This guideline was developed in accordance with WHO evidence-informed guideline development procedures, as outlined in the WHO handbook for guideline development(27).
Advisory groups
A WHO Steering Committee for Nutrition Guidelines Development, led by the Department of Nutrition for Health and Development and the Department of Research Policy and Cooperation, was established in 2009 with representatives from all WHO departments with an interest in the provision of scientific nutrition advice including Child and Adolescent Health and Development, Reproductive Health and Research, and the Global Malaria Programme. The Steering Committee guided the development of this guideline and provided overall supervision of the guideline development process (Annex 2). Two additional groups were formed: an advisory guideline group and an External Experts and Stakeholders Panel.
The Nutrition Guidance Expert Advisory Group, NUGAG, was also established in 2009 (Annex 3). NUGAG consists of four subgroups: (i) Micronutrients, (ii) Diet and Health, (iii) Nutrition in Life course and Undernutrition, and (iv) Monitoring and Evaluation. Its role is to advise WHO on the choice of important outcomes for decision-making and in the interpretation of the evidence. The group includes experts from various WHO expert advisory panels and those identified through open calls for specialists, taking into consideration a balanced gender mix, multiple disciplinary areas of expertise and representation from all WHO regions. Efforts were made to include content experts, methodologists, representatives of potential stakeholders (such as managers and other health professionals involved in the health-care process) and consumers. Representatives of commercial organizations may not be members of a WHO guideline group.
The External Experts and Stakeholders Panel was consulted on the scope of the guideline, the questions addressed, and the choice of important outcomes for decision-making, as well as with regard to review of the completed draft guideline (Annex 4). This was done through the WHO Micronutrients and SCN mailing lists that together include over 5500 subscribers, and through the WHO nutrition web site.
Scope of the guideline, evidence appraisal and decision-making
An initial set of questions (and the components of the questions) to be addressed in the guideline was the critical starting point for formulating the recommendation. The questions were drafted by technical staff at the Micronutrients Unit, Department of Nutrition for Health and Development, based on policy and programme guidance needs of Member States and their partners. The population, intervention, control, outcomes (PICO) format was used (Annex 5). The questions were discussed and reviewed by the WHO Steering Committee for Nutrition Guidelines Development, and feedback was received from 48 stakeholders.
The first NUGAG meeting was held on 22–26 February 2010 in Geneva, Switzerland, to finalize the scope of the questions and rank the critical outcomes and populations of interest. The NUGAG – Micronutrients Subgroup discussed the relevance of the questions and modified them as needed. The guideline group members scored the relative importance of each outcome from 1 to 9 (where 7–9 indicated that the outcome was critical for a decision, 4–6 indicated that it was important and 1–3 indicated that it was not important). The final key questions on the use of iron supplements in children 24–59 months of age and those 60 months and older, along with the outcomes that were identified as critical and important for decision-making are listed using the PICO format in Annex 5.
WHO staff, in collaboration with researchers from other institutions, summarized and appraised the evidence by using the Cochrane methodology for randomized controlled trials.1 For identifying unpublished studies or trials still in progress, a standard procedure was followed to contact more than 10 international organizations working on micronutrients interventions. In addition, the International Clinical Trials Registry Platform (ICTRP), hosted at WHO, was systematically searched for any trials still in progress. No language restrictions were applied to the search. Evidence summaries were prepared according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the overall quality of the evidence (28). GRADE considers the study design; the limitations of the studies in terms of their conduct and analysis; the consistency of the results across the available studies; the directness (or applicability and external validity) of the evidence with respect to the populations, interventions and settings where the proposed intervention may be used; and the precision of the summary estimate of the effect.
Both the systematic reviews and the GRADE evidence profiles for each of the critical outcomes were used for drafting this guideline. The draft recommendation was discussed by the WHO Nutrition Guidance Steering Committee and NUGAG at a second NUGAG consultation, held on 15–18 November 2010, in Amman, Jordan, and the third consultation, held on 14–16 March 2011 in Geneva, Switzerland, where NUGAG members also voted on the strength of the recommendation, taking into account: (i) desirable and undesirable effects of this intervention; (ii) the quality of the available evidence; (iii) values and preferences related to the intervention in different settings; and (iv) the cost of options available to health-care workers in different settings (Annex 6). Consensus was defined as agreement by simple majority of guideline group members. WHO staff present at the meeting as well as other external technical experts involved in the collection and grading of the evidence were not allowed to vote. There were no strong disagreements among the guideline group members.
A public call for comments on the final draft guideline was then released. All interested stakeholders became members of the External Experts and Stakeholders Panel but were only allowed to comment on the draft guideline after submitting a signed Declaration of Interests Form. Feedback was received from 15 stakeholders. WHO staff then finalized the guideline and submitted it for clearance by WHO before publication.
