This recommendation is an update of one of 49 recommendations that were published in the WHO recommendations on antenatal care for a positive pregnancy experience (2016) guideline (1). The recommendation was developed initially using the standardized operating procedures described in the WHO handbook for guideline development (15). In summary, the process included: (i) identification of priority questions and outcomes, (ii) retrieval of evidence, (iii) assessment and synthesis of the evidence, (iv) formulation of recommendations, and (v) planning for the implementation, dissemination, impact evaluation and updating of the recommendation. This recommendation was identified by the Executive GSG as a high priority for updating in response to new evidence on MMS.
Contributors to the guideline
Executive Guideline Steering Group (Executive GSG)
The Executive GSG is an independent panel of external experts and relevant stakeholders from the six WHO regions. This group advises WHO on the prioritization of new and existing questions in maternal and perinatal health for recommendation development or updating.
WHO Steering Group
The WHO Steering Group that managed the updating process comprised the same staff members from the Departments of SRH, MCA and NFS who were part of the Steering Group for the WHO ANC guideline of 2016 (see Annex 1 for the list of members). The Steering Group drafted the key recommendation question in PICO (population, intervention, comparator, outcome) format and identified individuals to be invited to participate as guideline methodologists, as well as the guideline development and external review groups. In addition, the WHO Steering Group supervised the evidence retrieval and synthesis, organized the technical consultation, and drafted and finalized the guideline document. The Steering Group in collaboration with WHO regional offices will oversee the dissemination of the updated recommendation.
Guideline Development Group (GDG)
The Steering Group identified and invited 15 external experts and stakeholders from the six WHO regions to constitute the GDG, ensuring geographic representation, gender balance, and no important conflicts of interest. These were the experts who had also served in the GDG for the WHO ANC guideline’s nutrition recommendations of 2016. This is a diverse group of individuals with expertise in research, guideline development methods, and clinical policy and programmes relating to ANC interventions, and includes a patient/consumer representative. The GDG appraised the evidence used to inform the recommendation, advised on the interpretation of this evidence, and formulated the final recommendation during an online GDG meeting on 4–5 December 2019. In addition, GDG members reviewed and approved the final guideline document before its submission to the WHO Guidelines Review Committee for approval. A list of the GDG members can be found in Annex 1.
External Review Group (ERG)
The External Review Group was a geographically and gender-balanced group with no important conflicts of interest (see Annex 1 for ERG members). There were four members, including technical experts and other stakeholders with interests in the provision of evidence-informed ANC. This group peer-reviewed a preliminary version of the guideline document to identify any factual errors and to comment on the clarity of the language, contextual issues and implications for implementation. The group ensured that the guideline decision-making processes had considered and incorporated the contextual values and preferences of persons affected by the recommendation, including pregnant women and adolescent girls, health-care professionals and policy-makers. It was not within the ERG’s remit to change recommendations previously formulated by the GDG.
Systematic review team and guideline methodologists
The managing editors of the Cochrane Pregnancy and Childbirth Group coordinated the updating of the quantitative systematic review and facilitated collaboration between systematic review authors and guideline methodologists. Methodologists from the Evidence-based Medicine Consultancy Ltd in the United Kingdom worked closely with the WHO Steering Group to conduct the additional pre-specified analysis required by the GDG for this recommendation, and with methodologists from the Centro Rosarino de Estudios Perinatales (CREP) in Argentina, who appraised the quantitative evidence using standard operating procedures using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology (16). Two qualitative evidence experts from the University of Central Lancashire in the United Kingdom systematically reviewed qualitative studies related to women’s and health professionals’ views on ANC, and synthesized this evidence.
External partners and observers
Representatives of the International Federation of Gynaecology and Obstetrics (FIGO), the International Confederation of Midwives (ICM), the United Nations Population Fund (UNFPA), the United States Agency for International Development (USAID), the United Nations Children’s Fund (UNICEF) and the Bill & Melinda Gates Foundation were invited to the final GDG meeting to serve as observers. All these organizations are potential implementers of the proposed guideline with a history of collaboration with WHO in guideline dissemination and implementation. Observers do not participate in the formulation of recommendations.
Declaration of interests by external contributors
WHO requires that experts serving in an advisory role disclose any circumstances that could give rise to actual or ostensible conflicts of interest. In accordance with the WHO guidelines for declarations of interests (WHO Experts) (17), all GDG members, as well as ERG members and other external collaborators, were asked to declare in writing any competing interests (whether academic, financial or other) at the time of the invitation to participate in the ANC guideline development process. The standard WHO form for declarations of interest (DOI) was completed and signed by each expert and sent electronically to the responsible technical officer. The WHO Steering Group reviewed all the DOI forms before finalizing experts’ invitations to participate. Where any conflicts of interest were declared, the Steering Group determined whether they were serious enough to affect the individual’s ability to make objective judgements about the evidence or recommendation. To ensure consistency, the Steering Group applied the criteria for assessing the severity of a conflict of interest in the WHO handbook for guideline development (15).
All findings from DOI statements were managed in accordance with the WHO DOI guidelines on a case-by-case basis and communicated to the experts. Where a conflict of interest was not considered significant enough to pose any risk to the guideline development process or reduce its credibility, the expert was only required to declare such conflict at the GDG meeting and no further action was taken. A summary of the DOI statements and information on how conflicts of interest were managed are included in Annex 2. In order to strengthen public trust and transparency in connection with WHO meetings involving the provision of expert advice in developing technical norms and standards, the names and brief biographies of individuals considered for participation on this guideline – together with a description of the objectives of relevant meetings – were made public ahead of the first meeting planned to allow time for public notice and comment.
Identifying priority questions and outcomes
The priority question and outcomes were aligned with those of the ANC guideline (1). This question and its outcomes were originally informed through an extensive scoping exercise of existing clinical practice guidelines relevant to routine ANC, supplemented by searching the Cochrane Database of Systematic Reviews for existing key systematic reviews relevant to ANC. Critical and important outcomes were informed by these reviews, as well as by a WHO-commissioned scoping qualitative review of what women want during pregnancy (18). The findings of the latter revealed that pregnant women want a positive pregnancy experience, defined as maintaining physical and sociocultural normality; maintaining a healthy pregnancy and baby; having an effective transition to positive labour and birth; and achieving a positive motherhood. This composite outcome of a “positive pregnancy experience” became the overarching principle of ANC guideline recommendations.
Evidence identification and retrieval
Evidence to support this recommendation was derived from a number of sources by the methodologists working closely with the WHO Steering Group. An updated Cochrane systematic review was the primary source of evidence on effectiveness of oral antenatal MMS. Earlier versions of this review, in which evidence on effectiveness was derived from randomized controlled trial (RCT) data assessed and synthesized using standardized Cochrane methodology, supported the ANC guideline recommendation of 2016. The up-to-date RevMan file was retrieved from the Cochrane Pregnancy and Childbirth Group and customized to reflect the key comparisons, GDG-specified subgroup analyses, and outcomes relevant to the ANC guideline. Evidence was evaluated according to standard operating procedures approved by the WHO Steering Group, and evidence profiles (in the form of GRADE tables) were prepared, including assessment of the certainty of the evidence, for comparisons of interest.
The latest versions of two qualitative systematic reviews commissioned by the WHO Steering Group for the 2016 guideline development process informed the values, acceptability and feasibility criteria of these evidence-to-decision (EtD) frameworks (18,19). Additionally, systematic reviews of cost-effectiveness were identified through PubMed searches of the literature.
Quality assessment and grading of the evidence
The GRADE approach (16) to appraising the certainty of quantitative evidence was used, meaning that the certainty of evidence for each outcome was rated as “high”, “moderate”, “low”, or “very low” based on a set of established criteria. As a baseline, the evidence from the Cochrane reviews was rated “high certainty” because it was derived from RCTs; this rating was then downgraded according to considerations of risk of bias, inconsistency, imprecision, indirectness, and publication bias or other considerations.
Qualitative evidence was derived from qualitative evidence syntheses (QES) performed for the WHO 2016 ANC guideline (18,19). Previously subjected to quality appraisal using the Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual) tool, the evidence was not re-graded for this updated recommendation. The GRADE-CERQual tool, which uses a similar approach conceptually to other GRADE tools, rates the level of confidence that can be placed in QES evidence according to four components: methodological limitations of the individual studies; adequacy of data; coherence; and relevance to the review question of the individual studies contributing to a QES finding (20).
Preparation of the evidence summary
The WHO Steering Group supervised and finalized the preparation of the evidence summary and profile, in collaboration with the guideline methodologists, using the DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) framework. DECIDE is an EtD tool that includes explicit and systematic consideration of research evidence on interventions according to six criteria, namely, effects, values, resources, equity, acceptability and feasibility (21). These six EtD criteria were populated with the research evidence, where available; in addition, information from other sources was described in the “additional considerations” subsections of each criterion. Certainty of the graded evidence on intervention effectiveness was systematically interpreted in EtD frameworks according to Cochrane Effective Practice and Organization of Care (EPOC) Group guidance (22).
Formulation of the recommendation
GDG members and other participants were provided with the evidence summary in advance of the online GDG meeting held on 4–5 December 2019, organized by the Steering Group from Geneva, Switzerland. During the technical consultation, under the leadership of the GDG chair, the GDG members reviewed, discussed and made judgements on the impact of the interventions for each of the EtD criteria. GDG judgements were summarized in a table before finalization of the recommendation and remarks. The intervention could either be recommended, not recommended, or recommended in specific contexts, namely, rigorous research, targeted monitoring and evaluation, or another GDG-specified context.
Decision-making process
The online GDG meeting was guided by a clear protocol, designed to allow the recommendation to be formulated through a process of group discussion, until consensus was reached. The final adoption of the recommendation and its context, if applicable, was confirmed by unanimous consensus (i.e. full agreement among all GDG members).
Guideline preparation and peer review
Following the online GDG meeting, members of the WHO Steering Group, assisted by a methodologist, drafted a full guideline document to accurately reflect the deliberations and decisions of participants. A preliminary version of the document was sent electronically to participants and the ERG for final review and technical comments. The Steering Group carefully evaluated the input of the peer reviewers for inclusion in the guideline document and made revisions to the guideline draft as needed. After the GDG meetings and peer-review process, further modifications to the guideline by the Steering Group were limited to corrections of factual errors and improvements in language to address any lack of clarity. The document was then submitted for executive clearance according to established WHO publication procedures.
