This study examined the effects of IDA and ID without anemia on infant motor development by assessing motor skills that relate to brain areas and/or processes known to be altered by early ID, namely myelination and basal ganglia function, especially related to the dopamine system. Several tests that are sensitive to overall motor delays, which may be affected by impaired myelination, indicated linear effects of iron status, specifically, developmental milestones, Peabody gross motor (suggestive trend), INFANIB standing item, and the BRS Motor Quality factor. The threshold for the effects on developmental milestones, INFANIB standing item, and motor quality was ID with or without anemia, and scores for the NA ID group were significantly lower than the IS group. The toy retrieval task, where performance may depend on basal ganglia function, also showed linear effects of iron status, and the threshold for this effect was IDA. These results controlled for background factors that correlated with outcome. A few previous studies found motor effects of ID without anemia (e.g., (26
)), but most did not (see review (7
)). Our detection of such effects may be due to using a more comprehensive and more sensitive motor assessment.
We will first discuss how ID effects on impaired myelination and poor function of the basal ganglia could affect and impair motor performance. We will point to some limitations of our study and end with a suggestion for a future intervention, aimed at overcoming these effects.
Impaired myelination is one potential mechanism for ID effects on overall motor development. Iron is essential for oligodendrocyte function, which is crucial for myelin production. ID during gestation and lactation in the rat induces changes in myelin components (protein, cholesterol, phospholipids and galactolipids) and compaction in adulthood, despite an iron-sufficient diet beginning at weaning (8
). In the human IDA infant, slower transmission in the auditory and/or visual systems, both short-term and years after iron therapy (28
), suggests that effects of ID in infancy on myelination may be widespread and long-lasting. The corticospinal tract, in which motor commands traverse from the motor and sensory regions of the cerebral cortex to the spinal cord, is not completely myelinated at birth and thus may be particularly vulnerable to early ID effects. Impaired myelination in the entire brain and especially the corticospinal tract may delay and/or alter the normal development and refinement of motor skills.
Another potential mechanism for the effects of early ID on motor development is through altered basal ganglia function. In rodent models of diet-induced ID during gestation and lactation, severe IDA reduced D1
dopamine receptor densities in the striatum (8
), along with poor growth. To be more relevant to IDA in human infants, the rodent model in our program project produced ID with a more moderate level of brain ID than previous studies and avoided marked growth restriction (29
). Even in the more moderate ID model, deficits in a natural grooming sequence that depends on striatal dopamine function were observed in adulthood, despite correction of IDA and normalization of brain iron content in all areas but the thalamus (29
The basal ganglia play important roles in learning and execution of sequential movements (20
) and also control of bi-manual coordination, through motor inhibition of contralateral movements (21
). Thus, the difficulty ID infants showed on the toy retrieval task, which requires sequential movements during bi-manual coordination, may relate to IDinduced changes in striatal dopamine function.
Although postural control has not been traditionally considered a major function of the basal ganglia, a recent review emphasizes their important contribution to regulation of postural control (31
). Other outcomes with a threshold of ID with or without anemia (developmental milestones and INFANIB standing) depend on postural control at this age. Postural control may be sensitive even to ID without anemia because it involves more than one CNS process impaired by ID (i.e., myelination and basal ganglia function).
The study is limited by small sample size, and results may not generalize to other populations. Uncertainty concerning compliance with iron intake and the high proportion of missing hematology data at 12 months mean that the study could not assess the ability of iron therapy to improve infant motor development.
In sum, using a comprehensive and sensitive assessment of motor development, this study found poorer motor function in ID infants with and without anemia. These findings were independent of family background, suggesting that poorer development was not due to family factors, such as lack of maternal stimulation and encouragement/attention. The observed effects of ID without anemia are particularly concerning, since ID without anemia is not detected by common screening procedures and is more widespread than IDA. The observed motor deficits in early ID are consistent with impaired myelination and oligodendrocyte function, both of which appear to be sensitive to developmental experience (32
). Thus, future interventions for ID in infancy that include motor training or other environmental enrichment might help reduce long-term effects.