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.
Int J Epidemiol. 2013 Oct;42(5):1390-8. doi: 10.1093/ije/dyt116. Epub 2013 Aug 7.
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.
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.
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.
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.
先前关于疟疾与发育迟缓之间关联的研究结果不一致。这些相互矛盾的结果可能是由于混杂程度不同，以及阐明因果关系存在相当大的困难。随机试验是不切实际的，而先前的观察性研究并没有充分控制潜在的混杂因素，包括营养缺乏、母乳喂养习惯、其他传染病和社会经济地位。
本研究旨在通过应用孟德尔随机化（利用镰状细胞特征）和匹配相结合的方法来估计疟疾发作与发育迟缓之间的因果关系。我们在加纳阿散蒂地区的一个儿童队列中演示了该方法。
我们发现，每发生一次疟疾发作，发育迟缓的风险就会增加 0.32（P 值：0.004，95%CI：0.09，1.0）。基于孟德尔随机化的风险估计与多重回归估计的 0.02（P 值：0.02，95%CI：0.003，0.03）有很大的不同。此外，基于敏感性分析，我们的结果对未测量的混杂因素具有相当的稳健性。
本研究中应用的方法表明，在高流行地区的幼儿中，疟疾与发育迟缓之间存在因果关系，并展示了镰状细胞特征作为分析可能与疟疾有关的疾病的工具的有用性。
