Non-anaemic iron deficiency - a disease looking for recognition of diagnosis: a systematic review

ObjectiveTo capture all data meeting a rigid definition of non-anaemic iron deficiency (NAID) and determine whether it is associated with poor outcomes compared with normal iron status and whether iron supplementation improves outcomes in NAID. DesignSystematic review. Data sourcesEMBASE, Medline, Web of Science, , International Clinical Trials Registry Platform (ICTRP) and Central from database inception to April 2014. Eligibility criteriaFerritin <16g/L (<12g/L if age <5yr) in the absence of anaemia in observational studies or randomised trials. Where populations were deemed to be sufficiently similar, meta-analysis was undertaken. ResultsThere were 21 studies included. NAID in pregnancy associated with reduction in birthweight (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 (VO2maxP=0.21, RERmaxP=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). ConclusionsThere 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.