Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

Abstract

Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia (IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel technique to explore patterns of functional connectivity. Default Mode Network (DMN), one of the resting state networks, is deeply involved in memory, social cognition and self-referential processes. The four core regions consistently identified in the DMN are the medial prefrontal cortex, posterior cingulate/retrosplenial cortex and left and right inferior parietal cortex. Therefore to investigate the DMN in former iron deficient anemic adults is a particularly useful approach to elucidate de long term effects on functional brain. We conducted this research to explore the connection between IDA in infancy and altered patterns of resting state brain functional networks in young adults. Resting-state fMRI studies were performed to 31 participants that belong to a follow-up study since infancy. Of them, 14 participants were former iron deficient anemic in infancy and 17 were controls, with mean age of 21.5 years (±1.5) and 54.8% were males. Resting-state fMRI protocol was used and the data was analyzed using the seed based connectivity statistical analysis to assess the DMN. We found that compared to controls, former iron deficient anemic subjects showed posterior DMN decreased connectivity to the left posterior cingulate cortex (PCC), whereas they exhibited increased anterior DMN connectivity to the right PCC. Differences between groups were also apparent in the left medial frontal gyrus, with former iron deficient anemic participants having increased connectivity with areas included in DMN and dorsal attention networks. These preliminary results suggest different patterns of functional connectivity between former iron deficient anemic and control young adults. Indeed, IDA in infancy, a common nutritional problem among human infants, may turn out to be important for understanding the mechanisms of cognitive alterations, common in adulthood.

Iron Nutriture of the Fetus, Neonate, Infant, and Child

“…Infants with ID can have multiple symptoms that are consistent with impaired hippocampal function, reduced myelination, and altered temperament and altered dopamine metabolism. For example, iron-deficient infants can present with decreased attention and memory [16, 17]; deficits in visual and auditory systems [18, 19]; and altered temperament and social and emotional behaviors [20–22]. Taken together, the evidence implies that ID in early life can permanently alter the brain and nervous system and may explain at least in part why little efficacy has been shown on neurodevelopmental outcomes in iron supplementation trials in young children [23–26].…”

All Wrapped Up: Environmental Effects on Myelination

“…This has important clinical implications during development, as the neurological sequelae (behavioral disorders, decreased cognitive ability, poor school performance) are long-lasting [147,148,149]. Developmental disturbances in myelin synthesis and composition are not corrected with iron repletion [150].…”

Efecto de la anemia en el desarrollo infantil: consecuencias a largo plazo

“…Por otro lado, en una cohorte realizada en Chile, se encontró que en adultos que tuvieron anemia en su primer año de vida y que luego fue corregida mediante suplementación, se presentaron patrones alterados de la conectividad cerebral a la edad promedio de 21,5 años, lo que sugiere que la anemia produce algún efecto en el desarrollo mental a largo plazo (24) , a pesar de la corrección de los niveles de hemoglobina.…”