Background: Despite a reduction of child mortality in low-income countries, acutely ill undernourished children still have an elevated risk of death. Those at highest risk are children with severe acute malnutrition (SAM) who often show metabolic dysregulation that remains poorly understood. Objective: We performed a pilot study to examine changes in urinary organic acids during nutritional rehabilitation of children with SAM, and to identify metabolites associated with the presence of edema or with mortality. Methods: This study included 76 children aged between 6 and 60 months, hospitalized for SAM at the Moyo Nutritional Rehabilitation and Research Unit in Blantyre, Malawi. Urine was collected at admission and 3 days after clinical stabilization and metabolomics were performed using gas chromatography–mass spectrometry. Metabolite concentrations were evaluated with both uni- and multivariate approaches. Results: Most metabolites increased 3 days after clinical stabilization, and total urinary concentration changed from 1.2 mM (interquartile range [IQR], 0.78-1.7) at admission to 3.8 mM (IQR, 2.1-6.6) after stabilization (P < .0001). In particular, 6 metabolites showed increases: 3-hydroxybutyric, 4-hydroxyhippuric, p-hydroxyphenylacetic, oxoglutaric, succinic, and lactic acids. Urinary creatinine was low at both time points, but levels did increase from 0.63 mM (IQR, 0.2-1.2) to 2.6 mM (IQR,1.6-4.4; P < .0001). No differences in urinary profiles were found between children who died versus those who survived, nor between children with severe wasting or edematous SAM. Conclusions: Total urinary metabolites and creatinine increase after stabilization and may reflect partial recovery of overall metabolism linked to refeeding. The use of urinary metabolites for risk assessment should be furthered explored. Trial registration: TranSAM study (ISRCTN13916953).

中文翻译：

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严重急性营养不良住院儿童临床稳定后尿有机酸升高

背景：尽管低收入国家的儿童死亡率有所下降，但严重营养不良的儿童的死亡风险仍然较高。那些风险最高的是患有严重急性营养不良 (SAM) 的儿童，他们经常表现出代谢失调，但人们对此知之甚少。目标：我们进行了一项初步研究，以检查 SAM 儿童营养康复期间尿有机酸的变化，并确定与水肿或死亡率相关的代谢物。方法：这项研究包括 76 名年龄在 6 至 60 个月之间的儿童，他们在马拉维布兰太尔的 Moyo 营养康复和研究中心因 SAM 住院。在入院时和临床稳定后 3 天收集尿液，并使用气相色谱-质谱法进行代谢组学。使用单变量和多变量方法评估代谢物浓度。结果：大多数代谢物在临床稳定后 3 天增加，总尿浓度从入院时的 1.2 mM（四分位距 [IQR]，0.78-1.7）变为稳定后的 3.8 mM（IQR，2.1-6.6）（P < .0001） . 特别是，6 种代谢物显示出增加：3-羟基丁酸、4-羟基马尿酸、对羟基苯乙酸、氧代戊二酸、琥珀酸和乳酸。尿肌酐在两个时间点都较低，但水平确实从 0.63 mM（IQR，0.2-1.2）增加到 2.6 mM（IQR，1.6-4.4；P < .0001）。死亡儿童与幸存儿童之间的尿液特征没有差异，严重消瘦或水肿性 SAM 的儿童之间也没有发现差异。结论：稳定后总尿代谢物和肌酐增加，可能反映与再喂养相关的整体代谢的部分恢复。应进一步探索使用尿液代谢物进行风险评估。试验注册：TranSAM 研究 (ISRCTN13916953)。