Background & rationale

1. Effect of daily versus weekly home fortification with multiple Micronutrient powder on haemoglobin concentration of young children in a rural area, Lao People’s Democratic Republic: a Randomized Trial SengchanhKounnavonga,b, Toshihiko Sunaharab, Masahiro Hashizumeb, C.G. Nicholas Mascie-Taylorc, Junko Okumurab, Kazuhiko Mojid, BoungnongBouphaa,Taro Yamamotob a National Institute of Public Health, MOH, Vientiane, Lao People’s Democratic Republic b Department of International Health, Institute of Tropical Medicine (NEKKEN) and the Global Centre of Excellence Program (GCOE), Nagasaki University, Japan c Department of Biological Anthropology, University of Cambridge, United Kingdom d Research Institute for Humanity and Nature, Kyoto, Japan

2. Background & rationale • As in many developing countries, micronutrient malnutrition, namely iron deficiency which causes anemia and suppress motor and mental developments, is a severe public health problem among pre-school children in Lao PDR. • Previous intervention, iron tablet or iron drops were less acceptable to local people because of the bad taste, teeth stain and color. • Recently developed Multivitamins and Minerals Powder (MMP, Sprinkles®) resolved these problems by lipid coating of powder and so far trials in several countries showed encouraging results. • Effectiveness of micronutrient supplementation depends on local food culture and acceptance of people. • It is unknown how it works in Lao PDR.

3. Objective • To examine the efficacy of daily and of twice weekly supplementation using Multi-vitamins & micronutrients powder (MMP) in children 6 to 59 months of age on haemoglobin concentration and on growth

4. The product • MMP- MixMe TM (DSM Nutritional Products Europe Ltd. CH 4002 Basel) • MMP - in single dose sachet (dose=1 sachet/day), Powder form • Minimum changes to the taste, colour or texture of the food • No change in food habit • One dose for one child for one day contains one full recommended nutrient intake (RNI) of vitamins and minerals in one gram of powder • Food based not medical intervention • The nutrient contents per 1g contained of 15 micronutrients: • vitamin A (RE 400µg), • vitamin D3 (5µg, • vitamin E (TE 5mg), • vitamin B1, B2, B6 each (0.5 mg), • Folic acid (150µg), Niacin (6 mg), • vitamin B12 (0.9µg), vitamin C (30mg), • iron (10 mg), zinc (4.1 mg), • Selenium (17µg), copper (0.56 mg), • Iodine (90 µg). • One pack content 1g X 30 sachets.

5. Excluded (n= 31) - Absent at the day of enrolment (n=17) - Having fever at the day of enrolment Methodology Enrolment procedure • age, sex, • socio-economic background Randomly allocated N= 336 Lahanam zone Control group: ( n=110) Twice weekly group (n=115) Daily group ( n=111) 8 months Follow up from March to October 2009 Discontinued - Moved (n=3) -Got diarrhoea (n=1) Discontinued - Got diarrhoea (n=1) Analyzed (n=110) Analyzed (n=111) Analyzed (n=110) 24 0 sachets of MMP provided 64 sachets of MMP provided

6. Anthropometric measurement (Height & weight) • Haemoglobin concentration • Morbidity status: Presence of ARI, Diarrhoea, and other illness conditions • Compliance (weekly counting sachets) • Acceptability based on questionnaire interview & FGD with mothers/care takers at the end of study Outcome measurements

7. Data analysis • PASW statistical package, version 18.0 (SPSS Inc., Chicago, IL, USA). • Socio-demographic, health, and nutrition characteristics (mean and standard deviation (SD) for continuous variables and as frequency for categorical variables) • Differences in prevalence (the Pearson chi-squared test) • Differences in mean haemoglobin concentration and Z-scores between the groups at the beginning and at the end of the intervention were examined using Repeated Measures Analysis of Variance. • The McNemar test was used to assess within group differences at three time points in the study subjects with anaemia and one-way ANOVA was used to assess changes in mean haemoglobin concentration in the treatment groups. • All the analyses were carried out for all subjects and separately for the children who were anaemic at baseline. • Values of p <0.05 were considered to be significant for all tests.

8. Prevalence of anemia & risk factors at the baseline

9. Effect of MMP supplementation on Hb concentration and anemia Improving in Hb concentration: Daily: 120 (± 11.6) - 107.1 (± 12.9) = 12.9 Weekly: 118.0 (± 13.9) - 105.1 (± 13.2) = 12.9 Control: 117.4 (± 12.8) - 114.3 (± 15.2) = 3.1 Reduction in anemia Daily (W24-W0) :53.6-20.0=33.6% Weekly (W24-W0) : 58.6-27.9=30.7% Control (W24-W0) : 34.5-29.1=5.4%

10. Change in Haemoglobin concentration from Week 0 to Week 24 in children who were non-anaemic (haemoglobin concentration ≥ 110 g/L), mild anaemic (100-109 g/L), and moderate to severe anaemic (< 100 g/L) at Week 0. The box indicates the range of the 1st to 3rd quartile with central line at median; Vertical bars indicate the 1.5 times inter-quartile range outside 1st and 3rd quartiles. Within each panel, groups with different letters have significant difference (Mann Whitney U test, P < 0.05). Change in Haemoglobin concentration from Week 0 to Week 12 in children who were non-anaemic (haemoglobin concentration ≥ 110 g/L), mild anaemic (100-109 g/L), and moderate to severe anaemic (< 100 g/L) at Week 0. The box indicates the range of the 1st to 3rd quartile with central line at median; Vertical bars indicate the 1.5 times inter-quartile range outside 1st and 3rd quartiles. Within each panel, groups with different letters have significant difference (Mann Whitney U test, P < 0.05).

11. Overall, the Z-scores of height for age increased • The Z-scores of weight for age showed no major improvements • The weight for height Z-scores decreased in all groups. • The increase in height for age Z-scores and the decrease in weight for height Z-scores were significantly greater in the control and DS groups than in the TWS groups.

12. Compliance & acceptability • Compliance: • was high among group received two sachets of MMP per week (100%), • 72.7% of children consumed five or more sachets of MMP per week and • 43.6% of the children consumed all seven sachets per week for all 24 weeks. • The most common reason for not taking powder in the DS group was illness, such as diarrhoea (n=20), cough (n=10) and forgetting to take supplements (n=32). • No side effects were reported among children received supplementation • Overall, MMP were well accepted by mothers of study subjects.

13. Conclusions • Anaemia prevalence was high especially among young children, children in big families, and those in remote villages • MMP was effective to improve hemoglobin concentration and to reduce anemia • The effects of MMP did not differ significantly between the daily and twice-weekly supplementation arms but compliance was higher in the latter • Implications: • 2 sachets per week would be the recommended dose for the intervention program in this population • For severe to moderate anaemic children daily MMP supplementation was more effective in improving haemoglobin concentration and in reduction in anaemia prevalence • In a longer term, health education that aims to modify food habit would be necessary to improve child growth