1 Paediatric and International Nutrition, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet2 Paediatric Nutrition and International Nutrition, Department of Human Nutrition, Faculty of Life Sciences, Københavns Universitet3 Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.4 Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark; Department for International Health, University of Tampere, School of Medicine, Tampere, Finland.5 Curriculum Comittee of the Master of International Health, Faculty of Health and Medical Sciences, Københavns Universitet6 Paediatric Nutrition and International Nutrition, Department of Human Nutrition, Faculty of Life Sciences, Københavns Universitet7 Paediatric and International Nutrition, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet8 Curriculum Comittee of the Master of International Health, Faculty of Health and Medical Sciences, Københavns Universitet
BACKGROUND: Malnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed. OBJECTIVES: To review the scientific literature about immune function in children with malnutrition. METHODS: A systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1-60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition. RESULTS: The literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied. CONCLUSION: The immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.