Iron and Vitamin A in School Children (IronVitA)

Effects of Intermittent Iron and Vitamin A Supplementation on Nutritional Status and Development of Schoolchildren in Arba Minch Zuria District, Ethiopia.

The WHO recommended intermittent iron supplementation as a strategy for prevention of anemia and iron deficiency among school age children. Several aspects of cognitive development, co-supplementation with other micronutrients, severe adverse events especially in the context of malaria were missing.

The investigators will evaluate the effectiveness of intermittent iron and vitamin A supplementation on cognitive development and anemia and iron status of Rural Ethiopian school children.

Study Overview

• Status: Completed
• Conditions: Vitamin A Deficiency; Anemia, Iron Deficiency; Cognitive Development; Helminthic Infection
• Intervention / Treatment: Other: Intermittent placebo iron supplement; Other: Placebo Vitamin A; Other: High-dose Vitamin A supplement; Other: Intermittent iron supplement

Detailed Description

Iron deficiency is the commonest micronutrient deficiency worldwide and the major cause of specific anemia - iron deficiency anemia. Iron is an essential mineral with lots of functions in the human body; its deficiency is associated with cognitive impairment, emotional alteration, and altered homeostasis in myelination and neurotransmission. Vitamin A deficiency can lead to anemia, weakened resistance to infection, blindness, and death. Animal model studies showed that vitamin A could affect cognition. Cognitive skills, influenced by cognitive development of the individual, are related with academic performance of the student and long-term success. One target of the Sustainable Development Goals (SDG 4) is to ensure inclusive and equitable quality education and promote lifelong learning opportunities for all. Poor health and undernutrition of children in Low- and Middle-Income Countries (LMIC) are the major limitations to reach their potential school performance and learning skills. The evidence on the role of intermittent iron supplementation in preventing anemia is strong but several aspects of cognitive development, co-supplementation with other micronutrients such as vitamin A are missing.

The aim of this study is to evaluate the effectiveness of intermittent iron and high-dose vitamin A supplementation integrated within school nutritional plan on anemia, iron status and cognitive development of school children (7 - 10 year old) who live in areas with high rates of food insecurity in Ethiopia.

Method: The study will be carried out at primary schools in Arba Minch Zuria District, Ethiopia in children aged from 7 to 10 years. Eligible children (a total of 504 children) will be randomly assigned to one of the four groups: 1) Control placebo receiving placebo vitamin A and placebo iron supplement; 2) Vitamin A group will receive a high dose vitamin A capsule (200,000 IU) and placebo iron supplement.;3) Iron group will receive weekly iron supplementation (42 mg of elemental iron) and placebo vitamin A; and 4)Iron-vitamin A group will receive a combined weekly iron supplementation and high dose vitamin A.

Iron supplements (42mg of elemental iron)/placebo will be given to school chidlren weekly for 10 months and 200,000 IU of vitamin A/placebo will be given at baseline and after 5 months.

• Study Type: Interventional
• Enrollment (Actual): 504
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ethiopia
  • Arba Minch, Ethiopia
    • Arba Minch University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 10 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• One or both their parents signed informed consent form;
• Their parents planned to stay during the period of the study (for the full academic year) in the kebele; and
• They accept of the intervention package including blood draw and home visits. School children with severe anemia (Hb concentration <80 g/L) will be treated by conventional protocol for three months at nearby health centres. After reassessing their haemoglobin concentrations, they can be assigned to their intervention groups if they become eligible as described above.

Exclusion Criteria:

• Chronically ill children like diagnosed diabetic and asthma
• Severely under nourished children (defined as body mass index z-score <-3 standard deviations of the median WHO reference population)
• Those who are treated for tuberculosis or suspected to have tuberculosis
• Children with diagnosed haemoglobinopathy (sickle cell and thalassemias)
• Children with night blindness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Iron&Vitamin A Placebo; Children randomly assigned to the placebo iron & vitamin A control group will receive weekly three placebo tablets that are identical to the iron tablets (blinded) for the whole duration of the study (9 months of the school year). They will also receive placebo vitamin A at baseline and at mid-line (after 4.5 months).	Other: Intermittent placebo iron supplement; Placebo iron supplements are also three tablets containing the same ingredients as for iron tablets and will be given to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months); Other Names: Control iron; Other: Placebo Vitamin A; Children will receive in a colorful Eppendorf tube 400 micro-liter of corn oil stabilized with vitamin A twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months).; Other Names: Control Vitamin A
Experimental: Vitamin A & Placebo Iron Supplements; Children is this group will receive weekly three placebo tablets that are identical to the iron tablets (blinded) for the whole duration of the study (9 months of the school year). They will also receive a high dose vitamin A capsule (200,000IU) at baseline and after 4.5 months (at mid-line)	Other: Intermittent placebo iron supplement; Placebo iron supplements are also three tablets containing the same ingredients as for iron tablets and will be given to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months); Other Names: Control iron; Other: High-dose Vitamin A supplement; Children will receive in a colorful Eppendorf tube 400 micro-liter of oil-based preparation of retinyl palmitate that contains the equivalent of 100,000 IU (110μmol) of vitamin A and stabilized with 20IU of vitamin E twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months).; Other Names: Experimental Vitamin A
Experimental: Intermittent Iron Supplements & Placebo Vitamin A; Children is this group will receive weekly three tablets of iron (42mg of elemental iron once a week) for 9 months (equivalent to a one school year). They will also receive placebo vitamin A at baseline and at mid-line (after 4.5 months).	Other: Placebo Vitamin A; Children will receive in a colorful Eppendorf tube 400 micro-liter of corn oil stabilized with vitamin A twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months).; Other Names: Control Vitamin A; Other: Intermittent iron supplement; Three iron tablets containing 42 mg of elemental iron will be provided to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months); Other Names: Experimental iron
Experimental: Intermittent Iron Supplements & High dose Vitamin A; Combined weekly iron supplementation (42mg of elemental iron once a week) for 9 months and high dose vitamin A (200,000IU) at baseline and after 4.5 months (mid-line).	Other: High-dose Vitamin A supplement; Children will receive in a colorful Eppendorf tube 400 micro-liter of oil-based preparation of retinyl palmitate that contains the equivalent of 100,000 IU (110μmol) of vitamin A and stabilized with 20IU of vitamin E twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months).; Other Names: Experimental Vitamin A; Other: Intermittent iron supplement; Three iron tablets containing 42 mg of elemental iron will be provided to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months); Other Names: Experimental iron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory span	Digit span (forward and backward) is a standardized test that assess the working memory of the children, one indicator of cognitive development	Memory span of the children will be assessed at 9 months
Spatial exploration and awareness	Vision search using cancellation task of the children, the second indicator of cognitive development	Spatial exploration and awareness of the children will be assessed at 9 months
Reasoning ability	Raven's colored progressive matrices, the third indicator of cognitive development	The reasoning ability of the children will be assessed at 9 months
Anemia	Hemoglobin concentrations (g/dL)	Hemoglobin concentrations of children will be assessed at 9 months
Plasma ferritin	Iron status as indicated plasma ferritin (micro_g/L) is a test to evaluate iron stores	Plasma ferritin is assessed in all children at 9 months
Soluble transferrin receptor	Soluble transferrin receptor (mg/L) is an indicator for iron deficiency especially in high inflammation settings	Soluble transferrin receptor is assessed in all children at 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentrations in Vitamin A (retinol)	Retinol concentrations in serum is an indicator of vitamin A status of children	Retinol concentrations will be assessed in all children at 9 months
Serum concentrations in vitamin B12	Serum concentrations in vitamin B12	Vitamin B12 concentrations will be assessed in all children at 9 months
Prevalence of soil-transmitted helminths	The presence of worm parasites and egg density in the stools. Three common parasites and their eggs will be investigated, i.e. Ascaris lumbricoides (round worm), Trichuris trichiura (whipworm) and Ancyclostoma duodenale or Necater americanus (hookworms).	The prevalence of soil-transmitted helminths will be assessed at 4.5 months and at 9 months
Prevalence of Schistosome infection	The prevalence of Schistosoma mansoni infection	Prevalence of Schistosome infection will be assessed at 4.5 months and at 9 months
Adherence to the iron/placebo supplements	Adherence to the tablets of Iron/Placebo will be assessed through teacher's reports. Teachers are the ones who are providing the supplements in a weekly basis.	Weekly for the whole period of the intervention of 9 months.

Collaborators and Investigators

• Sponsor: University Ghent
• Collaborators: Flemish Interuniversity Council (VLIR); Arba Minch University, Ethiopia

Publications and helpful links

General Publications

• Guideline: Intermittent Iron Supplementation in Preschool and School-Age Children. Geneva: World Health Organization; 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK179850/
• De-Regil LM, Jefferds ME, Sylvetsky AC, Dowswell T. Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD009085. doi: 10.1002/14651858.CD009085.pub2.
• Friis H, Mwaniki D, Omondi B, Muniu E, Magnussen P, Geissler W, Thiong'o F, Michaelsen KF. Serum retinol concentrations and Schistosoma mansoni, intestinal helminths, and malarial parasitemia: a cross-sectional study in Kenyan preschool and primary school children. Am J Clin Nutr. 1997 Sep;66(3):665-71. doi: 10.1093/ajcn/66.3.665.
• Zimmermann MB, Biebinger R, Rohner F, Dib A, Zeder C, Hurrell RF, Chaouki N. Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron. Am J Clin Nutr. 2006 Sep;84(3):580-6. doi: 10.1093/ajcn/84.3.580.
• Mwaniki D, Omondi B, Muniu E, Thiong'o F, Ouma J, Magnussen P, Geissler PW, Michaelsen KF, Friis H. Effects on serum retinol of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomised, controlled trial in Kenyan school children. Eur J Clin Nutr. 2002 Jul;56(7):666-73. doi: 10.1038/sj.ejcn.1601376.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Actual): December 28, 2021
• Study Completion (Actual): December 28, 2021

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Anemia; Vitamin A; Cognitive Development; Intermittent Iron supplementation
• Additional Relevant MeSH Terms: Metabolic Diseases; Infections; Eye Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Parasitic Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Vision Disorders; Anemia, Iron-Deficiency; Night Blindness; Vitamin A Deficiency; Helminthiasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Trace Elements; Micronutrients; Antioxidants; Anticarcinogenic Agents; Vitamins; Iron; Vitamin A; Retinol palmitate
• Other Study ID Numbers: EC/2019/1289

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

All the data that can affect the main or the secondary outcomes will be used in the analyses and shared as necessary.

Data on helminthic infection will use characteristics of the attended schools, villages and of the child (date of birth).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No