Changes in Microbiota and Iron Status After Iron Fortification of Complementary Foods

Study Overview
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Brief Summary
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Infants and children under two years are the group with the highest rates of iron deficiency anemia. Provision of sufficient dietary iron to this age group is a challenge, and in-home iron fortification of complementary foods using micronutrient powders can be an effective approach. However, WHO has recently cautioned against untargeted use of in-home micronutrient powders that contain the entire iron RDA for a child in a single dose in areas with high rates of infections from malaria and diarrheal disease. Therefore, in this study, we will investigate the effect on the infant gut microbiota of a low dose (ca. 25% of the RDA) of highly bioavailable iron, provided by a micronutrient powder added to a complementary food. The study aim is to determine if in-home fortification using an iron-containing micronutrient powder in Kenyan infants will improve iron status and/or modify the composition and metabolic activity of the gut microbiota. Active surveillance will be done weekly to monitor the health of the infants. Our study will be done in a subgroup (n=160) of a larger double-blind controlled feeding trial in which 330 infants will be randomized to receive a micronutrient powder containing either 2.5 mg iron or no iron for 1 year. In our substudy, the infants will be studied only over the first 6 months of the 1 year intervention. Blood samples, taken at baseline and after 6 months will be used to define the iron status and the anemia level of the infants. Stool samples (2 at baseline before intervention, 6 throughout the study and additional samples in case of diarrhea) will be obtained for analysis of the gut microbiota. In the entire study (n=330), we will measure changes in iron status over 1 year.

Official Title
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The Effect of Iron Fortification of Complementary Foods on Iron Status and Infant Gut Microbiota in Kenya

Conditions
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Bacterial Infections

Intervention / Treatment
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* Dietary Supplement: fortification with iron and micronutrients
* Dietary Supplement: Sprinkles


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mother at least ≥15 years of age, infants 5.5- 6.5 months Willingness to provide informed consent Apparent good health Long-term residence in study site and anticipating residing in the area for at least 3 years Speak a Mjikenda language or Kiswahili in the home Willingness to provide blood samples during clinic visits Exclusion Criteria: Hemoglobin <70 g/L for infants; these infants will be referred for treatment at the local health clinic/hospital. Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurological condition or any other finding that in the opinion of the PI or co-researchers that would increase risk of participating in the study. Other conditions that in the opinion of the PI or co-researchers would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 28 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MixMe powder (iron & micronutrients)<br> | Dietary Supplement: fortification with iron and micronutrients<br>* Iron 0 or 2.5 mg; Copper 0.34 mg; 30 µg Iodine; 7 µg Selenium; 2.5 mg Zinc; 100 µg Vitamin A; Vitamin D 5 µg; 5 mg Tocopherol Equivalent; 30 µg Vitamin K1; 10.5 mg Thiamine; 0.5 mg Riboflavin; 0.5 mg Pyridoxine; 90 µg Folic Acid Anhydrous; 6 mg Niacinamide; 60 mg Vitamin C; 0.9 µg Vitamin B12<br>|
| Placebo Comparator: MixMe powder (micronutrients, no iron)<br> | Dietary Supplement: fortification with iron and micronutrients<br>* Iron 0 or 2.5 mg; Copper 0.34 mg; 30 µg Iodine; 7 µg Selenium; 2.5 mg Zinc; 100 µg Vitamin A; Vitamin D 5 µg; 5 mg Tocopherol Equivalent; 30 µg Vitamin K1; 10.5 mg Thiamine; 0.5 mg Riboflavin; 0.5 mg Pyridoxine; 90 µg Folic Acid Anhydrous; 6 mg Niacinamide; 60 mg Vitamin C; 0.9 µg Vitamin B12<br>|
| Experimental: Sprinkles (iron and micronutrients)<br>Vitamin A 300 µg; Vitamin C 30 mg; Folic Acid 160 µg; Iron 12.5 mg; Zinc 5 mg | Dietary Supplement: Sprinkles<br>* Daily 12.5mg Ferrous fumarate iron with microntrient is compared to no iron with micronutrients. Duration of intervention is 4 months, 80 infants will be inclulded.<br>|
| Placebo Comparator: Sprinkles (micronutrients, no iron)<br>Vitamin A 300 µg; Vitamin C 30 mg; Folic Acid 160 µg; Zinc 5 mg | Dietary Supplement: Sprinkles<br>* Daily 12.5mg Ferrous fumarate iron with microntrient is compared to no iron with micronutrients. Duration of intervention is 4 months, 80 infants will be inclulded.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut microbiota composition | Changes in gut microbiota composition | Fecal sample after 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| iron status | Efficacy of iron fortification in complementary foods | 12 months |