Abstract
Early-life iron deficiency has lifelong influences on brain structure and cognitive function, however characterization of these changes often requires invasive techniques. There is a need for non-invasive assessment of early-life iron deficiency with potential to translate findings to the human clinical setting. In this study, 28 male pigs were provided either a control diet (CONT; n = 14; 23.5 mg Fe/L milk replacer) or an iron-deficient diet (ID; n = 14; 1.56 mg Fe/L milk replacer) for phase 1 of the study, from postnatal day (PND) 2 until 32. Twenty pigs (n = 10/diet from phase 1 were used in phase 2 of the study from PND 33 to 61, where all pigs were provided a common iron-sufficient diet, regardless of their phase 1 dietary iron status. All pigs were subjected to magnetic resonance imaging at PND 32 and again at PND 61, and quantitative susceptibility mapping was used to assess brain iron content at both imaging time-points. Data collected on PND 61 were analyzed using voxel-based morphometry and tract-based spatial statistics to determine tissue concentration difference and white matter tract integrity, respectively. Quantitative susceptibility mapping outcomes indicated reduced iron content in the pons, medulla, cerebellum, left cortex, and left hippocampus of ID pigs compared with CONT pigs, regardless of imaging time-point. In contrast, iron contents were increased in the olfactory bulbs of ID pigs compared with CONT pigs. Voxel-based morphometric analysis indicated increased grey and white matter concentrations in CONT pigs compared with ID pigs that were evident at PND 61. Differences in tissue concentrations were predominately located in cortical tissue as well as the cerebellum, thalamus, caudate, internal capsule, and hippocampi. Tract-based spatial statistics indicated increased fractional anisotropy values along subcortical white matter tracts in CONT pigs compared with ID pigs that were evident on PND 61. All described differences were significant at p ≤ 0.05. Results from this study indicate that neuroimaging can sensitively detect structural and physiological changes due to early-life iron deficiency, including grey and white matter volumes, iron contents, as well as reduced subcortical white matter integrity, despite a subsequent period of dietary iron repletion.
Highlights
Iron deficiency is the most common micronutrient deficiency worldwide [1,2] and a deficiency during the perinatal period has lifelong implications
Our results indicate that pigs provided an early-life iron deficient (ID) diet exhibited decreased brain iron concentrations in the cerebellum, pons, medulla, left cortex, and right cortex compared with CONT pigs at postnatal day (PND) 32 and after receiving iron replete diets
We previously showed that iron deficiency alters whole brain volumes at PND 32 but iron repletion was able to correct for observed differences by PND 61
Summary
Iron deficiency is the most common micronutrient deficiency worldwide [1,2] and a deficiency during the perinatal period has lifelong implications. It is clear that early-life iron deficiency has lasting effects on cognitive performance, yet it remains to be elucidated what structural differences in brain development might underlie these persistent cognitive changes. Some studies in humans have used other non-invasive techniques such as evoked potential recordings [12], electrophysiological recording and processing [9] and electroencephalography [13] to explain structural alterations in brain development related to iron deficiency. While these methods may potentially explain a mechanism for altered brain development, more sensitive assessments are needed to non-invasively characterize the brain regions influenced by iron deficiency
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
