Why is multiple micronutrient powder ineffective at reducing anaemia among 12-24 month olds in Colombia? Evidence from a randomised controlled trial

Alison Andrew, Orazio Attanasio, Emla Fitzsimons, Marta Rubio-Codina, Alison Andrew, Orazio Attanasio, Emla Fitzsimons, Marta Rubio-Codina

Abstract

In Colombia's bottom socio-economic strata, 46.6% of children under two are anaemic. A prevalence of above 20% falls within the WHO guidelines for daily supplementation with multiple micronutrient powder (MNP). To evaluate the effect of daily MNP supplementation on anaemia amongst Colombian children aged 12-24 months we ran a cluster RCT (n=1440). In previous work, we found the intervention had no impact on haemoglobin or anaemia in this population. In this current paper, we investigate this null result and find it cannot be explained by an underpowered study design, inaccurate measurements, low adoption of and compliance with the intervention, or crowding out through dietary substitution. We conclude that our intervention was ineffective at reducing rates of childhood anaemia because MNP itself was inefficacious in our population, rather than poor implementation of or adherence to the planned intervention. Further analysis of our data and secondary data suggests that the evolution with age of childhood anaemia in Colombia, and its causes, appear different from those in settings where MNP has been effective. Firstly, rates of anaemia peak at much earlier ages and then fall rapidly. Secondly, anaemia that remains after the first year of life is relatively, and increasingly as children get older, unrelated to iron deficiency. We suggest that factors during gestation, birth, breastfeeding and early weaning may be important in explaining very high rates of anaemia in early infancy. However, the adverse effects of these factors appear to be largely mitigated by the introduction of solid foods that often include meat. This renders population wide MNP supplementation, provided after a diet of solid foods has become established, an ineffective instrument with which to target Colombia's childhood anaemia problem.

Keywords: Anaemia; Child; Colombia; Haemoglobin; Iron-deficiency; Micronutrients; Multiple micronutrient powder; Nutrition.

Figures

Fig. 1
Fig. 1
Meta analysis of the effect of MNP interventions on mean haemoglobin. Random effects meta-analysis performed using STATA’s metan command. Age(months)=age in months at the start of intervention. WMD=Weighted Mean Difference. Hb(BL)=baseline haemoglobin (g/L). Hb(FU-control)=haemoglobin (g/L) of the control group at follow-up. Bottom row excludes our study. Studies weighted using effective sample size accounting for design effects in cluster randomised controlled trials. For studies that do not report the intra-cluster correlation coefficient (ICC) we use 0.07 (mid point between the two studies that report an ICC: Attanasio et al. (2014) and Jack et al. (2012)) to calculate the effective sample size. Details of all studies provided in Table A1.
Fig. 2
Fig. 2
Coefficient plot of estimated effects of MNP on haemoglobin for subgroups of children with baseline haemoglobin below successively lower thresholds. For each baseline haemoglobin cut-off on the x-axis the plot shows the estimated effect of MNP on follow-up haemoglobin for the subgroup of children whose baseline haemoglobin was below that cut-off. Points represent point estimates and bars represent the 95% confidence interval around each estimate. All estimated effects adjusted for sex, tester, region, second order polynomials in age and altitude and baseline haemoglobin using linear regression. Confidence intervals adjusted for clustering at the town level.
Fig. 3
Fig. 3
Prevalence of childhood anaemia by age across different regions. Colombian data from ENSIN 2010 for sub-sample SISBEN level one households. USA data from PEDNSS. Continent level data from all DHS surveys which collected childhood anaemia rates. Most recent data used when more than one survey available. Country data weighted by World Bank population estimates of children under four to estimate the combined prevalence, grouped at the continent level. Countries included in continent level averages are listed in the online appendix (Table A5).

References

    1. Attanasio O.P., Fernandez C., Fitzsimons E.O., Grantham-McGregor S.M., Meghir C., Rubio-Codina M. Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: Cluster randomized controlled trial. British Medical Journal. 2014;349
    1. Adu-Afarwuah S., Lartey A., Brown K.H., Zlotkin S., Briend A., Dewey K.G. Randomized comparison of 3 types of micronutrient supplements for home fortification of complementary foods in Ghana: Effects on growth and motor development. American Journal of Clinical Nutrition. 2007;86:412–420.
    1. Allen L.H. Anemia and iron deficiency: Effects on pregnancy outcome. American Journal of Clinical Nutrition. 2000;71:1280S–1284SS.
    1. Brabin B.J., Premji Z., Verhoeff F. An analysis of anemia and child mortality. J. Nutr. 2001;131:636S–645S. (discussion 646S–648S)
    1. Balarajan Y., Ramakrishnan U., Ozaltin E., Shankar A.H., Subramanian S.V. Anaemia in low-income and middle-income countries. Lancet. 2011;378:2123–2135.
    1. Beutler E., Waalen J. The definition of anemia: What is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107:1747–1750.
    1. Brault-Dubuc M., Nadeau M., Dickie J. Iron status of French-Canadian children: A three year follow-up study. Human Nutrition Applied Nutrition. 1983;37A:210–221.
    1. Centers for Disease Control and Prevention (2011). Pediatric Data Tables-Table 8D. 〈 Accessed 03.12.15.
    1. DeMaeyer E., Adiels-Tegman M. The prevalence of anaemia in the world. World Health Statistics Quarterly. 1985;38:302–316.
    1. De-Regil L.M., Suchdev P.S., Vist G.E., Walleser S., Peña-Rosas J.P. Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age. Cochrane Database of Systematic Reviews. 2011
    1. Grantham-McGregor S., Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. Journal of Nutrition. 2001;131:649S–666S. (discussion 666S–668S)
    1. Giovannini M., Sala D., Usuelli M., Livio L., Francescato G., Braga M. Double-blind, placebo-controlled trial comparing effects of supplementation with two different combinations of micronutrients delivered as sprinkles on growth, anemia, and iron deficiency in cambodian infants. Journal of Pediatric Gastroenterology Nutrition. 2006;42:306–312.
    1. Greenland S. An introduction to instrumental variables for epidemiologists. International of Journal Epidemiology. 2000;29:722–729.
    1. Geissler C., Powers H. Elsevier Health Sciences; 2010. Human nutrition.
    1. Higgins J.P.T., Thompson S.G., Deeks J.J., Altman D.G. Measuring inconsistency in meta-analyses. British Medical Journal. 2003;327:557–560.
    1. Hoenig J.M.H., Eisey D.M.H. The abuse of power: The pervasive fallacy of power calculations for data analysis. The American Statistician. 2001;55:1–6. .
    1. Instituto Colombiano de Bienestar Familiar, Encuesta Nacional de Situación Nutricional en Colombia (2010). 〈 Accessed 03.12.15.
    1. Jack S.J., Ou K., Chea M., Chhin L., Devenish R., Dunbar M. Effect of micronutrient sprinkles on reducing anemia: A cluster-randomized effectiveness trial. Archives of Pediatrics and Adolescent Medicine. 2012;166:842–850.
    1. Kounnavong S., Sunahara T., Mascie-Taylor C.G.N., Hashizume M., Okumura J., Moji K. 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 randomised trial. Nutrition Journal. 2011;10:129.
    1. Lemaire M., Islam Q.S., Shen H., Khan M.A., Parveen M., Abedin F. Iron-containing micronutrient powder provided to children with moderate-to-severe malnutrition increases hemoglobin concentrations but not the risk of infectious morbidity: A randomized, double-blind, placebo-controlled, noninferiority safety trial. American Journal of Clinical Nutrition. 2011;94:585–593.
    1. Lundeen E., Schueth T., Toktobaev N., Zlotkin S., Hyder S.M.Z., Houser R. Daily use of Sprinkles micronutrient powder for 2 months reduces anemia among children 6 to 36 months of age in the Kyrgyz Republic: A cluster-randomized trial. Food and Nutrition Bulletin. 2010;31:446–460.
    1. Macharia-Mutie C.W., Moretti D., Van Den Briel N., Omusundi A.M., Mwangi A.M., Kok F.J. Maize porridge enriched with a micronutrient powder containing low-dose iron as NaFeEDTA but not Amaranth grain flour reduces anemia and iron deficiency in Kenyan preschool children. Journal of Nutrition. 2012
    1. Menon P., Ruel M.T., Loechl C.U., Arimond M., Habicht J.-P., Pelto G. Micronutrient Sprinkles reduce anemia among 9- to 24-mo-old children when delivered through an integrated health and nutrition program in rural Haiti. Journal of Nutrition. 2007;137:1023–1030.
    1. Murphy S.P., Allen L.H. Animal source foods to improve micronutrient nutrition and human function in developing countries nutritional importance of animal source foods. Journal of Nutrition. 2003;133:3932S–3935S. .
    1. McDonald S.J., Middleton P., Dowswell T., Morris P.S. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database of Systematic Reviews. 2013
    1. Nkrumah B., Nguah S.B., Sarpong N., Dekker D., Idriss A., May J. Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting. BMC Clinical Pathology. 2011;11:5.
    1. Olaya G.A., Lawson M., Fewtrell M.S. Efficacy and safety of new complementary feeding guidelines with an emphasis on red meat consumption: A randomized trial in Bogota, Colombia. American Journal of Clinical Nutrition. 2013;98:983–993.
    1. Stoltzfus R. Defining iron-deficiency anemia in public health terms: A time for reflection. Journal of Nutrition. 2001;131:565S–567S.
    1. Soofi S., Cousens S., Iqbal S.P., Akhund T., Khan J., Ahmed I. Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: A cluster-randomised trial. Lancet. 2013;382:29–40.
    1. Suchdev P.S., Ruth L.J., Woodruff B.A., Mbakaya C., Mandava U., Flores-Ayala R. Selling Sprinkles micronutrient powder reduces anemia, iron deficiency, and vitamin A deficiency in young children in Western Kenya: A cluster-randomized controlled trial. American Journal of Clinical Nutrition. 2012;95:1223–1230.
    1. Sharieff W., Bhutta Z., Schauer C., Tomlinson G., Zlotkin S. Micronutrients (including zinc) reduce diarrhoea in children: The Pakistan sprinkles diarrhoea study. Archives of Disease in Childhood. 2006;91:573–579.
    1. Stoltzfus R.J. How can the scientific community support the generation of the evidence needed to improve the quality of guidelines for micronutrient interventions? Advanced Nutrition: An International Review Journal. 2014;5:40–45.
    1. Sterne J.A.C., White I.R., Carlin J.B., Spratt M., Royston P., Kenward M.G. Multiple imputation for missing data in epidemiological and clinical research: Potential and pitfalls. British Medical Journal. 2009;338
    1. Thompson J., Biggs B.-A., Pasricha S.-R. Effects of daily iron supplementation in 2- to 5-year-old children: Systematic review and meta-analysis. Pediatrics. 2013;131:739–753.
    1. Veenemans J., Milligan P., Prentice A.M., a Schouten L.R., Inja N., van der Heijden A.C. Effect of supplementation with zinc and other micronutrients on malaria in Tanzanian children: A randomised trial. PLoS Medicine. 2011;8:1–15.
    1. World Health Organization (2005). Food and agriculture organization, vitamin and mineral requirements in human nutrition, Geneva
    1. World Health Organization (2011a). WHO Guildline: Use of multiple micronutrient powders for home fortification of foods consumed by infants and children 6–23 months of age, Geneva.
    1. World Health Organization (2011b). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity, Geneva.
    1. Zlotkin S.H., Schauer C., Christofides A., Sharieff W., Tondeur M.C., Ziauddin Hyder S.M. Micronutrient sprinkles to control childhood anaemia: A simple powdered sachet may be the key to addressing a global problem. PLoS Medicine. 2005;2:0024–0028.
    1. Zlotkin S., Newton S., Aimone A.M., Azindow I., Amenga-Etego S., Tchum K. Effect of iron fortification on malaria incidence in infants and young children in Ghana: A randomized trial. Journal of American Medical Association. 2013;310:938–947.

Source: PubMed

3
Subskrybuj