Gestational Stress and Impaired Iron Homeostasis in the Young Infant

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DESCRIPTION (provided by applicant): Chronic inflammatory states, steroid hormone exposure, and stress can affect iron-related biology, an essential micronutrient needed for infant growth and normal brain development. This project will investigate the novel hypothesis that some of the disabling effects of a stressful prenatal environment are mediated by undermining the placental transfer of maternal iron, which results in the subsequent depletion of iron stores in the growing infant. A nonhuman primate model will be used to determine how gestational stress impairs the placental transfer, sequestering, and use of iron by the young infant. One aim focuses on the timing of the gestational disturbance, comparing the effects of maternal stress during early, mid, or late pregnancy. To quantify placental transfer and bioavailability of iron in the neonate, an innovative approach with stable iron isotopes will be employed, contrasting absorption and transfer of 57Fe provided orally to 58Fe infused intravenously into the pregnant female. Iron-sensitive hematological measures will then be monitored in the developing infants from the stressed and undisturbed control pregnancies to prove that the postnatal iron deficiency is temporally associated with the occurrence of abnormal brain and renal functions. Based on previous findings in anemic monkeys, neural dysfunction will be indexed by the protein and metabolite profile of cerebrospinal fluid using Western blot and nuclear Magnetic Resonance Spectroscopy techniques. To further demonstrate the clinical significance of these deficits, the effects of prenatal stress and anemia on renal functioning observed in other species will be verified. When infants are 8 months of age, measures of glomerular filtration rate and renal sympathetic input will be obtained. A second study will support the veracity of iron mediation hypothesis by showing that oral iron supplementation during pregnancy can lessen the effects of prenatal stress on the developing infants. The two studies are comprised of 126 mother-infant pairs of rhesus monkeys, with the behavior and physiology of each infant evaluated prospectively from birth across the first year of life. This research will contribute to the growing awareness about the formative role of the fetal period in laying the foundation for postnatal health. Demonstrating that gestational stress affects iron homeostasis would reveal a deficit amenable to treatment. Iron deficiency has a broad public health significance because it is the most prevalent single nutrient deficiency worldwide.