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.

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.

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

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).

Iron supplements and their placebo: Both iron and placebo supplements will be produced by Metagenics (Belgium) for the context of this study. Placebo tablets will have the same taste, and shape of the iron tablets, the colour is slightly different because of the characteristics of the products but the blinding is ensured. The blister/ the tablets will be packed and only coded.

Vitamin A and its placebo: Vitamin A capsule is oral liquid, red, 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. The placebo supplement will have the same oil composition except that it will not contain vitamin A equivalent. Placebo oil and vitamin A preparation will be transferred to two colored (red and orange) Eppendorf® Safe-Lock microcentrifuge tubes volume 0.6 mL by a researcher who is not involved in the study.