Postnatal Iron Deficiency Impairs White Matter Development in Neonatal Piglets

Abstract

Iron deficiency (ID) is the most prevalent micronutrient deficiency in the world. Twenty-five percent of infants in the world are born ID; and severe ID resulting in anemia affects 16% of infants in industrialized countries and 40% of infants in developing countries. This is critical, as studies in older children link ID in early life with poorer math and writing abilities, reduced attention, and increased sensory latencies. Additional research is needed for understanding how ID affects brain development, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Therefore, the present study examined the effects of ID on brain development in a translatable neonatal piglet model. The hypothesis was that postnatal ID would alter brain development, particularly by reducing white matter integrity. Artificially reared piglets were fed either an ID or iron adequate sow milk replacer for 28 d, after which they were subjected to magnetic resonance imaging (MRI) to assess brain macrostructure (T1 MP RAGE), microstructure [diffusion tensor imaging (DTI)], and neurochemistry (MR spectroscopy). Voxel-based morphometry revealed widespread decreases in white matter in ID piglets, including areas of the hippocampus, thalamus, and corpus callosum. Further, in ID piglets gray matter volume decreased in the thalamus, prefrontal cortex and parietal lobe, and increased in the olfactory bulbs and hippocampus. DTI revealed reduced fractional anisotropy in ID piglets, suggesting a decrease in white matter integrity. No significant changes were found in brain metabolites. These results indicate postnatal ID affects both macrostructural and microstructural brain development, particularly in white matter. Supported by NIH R01 HD069899.