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

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume65
Issue number1
DOIs
StatePublished - Jul 1 2017

Fingerprint

Lactulose
Mannitol
Permeability
Sex Characteristics
Brazil
Diarrhea
Cohort Studies
Parturition

Keywords

  • environmental enteropathy
  • intestinal permeability
  • lactulose
  • mannitol
  • reference values

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

Cite this

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. / 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 Alvis; Lima, Aldo A.M.; Paredes Olortegui, Maribel; Mason, Carl; Babji, Sudhir; Singh, Ravinder Jit; 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.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 65, No. 1, 01.07.2017, p. 31-39.

Research output: Contribution to journalArticle

Kosek, MN, Lee, GO, Guerrant, RL, Haque, R, Kang, G, Ahmed, T, Bessong, P, Ali, A, Mduma, E, Peñataro Yori, P, Faubion, WA, Lima, AAM, Paredes Olortegui, M, Mason, C, Babji, S, Singh, RJ, Qureshi, S, Kosek, PS, Samie, A, Pascal, J, Shrestha, S, McCormick, BJJ, Seidman, JC, Lang, DR, Zaidi, A, Caulfield, LE & Gottlieb, M 2017, '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', Journal of Pediatric Gastroenterology and Nutrition, vol. 65, no. 1, pp. 31-39. https://doi.org/10.1097/MPG.0000000000001610
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 Alvis ; Lima, Aldo A.M. ; Paredes Olortegui, Maribel ; Mason, Carl ; Babji, Sudhir ; Singh, Ravinder Jit ; 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. / 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. In: Journal of Pediatric Gastroenterology and Nutrition. 2017 ; Vol. 65, No. 1. pp. 31-39.
@article{3802a7da81374e3eb32a0f513919c07b,
title = "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",
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.",
keywords = "environmental enteropathy, intestinal permeability, lactulose, mannitol, reference values",
author = "Kosek, {Margaret N.} and Lee, {Gwenyth O.} and Guerrant, {Richard L.} and Rashidul Haque and Gagandeep Kang and Tahmeed Ahmed and Pascal Bessong and Asad Ali and Estomih Mduma and {Pe{\~n}ataro Yori}, Pablo and Faubion, {William Alvis} and Lima, {Aldo A.M.} and {Paredes Olortegui}, Maribel and Carl Mason and Sudhir Babji and Singh, {Ravinder Jit} and Shahida Qureshi and Kosek, {Peter S.} and Amidou Samie and John Pascal and Sanjaya Shrestha and McCormick, {Benjamin J.J.} and Seidman, {Jessica C.} and Lang, {Dennis R.} and Anita Zaidi and Caulfield, {Laura E.} and Michael Gottlieb",
year = "2017",
month = "7",
day = "1",
doi = "10.1097/MPG.0000000000001610",
language = "English (US)",
volume = "65",
pages = "31--39",
journal = "Journal of Pediatric Gastroenterology and Nutrition",
issn = "0277-2116",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Age and Sex Normalization of Intestinal Permeability Measures for the Improved Assessment of Enteropathy in Infancy and Early Childhood

T2 - Results from the MAL-ED Study

AU - Kosek, Margaret N.

AU - Lee, Gwenyth O.

AU - Guerrant, Richard L.

AU - Haque, Rashidul

AU - Kang, Gagandeep

AU - Ahmed, Tahmeed

AU - Bessong, Pascal

AU - Ali, Asad

AU - Mduma, Estomih

AU - Peñataro Yori, Pablo

AU - Faubion, William Alvis

AU - Lima, Aldo A.M.

AU - Paredes Olortegui, Maribel

AU - Mason, Carl

AU - Babji, Sudhir

AU - Singh, Ravinder Jit

AU - Qureshi, Shahida

AU - Kosek, Peter S.

AU - Samie, Amidou

AU - Pascal, John

AU - Shrestha, Sanjaya

AU - McCormick, Benjamin J.J.

AU - Seidman, Jessica C.

AU - Lang, Dennis R.

AU - Zaidi, Anita

AU - Caulfield, Laura E.

AU - Gottlieb, Michael

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - environmental enteropathy

KW - intestinal permeability

KW - lactulose

KW - mannitol

KW - reference values

UR - http://www.scopus.com/inward/record.url?scp=85018232416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018232416&partnerID=8YFLogxK

U2 - 10.1097/MPG.0000000000001610

DO - 10.1097/MPG.0000000000001610

M3 - Article

C2 - 28644347

AN - SCOPUS:85018232416

VL - 65

SP - 31

EP - 39

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

SN - 0277-2116

IS - 1

ER -