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      Blastopathies and microcephaly in a Chornobyl impacted region of Ukraine

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          Abstract

          This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors.

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          Most cited references150

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          Congenital Diaphragmatic Hernia

          Juan Tovar (2012)
          Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted.
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            Role of epigenetics in developmental biology and transgenerational inheritance.

            The molecular mechanisms involved in developmental biology and cellular differentiation have traditionally been considered to be primarily genetic. Environmental factors that influence early life critical windows of development generally do not have the capacity to modify genome sequence, nor promote permanent genetic modifications. Epigenetics provides a molecular mechanism for environment to influence development, program cellular differentiation, and alter the genetic regulation of development. The current review discusses how epigenetics can cooperate with genetics to regulate development and allow for greater plasticity in response to environmental influences. This impacts area such as cellular differentiation, tissue development, environmental induced disease etiology, epigenetic transgenerational inheritance, and the general systems biology of organisms and evolution. Copyright © 2011 Wiley-Liss, Inc.
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              Fortification of flour with folic acid.

              After randomized, controlled trials established that consumption of folic acid before pregnancy and during the early weeks of gestation reduces the risk of a neural tube defect (NTD)-affected pregnancy, the United States Public Health Service recommended in 1992 that all women capable of becoming pregnant consume 400 microg folic acid daily. In 1998, folic acid fortification of all enriched cereal grain product flour was fully implemented in the United States and Canada. To provide guidance on national fortification of wheat and maize flours to prevent 50 to 70% of the estimated 300,000 NTD-affected pregnancies worldwide. An expert workgroup reviewed the latest evidence of effectiveness of folic acid flour fortification and the safety of folic acid. Recent estimates show that in the United States and Canada, the additional intake of about 100 to 150 microg/day of folic acid through food fortification has been effective in reducing the prevalence of NTDs at birth and increasing blood folate concentrations in both countries. Most potential adverse effects associated with folic acid are associated with extra supplement use not mandatory fortification. Fortification of wheat flour has a proven record of prevention in other developed countries. In 2009, 51 countries had regulations written for mandatory wheat flour fortification programs that included folic acid. NTDs remain an important cause of perinatal mortality and infantile paralysis worldwide. Mandatory fortification of flour with folic acid has proved to be one of the most successful public health interventions in reducing the prevalence of NTD-affected pregnancies. Most developing countries have few, if any, common sources of folic acid, unlike many developed countries, which have folic acid available from ready-to-eat cereals and supplements. Expanding the number of developed and developing countries with folic acid flour fortification has tremendous potential to safely eliminate most folic acid-preventable NTDs.
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                Author and article information

                Journal
                Congenit Anom (Kyoto)
                Congenit Anom (Kyoto)
                cga
                Congenital Anomalies
                BlackWell Publishing Ltd (Oxford, UK )
                0914-3505
                1741-4520
                August 2014
                21 August 2014
                : 54
                : 3
                : 125-149
                Affiliations
                [1 ]Department of Medical Genetics, College of Medicine, University of South Alabama Mobile, Alabama, USA
                [2 ]Department of Mathematics and Statisitcs, University of South Alabama Mobile, Alabama, USA
                [3 ]OMNI-Net for Children International Charitable Fund Rivne, Rivne Province, Ukraine
                [4 ]Rivne Regional Medical Diagnostic Center Rivne, Rivne Province, Ukraine
                [5 ]Khmelnytsky Perinatal Center Khmelnytsky, Khmelnytsky Province, Ukraine
                [6 ]Cyto-Genetics Laboratory, Department of Pathology, University of Mississippi Medical Center Jackson, Mississippi, USA
                Author notes
                Correspondence: Wladimir Wertelecki, MD, 9 Oakway Drive, Mobile, AL 36608, USA. Email: werteleckiomni@ 123456gmail.com
                Article
                10.1111/cga.12051
                4233949
                24666273
                af8c63c8-700b-401a-ae8c-4841725bcd77
                © 2014 The Authors. Congenital Anomalies published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Teratology Society.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 30 September 2013
                : 05 January 2014
                Categories
                Invited Review Article

                blastopathies,chornobyl,congenital malformations,ionizing radiation,sex ratio

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