+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring.

          Our data may have significant relevance for understanding the impact of suboptimal iron levels during pregnancy not only on the mother but also on the developing fetus and hence might lead to a more informed timing of iron supplementation during pregnancy.

          Related collections

          Most cited references 106

          • Record: found
          • Abstract: found
          • Article: not found

          A review of studies on the effect of iron deficiency on cognitive development in children.

          Studies on the effect of iron deficiency on children's cognition and behavior are selectively reviewed, looking for evidence of a causal relationship. Most correlational studies have found associations between iron-deficiency anemia and poor cognitive and motor development and behavioral problems. Longitudinal studies consistently indicate that children anemic in infancy continue to have poorer cognition, school achievement, and more behavior problems into middle childhood. However, the possible confounding effects of poor socioeconomic backgrounds prevent causal inferences from being made. In anemic children 2 y old, the evidence from RCT is reasonably convincing but not conclusive. RCT of iron treatment are warranted especially in younger children.
            • Record: found
            • Abstract: found
            • Article: not found

            Iron status during pregnancy: setting the stage for mother and infant.

            Supplementation with iron is generally recommended during pregnancy to meet the iron needs of both mother and fetus. When detected early in pregnancy, iron deficiency anemia (IDA) is associated with a > 2-fold increase in the risk of preterm delivery. Maternal anemia when diagnosed before midpregnancy is also associated with an increased risk of preterm birth. Results of recent randomized clinical trials in the United States and in Nepal that involved early supplementation with iron showed some reduction in risk of low birth weight or preterm low birth weight, but not preterm delivery. During the 3rd trimester, maternal anemia usually is not associated with increased risk of adverse pregnancy outcomes and may be an indicator of an expanded maternal plasma volume. High levels of hemoglobin, hematocrit, and ferritin are associated with an increased risk of fetal growth restriction, preterm delivery, and preeclampsia. While iron supplementation increases maternal iron status and stores, factors that underlie adverse pregnancy outcome are considered to result in this association, not iron supplements. On the other hand, iron supplements and increased iron stores have recently been linked to maternal complications (eg, gestational diabetes) and increased oxidative stress during pregnancy. Consequently, while iron supplementation may improve pregnancy outcome when the mother is iron deficient it is also possible that prophylactic supplementation may increase risk when the mother does not have iron deficiency or IDA. Anemia and IDA are not synonymous, even among low-income minority women in their reproductive years.
              • Record: found
              • Abstract: found
              • Article: not found

              Prevalence of iron deficiency in the United States.

              To determine the prevalence of iron deficiency and iron deficiency anemia in the US population. Nationally representative cross-sectional health examination survey that included venous blood measurements of iron status. Iron deficiency, defined as having an abnormal value for at least 2 of 3 laboratory tests of iron status (erythrocyte protoporphyrin, transferrin saturation, or serum ferritin); and iron deficiency anemia, defined as iron deficiency plus low hemoglobin. A total of 24,894 persons aged 1 year and older examined in the third National Health and Nutrition Examination Survey (1988-1994). Nine percent of toddlers aged 1 to 2 years and 9% to 11% of adolescent girls and women of childbearing age were iron deficient; of these, iron deficiency anemia was found in 3% and 2% to 5%, respectively. These prevalences correspond to approximately 700,000 toddlers and 7.8 million women with iron deficiency; of these, approximately 240,000 toddlers and 3.3 million women have iron deficiency anemia. Iron deficiency occurred in no more than 7% of older children or those older than 50 years, and in no more than 1% of teenage boys and young men. Among women of childbearing age, iron deficiency was more likely in those who are minority, low income, and multiparous. Iron deficiency and iron deficiency anemia are still relatively common in toddlers, adolescent girls, and women of childbearing age.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                15 March 2011
                : 6
                : 3
                [1 ]Department of Biomedical Genetics, University of Rochester, Rochester, New York, United States of America
                [2 ]Department of Neurobiology and Anatomy, University of Rochester, Rochester, New York, United States of America
                [3 ]Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States of America
                [4 ]Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, New York, United States of America
                [5 ]Department of Environmental Medicine, University of Rochester, Rochester, New York, United States of America
                University of Queensland, Australia
                Author notes

                Conceived and designed the experiments: MMP AEL CM. Performed the experiments: CM FGS DLL RMG. Analyzed the data: MMP AEL CM JS. Contributed reagents/materials/analysis tools: MMP AEL RMG. Wrote the paper: MMP CM.


                Current address: Department of Laboratory Medicine at the University of Washington, Seattle, Washington, United States of America

                Mihaila et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Pages: 13
                Research Article
                Developmental Neuroscience
                Neuroglial Development
                Central Nervous System
                Neurobiology of Disease and Regeneration
                Micronutrient Deficiencies



                Comment on this article