Iron deficiency remains one of the foremost nutrient deficiencies in the world. Its effect on the developing brain and subsequent neurodevelopmental outcome is of particular importance. Our laboratory has characterized two groups of infants at increased risk of iron deficiency in the fetal and neonatal period; infants born to diabetic mothers (IDM) and intrauterine growth-retarded (IUGR) infants. Altered perinatal iron metabolism affects approximately 225,000 newborn infants per year in the United States. Both risk groups have altered neurodevelopment. We hypothesize that fetal iron deficiency contributes to their long-term neurological abnormalities. Our long-term objectives are to: 1) study the ontogeny of proteins involved in regulation of placental iron transport during pregnancies complicated by fetal iron deficiency; and 2) document the postnatal neurological sequelae of fetal iron deficiency. We hypothesize that: 1) placental transferring receptor (TfR) and HFE protein expression are regulated by fetal iron demand in IUGR pregnancies.; 2) fetal brain iron deficiency in IUGR pregnancies; 2) fetal brain iron deficiency in IUGR contributes to abnormalities of hypocampally based recognition memory processing by selectively reducing neuronal metabolism in the hippocampus. TfR and HFE protein expression and localization, iron responsive protein-1 and TfR mRNA expression, and TfR binding characteristics will be compared between 10 term iron-deficient IUGR placentas and 10 iron-sufficient controls. Ten placentas at 14, 18, 22, 24-28, 30-34 and >34 weeks gestation from normal pregnancies will be studied immunohistochemically to determine the ontogeny of TfR and HFE expression and contrasted to expression of these proteins in iron-deficient IUGR placentas. Recognition memory processing in 16 iron-deficient IUGR infants will be compared electrophysiologically at birth, 6 and 24 months and behaviorally at 6, 12 and 24 months to 16 controls. Perinatally iron-deficient rats (+/- perinatal stressors) will have their cerebral metabolism assessed longitudinally by 9.4 T magnetic resonance spectroscopy to identify hippocampal abnormalities due to iron deficiency. The metabolic results will be correlated with behavior and histochemical changes.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Nutrition Study Section (NTN)
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Grave, Gilman D
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University of Minnesota Twin Cities
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Georgieff, Michael K; Tran, Phu V; Carlson, Erik S (2018) Atypical fetal development: Fetal alcohol syndrome, nutritional deprivation, teratogens, and risk for neurodevelopmental disorders and psychopathology. Dev Psychopathol 30:1063-1086
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