Hyunseung Kang1, Benno Kreuels, Ohene Adjei, Ralf Krumkamp, Jürgen May, Dylan S Small. 1. Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA, Section for Tropical Medicine, I. Department of Internal Medicine, University Medical Center Eppendorf, Hamburg, Germany, Research Group Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany and Kumasi Center for Collaborative Research in Tropical Medicine, Kumasi, Ghana.
Abstract
BACKGROUND: Previous studies on the association of malaria and stunted growth delivered inconsistent results. These conflicting results may be due to different levels of confounding and to considerable difficulties in elucidating a causal relationship. Randomized experiments are impractical and previous observational studies have not fully controlled for potential confounding including nutritional deficiencies, breastfeeding habits, other infectious diseases and socioeconomic status. METHODS: This study aims to estimate the causal effect between malaria episodes and stunted growth by applying a combination of Mendelian randomization, using the sickle cell trait, and matching. We demonstrate the method on a cohort of children in the Ashanti Region, Ghana. RESULTS: We found that the risk of stunting increases by 0.32 (P-value: 0.004, 95% CI: 0.09, 1.0) for every malaria episode. The risk estimate based on Mendelian randomization substantially differs from the multiple regression estimate of 0.02 (P-value: 0.02, 95% CI: 0.003, 0.03). In addition, based on the sensitivity analysis, our results were reasonably insensitive to unmeasured confounders. CONCLUSIONS: The method applied in this study indicates a causal relationship between malaria and stunting in young children in an area of high endemicity and demonstrates the usefulness of the sickle cell trait as an instrument for the analysis of conditions that might be causally related to malaria.
BACKGROUND: Previous studies on the association of malaria and stunted growth delivered inconsistent results. These conflicting results may be due to different levels of confounding and to considerable difficulties in elucidating a causal relationship. Randomized experiments are impractical and previous observational studies have not fully controlled for potential confounding including nutritional deficiencies, breastfeeding habits, other infectious diseases and socioeconomic status. METHODS: This study aims to estimate the causal effect between malaria episodes and stunted growth by applying a combination of Mendelian randomization, using the sickle cell trait, and matching. We demonstrate the method on a cohort of children in the Ashanti Region, Ghana. RESULTS: We found that the risk of stunting increases by 0.32 (P-value: 0.004, 95% CI: 0.09, 1.0) for every malaria episode. The risk estimate based on Mendelian randomization substantially differs from the multiple regression estimate of 0.02 (P-value: 0.02, 95% CI: 0.003, 0.03). In addition, based on the sensitivity analysis, our results were reasonably insensitive to unmeasured confounders. CONCLUSIONS: The method applied in this study indicates a causal relationship between malaria and stunting in young children in an area of high endemicity and demonstrates the usefulness of the sickle cell trait as an instrument for the analysis of conditions that might be causally related to malaria.
Authors: Emily Mosites; Samuel M Thumbi; Elkanah Otiang; Terry F McElwain; M K Njenga; Peter M Rabinowitz; Ali Rowhani-Rahbar; Marian L Neuhouser; Susanne May; Guy H Palmer; Judd L Walson Journal: J Nutr Date: 2016-04-13 Impact factor: 4.798
Authors: François Freddy Ateba; Seydou Doumbia; Feiko O Ter Kuile; Dianne J Terlouw; Genevieve Lefebvre; Simon Kariuki; Dylan S Small Journal: Trans R Soc Trop Med Hyg Date: 2021-09-03 Impact factor: 2.184
Authors: Bruno P Mmbando; Richard O Mwaiswelo; Frank Chacky; Fabrizio Molteni; Ally Mohamed; Samwel Lazaro; Billy Ngasala Journal: PLoS One Date: 2022-04-29 Impact factor: 3.752
Authors: Efrem d'Avila Ferreira; Márcia A Alexandre; Jorge L Salinas; André M de Siqueira; Silvana G Benzecry; Marcus V G de Lacerda; Wuelton M Monteiro Journal: Malar J Date: 2015-09-17 Impact factor: 2.979
Authors: Sonja Y Hess; Souheila Abbeddou; Elizabeth Yakes Jimenez; Jérôme W Somé; Stephen A Vosti; Zinéwendé P Ouédraogo; Rosemonde M Guissou; Jean-Bosco Ouédraogo; Kenneth H Brown Journal: PLoS One Date: 2015-03-27 Impact factor: 3.240