WHO recommendations for the prevention and treatment of postpartum haemorrhage
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 recommendations for the prevention and treatment of postpartum haemorrhage
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: RecommendationsforthepreventionofPPH–uterotonics 15
Box2: RecommendationsforthepreventionofPPH–cordmanagement anduterinemassage 16
Table1:Recommendationstatusoftheindividualcomponentsof theactivemanagementofthethirdstageoflabour,basedonwho delivers the intervention 18
Box3: RecommendationsforthepreventionofPPHincaesareansections 18
Box4: RecommendationsforthetreatmentofPPH–uterotonics 19
Box5: RecommendationsforthetreatmentofPPH–fluidresuscitation andtranexamicacid 19
Box6: RecommendationsforthetreatmentofPPH–manoeuvresand 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(Recommendations1–5) 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 base”andcanbeaccessedonlineat:www.who.int/reproductivehealth/publications/maternal_perinatal_health/9789241548502/en/
Box2. Summaryofconsiderationsrelatedtothestrengthof therecommendations(Recommendations6–10) 35
Box3. Summaryofconsiderationsrelatedtothestrengthof therecommendations(Recommendations11–15) 36
Box4. Summaryofconsiderationsrelatedtothestrengthof therecommendations(Recommendations16–20) 37
Box5. Summaryofconsiderationsrelatedtothestrengthof therecommendations(Recommendations21–25) 38
Box6. Summaryofconsiderationsrelatedtothestrengthof therecommendations(Recommendations26–30) 39
Box7. Summaryofconsiderationsrelatedtothestrengthof therecommendations(Recommendations31–32) 40
Box8. Templateforthesummaryofconsiderationsrelatedto thestrengthoftherecommendationswithexplanationsfor completing the template 41
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AcknowledgementsWorkonthisguidelinewasinitiatedbyA.MetinGülmezogluandJoãoPauloSouza,oftheWHODepartmentofReproductiveHealthandResearch,andbyMatthewsMathai,oftheWHODepartmentofMaternal,Newborn,ChildandAdolescentHealth.JoãoPauloSouzacoordinatedthedevelopmentofthepresentguidelineanddraftedthisdocument.EdgardoAbalosandVirginiaDiaz,oftheCentroRosarinodeEstudiosPerinatales(CREP),Rosario,Argentina,reviewedthescientificevidencerelatedtothepreventionandtreatmentofPostpartumHaemorrhage(PPH)andproducedtheGRADEtablesusedinthisguideline.NatashaHezelgrave,oftheAcademicWomen’sHealthCentre,King’sCollegeLondon(KCL),UnitedKingdom(UK),draftedthenar-rativesummariesofevidence.TheGRADEtablesweredouble-checkedbyKanokwa-roonWatananirun(Fon)oftheUniversityofBangkok,Thailand.A.MetinGülmezo-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
µg 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 development”1.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,6–8March2012.
The WHO Technical Consultation adopted 32 recommendations and these are shown inBoxesA,BandC.Foreachrecommendation,thequalityofthesupportingevi-denceisgradedas‘verylow’,‘low’,‘moderate’or‘high’.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 thirdstageoflabour’wasexaminedinlightofnewavailableevidence,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 µg)isrecommended.(Strongrecommendation,moderate-qualityevidence)
4. Insettingswhereskilledbirthattendantsarenotpresentandoxytocinisunavailable,theadministrationofmisoprostol(600 µgPO)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(<1minuteafterbirth)isnotrecommendedunlesstheneonateisas-phyxiatedandneedstobemovedimmediatelyforresuscitation.(Strongrecommendation,moderate-qualityevidence)
9. Sustained uterine massage is not recommended as an intervention to prevent PPH in women whohavereceivedprophylacticoxytocin.(Weakrecommendation,low-qualityevidence)
10. Postpartumabdominaluterinetonusassessmentforearlyidentificationofuterineatonyisrecommendedforallwomen.(Strongrecommendation,very-low-qualityevidence)
11. Oxytocin(IVorIM)istherecommendeduterotonicdrugforthepreventionofPPHincaesar-eansection.(Strongrecommendation,moderate-qualityevidence)
12. Controlled cord traction is the recommended method for removal of the placenta in caesar-eansection.(Strongrecommendation,moderate-qualityevidence)
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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,800µg)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.(1–3)
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.Thisapproachbecameknownasthe“activemanagementofthethirdstageoflabour”andconsistedinitiallyofthefollowingcomponents: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 placenta”publishedin2009(6,7).ThisdocumentrepresentsWHO’snor-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.AsmalloperativegroupcomposedofstafffromtheWHO’sDepartmentofReproductiveHealthandResearch,andDepartmentofMaternal,Newborn,ChildandAdolescentHealth(MCA),aswellastwoexternalexperts(seeAnnex1–Theguidelinesteer-inggroup)andalargergroupwithinternationalstakeholdersincludingmidwives,obstetricians,neonatologists,researchers,expertsinresearchsynthesis,expertsinhealthcareprogrammes,andconsumerrepresentatives(theGuidelineDevelopmentGroup–GDG).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.Aquestionoroutcomewasdefinedas‘critical’ifitwasgivenanaveragescoreof7ormore.Questionsandoutcomeswithascoreofbetween4and6wereconsidered‘importantbutnotcritical’,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)andtheGroup’sStatisticalAdviser(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,6–8March2012.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 ofconflictsofinterestswereundertakeninaccordancewiththe“WHO 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.Thefinaladoptionofeachrecommendationwasmadebyconsensus–definedastheagree-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,strongrecommendationswerebasedonevidenceof‘moderate’and‘high’quality,whileweakrecommendationswerebasedonevidenceof‘low’and‘verylow’quality). 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 developedaspartoftheWHO’sGREATproject.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(seethe“WHO 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 labour’wasexaminedinlightofnewavailableevidence,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 µg)isrecommended.(Strongrecommendation,moderate-qualityevidence)
4. Insettingswhereskilledbirthattendantsarenotpresentandoxytocinisunavailable,theadministrationofmisoprostol(600 µgPO)bycommunityhealthcareworkersandlayhealthworkersisrecommendedforthepreventionofPPH.(Strongrecommendation,moderate-qualityevidence)
Remarks
• Availablecomparisonsarelimited,butasignificantdifferencebetweenthebenefitsofoxytocinandergometrineisunlikely.TheserecommendationsplaceahighvalueonavoidingtheadverseeffectsofergometrineandassumeasimilarbenefitfromusingoxytocinandergometrineforthepreventionofPPH.
• CautionshouldbeexercisedwhenoptingforergotderivativesforthepreventionofPPHasthesedrugshaveclearcontraindicationsinwomenwithhypertensivedisorders.Thus,itisprobablysafertoavoidthe use of ergot derivatives in unscreened populations.
• Misoprostol(600�gPO)wasregardedbytheGDGasaneffectivedrugforthepreventionofPPH.How-�gPO)wasregardedbytheGDGasaneffectivedrugforthepreventionofPPH.How-PO)wasregardedbytheGDGasaneffectivedrugforthepreventionofPPH.How-ever,theGDGconsideredtherelativebenefitsofoxytocincomparedtomisoprostolinpreventingbloodloss,aswellastheincreasedadverseeffectsofmisoprostolcomparedtooxytocin.TheGDGacknowl-edgedthatthereisnoevidencetoshowthata600 µgdoseofmisoprostolprovidesgreaterefficacyovera400�g�gdose.Lowerdoseshavealowerside-effectprofilebuttheefficacyoflowerdosesofmiso-�g�gdose.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)
6. Insettingswhereskilledbirthattendantsareunavailable,CCTisnotrecommended.(Strongrecommendation,moderate-qualityevidence)
7. Latecordclamping(performedapproximately1to3minutesafterbirth)isrecommendedforallbirthswhileinitiatingsimultaneousessentialnewborncare.(Strongrecommendation,moderate-qualityevidence)
8. Earlycordclamping(<1minuteafterbirth)isnotrecommendedunlesstheneonateisas-phyxiatedandneedstobemovedimmediatelyforresuscitation.(Strongrecommendation,moderate-qualityevidence)
9. Sustained uterine massage is not recommended as an intervention to prevent PPH in women whohavereceivedprophylacticoxytocin.(Weakrecommendation,low-qualityevidence)
10. Postpartumabdominaluterinetonusassessmentforearlyidentificationofuterineatonyisrecommendedforallwomen.(Strongrecommendation,very-low-qualityevidence)
Remarks
• Recommendations5and6arebasedonalargeRCTinwhichoxytocin10IUwasusedforthepreventionofPPHinallparticipants.Basedonthisevidence,CCTwasregardedassafewhenappliedbyskilledbirthattendantsasitprovidessmallbeneficialeffectsonbloodloss(averagereductionof11mlonbloodloss)andonthedurationofthethirdstageoflabour(averagereductionof6minutes).Thedeci-siontoimplementCCTinthecontextofaprophylacticuterotonicdrugshouldbediscussedbythecareprovider and the woman herself.
• IfergotalkaloidsareusedforthepreventionofPPH,thenCCTtominimizeplacentaretentionisre-garded as essential.
• ThereisinsufficientevidencetodeterminethebenefitorriskofCCTwhenusedinconjunctionwithmisoprostol.
• CCTisthefirstinterventiontotreatretainedplacenta,thereforetheteachingofCCTinmedicalandmidwifery curricula is essential.
• The evidence base for recommendations for the timing of cord clamping includes both vaginal and cae-sarean births. The GDG considers this recommendation to be equally important for caesarean sections.
• Delayed clamping should be performed during the provision of essential newborn care. For essential newborncareandresuscitation,pleaserefertotheWHOguidelinesonneonatalresuscitation.(10)
• The recommendations for the timing of cord clamping apply equally to preterm and term births. The GDGconsidersthebenefitsofdelayedclampingforpreterminfantstobeparticularlyimportant.
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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)
6. Insettingswhereskilledbirthattendantsareunavailable,CCTisnotrecommended.(Strongrecommendation,moderate-qualityevidence)
7. Latecordclamping(performedapproximately1to3minutesafterbirth)isrecommendedforallbirthswhileinitiatingsimultaneousessentialnewborncare.(Strongrecommendation,moderate-qualityevidence)
8. Earlycordclamping(<1minuteafterbirth)isnotrecommendedunlesstheneonateisas-phyxiatedandneedstobemovedimmediatelyforresuscitation.(Strongrecommendation,moderate-qualityevidence)
9. Sustained uterine massage is not recommended as an intervention to prevent PPH in women whohavereceivedprophylacticoxytocin.(Weakrecommendation,low-qualityevidence)
10. Postpartumabdominaluterinetonusassessmentforearlyidentificationofuterineatonyisrecommendedforallwomen.(Strongrecommendation,very-low-qualityevidence)
Remarks
• Recommendations5and6arebasedonalargeRCTinwhichoxytocin10IUwasusedforthepreventionofPPHinallparticipants.Basedonthisevidence,CCTwasregardedassafewhenappliedbyskilledbirthattendantsasitprovidessmallbeneficialeffectsonbloodloss(averagereductionof11mlonbloodloss)andonthedurationofthethirdstageoflabour(averagereductionof6minutes).Thedeci-siontoimplementCCTinthecontextofaprophylacticuterotonicdrugshouldbediscussedbythecareprovider and the woman herself.
• IfergotalkaloidsareusedforthepreventionofPPH,thenCCTtominimizeplacentaretentionisre-garded as essential.
• ThereisinsufficientevidencetodeterminethebenefitorriskofCCTwhenusedinconjunctionwithmisoprostol.
• CCTisthefirstinterventiontotreatretainedplacenta,thereforetheteachingofCCTinmedicalandmidwifery curricula is essential.
• The evidence base for recommendations for the timing of cord clamping includes both vaginal and cae-sarean births. The GDG considers this recommendation to be equally important for caesarean sections.
• Delayed clamping should be performed during the provision of essential newborn care. For essential newborncareandresuscitation,pleaserefertotheWHOguidelinesonneonatalresuscitation.(10)
• The recommendations for the timing of cord clamping apply equally to preterm and term births. The GDGconsidersthebenefitsofdelayedclampingforpreterminfantstobeparticularlyimportant.
• SomehealthprofessionalsworkinginareasofhighHIVprevalencehaveexpressedconcernregard-ing delayed cord clamping as part of management of the third stage of labour. These professionals are concernedthatduringplacentalseparation,apartiallydetachedplacentacouldbeexposedtomaternalblood and this could lead to a micro-transfusion of maternal blood to the baby. It has been demonstrat-edthatthepotentialformaternal-to-childtransmissionofHIVcantakeplaceatthreedifferentpointsintime:micro-transfusionsofmaternalbloodtothefetusduringpregnancy(intra-uterineHIVtransmis-sion),exposuretomaternalbloodandvaginalsecretionswhenthefetuspassesthroughthebirthcanalinvaginaldeliveries(intra-partumtransmission),andduringbreastfeeding(postnatalinfection).Forthisreason,themaininterventiontoreducethematernal-to-childtransmissionisthereductionofmater-nalviralloadthroughtheuseofantiretroviraldrugsduringpregnancy,childbirthandpostnatalperiod.There is no evidence that delaying the cord clamping increases the possibility of HIV transmission from the mother to the newborn. Maternal blood percolates through the placental intervillous space through-outpregnancywitharelativelylowriskofmaternalfetaltransmissionbeforedelivery.Itishighlyun-likelythatseparationoftheplacentaincreasesexposuretomaternalblood,andishighlyunlikelythatitdisruptsthefetalplacentalcirculation(i.e.itisunlikelythatduringplacentaseparationthenewborncirculationisexposedtomaternalblood).Thus,theprovenbenefitsofa1–3minutedelayatleastinclampingthecordoutweighthetheoretical,andunproven,harms.LatecordclampingisrecommendedevenamongwomenlivingwithHIVorwomenwithunknownHIVstatus.
• ThereisalackofevidenceregardingtheroleofuterinemassageforPPHpreventionwhennouterotonicdrugsareused,orifauterotonicdrugotherthanoxytocinisused.
• AlthoughtheGDGacknowledgedthatonesmallstudyreportedthatsustaineduterinemassageandclotexpulsionwereassociatedwithareductionintheuseofadditionaluterotonics,thereislackofrobustevidencesupportingotherbenefits.However,theGDGconsideredthatroutineandfrequentuterinetoneassessmentremainsacrucialpartofimmediatepostpartumcare,particularlyfortheoptimizationof early PPH diagnosis.
• Basedonthemostrecentevidence,understandingofthecontributionofeachcomponentoftheactivemanagementofthethirdstageoflabourpackagehasevolved.TheGDGconsideredthatthispackagehasaprimaryintervention:theuseofanuterotonic.Inthecontextofoxytocinuse,CCTmayaddasmallbenefit,whileuterinemassagemayaddnobenefitforthepreventionofPPH.Earlycordclampingis generally contraindicated.
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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,800µg)isrecommended.(Strongrecommendation,low-qualityevidence)
Remarks
• TheGDGrecommendedIVoxytocinasthefirstlineuterotonicdrugforthetreatmentofPPH,includingwhenwomenhavealreadyreceivedthisdrugfortheprophylaxisofPPH.
• TheGDGrecognizedthatIVoxytocinmaynotbeavailableinallsettings.Itencourageshealthcaredecision-makersinthesesettingstostrivetomakeoxytocinavailable.
• InsettingswhereIVoxytocinisunavailabletowomenwhohavereceivedprophylacticIMoxytocinduringthethirdstageoflabour,theGDGconsideredmisoprostoltobeavalidalternative.
• IfPPHprophylaxiswithmisoprostolhasbeenadministeredandifinjectableuterotonicsareunavailable,thereisinsufficientevidencetoguidefurthermisoprostoldosingandconsiderationmustbegiventotheriskofpotentialtoxicity.
• ThereisnoaddedbenefittoofferingmisoprostolsimultaneouslytowomenreceivingoxytocinforthetreatmentofPPH(i.e.adjunctmisoprostol).
• TheGDGnotedthatthetwolargesttrialsofmisoprostolforthetreatmentofPPH(Winikoff2010,Blum2010)reportedtheuseofa800μgdose administered sublingually. The majority of the GDG members agreed that 800μgisanacceptablesublingualmisoprostoldoseforthetreatmentofPPH,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#17as‘strong’,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.
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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)
WHO recommendations for the prevention and treatment of postpartum haemorrhage
22
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.
WHO recommendations for the prevention and treatment of postpartum haemorrhage
23
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.
WHO recommendations for the prevention and treatment of postpartum haemorrhage
24
4. Research implicationsTheGDGidentifiedimportantknowledgegapsthatneedtobeaddressedthroughprimaryresearch.Inthisguideline,recommendationsbasedonevidencequalitythatwasratedas‘verylow’or‘low’requirefurtherresearch.Conversely,furtherre-searchisnotapriorityforthoserecommendationsbasedonevidenceof‘moderate’or‘high’quality.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?
WHO recommendations for the prevention and treatment of postpartum haemorrhage
25
• 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-
WHO recommendations for the prevention and treatment of postpartum haemorrhage
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.TheWHO’sDepartmentofReproductiveHealthandResearchhaspublishedspecificguidanceontheintroduc-tionoftheWHO’sreproductivehealthguidelinesandtoolsinnationalprogrammes.
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-
WHO recommendations for the prevention and treatment of postpartum haemorrhage
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,GülmezogluAM,VanLookPF.WHOanalysisofcauses
ofmaternaldeath:Asystematicreview.Lancet.2006;367(9516):1066–74.
2. CampbellOM,GrahamWJ.LancetMaternalSurvivalSeriesSteeringGroup.Strategiesforreducingmaternalmortality:gettingonwithwhatworks.Lancet. 2006;368(9543):1284–99.
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
WHO recommendations for the prevention and treatment of postpartum haemorrhage
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 WHO’s 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/
WHO recommendations for the prevention and treatment of postpartum haemorrhage
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 GynecologyWomen’sHealthCenterAssiutUniversityHospitalAssiutEgypt
Dr Catherine Deneux-TharauxMedical Epidemiologist and ResearcherInsermU953Recherche épidémiologique en santé périnatale et santé des femmes et des enfantsHôpital TenonParisFrance
Dr Bukola FawoleSenior LecturerDepartment of Obstetrics and GynaecologyCollege of MedicineUniversityofIbadanIbadanNigeria
Dr Atf GhérissiMaîtreAssistanteUniversitaireenSciencesdel’EducationappliquéesàlaSantéEcole Supérieure des Sciences et Techniques de la SantéUniversitéTunis-El ManarTunisia
Ms Gill GyteResearch Associate Cochrane Pregnancy and Childbirth Group UniversityofLiverpool LiverpoolWomen’sHospitalNHSTrust 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 MedicinaPontificiaUniversidadCatólicadeChileSantiagoChile
WHO recommendations for the prevention and treatment of postpartum haemorrhage
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 GynaecologyTheUniversityofAdelaideWomen’sandChildren’sHospitalKingWilliamRoadAustralia
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
WHO recommendations for the prevention and treatment of postpartum haemorrhage
31
WHO Regional and Country Offices
AFRO
Dr Alicia CarbonellNationalProfessionalOfficerMakingPregnancySaferandReproductiveHealthBureaudepaysdel’OMS 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,ObstetricsandGynaecologyKingsCollegeLondonGuy’s&StThomas’NHSFoundationTrustLondonUnitedKingdom
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 GülmezogluLead SpecialistImproving Maternal and Perinatal HealthResearch,EvidenceandNormsDepartment of Reproductive Health and Research
Dr Matthews MathaiCoordinatorEpidemiology,MonitoringandEvaluationDepartment of Maternal,Newborn,ChildandAdolescentHealth(MCA)
Dr João 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 Gülmezoglu (WHO)
Dr Matthews Mathai (WHO)
Dr João Paulo Souza (WHO)
Dr Edgardo Abalos (CREP)
Dr Virginia Diaz (CREP)
Dr Natasha Hezelgrave (KCL)
WHO recommendations for the prevention and treatment of postpartum haemorrhage
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 Ghérissi 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
WHO recommendations for the prevention and treatment of postpartum haemorrhage
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
Bloodloss≥500ml
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
Maternaltemperature≥38°C
Maternaltemperature≥40°C
PPH treatment
Critical outcomes
Additionalbloodloss≥500ml
Additionalbloodloss≥1000ml
Blood transfusion
Additional uterotonics
Invasive non-surgical interventions
Surgicalinterventions(includinghysterectomy)
Maternaltemperature≥40°C
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
Maternaltemperature≥38°C
Delayed initiation of breastfeeding
Prolonged hospitalization
WHO recommendations for the prevention and treatment of postpartum haemorrhage
34
Ann
ex 3
: Su
mm
ary
of t
he c
onsi
dera
tion
s re
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the
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igh
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low
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Nosignificantvariability
Signific
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Signific
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Signific
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Signific
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Abso
lute
m
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tude
of
effe
ct
L
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eff
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(RR>
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L
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eff
ect
(RR>
2 or
RR
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Smalle
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L
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(RR>
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RR
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ect
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Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
WHO recommendations for the prevention and treatment of postpartum haemorrhage
35
Ann
ex 3
: Su
mm
ary
of t
he c
onsi
dera
tion
s re
late
d to
the
str
engt
h of
the
rec
omm
en-
dati
ons
(Bal
ance
Wor
kshe
ets)
Box1.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s1–5)
Reco
mm
enda
tion
12
34
5
Inte
rven
tion
Ute
roto
nics
for
PPH
pr
even
tion
Oxy
toci
n fo
r PP
H p
reve
ntio
nO
ther
ute
roto
nics
for
PPH
pr
even
tion
Mis
opro
stol
by
com
mun
ity
heal
th w
orke
rs f
or P
PH
prev
enti
on
CCT
by s
kille
d bi
rth
atte
ndan
ts f
or P
PH
prev
enti
on
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
Box2.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s6–10)
Reco
mm
enda
tion
67
89
10
Inte
rven
tion
CCT
by u
nski
lled
birt
h at
tend
ants
for
PPH
pr
even
tion
Late
cor
d cl
ampi
ng f
or P
PH
prev
enti
onEa
rly
cord
cla
mpi
ng f
or P
PH
prev
enti
onSu
stai
ned
uter
ine
mas
sage
fo
r PP
H p
reve
ntio
nPo
stpa
rtum
abd
omin
al
asse
ssm
ent
of u
teri
ne t
onus
Qua
lityofthe
evid
ence
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
WHO recommendations for the prevention and treatment of postpartum haemorrhage
36
Box3.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s11–15)
Reco
mm
enda
tion
1112
1314
15
Inte
rven
tion
Oxy
toci
n fo
r PP
H p
reve
ntio
n in
CS
CCT
for
PPH
pre
vent
ion
in
CSO
xyto
cin
for
PPH
tre
atm
ent
Oth
er u
tero
toni
c dr
ugs
for
PPH
tre
atm
ent
Isot
onic
cry
stal
loid
s fo
r PP
H
trea
tmen
t
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
WHO recommendations for the prevention and treatment of postpartum haemorrhage
37
Box3.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s11–15)
Reco
mm
enda
tion
1112
1314
15
Inte
rven
tion
Oxy
toci
n fo
r PP
H p
reve
ntio
n in
CS
CCT
for
PPH
pre
vent
ion
in
CSO
xyto
cin
for
PPH
tre
atm
ent
Oth
er u
tero
toni
c dr
ugs
for
PPH
tre
atm
ent
Isot
onic
cry
stal
loid
s fo
r PP
H
trea
tmen
t
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
Box4.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s16–20)
Reco
mm
enda
tion
1617
1819
20
Inte
rven
tion
Tran
exam
ic a
cid
for
PPH
tr
eatm
ent
Ute
rine
mas
sage
for
PPH
tr
eatm
ent
Intr
aute
rine
bal
loon
ta
mpo
nade
for
PPH
tr
eatm
ent
Ute
rine
art
ery
embo
lizat
ion
for
PPH
tre
atm
ent
Surg
ical
inte
rven
tion
s fo
r PP
H t
reat
men
t
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on*
W
eakrecommen
dation
WHO recommendations for the prevention and treatment of postpartum haemorrhage
38
Box5.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s21–25)
Reco
mm
enda
tion
2122
2324
25
Inte
rven
tion
Bim
anua
l ute
rine
co
mpr
essi
on f
or P
PH
trea
tmen
t
Exte
rnal
aor
tic
com
pres
sion
fo
r PP
H t
reat
men
tN
on-p
neum
atic
ant
i-sh
ock
garm
ent
for
PPH
tre
atm
ent
Ute
rine
pac
king
for
PPH
tr
eatm
ent
Ute
roto
nics
and
CCT
for
re
tain
ed p
lace
nta
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
WHO recommendations for the prevention and treatment of postpartum haemorrhage
39
Box5.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s21–25)
Reco
mm
enda
tion
2122
2324
25
Inte
rven
tion
Bim
anua
l ute
rine
co
mpr
essi
on f
or P
PH
trea
tmen
t
Exte
rnal
aor
tic
com
pres
sion
fo
r PP
H t
reat
men
tN
on-p
neum
atic
ant
i-sh
ock
garm
ent
for
PPH
tre
atm
ent
Ute
rine
pac
king
for
PPH
tr
eatm
ent
Ute
roto
nics
and
CCT
for
re
tain
ed p
lace
nta
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
Box6.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s(Recom
men
dation
s26–30)
Reco
mm
enda
tion
2627
2829
30
Inte
rven
tion
Ergo
met
rine
for
ret
aine
d pl
acen
taPr
osta
glan
din
E2 a
lpha
for
re
tain
ed p
lace
nta
Ant
ibio
tics
wit
h m
anua
l re
mov
al f
or r
etai
ned
plac
enta
Form
al p
roto
cols
for
PPH
tr
eatm
ent
Form
al p
roto
cols
for
pat
ient
re
ferr
al
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
m
agni
tude
of
effe
ct
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
WHO recommendations for the prevention and treatment of postpartum haemorrhage
40
Box7.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s
(Recom
men
dation
s31–32)
Reco
mm
enda
tion
3132
Inte
rven
tion
Sim
ulat
ions
of
PPH
tr
eatm
ent
Mon
itor
ing
the
use
of
uter
oton
ics
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
mag
nitu
de
of e
ffec
t
Lar
ge e
ffec
t (R
R>2
or
RR<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
WHO recommendations for the prevention and treatment of postpartum haemorrhage
41
Box7.Sum
maryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
s
(Recom
men
dation
s31–32)
Reco
mm
enda
tion
3132
Inte
rven
tion
Sim
ulat
ions
of
PPH
tr
eatm
ent
Mon
itor
ing
the
use
of
uter
oton
ics
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
H
igh
M
oder
ate
L
ow
V
ery
low
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Nosignificantvariability
Signific
antvariab
ility
Abso
lute
mag
nitu
de
of e
ffec
t
Lar
ge e
ffec
t (R
R>2
or
RR<0.5)
Smalle
ffect(0.5<R
R<2)
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
disad
vantages
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Yes,glob
ally
Yes,cond
itiona
lly
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
Box8.Tem
plateforthesummaryofcon
side
ration
srelatedtothe
stren
gthofthe
recom
men
dation
swithexplan
ationsforcom
pletingthetemplate
Reco
mm
enda
tion
Whi
ch r
ecom
men
dati
on?
Inte
rven
tion
Wha
t is
the
inte
rven
tion
?
Qua
lityofthe
ev
iden
ce
Hig
h
M
oder
ate
L
ow
V
ery
low
Thehigherthe
qua
lityofthe
evide
nce,the
stron
gertherecommen
dation
.
Ifthe
evide
ncequ
alityis‘low’or‘verylo
w’,con
side
rmorecarefully
the
othercriteriabe
lowin
decidingthestrengthofthe
reco
mm
enda
tion
.
Valu
es a
nd
pref
eren
ces
Nosignificantvariability
Signific
antvariab
ility
Thisreferstovalue
splaced
byhe
althworke
rs,po
licy-makers,patientsan
dothe
rstakeh
olde
rsontheintend
edoutcomesof
the
inte
rven
tion
s.
Ifthe
reiswidevariab
ilitybetwee
nthevaluesand
preferencesofvariou
sstakeh
olde
rs,theinterven
tion
isle
sslike
lytoha
vea
stro
ng r
ecom
men
dati
on.
Mag
nitu
de o
f ef
fect
in c
riti
cal
outc
omes
L
arge
eff
ect
(RR>
2 or
RR
<0.5)
Smalle
ffect(0.5<R
R<2)
This
ref
ers
to t
he p
oten
tial
of
the
inte
rven
tion
to
have
larg
e ef
fect
s. T
he e
ffec
ts c
an b
e en
hanc
ed b
y be
ing
com
bine
d w
ith
othe
rinterven
tion
s.Con
side
rwhichpoten
tialassociation
s(or‘bun
dles’)can
enh
anceeffects.
Thelargerthe
poten
tialeffectsand
the
longerthe
tim
epe
riod
ofthepo
tentiale
ffects,themorelik
elytheinterven
tion
isto
have
a s
tron
g re
com
men
dati
on.
Bala
nce
of
bene
fitsversus
disa
dvan
tage
s
Ben
efitsoutweigh
disa
dvan
tage
s
Ben
efitsand
di
sadv
anta
ges
are
bala
nced
D
isad
vant
ages
out
wei
gh
bene
fits
Bene
fitsrefertothe
intend
edpositiveeffectsofaninterven
tion
.
Dis
adva
ntag
es r
efer
to
the
pote
ntia
lly n
egat
ive
effe
cts
of a
n in
terv
enti
on a
s w
ell a
s it
s un
inte
nded
eff
ects
.
Thefewerthe
poten
tiallynegativeeffectsthereare,the
morelik
elytheinterven
tion
istoreceiveastrongrecom
men
dation
.
Reso
urce
use
L
ess
reso
urce
inte
nsiv
e
M
ore
reso
urce
inte
nsiv
e
Theresourcesne
eded
forthe
implem
entation
ofarecommen
dation
mayin
clud
efin
ancialresou
rces,hu
man
resou
rces,
andinfrastructureoreq
uipm
ent.Id
eally,thecostofthebe
nefitsofaninterven
tion
sho
uldbe
rea
sona
ble,afforda
blean
dsustaina
ble.Itsho
uldbe
rem
embe
redthatcap
italcosts,suchasthoserequ
ired
forin
frastructurald
evelop
men
t,m
aybe
initially
highbu
tmayalsoyieldlong-termben
efits.
Gen
erally,interven
tion
sthatin
curhigherin
crem
entalo
rrecurren
tcostsarelesslike
lytobe
stron
glyrecommen
ded.
Feas
ibili
tyYes,glob
ally
Yes,cond
itiona
lly
Politicalcom
mitmen
tan
dwidestakeh
olde
ren
gagemen
tareprereq
uisitesforinterven
tion
s.The
‘technical’fea
sibilityof
interven
tion
salsodep
endsonsufficien
tlyfunction
alorgan
izationa
land
institutiona
lstructurestom
anage,followthrou
gh,
and
mon
itor
the
impl
emen
tati
on o
f th
e re
com
men
dati
on.
The
elem
ents
of
tech
nica
l fea
sibi
lity
vary
con
side
rabl
y by
cou
ntry
an
dby
con
text;whe
rethe
seelemen
tsarelike
lytobe
fun
ctiona
lacrossawidevarietyofsettingsitism
orelik
elythat
inte
rven
tion
s w
ill r
ecei
ve s
tron
g re
com
men
dati
ons.
Reco
mm
enda
tion
di
rect
ion
In
fav
our
of t
he
inte
rven
tion
A
gain
st t
he in
terv
enti
on
Overallrank
ing
S
tron
g re
com
men
dati
on
W
eakrecommen
dation
Stre
ngth
of
the
reco
mm
enda
tion
.
WHO recommendations for the prevention and treatment of postpartum haemorrhage
For more information, please contact:
Department of Reproductive Health and Research E-mail: [email protected] www.who.int/reproductivehealth
Maternal, Newborn, Child and Adolescent HealthE-mail: [email protected]/maternal_child_adolescent
World Health Organization Avenue Appia 20, CH-1211 Geneva 27 Switzerland