The impact of iron deficiency anemia on clinical outcomes across the lifespan: A systematic review

Abstract

Background: Iron-deficiency anemia (IDA) is characterized by depleted iron availability together with anemia and can occur during periods of rapid growth, pregnancy, chronic disease, and older age. Its clinical consequences are not uniform across the life course. Evidence is distributed across obstetric, pediatric, internal medicine, nephrology, cardiology, and inflammatory bowel disease literature, and studies frequently differ in how iron deficiency and anemia are defined. This review examines clinical outcomes associated with IDA across major life stages while explicitly separating evidence concerning IDA from evidence concerning anemia of unspecified cause or iron deficiency without anemia. Methods: This evidence review synthesizes published systematic reviews, meta-analyses, and representative primary studies concerning iron-deficiency anemia (IDA) and related iron-deficiency states across the lifespan. Evidence is organized by life stage and clinical domain, with attention to the distinction between confirmed IDA, iron deficiency without anemia, and anemia without documented iron deficiency. This manuscript is a narrative evidence synthesis; it does not report a newly conducted, reproducible database search or de novo study-selection process. Results: The verified literature supports clinically important associations between iron deficiency and outcomes across the life course, but the strength of evidence differs by age and outcome. During pregnancy, maternal anemia is associated with low birth weight, preterm birth, perinatal mortality, stillbirth, and maternal mortality in large meta-analyses, although these studies often evaluate anemia rather than laboratory-confirmed IDA. In childhood, observational evidence links early iron deficiency with later cognitive, behavioral, and motor outcomes, while intervention evidence is heterogeneous; a 2023 meta-analysis of 13 randomized-trial reports found improvements in intelligence, attention/concentration, and memory with iron supplementation among school-age children, but no significant improvement in school achievement. In adults with iron deficiency without anemia, randomized evidence supports improvement in self-reported fatigue but not objective physical capacity. In inflammatory bowel disease and chronic kidney disease, IDA and iron deficiency commonly coexist with substantial comorbidity, and iron treatment has been evaluated for hematologic and clinical outcomes. In heart failure, contemporary randomized evidence indicates that intravenous iron in iron-deficient patients can reduce recurrent heart-failure hospitalization and cardiovascular death composites, although the evidence concerns iron deficiency in heart failure and is not synonymous with isolated IDA. In older adults, anemia is associated with adverse outcomes, but attributing these associations specifically to IDA requires careful adjustment for inflammation, kidney disease, malignancy, nutritional status, and other comorbidities. Conclusions: IDA is clinically relevant across the lifespan, but the evidence should not be summarized as a single uniform causal effect. The most consistent evidence concerns pregnancy outcomes, symptomatic burden and fatigue, pediatric hematologic response to iron, and selected outcomes in chronic disease. Evidence for long-term neurodevelopmental and cardiovascular effects is biologically plausible but more heterogeneous and frequently confounded. Future systematic reviews should use explicit laboratory definitions of IDA, distinguish exposure from treatment, separate anemia of other causes, and report outcomes by age and clinical setting.