An Overview of Evidence for a Causal Relation between Iron Deficiency during Development and Deficits in Cognitive or Behavioral Function

Abstract

This review, intended for a broad scientific readership, summarizes evidence relevant to whether a causal relation exists between dietary iron deficiency with (ID+A) or without (ID-A) anemia during development and deficits in subsequent cognitive or behavioral performance. An overview of expert opinion and major evidence in humans and animals is provided. Cognitive and behavioral effects observed in humans with ID-A and in animals with ID+/-A are provided in tables. The degree to which 5 conditions of causality are satisfied and whether deleterious effects of ID-A might be expected to occur are discussed. On the basis of the existing literature, our major conclusions are as follows. Although most of the 5 conditions of causality (association, plausible biological mechanisms, dose response, ability to manipulate the effect, and specificity of cause and effect) are partially satisfied in humans, animals, or both, a causal connection has not been clearly established. In animals, deficits in motor activity are consistently associated with severe ID+A, but adverse effects on performance in tests that target cognitive function have not been clearly shown. Resistance to iron treatment was observed in most trials of children <2 y of age with ID+A, but not in older children. Similar observations were made in rodents when ID+A occurred before rather than after weaning. In children >2 y of age and in adolescents with ID-A, evidence suggests cognitive or behavioral deficits; however, the surprisingly small number of studies conducted in either humans or animals prevents a thorough assessment.