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

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

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.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Dietary supplement: fortification with iron and micronutrients; Dietary supplement: Sprinkles

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Kwale district
    • Kikoneni, Kwale district, Kenya
      • Kikoneni Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MixMe powder (iron & micronutrients)	Dietary supplement: fortification with iron and micronutrients; 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
Placebo Comparator: MixMe powder (micronutrients, no iron)	Dietary supplement: fortification with iron and micronutrients; 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
Experimental: Sprinkles (iron and micronutrients); Vitamin A 300 µg; Vitamin C 30 mg; Folic Acid 160 µg; Iron 12.5 mg; Zinc 5 mg	Dietary supplement: Sprinkles; 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.
Placebo Comparator: Sprinkles (micronutrients, no iron); Vitamin A 300 µg; Vitamin C 30 mg; Folic Acid 160 µg; Zinc 5 mg	Dietary supplement: Sprinkles; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: University of Nairobi; University of KwaZulu
• Investigators: Study Director: Michael B Zimmermann, M.D., Human Nutrition Laboratory, Swiss Federal Institute of Technology; Principal Investigator: Jane Kvalsvig, PhD, Department of Public Health Medicine, Nelson Mandela School of Medicine, South Africa

Publications and helpful links

General Publications

• Jaeggi T, Kortman GA, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, Njenga J, Mwangi A, Kvalsvig J, Lacroix C, Zimmermann MB. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut. 2015 May;64(5):731-42. doi: 10.1136/gutjnl-2014-307720. Epub 2014 Aug 20.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: April 23, 2010
• First Submitted That Met QC Criteria: April 26, 2010
• First Posted (Estimate): April 28, 2010

Study Record Updates

• Last Update Posted (Estimate): June 7, 2013
• Last Update Submitted That Met QC Criteria: June 6, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Physiological Effects of Drugs; Micronutrients; Trace Elements
• Other Study ID Numbers: 2-cercamondi