Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Department of Global Health, University of Washington School of Public Health, Seattle, WA, United States.
Am J Clin Nutr. 2024 Sep;120 Suppl 1:S65-S72. doi: 10.1016/j.ajcnut.2024.02.027.
Environmental enteric dysfunction (EED) is a precursor of growth faltering in children living in impoverished conditions who are frequently exposed to environmental toxins and enteropathogens, leading to small bowel inflammatory, malabsorptive, and permeability derangements and low-grade chronic systemic inflammation.
We explored the association between anthropometrics and duodenal histologic features of EED among children from 3 lower middle-income country centers.
In this cross-sectional study, Pakistani children (n = 63) with wasting, Bangladesh children (n = 116) with stunting or at risk for stunting (height-for-age Z score [HAZ] <-1 but ≥-2), and Zambian children (n = 108) with wasting or stunting received nutritional intervention. Children with anthropometric status refractory to intervention underwent endoscopy. Linear regression models included anthropometric around endoscopy, scores of histology parameters, and a global index score of EED-the total score percent-5 (TSP-5). Multivariable models were adjusted for center, age, sex, and histology slide quality.
Intersite variation was observed while exploring the association between anthropometrics and the TSP-5; for example, Pakistani children had the worst HAZ, yet their median TSP-5 score was lower than that of the other 2 centers. Even within each site, no overall pattern of higher TSP-5 score was observed with worsening HAZ. During univariate analysis, TSP-5 (coefficient: 0.01; 95% confidence interval [CI]: 0, 0.02), goblet cell depletion (coefficient: 0.22; 95% CI: 0.06, 0.37), and Paneth cell depletion (coefficient: 0.14; 95% CI: 0.01, 0.27) were associated with HAZ scores; however, they lost statistical significance in the multivariable models, with study center most strongly confounding the relationships seen in univariate models between anthropometry and histology.
This study contributes a crucial negative finding that duodenal morphological features did not associate with anthropometric phenotypes; hence, anthropometric measurements may not be a suitable outcome measure for use in EED trials. Trial outcomes may need to be defined by combining the functional and structural elements of the gut to monitor EED.
环境肠道功能障碍（EED）是生活在贫困环境中经常接触环境毒素和肠道病原体的儿童生长迟缓的前兆，导致小肠炎症、吸收不良和通透性紊乱以及低度慢性全身炎症。
我们探索了来自 3 个中低收入国家中心的儿童中，人体测量学与十二指肠 EED 组织学特征之间的关联。
在这项横断面研究中，巴基斯坦患有消瘦的儿童（n = 63）、孟加拉国患有发育迟缓或有发育迟缓风险的儿童（身高年龄 Z 评分[HAZ]<-1 但≥-2，n = 116）和赞比亚患有消瘦或发育迟缓的儿童（n = 108）接受了营养干预。对无法通过干预措施改善人体测量指标的儿童进行了内镜检查。线性回归模型包括内镜检查前后的人体测量指标、组织学参数评分和 EED 的总体指数评分-5（TSP-5）。多变量模型调整了中心、年龄、性别和组织学切片质量。
在探索人体测量学与 TSP-5 之间的关联时，观察到了站点间的差异；例如，巴基斯坦儿童的 HAZ 最差，但他们的 TSP-5 中位数得分低于其他 2 个中心。即使在每个中心内，也没有观察到随着 HAZ 恶化而出现 TSP-5 得分更高的总体模式。在单变量分析中，TSP-5（系数：0.01；95%置信区间[CI]：0，0.02）、杯状细胞耗竭（系数：0.22；95%CI：0.06，0.37）和潘氏细胞耗竭（系数：0.14；95%CI：0.01，0.27）与 HAZ 评分相关；然而，在多变量模型中，它们失去了统计学意义，研究中心最强烈地干扰了单变量模型中人体测量学与组织学之间的关系。
本研究提供了一个重要的阴性发现，即十二指肠形态特征与人体测量表型无关；因此，人体测量指标可能不是 EED 试验中合适的结果测量指标。试验结果可能需要通过结合肠道的功能和结构元素来定义，以监测 EED。
