This study adds to the accumulating evidence of social-emotional effects of early ID by its findings of dose-response relations between severity of ID and outcome. Linear effects indicated increasing shyness, decreasing orientation/engagement, and decreasing soothability with poorer iron status (maternal or examiner ratings) and when an examiner attempted to engage the infants in imitative play, decreasing positive affect and engagement (quantitative coding). That the threshold for effects was ID with or without anemia echoes Honig and Oski's early report of increased solemnity in NA ID infants19
and a recent preventive trial in which infants who did not receive supplemental iron were less likely to show positive affect or interact socially.20
Another new study observed a negative linear relation between cord-blood iron status across the full range and negative emotionality and a positive one for alertness and soothability.21
Taken together, these studies point to altered infant social-emotional behavior and affect with ID, with or without anemia.
The behavioral differences observed at 12 months might be interpreted as showing lack of improvement with iron. However, the present study could not determine the effects of iron therapy on infant behavior due to uncertainty about iron administration and a low proportion of infants with blood work at 12 months. Despite the unresolved question of iron therapy, other evidence points to lack of iron as the cause of the observed behavioral alterations: 1) Similar affective-social differences have been reported in studies of IDA infants in a wide variety of settings, circumstances, and study designs.5
2) Four of 6 recent randomized controlled trials of iron supplementation in infancy that assessed social-emotional behavior found benefits of iron.5
3) Animal models with experimental manipulation of iron status by diet show related affective-social differences. For instance, the effects of iron deprivation in our monkey project were most striking in the social-emotional domain.7
Post-natally iron-deprived monkeys were hyperemotional and “tense”, even though no animal ever had IDA.
We have speculated that affective-social alterations relate to effects of ID on dopamine function,20,22
which are consistently reported in rodent models.8
Dopamine plays a major role not only in systems of behavioral activation and inhibition but also in positive affect and the degree to which individuals experience inherent reward.23,24
We also considered that behavioral alterations might be especially apparent in circumstances of novelty, unfamiliarity, or stress.25,26
In the present study, there was little difference in free play behavior, but several differences became apparent when an examiner sought to engage the infant in elicited play. However, there had been little previous work specifically on related brain/behavior systems in ID animal models to support our speculations or to clarify the neural mechanisms. Our program project's rodent study systematically investigated the behavioral domain and related brain systems in an experimental paradigm of dietary iron restriction. Behaviors that depend on striatal dopamine function were delayed or disrupted, with alterations into adulthood despite iron repletion and normalization of brain iron.9
Other persistent consequences, such as less exploration and more hesitancy in a novel environment, were also consistent with altered dopaminergic function.8
These results contribute to our growing conviction that altered affect and response to novelty are among the core deficits in early ID. Altered affect or activity have become a fundamental component of conceptual frameworks for understanding poorer overall developmental outcome.25,27
Such alterations, combined with delayed or mistimed sensory input, and cognitive and motor delay or dysfunction,5,28
may adversely affect the infant's interactions with the physical and social environment, thereby compromising development even further. If an ID infant is unable to elicit or benefit from nurturant interactions with caregivers, the child may have fewer enriching experiences that foster optimal development. Over time, direct effects of ID on the developing brain and indirect effects via limited environmental input may, in combination, contribute to poorer long-term behavioral and developmental outcome.29
The study is clearly limited in sample size. In addition, ID could not be confirmed by the “gold standard” of an increase in HB, because iron therapy could not be personally supervised and post-treatment hematology data were unavailable for more than 40% of the infants. This is problematic because indications of ID/IDA were generally milder than in previous developmental studies and other factors may alter iron measures (especially HB and MCV) in African-Americans.14
However, all NA ID and IDA infants met the criterion of ≥ 2 abnormal iron measures and biomarkers did not suggest inflammation as the explanation.11
Available data showed a HB increase in the IDA group and normalization of iron measures in the NA ID group. The results may not generalize to other than inner-city African-American infants and require replication in larger samples in different populations.
In sum, this study demonstrated linear effects of iron status on social-emotional behavior in young infants. The threshold of effects in this sample was ID with or without anemia v. IS. Combined with other human infant studies and a new nonhuman primate model, the results suggest that the social-emotional domain is adversely affected by lack of iron. This finding is worrisome because ID is not detected by common screening procedures and is more widespread than IDA. Combined with results in a developing rodent model, the observed behavior pattern of shyness/hesitance, reduced engagement, and altered response to the unfamiliar is consistent with early disruption of the dopamine system. Infant affect, activity, and social behavior can profoundly influence the caregiving environment, with repercussions for the child's overall development.