This project in the P01 application will use a unique nonhuman primate model to evaluate the long-term consequences of iron deficiency during infancy during infancy on behavior and the central nervous system (CNS). The infant monkey model of iron deficiency (ID) will be generated by breeding adult female rhesus monkeys prescreened for iron deficiency prior to conception. Previous research has established that these females generate infants that have low ferritin levels at birth, and the infants' low iron store ultimately predispose them to an iron deficiency anemia (IDA) between 4-8 months postpartum. Three studies are proposed to evaluate the consequences of this IDA for behavioral and CNS development across the first 1.5 years of life. The second and third studies will evaluate the benefits of early and late iron repletion for preventing or ameliorating the effects of IDA on CNS functions related to dopamine, myelination, and hippocampal memory processes. Across a 5-year period, 3 studies involving 90 mother-infant dyads will be conducted. The first study will assess the developmental and hematological profiles of infants generated from 15 iron deficient (ID) and 15 iron sufficient (IS) adult females. The outcome measures focuses on 4 domains: Physical Growth, Hematology, Cognitive Performance, and CNS measures. It is predicted that ID infants will show delayed neuromotor maturation, less adept fine motor control, greater emotionality, and poor performance on cognitive tasks. CNS functioning will be evaluated both by electrophysiological techniques (Auditory Brainstem Event Related Potentials (ABR) and neuroimaging of biochemical markers of myelination by proton Magnetic Resonance Spectroscopy (MRS). The second study will assess the benefits of early iron supplementation beginning at either 1 or 4 months postpartum for preventing IDA and any effects on behavioral and CNS development. Finally, Study 3 will extend this evaluation to investigate the therapeutic gains of iron repletion in the older infant, either at 6 or 9 months of age, which is after the onset of IDA in the monkey. It is hypothesized that some cognitive and CNS effects will continue to be manifest in the latter groups of infant monkeys. This project would provide valuable information on the persistent sequelae of ID using an established nonhuman primate model.
Showing the most recent 10 out of 93 publications
