A cross-sectional study of associations between the C-sucrose breath test, the lactulose rhamnose assay, and growth in children at high risk of environmental enteropathy.

BACKGROUND

Environmental enteropathy' (EE) is common among children who are highly exposed to enteric pathogens in low-resource settings. We optimized and validated a stable isotope-based breath test of intestinal sucrase activity (C-SBT) as a noninvasive test of carbohydrate digestion and metabolism.

OBJECTIVES

The primary objective of this study was to assess the relationship between the C-SBT and the lactulose/rhamnose ratio (LR) and growth in children. Secondary objectives were to assess the relationship between the C-SBT and additional biomarkers of EE. We also characterized the relationship between the C-SBT and child sex and dietary diversity, as well as household socio-economic status and food security.

METHODS

In this cross-sectional study, 12-to-15-mo-old children were recruited in Bangladesh, India, Kenya, and Peru. Children were assessed with a 4-h C-SBT and a 90-min LR test. Plasma was collected to determine the citrulline and kynurenine/tryptophan ratio. Length and weight were measured, and other variables were assessed through questionnaires. For a subset of children, anthropometry was re-measured after 3 mo. Linear regression was used to examine associations corresponding to each objective.

RESULTS

Three sites generated C-SBT breath curves that enabled pooled analysis. Differences in C-SBT breath curves, LR ratios, and other EE biomarkers were observed between sites. No associations were observed for C-SBT summary measures and LR or child growth [e.g., the association between LR and cumulative percent dose recovered at 90 min: -0.39; 95% confidence interval (CI): -1.79, 0.70]. Length-for-age and weight-for-age were positively associated with the time to 50% of dose recovered (0.05; 95% CI: 0.01, 0.09, and 0.05; 95% CI: 0.02, 0.07, respectively), and dietary diversity was associated with time at which 50% of the dose recovered by 240 min is recovered and cumulative percent dose recovered at 90 min (-0.10; 95% CI: -0.18, -0.02 and 2.67; 95% CI: 0.47, 4.88, respectively).

CONCLUSIONS

In children at risk of EE, there were no associations between the C-SBT, LR, or other EE biomarkers encompassing different pathophysiological domains of EE. This trial was registered at clinicaltrials.gov as NCT04109352.