Olórtegui, Maribel Paredes

ABSTRACT Objectives: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings. Methods: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age‐ and sex‐specific z scores for mannitol and lactulose recoveries and the L:M ratio. Results: A total of 6602 tests demonstrated mannitol recovery, lactulose recovery, and the L:M ratio were associated with country, sex, and age. There was heterogeneity in the recovery of both probes between sites with mean mannitol recovery ranging for 1.34% to 5.88%, lactulose recovery of 0.19% to 0.58%, and L:M ratios 0.10 to 0.17 in boys of 3 months of age across different sites. We observed strong sex‐specific differences in both mannitol and lactulose recovery, with boys having higher recovery of both probes. Alterations in intestinal barrier function increased in most sites from 3 to 9 months of age and plateaued or diminished from 9 to 15 months of age. Conclusions: Alterations in recovery of the probes differ markedly in different epidemiologic contexts in children living in the developing world. The rate of change in the L:M‐ z ratio was most rapid and consistently disparate from the reference standard in the period between 6 and 9 months of age, suggesting that this is a critical period of physiologic impact of enteropathy in these populations.

ABSTRACTObjectives:The lactulose:mannitol (L:M) diagnostic test is frequently used in field studies of environmental enteropathy (EE); however, heterogeneity in test administration and disaccharide measurement has limited the comparison of results between studies and populations. We aim to assess the agreement between L:M measurement between high‐performance liquid chromatography with pulsed amperometric detection (HPLC‐PAD) and liquid chromatography‐tandem mass spectrometry (LC‐MSMS) platforms.Methods:The L:M test was administered in a cohort of Peruvian infants considered at risk for EE. A total of 100 samples were tested for lactulose and mannitol at 3 independent laboratories: 1 running an HPLC‐PAD platform and 2 running LC‐MSMS platforms. Agreement between the platforms was estimated.Results:The Spearman correlation between the 2 LC‐MSMS platforms was high (ρ ≥ 0.89) for mannitol, lactulose, and the L:M ratio. The correlation between the HPLC‐PAD platform and LC‐MSMS platform was ρ = 0.95 for mannitol, ρ = 0.70 for lactulose, and ρ = 0.43 for the L:M ratio. In addition, the HPLC‐PAD platform overestimated the lowest disaccharide concentrations to the greatest degree.Conclusions:Given the large analyte concentration range, the improved accuracy of LC‐MSMS has important consequences for the assessment of lactulose and mannitol following oral administration in populations at risk for EE. We recommend that researchers wishing to implement a dual‐sugar test as part of a study of EE use an LC‐MSMS platform to optimize the accuracy of results and increase comparability between studies.