Zambia Micronutrient Powder Trial Effectiveness Study
Condition: Iron Deficiency Anaemia; Stunting
MeSH terms: Anemia; Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional

Summary: 
      Addressing micronutrient deficiencies in Zambia is recognized as a national priority by the
      government due to its major contribution to morbidity and mortality among children,
      especially infants in their formative years. One of the most successful, cost-effective, and
      recommended strategy to address micronutrient malnutrition is 'in-home fortification' with
      micronutrient powders (Sprinkles being the most widely recognized) along with nutrition
      education. While this intervention has proven to be safe, effective, and efficacious in
      numerous other countries, a specific national protocol must be developed to maximize its
      effect on reducing anaemia in Zambian children. The proposed research aims to inform such
      protocol.
    

Detailed description: 
      1. Purpose While Zambia has made progress towards reducing under-nutrition among children,
           as measured by underweight, other indicators of nutritional status, particularly
           stunting and anaemia have remained unchanged over the past decades. Repeated national
           surveys show that anaemia remains of public health significance among Zambian children.
           According to WHO classification, a prevalence of anaemia above 40% is categorized as a
           severe public health problem. There has been no significant reduction in anaemia among
           children 6-59 months over the past two decades with an estimated prevalence of 60% in
           1998, 53% in 20032 and 49% in 20093. Further, younger infants were found to be more
           affected than older children with an estimated prevalence of 81% in children 6-18 months
           in 1992 and 61% in children 6-24 months in 2009. In developing countries approximately
           50% of all anaemia is attributed to iron deficiency. It is further estimated that the
           frequency of iron deficiency is about 2.5 times that of anaemia, and when anaemia
           prevalence exceeds 40%, it is assumed that the entire population is suffering from some
           degree of iron deficiency. It is therefore assumed that this is the case with young
           children in Zambia. It is well established that iron deficiency has adverse health
           consequences even before anaemia develops. These include cognitive impairment, decreased
           physical capacity and reduced immunity.

           The most promising strategy for this age group is 'home fortification' of staple
           complementary foods (foods that are consumed in addition to breast milk after 6 months
           of age) with small packets of Micronutrient Powders (MNP) that can be easily mixed with
           home-prepared food.

           MNP are packed in single-serve sachets of mixed vitamins and minerals in powder form,
           which can be instantly sprinkled on prepared ready-to-eat complementary foods for young
           children without changing the colour or taste of the food. The sachets are packed to
           ensure that the correct amounts of micronutrients are given.

           As 'stunting', low height for age, is a problem of public health significance in Zambia
           with 45% of children under five being stunted, this programme will specifically address
           practices that will help to improve nutritional intake and reduce infection in order to
           promote growth during the early years of life.

           Therefore the purpose of this project will be to conduct a 12 month trial of MNP in the
           Northern Province of Zambia, in order to inform a future scale up.

        2. Justification Home fortification with MNP has proved to be efficacious and effective in
           reducing the prevalence of iron deficiency anaemia in young children. Today, MNP are
           successfully used in 45-50 countries worldwide. Based on the large body of evidence
           available, the WHO strongly recommends the use of MNP containing at least iron, vitamin
           A and zinc to improve iron status and reduce anaemia in children 6-23 months of age
           where the prevalence of anaemia in children under two years or under five years of age
           is 20% or higher.

           Previous trials have shown a reduction in anaemia by 31%, iron deficiency by 51% in
           young children consuming MNP and by 20-30% in a few programmatic settings. Furthermore,
           MNP have been shown to be as effective in treating and preventing anaemia as iron syrup.
           In 2011, studies in both Nepal and Kenya reported a significant decrease in the
           prevalence of stunting following the inclusion of MNP in programmes for children 6-59
           months of age.

           While studies have demonstrated MNP to be efficacious and effective in specific
           settings, it is recognized that the findings from one country are not transferable to
           another due to differences in acceptability in accordance with cultural practices,
           economics, food availability and particularly infant and child feeding practices. This
           project was designed to fill the need for a country specific programme with regionally
           relevant training materials, packaging, messages for mothers and distribution system.

           Through our previous work we developed communications materials and packaging for MNP in
           Zambia following a feasibility study and 30-day trial. We evaluated acceptability,
           utilization and compliance of MNP and have modified training materials based on our
           findings. We are now prepared to conduct a 12-month pilot study on MNP integrated with
           IYCF in two districts as the basis for developing an evidence-based policy for
           implementing MNP at scale in Zambia.

        3. Objectives of the MNP Pilot

             -  To demonstrate effectiveness of MNP in reducing iron deficiency and anaemia in
                children 6-23 months after 12 months of supplementation;

             -  To evaluate the effectiveness of an integrated MNP and IYCF package in improving
                child nutritional status and growth;

             -  To quantify the impact of an integrated MNP and IYCF package on reducing iron
                deficiency and anaemia and improving the nutritional status of children.

             -  To develop a MNP communication strategy and Behaviour Change Communication
                materials.

             -  To develop a national plan and policy recommendations for the scale-up and
                integration of MNP into IYCF.

        4. Research Method The 'Home Fortification Programme with MNP for Young Children in Zambia'
           has been designed as a multiphase project with the first phase consisted of two
           components, a feasibility study and a 30-day trial of MNP. The findings of the
           previously conducted feasibility study and the 30-day trial have been integrated into
           the design of the pilot phase, which will inform how best to scale up the MNP
           intervention in Zambia.

      Methods have been developed in accordance with the overall pilot programme goals and
      objectives, taking into consideration the limitations of implementing a rigorous scientific
      design in resource poor settings where access, transportation and communication, are limited.
      Ethical considerations do not allow for a control group as the prevalence of anaemia is
      presumed to be high and the efficacy of MNP at reducing anaemia, established.

      The pilot will be conducted in rural communities of Mbala district in the Northern Province.

      The population for the government's MNP and IYCF intervention is all children 6-23 months and
      their caregivers, living in Mbala district, Northern Province. It is estimated that due to
      logistical constraints, of 26 health facilities, only 9 will be involved in the pilot.
      Therefore the target population will be approximately 2,350 children.

      The formulation for the MNP used in the pilot will contain 15 micronutrients including iron,
      zinc, vitamin A, C, D, B group vitamins, folic acid and iodine in order to control other
      micronutrient deficiencies commonly found in the same individuals. The formulation takes into
      account the recommended daily micronutrient requirements for children 6-23 months, the
      availability from other sources including on-going nutrition programmes and the upper level
      of individual micronutrients. The MNP formula can be safely provided to children that receive
      bi-annual high dose vitamin A, or consume iodized salt.

      Caregivers of children 6-23 months will be supplied with boxes of 30 sachets every two months
      over the duration of one year. This will cover 50% of the recommended Nutrient Intake for
      iron for a child in this age group. The MNP will be delivered to selected families through
      the primary health care system.

      An effectiveness study has been embedded within the pilot programme to assess the effect of
      the MNP plus IYCF intervention package in relation to the programme's goals and outcomes
      under programmatic conditions within the target population. There will be two distinct groups
      invited to participate in the effectiveness component of the pilot, both in the district of
      Mbala. One will serve as a control group, and as such will not receive MNP. Both the
      treatment group and control groups will receive IYCF and early child development (ECD)
      training, deworming tablets (Mebendazole) and insecticide-treated nets, while the treatment
      group will additionally receive MNP.

      Mother-child pairs from the two groups will be closely followed across the 12 month
      intervention period with an in-depth assessment taking place at three points in time;
      baseline, 6 months and 12 months after the intervention begins. The baseline evaluation will
      be conducted before the mothers are trained in the use of MNP as part of complementary
      feeding. The tools used for the assessment are described below.

      The primary outcome variable used for the determination of the sample size for the
      effectiveness component of the study is a change in prevalence of anaemia among participating
      children (defined as haemoglobin < 11.0 g/dL) over the course of the 12-month intervention in
      the district of Mbala

      Data collected will include anthropometry, in the form of MUAC, wasting (Weight-for-height),
      stunting (height-for-age), and weight-for-age. Biochemical data will be haemoglobin, serum
      ferritin, and serum transferrin receptor to measure iron status, C-reactive protein and
      alpha-1 acid glycoprotein will be used to control for infections, and retinol binding protein
      to measure vitamin A status. There will also be questionnaires, consisting of quantitative
      and qualitative questions, that will be administered.

      6) Statistical Analysis

      Data will be entered in the field into Excel and later transferred to an SPSS file for
      analysis. At baseline, descriptive characteristics will be calculated for all variables and
      key outcome variables compared across groups. At midline and end-line comparisons will be
      made across time among the three groups using means, standard deviation, and proportions as
      relevant. The p-value will be set at 0.05 with adjustments made for multiple comparisons.
    

Intervention name(s): Micronutrient Powders
Intervention type(s): Dietary Supplement
Intervention description(s): Mothers will receive a one box containing 30 sachets of Micronutrient Powders (MNP) every other month. MNP will be procured offshore with support from UNICEF Supply Division in Copenhagen, which maintains a list of approved MNP suppliers and ensures compliance with standard requirements and product specifications. For this study MNP will be purchased from Piramal Healthcare Ltd, India.
Intervention MeSH terms: Micronutrients; Trace Elements
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention