Effect of CFR and Iron Supplementation on Iron Status and Gut Microbiota of 1-2 Years Old Myanmar Children

Study Overview
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Brief Summary
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Complementary feeding diet in developing countries cannot meet iron requirements of infants and young children. Iron supplementation is mostly used to treat iron deficiency whereas iron fortification is cost-effective strategy to control iron deficiency in developing countries. However, a recent study showed that iron fortification imposed negative impact on gut microbiota by increasing colonization of gut pathogen over beneficial bacteria. Gut microbiota plays essential roles in nutrient absorption, vitamin synthesis; intestinal mucosal barrier function and pathogen displacement. Iron is essential for growth and virulence of most gut pathogens and so iron supplementation might have similar negative impact on gut microbiota composition. Therefore, nutrition interventions would not be justified by assessing micronutrient status alone ignoring any possible deterioration of gut microbiota. The investigators hypothesized that optimizing the nutrient intake from locally available foods according to complementary feeding recommendation (CFR) can improve the iron status of these children while maintaining healthy gut microbiota composition. A randomized, placebo-controlled, community-based, intervention trial will be conducted in Ayeyarwady division of Myanmar where childhood undernutrition is prevalent. The aim of this study is to compare the effect of optimized CFR to iron supplementation on iron status and gut microbiota composition of 1-2years old Myanmar children. Cluster randomization will be done at the village level to randomly allocate the villages into CFR or non-CFR villages. Individual randomization will be done to randomly assign each child into iron or placebo syrup so that individual children will receive one of 4 treatment groups (CFR, Fe, CFR + Fe, and Control) for a period of 24 weeks. Based on expected between-groups difference of hemoglobin 5g/L, at 80% power, 5% level of significance, 15% drop-out rate; after taking into account the cluster effect; required sample will be 109 per group (total = 436). A sub-sample of 15 children from each group will be randomly selected for gut microbiota assessment (total = 60). Blood samples for iron status and stool samples for gut microbiota assessment will be collected at baseline and endline. Anthropometric measurements, usual intake of iron and infectious disease morbidity will also be assessed.

Official Title
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The Effect of Optimized Local Food-based Complementary Feeding With or Without Iron Supplementation on Iron Status and Gut Microbiota of 1-2 Years Old Myanmar Children

Conditions
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Iron Deficiency, Iron Deficiency Anemia

Intervention / Treatment
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* Dietary Supplement: Iron supplementation
* Other: CFR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 12-18 months Apparently healthy Not consuming regular iron containing supplements during the last 4 months Exclusion Criteria: With severe anemia (Hemoglobin < 50g/L) Malaria test positive with Immuno-chromatographic test (ICT) Mothers/ Caregivers are not willing to join the study Suffer from chronic diseases which can affect their dietary intake

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CFR group<br>The children in this group will receive complementary feeding with locally available foods according to optimized complementary feeding recommendation (CFR) | Dietary Supplement: Iron supplementation<br> <br> |
| Experimental: Fe group<br>The children in this group will receive iron supplementation 2mg/kg/day of ferric Na EDTA (in the form of syrup) daily for 24 weeks duration. | Other: CFR<br>* Complementary feeding with locally available foods according to optimized complementary feeding recommendation (CFR)<br>* Other names: Complementary Feeding Recommendation;|
| Experimental: CFR + Fe group<br>The children in this group will receive both local food-based complementary feeding according to CFR and Iron supplementation for 24 weeks duration | Dietary Supplement: Iron supplementation<br> <br> Other: CFR<br>* Complementary feeding with locally available foods according to optimized complementary feeding recommendation (CFR)<br>* Other names: Complementary Feeding Recommendation;|
| Placebo Comparator: Control group<br>The children in this group will receive basic health services and placebo syrup. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Iron status | Iron status indicators including hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR) concentration will be measured at the beginning and at the end of 24 weeks intervention. | Baseline (at week 0) and Endline (at week 24) | 
| Change in Gut microbiota composition | Sub-samples analysis from 60 children (15 children from each group) will be done to detect the DNA-copy number of Total bacteria, Lactobacillus, Bifidobacteria and Enterobacteria in group and Enteropathogenic E.coli (EPEC), Enterotoxigenic E.coli (ETEC) and Enteroaggregative E.coli (EAEC) species by PCR analysis at the beginning and at the end of 24 weeks intervention. | Baseline (at week 0), Endline (at week 24) |