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      Maternal Iron Status in Pregnancy and Long-Term Health Outcomes in the Offspring

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          Abstract

          Iron is an essential micronutrient and is important not only in carrying oxygen but also to the catalytic activity of a variety of enzymes. In the fetus, it is vital to the synthesis of hemoglobin and in brain development. Iron deficiency (ID) anemia in pregnancy is a common problem, even in high-income country settings. Around 50% of pregnant women worldwide are anemic, with at least half of this burden due to ID. Iron supplements are widely recommended and used during pregnancy globally. However, the evidence on the extent of benefit they contribute to the offspring's health is not well established, and their routine use has its side effects and drawbacks. Dietary iron intake is difficult to assess accurately and it is unlikely to be sufficient to meet the demands of pregnancy if women start with inadequate body iron stores at conception. Evidence from experimental animal models suggests that maternal ID during pregnancy is associated with fetal growth restriction, as well as offspring obesity and high blood pressure later in life. The possible biological mechanisms for this observed association may be due to ID-induced changes in placental structure and function, enzyme expression, nutrient absorption, and fetal organ development. However, such evidence is limited in human studies. Prenatal ID in experimental animal models also adversely affected the developing brain structures, neurotransmitter systems, and myelination resulting in acute brain dysfunction during the period of deficiency and persistence of various postnatal neurobehavioral abnormalities as well as persistent dysregulation of some genes into adult life after iron repletion pointing to the possibility of gene expression changes. The evidence from human population studies is limited and heterogeneous and more research is needed in the future, investigating the effects of ID in pregnancy on future offspring health outcomes.

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          Most cited references102

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          Weight in infancy and death from ischaemic heart disease.

          Environmental influences that impair growth and development in early life may be risk factors for ischaemic heart disease. To test this hypothesis, 5654 men born during 1911-30 were traced. They were born in six districts of Hertfordshire, England, and their weights in infancy were recorded. 92.4% were breast fed. Men with the lowest weights at birth and at one year had the highest death rates from ischaemic heart disease. The standardised mortality ratios fell from 111 in men who weighed 18 pounds (8.2 kg) or less at one year to 42 in those who weighed 27 pounds (12.3 kg) or more. Measures that promote prenatal and postnatal growth may reduce deaths from ischaemic heart disease. Promotion of postnatal growth may be especially important in boys who weigh below 7.5 pounds (3.4 kg) at birth.
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            Maternal nutrition and fetal development.

            Nutrition is the major intrauterine environmental factor that alters expression of the fetal genome and may have lifelong consequences. This phenomenon, termed "fetal programming," has led to the recent theory of "fetal origins of adult disease." Namely, alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, and metabolism of the offspring, thereby predisposing individuals to metabolic, endocrine, and cardiovascular diseases in adult life. Animal studies show that both maternal undernutrition and overnutrition reduce placental-fetal blood flows and stunt fetal growth. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenesis factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for intrauterine growth retardation in response to the 2 extremes of nutritional problems with the same pregnancy outcome. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the impact of maternal nutrition on both fetal programming and genomic imprinting. Promoting optimal nutrition will not only ensure optimal fetal development, but will also reduce the risk of chronic diseases in adults.
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              Iron deficiency and brain development.

              Iron deficiency (ID) is common in pregnant women and infants worldwide. Rodent models show that ID during gestation/lactation alters neurometabolism, neurotransmitters, myelination, and gene/protein profiles before and after iron repletion at weaning. Human infants with iron deficiency anemia test lower in cognitive, motor, social-emotional, and neurophysiologic development than comparison group infants. Iron therapy does not consistently improve developmental outcome, with long-term differences observed. Poorer outcome has also been shown in human and monkey infants with fetal/neonatal ID. Recent randomized trials of infant iron supplementation show benefits, indicating that adverse effects can be prevented and/or reversed with iron earlier in development or before ID becomes severe or chronic. This body of research emphasizes the importance of protecting the developing brain from ID.
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                Author and article information

                Journal
                J Pediatr Genet
                J Pediatr Genet
                10.1055/s-00029027
                Journal of Pediatric Genetics
                Georg Thieme Verlag KG (Stuttgart · New York )
                2146-4596
                2146-460X
                June 2015
                : 4
                : 2
                : 111-123
                Affiliations
                [1 ]Academic Unit of Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
                [2 ]Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
                Author notes
                Address for correspondence Nisreen A. Alwan, MBChB, MRCP, FFPH, MPH, MSc, PhD Academic Unit of Primary Care and Population Sciences, Faculty of Medicine, University of Southampton South Academic Block (Level C), Southampton General Hospital, Southampton SO166YD, EnglandUnited Kingdom n.a.alwan@ 123456soton.ac.uk
                Article
                14139
                10.1055/s-0035-1556742
                4918713
                27617121
                43486e69-a0a1-4130-98d7-89fae09816c5
                © Thieme Medical Publishers
                History
                : 23 February 2015
                : 26 February 2015
                Categories
                Review Article
                Prenatal Exposures and Short and Long Term Developmental Outcomes
                Guest Editors: Sura Alwan, PhD and Christina D. Chambers, PhD, MPH

                iron,pregnancy,nutrition,cognitive function,cardiovascular disease,developmental origins

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