Kreuels Benno, Ehrhardt Stephan, Kreuzberg Christina, Adjei Samuel, Kobbe Robin, Burchard Gerd D, Ehmen Christa, Ayim Matilda, Adjei Ohene, May Jürgen
University Medical Centre Hamburg-Eppendorf, Germany.
Malar J. 2009 Jan 16;8:16. doi: 10.1186/1475-2875-8-16.
While the protective effects of sickle cell trait (HbAS) against severe malaria and the resulting survival advantage are well known, the impact on the physical development in young children remains unclear. This study was aimed to investigate the relationship between HbS carriage and stunting in children below two years of age in a cohort from the Ashanti Region, Ghana.
1,070 children were recruited at three months of age and followed-up for 21 months with anthropometric measurements performed every three months. Incidence rate ratios with 95% confidence intervals were calculated by Poisson regression to estimate the association of beta-globin genotypes with the number of malaria episodes. Odds ratios (OR) were calculated for the association between the occurrence of beta-globin genotypes and/or malaria episodes and stunting. The age-dependent between-group and within-group effects for the beta-globin genotypes were assessed by population-averaged models estimated by generalized estimation equation with autoregressive correlation structure.
Analyses showed a significantly lower age-dependent risk of stunting (OR 0.56; 95% CI 0.33-0.96) in carriers of the HbAS genotype (n = 102) in comparison to those with HbAA (n = 692). This effect was restricted to children who experienced malaria episodes during the observation period suggesting that the beneficial effect of the beta-globin HbS variant on the incidence of stunting is closely linked to its protection from mild malaria episodes.
The lower risk of chronic malnutrition in early childhood, mediated by protection against mild malaria episodes, may contribute to the survival advantage of HbAS carriers in areas of high malaria transmission.
虽然镰状细胞性状（HbAS）对重症疟疾的保护作用以及由此产生的生存优势已广为人知，但对幼儿身体发育的影响仍不清楚。本研究旨在调查加纳阿散蒂地区一个队列中2岁以下儿童的HbS携带情况与发育迟缓之间的关系。
招募了1070名3个月大的儿童，并进行了21个月的随访，每3个月进行一次人体测量。通过泊松回归计算发病率比及其95%置信区间，以估计β-珠蛋白基因型与疟疾发作次数之间的关联。计算β-珠蛋白基因型的出现和/或疟疾发作与发育迟缓之间关联的比值比（OR）。通过具有自回归相关结构的广义估计方程估计的总体平均模型，评估β-珠蛋白基因型的年龄依赖性组间和组内效应。
分析显示，与携带HbAA基因型（n = 692）的儿童相比，携带HbAS基因型（n = 102）的儿童发育迟缓的年龄依赖性风险显著降低（OR 0.56；95% CI 0.33 - 0.96）。这种效应仅限于在观察期内经历过疟疾发作的儿童，这表明β-珠蛋白HbS变异体对发育迟缓发生率的有益影响与其对轻度疟疾发作的保护密切相关。
通过预防轻度疟疾发作介导的幼儿期慢性营养不良风险降低，可能有助于HbAS携带者在高疟疾传播地区的生存优势。
