Optimal iron content in ready-to-use therapeutic foods for the treatment of severe acute malnutrition in the community settings: a protocol for the systematic review and meta-analysis

Abstract

IntroductionThe current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older.Methods and analysisWe will search multiple electronic databases. We will include randomised controlled trials and non-randomised studies with a control arm. The intervention group will be infants who received RUTF treatments other than the current recommended guidelines set forth by the WHO. The comparison group is children receiving RUTF containing iron at the current WHO-recommended level of 1.9 mg/100 kcal (10–14 mg/100 g). The primary outcomes of interest include blood haemoglobin concentration, any anaemia, severe anaemia, iron-deficiency anaemia, recovery from SAM and any adverse outcomes. We will use meta-analysis to pool findings if sufficient homogeneity exists among included studies. The risk of bias in studies will be evaluated using the Cochrane risk of bias-2. We will use the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach to examine the overall certainty of evidence.Ethics and disseminationThis is a systematic review and will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal and will guide the WHO’s recommendation on the optimal iron content in RUTFs for the treatment of SAM in children aged 6–59 months.

Increased vs. Standard Dose of Iron in Ready-to-Use Therapeutic Foods for the Treatment of Severe Acute Malnutrition in a Community Setting: A Systematic Review and Meta-Analysis

“…We followed the standardized methods of the Cochrane Collaboration to conduct this review. We wrote a protocol for the review that was externally reviewed and publicly available [ 18 ]. All titles and abstracts were screened in duplicate, and data extraction was also performed in duplicate for the included studies.…”

“…This systematic review was commissioned by the WHO, conducted according to the guidelines of the Cochrane Collaboration, and reported according to PRISMA 2020 guidelines [ 17 ]. The detailed protocol is published [ 18 ]. We describe the methods briefly in the sections below.…”

“…We did not apply any search restrictions to exclude studies based on the outcome, publication year, publication status, or language. Additional resources were also searched, as described in the published protocol [ 18 ]. The reference sections of the included studies and known systematic reviews on the topic were also hand-searched to include any eligible studies [ 9 ].…”

“…For continuous outcomes, we pooled the data to obtain an average mean difference and reported it with its 95% CI. Statistical heterogeneity of effect sizes within any given meta-analysis was assessed using the χ 2 , I 2 , and tau statistics [ 18 ].…”

“…We planned a number of subgroup analyses [ 18 ]. based on country: low-income country vs. middle-income country vs. high-income country; type of RUTF: standard RUTF with high iron content vs. non-standard RUTF with high iron content; type of participants: studies that included children with HIV vs. studies that did not include children with HIV; age: <24 months vs. 24–59 months vs. >59 months; hospitalization: children hospitalized (due to medical complication) prior to starting RUTF vs. children not hospitalized prior to starting RUTF; iron compound (formulation/chemical compound and amount); dose: intervention groups with a dose of iron higher than the WHO standard RUTF vs. intervention group receiving a dose lower the WHO standard RUTF; anemia status: children with anemia at baseline vs. those without anemia at baseline; and time of follow-up: 1 month vs. 3 months vs. 6 months follow-up, and longest follow-up [ 18 ]. None of these subgroup analyses were performed because the number of included studies was small.…”