal protocols for the prevention and treatment of PPH and for patient referral. The use of PPH treatment


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simulations for pre-service and in-service training programmes was recommended. Finally,theGDGrecommendedthattheuseofuterotonicsforthepreventionofPPHshouldbemonitoredandaspecificindicatorwassuggested.

Box A: Recommendations for the prevention of PPH

1. The use of uterotonics for the prevention of PPH during the third stage of labour is recom-mendedforallbirths.(Strongrecommendation,moderate-qualityevidence)

2. Oxytocin(10IU,IV/IM)istherecommendeduterotonicdrugforthepreventionofPPH.(Strongrecommendation,moderate-qualityevidence)

3. Insettingswhereoxytocinisunavailable,theuseofotherinjectableuterotonics(ifappro-priateergometrine/methylergometrineorthefixeddrugcombinationofoxytocinandergo-metrine)ororalmisoprostol(600 g)isrecommended.(Strongrecommendation,moderate-qualityevidence)

4. Insettingswhereskilledbirthattendantsarenotpresentandoxytocinisunavailable,theadministrationofmisoprostol(600 gPO)bycommunityhealthcareworkersandlayhealthworkersisrecommendedforthepreventionofPPH.(Strongrecommendation,moderate-qualityevidence)

5. Insettingswhereskilledbirthattendantsareavailable,CCTisrecommendedforvaginalbirths if the care provider and the parturient woman regard a small reduction in blood loss andasmallreductioninthedurationofthethirdstageoflabourasimportant(Weakrecom-mendation,high-qualityevidence)

6. Insettingswhereskilledbirthattendantsareunavailable,CCTisnotrecommended.(Strongrecommendation,moderate-qualityevidence)

7. Latecordclamping(performedafter1to3minutesafterbirth)isrecommendedforallbirthswhileinitiatingsimultaneousessentialnewborncare.(Strongrecommendation,moderate-qualityevidence)

8. Earlycordclamping(


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Box B: Recommendations for the treatment of PPH

13. IntravenousoxytocinaloneistherecommendeduterotonicdrugforthetreatmentofPPH.(Strongrecommendation,moderate-qualityevidence)

14. Ifintravenousoxytocinisunavailable,orifthebleedingdoesnotrespondtooxytocin,theuseofintravenousergometrine,oxytocin-ergometrinefixeddose,oraprostaglandindrug(includ-ingsublingualmisoprostol,800g)isrecommended.(Strongrecommendation,low-qualityevidence)

15. The use of isotonic crystalloids is recommended in preference to the use of colloids for the initialintravenousfluidresuscitationofwomenwithPPH.(Strongrecommendation,low-qual-ityevidence)

16.TheuseoftranexamicacidisrecommendedforthetreatmentofPPHifoxytocinandotheruterotonics fail to stop bleeding or if it is thought that the bleeding may be partly due to trauma.(Weakrecommendation,moderate-qualityevidence)

17. UterinemassageisrecommendedforthetreatmentofPPH.(Strongrecommendation,very-low-qualityevidence)

18. Ifwomendonotrespondtotreatmentusinguterotonics,orifuterotonicsareunavailable,the use of intrauterine balloon tamponade is recommended for the treatment of PPH due to uterineatony.(Weakrecommendation,very-low-qualityevidence)

19. Ifothermeasureshavefailedandifthenecessaryresourcesareavailable,theuseofuter-inearteryembolizationisrecommendedasatreatmentforPPHduetouterineatony.(Weakrecommendation,very-low-qualityevidence)

20. If bleeding does not stop in spite of treatment using uterotonics and other available conserva-tiveinterventions(e.g.uterinemassage,balloontamponade),theuseofsurgicalinterven-tionsisrecommended.(Strongrecommendation,very-low-qualityevidence)

21. The use of bimanual uterine compression is recommended as a temporizing measure until ap-propriate care is available for the treatment of PPH due to uterine atony after vaginal deliv-ery.(Weakrecommendation,very-low-qualityevidence)

22. TheuseofexternalaorticcompressionforthetreatmentofPPHduetouterineatonyaftervaginal birth is recommended as a temporizing measure until appropriate care is available. (Weakrecommendation,very-low-qualityevidence)

23. Theuseofnon-pneumaticanti-shockgarmentsisrecommendedasatemporizingmeasureuntilappropriatecareisavailable.(Weakrecommendation,low-qualityevidence)

24. TheuseofuterinepackingisnotrecommendedforthetreatmentofPPHduetouterineatonyaftervaginalbirth.(Weakrecommendation,very-low-qualityevidence)

25. Iftheplacentaisnotexpelledspontaneously,theuseofIV/IMoxytocin(10IU)incombina-tionwithcontrolledcordtractionisrecommended.(Weakrecommendation,very-low-qualityevidence)

26.The use of ergometrine for the management of retained placenta is not recommended as this maycausetetanicuterinecontractionswhichmaydelaytheexpulsionoftheplacenta.(Weakrecommendation,very-low-qualityevidence)

27. TheuseofprostaglandinE2alpha(dinoprostoneorsulprostone)forthemanagementofre-tainedplacentaisnotrecommended.(Weakrecommendation,very-low-qualityevidence)

28. Asingledoseofantibiotics(ampicillinorfirst-generationcephalosporin)isrecommendedifmanualremovaloftheplacentaispractised.(Weakrecommendation,very-low-qualityevi-dence)


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Box C: Organization of care

29. The use of formal protocols by health facilities for the prevention and treatment of PPH is recommended.(Weakrecommendation,moderate-qualityevidence)

30. The use of formal protocols for referral of women to a higher level of care is recommended forhealthfacilities.(Weakrecommendation,very-low-qualityevidence)

31. The use of simulations of PPH treatment is recommended for pre-service and in-service train-ingprogrammes.(Weakrecommendation,very-low-qualityevidence)

32. Monitoring the use of uterotonics after birth for the prevention of PPH is recommended as aprocessindicatorforprogrammaticevaluation.(Weakrecommendation,very-low-qualityevidence)


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1. BackgroundPostpartumHaemorrhage(PPH)iscommonlydefinedasabloodlossof500mlormorewithin24hoursafterbirth,whileseverePPHisdefinedasabloodlossof1000mlormorewithinthesametimeframe.PPHaffectsapproximately2%ofallwomenwhogivebirth:itisassociatednotonlywithnearlyonequarterofallma-ternal deaths globally but is also the leading cause of maternal mortality in most low-incomecountries.PPHisasignificantcontributortoseverematernalmorbidityand long-term disability as well as to a number of other severe maternal conditions generallyassociatedwithmoresubstantialbloodloss,includingshockandorgandys-function.(13)

UterineatonyisthemostcommoncauseofPPH,butgenitaltracttrauma(i.e.vagi-nalorcervicallacerations),uterinerupture,retainedplacentaltissue,ormaternalcoagulation disorders may also result in PPH. Although the majority of women who experiencePPHcomplicationshavenoidentifiableclinicalorhistoricalriskfactors,grandmultiparityandmultiplegestationareassociatedwithanincreasedriskofbleedingafterbirth.PPHmaybeaggravatedbypre-existinganaemiaand,insuchinstances,thelossofasmallervolumeofbloodmaystillresultinadverseclinicalsequelae.(4)

Duringthesecondhalfofthe20thcentury,apackageofinterventionsperformedduring the third stage of labour became the cornerstone for the prevention of PPH.Thisapproachbecameknownastheactivemanagementofthethirdstageoflabourandconsistedinitiallyofthefollowingcomponents:theadministrationofaprophylacticuterotonicafterthedeliveryofababy,earlycordclampingandcutting,andthecontrolledtractionoftheumbilicalcord.Uterinemassageisalsofrequently included as part of the active management of the third stage of labour. In contrast to activemanagement,expectant management involves instead waiting for signs of placenta separation and allows for the placenta to be delivered sponta-neously,oraidedbynipplestimulationorgravity.Comparedwithexpectantman-agement,theactivemanagementofthethirdstageoflabourisassociatedwithasubstantialreductionintheoccurrenceofPPH.(5)

ItisgenerallyassumedthatbypreventingandtreatingPPH,mostPPH-associateddeaths could be avoided. The prevention and treatment of PPH are therefore vital steps towards improving the health care of women during childbirth and the achievementoftheMillenniumDevelopmentGoals.Toreachtheseobjectives,healthworkersindevelopingcountriesshouldbegivenaccesstoappropriatemedi-cations and be trained in procedures relevant to the management of PPH. Countries also need evidence-based guidance to inform their health policies and improve their health outcomes.

Giventheavailabilityofnewscientificevidencerelatedtothepreventionandtreat-mentofPPH,theaimofthisdocumentistorevisepreviousWHOrecommendationsfor the prevention and treatment of PPH and to add new recommendations. The primary goal of this guideline is to provide a foundation for the implementation of strategic policy and programme developments for interventions shown to have been effective in reducing the burden of PPH. Health professionals responsible for de-veloping national and local protocols and health policies constitute the main target audienceofthisdocument.Obstetricians,midwives,generalmedicalpractitioners,healthcaremanagersandpublichealthpolicy-makers,particularlyinunder-re-


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sourced settings are also targeted. The guidance provided is evidence-informed and covers topics related to the management of PPH that were selected and prioritized byaninternational,multidisciplinarygroupofhealthcareworkers,consumersandotherstakeholders.ThisdocumentestablishesgeneralprinciplesofPPHcareanditis intended to inform the development of protocols and health policies related to PPH. This document is not intended to provide a comprehensive practical guide for the prevention and treatment of PPH.

2. MethodsThis guideline is an update of the WHO recommendations for the prevention of PPH published in 2007 and the WHO guidelines for the management of PPH and retained placentapublishedin2009(6,7).ThisdocumentrepresentsWHOsnor-mative support for using evidence-informed policies and practices in all countries. TheguidelineformspartofaWHOknowledge-to-actionprojectentitledGREAT(Guidelinedevelopment,Researchpriorities,Evidencesynthesis,Applicabilityofevidence,Transferofknowledge)(8)andwasdevelopedusingstandardizedoperat-ing procedures in accordance with the process described in the WHO handbook for guideline development (9).Insummary,theprocessincluded:(i) theidentificationofcriticalquestionsandcriticaloutcomes,(ii) theretrievaloftheevidence,(iii)theassessmentandsynthesisofevidence,(iv) theformulationofrecommendations,and(v) planningforthedissemination,implementation,impactevaluationandupdatingof the guideline.

Twotechnicalgroupshaveworkedinthedevelopmentofthisguideline.AsmalloperativegroupcomposedofstafffromtheWHOsDepartmentofReproductiveHealthandResearch,andDepartmentofMaternal,Newborn,ChildandAdolescentHealth(MCA),aswellastwoexternalexperts(seeAnnex1Theguidelinesteer-inggroup)andalargergroupwithinternationalstakeholdersincludingmidwives,obstetricians,neonatologists,researchers,expertsinresearchsynthesis,expertsinhealthcareprogrammes,andconsumerrepresentatives(theGuidelineDevelopmentGroupGDG).Theguidelinesteeringgroupwasformedintheverybeginningoftheproject and reviewed the previous WHO guidelines on prevention and treatment of PPH(6,7).ThisgrouppreparedalistofpotentialadditionalquestionsrelatedtothepreventionandtreatmentofPPH.Next,theGDGreviewedandprioritizedthedraftquestions. The guideline steering group then produced a list of all the questions to be addressed. This included both questions from the earlier versions of the guideline as well as new ones. The guideline steering group also adopted the outcomes used inthe2007and2009guidelinedocuments.Theseoutcomes,asbefore,wereratedonascalefrom1to9.Aquestionoroutcomewasdefinedascriticalifitwasgivenanaveragescoreof7ormore.Questionsandoutcomeswithascoreofbetween4and6wereconsideredimportantbutnotcritical,whilethosewithascorelowerthan 4 were not considered to be important for the purposes of the guideline (Annex2).


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Cochranesystematicreviewsofrandomizedcontrolledtrials(RCTs)werethepri-mary source of evidence for the recommendations2.Usingtheassembledlistofquestionsandoutcomes,theguidelinesteeringgroupidentifiedCochranesystematicreviews that were either relevant or potentially relevant and then evaluated wheth-eranyneededupdating.Areviewwasconsideredtobeoutdatedifthelastspecifieddatefornewtrialsearcheswastwoyearsagoormore,oriftherewererelevantstudiesstillawaitingassessment,asidentifiedbythestandardsearchproceduresoftheCochranePregnancyandChildbirthGroup.Updateswereperformedusingspe-cificstandardsearchstrategies.Thecorrespondingauthorsoftheoutdatedreviewswereinvitedtoupdatethemwithinaspecifiedtimeperiod.Ininstancesinwhichthecorrespondingauthorswereunabletodoso,theupdateswereundertakenbymembers of the guideline steering group. The search strategies employed to identify thetrialsandthespecificcriteriafortrialinclusionandexclusionaredescribedinthe individual systematic reviews. A systematic review of literature that included non-randomized trials was carried out by the guideline steering group members whenrandomized-trialdatarelatedtospecificquestionswerescarce.

Thefollowingprocedureswereusedtoextracttheevidenceforthisguidelinefromeachofthesesystematicreviews:first,themostrecentversionoftheReviewManager(RevMan)filewasretrievedfromtheCochranePregnancyandChildbirthCochraneGroupandcustomizedtoreflectthekeycomparisonsandoutcomes(thosethatwerenotrelevanttotheguidelinewereexcluded).ThentheRevManfilewasexportedtotheGRADEprofilersoftware(GradingofRecommendationsAssessment,DevelopmentandEvaluation)andGRADEcriteriawereusedtocriticallyappraisetheretrievedscientificevidence.Finally,evidenceprofiles(intheformofGRADEtables)were prepared for each comparison. An online content management system devel-opedfortheGREATproject,namelytheGuideline Production System, was used to handleandshareelectronicfiles.

The evidence presented in the GRADE tables was derived from a larger body of data extractedprimarilyfromCochranereviewswhich,inmanycases,containedmultiplecomparisons(EvidenceBase(EB)Tables1to70).EachGRADEtablerelatestoonespecificquestionorcomparison,butsomeGRADEtablesdonotcontaindataforallcritical outcomes. This is because data for those outcomes were not available in the Cochrane reviews. The raw data which constitute the basis of the GRADE tables are notincludedinthisdocument,butreadersinterestedinhowtheseGRADEtableswere constructed may request access to this information. The guideline steering groupusedtheinformationpresentedintheGRADEtablestocheckifanyexistingrecommendations(includedinthe2007or2009documents)neededtoberevised,and to draft recommendations that related to the new questions. Each recom-mendation was allocated to a thematic module which included the narrative sum-maries of evidence and the relevant GRADE tables. The standardized criteria used ingradingtheevidenceandthethematicmodules(includingtheGRADEtables)are not included in this document. They have been published separately online in a document entitled WHO recommendations for preventing and treating PPH: evidence base(www.who.int/reproductivehealth/publications/maternal_perina-tal_health/9789241548502/en).

2 AspartoftheCochranepre-publicationeditorialprocess,reviewsarecommentedonbythreepeers(oneeditorandtworefereesexternaltotheeditorialteam)andtheGroupsStatisticalAdviser(seehttp://www.cochrane.org/cochrane-reviews).The Cochrane Handbook for Systematic Reviews of Interventions describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of health care interventions.


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A preliminary online consultation was held to review the draft recommendations. The draft recommendations and supporting evidence were made available to a large numberofinternationalstakeholderswhowerethenaskedtorespondtoanonlinesurvey.Inaddition,thepreliminaryonlineconsultationidentifiedotherpreviousrecommendations that needed to be discussed at the WHO Technical Consultation onthePreventionandTreatmentofPPHheldinMontreux,Switzerland,68March2012.Asubsetoftheinternationalgroupofexperts(whohadparticipatedintheonlineconsultations)andotheradditionalexpertswereinvitedtoattendtheTechni-calConsultation(seeAnnex1forafulllistofparticipants).Thedraftrecommen-dations,thenarrativesummariesofevidence,theGRADEtablesforthenewandpreviousrecommendations,andotherrelateddocumentswereprovidedinadvancetoparticipants.BalanceworksheetswereusedduringtheTechnicalConsultationtosummarizethevalues,preferencesandjudgementsmadeaboutthestrengthofthenew and revised recommendations.

Declaration of interest by participants in the WHO Technical Con-sultation

AccordingtoWHOregulations,allexpertsmustdeclaretheirrelevantinterestspriorto participation in WHO meetings. All GDG members and participants were therefore required to complete a Declaration of Interest Form before the meeting. These were reviewed by the guideline steering group before the group composition and invita-tionswerefinalized.Theexternaladvisersalsoverballydeclaredpotentialconflictsof interest at the beginning of the meeting. The procedures for the management ofconflictsofinterestswereundertakeninaccordancewiththeWHO guidelines for declaration of interests (WHO experts).Insummary,allmembersoftheGDGdeclaredthattheyhadnocommercialorfinancialintereststhatweredirectlyorindirectlyrelatedtothetopicofthemeeting/guideline.SevenmembersoftheGDGwereinvolvedinacademicworkrelatedtothetopicoftheguideline,butthisinvolvementwasnotconsideredtobeaconflictofinterestandthefullparticipationofalltheselectedexpertswasdeemedappropriate.Atablesummarizingthedecla-rationsofinterestmadebymembersoftheGDGisincludedinAnnex1.

Decision-making during the Technical Consultation

AtthebeginningoftheTechnicalConsultation,theparticipantsdiscussedandad-opted a list of recommendations which needed to be addressed during the meeting. This included the new recommendations as well as previous recommendations that needed to be reviewed and possibly revised.

ThefollowingprotocolwasusedfortheTechnicalConsultation:themeetingwasstructured to allow participants to discuss the proposed list of recommendations and theserecommendationswererevised,asneeded,throughgroupdiscussion.Thefinaladoptionofeachrecommendationwasmadebyconsensusdefinedastheagree-ment by three quarters or more of the participants provided that those who dis-agreed did not feel strongly about their position. Strong disagreements were record-edassuchintheguideline.Iftheparticipantswereunabletoreachaconsensus,thedisputedrecommendation,oranyotherdecision,wasputtoavote.Arecom-mendationordecisionstoodifasimplemajority(morethanhalfoftheparticipants)votedinsupportofit,unlessthedisagreementrelatedtoasafetyconcern,inwhichcase the WHO Secretariat would choose not to issue a recommendation at all. WHO staffattendingthemeeting,externaltechnicalexpertsinvolvedinthecollection


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andgradingoftheevidence,andobserverswerenoteligibletovote.Inadditiontodiscussingthescientificevidenceanditsquality,relevantapplicabilityissues,costsandotherjudgementswerealsotakenintoconsiderationwhenformulatingthefinalrecommendations.

The strength of each recommendation was determined during the Technical Con-sultation.Bydefault,thestrengthoftherecommendationsdiscussedwasalignedinitially with the quality of the evidence (i.e. atthestartofthediscussion,strongrecommendationswerebasedonevidenceofmoderateandhighquality,whileweakrecommendationswerebasedonevidenceoflowandverylowquality). Inadditiontothequalityoftheevidence,thefollowingfactorswereconsideredwhendeterminingthefinalrecommendationanditsstrength:valuesandpreferenc-es,themagnitudeofeffect,thebalanceofbenefitsversusdisadvantages,resourceusage,andfeasibility.Valuesandpreferences,resourceusage,andthefeasibilityofeachrecommendationwerebasedontheexperienceandopinionoftheGDGmem-bers.Balanceworksheetswereusedtonoteandsynthesizetheseconsiderations(Annex3,Boxes1to8)andrecordthereasonsforchangesmadetothedefaultstrength of the recommendations.

Document preparation and peer review

PriortotheTechnicalConsultation,theguidelinesteeringgrouppreparedaprelimi-nary version of this document using a guideline reporting template which had been developedaspartoftheWHOsGREATproject.ThedraftguidelinewasreviewedbyTechnicalConsultationparticipantsatthemeetinginMontreux.Duringthemeeting,thedraftguidelinewasmodifiedinlinewithparticipantdeliberationandcomments.Feedbackreceivedduringthepreliminaryonlineconsultationwasalsodiscussedandincorporatedintothedocumentwhereappropriate.Afterthemeeting,membersoftheguidelinesteeringgroupworkedtoensurethatarevisedversionofthedocu-mentaccuratelyreflectedthedeliberationsanddecisionsoftheparticipants.Thereviseddraftguidelinedocumentwassenttotwoexternalpeerreviewersandtheirinputs were carefully evaluated by the guideline steering group and document revi-sionsmadeaccordingly.Theguidelinesteeringgrouprefrainedfrommakingsubstan-tivechangesafterthemeetinginMontreuxtotheguidelinescoping(suchasthefurtherexpansionoftheguidelinescoping)ortotherecommendations.Therevisedversion was returned electronically to those who had attended the Technical Consul-tation for their approval.

3. ResultsThis guideline includes 32 recommendations for the prevention and treatment of PPH.Sevenoftheserecommendationsarenew,whiletheothershavebeenrevisedin light of new evidence. Most of the previous 2007 and 2009 recommendations remainunchangedinessence,despiteupdatestotheevidencebase.Thewordingof the previous recommendations has been revised to enhance the clarity of the guidance provided. The recommendations included in this guideline are based on atotalof22Cochranesystematicreviewssummarizedin70GRADEtables.Boxes1 to 8 present the most up-to-date WHO recommendations for the prevention and treatmentofPPH.Whereapplicable,remarksrelatedtospecificrecommendationsarealsoshownintheseboxesandnewrecommendationsaremarkedwithasterisks.Narrative summaries of evidence supporting the recommendations are presented


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intheelectronicappendixtogetherwiththecorrespondingGRADEtables(seetheWHO recommendations for preventing and treating PPH: evidence base at www.who.int/reproductivehealth/publications/maternal_perinatal_health/ 9789241548502/en).Box9presentsstatementsrelatedtotopicsforwhich,accord-ingtotheassessmentsoftheGDG,therewasinsufficientevidencetoissuearecom-mendation.Balanceworksheetssummarizingthevalues,preferencesandjudge-mentsmadeaboutthestrengthoftherecommendationsarepresentedinAnnex3,Boxes1to8.

Thedevelopmentoftheserecommendationsinvolved130stakeholderswhopar-ticipatedintheonlinepreliminarysurvey(representingallWHOregions),and25expertswhoparticipatedintheWHOTechnicalConsultation.

Recommendations for PPH preventionThe contribution of each component of the active management of the third stage of labourwasexaminedinlightofnewavailableevidence,andrelevantrecommenda-tionsweremade.Box1presentsrecommendationsconcerningtheuseofuteroton-ics for the prevention of PPH. All women giving birth should be offered uteroton-icsduringthethirdstageoflabourtopreventPPHandIM/IVoxytocin(10IU)isrecommended as the uterotonic drug of choice. Other injectable uterotonics (i.e. ergometrine/methylergometrine,orthefixeddrugcombinationofoxytocinandergometrine)andmisoprostolarerecommendedasalternativesforthepreventionofPPHinsettingswhereoxytocinisunavailable.Box2containsrecommendationsrelated to cord management and uterine massage. The importance of controlled cordtraction(CCT)wasrevisitedbecauseofnewevidence.Thisinterventionisnowregardedasoptionalinsettingswhereskilledbirthattendantsareavailable,andiscontraindicatedinsettingswhereskilledattendantsdonotassistwithbirths.Early cord clamping is generally contraindicated. Continuous uterine massage is not recommended as an intervention to prevent PPH for women who have received prophylacticoxytocin,becausethemassagemaycausematernaldiscomfort,re-quireadedicatedhealthprofessional,andmaynotleadtoareductionofbloodloss.However,surveillanceoftheuterinetonusthroughabdominalpalpationisrecom-mendedforallwomenfortheearlyidentificationofpostpartumuterineatony.Table1 summarizes the recommendation status of the individual components of the active managementofthethirdstageoflabour.Insummary,theGDGconsideredtheuseof uterotonics as the main intervention within the active management of third stage oflabourpackage.Inthiscontext,theuseofmisoprostolforthepreventionofPPHbycommunityhealthcareworkersandlayhealthworkersissupportedinsettingswhereskilledbirthattendantsarenotpresent.

Recommendations for reducing blood loss during the third stage of labour in caesar-eansectionsarepresentedinBox3.Oxytocinistherecommendeduterotonicdrugfor the prevention of PPH in caesarean sections. Cord traction is recommended in preference to manual removal when assisting placental delivery in caesarean sec-tions.

Recommendations for PPH treatmentTheuseofuterotonics(oxytocinaloneasthefirstchoice)playsacentralroleinthetreatmentofPPH(seeBoxes4and5).UterinemassageisrecommendedforthetreatmentofPPHassoonasitisdiagnosed(seeBox6)andtheinitialfluidresus-


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citationwithisotoniccrystalloidsisrecommended.Theuseoftranexamicacidisadvised in cases of refractory atonic bleeding or persistent trauma-related bleed-ing(seeBox5).Theuseofintrauterineballoontamponadeisrecommendedforrefractorybleedingorifuterotonicsareunavailable.Bimanualuterinecompression,externalaorticcompression,andtheuseofnon-pneumaticanti-shockgarmentsarerecommended as temporizing measures until substantive care is available. If there is persistentbleedingandtherelevantresourcesareavailable,uterinearteryemboli-zation should be considered. If bleeding persists despite treatment with uterotonic drugsandotherconservativeinterventions,surgicalinterventionshouldbeusedwithout further delay.

Ifthethirdstageoflabourlastsmorethan30minutes,CCTandIV/IMoxytocin (10IU)shouldbeusedtomanagetheretainedplacenta.Iftheplacentaisretainedandbleedingoccurs,themanualremovaloftheplacentashouldbeexpedited.Wheneverthemanualremovaloftheplacentaisundertaken,asingledoseofpro-phylacticantibioticsisrecommended(seeBox7).

The GDG also issued recommendations related to the organization of PPH care (see Box8).Healthfacilitiesdeliveringmaternityservicesshouldadoptformalproto-cols for the prevention and treatment of PPH and for patient referral. The use of PPH treatment simulations for pre-service and in-service training programmes was recommended.Finally,theGDGrecommendedthattheuseofuterotonicsforthepreventionofPPHshouldbemonitoredandaspecificindicatorwassuggested.

TheGDGfoundinsufficientevidencetorecommendonerouteoveranotherforthepreventionofPPHwithoxytocin,theuseofrecombinantfactorVIIaforthetreat-mentofPPH,intraumbilicalveininjectionofoxytocinfortreatmentofretainedplacenta,andtheantenataldistributionofmisoprostol.TheGDGalsofoundinsuffi-cient evidence to recommend self-administration for the prevention of PPH and the measurementofbloodlossoverclinicalestimation(seeBox9).


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Box 1: Recommendations for the prevention of PPH uterotonics

1. The use of uterotonics for the prevention of PPH during the third stage of labour is recom-mendedforallbirths.(Strongrecommendation,moderate-qualityevidence)

2. Oxytocin(10IU,IV/IM)istherecommendeduterotonicdrugforthepreventionofPPH.(Strongrecommendation,moderate-qualityevidence)

3. Insettingswhereoxytocinisunavailable,theuseofotherinjectableuterotonics(e.g.er-gometrine/methylergometrineorthefixeddrugcombinationofoxytocinandergometrine)ororalmisoprostol(600 g)isrecommended.(Strongrecommendation,moderate-qualityevidence)

4. Insettingswhereskilledbirthattendantsarenotpresentandoxytocinisunavailable,theadministrationofmisoprostol(600 gPO)bycommunityhealthcareworkersandlayhealthworkersisrecommendedforthepreventionofPPH.(Strongrecommendation,moderate-qualityevidence)

Remarks

Availablecomparisonsarelimited,butasignificantdifferencebetweenthebenefitsofoxytocinandergometrineisunlikely.TheserecommendationsplaceahighvalueonavoidingtheadverseeffectsofergometrineandassumeasimilarbenefitfromusingoxytocinandergometrineforthepreventionofPPH.

CautionshouldbeexercisedwhenoptingforergotderivativesforthepreventionofPPHasthesedrugshaveclearcontraindicationsinwomenwithhypertensivedisorders.Thus,itisprobablysafertoavoidthe use of ergot derivatives in unscreened populations.

Misoprostol(600gPO)wasregardedbytheGDGasaneffectivedrugforthepreventionofPPH.How-gPO)wasregardedbytheGDGasaneffectivedrugforthepreventionofPPH.How-PO)wasregardedbytheGDGasaneffectivedrugforthepreventionofPPH.How-ever,theGDGconsideredtherelativebenefitsofoxytocincomparedtomisoprostolinpreventingbloodloss,aswellastheincreasedadverseeffectsofmisoprostolcomparedtooxytocin.TheGDGacknowl-edgedthatthereisnoevidencetoshowthata600 gdoseofmisoprostolprovidesgreaterefficacyovera400ggdose.Lowerdoseshavealowerside-effectprofilebuttheefficacyoflowerdosesofmiso-ggdose.Lowerdoseshavealowerside-effectprofilebuttheefficacyoflowerdosesofmiso-dose.Lowerdoseshavealowerside-effectprofilebuttheefficacyoflowerdosesofmiso-prostolhasnotbeenevaluatedsufficiently.

Therecommendationsconcerningalternativeuterotonicsshouldnotdetractfromtheobjectiveofmak-ingoxytocinaswidelyaccessibleaspossible.

In view of past concerns regarding the community-level distribution of misoprostol and the potential forseriousconsequencesofadministrationbeforebirth,theGDGplacesemphasisontrainingpersonsadministeringmisoprostolandmonitoringcommunitydistributioninterventionswithscientificallysoundmethods and appropriate indicators.


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Box 2: Recommendations for the prevention of PPH cord management and uterine massage

5. Insettingswhereskilledbirthattendantsareavailable,CCTisrecommendedforvaginalbirths if the care provider and the parturient woman regard a small reduction in blood loss andasmallreductioninthedurationofthethirdstageoflabourasimportant.(Weakrecom-mendation,high-qualityevidence)


7. Latecordclamping(performedapproximately1to3minutesafterbirth)isrecommendedforallbirthswhileinitiatingsimultaneousessentialnewborncare.(Strongrecommendation,moderate-qualityevidence)



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Box 2: Recommendations for the prevention of PPH cord management and uterine massage

5. Insettingswhereskilledbirthattendantsareavailable,CCTisrecommendedforvaginalbirths if the care provider and the parturient woman regard a small reduction in blood loss andasmallreductioninthedurationofthethirdstageoflabourasimportant.(Weakrecom-mendation,high-qualityevidence)


7. Latecordclamping(performedapproximately1to3minutesafterbirth)isrecommendedforallbirthswhileinitiatingsimultaneousessentialnewborncare.(Strongrecommendation,moderate-qualityevidence)



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Box 3: Recommendations for the prevention of PPH in caesarean sections

11. Oxytocin(IVorIM)istherecommendeduterotonicdrugforthepreventionofPPHincaesar-eansection.(Strongrecommendation,moderate-qualityevidence)

12. Cord traction is the recommended method for the removal of the placenta in caesarean sec-tion.(Strongrecommendation,moderate-qualityevidence)

Remarks

TheGDGnotedthat,intermsofbloodloss,therewasnotenoughevidencetorecommendoxytocininfusionoverIVbolusinjection.However,duetoconcernsregardingadversehaemodynamiceffects, theGDGconsideredthatifanIVbolusinjectionisused,aslowinjectionrateispreferredandarapidinjection rate should be avoided.

TheGDGnotedthatthecombinationofanoxytocininfusionafteraninitialIVbolusofoxytocinaftercaesarean delivery reduces the need for additional uterotonic agents but does not affect the overall occurrence of major obstetric haemorrhage.

The GDG noted that carbetocin is associated with a reduction in the use of additional uterotonic agents butwithnodifferenceintheoccurrenceofmajorobstetrichaemorrhage.Inaddition,theGDGnotedthattheuseofcarbetocinisconsiderablymoreexpensivethanoxytocin.Thisremarkisequallyappli-cable to vaginal deliveries.

Table1:Recommendationstatusoftheindividualcomponentsoftheactivemanagement ofthethirdstageoflabour,basedonwhodeliverstheintervention

Skilled birth attendant

Non-skilled birth attendant

Self-administered

Uterotonics In favour In favour Research*

Early cord clamping Against Against Against

Controlled cord traction Conditional** Against Against

Continuous uterine massage Against*** Against Research****

* Distribution of misoprostol during the antenatal period for self-administration during the third stage of labour

**Smallreductioninbloodlossandinthelengthofthethirdstage;adoptionbasedonthevaluesandpreferencesofthewoman and the health care provider

***Routineuterinetoneassessmentremainsavitalpartofclinicaldecisionmakingandshouldbepractisedduringthethirdstage of labour

**** Self-administered uterine massage in the absence of uterotonics


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Box 4: Recommendations for the treatment of PPH uterotonics

13. IntravenousoxytocinistherecommendeduterotonicdrugforthetreatmentofPPH.(Strongrecommendation,moderatequalityevidence)

14. Ifintravenousoxytocinisunavailable,orifthebleedingdoesnotrespondtooxytocin,theuseofintravenousergometrine,oxytocin-ergometrinefixeddose,oraprostaglandindrug(includ-ingsublingualmisoprostol,800g)isrecommended.(Strongrecommendation,low-qualityevidence)

Remarks

TheGDGrecommendedIVoxytocinasthefirstlineuterotonicdrugforthetreatmentofPPH,includingwhenwomenhavealreadyreceivedthisdrugfortheprophylaxisofPPH.

TheGDGrecognizedthatIVoxytocinmaynotbeavailableinallsettings.Itencourageshealthcaredecision-makersinthesesettingstostrivetomakeoxytocinavailable.

InsettingswhereIVoxytocinisunavailabletowomenwhohavereceivedprophylacticIMoxytocinduringthethirdstageoflabour,theGDGconsideredmisoprostoltobeavalidalternative.

IfPPHprophylaxiswithmisoprostolhasbeenadministeredandifinjectableuterotonicsareunavailable,thereisinsufficientevidencetoguidefurthermisoprostoldosingandconsiderationmustbegiventotheriskofpotentialtoxicity.

ThereisnoaddedbenefittoofferingmisoprostolsimultaneouslytowomenreceivingoxytocinforthetreatmentofPPH(i.e.adjunctmisoprostol).

TheGDGnotedthatthetwolargesttrialsofmisoprostolforthetreatmentofPPH(Winikoff2010,Blum2010)reportedtheuseofa800gdose administered sublingually. The majority of the GDG members agreed that 800gisanacceptablesublingualmisoprostoldoseforthetreatmentofPPH,thoughsomemembersoftheGDGexpressedconcernrelatedtotheriskofhyperpyrexiaassociatedwiththisdosage.

IfIVoxytocinhasbeenusedforthetreatmentofPPHandthebleedingdoesnotstop,thereisapaucityof data to recommend preferences for second line uterotonic drug treatment. Decisions in such situ-ationsmustbeguidedbytheexperienceoftheprovider,theavailabilityofthedrugs,andbyknowncontraindications.

InsituationsinwhichIMoxytocincanbeadministeredandthereisnopossibilityofIVtreatmentwithergotalkaloids/injectableprostaglandins,thereisapaucityofdatatorecommendapreferenceofIMoxytocinovermisoprostolorotheruterotonics.Decisionsinsuchsituationsmustbeguidedbytheexpe-rienceoftheprovider,theavailabilityofthedrugs,andbyknowncontraindications.

Box 5: Recommendations for the treatment of PPH fluid resuscitation and tranexamic acid

15. The use of isotonic crystalloids is recommended in preference to the use of colloids for the intravenousfluidresuscitationofwomenwithPPH.(Strongrecommendation,low-qualityevidence)

16.TheuseoftranexamicacidisrecommendedforthetreatmentofPPHifoxytocinandotheruterotonics fail to stop the bleeding or if it is thought that the bleeding may be partly due to trauma.(Weakrecommendation,moderate-qualityevidence)

Remarks

Evidencefortherecommendationoftranexamicacidwasextrapolatedfromtheliteratureonsurgeryandtrauma,whichshowstranexamicacidtobeasafeoptionforthetreatmentoftrauma-relatedbleeding.


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Box 6: Recommendations for the treatment of PPH manoeuvres and other procedures

17. UterinemassageisrecommendedforthetreatmentofPPH.(Strongrecommendation,very-low-qualityevidence)

18. Ifwomendonotrespondtotreatmentusinguterotonics,orifuterotonicsareunavailable,the use of intrauterine balloon tamponade is recommended for the treatment of PPH due to uterineatony.(Weakrecommendation,very-low-qualityevidence)

19. Ifothermeasureshavefailedandifthenecessaryresourcesareavailable,theuseofuter-inearteryembolizationisrecommendedasatreatmentforPPHduetouterineatony.(Weakrecommendation,very-low-qualityevidence)

20. If bleeding does not stop in spite of treatment using uterotonics and other available conserva-tiveinterventions(e.g.uterinemassage,balloontamponade),theuseofsurgicalinterven-tionsisrecommended.(Strongrecommendation,very-low-qualityevidence)

21. The use of bimanual uterine compression is recommended as a temporizing measure until appropriate care is available for the treatment of PPH due to uterine atony after vaginal delivery.(Weakrecommendation,very-low-qualityevidence)

22. TheuseofexternalaorticcompressionforthetreatmentofPPHduetouterineatonyaftervaginal birth is recommended as a temporizing measure until appropriate care is available. (Weakrecommendation,very-low-qualityevidence)

23. Theuseofnon-pneumaticanti-shockgarmentsisrecommendedasatemporizingmeasureuntilappropriatecareisavailable.(Weakrecommendation,low-qualityevidence)

24. TheuseofuterinepackingisnotrecommendedforthetreatmentofPPHduetouterineatonyaftervaginalbirth.(Weakrecommendation,very-low-qualityevidence)

Remarks

The GDG noted that the application of these interventions requires training and that maternal discom-fort and complications associated with these procedures have been reported.

Uterinemassageasatherapeuticmeasureisdefinedastherubbingoftheuterusachievedthroughthemanual massaging of the abdomen. This is typically sustained until the bleeding stops or the uterus con-tracts. The GDP considered that uterine massage should be started once PPH has been diagnosed.

Theinitialrubbingoftheuterusandexpressionofbloodclotsarenotregardedastherapeuticuterinemassage.

Whenratingtherecommendation#17asstrong,thelowcostandsafetyofuterinemassageweretakenintoaccount.

The use of balloon tamponade was considered by the GDG to be a measure that can potentially avoid surgeryorasatemporizingmeasurewhileawaitingtransfertoahigherlevelfacility.TheGDGacknowl-edgesthatballoontamponadecanbeobtainedwithspecificdevicesaswellaswithlowercostadapta-tions,includingthosebasedontheuseofcondomsandsurgicalgloves.

TheGDGnotedthatuterinearteryembolizationrequiressignificantresources,intermsofthecostofthetreatment,thefacilities,andthetrainingofhealthcareworkers.

TheGDGnotedthatconservativesurgicalapproachesshouldbetriedfirst.Ifthesedonotwork,theyshouldbefollowedbymoreinvasiveprocedures.Compressionsutures,forexample,maybeattemptedasafirstintervention,andifthesefail,thenuterine,utero-ovarianandhypogastricvesselligationmaybetried.Iflife-threateningbleedingcontinuesevenafterligation,thenasubtotal(otherwiseknownassupracervical)ortotalhysterectomyshouldbeperformed.

TheGDGacknowledgedthatthelevelofhealthcareproviderskillswillplayaroleintheselectionandsequence of the surgical interventions.

(Continued on next page)


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Externalaorticcompressionhaslongbeenrecommendedasapotentiallife-savingtechnique,andme-chanicalcompressionoftheaorta,ifsuccessful,slowsbloodloss.TheGDGplacedahighvalueonthisprocedure as a temporizing measure in the treatment of PPH.

TheGDGnotedthatresearchevaluatingthepotentialbenefitsandharmsofnon-pneumaticanti-shockgarmentsisongoing.Basedontheevidenceavailable,theGDGregardednon-pneumaticanti-shockgar-ments as a temporizing measure while transfer is awaited.

TheGDGnotedthattherewasnoevidenceofbenefitofuterinepackingandplacedahighvalueonconcerns regarding its potential harm.

Box 7: Recommendations for the treatment of retained placenta

25. Iftheplacentaisnotexpelledspontaneously,theuseofadditionaloxytocin(10 IU,IV/IM)incombinationwithcontrolledcordtractionisrecommended.(Weakrecommendation,very-low-qualityevidence)

26.The use of ergometrine for the management of a retained placenta is not recommended as thismaycausetetanicuterinecontractionswhichmaydelaytheexpulsionoftheplacenta.(Weakrecommendation,very-low-qualityevidence)

27. TheuseofprostaglandinE2alpha(dinoprostoneorsulprostone)inthemanagementofre-tainedplacentaisnotrecommended.(Weakrecommendation,very-low-qualityevidence)

28. Asingledoseofantibiotics(ampicillinorfirst-generationcephalosporin)isrecommendedifmanualremovaloftheplacentaispractised.(Weakrecommendation,very-low-qualityevi-dence)

Remarks

The GDG found no empirical evidence to support recommending the use of uterotonics for the manage-ment of a retained placenta in the absence of haemorrhage. The above recommendation was reached by consensus.

TheWHOguide,Managing complications in pregnancy and childbirth(WHO,2007),statesthatifaplacentaisnotexpelledwithin30minutesafterthedeliveryofababy,thewomanshouldbediagnosedashavingaretainedplacenta.Sincethereisnoevidencefororagainstthisdefinition,thedelayusedbefore this condition is diagnosed is left to the judgement of the clinician.

ThesameWHOguidealsosuggeststhatintheabsenceofhaemorrhage,thewomanshouldbeobservedforafurther30minutesaftertheinitial30minutes,beforethemanualremovaloftheplacentaisat-tempted.TheGDGnotedthatspontaneousexpulsionoftheplacentacanstilloccur,evenintheabsenceof bleeding. A conservative approach is therefore advised and the timing of the manual removal of the placentaasadefinitivetreatmentislefttothejudgementoftheclinician.

TherecommendationregardingtheuseofprostaglandinE2isinformedbyalackofevidenceonthisquestionandalsobyconcernsrelatedtoadverseevents,particularlycardiacevents.

Directevidenceofthevalueofantibioticprophylaxisafterthemanualremovaloftheplacentawasnotavailable.TheGDGconsideredindirectevidenceofthebenefitofprophylacticantibioticsfromstudiesofcaesareansectionandabortion,aswellasobservationalstudiesofotherintrauterinemanipulations.

Currentpracticesuggeststhatampicillinorfirst-generationcephalosporinsmaybeadministeredwhenthe manual removal of the placenta is performed.

Thisquestionwasidentifiedasaresearchpriorityforsettingsinwhichprophylacticantibioticsarenotroutinely administered and those with low infectious morbidity.

(Continued from previous page)


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Box 8: Health Systems and Organization of Care recommendations for the prevention and treatment of PPH

29. The use of formal protocols by health facilities for the prevention and treatment of PPH is recommended.(Weakrecommendation,moderate-qualityevidence)

30. The use of formal protocols for referral of women to a higher level of care is recommended forhealthfacilities.(Weakrecommendation,very-low-qualityevidence)

31. The use of simulations of PPH treatment is recommended for pre-service and in-service train-ingprogrammes.(Weakrecommendation,very-low-qualityevidence)

32. Monitoring the use of uterotonics after birth for the prevention of PPH is recommended as aprocessindicatorforprogrammaticevaluation.(Weakrecommendation,very-low-qualityevidence)

Remarks

Routineandfrequentuterinetoneassessmentremainsacrucialpartofimmediatepostpartumcare,particularly for optimizing the early diagnosis of PPH.

TheGDGacknowledgedthattheimplementationofformalprotocolsisacomplexprocesswhichwillrequire the local adaptation of general guidelines.

TheGDGplacedahighvalueonthecostsofsimulationprogrammesandacknowledgedthattherearedifferenttypesofsimulationprogrammes.Someprogrammesarehi-tech,computerizedandcostlywhileothersarelessexpensiveandmorelikelytobeaffordableinlow-andmiddle-incomecountries.TheGDGidentifiedimprovementincommunicationbetweenhealthcareprovidersandpatientsandtheirfamily members as an important priority in the training of health care providers in PPH management.

The GDG recommended monitoring the use of prophylactic uterotonics. This recommendation is based onexperiencefromotherareasofhealthcare,particularlychildhealth,wherecontent-basedhealthindicators are common and regarded as useful for programmatic purposes. The suggested indicator is calculated as the number of women receiving prophylactic uterotonic drugs after birth divided by all women giving birth.


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Box 9: Statements related to topics for which there is insufficient evidence to issue a recom-mendation

A. ThereisinsufficientevidencetorecommendoneoxytocinrouteoveranotherforthepreventionofPPH.

B. ThereisinsufficientevidencetorecommendtheuseofrecombinantfactorVIIaforthetreatmentofPPH.

C. Thereisinsufficientevidencetorecommendtheuseofintraumbilicalveininjectionofoxytocinasatreatment for retained placenta.

D. Thereisinsufficientevidencetorecommendtheantenataldistributionofmisoprostoltopregnantwomen for self-administration for the prevention of PPH.

E. Thereisinsufficientevidencetorecommendthemeasurementofbloodlossoverclinicalestimationofblood loss.

Remarks

TheGDGnotedthattherearethreeongoingtrialsinwhichtheIVandIMroutesforoxytocinadministra-tion are being compared for the prevention of PPH.

TheGDGconsideredtheretobeinsufficientevidencetorecommendtheuseofoxytocininfusionoverIVbolusinjectionwithregardtobloodloss.However,inlightofconcernsaboutthepotentialadversehaemodynamiceffects,theGDGconsideredthatifIVbolusinjectiontreatmentistobeusedthenaslow injection rate is preferred and a rapid injection rate should be avoided.

InthecontextofPPH,theGDPconsideredthattheuseofrecombinantfactorVIIashouldbelimitedtowomenwithspecifichaematologicalindications.ThegroupregardedtherecombinantfactorVIIaasapotentiallylife-savingdrug,butnotedthatitisalsoassociatedwithlife-threateningside-effects.More-over,recombinantfactorVIIaisexpensiveandmaybedifficulttoadminister.

TheGDGacknowledgedthatwhilethereisapaucityofdatatorecommendintraumbilicalveininjec-tionofoxytocinasatreatmentforretainedplacenta,theprocedureitselfhasnotbeenshowntocauseharmanddemonstratesanon-significanttrendtowardsalowerriskofrequiringthemanualremovalofthe placenta.

TheGDGacknowledgedthatanumberofcountrieshaveembarkedoncommunity-levelprogrammesofmisoprostoldistributionandconsideredthatthisshouldbedoneinthecontextofresearch(wherereli-abledataoncoverage,safetyandhealthoutcomescanbecollected).

The GDG noted that all trials included in the systematic review on the measurement of blood loss were conducted in developed countries and views the applicability of this evidence to low- and middle-income countries as very uncertain.


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4. Research implicationsTheGDGidentifiedimportantknowledgegapsthatneedtobeaddressedthroughprimaryresearch.Inthisguideline,recommendationsbasedonevidencequalitythatwasratedasveryloworlowrequirefurtherresearch.Conversely,furtherre-searchisnotapriorityforthoserecommendationsbasedonevidenceofmoderateorhighquality.Knowledgegapsidentifiedinthe2007and2009WHOdocumentswerealsoreviewed.Theidentifiedknowledgegapswereprioritizedbyconsideringwhethersuchresearchwouldbefeasible,innovative,original,likelytopromoteequity,andcontributetothereductionoftheburdenofPPH.Themainbarrierstoscalinguptheinterventionwerealsoconsideredinthisprioritizationexercise.

The GDG noted that research is either planned or ongoing for some of the research prioritiesidentified.However,thereisnocertaintythattheseinvestigationswillprovideconclusiveresults,andthetopicshavethereforeremainedlistedasre-search priorities in this document.

Key research priorityInsettingswheretheuseofinjectableuterotonicsisnotfeasible,whataretheef-fects of antenatal distribution of misoprostol to pregnant women for self-administra-tion during the third stage of labour?

Other research questions WhatistheminimumeffectivedoseofoxytocinforthepreventionofPPH?

WhataretheeffectsofIMoxytocin(versusIVoxytocin)forthepreventionofPPH?

Canoxytocinbeadministeredsafelybyunskilledattendants?

Whataretheeffectsofbuccalandsublingualuseofoxytocinforthepreventionof PPH?

What is the minimum effective dose of misoprostol for the prevention of PPH?

What is the minimum effective dose of misoprostol for the treatment of PPH?

WhatareeffectsandsafetyofmisoprostolastreatmentforPPH,inwomenwhoreceivedmisoprostolasPPHprophylaxis?

ShouldmisoprostolbeusedinadditiontooxytocinforPPHprevention?

WhataretheeffectsoftranexamicacidinPPHtreatment?

What are the effects of uterine massage for the prevention of PPH?

WhataretheeffectsofuterinemassagetopreventPPH,whereoxytocinisnotavailable?

What are the effects of uterine balloon or tamponade in the treatment of PPH?

WhataretheeffectsofuterinemassagetopreventPPH,whereonlymisoprostolis available?


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Whataretheeffectsofprophylacticantibioticsaftermanualextractionoftheplacenta as part of the treatment of retained placenta?

What are the effects of the use of misoprostol for the treatment of retained placenta?

Whatareeffectsofergometrine(incombinationornotwithoxytocin)aftercaesarean section for the prevention of PPH?

Whatistheoptimaltimeforcordclampinginthecontextofphysiologicandac-tive management of third stage of labour?

WhatistheappropriatetimetoadministeroxytocinforPPHprevention,rela-tivetocordclampingandplacentaldelivery?(i.e.before/aftercordclamping,before/afterplacentadelivery)

Which clinical consequences of blood loss are of greatest value for the diagnosis and treatment of PPH?

WhatistheroleoflayhealthworkersinmanagementofPPH?

5. Dissemination and implementation of the guidelineThe ultimate goal of this guideline is to improve the quality of care and health outcomes related to PPH. Therefore the dissemination and implementation of this guidelinearecrucialstepsthatshouldbeundertakenbytheinternationalcommu-nity and local health care services. The WHO Department of Reproductive Health andResearchhasadoptedaformalknowledge-to-actionframeworkforthedissemi-nation,adaptationandimplementationofguidelines(8).Inadditiontothisframe-work,alistofpriorityactionswasestablishedduringtheWHOTechnicalConsulta-tion which will be used by the WHO and other partners to foster the dissemination andimplementationofthisguideline(EBBox2).

Guideline dissemination and evaluationThe recommendations in this guideline will be disseminated through a broad net-workofinternationalpartners,includingWHOcountryandregionaloffices,min-istriesofhealth,WHOcollaboratingcentres,otherUnitedNationsagencies,andnon-governmental organizations. They will also be published on the WHO website andinTheWHOReproductiveHealthLibrary(11),wheretheywillbeaccompaniedby an independent critical appraisal based on the AGREE instrument (Appraisal of GuidelinesResearchandEvaluation)whichcanbefoundathttp://www.agreecol-laboration.org/instrument.Apolicybriefwillalsobedevelopedforawiderangeofpolicy-makers,programmemanagersandclinicians,andthendisseminatedthroughWHOcountryoffices.

Guideline implementationThe successful introduction of evidence-based policies related to the prevention and management of PPH into national programmes and health care services depends on well-planned and participatory consensus-driven processes of adaptation and imple-


26

mentation.Theseprocessesmayincludethedevelopmentorrevisionofexistingnational guidelines or protocols based on this document.

The recommendations contained in the present guideline should be adapted into locally-appropriatedocumentsthatareabletomeetthespecificneedsofeachcountryandhealthservice.Modificationstotherecommendations,wherenecessary,shouldbelimitedtoweakrecommendationsandjustificationsforanychangesmadeinanexplicitandtransparentmanner.

An enabling environment should be created for the use of these recommendations (forexample,bywideningtheavailabilityofuterotonics),includingchangesinthebehaviour of health care practitioners to enable the use of evidence-based practic-es. Local professional societies may play important roles in this process and an all-inclusiveandparticipatoryprocessshouldbeencouraged.TheWHOsDepartmentofReproductiveHealthandResearchhaspublishedspecificguidanceontheintroduc-tionoftheWHOsreproductivehealthguidelinesandtoolsinnationalprogrammes.

6. Applicability issuesAnticipated impact on the organization of care and resourcesThe evidence-based prevention and management of PPH can be achieved with the useofrelativelyinexpensivedrugs.However,theGDGnotedthatthefollowingis-sues should be considered before the recommendations made in this current guide-lineareapplied:

Womenshouldnotbeleftaloneduringthefirsthoursafterdeliveryofthebabyand the placenta

Insettingswhereoxytocinisused,attentionshouldbepaidtotheoxytocincoldchain(i.e.therequirementsofatemperature-controlledsupplychain)

Health services adopting late cord clamping should also adopt strategies to iden-tify(andifnecessarytotreat)neonataljaundice

Monitoring and evaluating the guideline implementationThe implementation of the recommendations in this guideline should be monitored atthehealth-servicelevel.Interruptedtimeseries,clinicalauditsorcriterion-basedclinical audits could be used to obtain relevant data related to the management of PPH.Clearly-definedreviewcriteriaandindicatorsareneededandthesecouldbeassociated with locally-agreed targets. The GDG strongly recommends that the cov-erage of prophylactic uterotonics be used as a process indicator for the monitoring and prevention of PPH.

ProphylacticUterotonicCoverageIndicator:Thesuggestedindicatoriscalculat-ed as the number of women receiving prophylactic uterotonics during the third stage of labour divided by all women giving birth

Thisindicatorprovidesanoverallassessmentofadherencetoakeyrecommendationincludedinthisguideline.Theuseofotherlocally-agreedandmorespecificindica-


27

tors(e.g.theassessmentoftheuseofspecificuterotonics)maybenecessarytoobtain a more complete assessment of the quality of care related to the prevention andtreatmentofPPH.WHOhasdevelopedspecificguidanceforevaluatingthequal-ityofcareforseverematernalcomplications(includingPPH)basedonthenear-missandcriterion-basedclinicalauditconcepts(13).

7. Updating the guidelineThisguidelinewillbeupdatedin2017orfollowingtheidentificationofnewevi-dence that indicates a need to revise these recommendations. WHO welcomes sug-gestions regarding additional questions for inclusion in the updated guideline. Please e-mailyoursuggestionsto:[email protected].

References1. KhanKS,WojdylaD,SayL,GlmezogluAM,VanLookPF.WHOanalysisofcauses

ofmaternaldeath:Asystematicreview.Lancet.2006;367(9516):106674.

2. CampbellOM,GrahamWJ.LancetMaternalSurvivalSeriesSteeringGroup.Strategiesforreducingmaternalmortality:gettingonwithwhatworks.Lancet. 2006;368(9543):128499.

3. World Health Organization. World Health Organization multicountry survey on maternal and newborn health.Geneva:WHO;2012

4. World Health Organization. Managing complication in pregnancy and childbirth: a guide for midwives and doctors.Geneva:WHO;2000.Availablefrom:http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/9241545879/en/index.html

5. BegleyCM,GyteGM,DevaneD,McGuireW,WeeksA.Activeversusexpect-ant management for women in the third stage of labour. Cochrane Database Syst Rev.2011(11).Availablefrom:http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007412.pub3/abstract

6. World Health Organization. WHO recommendations for the prevention of postpartum haemorrhage.Geneva:WHO;2007.Availablefrom:http://whqlibdoc.who.int/hq/2007/WHO_MPS_07.06_eng.pdf

7. World Health Organization. WHO guidelines for the management of postpartum haemorrhage and retained placenta.Geneva:WHO;2009.Availablefrom:http://whqlibdoc.who.int/publications/2009/9789241598514_eng.pdf

8. World Health Organization. Knowledge to action framework and the G.R.E.A.T project.Geneva:WHO;2010.Availablefrom:http://www.who.int/reproduc-tivehealth/topics/best_practices/greatproject_KTAframework/en/index.html

9. World Health Organization. WHO Handbook for guideline development. Geneva:WHO;2012.Availablefrom:http://apps.who.int/iris/bitstream/10665/75146/1/9789241548441_eng.pdf


28

10. World Health Organization. Guidelines on basic newborn resuscitation. Geneva:WHO;2012.Availablefrom:http://apps.who.int/iris/bitstream/10665/75157/1/9789241503693_eng.pdf

11. World Health Organization. The WHO Reproductive Health Library.Geneva:WHO.Availablefrom:www.who.int/rhl

12. World Health Organization. Introducing WHOs sexual and reproductive health guidelines and tools into national programmes: principles and process of adaptation and implementation.Geneva:WHO;2007.Availablefrom:http://www.who.int/reproductivehealth/publications/general/RHR_07_09/en/index.html

13. World Health Organization. Evaluating the quality of care for severe pregnancy complications: the WHO nearmiss approach for maternal health. Geneva:WHO;2011.Availablefrom:http://whqlibdoc.who.int/publica-tions/2011/9789241502221_eng.pdf

The full list of references that support the recommendations is included in the docu-ment entitled WHO recommendations for post partum haemorrhage: evidence base andcanbeaccessedonlineat:www.who.int/reproductivehealth/publications/mater-nal_perinatal_health/9789241548502/en/


29

Annex 1. External experts, WHO staff involved in the preparation of the guideline, and summary of decla-rations of interest

A. Guideline Development Group (participants in the WHO Technical Consultation)

Members (WHO External Advisers)

Professor Hany Abdel-AleemProfessor of Obstetrics and GynecologyWomensHealthCenterAssiutUniversityHospitalAssiutEgypt

Dr Catherine Deneux-TharauxMedical Epidemiologist and ResearcherInsermU953Recherche pidmiologique en sant prinatale et sant des femmes et des enfantsHpital TenonParisFrance

Dr Bukola FawoleSenior LecturerDepartment of Obstetrics and GynaecologyCollege of MedicineUniversityofIbadanIbadanNigeria

Dr Atf GhrissiMatreAssistanteUniversitaireenSciencesdelEducationappliqueslaSantEcole Suprieure des Sciences et Techniques de la SantUniversitTunis-El ManarTunisia

Ms Gill GyteResearch Associate Cochrane Pregnancy and Childbirth Group UniversityofLiverpool LiverpoolWomensHospitalNHSTrust Crown Street UnitedKingdom

Dr Justus HofmeyrDirectorEffectiveCareResearchUnitUniversityoftheWitwatersrand/ UniversityofFortHare/ Eastern Cape Department of HealthAmalinda DrivePrivate Bag X9047East London Eastern Cape 5201South Africa

Dr Simon LewinSenior ResearcherGlobalHealthUnitNorwegianKnowledgeCentrefortheHealthServices&MedicalResearchCouncil,SouthAfricaOsloNorway

Professor Syeda Batool MazharProfessor of Obstetrics and GynaecologyMotherandChildHealthCentre(MCH)PakistanInstitute of Medical SciencesIslamabadPakistan

Professor Suneeta MittalProfessor of Obstetrics and Gynecology Officer-in-ChargeoftheWHOCollaboratingCentre for Research on Human ReproductionAll India Institute of Medical SciencesNew DelhiIndia

Dr Enrique OyarzunChairman Department Obstetrics and GynaecologyFacultad de MedicinaPontificiaUniversidadCatlicadeChileSantiagoChile


30

Dr Zahida QureshiSenior LecturerDepartment of Obstetrics and GynaecologyUniversityofNairobiNairobiKenya

Professor Hamid RushwanChiefExecutive International Federation of Gynecology and ObstetricsFIGOHouse,Suite3WaterlooCourt,10TheedStreetLondon SE1 8STUnitedKingdom

Dr Jeffrey Michael SmithDirector,MaternalHealth,MCHIPWashingtonUSA

Dr Tran Son ThachPerinatal EpidemiologistAustralian Research Centre for Health of Women and BabiesDiscipline of Obstetrics and GynaecologyTheUniversityofAdelaideWomensandChildrensHospitalKingWilliamRoadAustralia

Dr Dilys WalkerAssociate ProfessorDepartment of Global Health and Obstetrics & GynecologyUniversityofWashingtonNinth&JeffersonBuilding,HarborviewMedicalCenter Seattle,WAUSA

Observers

Ms Deborah ArmbrusterSenior Maternal and Newborn Health AdvisorCenterforPopulation,HealthandNutritionUnitedStatesAgencyforInternationalDevelopmentWashington D.C.USA

Ms Jennifer BlumGynuity Health ProjectsNewYorkUSA

Ms Claire GlentonSenior ResearcherNordicCochraneCentre,NorwegianBranch/ GlobalHealthUnitNorwegianKnowledgeCentrefortheHealthServicesOsloNorway

Dr Sarah Rosenbaum NorwegianKnowledgeCentrefortheHealth ServicesOsloNorway

Ms Mary Ellen StantonSenior Reproductive Health AdvisorCenterforPopulation,HealthandNutritionUnitedStatesAgencyforInternationalDevelopmentWashington D.C.USA

Ms Clare WaiteProject ManagerMisoprostol for Post-Partum Haemorrhage in Low Resource SettingsInternational Federation of Gynecology and ObstetricsFIGO HouseLondon UnitedKingdom

Dr Beverly WinikoffGynuity Health ProjectsNewYorkUSA


31

WHO Regional and Country Offices

AFRO

Dr Alicia CarbonellNationalProfessionalOfficerMakingPregnancySaferandReproductiveHealthBureaudepaysdelOMS POBoxCP377 Maputo Mozambique

SEARO

Dr Narimah AwinMedicalOfficerMakingPregnancySaferandReproductiveHealthDepartment of Family and ResearchWorld Health Organization RegionalOfficeforSouth-EastAsia WorldHealthHouse,IndraprasthaEstate Mahatma Gandhi Marg New Delhi 110 002India

WPRO

Dr Hiromi ObaraMedicalOfficerMaternal and Child Health and NutritionBuilding Healthy Communities and PopulationsWorld Health Organization RegionalOfficefortheWesternPacificP.O.Box2932 1000 Manila Philippines

External Secretariat

Dr Edgardo AbalosCentro Rosarino de Estudios Perinatales(CREP)Rosario Argentina

Dr Virginia DiazCentroRosarinodeEstudiosPerinatales(CREP)Rosario Argentina

Dr Natasha HezelgraveAcademicClinicalFellow,ObstetricsandGynaecologyKingsCollegeLondonGuys&StThomasNHSFoundationTrustLondonUnitedKingdom

WHO Secretariat

Dr Michael MbizvoDirector Department of Reproductive Health and Research

Dr Ana Pilar BetranMedicalOfficerImproving Maternal and Perinatal HealthResearch,EvidenceandNormsDepartment of Reproductive Health and Research

Dr Metin GlmezogluLead SpecialistImproving Maternal and Perinatal HealthResearch,EvidenceandNormsDepartment of Reproductive Health and Research

Dr Matthews MathaiCoordinatorEpidemiology,MonitoringandEvaluationDepartment of Maternal,Newborn,ChildandAdolescentHealth(MCA)

Dr Joo Paulo SouzaMedicalOfficerImprovingMaternalandPerinatalHealthResearch,Evidence and NormsDepartment of Reproductive Health and Research

Dr Joshua VogelImprovingMaternalandPerinatalHealthResearch,Evidence and NormsDepartment of Reproductive Health and Research

Dr Mariana WidmerTechnicalofficerImprovingMaternalandPerinatalHealthResearch,Evidence and NormsDepartment of Reproductive Health and Research

B. Guideline Steering Group

Dr A. Metin Glmezoglu (WHO)

Dr Matthews Mathai (WHO)

Dr Joo Paulo Souza (WHO)

Dr Edgardo Abalos (CREP)

Dr Virginia Diaz (CREP)

Dr Natasha Hezelgrave (KCL)


32

C. Summary of the declarations of interest: Members of the GDGName Region Country Declaration of Conflict

of interest (please indicate yes or no for each section)

Advice from Legal Department (please indicate yes or no)

Meeting restriction: Please indicate see below for explanation)

A B C D

Professor Hany Abdel-Aleem

EMRO Egypt Y N N N N N

Dr Catherine Deneux-Tharaux

EURO France Y N N N N N

DrBukolaFawole AFRO Nigeria N N N N N N

Dr Atf Ghrissi EMRO Tunisia N N N N N N

Ms Gill Gyte EURO UK Y N N N N N

DrJustusHofmeyr AFRO South Africa

Y N N N N N

Dr Simon Lewin EURO Norway/South Africa

N N N N N N

Professor Syeda Batool Mazhar

EMRO Pakistan N N N N N N

Dr Enrique Oyarzun

AMRO Chile N N N N N N

DrZahidaQureshi AFRO Kenya Y N N N N N

Professor Hamid Rushwan

EURO Sudan/UK N N N N N N

DrJeffreyMichaelSmith

AMRO USA N N N N N N

Dr Tran Son Thach WPRO Vietnam/Australia

Y N N N N N

DrDilysWalker AMRO USA Y N N N N N

A:Involvedinacademicworkrelatedtothetopicofthemeeting/guideline

B:Declaredanycommercialfinancialinterest,relatedtothetopicofthemeeting/guideline

C:Declaredanycommercialfinancialinterest,not directlyrelatedtothetopicofthemeeting/guideline

D:Declarednon-commercialinterestorgrantsrelatedtothetopicofthemeeting/guideline


33

Annex 2. Critical outcomes for decision making

PPH prevention

Critical outcomes

Fewer maternal deaths

FewereventsofseverePPH(bloodloss>1000ml)

Less use of blood transfusion

Important outcomes

Fewer admissions to intensive care unit

Bloodloss500ml

Additional uterotonics

Mean blood loss

Postpartum anaemia

Breastfeeding

Less anaemia in infancy

Any side effect of intervention

Any side effect requiring treatment

Nausea

Vomiting

Diarrhoea

Headache

Abdominal pain

High blood pressure

Shivering

Maternaltemperature38C


PPH treatment

Critical outcomes

Additionalbloodloss500ml

Additionalbloodloss1000ml

Blood transfusion

Additional uterotonics

Invasive non-surgical interventions

Surgicalinterventions(includinghysterectomy)


Procedure-related complications

Infections

Severe morbidity

Maternal transfer

Reductionoftimefromdecision-makingtoimplemen-tation

Availability of drugs and treatment

Important outcomes

Accuracy in blood loss assessment

Mean blood loss

Postpartum anaemia

Additionalnon-surgicalinterventions(e.g.externalaorticcompressionandcompressiongarments)

Artery embolization

Nausea,vomitingorshivering


Delayed initiation of breastfeeding

Prolonged hospitalization


34

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36

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