NCT02441426

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.

Trial Health

50
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,796

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Nov 2008

Longer than P75 for all trials

Geographic Reach
8 countries

8 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2008

Completed
6.5 years until next milestone

First Submitted

Initial submission to the registry

May 4, 2015

Completed
8 days until next milestone

First Posted

Study publicly available on registry

May 12, 2015

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2017

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
Last Updated

May 12, 2015

Status Verified

May 1, 2015

Enrollment Period

8.3 years

First QC Date

May 4, 2015

Last Update Submit

May 7, 2015

Conditions

DiarrheaMalnutritionStuntingWastingImmune ResponseCognitive Development

Keywords

Cognitive developmentDiarrheal diseaseEnteric infectionsMalnutritionVaccine ResponseEnteropathyAntibiotic useMicronutrientsBreast feedingGut inflammation

Outcome Measures

Primary Outcomes (9)

  • Diarrhea

    All diarrheal samples are analyzed for the presence of bacterial, viral, and parasitic pathogens. Normal stool is collected monthly and analyzed for the same list of 57 different pathogens.

    Each diarrheal episode willbe recorded for up to 24 months of age.

  • Anthropometry

    Head Circumference, length, and weight are measured monthly on the anniversary of the child's birth.

    Anthropomentry will be recorded each month for up to 24 months of age.

  • Cognitive development

    A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices.

    Cognitive development will be recorded at 6 months of age.

  • Vaccine response

    Antibody titers will be determined following immunization against rotavirus, polio virus, tetanus toxoid, pertussis toxin and measles vaccines.

    Vaccine response will be recorded at 7 months of age.

  • Cognitive development

    A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices.

    Cognitive development will be recorded at 8 months of age.

  • Cognitive development

    A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices.

    Cognitive development will be recorded at 15 months of age.

  • Vaccine response

    Antibody titers will be determined following immunization against rotavirus, polio virus, tetanus toxoid, pertussis toxin and measles vaccines.

    Vaccine response will be recorded at 15 months of age.

  • Cognitive development

    A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices.

    Cognitive development will be recorded 24 months of age.

  • Vaccine response

    Antibody titers will be determined following immunization against rotavirus, polio virus, tetanus toxoid, pertussis toxin and measles vaccines.

    Vaccine response will be recorded at 24 months of age.

Secondary Outcomes (5)

  • Gut inflammation

    Gut inflammation will be recorded each month for up to 24 months of age.

  • Gut integrity

    Gut integritywill be recorded at at 3 months of age.

  • Gut integrity

    Gut integritywill be recorded at at 6 months of age.

  • Gut integrity

    Gut integritywill be recorded at at 9 months of age.

  • Gut integrity

    Gut integritywill be recorded at at 15 months of age.

Study Arms (8)

Bangladesh

Birth cohort study community in Bangladesh is urban, and located in the Mirpur neighborhood of Dhaka. Case control study is being conducted in the same catchment area. Cases defined as children 6-24 months of age with \<-2WAZ (weight for age) score, controls are age and community matched with \>-1WAZ.

Brazil

Birth cohort study community in Brazil is urban, and located within the Papoco area of Fortaleza. Case control study is being conducted in the same area as the cohort study. Cases are children 6 - 24 months of age, with \<-2 WAZ (weight for age) score, controls are age and community matched children with \>-1 WAZ.

India

Birth cohort study community in India is urban, and located in the southern state of Tamil Nadu, specifically in Vellore.

Nepal

Birth cohort study community in Nepal is semi-urban, and located in Bhaktapur, approximately 25km from Kathmandu.

Pakistan

Birth cohort study community in Pakistan is rural, and located in Naushero Feroze, Sindh.

Peru

Birth cohort study community in Peru is rural, and located approximately 15km from Iquitos in Loreto.

South Africa

Birth cohort study community in South Africa is rural/peri-urban, and comprised of nine settlements within Limpopo Province.

Tanzania

Birth cohort study community in Tanzania is rural, and located within Haydom.

Eligibility Criteria

Age1 Minute - 17 Days
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)
Sampling MethodProbability 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.

You may qualify if:

  • Less than 17 days old.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

International Centre for Diarrheal Disease Research, Bangladesh

Dhaka, Bangladesh

Location

Universidade Federal do Ceará

Fortaleza, Brazil

Location

Christian Medical College

Vellore, India

Location

Institute of Medicine

Kathmandu, Nepal

Location

Aga Khan University

Karachi, Pakistan

Location

JHSPH Satellite Laboratory

Iquitos, Peru

Location

University of Venda

Limpopo, South Africa

Location

Haydom Lutheran Hospital

Haydom, Tanzania

Location

Related Publications (5)

  • Nemati K, Michael YZ, Hhando BP, Jatosh S, Houpt ER, Mduma E, DeBoer MD. Catch-up growth following early-life stunting in a low-resource area in rural Tanzania: the MAL-ED Metabolic study. BMJ Open. 2025 Aug 21;15(8):e100955. doi: 10.1136/bmjopen-2025-100955.

    PMID: 40840991DERIVED

  • 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.

    PMID: 31093598DERIVED

  • 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.

    PMID: 29684739DERIVED

  • 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.

    PMID: 28592604DERIVED

  • 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.

    PMID: 28381477DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

plasma, stool, urine, saliva

MeSH Terms

Conditions

DiarrheaMalnutritionGrowth DisordersCachexiaIntestinal DiseasesBreast Feeding

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and SymptomsNutrition DisordersNutritional and Metabolic DiseasesPathologic ProcessesWeight LossBody Weight ChangesBody WeightThinnessGastrointestinal DiseasesDigestive System DiseasesFeeding BehaviorBehavior

Study Officials

  • Michael Gottlieb, Ph.D.

    Fountation for the National Institutes of Health

    PRINCIPAL INVESTIGATOR

  • Roger Glass, M.D.

    Fogarty International Center of the National Institute of Health

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 4, 2015

First Posted

May 12, 2015

Study Start

November 1, 2008

Primary Completion

February 1, 2017

Study Completion

April 1, 2017

Last Updated

May 12, 2015

Record last verified: 2015-05

Locations

TA(1)BR(1)PE(1)NE(1)PA(1)ZA(1)IN(1)BA(1)