Clinical trial NCT02441426: Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development
Official title: Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diarrhea
Malnutrition
Stunting
Wasting
Immune Response
Cognitive Development
Keywords: Cognitive development
Diarrheal disease
Enteric infections
Malnutrition
Vaccine Response
Enteropathy
Antibiotic use
Micronutrients
Breast feeding
Gut inflammation
Lead sponsor: Foundation for the National Institutes of Health
Sponsor class: OTHER
Collaborators: name: University of Virginia
name: Johns Hopkins University
name: Aga Khan University
name: Christian Medical College, Vellore, India
name: Henry M. Jackson Foundation for the Advancement of Military Medicine
name: Fogarty International Center of the National Institute of Health
name: Penn State University
First posted: 2015-05-12
Enrollment: 1796
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population for the MAL-ED Project is a birth cohort. Pregnant women were identified from their communities, consented and the child will be enrolled.

Brief summary: Malnutrition is considered one of the most prevalent risk factors for morbidity and mortality in children under five. An estimated 20% of children in the developing world are malnourished \[1\] and poor nutrition is linked to more than half of all child deaths worldwide \[2\]. Malnutrition in early childhood may lead to cognitive and physical deficits and may cause similar deficits in future generations as malnourished mothers give birth to low birth weight children \[3\]. In addition, malnutrition increases susceptibility and incidence of infections and is associated with diminished response to vaccines.

The MAL-ED Project is designed to determine the impact of enteric infections/diarrhea that alter gut function and impair children's nutrition, growth and development to help develop new intervention strategies that can break the vicious enteric infection-malnutrition cycle and reduce its global burden.

The overall objective of the MAL-ED Project is to quantify the associations of specific enteric pathogens, measures of physical and mental development, micronutrient malnutrition, gut function biomarkers, the gut microbiome, and immune responses in very young children in resource-limited settings across eight sites that vary by culture, economics, geography, and climate.

The central hypothesis of the MAL-ED Project is that infection (and co-infection) with specific enteropathogens leads to impaired growth and development and to diminished immune response to orally administered vaccines by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. Data analyses will test for associations between enteropathogen infections and growth/development to help illuminate:

* which micro-organisms or mixed infections are most frequently associated with growth faltering and poor development; and
* at what age specific infections cause the most disruption to growth and development and impair immune response.


Eligibility criteria: Inclusion Criteria:

* Less than 17 days old.

Exclusion Criteria:

* Mother is less than 16 years of age.
* Mother has another child inthe MAL-ED study.
* Pregnancy resulted in multiple birth (e.g., twins).
* Child has a severe disease requiring hospitalization for something other than for a typical healthy birth.
* Child has a severe or chronic condition diagnosed by a medical doctor (e.g., neonatal disease, renal disease, chronic heart failure, liver disease, cystic fibrosis, congenital conditions).
* Child has enteropathies diagnosed by medical doctor.
* Mother is living and unable to provide informed consent.

Primary outcomes:
measure: Diarrhea
timeFrame: Each diarrheal episode willbe recorded for up to 24 months of age.
measure: Anthropometry
timeFrame: Anthropomentry will be recorded each month for up to 24 months of age.
measure: Cognitive development
timeFrame: Cognitive development will be recorded at 6 months of age.
measure: Vaccine response
timeFrame: Vaccine response will be recorded at 7 months of age.
measure: Cognitive development
timeFrame: Cognitive development will be recorded at 8 months of age.
measure: Cognitive development
timeFrame: Cognitive development will be recorded at 15 months of age.
measure: Vaccine response
timeFrame: Vaccine response will be recorded at 15 months of age.
measure: Cognitive development
timeFrame: Cognitive development will be recorded 24 months of age.
measure: Vaccine response
timeFrame: Vaccine response will be recorded at 24 months of age.
Secondary outcomes:
measure: Gut inflammation
timeFrame: Gut inflammation will be recorded each month for up to 24 months of age.
measure: Gut integrity
timeFrame: Gut integritywill be recorded at at 3 months of age.
measure: Gut integrity
timeFrame: Gut integritywill be recorded at at 6 months of age.
measure: Gut integrity
timeFrame: Gut integritywill be recorded at at 9 months of age.
measure: Gut integrity
timeFrame: Gut integritywill be recorded at at 15 months of age.
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrheal Disease Research, Bangladesh
city: Fortaleza
country: Brazil
facility: Universidade Federal do Ceará
city: Vellore
country: India
facility: Christian Medical College
city: Kathmandu
country: Nepal
facility: Institute of Medicine
city: Karachi
country: Pakistan
facility: Aga Khan University
city: Iquitos
country: Peru
facility: JHSPH Satellite Laboratory
city: Limpopo
country: South Africa
facility: University of Venda
city: Haydom
country: Tanzania
facility: Haydom Lutheran Hospital
Study officials:
affiliation: Fountation for the National Institutes of Health
name: Michael Gottlieb, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Fogarty International Center of the National Institute of Health
name: Roger Glass, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arndt MB, Richardson BA, Mahfuz M, Ahmed T, Haque R, Gazi MA, John-Stewart GC, Denno DM, Scarlett JM, Walson JL; coordination with The Interactions of Malnutrition & Enteric Infections: Consequences for Child Health and Development Project Network. Plasma Fibroblast Growth Factor 21 Is Associated with Subsequent Growth in a Cohort of Underweight Children in Bangladesh. Curr Dev Nutr. 2019 Mar 30;3(5):nzz024. doi: 10.1093/cdn/nzz024. eCollection 2019 May.
citation: Colston JM, Ahmed T, Mahopo C, Kang G, Kosek M, de Sousa Junior F, Shrestha PS, Svensen E, Turab A, Zaitchik B; MAL-ED Network. Evaluating meteorological data from weather stations, and from satellites and global models for a multi-site epidemiological study. Environ Res. 2018 Aug;165:91-109. doi: 10.1016/j.envres.2018.02.027. Epub 2018 Apr 21.
citation: Colston JM, Penataro Yori P, Colantuoni E, Moulton LH, Ambikapathi R, Lee G, Rengifo Trigoso D, Siguas Salas M, Kosek MN. A methodologic framework for modeling and assessing biomarkers of environmental enteropathy as predictors of growth in infants: an example from a Peruvian birth cohort. Am J Clin Nutr. 2017 Jul;106(1):245-255. doi: 10.3945/ajcn.116.151886. Epub 2017 Jun 7.
citation: Platts-Mills JA, Taniuchi M, Uddin MJ, Sobuz SU, Mahfuz M, Gaffar SA, Mondal D, Hossain MI, Islam MM, Ahmed AS, Petri WA, Haque R, Houpt ER, Ahmed T. Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study. Am J Clin Nutr. 2017 May;105(5):1132-1138. doi: 10.3945/ajcn.116.138800. Epub 2017 Apr 5.