title: Vitamin D status is associated with mortality, morbidity, and growth failure among a prospective cohort of HIV-infected and HIV-exposed Tanzanian infants.
abstract: BACKGROUND
  Vitamin D is a potent immunomodulator, but its impact on morbidity and mortality among infants remains unclear.
  
  
  OBJECTIVE
  The objective of the study was to prospectively assess the association of vitamin D status with mortality, morbidity, and growth during the first 2 y of life.
  
  
  METHODS
  A prospective cohort of 253 HIV-infected and 948 HIV-exposed Tanzanian infants enrolled in a randomized trial of multivitamins (not including vitamin D) was studied. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 5-7 wk of age and infants were followed at monthly clinic visits until 24 mo. Physicians performed a clinical exam every 3 mo or when an illness was noted.
  
  
  RESULTS
  Serum 25(OH)D concentrations were (means ± SDs) 18.6 ± 10.3 ng/mL and 18.1 ± 9.2 ng/mL for HIV-infected and HIV-exposed infants, respectively. Unexpectedly, serum 25(OH)D concentrations ≥30 ng/mL were significantly associated with higher mortality as compared to the 20-29.9 ng/mL reference for HIV-infected (HR: 2.47; 95% CI: 1.13, 5.44; P = 0.02) and HIV-exposed (HR: 4.00; 95% CI: 1.67, 9.58; P < 0.01) infants after multivariate adjustment. We found no statistically significant association between 25(OH)D concentrations <10 ng/mL and mortality for HIV-infected (HR: 1.43; 95% CI: 0.74, 2.78; P = 0.29) and HIV-exposed (HR: 1.56; 95% CI: 0.60, 4.03; P = 0.36) infants. Among HIV-exposed infants, 25(OH)D concentrations ≥30 ng/mL were significantly associated with clinical [incidence ratio rate (IRR): 1.34; 95% CI: 1.06,1.70; P = 0.02] and confirmed (IRR: 1.71; 95% CI: 1.71; 1.15, 2.54; P < 0.01) malaria diagnoses, whereas concentrations of <10 ng/mL were associated with oral candidiasis (IRR: 1.47; 95% CI: 1.00-2.15; P = 0.046) and wasting (HR: 1.71; 95% CI: 1.20, 2.43; P < 0.01).
  
  
  CONCLUSIONS
  The observational design of this study does not allow for causal interpretation; however, the results indicate a strong need for additional studies of vitamin D among HIV-infected and -exposed children, particularly in malaria-endemic settings. The parent trial was registered at clinicaltrials.gov as NCT00197730.
authors.affiliation: Departments of Global Health and Population, csudfeld@hsph.harvard.edu.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Sudfeld
authors.affiliation: Nutrition, and Division of Gastroenterology and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA; Departments of.
authors.forename: Christopher
authors.initials: C
authors.lastname: Duggan
authors.affiliation: Microbiology and Immunology and.
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.affiliation: Nutrition, and UNICEF Headquarters, New York, NY.
authors.forename: Roland
authors.initials: R
authors.lastname: Kupka
authors.affiliation: Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; and.
authors.forename: Karim P
authors.initials: KP
authors.lastname: Manji
authors.affiliation: Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; and.
authors.forename: Rodrick
authors.initials: R
authors.lastname: Kisenge
authors.affiliation: Departments of Global Health and Population, Nutrition, and Epidemiology, Harvard School of Public Health, Boston, MA;
authors.forename: Wafaie W
authors.initials: WW
authors.lastname: Fawzi
mesh_terms: D000328:Adult; D001827:Body Height; D001835:Body Weight; D015331:Cohort Studies; D019587:Dietary Supplements; D019353:Endemic Diseases; D005260:Female; D006130:Growth Disorders / Q000097:blood* / Q000821:virology; D015658:HIV Infections / Q000097:blood / Q000401:mortality*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000150:complications / Q000453:epidemiology; D008297:Male; D009017:Morbidity; D009752:Nutritional Status; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011446:Prospective Studies; D013636:Tanzania / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood*; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: HIV; child nutrition sciences; cohort studies; infant; malaria; micronutrients; vitamin D