Dietary Iron Fortification Normalizes Fetal Hematology, Hepcidin, and Iron Distribution in a Rat Model of Prenatal Alcohol Exposure. (19th May 2018)

• Record Type: Journal Article
• Authors: Huebner, Shane M.; Helfrich, Kaylee K.; Saini, Nipun; Blohowiak, Sharon E.; Cheng, Adrienne A.; Kling, Pamela J.; Smith, Susan M.
• Is Part Of: Alcoholism. Volume 42:Number 6(2018)
• Page Start: 1022
• Page End: 1033
• Publication Date: 2018-05-19
• Subjects: Fetal Alcohol Spectrum Disorder -- Iron Deficiency -- Hepcidin -- Anemia -- Iron Homeostasis; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13754
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : Background: Prenatal alcohol exposure (PAE) causes neurodevelopmental disability. Clinical and animal studies show gestational iron deficiency (ID) exacerbates PAE's behavioral and growth deficits. In rat, PAE manifests an inability to establish iron homeostasis, increasing hepcidin (maternal and fetal), and fetal liver iron while decreasing brain iron and promoting anemia. Here, we hypothesize dietary iron fortification during pregnancy may mitigate alcohol's disruption of fetal iron homeostasis. Methods: Pregnant Long‐Evans rats, fed iron‐sufficient (100 ppm iron) or iron‐fortified (IF; 500 ppm iron) diets, received either 5 g/kg alcohol (PAE) or isocaloric maltodextrin daily on gestational days (GD) 13.5 through 19.5. Maternal and fetal outcomes were evaluated on GD20.5. Results: PAE reduced mean fetal weight ( p < 0.001) regardless of maternal iron status, suggesting iron fortification did not improve fetal growth. Both PAE ( p < 0.01) and IF ( p = 0.035) increased fetal liver iron. In fetal brain, PAE ( p = 0.015) affected total ( p < 0.001) and nonheme iron ( p < 0.001) such that iron fortification normalized ( p = 0.99) the alcohol‐mediated reductions in brain iron and nonheme iron. Iron fortification also improved fetal hematologic indices in PAE including hemoglobin, hematocrit, and mean cell volume ( p s<0.001). Iron fortification also normalized hepcidin expression in alcohol‐exposed maternal and fetal liver. Neither diet nor PAE affected transferrin (Tf) and ferritin (FTN) content in fetal liver, nor Tf or transferrin receptor in fetal brain. However, IF‐PAE fetal brains trended to less FTN content ( p = 0.074), suggesting greater availability of nonstorage iron. In PAE, hepcidin levels were linearly related to increased liver iron stores and decreased red blood cell count and brain iron. Conclusions: Maternal oral iron fortification mitigated PAE's disruption of fetal iron homeostasis and improved brain iron content, hematologic indices, and hepcidin production in this rat PAE model. Clinical studies show maternal ID substantially enhances fetal vulnerability to PAE, and our work supports increased maternal dietary iron intake may improve fetal iron status in alcohol‐exposed pregnancies. Abstract : Maternal nutrition affects fetal outcomes in response to prenatal alcohol exposure (PAE). Low maternal iron stores render fetuses vulnerable to PAE‐mediated disruption of fetal iron homeostasis and brain iron content. This increases the risk of impaired brain function and fetal anemia. We show here that maternal dietary iron fortification reduces fetal vulnerability to PAE and improves fetal iron homeostasis, hematological indices, and brain iron content, thereby partially mitigating some negative outcomes associated with fetal alcohol spectrum disorders.