Early Childhood Diarrhea Predicts Cognitive Delays in Later Childhood Independently of Malnutrition

Relana Pinkerton Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.

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Reinaldo B. Oriá Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.
Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
Institute of Biomedicine and Clinical Research Unit, University Hospital, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.

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Aldo A. M. Lima Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.
Institute of Biomedicine and Clinical Research Unit, University Hospital, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
Physiology and Pharmacology Department, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.

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Elizabeth T. Rogawski Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.

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Mônica O. B. Oriá Department of Nursing, Federal University of Ceará, Fortaleza, Brazil.

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Peter D. Patrick Kluge Children Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.

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Sean R. Moore Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

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Benjamin L. Wiseman Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.
Psychiatry, Johnston-Willis Hospital, Richmond, Virginia.

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Mark D. Niehaus Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.

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Richard L. Guerrant Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia.
Institute of Biomedicine and Clinical Research Unit, University Hospital, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.

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Understanding the complex relationship between early childhood infectious diseases, nutritional status, poverty, and cognitive development is significantly hindered by the lack of studies that adequately address confounding between these variables. This study assesses the independent contributions of early childhood diarrhea (ECD) and malnutrition on cognitive impairment in later childhood. A cohort of 131 children from a shantytown community in northeast Brazil was monitored from birth to 24 months for diarrhea and anthropometric status. Cognitive assessments including Test of Nonverbal Intelligence (TONI), coding tasks (WISC-III), and verbal fluency (NEPSY) were completed when children were an average of 8.4 years of age (range = 5.6–12.7 years). Multivariate analysis of variance models were used to assess the individual as well as combined effects of ECD and stunting on later childhood cognitive performance. ECD, height for age (HAZ) at 24 months, and weight for age (WAZ) at 24 months were significant univariate predictors of the studies three cognitive outcomes: TONI, coding, and verbal performance (P < 0.05). Multivariate models showed that ECD remained a significant predictor, after adjusting for the effect of 24 months HAZ and WAZ, for both TONI (HAZ, P = 0.029 and WAZ, P = 0.006) and coding (HAZ, P = 0.025 and WAZ, P = 0.036) scores. WAZ and HAZ were also significant predictors after adjusting for ECD. ECD remained a significant predictor of coding (WISC III) after number of household income was considered (P = 0.006). This study provides evidence that ECD and stunting may have independent effects on children's intellectual function well into later childhood.

Author Notes

* Address correspondence to Richard L. Guerrant, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, 2507 Northfield Road, Charlottesville, VA 22901. E-mail: rlg9a@virginia.edu

Authors' addresses: Relana Pinkerton, Elizabeth T. Rogawski, Mark D. Niehaus, and Richard L. Guerrant, Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA, E-mails: rcp3w@virginia.edu, etr5m@virginia.edu, mniehaus@lifespan.org, and rlg9a@virginia.edu. Reinaldo B. Oriá and Mônica O. B. Oriá, Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil, E-mails: oria@ufc.br and oriarte@aol.com.br. Aldo A. M. Lima, Institute of Biomedicine and Clinical Research Unit, University Hospital, School of Medicine, Federal University of Ceará, Fortaleza, Brazil, E-mail: alima@ufc.br. Peter D. Patrick, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, E-mail: pdp2n@virginia.edu. Sean R. Moore, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, E-mail: sean.moore.md@gmail.com. Benjamin L. Wiseman, Psychiatry, CJW Medical Center, Johnston-Willis Hospital, Richmond, VA, E-mail: blw4u@virginia.edu.

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