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Relationship between growth and illness, enteropathogens and dietary intakes in the first 2 years of life: findings from the MAL-ED birth cohort study
  1. MAL-ED Network Investigators
  1. Correspondence to The MAL-ED Network Investigators and c/o Prof. Laura E Caulfield, International Health/Nutrition, Johns Hopkins Bloomberg School of Public Health; lcaulfie{at}


Background Dietary and illness factors affect risk of growth faltering; the role of enteropathogens is less clear. As part of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, we quantify the effects of enteropathogen infection, diarrhoea and diet on child growth.

Methods Newborns were enrolled and followed until 24 months. Length and weight were assessed monthly. Illnesses and breastfeeding practices were documented biweekly; from 9 to 24 months, non-breast milk intakes were quantified monthly. Routinely collected non-diarrhoeal stools were analysed for a broad array of enteropathogens. A linear piecewise spline model was used to quantify associations of each factor with growth velocity in seven of eight MAL-ED sites; cumulative effects on attained size at 24 months were estimated for mean, low (10th percentile) and high (90th percentile) exposure levels. Additionally, the six most prevalent enteropathogens were evaluated for their effects on growth.

Results Diarrhoea did not have a statistically significant effect on growth. Children with high enteropathogen exposure were estimated to be 1.21±0.33 cm (p<0.001; 0.39 length for age (LAZ)) shorter and 0.08±0.15 kg (p=0.60; 0.08 weight-for-age (WAZ)) lighter at 24 months, on average, than children with low exposure. Campylobacter and enteroaggregativeEscherichia coli detections were associated with deficits of 0.83±0.33 and 0.85±0.31 cm in length (p=0.011 and 0.001) and 0.22±0.15 and 0.09±0.14 kg in weight (p=0.14 and 0.52), respectively. Children with low energy intakes and protein density were estimated to be 1.39±0.33 cm (p<0.001; 0.42 LAZ) shorter and 0.81±0.15 kg (p<0.001; 0.65 WAZ) lighter at 24 months than those with high intakes.

Conclusions Reducing enteropathogen burden and improving energy and protein density of complementary foods could reduce stunting.

  • child health
  • nutritional and metabolic disorders
  • cohort study
  • environmental health
  • pneumonia

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  • Handling editor Alberto Garcia-Basteiro

  • Contributors Three members of the MAL-ED Investigators Network led the analysis and preparation of this manuscript on behalf of the Network. Stephanie A Richard conducted the statistical analyses; Laura E Caulfield, Benjamin J J McCormick and SAR participated in the interpretation of the results and drafted the manuscript. The MAL-ED Investigators participated in the design, conduct and analysis of the MAL-ED study and interpretation of its results.

  • Funding The Bill & Melinda Gates Foundation did not play any role in the writing of the manuscript nor did the funders of the study have any role in the study design, data collection, data analysis or interpretation of study results. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

  • Competing interests None declared.

  • Ethics approval Multiple institutions in multiple countries.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data are not publicly available due to ethical restrictions on participant privacy. Data for this study are available upon request to others in the scientific community. For access, please contact David Spiro at Fogarty International Center;

  • Collaborators MAL-ED Network Investigators: Angel Mendez Acosta, Rosa Rios de Burga , Cesar Banda Chavez, Julian Torres Flores, Maribel Paredes Olotegui, Silvia Rengifo Pinedo, Mery Siguas Salas, Dixner Rengifo Trigoso, Angel Orbe Vasquez (A.B. PRISMA, Iquitos, Peru); Imran Ahmed, Didar Alam, Asad Ali, Zulfiqar A Bhutta, Shahida Qureshi, Muneera Rasheed, Sajid Soofi, Ali Turab, Anita KM Zaidi (Aga Khan University, Karachi, Pakistan); Ladaporn Bodhidatta, Carl J Mason (Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand); Sudhir Babji, Anuradha Bose, Ajila T George, Dinesh Hariraju, M. Steffi Jennifer, Sushil John, Shiny Kaki, Gagandeep Kang, Priyadarshani Karunakaran, Beena Koshy, Robin P Lazarus, Jayaprakash Muliyil, Mohan Venkata Raghava, Sophy Raju, Anup Ramachandran, Rakhi Ramadas, Karthikeyan Ramanujam, Anuradha Bose, Reeba Roshan, Srujan L Sharma, Shanmuga Sundaram E, Rahul J Thomas (Christian Medical College, Vellore, India); William K Pan (Duke University, Durham, NC, USA, Fogarty International Center/National Institutes of Health, Bethesda, MD, USA); Ramya Ambikapathi, J Daniel Carreon, Vivek Charu, Viyada Doan, Jhanelle Graham, Christel Hoest, Stacey Knobler (Fogarty International Center/National Institutes of Health, Bethesda, MD, USA); Dennis R Lang (Fogarty International Center/National Institutes of Health, Bethesda, MD, USA, Foundation for the NIH, Bethesda, MD, USA); Benjamin JJ McCormick, Monica McGrath, Mark A Miller, Archana Mohale, Gaurvika Nayyar, Stephanie Psaki, Zeba Rasmussen, Stephanie A Richard, Jessica C Seidman, Vivian Wang (Fogarty International Center/National Institutes of Health, Bethesda, MD, USA); Rebecca Blank, Michael Gottlieb, Karen H Tountas (Foundation for the NIH, Bethesda, MD, USA); Caroline Amour, Eliwaza Bayyo, Estomih R Mduma, Regisiana Mvungi, Rosemary Nshama, John Pascal, Buliga Mujaga Swema, Ladislaus Yarrot (Haydom Lutheran Hospital, Haydom, Tanzania); Tahmeed Ahmed, AM Shamsir Ahmed, Rashidul Haque, Iqbal Hossain, Munirul Islam, Mustafa Mahfuz, Dinesh Mondal, Fahmida Tofail (icddr,b, Dhaka, Bangladesh); Ram Krishna Chandyo, Prakash Sunder Shrestha, Rita Shrestha, Manjeswori Ulak (Institute of Medicine, Tribhuvan University, Kathmandu, Nepal); Aubrey Bauck, Robert E Black, Laura E Caulfield (Johns Hopkins University, Baltimore, MD, USA); William Checkley (Johns Hopkins University, Baltimore, MD, USA, Fogarty International Center/National Institutes of Health, Bethesda, MD, USA); Margaret N Kosek, Gwenyth Lee, Kerry Schulze, Pablo Peñataro Yori (Johns Hopkins University, Baltimore, MD, USA); Laura E. Murray-Kolb (The Pennsylvania State University, University Park, PA, USA); A Catharine Ross (The Pennsylvania State University, University Park, PA, USA); Barbara Schaefer (The Pennsylvania State University, University Park, PA, USA, Fogarty International Center/National Institutes of Health, Bethesda, MD, USA); Suzanne Simons (The Pennsylvania State University, University Park, PA, USA); Laura Pendergast (Temple University, Philadelphia, PA, USA); Cláudia B Abreu, Hilda Costa, Alessandra Di Moura (Universidade Federal do Ceara, Fortaleza, Brazil); José Quirino Filho (Universidade Federal do Ceara, Fortaleza, Brazil, Fogarty International Center/National Institutes of Health, Bethesda, MD, USA); Alexandre Havt, Álvaro M Leite, Aldo AM Lima, Noélia L Lima, Ila F Lima, Bruna LL Maciel, Pedro HQS Medeiros, Milena Moraes, Francisco S Mota, Reinaldo B Oriá (Universidade Federal do Ceara, Fortaleza, Brazil); Josiane Quetz, Alberto M Soares, Rosa MS Mota (Universidade Federal do Ceara, Fortaleza, Brazil); Crystal L Patil (University of Illinois, Chicago, IL, USA); Pascal Bessong, Cloupas Mahopo, Angelina Maphula, Emanuel Nyathi, Amidou Samie (University of Venda, Thohoyandou, South Africa); Leah Barrett, Rebecca Dillingham, Jean Gratz, Richard L Guerrant, Eric Houpt, William A Petri, Jr, James Platts-Mills, Rebecca Scharf (University of Virginia, Charlottesville, VA, USA); Binob Shrestha, Sanjaya Kumar Shrestha (Walter Reed/AFRIMS Research Unit, Kathmandu, Nepal); Tor Strand (Walter Reed/AFRIMS Research Unit, Kathmandu, Nepal; University of Bergen, Norway); Erling Svensen (Haukeland University Hospital, Bergen, Norway, Haydom Lutheran Hospital, Haydom, Tanzania).

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