This 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” published in 2009 (6,7). This document represents WHO's normative support for using evidence-informed policies and practices in all countries. The guideline forms part of a WHO knowledge-to-action project entitled GREAT (Guideline development, Research priorities, Evidence synthesis, Applicability of evidence, Transfer of knowledge) (8) and was developed using standardized operating procedures in accordance with the process described in the “WHO handbook for guideline development” (9). In summary, the process included: (i) the identification of critical questions and critical outcomes, (ii) the retrieval of the evidence, (iii) the assessment and synthesis of evidence, (iv) the formulation of recommendations, and (v) planning for the dissemination, implementation, impact evaluation and updating of the guideline.

Two technical groups have worked in the development of this guideline. A small operative group composed of staff from the WHO's Department of Reproductive Health and Research, and Department of Maternal, Newborn, Child and Adolescent Health (MCA), as well as two external experts (see Annex 1 - The guideline steering group) and a larger group with international stakeholders including midwives, obstetricians, neonatologists, researchers, experts in research synthesis, experts in health care programmes, and consumer representatives (the Guideline Development Group - GDG). The guideline steering group was formed in the very beginning of the project and reviewed the previous WHO guidelines on prevention and treatment of PPH (6,7). This group prepared a list of potential additional questions related to the prevention and treatment of PPH. Next, the GDG reviewed and prioritized the draft questions. 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 in the 2007 and 2009 guideline documents. These outcomes, as before, were rated on a scale from 1 to 9. A question or outcome was defined as ‘critical’ if it was given an average score of 7 or more. Questions and outcomes with a score of between 4 and 6 were considered ‘important but not critical’, while those with a score lower than 4 were not considered to be important for the purposes of the guideline (Annex 2).

Cochrane systematic reviews of randomized controlled trials (RCTs) were the primary source of evidence for the recommendations2. Using the assembled list of questions and outcomes, the guideline steering group identified Cochrane systematic reviews that were either relevant or potentially relevant and then evaluated whether any needed updating. A review was considered to be outdated if the last specified date for new trial searches was two years ago or more, or if there were relevant studies still awaiting assessment, as identified by the standard search procedures of the Cochrane Pregnancy and Childbirth Group. Updates were performed using specific standard search strategies. The corresponding authors of the outdated reviews were invited to update them within a specified time period. In instances in which the corresponding authors were unable to do so, the updates were undertaken by members of the guideline steering group. The search strategies employed to identify the trials and the specific criteria for trial inclusion and exclusion are described in the individual systematic reviews. A systematic review of literature that included non-randomized trials was carried out by the guideline steering group members when randomized-trial data related to specific questions were scarce.

The following procedures were used to extract the evidence for this guideline from each of these systematic reviews: first, the most recent version of the Review Manager (RevMan) file was retrieved from the Cochrane Pregnancy and Childbirth Cochrane Group and customized to reflect the key comparisons and outcomes (those that were not relevant to the guideline were excluded). Then the RevMan file was exported to the GRADE profiler software (Grading of Recommendations Assessment, Development and Evaluation) and GRADE criteria were used to critically appraise the retrieved scientific evidence. Finally, evidence profiles (in the form of GRADE tables) were prepared for each comparison. An online content management system developed for the GREAT project, namely the Guideline Production System, was used to handle and share electronic files.

The evidence presented in the GRADE tables was derived from a larger body of data extracted primarily from Cochrane reviews which, in many cases, contained multiple comparisons (Evidence Base (EB) Tables 1 to 70). Each GRADE table relates to one specific question or comparison, but some GRADE tables do not contain data for all critical 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 not included in this document, but readers interested in how these GRADE tables were constructed may request access to this information. The guideline steering group used the information presented in the GRADE tables to check if any existing recommendations (included in the 2007 or 2009 documents) needed to be revised, and to draft recommendations that related to the new questions. Each recommendation was allocated to a thematic module which included the narrative summaries of evidence and the relevant GRADE tables. The standardized criteria used in grading the evidence and the thematic modules (including the GRADE tables) 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_perinatal_health/9789241548502/en).

A preliminary online consultation was held to review the draft recommendations. The draft recommendations and supporting evidence were made available to a large number of international stakeholders who were then asked to respond to an online survey. In addition, the preliminary online consultation identified other previous recommendations that needed to be discussed at the WHO Technical Consultation on the Prevention and Treatment of PPH held in Montreux, Switzerland, 6-8 March 2012. A subset of the international group of experts (who had participated in the online consultations) and other additional experts were invited to attend the Technical Consultation (see Annex 1 for a full list of participants). The draft recommendations, the narrative summaries of evidence, the GRADE tables for the new and previous recommendations, and other related documents were provided in advance to participants. Balance worksheets were used during the Technical Consultation to summarize the values, preferences and judgements made about the strength of the new and revised recommendations.

Declaration of interest by participants in the WHO Technical Consultation

According to WHO regulations, all experts must declare their relevant interests prior to 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 invitations were finalized. The external advisers also verbally declared potential conflicts of interest at the beginning of the meeting. The procedures for the management of conflicts of interests were undertaken in accordance with the “WHO guidelines for declaration of interests (WHO experts)”. In summary, all members of the GDG declared that they had no commercial or financial interests that were directly or indirectly related to the topic of the meeting/guideline. Seven members of the GDG were involved in academic work related to the topic of the guideline, but this involvement was not considered to be a conflict of interest and the full participation of all the selected experts was deemed appropriate. A table summarizing the declarations of interest made by members of the GDG is included in Annex 1.

Decision-making during the Technical Consultation

At the beginning of the Technical Consultation, the participants discussed and adopted 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.

The following protocol was used for the Technical Consultation: the meeting was structured to allow participants to discuss the proposed list of recommendations and these recommendations were revised, as needed, through group discussion. The final adoption of each recommendation was made by consensus - defined as the agreement by three quarters or more of the participants - provided that those who disagreed did not feel strongly about their position. Strong disagreements were recorded as such in the guideline. If the participants were unable to reach a consensus, the disputed recommendation, or any other decision, was put to a vote. A recommendation or decision stood if a simple majority (more than half of the participants) voted in support of it, unless the disagreement related to a safety concern, in which case the WHO Secretariat would choose not to issue a recommendation at all. WHO staff attending the meeting, external technical experts involved in the collection and grading of the evidence, and observers were not eligible to vote. In addition to discussing the scientific evidence and its quality, relevant applicability issues, costs and other judgements were also taken into consideration when formulating the final recommendations.

The strength of each recommendation was determined during the Technical Consultation. By default, the strength of the recommendations discussed was aligned initially with the quality of the evidence (i.e. at the start of the discussion, strong recommendations were based on evidence of ‘moderate’ and ‘high’ quality, while weak recommendations were based on evidence of ‘low’ and ‘very low’ quality). In addition to the quality of the evidence, the following factors were considered when determining the final recommendation and its strength: values and preferences, the magnitude of effect, the balance of benefits versus disadvantages, resource usage, and feasibility. Values and preferences, resource usage, and the feasibility of each recommendation were based on the experience and opinion of the GDG members. Balance worksheets were used to note and synthesize these considerations (Annex 3, Boxes 1 to 8) and record the reasons for changes made to the default strength of the recommendations.

Document preparation and peer review

Prior to the Technical Consultation, the guideline steering group prepared a preliminary version of this document using a guideline reporting template which had been developed as part of the WHO's GREAT project. The draft guideline was reviewed by Technical Consultation participants at the meeting in Montreux. During the meeting, the draft guideline was modified in line with participant deliberation and comments. Feedback received during the preliminary online consultation was also discussed and incorporated into the document where appropriate. After the meeting, members of the guideline steering group worked to ensure that a revised version of the document accurately reflected the deliberations and decisions of the participants. The revised draft guideline document was sent to two external peer reviewers and their inputs were carefully evaluated by the guideline steering group and document revisions made accordingly. The guideline steering group refrained from making substantive changes after the meeting in Montreux to the guideline scoping (such as the further expansion of the guideline scoping) or to the recommendations. The revised version was returned electronically to those who had attended the Technical Consultation for their approval.

Footnotes

2

As part of the Cochrane pre-publication editorial process, reviews are commented on by three peers (one editor and two referees external to the editorial team) and the Group's Statistical Adviser (see http://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.