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.
*Department of International Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore
†Fogarty International Center/National Institutes of Health, Bethesda, MD
‡Department of Global Community Health and Behavioral Sciences, Tulane University, New Orleans, LA
§University of Virginia, Charlottesville, VA
¶ICDDR, b, Dhaka, Bangladesh
||Christian Medical College, Vellore, India
**University of Venda, Thohoyandou, South Africa
††Center of Excellence in Women and Child Health, the Aga Khan University, Karachi, Pakistan
‡‡Haydom Lutheran Hospital, Haydom, Tanzania
§§Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
¶¶Universidade Federal do Ceara, Fortaleza, Brazil
||||A.B. PRISMA, Iquitos, Peru
***Walter Reed/AFRIMS Research Unit, Kathmandu, Nepal
†††Immunochemical Core Laboratory, Mayo Clinic, Rochester, MN
‡‡‡Pain Consultants of Oregon, Eugene, OR
§§§Foundation for the NIH, Bethesda, MD.
Address correspondence and reprint requests to Margaret N. Kosek, Bloomberg School of Public Health, Department of International Health, Johns Hopkins University, 615 North Wolfe St., E5545, Baltimore, MD 21205 (mkosek@jhmi.edu).
Received 11 July, 2016
Accepted 27 February, 2017
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).
The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the National Institutes of Health, Fogarty International Center.
Members and affiliations of MAL-ED Network available as Supplemental Digital Content, Material 1, http://links.lww.com/MPG/A980.
The authors report no conflicts of interest.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
