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Everson JL, Eberhart JK. Gene-alcohol interactions in birth defects. Curr Top Dev Biol 2022; 152:77-113. [PMID: 36707215 PMCID: PMC9897481 DOI: 10.1016/bs.ctdb.2022.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Most human birth defects are thought to result from complex interactions between combinations of genetic and environmental factors. This is true even for conditions that, at face value, may appear simple and straightforward, like fetal alcohol spectrum disorders (FASD). FASD describe the full range of structural and neurological disruptions that result from prenatal alcohol exposure. While FASD require alcohol exposure, evidence from human and animal model studies demonstrate that additional genetic and/or environmental factors can influence the embryo's susceptibility to alcohol. Only a limited number of alcohol interactions in birth defects have been identified, with many sensitizing genetic and environmental factors likely yet to be identified. Because of this, while unsatisfying, there is no definitively "safe" dose of alcohol for all pregnancies. Determining these other factors, as well as mechanistically characterizing known interactions, is critical for better understanding and preventing FASD and requires combined scrutiny of human and model organism studies.
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Affiliation(s)
- Joshua L Everson
- Department of Molecular Biosciences, School of Natural Sciences, University of Texas at Austin, Austin, TX, United States; Waggoner Center for Alcohol and Addiction Research, School of Pharmacy, University of Texas at Austin, Austin, TX, United States.
| | - Johann K Eberhart
- Department of Molecular Biosciences, School of Natural Sciences, University of Texas at Austin, Austin, TX, United States; Waggoner Center for Alcohol and Addiction Research, School of Pharmacy, University of Texas at Austin, Austin, TX, United States.
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Ling S, Jenkins MW, Watanabe M, Ford SM, Rollins AM. Prenatal ethanol exposure impairs the conduction delay at the atrioventricular junction in the looping heart. Am J Physiol Heart Circ Physiol 2021; 321:H294-H305. [PMID: 34142884 PMCID: PMC8526336 DOI: 10.1152/ajpheart.00107.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 06/07/2021] [Accepted: 06/08/2021] [Indexed: 12/27/2022]
Abstract
The etiology of ethanol-related congenital heart defects has been the focus of much study, but most research has concentrated on cellular and molecular mechanisms. We have shown with optical coherence tomography (OCT) that ethanol exposure led to increased retrograde flow and smaller atrioventricular (AV) cushions compared with controls. Since AV cushions play a role in patterning the conduction delay at the atrioventricular junction (AVJ), this study aims to investigate whether ethanol exposure alters the AVJ conduction in early looping hearts and whether this alteration is related to the decreased cushion size. Quail embryos were exposed to a single dose of ethanol at gastrulation, and Hamburger-Hamilton stage 19-20 hearts were dissected for imaging. Cardiac conduction was measured using an optical mapping microscope and we imaged the endocardial cushions using OCT. Our results showed that, compared with controls, ethanol-exposed embryos exhibited abnormally fast AVJ conduction and reduced cushion size. However, this increased conduction velocity (CV) did not strictly correlate with decreased cushion volume and thickness. By matching the CV map to the cushion-size map along the inflow heart tube, we found that the slowest conduction location was consistently at the atrial side of the AVJ, which had the thinner cushions, not at the thickest cushion location at the ventricular side as expected. Our findings reveal regional differences in the AVJ myocardium even at this early stage in heart development. These findings reveal the early steps leading to the heterogeneity and complexity of conduction at the mature AVJ, a site where arrhythmias can be initiated.NEW & NOTEWORTHY To the best of our knowledge, this is the first study investigating the impact of ethanol exposure on the early cardiac conduction system. Our results showed that ethanol-exposed embryos exhibited abnormally fast atrioventricular conduction. In addition, our findings, in CV measurements and endocardial cushion thickness, reveal regional differences in the AVJ myocardium even at this early stage in heart development, suggesting that the differentiation and maturation at this site are complex and warrant further studies.
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Affiliation(s)
- Shan Ling
- Department of Biomedical Engineering, School of Engineering and School of Medicine, Case Western Reserve University, Cleveland, Ohio
| | - Michael W Jenkins
- Department of Biomedical Engineering, School of Engineering and School of Medicine, Case Western Reserve University, Cleveland, Ohio
| | - Michiko Watanabe
- Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, Ohio
- Division of Pediatric Cardiology, The Congenital Heart Collaborative, Rainbow Babies and Children's Hospital, Cleveland, Ohio
| | - Stephanie M Ford
- Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, Ohio
- Division of Pediatric Cardiology, The Congenital Heart Collaborative, Rainbow Babies and Children's Hospital, Cleveland, Ohio
- Division of Neonatology, Rainbow Babies and Children's Hospital, Cleveland, Ohio
| | - Andrew M Rollins
- Department of Biomedical Engineering, School of Engineering and School of Medicine, Case Western Reserve University, Cleveland, Ohio
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Obladen M. Ignored Papers, Invented Quotations: A History of Fetal Alcohol Syndrome. Neonatology 2021; 118:647-653. [PMID: 34535605 DOI: 10.1159/000518534] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 07/12/2021] [Indexed: 11/19/2022]
Abstract
Given the high rate of alcoholism throughout history, its effects on the fetus may have existed for millennia. But, the claim that Greeks and Romans were aware of fetal alcohol syndrome rests on incorrect citations. From 1725, maternal alcohol consumption was associated with retarded fetal growth and neurological anomalies. From 1809, scientists followed Lamarck's theory that the disorders parents acquire during their lifetime are passed on to their offspring. Fetal effects were thought to be inherited mainly from the father. During the 19th century, parental alcoholism became associated with malformations. In 1915, Ballantyne distinguished genetic influence via germ cells from toxin's effect on the embryo. Fetal alcohol syndrome was characterized by Rouquette [Influence de la toxicomanie alcoolique parentale sur le développement physique et psychique des jeunes enfants] in 1957 and Lemoine et al. [Ouest Medical. 1968;21:476-482] in 1968 as consisting of 4 features: (A) facial anomalies (narrow forehead, retracted upper lip, and cupped ears), (B) severe growth retardation (prenatal and postnatal), (C) malformations (limbs, cardiac, and visceral), and (D) central nervous system anomalies (hyperexcitability and mental retardation). But, their studies, written in French, remained disregarded. In 1973, Jones et al. [Lancet. 1973;302:999-1001] reported "the first association between maternal alcoholism and aberrant morphogenesis in the offspring." The history of fetal alcohol syndrome reveals shortcomings in citation practice. Alleged quotations remained unverified, non-English publications neglected, and short quotations taken out of context. Prejudiced by religious and abstinence groups, reports on alcohol damage to the unborn were fraught with emotions, moralizing, social implications, and presentism, the interpretation of past events with present knowledge.
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Affiliation(s)
- Michael Obladen
- Department of Neonatology, Charité University Medicine, Berlin, Germany
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Abstract
SummaryPart of the familial factor of alcoholism is associated with the existence of genetic vulnerability. Genetic factors which interact with the pathogenesis of alcoholism are nevertheless complex, partial and for the moment partly unknown at the biological level. Recently, many association studies have been published concerning alcohol-dependence and genes coding for the second dopamine receptor. These associations, which have had positive replications, raise many questions. First of all, should the inheritance of alcoholism be regarded as a definitive fact? Secondly what is inherited? It could be alcoholism in general, a component of this disease (for instance, dependence on, sensitivity to or the seeking-process for alcohol), a specific pattern of drinking, presence of complications linked to alcohol abuse, or more general features, common to many addiction diseases. Thirdly, how could dopamine be linked to alcoholism? Furthermore, how should these positive associations be considered, given that two of these studies were negative, and that all linkage studies were negative. Lastly, are there other clues and ways of finding genetic vulnerability factors for alcohol abuse?
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Fainsod A, Bendelac-Kapon L, Shabtai Y. Fetal Alcohol Spectrum Disorder: Embryogenesis Under Reduced Retinoic Acid Signaling Conditions. Subcell Biochem 2020; 95:197-225. [PMID: 32297301 DOI: 10.1007/978-3-030-42282-0_8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Fetal Alcohol Spectrum Disorder (FASD) is a complex set of developmental malformations, neurobehavioral anomalies and mental disabilities induced by exposing human embryos to alcohol during fetal development. Several experimental models and a series of developmental and biochemical approaches have established a strong link between FASD and reduced retinoic acid (RA) signaling. RA signaling is involved in the regulation of numerous developmental decisions from patterning of the anterior-posterior axis, starting at gastrulation, to the differentiation of specific cell types within developing organs, to adult tissue homeostasis. Being such an important regulatory signal during embryonic development, mutations or environmental perturbations that affect the level, timing or location of the RA signal can induce multiple and severe developmental malformations. The evidence connecting human syndromes to reduced RA signaling is presented here and the resulting phenotypes are compared to FASD. Available data suggest that competition between ethanol clearance and RA biosynthesis is a major etiological component in FASD.
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Affiliation(s)
- Abraham Fainsod
- Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, POB 12271, 9112102, Jerusalem, Israel.
| | - Liat Bendelac-Kapon
- Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, POB 12271, 9112102, Jerusalem, Israel
| | - Yehuda Shabtai
- Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, POB 12271, 9112102, Jerusalem, Israel
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Tharinger DJ, Koranek ME. Children of Alcoholics — At Risk and Unserved: a Review of Research and Service Roles for School Psychologists. SCHOOL PSYCHOLOGY REVIEW 2019. [DOI: 10.1080/02796015.1988.12085335] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Brown JM, Bland R, Jonsson E, Greenshaw AJ. A Brief History of Awareness of the Link Between Alcohol and Fetal Alcohol Spectrum Disorder. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2019; 64:164-168. [PMID: 29807454 PMCID: PMC6405809 DOI: 10.1177/0706743718777403] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Fetal alcohol spectrum disorder (FASD) is a medical term used to describe a range of mental and physical disabilities caused by maternal alcohol consumption. The role of alcohol as a teratogen and its effects on the cellular growth of the embryo and the fetus were not determined on scientific grounds until the late 1960s. However, the link between alcohol use during pregnancy and its harms to offspring might have been observed frequently over the many thousands of years during which alcohol has been available and used for social and other reasons. METHODS AND RESULTS Using sources ranging from the biblical Book of Judges (pre-1700) up until the first public health bulletin (1977), we seek to provide an overview of the academic debate around early historical accounts ostensibly attributed to the awareness of alcohol as a prenatal teratogen as well as to describe the social and political influences that sculpted developments leading to the public recognition of FASD. CONCLUSIONS Our analysis provides a brief overview of the discourse regarding historical awareness of the detrimental effects of prenatal alcohol exposure on fetal development leading to the formal recognition of FASD as a distinct clinical entity. Further research will be required to fully appreciate the scientific, medical, and societal ills associated with prenatal alcohol exposure.
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Affiliation(s)
- Jasmine M Brown
- 1 Department of Psychiatry, University of Alberta, Edmonton, Alberta
| | - Roger Bland
- 1 Department of Psychiatry, University of Alberta, Edmonton, Alberta
| | - Egon Jonsson
- 1 Department of Psychiatry, University of Alberta, Edmonton, Alberta
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Parnell SE, Riley EP, Warren KR, Mitchell KT, Charness ME. The contributions of Dr. Kathleen K. Sulik to fetal alcohol spectrum disorders research and prevention. Alcohol 2018; 69:15-24. [PMID: 29571046 DOI: 10.1016/j.alcohol.2017.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 10/30/2017] [Accepted: 10/30/2017] [Indexed: 10/17/2022]
Abstract
Dr. Kathleen Sulik (Kathy) has spent 35 years studying fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD). Beginning with her landmark 1981 Science paper describing the early gestational window when alcohol can cause the craniofacial malformations characteristic of FAS, Kathy has contributed a vast amount of research furthering our knowledge of FASD. After her seminal work that definitively demonstrated that alcohol is the causative factor in FAS, she and her lab went on to explore and define the stage-dependent effects of early gestational alcohol exposure on the face and brain in numerous different ways throughout her career. She explored and discovered numerous mechanisms of alcohol's effects on the embryo, as well as describing several genetic factors that can modify susceptibility to developmental alcohol exposure. She did not restrict her research to the face and brain; her lab described in intricate detail the effects of developmental alcohol exposure on many different organs, including the heart, ears, kidneys, and limbs. In addition to her research, and in conjunction with NIAAA and the National Organization on Fetal Alcohol Syndrome (NOFAS), Kathy developed several FASD prevention curricula that are still in use today. Finally, as part of her drive to eradicate FAS and FASD, Kathy labored tirelessly with public policy makers to change how FASD is viewed by the public, how FASD is identified in affected individuals, and how FASD is studied by researchers. While no article could fully cover Kathy's contributions to FASD research and prevention, or her other contributions to embryology and teratology, this review will attempt to illustrate some of the highlights of Kathy's remarkable career.
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Kesmodel US. Risks and guidelines for the consumption of alcohol during pregnancy. World J Obstet Gynecol 2016; 5:162-174. [DOI: 10.5317/wjog.v5.i2.162] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 11/13/2015] [Accepted: 01/22/2016] [Indexed: 02/05/2023] Open
Abstract
Daily average intake of alcohol during pregnancy has consistently been associated with short term adverse outcomes such as miscarriage, preterm birth and intrauterine growth restriction, a large variety of malformations, as well as long term adverse outcomes such as foetal alcohol syndrome, mental retardation and general impairment of cognitive functions including intelligence, attention, learning abilities as well as social and behavioural functions. Weekly average consumption and alcohol binge drinking (usually defined as ≥ 5 drinks on a single occasion) independently of high daily average intake has not been consistently associated with short and long term adverse outcomes. Health authorities in most countries recommend that pregnant women completely abstain from alcohol. Even so, many health professionals including doctors, midwives and nurses do not provide information to pregnant women in accordance with the official recommendations, although a large proportion of women of child bearing age and pregnant women drink alcohol, especially before recognition of pregnancy. The discrepancy between guidelines and the information practice of health personnel is likely to continue to exist because guidelines of abstinence are not clearly evidence-based and not in line with current focus on autonomy and informed choice for patients, and because guidelines do not consider the everyday clinical communication situation.
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Warren KR. A Review of the History of Attitudes Toward Drinking in Pregnancy. Alcohol Clin Exp Res 2016; 39:1110-7. [PMID: 26137906 DOI: 10.1111/acer.12757] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 04/22/2015] [Indexed: 11/28/2022]
Abstract
BACKGROUND It is now well accepted in pediatrics and obstetrics that prenatal alcohol is a teratogenic agent and the primary causative factor underlying fetal alcohol spectrum disorders (FASDs), although for the majority of the 20th century that knowledge was either unknown or ignored. At least 2 factors contributed to the delay in recognizing alcohol's role in teratogenicity: the rejection of earlier evidence pertaining to alcohol and pregnancy following the repeal of Prohibition in the United States, Canada, and several European countries; and misinterpretation of earlier research findings in a eugenic rather than toxicological context. The pervasive belief held well into the 1970s that there was no risk to either mother or fetus from prenatal alcohol posed a major challenge to changing physician and public attitudes on alcohol and pregnancy. This review provides insight on key events that occurred in changing physician and public understanding of the risks posed by prenatal alcohol use in pregnancy. METHODS Historical review of events primarily in the U.S. federal government, found in referenced documents. RESULTS The transition in physician and public understanding of the risks posed by prenatal alcohol use was aided by the existence of National Institute on Alcohol Abuse and Alcoholism (NIAAA) which was created in 1971. This government agency was able to support research on alcohol and pregnancy immediately following the 1973 published clinical reports calling attention to a proposed fetal alcohol syndrome (FAS). These early research studies provided the foundation for the first government health advisory on alcohol and pregnancy, issued by NIAAA in 1977. Subsequently, the U.S. Food and Drug Administration (FDA) used this new knowledge on FAS in their effort to add alcoholic beverages to the range of products with ingredient and consumer information labeling. The ensuing hearings and actions resulted in a new health advisory under the auspices of the Surgeon General, encouraging avoidance of alcohol consumption in pregnancy. In subsequent years, Congressional attention to the FAS issue resulted in the Alcoholic Beverage Labeling Law. CONCLUSIONS The pace at which understanding of the risks of prenatal alcohol moved forward from a total misunderstanding to acceptance was aided by both the efforts of the NIAAA in its support of research, and the FDA in its efforts to improve consumer information. Today, many women in the United States as well as other countries continue to ignore advisories on avoiding alcohol consumption in pregnancy, emphasizing the need for persistence in education on these health risks.
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Affiliation(s)
- Kenneth R Warren
- National Institute on Alcohol Abuse and Alcoholism , National Institutes of Health, Bethesda, Maryland
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Kampf A. Times of danger: embryos, sperm and precarious reproduction ca. 1870s-1910s. HISTORY AND PHILOSOPHY OF THE LIFE SCIENCES 2015; 37:68-86. [PMID: 26013436 DOI: 10.1007/s40656-014-0055-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Accepted: 11/16/2014] [Indexed: 06/04/2023]
Abstract
This paper discusses the rise and fall of the theory of paternal transmission, drawing attention to the hitherto underresearched debates about the importance and impact of male-mediated harm to the embryo in reproduction that peaked around the turn of the twentieth century. The focus is on the implications of the twin "great social evils," syphilis and alcohol, which converged at the time of a general transformation of medicine into experimental science and a concomitant rise in new concepts of heredity. Looking at the way in which the issue of time added to profound changes which were linked to particular visions of society and changes in the politics of gender at the turn of the century, I examine the asymmetrical relationship of sociopolitical and epistemological dimensions of time and reproduction. The paper shows how these debates were positioned within the wider context of eugenics and in relation to concepts of male reproduction that involved fundamental political, social and moral dimensions.
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Vassoler FM, Byrnes EM, Pierce RC. The impact of exposure to addictive drugs on future generations: Physiological and behavioral effects. Neuropharmacology 2013; 76 Pt B:269-75. [PMID: 23810828 DOI: 10.1016/j.neuropharm.2013.06.016] [Citation(s) in RCA: 99] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Revised: 04/30/2013] [Accepted: 06/07/2013] [Indexed: 11/25/2022]
Abstract
It is clear that both genetic and environmental factors contribute to drug addiction. Recent evidence indicating trans-generational influences of drug abuse highlight potential epigenetic factors as well. Specifically, mounting evidence suggests that parental ingestion of abused drugs influence the physiology and behavior of future generations even in the absence of prenatal exposure. The goal of this review is to describe the trans-generational consequences of preconception exposure to drugs of abuse for five major classes of drugs: alcohol, nicotine, marijuana, opioids, and cocaine. The potential epigenetic mechanisms underlying the transmission of these phenotypes across generations also are detailed. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
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Affiliation(s)
- F M Vassoler
- Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, MA 01536, USA.
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Killinger CE, Robinson S, Stanwood GD. Subtle biobehavioral effects produced by paternal cocaine exposure. Synapse 2012; 66:902-8. [PMID: 22807092 DOI: 10.1002/syn.21582] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Revised: 07/02/2012] [Accepted: 07/04/2012] [Indexed: 01/18/2023]
Abstract
Despite the increased prevalence of cocaine use and abuse in males when compared with females, possible effects of paternal cocaine exposure on biobehavioral development have received little attention. We therefore exposed male mice to cocaine (20 mg/kg, i.p.) or vehicle for 10 weeks and then used those mice as sires. We then behaviorally phenotyped the F1 offspring to assess the consequences of paternal cocaine exposure on brain function. We report the presence of a subtle but significant increase in immobility in the tail suspension test, a measure of behavioral depression, following paternal cocaine. Body weight was also significantly decreased in paternal cocaine-exposed offspring. Other aspects of neurobehavioral function, including locomotor activity, anxiety, and learning and memory, were not affected by paternal cocaine history. These data suggest alterations in brain systems and/or circuitry underlying mood regulation in the offspring of cocaine-using fathers. Synapse 2012. © 2012 Wiley Periodicals, Inc.
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Affiliation(s)
- Catherine E Killinger
- Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
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Sanders JL. Commentary: What might have been: Sullivan may have impacted modern prenatal alcohol research under different circumstances. Int J Epidemiol 2011; 40:283-5. [DOI: 10.1093/ije/dyr003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Abstract
The magnitude of the detrimental effects following in utero alcohol exposure, including fetal alcohol syndrome and other fetal alcohol spectrum disorders (FASD), is globally underestimated. The effects include irreversible cognitive and behavioral disabilities as a result of abnormal brain development, pre- and postnatal growth retardation and facial dysmorphism. Parental alcohol exposure and its effect on offspring has been recognized for centuries, but only recently have we begun to gain molecular insight into the mechanisms involved in alcohol teratogenesis. Genetic attributes (susceptibility and protective alleles) of the mother and the fetus contribute to the risk of developing FASD and specific additional environmental conditions, including malnutrition, have an important role. The severity of FASD depends on the level of alcohol exposure, the developmental stage at which exposure occurs and the nature of the exposure (chronic or acute), and although the most vulnerable period is during the first trimester, damage can occur throughout gestation. Preconception alcohol exposure can also have a detrimental effect on the offspring. Several developmental pathways are affected in FASD, including nervous system development, growth and remodeling of tissues, as well as metabolic pathways that regulate glucocorticoid signaling and balanced levels of retinol, insulin and nitric oxide. A body of knowledge has accumulated to support the role of environmentally induced epigenetic remodeling during gametogenesis and after conception as a key mechanism for the teratogenic effects of FASD that persist into adulthood. Transgenerational effects are likely to contribute to the global burden of alcohol-related disease. FASD results in lifelong disability and preventative programs should include both maternal alcohol abstention and preconception alcohol avoidance.
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Affiliation(s)
- Michèle Ramsay
- Division of Human Genetics, National Health Laboratory Service and School of Pathology, University of the Witwatersrand, Johannesburg, 2000, South Africa.
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Tan EC, Lim L, Leong JY, Lim JY, Lee A, Yang J, Tan CH, Winslow M. Alcohol and aldehyde dehydrogenase polymorphisms in Chinese and Indian populations. Subst Use Misuse 2010; 45:1-14. [PMID: 20025435 DOI: 10.3109/10826080802490584] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The association between two functional polymorphisms in alcohol dehydrogenase (ADH2/ADH1B) and aldehyde dehydrogenase (ALDH2) genes and alcohol dependence was examined in 182 Chinese and Indian patients undergoing treatment for alcohol dependence and 184 screened control subjects from Singapore. All subjects were screened by the Alcohol Use Disorders Identification Test (AUDIT). Patients were also administered the Severity of Alcohol Dependence Questionnaire (SADQ). Polymorphisms were genotyped by allele-specific polymerase chain reaction and selected genotypes confirmed by DNA sequencing or restriction fragment length polymorphism. Our results showed that frequencies of ADH1B*2 and ALDH2*2 were higher in controls compared to alcohol-dependent subjects for both Chinese and Indians. Frequencies of these two alleles were also higher in the 104 Chinese controls compared to the 80 Indian controls. None of the eight Chinese who were homozygous for both protective alleles was alcohol dependent. The higher frequencies of the protective alleles could explain the lower rate of alcohol dependence in Chinese.
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Affiliation(s)
- Ene-Choo Tan
- KK Research Centre, KK Women's and Children's Hospital, Singapore.
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Warren KR, Hewitt BG. Fetal alcohol spectrum disorders: when science, medicine, public policy, and laws collide. ACTA ACUST UNITED AC 2009; 15:170-5. [PMID: 19731390 DOI: 10.1002/ddrr.71] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Historically, alcohol has been used for different purposes including as a part of religious observances, as a food, at times as a medicine and its well-known use as a beverage. Until relatively recently these purposes have not changed and have at times been at odds with one another, resulting in collisions among policies and practices in science, medicine, public policy and the law. One area in which this has been particularly true is that of fetal alcohol spectrum disorders (FASD) where the adverse consequences of consumed alcohol on children in the womb and after birth may have been observed since antiquity, but the actions taken based on such observations have been influenced as much by the socio/cultural/political context of the times in which they were made as by evidence of harm. This article provides an overview of the inherent confusion when new scientific findings confront prevailing medical practice, the history involved in this confusion with respect to FASD, including public policy and legal issues that have arisen around alcohol and pregnancy, and the research and clinical challenges still being faced.
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Affiliation(s)
- Kenneth R Warren
- National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA
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Abstract
Alcohol was discovered soon after the development of waterproof pots to store and transport water and fruit. Liquids produced by spontaneous fermentation of grains, sugars and fruits were found to enhance pleasure. During the middle ages alchemists discovered that distillation increased this power and thought they had found the elixir of life. Since then almost every culture has used alcohol. Each society has introduced its own restrictions on the availability, exports, imports and consumption of alcoholic beverages within its religious and political structure. Generally, drinking levels which interfere with self-control or result in individual, familial or societal harm are disapproved by all cultures.
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De Santis M, Cesari E, Cavaliere A, Ligato MS, Nobili E, Visconti D, Caruso A. Paternal exposure and counselling: Experience of a Teratology Information Service. Reprod Toxicol 2008; 26:42-6. [DOI: 10.1016/j.reprotox.2008.06.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2008] [Revised: 06/04/2008] [Accepted: 06/05/2008] [Indexed: 01/12/2023]
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Kvigne VL, Leonardson GR, Borzelleca J, Welty TK. Characteristics of grandmothers who have grandchildren with fetal alcohol syndrome or incomplete fetal alcohol syndrome. Matern Child Health J 2008; 12:760-5. [PMID: 18196450 DOI: 10.1007/s10995-007-0308-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2006] [Accepted: 12/21/2007] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Characteristics of Northern Plains American Indian maternal grandmothers who had grandchildren with fetal alcohol syndrome (FAS) or incomplete FAS are described to more effectively prevent fetal FAS and alcohol use during pregnancy. METHODS Study 1 had 27 maternal grandmothers who had grandchildren with FAS and Study 2 had 18 grandmothers with grandchildren who had incomplete FAS (cases) which were compared with 119 maternal grandmothers who had grandchildren without FAS (controls). The grandchildren were born between 1981 and 1993 on the Northern Plains. Medical records were manually reviewed for each case and control grandmother. Data were analyzed using Mantel-Haenszel chi square. RESULTS Study 1 case grandmothers were more likely to experience medical problems (70.4%) including trauma (48.1%) and injuries (51.9%) than the controls. Most of the Study 1 and 2 case grandmothers (92.6% and 77.8%, respectively) had alcohol use documented in their medical records compared to less than half of the control grandmothers. Seven (15.6%) of the case grandmothers had more than one grandchild in either Study 1 or Study 2. CONCLUSION Maternal grandmothers who had grandchildren with FAS had significantly higher rates of alcohol use and alcohol-related medical problems than control grandmothers. Antenatal care providers should screen pregnant women for alcohol use at their first visit. The provider needs to ask the women who are using alcohol about their mothers' use of alcohol to provide appropriate care and counseling for the women and prevent FAS.
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Köksal M, Ilgaz C, Erdogan D, Ozogul C, Tong EK, Kalender H. Ultrastructure of rat pup's Purkinje neurons whose mothers were exposed to ethanol during pregnancy and lactation. Int J Neurosci 2006; 115:1669-86. [PMID: 16287633 DOI: 10.1080/00207450590958510] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
This study was intended to investigate the effects of alcohol on the ultrastructure of fetal cerebellar Purkinje cells. Twelve adult female rats of Sprague-Dawley species were utilized. Control and experiment groups were formed. Rats were made pregnant. Rats in experiment group were administered liquid diet containing 6% alcohol. Cerebellums of infant rats were taken on 6th, 8th, and 10th days after birth. For electron microscopy, tissue sections were processed and stained with the usual methods. When control and experiment groups were compared for electron microscopic investigation, degeneration of mithocondria as cristolysis, dilatations of rough endoplasmic reticulum tubuli, and ring-shaped appearance of Golgi apparatus unit were determined. In some groups, nuclear membrane disintegrated. In cytoplasms of Purkinje cells, multivesicular bodies were distinguished. It was determined that liquid diet containing 6% alcohol had toxic effects on Purkinje cells and caused ultrastructural signs of degeneration in these cells.
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Affiliation(s)
- Mete Köksal
- Gazi University Faculty of Medicine Department of Histology and Embryology Beşevler, Ankara, Turkey.
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22
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Spear NE, Molina JC. Fetal or Infantile Exposure to Ethanol Promotes Ethanol Ingestion in Adolescence and Adulthood: A Theoretical Review. Alcohol Clin Exp Res 2005; 29:909-29. [PMID: 15976517 DOI: 10.1097/01.alc.0000171046.78556.66] [Citation(s) in RCA: 150] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Despite good evidence that ethanol abuse in adulthood is more likely the earlier human adolescents begin drinking, it is unclear why the early onset of drinking occurs in the first place. A review of experimental studies with animals complemented by clinical, epidemiologic and experimental studies with humans supports the idea that precipitating conditions for ethanol abuse occur well before adolescence, in terms of very early exposure to ethanol as a fetus or infant. Experimental studies with animals indicate, accordingly, that ethanol intake during adolescence or adulthood is potentiated by much earlier exposure to ethanol as a fetus or infant. METHODS Two broad theoretical frameworks are suggested to explain the increase in affinity for ethanol that follows very early exposure to ethanol, one based on effects of mere exposure and the other on associative conditioning. Studied for 50 years or more in several areas of psychology, "effects of mere exposure" refers to enhanced preference expressed for flavors, or just about any stimuli, that are relatively familiar. An alternative framework, in terms of associative conditioning, is guided by this working hypothesis: During ethanol exposure the fetus or infant acquires an association between ethanol's orosensory (odor/taste) and pharmacological consequences, causing the animal subsequently to seek out ethanol's odor and taste. RESULTS AND CONCLUSIONS The implication that ethanol has rewarding consequences for the fetus or young infant is supported by recent evidence with perinatal rats. Paradoxically, several studies have shown that such early exposure to ethanol may in some circumstances make the infant treat ethanol-related events as aversive, and yet enhanced intake of ethanol in adolescence is nevertheless a consequence. Alternative interpretations of this paradox are considered among the varied circumstances of early ethanol exposure that lead subsequently to increased affinity for ethanol.
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Affiliation(s)
- Norman E Spear
- Department of Psychology, Center for Developmental Psychobiology, Binghamton University, Binghamton, NY 13902, USA.
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23
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Abstract
FETAL ALCOHOL SYNDROME (FAS) is the leading known cause of mental retardation and birth defects in the world.1,2 It is caused by in utero exposure to alcohol and is entirely preventable. Because alcohol is a known teratogen and the damage done to a fetus by alcohol exposure is permanent, public education about the dangers of prenatal alcohol exposure has been extensive. Nevertheless, alcohol is a widely accepted and legal social drug, and many pregnant mothers continue to drink it while pregnant. Other mothers drink before they are aware of their pregnancy. This column provides information regarding the incidence of FAS, its etiology, spectrum of effects, and diagnosis. We also discuss potential disabilities that these infants may face as they grow and suggest how to work effectively with the families.
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Affiliation(s)
- Martha Wilson Jones
- Neonatal Follow-up Program, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA
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24
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Abstract
Genetic screens in Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio clarified the logic of metazoan development by revealing critical unitary steps and pathways to embryogenesis. Can genetic screens similarly organize medicine? We here examine human diseases that resemble mutations in Danio rerio, the zebrafish, the one vertebrate species for which large-scale genetic screens have been performed and extensively analyzed. Zebrafish mutations faithfully phenocopy many human disorders. Each mutation, once cloned, provides candidate genes and pathways for evaluation in the human. The collection of mutations in their entirety potentially provides a medical taxonomy, one based in developmental biology and genetics.
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Affiliation(s)
- Jordan T Shin
- Cardiovascular Research Center and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
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25
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Burgos MGPDA, Medeiros MDC, Bion FM, Pessoa DCNDP. Efeitos de bebidas alcóolicas em mães lactantes e suas repercussões na prole. REVISTA BRASILEIRA DE SAÚDE MATERNO INFANTIL 2002. [DOI: 10.1590/s1519-38292002000200005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Foi feita uma revisão de estudos sobre os efeitos ocasionados pelo consumo de bebidas alcóolicas por lactantes, analisando os múltiplos distúrbios metabólicos, nutricionais e psicológicos evidenciados no organismo materno e dos recém-nascidos. É enfatizada a necessidade de orientações clínico-nutricionais nos serviços de pré-natal e puericultura acerca dos riscos da ingestão de bebidas alcoólicas em qualquer quantidade, por mães no período de gestação e aleitamento.
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26
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Abstract
International variations in intrauterine growth have consistently been judged in terms of average birthweight, low birthweight or birthweight-for-gestational age criteria. Neither of these provide an appropriate assessment of fetal growth. Notwithstanding these limitations the available evidence indicates that variations in growth, both within and among populations, relate predominantly to differences in the prevalence of factors that restrain growth rather than to inherent differences in growth potential. The evidence also indicates that differences in the frequency of low weight-for-gestation among populations do not only reflect factors that restrict fetal growth. They are also intimately linked to variations in gestational age and to frequencies of preterm birth in particular. Hence, if weight-for-gestational standards are to become more informative and more universally applied than they have been so far, it may be useful to acknowledge their limitations more explicitly and simplify their implementation in a wider range of communities.
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Affiliation(s)
- M J Keirse
- Department of Obstetrics, Gynaecology, and Reproductive Medicine, Flinders Medical Centre and Flinders University, Adelaide, Australia.
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27
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Abstract
The diagnosis of fetal alcohol syndrome (FAS) was invented in 1973. This paper investigates the process by which a cluster of birth defects associated with exposure to alcohol in utero came to be a distinct medical diagnosis, focusing on the first ten years of the medical literature on FAS. Fetal alcohol syndrome was "discovered" by a group of American dysmorphologists who published the first case reports and coined the term FAS. However, the nature of the diagnosis and its salient symptoms were determined collectively over time by the medical profession as a whole. The paper traces the natural history of the diagnosis in the U.S. through five stages: introduction, confirmation and corroboration, dissent, expansion, and diffusion. FAS serves as an example of the social construction of clinical diagnosis; moral entrepreneurship plays a key role and the medical literature on FAS is infused with moral rhetoric, including passages from classical mythology, philosophy, and the Bible. FAS is a moral as well as a medical diagnosis, reflecting the broader cultural concerns of the era in which it was discovered, including a greater awareness of environmental threats to health, the development of fetal medicine, an emphasis on "the perfect child," and a growing paradigm of maternal-fetal conflict.
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Affiliation(s)
- E M Armstrong
- Department of Health Management and Policy, University of Michigan, Ann Arbor 48109, USA
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28
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Shibley IA, Pennington SN. Historical misrepresentation in science: the case of fetal alcohol syndrome. SCIENCE AND ENGINEERING ETHICS 1998; 4:427-435. [PMID: 11658056 DOI: 10.1007/s11948-998-0037-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
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Mattson SN, Riley EP. A review of the neurobehavioral deficits in children with fetal alcohol syndrome or prenatal exposure to alcohol. Alcohol Clin Exp Res 1998; 22:279-94. [PMID: 9581631 DOI: 10.1111/j.1530-0277.1998.tb03651.x] [Citation(s) in RCA: 400] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Fetal alcohol syndrome is a devastating developmental disorder caused by prenatal exposure to high amounts of alcohol. In addition to structural abnormalities and growth deficits, fetal alcohol syndrome is associated with a broad spectrum of neurobehavioral anomalies. This paper reviews the behavioral and cognitive effects of prenatal alcohol exposure. More than 20 years of research are discussed, with a focus on IQ, activity, attention, learning, memory, language, motor, and visuospatial abilities in children prenatally exposed to varying amounts of alcohol, including those with fetal alcohol syndrome.
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Affiliation(s)
- S N Mattson
- Center for Behavioral Teratology, Department of Psychology, San Diego State University, California 92120, USA
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30
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Daley M, Argeriou M, McCarty D. Substance abuse treatment for pregnant women: a window of opportunity? Addict Behav 1998; 23:239-49. [PMID: 9573427 DOI: 10.1016/s0306-4603(97)00029-4] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The use of substance abuse treatment services by pregnant and nonpregnant women was compared to explore the effects of pregnancy on treatment utilization and outcomes. Treatment service records for 227 pregnant drug- and alcohol-dependent women and a matched comparison group of 277 nonpregnant women were retrieved from the Massachusetts Bureau of Substance Abuse Services Management Information System. Treatment services received by the two groups of women during a 6-month period following an index detoxification were tabulated and compared. Treatment services for pregnant women differed quantitatively and qualitatively from the services received by nonpregnant women over the 6-month time period. After controlling for background characteristics and substance abuse history, pregnant women were 1.7 times more likely to be readmitted to detoxification, 2.8 times more likely to enter residential facilities, and 5.4 times more likely to enter methadone programs. For both groups, the use of outpatient and/or residential treatment services following discharge from detoxification significantly reduced the risk of subsequent detoxification admissions. The increased likelihood of admission to detoxification, residential, and methadone services suggests that treatment programs have improved access to care for pregnant women. Multiple detoxification admissions suggest, however, that some pregnant women have difficulty entering stable recovery. Given the brevity of the gestational period and the detrimental effects of drug and alcohol use on fetal outcomes, the use of continuing treatment services for pregnant women is strongly recommended.
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Affiliation(s)
- M Daley
- Health and Addictions Research, Inc., Boston, MA 02116, USA
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31
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Rydelius PA. Annotation: are children of alcoholics a clinical concern for child and adolescent psychiatrists of today? J Child Psychol Psychiatry 1997; 38:615-24. [PMID: 9315971 DOI: 10.1111/j.1469-7610.1997.tb01688.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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32
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Abstract
Experimental and epidemiologic investigations document the adverse consequences of an array of paternal exposures on the development of subsequent offspring. Male-mediated abnormalities have been reported after exposure to therapeutic and recreational drugs, to chemicals in the workplace and environment and to ionizing radiation. The impact on progeny outcome includes: an increase in congenital malformations, spontaneous abortions, fetal resorptions; low birth weight; increase in childhood cancers; developmental, neurobehavioral, neuroendocrine, neurochemical abnormalities; effects in F2 generation progeny. Fertility is often unaffected. The comparative influence of genetic, epigenetic and nongenetic mechanisms in the etiology of paternally-mediated adverse outcomes is unknown. There is no a priori reason to assume that male-mediated effects are limited to the agents studied to date. The broad spectrum of alterations recorded after exposure to a variety of unrelated agents suggests the need for a more focused effort and multidisciplinary exploration of the potential impact of the male parent on reproductive outcome.
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Affiliation(s)
- G Friedler
- Boston University School of Medicine, MA 02118, USA
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33
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Affiliation(s)
- J Gladstone
- Motherisk Program, Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada
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34
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Pauly PJ. How did the effects of alcohol on reproduction become scientifically uninteresting? JOURNAL OF THE HISTORY OF BIOLOGY 1996; 29:1-28. [PMID: 11609217 DOI: 10.1007/bf00129695] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Affiliation(s)
- P J Pauly
- Department of History, Rutgers University, New Brunswick, New Jersey 08903, USA
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35
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Kaskutas LA. Interpretations of risk: the use of scientific information in the development of the alcohol warning label policy. THE INTERNATIONAL JOURNAL OF THE ADDICTIONS 1995; 30:1519-48. [PMID: 8557408 DOI: 10.3109/10826089509104416] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
In 1988 the US Congress passed a law requiring a health warning label on alcoholic beverage containers, to include the message that pregnant women should not drink alcohol. This paper addresses the role that scientific knowledge played in the formation and passage of the alcohol warning label policy. The constellation of birth defects implicated in the fetal alcohol syndrome (FAS) (including fetal alcohol effects) is sketched, and the FAS-related legislative events leading to the law's passage are described. A synopsis of the state of knowledge in 1988 regarding the effects of alcohol on the fetus is presented, and a snapshot of the social climate at that time is offered. The paper concludes with an update of relevant FAS research since the legislation was passed, and considers implications for future research and policy in the prevention of FAS.
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Affiliation(s)
- L A Kaskutas
- Alcohol Research Group, Berkeley, California 94709, USA
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36
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Kim CK, Dalal S, Pinel JP, Weinberg J. Prenatal ethanol exposure: susceptibility to convulsions and ethanol's anticonvulsant effect in amygdala-kindled rats. Alcohol Clin Exp Res 1994; 18:1506-14. [PMID: 7695052 DOI: 10.1111/j.1530-0277.1994.tb01458.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The present experiments assessed the effects of prenatal ethanol exposure on the susceptibility to convulsions and on the anticonvulsant effect of ethanol using the electrical kindling model of epilepsy in rats. Adult male Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment groups were tested following the implantation of a stimulation electrode in the left amygdala complex. The same rats were tested in four consecutive experiments. Both E and PF rats showed a slightly slower rate of kindling than C rats, as measured by convulsion class but not as measured by forelimb clonus duration (experiment 1). However, the groups did not differ significantly in the electrical stimulation threshold for kindled convulsions (experiment 2). Furthermore, prenatal ethanol exposure had no significant effect on the dose-response curve for ethanol's (0, 0.9, 1.1, 1.3, and 1.5 g/kg, ip) anticonvulsant effect (experiment 3), or on the rate of tolerance development to ethanol's (1.5 g/kg, ip) anticonvulsant effect (experiment 4) on kindled convulsions. Thus, prenatal exposure to ethanol does not appear to have long-term effects on the susceptibility to convulsions or on the anticonvulsant effect of ethanol in adult male rats in the kindling model as used in the present experiments.
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Affiliation(s)
- C K Kim
- Department of Anatomy, University of British Columbia, Vancouver, Canada
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37
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Padmanabhan R, Wasfi IA, Craigmyle MB. Effect of pre-treatment with aspirin on alcohol-induced neural tube defects in the TO mouse fetuses. Drug Alcohol Depend 1994; 36:175-86. [PMID: 7889808 DOI: 10.1016/0376-8716(94)90143-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
This study was planned to investigate the effects of ethanol on the genetic susceptibility of the TO mouse to neural tube malformations and to determine the ameliorative effects, if any, of aspirin a potent prostaglandin inhibitor. The TO mouse exhibits a spontaneous incidence of 3.6% exencephaly. The mice were exposed to single (i.p.) dose of 0.03 ml/gm body weight of a solution of (25%v/v) of absolute alcohol in physiological saline on day 7 or 8 of gestation. Subteratogenic doses (150 or 200 mg/kg) of aspirin were administered (i.p.) an hour before ethanol exposure. Fetuses were collected on day 18 and compared with those of the untreated, and saline treated pair-fed pair-watered controls as well as with those of the aspirin alone treatment group. A total of 175 litters were studied. Alcohol caused a three-fold increase against the background incidence of exencephaly. Several craniofacial anomalies and growth retardation were also observed. Alizarin red-S stained skeletal preparations revealed extensive malformations of the craniofacial skeleton in the exencephalic fetuses. Both doses of aspirin administered prior to alcohol treatment significantly accentuated the alcohol-induced prenatal mortality. The rescue effect of aspirin on alcohol-induced intrauterine growth retardation was also significant although fetal weight was not restored to levels comparable to those of the controls. Pre-treatment with aspirin (both 150 and 200 mg/kg) on day 8 of gestation resulted in a numerical, though not statistically significant increase in alcohol-induced exencephaly. On the other hand pre-administration of the lower dose on day 7 exencephaly. On the other hand pre-administration of the lower dose on day 7 of gestation caused a significant reduction while the higher dose gave rise to a significant increase in the incidence of this malformation. Aspirin also reduced the frequency of alcohol-induced arched palate and the baseline exencephaly. These data provide evidence for the possible interaction of alcohol with the genetic susceptibility to exencephaly in this strain of mice. The lack of a clear dose-dependent antagonistic effect of aspirin on alcohol-induced exencephaly suggests that the production of this malformation is probably not mediated by prostaglandin as it was shown for limb and renal abnormalities (Randall, C.L., Anton, R.F. and Becker, H.C. (1991). Aspirin dose dependently reduces alcohol induced birth defects and prostaglandin E levels in mice. Teratology 44, 521-529).
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Affiliation(s)
- R Padmanabhan
- Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, Al Ain
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38
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Nordberg L, Rydelius PA, Zetterström R. Parental alcoholism and early child development. ACTA PAEDIATRICA (OSLO, NORWAY : 1992). SUPPLEMENT 1994; 404:14-8. [PMID: 7531037 DOI: 10.1111/j.1651-2227.1994.tb13378.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
In a cohort of 532 pregnant women from the general population, it was found by compilation of the results from interviews, police records, hospital records and social welfare records that 23 mothers and 51 fathers in 64 families (12%) were suffering from alcoholism/heavy drinking. In these 64 families, the mother was an addict in only 13 families, both parents were addicts in 10 families, and in the remaining 41 families only the father was an addict. Pregnancy, delivery, the newborn child and the child's development until their fourth year of life have been described using a multidisciplinary approach and a longitudinal prospective design. An hypothesis on mental and physical development, and the occurrence of psychopathological symptoms in the children was tested. None of the children of the 13 alcoholic mothers was born with foetal alcohol syndrome, but foetal hazard was indicated by lower birth weight and a higher rate of perinatal deaths. Children of alcoholic parents had retarded mental development and showed more behavioural problems until 4 years of age than controls, but the differences related to physical development during the first year of life had then disappeared. Boys were found to be more vulnerable than girls. The consequences of behaviour seemed to be more pronounced when both parents were alcoholics. No obvious deviation was found when only the father was addicted. Regarding mental development, it appears that factors related to parental alcoholism, including genetic and social factors, and the sex of the child, are of greater importance than the neonatal score on reduced optimality.
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Affiliation(s)
- L Nordberg
- Karolinska Institute, Department of Woman and Child Health, St Göran's Children's Hospital, Stockholm, Sweden
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39
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Maldaner FH, Durgante LP, Murussi M, Xavier MK, Dalmaz C, Ferreira MB. Effects of chronic ethanol consumption on gestation and lactation in rats. INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE : THE OFFICIAL JOURNAL OF THE PAVLOVIAN SOCIETY 1994; 29:141-50. [PMID: 7947329 DOI: 10.1007/bf02691011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Chronic consumption of ethanol during pregnancy and lactation may lead to abnormalities in the fetus or infant. A group of female Wistar rats was submitted to ethanol treatment over a period of a month. A pair-fed control group received sucrose solution isocaloric to ethanol and the control group received water "ad libitum." Afterward, the females were mated with males over a period of 20 days. At birth, each litter was maximized to eight pups and the remaining ones were decapitated to remove the fetal blood and brains. No significant difference was observed in fetal body and brain weight at birth. During lactation the ethanol and pair-fed groups gained less weight than the control group. After weaning, their weight became similar. Fetal blood glucose levels were decreased in the ethanol-treated group. One hundred percent of the pair-fed and control females delivered live fetuses at term and all survived; only 40% of the females in the ethanol group delivered, and one pup did not survive. Chronic ethanol treatment pointed to a possible reduction in the fertility. It seems likely that the change in body weight of ethanol-fed dams was caused by undernutrition.
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Affiliation(s)
- F H Maldaner
- Universidade Federal do Rio Grande do Sul, Brasil
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40
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Finkelstein N. Treatment programming for alcohol and drug-dependent pregnant women. THE INTERNATIONAL JOURNAL OF THE ADDICTIONS 1993; 28:1275-309. [PMID: 8294172 DOI: 10.3109/10826089309062189] [Citation(s) in RCA: 90] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
National concern regarding the problem of alcohol and drug use during pregnancy has brought to the forefront the lack of treatment programs specifically targeted to pregnant women. Many programs are seeking guidance in establishing services for pregnant women. Research suggests that programs that provide comprehensive, coordinated, and "holistic" treatment are better able to draw pregnant women into care as well as provide more effective treatment. This paper presents an overview of written guidelines and protocols for treating pregnant chemically dependent women, including an elaboration of guiding principles for care. Unresolved policy issues are identified as well as recommendations for future research directions.
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Affiliation(s)
- N Finkelstein
- Coalition on Addiction, Pregnancy, and Parenting, Cambridge, Massachusetts 02139
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42
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Abstract
National Prohibition in the USA (1919-1933) was followed by an era in which medical scientists played an important role in minimizing the harmful effects of alcohol. Cirrhosis, cardiomyopathy, adverse fetal effects, and esophageal cancer are examples of alcohol-related health problems that were well known at the beginning of the 20th century but were dismissed during the late 1930's and early 1940's, only to be rediscovered during the 1960's and afterwards. This eclipse in knowledge occurred because of skepticism about earlier claims that had been made in the name of scientific temperance and, most importantly, because of changing standards for medical evidence. The paradigm for disease causation that gave birth to modern medicine was based on microbiology and reinforced by hormone and nutrition discoveries. Most alcohol-related health problems are poorly explained by this paradigm. The more recent epidemiologic paradigm for noninfectious disease is more applicable to the health risks associated with heavy drinking. A transformation of knowledge about alcohol's relationship to disease has occurred.
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43
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Affiliation(s)
- I E Dreosti
- CSIRO Division of Human Nutrition, Adelaide, Australia
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44
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Borges G, Lopez-Cervantes M, Medina-Mora ME, Tapia-Conyer R, Garrido F. Alcohol consumption, low birth weight, and preterm delivery in the National Addiction Survey (Mexico). THE INTERNATIONAL JOURNAL OF THE ADDICTIONS 1993; 28:355-68. [PMID: 8463022 DOI: 10.3109/10826089309039633] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
In 1988 the Mexican General Directorate of Epidemiology and the Mexican Institute of Psychiatry carried out the first National Addiction Survey that provided prevalence estimates at national and regional levels of alcohol consumption, tobacco smoking, and several other drugs use. In addition, a questionnaire included questions regarding alcohol consumption during pregnancy and adverse outcomes. According to the results of logistic regression, women classified as suffering from Alcohol Dependence Syndrome had a very high risk of low birth weight and/or preterm delivery: Odds ratio = 12.1 with a 95% confidence interval of (1.3, 108.9) and p = .026. After controlling for several confounding variables, the findings remained basically the same.
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Affiliation(s)
- G Borges
- Dirección General de Epidemiología, Mexico D.F
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45
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Abstract
The objectives of this study were to investigate (1) changes in consumption of alcohol among pregnant women over a period of 5 years (1984/85-1990), (2) changes of attitudes towards drinking during pregnancy in the general population over the same period of time, and (3) possible connections between (1) and (2). The investigation was designed as a cross-sectional study. Our subjects were two representative samples of pregnant women in Oslo, n = 377 and 425, and two representative samples of the Norwegian population, n = 1004 and 1204. The main outcome measures were a self-completed questionnaire for the pregnant women and a personal interview for the general population sample. There was a significant reduction (50% decrease) in alcohol consumption among the second cohort of pregnant women compared with the first. Furthermore, we found an increase during the 5-year period in the number of persons with a restrictive attitude towards alcohol use during pregnancy. There seems to be a connection between these two phenomena, but with our present state of knowledge it is hard to say anything about the causal relationship between them.
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Affiliation(s)
- B M Ihlen
- National Institute for Alcohol and Drug Research, Oslo, Norway
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Nordberg L, Rydelius PA, Zetterström R. Children of alcoholic parents: health, growth, mental development and psychopathology until school age. Results from a prospective longitudinal study of children from the general population. ACTA PAEDIATRICA (OSLO, NORWAY : 1992). SUPPLEMENT 1993; 387:1-24. [PMID: 8461621 DOI: 10.1111/j.1651-2227.1993.tb12824.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Of 640 women who paid their first visit to the two maternal welfare centres in a new Stockholm suburb during one prospective year, 532 (85%) were interviewed with regard to 41 stress factors forming a "life stress score" (LSS). The interviews were supplemented with data from hospital, social welfare and police records concerning the expectant mother and the father. The 532 mothers were divided into three groups according to the degree of psychosocial stress (group 1 (n = 194) without psychosocial stress; group 2 (n = 171) with severe psychosocial stress; and group 3 (n = 167) in an intermediate group). In group 2, there were 23 mothers and 51 fathers in 64 families known to suffer from alcoholism/heavy drinking at the time of the first interview and these comprised our study group. The pregnancies and deliveries in the families were investigated with prospective methods. There were 497 liveborn children of whom 54 were born into families known for alcoholism/heavy drinking. The physical health and development of the children was followed by prospective data from the child welfare centers. Data concerning psychological development and psychiatric health of the child were obtained by interviewing the mother and evaluating the child during visits at home at one and four years of age. At one year of age, 452 of the children (226 boys, 226 girls) and at four to five years of age, 412 of the children (202 boys, 210 girls), were evaluated using the Griffiths' Development Scales. Findings from these evaluations form the basis for comparison of development of children from alcoholic/heavy drinking parents with all other children. For 388 children, data were available from all examinations up to the end of the fourth year, including 38 children (12 boys, 26 girls) in the study group and 350 other children (183 boys, 167 girls). The present findings indicate that children of alcoholic parents in the general population who were followed from pregnancy up to the end of their fourth year have a higher risk of pre- and postnatal death, and have poorer mental development and more symptoms of a psychopathological child psychiatric nature (DSM-III) than other children. Differences related to physical development during infant years disappeared during the observation time. With regard to mental development over a longer period, it appears that factors related to the parent's addictions and the child's sex (i.e. male child) are more important than pediatric risk factors in the form of a score of reduced optimality.
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Affiliation(s)
- L Nordberg
- Karolinska Institutet, Department of Child and Adolescent Psychiatry, St Göran's Children's Hospital, Stockholm, Sweden
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Reyes E, Duran E, Switzer SH. Effects of in utero administration of alcohol on alcohol sensitivity in adult rats. Pharmacol Biochem Behav 1993; 44:307-12. [PMID: 8446664 DOI: 10.1016/0091-3057(93)90466-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
In utero exposure to alcohol has been associated with many physical deficits and behavioral abnormalities. The purpose of these studies was to determine the effects of in utero administration of alcohol on behaviors related to tolerance and sensitivity to alcohol in adult rats. Pregnant rats were maintained on a liquid diet containing alcohol [35% ethanol-derived calories (EDC)] throughout pregnancy. Offspring manifested physical characteristics of Fetal Alcohol Syndrome. The 35% EDC group was able to stay on a wooden dowel longer and at higher blood alcohol concentrations than were pair-fed controls. Following a hypnotic dose of alcohol, rats in the 35% EDC group slept longer than pair-fed controls. A greater alcohol-induced hypothermic effect was seen in females in the 35% EDC group than in controls. Treatment did not affect rate of metabolism of alcohol. These studies suggest that in utero administration of alcohol may be a factor in determining an individual's sensitivity and tolerance to alcohol and possibly their preference for alcohol.
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Affiliation(s)
- E Reyes
- Department of Pharmacology, University of New Mexico School of Medicine, Albuquerque 87131
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Abstract
Fluctuating asymmetry was evaluated in the dental arcades of 112 children (60 male, 52 female) of alcoholic mothers. Only individuals who showed no signs of the fetal alcohol syndrome were included. When these results were compared with those of a control group of 120 normal children, the former group was found to be significantly more asymmetric. The present study showed that canines were the least asymmetric whilst lateral incisors showed the greatest levels of asymmetry. It is suggested that the elevated levels of fluctuating odontometric asymmetry in children of alcoholic mothers may be ascribed to prenatal stress, especially during the soft tissue stage of odontogenesis.
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Affiliation(s)
- J A Kieser
- Department of Oral Pathology, University of the Witwatersrand, Johannesburg, South Africa
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Velleman R. Intergenerational effects--a review of environmentally oriented studies concerning the relationship between parental alcohol problems and family disharmony in the genesis of alcohol and other problems. I: The intergenerational effects of alcohol problems. THE INTERNATIONAL JOURNAL OF THE ADDICTIONS 1992; 27:253-80. [PMID: 1563885 DOI: 10.3109/10826089209068741] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
This paper is the first in a two-part series. In this paper the literature on the intergenerational transmission of alcohol problems is reviewed from an environmental perspective. It is concluded that there are effects of problem drinking on children, but that the long-term effects of parental problem drinking on the offspring once they reach adulthood are not so well documented. It is suggested that whether or not intergenerational continuities are found depends largely upon the source of the sample, that very little is known about adulthood outcomes other than drinking status, and that there is a striking sex bias in the literature, with most research examining the effects of problem-drinking fathers upon their male offspring. Possible mechanisms whereby parental problem drinking could affect adjustment are outlined and discussed. The notion of disturbed family relationships acting as a possible mediator for the transmission of problems is raised.
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Affiliation(s)
- R Velleman
- School of Social Sciences, University of Bath, Avon, United Kingdom
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Ledig M, Misslin R, Kopp P, Vogel E, Tholey G, Mandel P. Alcohol exposure before pregnancy: biochemical and behavioral effects on the offspring of rats. Pharmacol Biochem Behav 1990; 36:279-85. [PMID: 2356201 DOI: 10.1016/0091-3057(90)90404-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The effect of maternal alcohol exposure before mating was investigated in the offspring over a period of 6 months concerning some specific aspects of energy metabolism in the brain and the liver. The following biochemical parameters were analyzed: superoxide dismutase (involved in elimination of free radicals produced during ethanol oxidation), enolase isoenzymes (markers of nerve cell maturation), and alcohol and aldehyde dehydrogenase (the main alcohol degradating enzymes). These enzymatic activities were measured at their subcellular level. In these animals never directly exposed to alcohol, superoxide dismutase activity was decreased mainly in the liver cytosol. Only the nonneuronal form of enolase activity was modified. Alcohol dehydrogenase was decreased in the liver as well as in the brain. Aldehyde dehydrogenase was also decreased in the liver and in the brain, mainly in the mitochondria. Behavioral observations showed decreased emotional reactivity as well as an increase in locomotor activity. Our results suggest that long-lasting biochemical and behavioral effects of alcohol may occur in the offspring starting at the earliest stage of development.
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Affiliation(s)
- M Ledig
- Centre de Neurochimie du CNRS, Strasbourg
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