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用于改善婴幼儿肠病评估的肠道通透性测量的年龄和性别标准化:MAL-ED研究结果

Age and Sex Normalization of Intestinal Permeability Measures for the Improved Assessment of Enteropathy in Infancy and Early Childhood: Results From the MAL-ED Study.

作者信息

Kosek Margaret N, Lee Gwenyth O, Guerrant Richard L, Haque Rashidul, Kang Gagandeep, Ahmed Tahmeed, Bessong Pascal, Ali Asad, Mduma Estomih, Peñataro Yori Pablo, Faubion William A, Lima Aldo A M, Paredes Olortegui Maribel, Mason Carl, Babji Sudhir, Singh Ravinder, Qureshi Shahida, Kosek Peter S, Samie Amidou, Pascal John, Shrestha Sanjaya, McCormick Benjamin J J, Seidman Jessica C, Lang Dennis R, Zaidi Anita, Caulfield Laura E, Gottlieb Michael

机构信息

*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.

出版信息

J Pediatr Gastroenterol Nutr. 2017 Jul;65(1):31-39. doi: 10.1097/MPG.0000000000001610.

DOI:10.1097/MPG.0000000000001610
PMID:28644347
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.

摘要

目的

本研究旨在描述不同流行病学背景下幼儿肠道通透性的变化。

方法

在一项出生队列研究中,对来自8个国家的1980名儿童在出生后头24个月的4个时间点进行了乳果糖:甘露醇(L:M)测试。巴西研究点的数据(腹泻发病率与美国相似且无生长发育迟缓)被用作内部研究参考,以得出甘露醇和乳果糖回收率及L:M比值的年龄和性别特异性z分数。

结果

总共6602次测试表明,甘露醇回收率、乳果糖回收率和L:M比值与国家、性别和年龄有关。不同研究点之间两种探针的回收率存在异质性,3个月大男孩的平均甘露醇回收率在1.34%至5.88%之间,乳果糖回收率在0.19%至0.58%之间,不同研究点的L:M比值在0.10至0.17之间。我们观察到甘露醇和乳果糖回收率在性别上存在显著差异,男孩的两种探针回收率都更高。大多数研究点的肠道屏障功能改变在3至9个月龄时增加,在9至15个月龄时趋于平稳或减弱。

结论

在发展中国家儿童的不同流行病学背景下,探针回收率的改变存在显著差异。L:M-z比值的变化率在6至9个月龄期间最为迅速,且始终与参考标准不同,这表明这是这些人群中肠病生理影响的关键时期。

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