Progress 10/01/06 to 09/30/09
Outputs
OUTPUTS: This study had three primary objectives. The first was to obtain the first data on heme iron absorption among pregnant women and examine the hormonal control of iron absorption during pregnancy. We undertook a case-control study in a group of 18 pregnant women (ages 16-32 y; week 32-35 of gestation) and 11 non-pregnant women (ages 18-27 y). Women were randomly assigned to receive both a heme meal (intrinsically labeled 58Fe pork) and ferrous sulfate (57Fe). Blood samples obtained two weeks post-dosing were used for assessment of iron absorption, iron status and serum hepcidin. Iron deficiency was prevalent among the pregnant subjects enrolled in the study; 61% had depleted Fe stores (serum ferritin < 20 μg/L) and 22% had negative total body Fe values. At delivery 50% of the women had iron deficiency anemia. Heme iron absorption was significantly greater than non-heme iron absorption in both pregnant (47.9 14.4 vs. 40.4 13.2%) and non-pregnant subjects (50.2 14.8 vs. 15.3 9.7%). During the third trimester of pregnancy absorption of non-heme iron was significantly upregulated in women with low iron stores. Heme iron absorption was not influenced by maternal iron stores but was inversely associated with age. Hepcidin was significantly inversely associated with non-heme iron absorption, but had no significant impact on heme iron absorption in either pregnant or non-pregnant women. Unlike non-heme iron absorption, absorption of heme iron is not affected by hepcidin concentrations or iron stores. These data indicate that absorption of heme iron from animal based foods provides a highly bioavailable source of dietary iron during pregnancy. Ability of pregnant women to transfer maternally ingested dietary heme and non-heme iron to the fetus over the last trimester of pregnancy was also monitored by measuring Fe57 and Fe58 enrichment in maternal and cord blood samples obtained at delivery. A significantly greater fraction of maternally absorbed dietary heme iron was transferred to the fetus compared to non-heme iron. Fetal non-heme enrichment was significantly related to maternal iron status and serum hepcidin at delivery. Likewise, fetal heme enrichment was associated with maternal iron status and serum hepcidin. Both heme and non-heme iron transport were associated with neonatal hemoglobin at delivery. Mothers with low iron status and undetectable serum hepcidin at delivery transferred significantly more non-heme and heme iron to their neonates than women with detectable levels. These data indicate that there may be a preferential fetal utilization of maternally ingested heme iron compared to non-heme iron during pregnancy. In addition, maternal serum hepcidin plays a role in regulation of both heme and non-heme iron transfer to the fetus during the third trimester of gestation. Our final study aim was to assess the expression of iron transporters in the placental tissue in relation to the isotopic excess observed in the newborn. Data from this objective is nearly complete and all data will be submitted for publication over the coming months. PARTICIPANTS: Dr. Kimberly O'Brien is the principal investigator of the study and is responsible for the oversight of the project and analysis and publication of these data. Dr. Ian Griffin is a project director. Dr. Griffin is a neonatologist at the University of California, Davis. His role in the project was to intrinsically label the pork with 58Fe and assist in data interpretation. Dr Eva Pressman is a project director and is a practicing obstetrician/gynecologist at The University of Rochester, Strong Memorial Hospital in Rochester, NY. She was medically responsible for the studies undertaken among pregnant women recruited from Rochester, NY and she assisted in obtaining the cord blood and placental tissue. Dr. Leah Harris is a project director and is a pediatric anesthesiologist at Vanderbilt University School of Medicine. Dr. Harris assisted with method development for the iron transport proteins and with data interpretation and publication. Dr. Patrick Stover is the Director of the Division of Nutritional Sciences at Cornell. He will assist with the molecular biology work in placental tissues as needed. Melissa Young is a doctoral student in DNS working on this project for her doctoral dissertation. Dr. Marisa Foehr is a post-doctoral student working on this project as needed to assist in methodological development. TARGET AUDIENCES: This study will provide results relevant to the US population; in particular to non-pregnant and pregnant women. Results are particularly relevant to minority women and to pregnant adolescents as these groups are disproportionately affected by iron deficiency anemia. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Iron deficiency is the most common nutrient deficiency in the world. Women are at increased risk; particularly during pregnancy. Iron is obtained from the diet from both plant (non-heme) and animal sources (heme sources). The absorption of these 2 forms of iron in the intestine occurs through different pathways. Absorption of non-heme iron is well characterized but at present, mechanisms involved in absorption of heme based iron are not well understood. Additional questions remain with respect to how the iron that is absorbed into the body is then transferred across the placenta and which proteins are involved in placental iron transport. The degree to which the fetus can acquire sufficient iron when maternal intake is suboptimal is not known. This is an important question as many women do not consume enough iron to meet the iron demands of pregnancy and they become anemic during pregnancy. Moreover, it is increasingly recognized that maternal iron deficiency during pregnancy can limit the amount of iron stores that a neonate has at birth. In addition, iron deficiency anemia during early childhood can result in long term adverse and irreversible effects on infant cognition. To achieve the USDA's goal of restructuring the wholesomeness of the food supply, and promoting healthy dietary habits, dietary recommendations must be increasingly grounded in an understanding of human nutrient dynamics. Obtaining this information will allow for the development of accurate and scientifically informed nutrition and agriculture policies for public health benefit. Results from this study will provide novel information on how plant vs. meat sources of iron are absorbed during pregnancy, and how these forms of iron are utilized by pregnant women to meet fetal iron demands. Additional work from this study will provide information on mechanisms of placental iron transfer
Publications
- Young MF, Glahn RP, Ariza-Nieto M et al. Serum hepcidin is significantly associated with iron absorption from food and supplemental sources in healthy young women. Am J Clin Nutr 2009;89:533-8.
- Young MF, Griffin I, Pressman E, McIntyre A, Cooper E, McNanley T, Harris L, Westerman M, O'Brien KO. Non-heme and heme iron absorption during pregnancy. Accepted for oral presentation at the 2010 Experimental Biology Meeting. To be published in the FASEB Journal.
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Progress 10/01/07 to 09/30/08
Outputs
OUTPUTS: The proposed study will utilize stable mineral isotopes to safely measure relative differences in how iron is absorbed from plant based (non-heme) and animal based (heme) iron sources in both pregnant and non-pregnant women. By obtaining cord blood from pregnant women at delivery we will also determine if there are differences in how much of the heme and non-heme absorbed iron is transferred to the fetus during the final weeks of pregnancy. Placental tissue will also be collected at delivery to measure iron transport protein in relation to iron absorption and iron transfer to the fetus. These findings will increase the knowledge available on iron absorption and transfer to the fetus and will provide data that will assist in developing targeted interventions to improve the iron status of women during their reproductive years. To date studies have been undertaken in non-pregnant (n=1) and pregnant women (n=3) and analyses of isotopic ratios in cord blood and maternal blood are on-going. Placental measures of iron transport proteins are also underway. Preliminary results from the study have been disseminated at the departmental human and molecular nutrition seminar and at the departmental maternal and child nutrition seminar. PARTICIPANTS: Dr. Kimberly O'Brien is the principal investigator of the study and is responsible for the oversight of the project and analysis and publication of these data. Dr. Ian Griffin is a project director. Dr. Griffin is a neonatologist at the University of California, Davis. His role in the project is to intrinsically label the pork with 58Fe. R. Eva Pressman is a project director and is a practicing obstetrician/gynecologist at The University of Rochester, Strong Memorial Hospital in Rochester, NY. She will be medically responsible for the studies undertaken among pregnant women that will be recruited from Rochester, NY and she will assist in obtaining the cord blood and placental tissue. Dr. Leah Harris is a project director and is a pediatric anesthesiologist at Johns Hopkins School of Medicine in Baltimore, Maryland. Dr. Harris will assist in the method development for the iron transport proteins and will assist in the processing and histology of the placental tissue collected. Dr. Subash Chandra is a project director and is an adjunct assistant professor in the Cornell SIMS lab. He will investigate the possibility of screening the placental tissue for iron isotopes using SIMS. Dr. Patrick Stover is the Director of the Division of Nutritional Sciences at Cornell. He will assist with the molecular biology work in placental tissues as needed. Melissa Young is a doctoral student in DNS working on this project for her doctoral dissertation. Dr. Marisa Foehr is a post-doctoral student working on this project as needed to assist in methodological development. TARGET AUDIENCES: This study will provide results relevant to the US population; in particular to non-pregnant and pregnant women. Results are relevant to minority women that are disproportionately affected by iron deficiency anemia. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Iron deficiency is the most common nutrient deficiency in the world. Women are at increased risk; particularly during pregnancy. Iron is obtained from the diet from both plant (non-heme) and animal sources (heme sources). The absorption of these 2 forms of iron in the intestine occurs through different pathways. Absorption of non-heme iron is well characterized but at present, mechanisms involved in absorption of heme based iron are not well understood. Additional questions remain with respect to how the iron that is absorbed into the body is then transferred across the placenta and which proteins are involved in placental iron transport. The degree to which the fetus can acquire sufficient iron when maternal intake is suboptimal is not known. This is an important question as many women do not consume enough iron to meet the iron demands of pregnancy and they become anemic during pregnancy. Moreover, it is increasingly recognized that maternal iron deficiency during pregnancy can limit the amount of iron stores that a neonate has at birth. In addition, iron deficiency anemia during early childhood can result in long term adverse and irreversible effects on infant cognition. To achieve the USDA's goal of restructuring the wholesomeness of the food supply, and promoting healthy dietary habits, dietary recommendations must be increasingly grounded in an understanding of human nutrient dynamics. Obtaining this information will allow for the development of accurate and scientifically informed nutrition and agriculture policies for public health benefit. Results from this study will provide novel information on how plant vs. meat sources of iron are absorbed during pregnancy, and how these forms of iron are utilized by pregnant women to meet fetal iron demands. Additional work from this study will provide information on mechanisms of placental iron transfer.
Publications
- Young MF, Glahn RP, Inglis J, Olbina G, Westerman M, OBrien KO. Serum Hepcidin is Associated with Iron Absorption in Healthy Young Women. Am J Clin Nutr; 2008 (In Press).
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Progress 10/01/06 to 09/30/07
Outputs
OUTPUTS: The proposed study will assess how non-heme iron and heme-iron are absorbed in women and how these two different forms of dietary iron are transferred to the fetus. To trace the absorption of iron from the diet we will utilize both a non-heme source of iron and a heme-source of iron; each of which will be labeled with a stable iron isotope. To examine the absorption of non-heme iron we have prepared ferrous sulfate labeled with a naturally occurring, stable tracer of iron (57Fe) that is found naturally in our body at very low levels. To compare absorption of heme iron we are in the process of intrinsically labeling pork with 58Fe; another naturally occurring stable tracer of iron that is found at low levels naturally in our body. The two labeled forms of iron will be ready to utilize within the next few weeks. Studies in non-pregnant women will be undertaken in the Human Metabolic Research Unit at Cornell University. This study has been approved by UCHS and recruitment of
volunteers will start this month. The study in pregnant women is currently under review by the Institutional Review Board at the University of Rochester. We have replied to their initial comments and expect this study to be approved by their IRB within the month at which time we will submit this to Cornell's human use review committee We have the methods developed and ready to screen for iron status indicators in blood obtained from these subjects and are currently working out the methods needed to screen the placental tissue for the iron transport proteins. We are also validating an assay for the measurement of hepcidin, a recently developed hormone that is responsible for regulation of non-heme iron. Over the coming year we will complete the absorption studies in the non-pregnant women and complete approximately one-half of the planned studies in the pregnant women. We obtained additional student support funding for this project to allow Cornell undergraduates to work on this study
and learn the molecular biology techniques needed to screen placental tissue for iron transport proteins. The study will be the primary doctoral thesis for one of the Division of Nutritional Sciences graduate students; Melissa Young. Dr. Marisa Foehr is a developmental biologist who is also working on this project as a post-doctoral fellow. She is funding by an NIH maternal and child nutrition training grant and will be developing the methods needed to screen placental tissue for iron transport proteins.
PARTICIPANTS: Dr. Kimberly O'Brien: is the principal investigator of the study and is responsible for the oversight of the project and analysis and publication of these data. Dr. Ian Griffin is a project director. Dr. Griffin is a neonatologist at Baylor College of Medicine in the USDA/ARS Children's Nutrition Research Center in Houston Texas. His role in the project is to intrinsically label pork with 58Fe. Dr. Eva Pressman is a project director and is a practicing obstetrician/gynecologist at The University of Rochester/ Strong Memorial Hospital in Rochester, NY. She will be medically responsible for the studies undertaken among pregnant women that will be recruited from Rochester, NY and she will assist in obtaining the cord blood and placental tissue. Dr. Leah Harris is project director and is a pediatric anesthesiologist at Johns Hopkins School of Medicine in Baltimore, Maryland. Dr. Harris will assist in the method development for the iron transport proteins and will assist in
the processing and histology of the placental tissue collected. Dr. Subash Chandra is a project director and is an adjunct assistant professor in the Cornell SIMS lab. He will investigate the possibility of screening the placental tissue for iron isotope using SIMS. Dr. Jeremy Inglis was a project director and was assisting with the TIMS analyses as the laboratory director in my laboratory. He has since left the project to accept a faculty position at Boston University. A new laboratory director has been hired and will oversee these analyses in his place but will not be listed as a project director on this project. Dr. Patrick Stover has been added to this project as a project director. He will assist in the molecular biology studies of the placental tissue as needed. Partner Organizations Involved on this Project: 1 - USDA/ARS Children's Nutrition Research Center in Houston, Texas 2 - Johns Hopkins School of Medicine, Baltimore, Maryland 3 - University of Rochester, Strong Memorial
Hospital, Rochester, NY Training or professional development: Melissa Young is a doctoral student in DNS working on this project for her doctoral dissertation. Dr. Marisa Foehr is a post-doctoral student working in part on this project for her postdoctoral fellowship. Casey Sanossian is a Cornell undergraduate working on this project supported by undergraduate HATCH support. Kimberly Owens is a Cornell undergraduate working on this project supported by undergraduate HATCH support
TARGET AUDIENCES: This study will provide results relevant to the US population; in particular to non-pregnant and pregnant women. Results are relevant to minority women that are disproportionately affected by iron deficiency anemia.
Impacts
Iron deficiency is the most common nutrient deficiency in the world. Women are at increased risk; particularly during pregnancy. Iron is obtained from the diet from both plant (non-heme) and animal sources (heme sources). Absorption of non-heme iron and heme iron in the intestine occurs through different pathways. The proteins needed to absorb non-heme iron have been identified but at present the process by which heme iron is absorbed is not known. What is known is that absorption of iron from meat sources is considerably higher than that possible from plant based iron sources. There is also much to be learned about how absorbed iron is transferred to the fetus during pregnancy. It is known that pregnant women have increased iron demands to support the iron needs of pregnancy and the needs of the developing fetus. Many women do not consume enough iron to meet these needs and they become anemic during pregnancy. It is not known if anemic women will be able to provide
enough iron to their developing fetus when dietary iron is limited. In addition, few studies have looked at proteins in the placenta to characterize how these proteins are regulated in response to maternal and fetal iron demands. The proposed study will utilized stable mineral isotopes to safely measure relative differences in how iron is absorbed from plant based and animal based iron sources in both pregnant and non-pregnant women. By obtaining cord blood from pregnant women at delivery we will also determine if there are differences in how much of the heme and non-heme absorbed iron is transferred to the fetus during the final weeks of pregnancy. Placental tissue will also be collected at delivery to measures iron transport proteins in relation to iron absorption and iron transfer to the fetus. These findings will increase the knowledge available on iron absorption and transfer to the fetus and will provide data that will assist in developing targeted interventions to improve the
iron status of women during their reproductive years.
Publications
- No publications reported this period
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