Non-Anaemic Iron Deficiency - a disease looking for recognition of diagnosis: a systematic review.

OBJECTIVE: To capture all data meeting a rigid definition of Non-Anaemic Iron Deficiency (NAID) and determine if it is associated with poor outcome compared to normal iron status, and if iron supplementation improves outcomes in NAID. DESIGN: Systematic review. DATA SOURCES: EMBASE, Medline, Web of Science, clinicaltrials. gov, International Clinical Trials Registry Platform (ICTRP) and Central from database inception to April 2014. ELIGIBILITY CRITERIA: Ferritin <16μg/L (<12 μg/L if age <5years) in the absence of anaemia in observational studies or randomised trials. Where populations were deemed to be sufficiently similar meta-analysis was undertaken. RESULTS: There were 21 studies included. NAID in pregnancy associated with reduction in birth weight (p=0.028). Iron supplementation in NAID was associated with improvement in objective scores (p=0.005) and self-rating (p=0.03) of fatigue. Meta-analysis was limited and, where possible, was not statistically significant including the comparison of NAID with cardiovascular function in adults (VO2max p=0.21, RERmax p=0.68), educational attainment in children (p=0.14), infant mental (p=0.29) and psychomotor (p=0.07) development, and iron supplementation in NAID with educational attainment in language (p=0.31). CONCLUSIONS: There is emerging evidence that NAID is a disease in its own right, deserving of further research in the development of strategies for detection and treatment. This article is protected by copyright. All rights reserved.