The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: the potential influence of zinc status as an example.

PubMed

Keen, Carl L; Uriu-Adams, Janet Y; Skalny, Anatoly; Grabeklis, Andrei; Grabeklis, Sevil; Green, Kerri; Yevtushok, Lyubov; Wertelecki, Wladimir W; Chambers, Christina D

2010-01-01

There is increasing evidence that human pregnancy outcome can be significantly compromised by suboptimal maternal nutritional status. Poor diet results in a maternal-fetal environment in which the teratogenicity of other insults such as alcohol might be amplified. As an example, there is evidence that zinc (Zn) can interact with maternal alcohol exposure to influence the risk for fetal alcohol spectrum disorders (FASD). Studies with experimental animals have shown that the teratogenicity of alcohol is increased under conditions of Zn deficiency, whereas its teratogenicity is lessened when animals are given Zn-supplemented diets or Zn injections before the alcohol exposure. Alcohol can precipitate an acute-phase response, resulting in a subsequent increase in maternal liver metallothionein, which can sequester Zn and lead to decreased Zn transfer to the fetus. Importantly, the teratogenicity of acute alcohol exposure is reduced in metallothionein knockout mice, which can have improved Zn transfer to the conceptus relative to wild-type mice. Consistent with the above, Zn status has been reported to be low in alcoholic women at delivery. Preliminary data from two basic science and clinical nutritional studies that are ongoing as part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders support the potential role of Zn, among other nutritional factors, relative to risk for FASD. Importantly, the nutrient levels being examined in these studies are relevant to general clinical populations and represent suboptimal levels rather than severe deficiencies. These data suggest that moderate deficiencies in single nutrients can act as permissive factors for FASD, and that adequate nutritional status or intervention through supplementation may provide protection from some of the adverse effects of prenatal alcohol exposure.

Alcohol and pregnancy

MedlinePlus

Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... lead to lifelong damage. DANGERS OF ALCOHOL DURING PREGNANCY Drinking a lot of alcohol during pregnancy can ...

Preschool Teacher Attitude and Knowledge Regarding Fetal Alcohol Syndrome and Fetal Alcohol Effects.

ERIC Educational Resources Information Center

Mack, Faite R-P.

The Centers for Disease Control estimate that each year more than 8,000 Fetal Alcohol Syndrome (FAS) babies are born, and that many more babies go undiagnosed with Fetal Alcohol Effects (FAE), a less severe condition. FAS and FAE have been identified as major contributors to poor memory, shorter attention spans, lower IQs, diminished achievement…

Fetal Alcohol Spectrum Disorders: Understanding the Effects of Prenatal Alcohol Exposure and Supporting Students

ERIC Educational Resources Information Center

Green, Jennifer H.

2007-01-01

Background: Fetal Alcohol Spectrum Disorders (FASD) affect a significant number of children in this country. This article addresses diagnostic issues related to fetal alcohol syndrome (FAS) and other alcohol-related disabilities, discusses associated features and behaviors of FASD, and introduces interventions to support children with FASD in…

Intervention for individuals with fetal alcohol spectrum disorders: treatment approaches and case management.

PubMed

Paley, Blair; O'Connor, Mary J

2009-01-01

Exposure to alcohol in utero is considered to be the leading cause of developmental disabilities of known etiology. The most severe consequence of such exposure, fetal alcohol syndrome (FAS), is characterized by a distinct constellation of characteristic facial anomalies, growth retardation, and central nervous system (CNS) dysfunction. Some individuals with prenatal alcohol exposure (PAE) do not meet the full criteria for FAS, but instead are diagnosed with partial FAS, alcohol related neurodevelopmental disorder (ARND), or alcohol related birth defects (ARBD). The entire continuum of effects from PAE is increasingly being referred to under the umbrella term of fetal alcohol spectrum disorders (FASDs). An extensive body of research has documented major cognitive, behavioral, adaptive, social, and emotional impairments among individuals with FASDs. Although FAS was identified in the U.S. over 35 years ago, the development, evaluation, and dissemination of evidence-based interventions for individuals with FASDs have lagged behind significantly. Encouragingly, however, in recent years there has been a marked increase in efforts to design and test interventions to remediate the impairments associated with prenatal alcohol exposure. This article will review treatment needs and considerations for individuals with FASDs and their families, current empirically tested treatment approaches, case management issues, and suggestions for future directions in research on the treatment of FASDs. (c) 2009 Wiley-Liss, Inc.

The protective effect of astaxanthin on fetal alcohol spectrum disorder in mice.

PubMed

Zheng, Dong; Li, Yi; He, Lei; Tang, Yamei; Li, Xiangpen; Shen, Qingyu; Yin, Deling; Peng, Ying

2014-09-01

Astaxanthin is a strong antioxidant with the ability of reducing the markers of inflammation. To explore the protective effect of astaxanthin on maternal ethanol induced embryonic deficiency, and to investigate the underlying mechanisms, we detected the morphology, expression of neural marker genes, oxidative stress indexes, and inflammatory factors in mice model of fetal alcohol spectrum disorder with or without astaxanthin pretreatment. Our results showed that astaxanthin blocked maternal ethanol induced retardation of embryonic growth, and the down-regulation of neural marker genes, Otx1 and Sox2. Moreover, astaxanthin also reversed the increases of malondialdehyde (MDA), hydrogen peroxide (H2O2), and the decrease of glutathione peroxidase (GPx) in fetal alcohol spectrum disorder. In addition, maternal ethanol induced up-regulation of toll-like receptor 4 (TLR4), and the down-streaming myeloid differentiation factor 88 (MyD88), NF-κB, TNF-α, and IL-1β in embryos, and this was inhibited by astaxanthin pretreatment. These results demonstrated a protective effect of astaxanthin on fetal alcohol spectrum disorder, and suggested that oxidative stress and TLR4 signaling associated inflammatory reaction are involved in this process. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fetal Alcohol Syndrome: An International Concern.

ERIC Educational Resources Information Center

Asetoyer, Charon

1987-01-01

Describes Fetal Alcohol Effects (FAE) and Fetal Alcohol Syndrome (FAS) in infants, caused by mothers' consumption of alcohol during pregnancy. Both disabilities found in relatively high proportions of American Indian children. Discusses impact of disabilities on education. Discusses parent education programs in United States and abroad. (TES)

Educating Health Professionals about Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

American Journal of Health Education, 2007

2007-01-01

Prenatal exposure to alcohol is a leading preventable cause of birth defects and developmental disabilities. Individuals exposed to alcohol during fetal development can have physical, mental, behavioral, and learning disabilities, with lifelong implications. These conditions are known as fetal alcohol spectrum disorders (FASDs). Health care…

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

PubMed Central

Sari, Youssef; Chiba, Tomohiro; Yamada, Marina; Rebec, George V.; Aiso, Sadakazu

2009-01-01

Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ALC combined with administration (i.p.) of CLN (20 μg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 μg/20 g body weight). On E13, fetal brains were collected and assayed for TUNEL staining, caspase-3 colorimetric assay, ELISA, and MSD electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c. Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies. PMID:19782727

Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

PubMed

Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

2015-06-01

Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

PubMed

Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

2001-05-01

Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

Fetal Alcohol Syndrome: The Impact on Children's Ability To Learn. Occasional Paper #10.

ERIC Educational Resources Information Center

Troccoli, Karen B.

This paper provides information on the incidence and prevalence of alcohol-related birth defects, the human and economic costs of fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE), and examples of prevention and intervention strategies that can help reduce the occurrence of and ameliorate the consequences of FAS/FAE. It discusses the…

Teaching Students with Fetal Alcohol Spectrum Disorder: Building Strengths, Creating Hope. Programming for Students with Special Needs. Book 10

ERIC Educational Resources Information Center

Clarren, Sandra G. Bernstein

2004-01-01

"Teaching Students with Fetal Alcohol Spectrum Disorder: Building Strengths, Creating Hope" is Book 10 in the Programming for Students with Special Needs series; a revision and expansion of the 1997 Alberta Learning teacher resource, "Teaching Students with Fetal Alcohol Syndrome and Possible Prenatal Alcohol-Related Effects."…

Bibliography on Fetal Alcohol Syndrome and Related Issues. Second Edition.

ERIC Educational Resources Information Center

All Indian Pueblo Council, Albuquerque, NM.

The bibliography on Fetal Alcohol Syndrome presents 312 unannotated journal articles for use by professionals working with American Indian people and is designed to serve as a vital source of knowledge on alcohol and child health. The bibliography is intended to list articles on Fetal Alcohol Syndrome and humans, and only highlight a minimal…

Evaluation of an Educational Program on the Fetal Alcohol Syndrome for Health Professionals.

ERIC Educational Resources Information Center

Russell, Marcia; And Others

1983-01-01

Describes knowledge, attitudes and intervention policies regarding fetal alcohol syndrome (FAS) and fetal alcohol effects among obstetricians and gynecologists (N=1,128) in New York State. Survey results showed that subjects were well-informed about FAS, and almost all advised their obstetric patients to abstain or limit their alcohol intake. (LLL)

Effects of Moderate Prenatal Alcohol Exposure during Early Gestation in Rats on Inflammation across the Maternal-Fetal-Immune Interface and Later-Life Immune Function in the Offspring

PubMed Central

Terasaki, Laurne S.; Schwarz, Jaclyn M.

2017-01-01

During early brain development, microglial activation can negatively impact long-term neuroimmune and cognitive outcomes. It is well-known that significant alcohol exposure during early gestation results in a number of cognitive deficits associated with fetal alcohol spectrum disorders (FASD). Additionally, microglia are activated following high levels of alcohol exposure in rodent models of FASD. We sought to examine whether moderate prenatal alcohol exposure (70 mg/dL blood alcohol concentration) activates microglia in the fetal rat brain, and whether moderate fetal alcohol exposure has long-term negative consequences for immune function and cognitive function in the rat. We also measured inflammation within the placenta and maternal serum following moderate alcohol exposure to determine whether either could be a source of cytokine production in the fetus. One week of moderate prenatal alcohol exposure produced a sex-specific increase in cytokines and chemokines within the fetal brain. Cytokines were also increased within the placenta, regardless of the sex of the fetus, and independent of the low levels of circulating cytokines within the maternal serum. Adult offspring exposed to alcohol prenatally had exaggerated cytokine production in the brain and periphery in response to lipopolysaccharide (25 μg/kg), as well as significant memory deficits precipitated by this low-level of inflammation. Thus the immune system, including microglia, may be a key link to understanding the etiology of fetal alcohol spectrum disorders and other unexplored cognitive or health risks associated with even low levels of fetal alcohol exposure. PMID:27318824

Dietary Iron Fortification Normalizes Fetal Hematology, Hepcidin, and Iron Distribution in a Rat Model of Prenatal Alcohol Exposure.

PubMed

Huebner, Shane M; Helfrich, Kaylee K; Saini, Nipun; Blohowiak, Sharon E; Cheng, Adrienne A; Kling, Pamela J; Smith, Susan M

2018-06-01

Prenatal alcohol exposure (PAE) causes neurodevelopmental disability. Clinical and animal studies show gestational iron deficiency (ID) exacerbates PAE's behavioral and growth deficits. In rat, PAE manifests an inability to establish iron homeostasis, increasing hepcidin (maternal and fetal), and fetal liver iron while decreasing brain iron and promoting anemia. Here, we hypothesize dietary iron fortification during pregnancy may mitigate alcohol's disruption of fetal iron homeostasis. Pregnant Long-Evans rats, fed iron-sufficient (100 ppm iron) or iron-fortified (IF; 500 ppm iron) diets, received either 5 g/kg alcohol (PAE) or isocaloric maltodextrin daily on gestational days (GD) 13.5 through 19.5. Maternal and fetal outcomes were evaluated on GD20.5. PAE reduced mean fetal weight (p < 0.001) regardless of maternal iron status, suggesting iron fortification did not improve fetal growth. Both PAE (p < 0.01) and IF (p = 0.035) increased fetal liver iron. In fetal brain, PAE (p = 0.015) affected total (p < 0.001) and nonheme iron (p < 0.001) such that iron fortification normalized (p = 0.99) the alcohol-mediated reductions in brain iron and nonheme iron. Iron fortification also improved fetal hematologic indices in PAE including hemoglobin, hematocrit, and mean cell volume (ps<0.001). Iron fortification also normalized hepcidin expression in alcohol-exposed maternal and fetal liver. Neither diet nor PAE affected transferrin (Tf) and ferritin (FTN) content in fetal liver, nor Tf or transferrin receptor in fetal brain. However, IF-PAE fetal brains trended to less FTN content (p = 0.074), suggesting greater availability of nonstorage iron. In PAE, hepcidin levels were linearly related to increased liver iron stores and decreased red blood cell count and brain iron. Maternal oral iron fortification mitigated PAE's disruption of fetal iron homeostasis and improved brain iron content, hematologic indices, and hepcidin production in this rat PAE model. Clinical studies show maternal ID substantially enhances fetal vulnerability to PAE, and our work supports increased maternal dietary iron intake may improve fetal iron status in alcohol-exposed pregnancies. Copyright © 2018 by the Research Society on Alcoholism.

Impact of fetal alcohol exposure on body systems: A systematic review.

PubMed

Caputo, Courtney; Wood, Erin; Jabbour, Leila

2016-06-01

Review of published manuscripts on fetal alcohol exposure on several body systems. Articles in this review were found online using databases such as Medline, Medline Complete, PubMed, and Health Source: Nursing/Academic Edition. The following terms were searched: fetal alcohol spectrum disorders, fetal alcohol syndrome, prenatal alcohol exposure, and alcohol related birth defects. Thirteen articles were gathered, five original investigations and eight reviews. This review identified several abnormalities in the body systems discussed and their associations to fetal alcohol syndrome. Evidence shows that the brain was the most severely impacted organ of the body systems discussed. However, prenatal alcohol exposure causes several abnormalities within the heart, kidney, liver, gastrointestinal tract, and the endocrine systems. In addition, preventative measures need to be taken by mothers during pregnancy. Birth Defects Research (Part C), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part C) 108:174-180, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fetal Alcohol Exposure

MedlinePlus

... categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder (ARND) » Alcohol-Related Birth ... either prenatally, after birth, or both Partial FAS (pFAS) Partial FAS (pFAS) involves prenatal alcohol exposure, and ...

Experimental methods for testing the effects of neurotrophic peptide, ADNF-9, against alcohol-induced apoptosis during pregnancy in c57bl/6 mice.

PubMed

Sari, Youssef

2013-04-24

Experimental designs for investigating the effects of prenatal alcohol exposure during early embryonic stages in fetal brain growth are challenging. This is mostly due to the difficulty of microdissection of fetal brains and their sectioning for determination of apoptotic cells caused by prenatal exposure to alcohol. The experiments described here provide visualized techniques from mice breeding to the identification of cell death in fetal brain tissue. This study used C57BL/6 mice as the animal model for studying fetal alcohol exposure and the role of trophic peptide against alcohol-induced apoptosis. The breeding consists of a 2-hr matting window to determine the exact stage of embryonic age. An established fetal alcohol exposure model has been used in this study to determine the effects of prenatal alcohol exposure in fetal brains. This involves free access to alcohol or pair-fed liquid diets as the sole source of nutrients for the pregnant mice. The techniques involving dissection of fetuses and microdissection of fetal brains are described carefully, since the latter can be challenging. Microdissection requires a stereomicroscope and ultra-fine forceps. Step-by-step procedures for dissecting the fetal brains are provided visually. The fetal brains are dissected from the base of the primordium olfactory bulb to the base of the metencephalon. For investigating apoptosis, fetal brains are first embedded in gelatin using a peel-away mold to facilitate their sectioning with a vibratome apparatus. Fetal brains embedded and fixed in paraformaldehyde are easily sectioned, and the free floating sections can be mounted in superfrost plus slides for determination of apoptosis or cell death. TUNEL (TdT-mediated dUTP Nick End Labeling; TdT: terminal deoxynucleotidyl transferase) assay has been used to identify cell death or apoptotic cells. It is noteworthy that apoptosis and cell-mediated cytotoxicity are characterized by DNA fragmentation. Thus, the visualized TUNEL-positive cells are indicative of cell death or apoptotic cells. The experimental designs here provide information about the use of an established liquid diet for studying the effects of alcohol and the role of neurotrophic peptides during pregnancy in fetal brains. This involves breeding and feeding pregnant mice, microdissecting fetal brains, and determining apoptosis. Together, these visual and textual techniques might be a source for investigating prenatal exposure of harmful agents in fetal brains.

In Utero Alcohol Exposure and the Alteration of Histone Marks in the Developing Fetus: An Epigenetic Phenomenon of Maternal Drinking

PubMed Central

Mandal, Chanchal; Halder, Debasish; Jung, Kyoung Hwa; Chai, Young Gyu

2017-01-01

Ethanol is well known for its teratogenic effects during fetal development. Maternal alcohol consumption allows the developing fetus to experience the detrimental effects of alcohol exposure. Alcohol-mediated teratogenic effects can vary based on the dosage and the length of exposure. The specific mechanism of action behind this teratogenic effect is still unknown. Previous reports demonstrated that alcohol participates in epigenetic alterations, especially histone modifications during fetal development. Additional research is necessary to understand the correlation between major epigenetic events and alcohol-mediated teratogenesis such as that observed in fetal alcohol spectrum disorder (FASD). Here, we attempted to collect all the available information concerning alcohol-mediated histone modifications during gestational fetal development. We hope that this review will aid researchers to further examine the issues associated with ethanol exposure. PMID:29104501

Palmar Creases: Classification, Reliability and Relationships to Fetal Alcohol Spectrum Disorders (FASD).

PubMed

Mattison, Siobhán M; Brunson, Emily K; Holman, Darryl J

2015-09-01

A normal human palm contains 3 major creases: the distal transverse crease; the proximal transverse crease; and the thenar crease. Because permanent crease patterns are thought to be laid down during the first trimester, researchers have speculated that deviations in crease patterns could be indicative of insults during fetal development. The purpose of this study was twofold: (1) to compare the efficacy and reliability of two coding methods, the first (M1) classifying both "simiana" and Sydney line variants and the second (M2) counting the total number of crease points of origin on the radial border of the hand; and (2) to ascertain the relationship between palmar crease patterns and fetal alcohol spectrum disorders (FASD). Bilateral palm prints were taken using the carbon paper and tape method from 237 individuals diagnosed with FASD and 190 unexposed controls. All prints were coded for crease variants under M1 and M2. Additionally, a random sample of 98 matched (right and left) prints was selected from the controls to determine the reliabilities of M1 and M2. For this analysis, each palm was read twice, at different times, by two readers. Intra-observer Kappa coefficients were similar under both methods, ranging from 0.804-0.910. Inter-observer Kappa coefficients ranged from 0.582-0.623 under M1 and from 0.647-0.757 under M2. Using data from the entire sample of 427 prints and controlling for sex and ethnicity (white v. non-white), no relationship was found between palmar crease variants and FASD. Our results suggest that palmar creases can be classified reliably, but palmar crease patterns may not be affected by fetal alcohol exposure.

Journey to the Center of the Fetal Brain: Environmental Exposures and Autophagy.

PubMed

Lei, Jun; Calvo, Pilar; Vigh, Richard; Burd, Irina

2018-01-01

Fetal brain development is known to be affected by adverse environmental exposures during pregnancy, including infection, inflammation, hypoxia, alcohol, starvation, and toxins. These exposures are thought to alter autophagy activity in the fetal brain, leading to adverse perinatal outcomes, such as cognitive and sensorimotor deficits. This review introduces the physiologic autophagy pathways in the fetal brain. Next, methods to detect and monitor fetal brain autophagy activity are outlined. An additional discussion explores possible mechanisms by which environmental exposures during pregnancy alter fetal brain autophagy activity. In the final section, a correlation of fetal autophagy activity with the observed postnatal phenotype is attempted. Our main purpose is to provide the current understanding or a lack thereof mechanisms on autophagy, underlying the fetal brain injury exposed to environmental insults.

Development of a media campaign on fetal alcohol spectrum disorders for Northern Plains American Indian communities.

PubMed

Hanson, Jessica D; Winberg, Austin; Elliott, Amy

2012-11-01

Alcohol-exposed pregnancies are especially of concern for American Indians. The Indian Health Service reported that 47% to 56% of pregnant patients admitted to drinking alcohol during their pregnancy. In addition, rates of Fetal Alcohol Syndrome are estimated to be as high as 3.9 to 9.0 per 1,000 live births among American Indians in the Northern Plains, making prevention of alcohol-exposed pregnancies an important public health effort for this population. The goal of this article is to add to the literature on universal prevention of Fetal Alcohol Spectrum disorders by describing the development, dissemination, and evaluation of a media campaign on Fetal Alcohol Spectrum Disorders that was created by and for American Indian communities in the Northern Plains.

Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

PubMed

Mantella, Nicole M; Youngentob, Steven L

2014-01-01

Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our results suggest broader implications related to the consequence of fetal exposure with one substance of abuse and initial acceptability of others.

Prenatal Alcohol Exposure Increases Postnatal Acceptability of Nicotine Odor and Taste in Adolescent Rats

PubMed Central

Mantella, Nicole M.; Youngentob, Steven L.

2014-01-01

Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our results suggest broader implications related to the consequence of fetal exposure with one substance of abuse and initial acceptability of others. PMID:25029285

Fetal Alcohol Syndrome "Chemical Genocide."

ERIC Educational Resources Information Center

Asetoyer, Charon

In the Northern Plains of the United States, 100% of Indian reservations are affected by alcohol related problems. Approximately 90% of Native American adults are currently alcohol users or abusers or are recovering from alcohol abuse. Alcohol consumption has a devastating effect on the unborn. Fetal Alcohol Syndrome (FAS) is an irreversible birth…

Parallels between Learning Disabilities and Fetal Alcohol Syndrome/Effect: No Need To Reinvent the Wheel.

ERIC Educational Resources Information Center

Johnson, Carol L.; Lapadat, Judith C.

2000-01-01

A survey of the research and practice literatures on learning disabilities and on Fetal Alcohol Syndrome/Effect revealed parallels in learning characteristics, as well as in the recommended interventions. Based on these parallels, an adolescent with Fetal Alcohol received intervention. Teaching strategies for students with learning disabilities…

Up Front, in Hope: The Value of Early Intervention for Children with Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Harwood, Maureen; Kleinfeld, Judith Smilg

2002-01-01

Differentiates fetal alcohol syndrome (FAS) from fetal alcohol effects (FAE) and discusses difficulties in diagnosing these conditions. Describes the effects of FAS/FAE on young children, detailing impact on sensory processing, focusing attention, and cognitive development in infants, toddlers, and preschoolers. Presents suggestions for caregivers…

Pediatricians' Knowledge, Training, and Experience in the Care of Children with Fetal Alcohol Syndrome

ERIC Educational Resources Information Center

Gahagan, Sheila; Sharpe, Tanya Telfair; Brimacombe, Michael; Fry-Johnson, Yvonne; Levine, Robert; Mengel, Mark; O'Connor, Mary; Paley, Blair; Adubato, Susan; Brenneman, George

2007-01-01

Objectives: Prenatal exposure to alcohol interferes with fetal development and is the leading preventable cause of birth defects and developmental disabilities. The purpose of this study was to identify current knowledge, diagnosis, prevention, and intervention practices related to fetal alcohol syndrome and related conditions by members of the…

Behavioral Aspects of Fetal Alcohol Syndrome. Mountain Plains Information Bulletin.

ERIC Educational Resources Information Center

Rice, Karen Stuut

This paper discusses the symptoms, causes, and diagnosis of fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE). It then presents information from biological and adopted parents of 14 individuals (ages 4-23 years) diagnosed with FAS or FAE, based on a parent survey concerning behavioral and educational histories of their children.…

Prenatal alcohol exposure increases the susceptibility to develop aggressive prolactinomas in the pituitary gland.

PubMed

Jabbar, Shaima; Reuhl, Kenneth; Sarkar, Dipak K

2018-05-16

Excess alcohol use is known to promote development of aggressive tumors in various tissues in human patients, but the cause of alcohol promotion of tumor aggressiveness is not clearly understood. We used an animals model of fetal alcohol exposure that is known to promote tumor development and determined if alcohol programs the pituitary to acquire aggressive prolactin-secreting tumors. Our results show that pituitaries of fetal alcohol-exposed rats produced increased levels of intra-pituitary aromatase protein and plasma estrogen, enhanced pituitary tissue growth, and upon estrogen challenge developed prolactin-secreting tumors (prolactinomas) that were hemorrhagic and often penetrated into the surrounding tissue. Pituitary tumors of fetal alcohol-exposed rats produced higher levels of hemorrhage-associated genes and proteins and multipotency genes and proteins. Cells of pituitary tumor of fetal alcohol exposed rat grew into tumor spheres in ultra-low attachment plate, expressed multipotency genes, formed an increased number of colonies, showed enhanced cell migration, and induced solid tumors following inoculation in immunodeficient mice. These data suggest that fetal alcohol exposure programs the pituitary to develop aggressive prolactinoma after estrogen treatment possibly due to increase in stem cell niche within the tumor microenvironment.

Fetal Alcohol Syndrome and Fetal Alcohol and Other Drug Effects. A Guide for Teachers.

ERIC Educational Resources Information Center

New Jersey State Dept. of Education, Trenton. Div. of General Academic Education.

This curriculum guide on Fetal Alcohol Syndrome (FAS) is intended to help meet New Jersey secondary-level learning objectives in the area of chemical health education. The guide is organized into six sections, each with a conceptual statement, content outline, specific objectives, and lesson plans. The six sections and corresponding major concepts…

Challenges of Parenting Children with a Fetal Alcohol Spectrum Disorder: A Concept Map

ERIC Educational Resources Information Center

Brown, Jason D.; Bednar, Lisa M.

2004-01-01

The purpose of the study was to describe the challenges of parents of children with a fetal alcohol spectrum disorder (FASD). Nineteen birth, foster or adoptive parents were asked to answer the following question: "What are the challenges you face parenting a child with a fetal alcohol spectrum disorder?" The data were analyzed using…

Teaching Students with Fetal Alcohol Syndrome/Effects: A Resource Guide for Teachers.

ERIC Educational Resources Information Center

Conry, Julie

This teacher's resource guide from British Columbia provides an overview of the needs of students with fetal alcohol syndrome (FAS). It begins by discussing the definition of FAS and fetal alcohol effects (FAE), characteristics of students with FAS/E, and steps for preparing to teach students with FAS/E (collecting information, making and carrying…

Recognizing and Managing Children with Fetal Alcohol Syndrome/Fetal Alcohol Effects: A Guidebook.

ERIC Educational Resources Information Center

McCreight, Brenda

A family counselor and mother of adopted children with Fetal Alcohol Syndrome/Effects (FAS/E) offers practical advice and information on dealing with FAS/E's lifelong effects on behavior and learning. The book begins by discussing the historical, medical, and social aspects of FAS/E, and details common behavioral characteristics associated with…

A School Curriculum for Fetal Alcohol Spectrum Disorder: Advice from a Young Adult with FASD

ERIC Educational Resources Information Center

Brenna, Beverley; Burles, Meridith; Holtslander, Lorraine; Bocking, Sarah

2017-01-01

While a significant number of individuals in Canada and globally are affected by prenatal fetal alcohol exposure, scant research exists that focuses specifically on the subjective experiences of this population. Based on a single case study exploring through Photovoice methodology the life experiences of a young adult with Fetal Alcohol Spectrum…

From research to practice: an integrative framework for the development of interventions for children with fetal alcohol spectrum disorders.

PubMed

Kodituwakku, Piyadasa W; Kodituwakku, E Louise

2011-06-01

Since fetal alcohol syndrome was first described over 35 years ago, considerable progress has been made in the delineation of the neurocognitive profile in children with prenatal alcohol exposure. Preclinical investigators have made impressive strides in elucidating the mechanisms of alcohol teratogenesis and in testing the effectiveness of pharmacological agents and dietary supplementation in the amelioration of alcohol-induced deficits. Despite these advances, only limited progress has been made in the development of evidence-based comprehensive interventions for functional impairment in alcohol-exposed children. Having performed a search in PubMed and PsycINFO using key words, interventions, treatment, fetal alcohol syndrome, prenatal alcohol exposure, and fetal alcohol spectrum disorders, we found only 12 papers on empirically-based interventions. Only two of these interventions had been replicated and none met the criteria of "well-established," as defined by Chambless and Hollon (Journal of Consulting and Clinical Psychology 66(1):7-18, 1998). There has been only limited cross-fertilization of ideas between preclinical and clinical research with regard to the development of interventions. Therefore, we propose a framework that allows integrating data from preclinical and clinical investigations to develop comprehensive intervention programs for children with fetal alcohol spectrum disorders. This framework underscores the importance of multi-level evaluations and interventions.

Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leichter, J.

1991-03-15

The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitummore » controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.« less

Parietal dysfunction during number processing in children with fetal alcohol spectrum disorders

PubMed Central

Woods, K.J.; Meintjes, E.M.; Molteno, C.D.; Jacobson, S.W.; Jacobson, J.L.

2015-01-01

Number processing deficits are frequently seen in children prenatally exposed to alcohol. Although the parietal lobe, which is known to mediate several key aspects of number processing, has been shown to be structurally impaired in fetal alcohol spectrum disorders (FASD), effects on functional activity in this region during number processing have not previously been investigated. This fMRI study of 49 children examined differences in activation associated with prenatal alcohol exposure in five key parietal regions involved in number processing, using tasks involving simple addition and magnitude comparison. Despite generally similar behavioral performance, in both tasks greater prenatal alcohol exposure was related to less activation in an anterior section of the right horizontal intraparietal sulcus known to mediate mental representation and manipulation of quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome appeared to compensate for this deficit by increased activation of the angular gyrus during the magnitude comparison task. PMID:26199871

Spatial but not object memory impairments in children with fetal alcohol syndrome.

PubMed

Uecker, A; Nadel, L

1998-07-01

Behavioral dissociations on tests of cognitive abilities are powerful tools that can help define the neuropsychology of developmentally disabling conditions. Animals gestationally exposed to alcohol demonstrate spatial (place) but not object (cue) memory impairments. Whether children with fetal alcohol syndrome demonstrate a similar dissociation has received little attention. In this experiment, 30 Native American children, 15 previously identified with fetal alcohol syndrome and 15 control children, were asked to recall places and objects in a task previously shown to be sensitive to memory skills in individuals with and without mental retardation. As in animal models, children with fetal alcohol syndrome demonstrated a spatial but not an object memory impairment. A possible role for the hippocampus was discussed.

Fetal Alcohol Syndrome: A Behavioral Teratology.

ERIC Educational Resources Information Center

Kavale, Kenneth A.; Karge, Belinda D.

1986-01-01

The review examines the literature on the behaviorally teratogenic aspects of Fetal Alcohol Syndrome, including: (1) prevalence of alcohol abuse among women, (2) acute and chronic effects of alcohol on the fetus, (3) genetic susceptibility, (4) neuropathology, (5) correlative conditions, and (6) animal studies. (Author/DB)

5-Mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities.

PubMed

Shi, Yu; Li, Jiejing; Chen, Chunjiang; Gong, Manzi; Chen, Yuan; Liu, Youxue; Chen, Jie; Li, Tingyu; Song, Weihong

2014-09-16

Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis. Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies. Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.

National Organization on Fetal Alcohol Syndrome

MedlinePlus

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Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders

PubMed Central

Kalberg, Wendy O.; Elliott, Amy J.; Blankenship, Jason; Buckley, David; Marais, Anna-Susan; Manning, Melanie A.; Robinson, Luther K.; Adam, Margaret P.; Abdul-Rahman, Omar; Jewett, Tamison; Coles, Claire D.; Chambers, Christina; Jones, Kenneth L.; Adnams, Colleen M.; Shah, Prachi E.; Riley, Edward P.; Charness, Michael E.; Warren, Kenneth R.; May, Philip A.

2016-01-01

The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors’ combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism–funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol. PMID:27464676

Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

PubMed Central

Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima; Nasello, Cara; Sarkar, Dipak K.

2015-01-01

Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells. PMID:26509893

Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography.

PubMed

Raghunathan, Raksha; Wu, Chen; Singh, Manmohan; Liu, Chih-Hao; Miranda, Rajesh C; Larin, Kirill V

2018-05-01

Prenatal alcohol exposure (PAE) can result in a range of anomalies including brain and behavioral dysfunctions, collectively termed fetal alcohol spectrum disorder. PAE during the 1st and 2nd trimester is common, and research in animal models has documented significant neural developmental deficits associated with PAE during this period. However, little is known about the immediate effects of PAE on fetal brain vasculature. In this study, we used in utero speckle variance optical coherence tomography, a high spatial- and temporal-resolution imaging modality, to evaluate dynamic changes in microvasculature of the 2nd trimester equivalent murine fetal brain, minutes after binge-like maternal alcohol exposure. Acute binge-like PAE resulted in a rapid (<1 hour) and significant decrease (P < .001) in vessel diameter as compared to the sham group. The data show that a single binge-like maternal alcohol exposure resulted in swift vasoconstriction in fetal brain vessels during the critical period of neurogenesis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Collaborative Initiative on Fetal Alcohol Spectrum Disorders: Methodology of Clinical Projects

PubMed Central

Mattson, Sarah N.; Foroud, Tatiana; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Coles, Claire D.; Fagerlund, Åse; Autti-Rämö, Ilona; May, Philip A.; Adnams, Colleen M.; Konovalova, Valentina; Wetherill, Leah; Arenson, Andrew D.; Barnett, William K.; Riley, Edward P.

2009-01-01

The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) was created in 2003 to further understanding of fetal alcohol spectrum disorders. Clinical and basic science projects collect data across multiple sites using standardized methodology. This paper describes the methodology being used by the clinical projects that pertain to assessment of children and adolescents. Domains being addressed are dysmorphology, neurobehavior, 3D facial imaging, and brain imaging. PMID:20036488

Fetal Alcohol Syndrome, Chemo-Biology and OMICS: Ethanol Effects on Vitamin Metabolism During Neurodevelopment as Measured by Systems Biology Analysis

PubMed Central

Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães

2014-01-01

Abstract Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment. PMID:24816220

Fetal alcohol syndrome, chemo-biology and OMICS: ethanol effects on vitamin metabolism during neurodevelopment as measured by systems biology analysis.

PubMed

Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães; Bonatto, Diego

2014-06-01

Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment.

β-Endorphin Neuronal Cell Transplant Reduces Corticotropin Releasing Hormone Hyperresponse to Lipopolysaccharide and Eliminates Natural Killer Cell Functional Deficiencies in Fetal Alcohol Exposed Rats

PubMed Central

Boyadjieva, Nadka I.; Ortigüela, María; Arjona, Alvaro; Cheng, Xiaodong; Sarkar, Dipak K.

2010-01-01

Background Natural killer (NK) cell dysfunction is associated with hyperresponse of corticotropin releasing hormone (CRH) to immune challenge and with a loss of β-endorphin (BEP) neurons in fetal alcohol exposed animals. Recently, we established a method to differentiate neural stem cells into BEP neurons using cyclic adenosine monophosphate (cAMP)-elevating agents in cultures. Hence, we determined whether in vitro differentiated BEP neurons could be used for reversing the compromised stress response and immune function in fetal alcohol exposed rats. Methods To determine the effect of BEP neuron transplants on NK cell function, we implanted in vitro differentiated BEP neurons into the paraventricular nucleus of pubertal and adult male rats exposed to ethanol or control in utero. The functionality of transplanted BEP neurons was determined by measuring proopiomelanocortin (POMC) gene expression in these cells and their effects on CRH gene expression under basal and after lipopolysaccaride (LPS) challenge. In addition, the effectiveness of BEP neurons in activating NK cell functions is determined by measuring NK cell cytolytic activity and interferon-γ (IFN-γ) production in the spleen and in the peripheral blood mononuclear cell (PBMC) following cell transplantation. Results We showed here that when these in vitro differentiated BEP neurons were transplanted into the hypothalamus, they maintain biological functions by producing POMC and reducing the CRH neuronal response to the LPS challenge. BEP neuronal transplants significantly increased NK cell cytolytic activity in the spleen and in the PBMC and increased plasma levels of IFN-γ in control and fetal alcohol exposed rats. Conclusions These data further establish the BEP neuronal regulatory role in the control of CRH and NK cell cytolytic function and identify a possible novel therapy to treat stress hyper-response and immune deficiency in fetal alcohol exposed subjects. PMID:19320628

Teaching Students with Fetal Alcohol Syndrome and Possible Prenatal Alcohol-Related Effects.

ERIC Educational Resources Information Center

Alberta Dept. of Education, Edmonton. Special Education Branch.

This guide provides a review of the characteristics of children with fetal alcohol syndrome (FAS) or possible prenatal alcohol-related effects (PPAE) and describes specific intervention strategies. Section 1 offers a general review of the diagnostic procedures, the prevalence of FAS and the physical, educational, and behavioral characteristics of…

Fetal Alcohol Spectrum Disorders: A Case Study

PubMed Central

Glass, Leila; Mattson, Sarah N.

2017-01-01

This grand rounds manuscript reviews important considerations in developing case conceptualizations for individuals with a history of prenatal alcohol exposure. This case study provides an introduction to fetal alcohol spectrum disorders, diagnostic issues, a detailed description of the individual's history, presenting symptoms, neuropsychological test results, and an integrated summary. We describe a 9-year old girl diagnosed with a fetal alcohol spectrum disorder (FASD): Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE). This patient is a composite of a prototypical child who participated as part of a research project at the Center for Behavioral Teratology who was subsequently seen at an outpatient child psychiatry facility. PMID:28948136

Fetal Alcohol Spectrum Disorders.

PubMed

Williams, Janet F; Smith, Vincent C

2015-11-01

Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. Copyright © 2015 by the American Academy of Pediatrics.

Alcohol and B1 vitamin deficiency-related stillbirths.

PubMed

Bâ, Abdoulaye

2009-05-01

The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

The Fetal Alcohol Syndrome Public Awareness Campaign, 1979: Progress Report Concerning the Advance Notice of Proposed Rulemaking on Warning Labels on Containers of Alcoholic Beverages and Addendum.

ERIC Educational Resources Information Center

Department of the Treasury, Washington, DC.

This report provides expert opinion on the problems of fetal alcohol syndrome (FAS) and ways to inform the public of teratogenic risk of alcohol consumption during pregnancy. In the absence of firm evidence that moderate drinking of alcoholic beverages leads to FAS and uncertainty concerning the effectiveness of labeling of alcoholic beverages, a…

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

PubMed

Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

2011-07-07

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

Alterations in phosphorylated cyclic adenosine monophosphate response element of binding protein activity: a pathway for fetal alcohol syndrome-related neurotoxicity.

PubMed

Roberson, Robin; Cameroni, Irene; Toso, Laura; Abebe, Daniel; Bissel, Stephanie; Spong, Catherine Y

2009-02-01

Fetal alcohol syndrome (FAS) is the leading cause of a spectrum of preventable nongenetic learning and behavioral disorders. In adult (FAS) mice, we measured phosphorylated cyclic adenosine monophosphate response element of binding protein (pCREB) staining in hippocampal subregions to evaluate a possible mechanism underlying FAS learning deficits. Pregnant C57BL6/J mice were treated on gestational day 8 with alcohol or control (saline). After learning assessment, the offspring were perfused for immunohistochemistry and brain sections probed using SER 133 pCREB antibody. Relative staining density was assessed using National Institutes of Health Image software. Statistical analysis included analysis of variance with P < .05 considered significant. In all hippocampal subregions, pCREB staining was greater in the control animals than in the alcohol-treated group (P < or = .0001). In utero alcohol exposure decreased pCREB activity in hippocampal subregions of adult mice. The dentate gyrus had the most robust cumulative decrease in pCREB staining, suggesting FAS adult learning deficits may correlate to enhanced dentate gyrus neurodegeneration.

Neuroimaging and Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

2009-01-01

The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and…

Fetal Alcohol Syndrome: Diagnostic Features and Psychoeducational Risk Factors.

ERIC Educational Resources Information Center

Phelps, LeAdelle; Grabowski, Jo-Anne

1992-01-01

Discusses Fetal Alcohol Syndrome (FAS), accepted as leading known cause of mental retardation. Relates chronicity, timing, and severity of alcohol exposure to age-specific developmental and behavioral consequences. Delineates specific interventions with infants, preschoolers, school-age children, and adolescents. Advocates for accurate diagnosis…

Intelligence and Fetal Alcohol Spectrum Disorders: A Review.

PubMed

Ferreira, Vanessa K de L; Cruz, Marcelo S

2017-01-08

Background: The studies on intelligence in individuals with fetal alcohol exposure are conflicting. Some have found a relevant impairment in this population, while others found results that were consistent with the population at large. Describe the results of studies on intelligence in individuals with Fetal Alcohol Spectrum Disorders. Indexed articles of the last 10 years were selected for an integrative literature review. After inclusion and exclusion criteria were satisfied 37 articles were selected. General intelligence, both verbal and non-verbal, is impaired in people who are prenatally exposed to alcohol. There is a tendency to a greater reduction in the Freedom from Distractibility/Working Memory Index of Wechsler Scales. Reduction in intelligence seems to occur on a continuum similar to the fetal alcohol spectrum. The reduction of the Freedom from Distractibility/Working Memory Index appears to be a reflection of a greater impairment of mathematical ability. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Fetal Alcohol Syndrome in Adolescents and Adults.

ERIC Educational Resources Information Center

Bert, Cynthia R. Greene; Bert, Minnie

Persons with fetal alcohol syndrome (FAS) may be diagnosed at birth based on specific symptoms and anomalies. These are history of prenatal alcohol exposure, mental retardation, central nervous system dysfunctions, growth deficiency, particular physical anomalies, and speech and language anomalies. With aging, cranial and skeletal anomalies become…

The Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Umbreit, John; Ostrow, Lisa S.

1980-01-01

Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

Psychiatry Trainees' Training and Experience in Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Eyal, Roy; O'Connor, Mary J.

2011-01-01

Background/Objective: Alcohol is a teratogen. Fetal alcohol spectrum disorders (FASDs) affect about 1% of live births, causing severe impairment. Individuals affected by FASDs are overrepresented in psychiatric settings. This study reports on the education and experience of psychiatry trainees in approaching FASDs. Method: Data were collected from…

Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Zerrer, Peggy

The paper reviews Fetal Alcohol Syndrome (FAS), a series of effects seen in children whose mothers drink alcohol to excess during pregnancy. The identification of FAS and its recognition as a major health problem in need of prevention are traced. Characteristics of children with FAS are described and resultant growth retardation, abnormal physical…

Fetal Alcohol Syndrome (FAS)--A Review.

ERIC Educational Resources Information Center

Holzman, Ian R.

1982-01-01

At least 30 percent of newborn children of alcoholic mothers are affected severely by the fetal alcohol syndrome and 40-45 percent show some stigmata. Risks to offspring of mothers who drink occasionally or binge drink are not clear, but the danger is probably greatest in the first trimester of pregnancy. (CMG)

Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences.

PubMed

Abel, E L; Hannigan, J H

1995-01-01

We present an hypothesis integrating epidemiological, clinical case, and basic biomedical research to explain why only relatively few women who drink alcohol during pregnancy give birth to children with alcohol-related birth defects (ARBDs), in particular, Fetal Alcohol Syndrome (FAS). We argue that specific sociobehavioral risk factors, e.g., low socioeconomic status, are permissive for FAS in that they provide the context for increased vulnerability. We illustrate how these permissive factors are related to biological factors, e.g., decreased antioxidant status, which in conjunction with alcohol, provoke FAS/ARBDs in vulnerable fetuses. We propose an integrative heuristic model hypothesizing that these permissive and provocative factors increase the likelihood of FAS/ARBDs because they potentiate two related mechanisms of alcohol-induced teratogenesis, specifically, maternal/fetal hypoxia and free radical formation.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

PubMed Central

2011-01-01

Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

Midline corpus callosum is a neuroanatomical focus of fetal alcohol damage.

PubMed

Bookstein, Fred L; Sampson, Paul D; Connor, Paul D; Streissguth, Ann P

2002-06-15

Prenatal exposure to high levels of alcohol often induces birth defects that combine morphological stigmata with neurological or neuropsychological deficits. But it has proved problematic to diagnose these syndromes in adolescents and adults, in whom the morphological signs are absent or attenuated, the behavioral deficits nonspecific, and the exposure history often difficult to reconstruct. Localizing the associated brain abnormalities might circumvent most of these difficulties. To this end, three-dimensional (3D) locations were recorded for 67 homologous points on or near the corpus callosum in magnetic resonance (MR) brain images from 60 adolescents and adults who were normal, 60 diagnosed with fetal alcohol syndrome, and 60 diagnosed with fetal alcohol effects. We combined the standard statistical approach to this type of geometric data, Procrustes analysis, with a multivariate strategy focusing on differences in variability. In this data set, the shape of the corpus callosum and its vicinity proves systematically much more variable in the alcohol-affected brains than in those of the normal subjects. From this excess variability follows a promising classification rule, having both high sensitivity (100 out of 117) and high specificity (49 out of 60) in this sample. The discrimination uses four landmark points and two summary scores of callosal outline shape. The information from the corpus callosum and vicinity, as viewed in MR brain images of full-grown subjects, may serve as a permanent record of the prenatal effects of alcohol, even in patients who are first suspected of these syndromes relatively late in life or who lack the facial signs of prenatal alcohol damage. The statistical pattern underlying the callosal diagnosis also leads to speculations on mechanisms of the prenatal damage. Copyright 2002 Wiley-Liss, Inc.

DNA Methylation Program in Developing Hippocampus and Its Alteration by Alcohol

PubMed Central

Chen, Yuanyuan; Ozturk, Nail Can; Zhou, Feng C.

2013-01-01

During hippocampal development, the Cornus Ammonis (CA) and the dentate gyrus (DG) undergo waves of neurogenesis and neuronal migration and maturation independently. This stage is widely known to be vulnerable to environmental stresses, but its underlying mechanism is unclear. Alcohol exposure has been shown to alter the expression of genes that regulate the fate, survival, migration and differentiation of pyramidal and granule cells. Undermining this process might compromise hippocampal development underlying the learning and memory deficits known in Fetal Alcohol Spectrum Disorders (FASD). We have previously demonstrated that DNA methylation was programmed along with neural tube development. Here, we demonstrated that DNA methylation program (DMP) proceeded along with hippocampal neuronal differentiation and maturation, and how this DMP was affected by fetal alcohol exposure. C57BL/6 mice were treated with 4% v/v ethanol through a liquid diet along with pair-fed and chow-fed controls from gestation day (E) 7 to E16. We found that a characteristic DMP, including 5-methylcytidine (5mC), 5-hydroxylmethylcytidine (5hmC) and their binding proteins, led the hippocampal neuronal differentiation and maturation spatiotemporally as indicated by their phenotypic marks in the CA and DG pre- and post-natally. Alcohol hindered the acquisition and progression of methylation marks, and altered the chromatin translocation of these marks in the nucleus, which was correlated with developmental retardation. PMID:23544149

Fetal alcohol syndrome and secondary schizophrenia: a unique neuropathologic study.

PubMed

Stoos, Catherine; Nelsen, Laura; Schissler, Kathryn A; Elliott, Amy J; Kinney, Hannah C

2015-04-01

We report the unique neuropathologic study of an adult brain of a patient with fetal alcohol syndrome who developed the well-recognized complication of schizophrenia in adolescence. The major finding was asymmetric formation of the lateral temporal lobes, with marked enlargement of the right superior temporal gyrus, suggesting that alcohol is preferentially toxic to temporal lobe patterning during gestation. Critical maturational changes unique to adolescence can unmask psychotic symptomatology mediated by temporal lobe pathology that has been clinically dormant since birth. Elucidating the neuropathologic basis of the secondary psychiatric disorders in fetal alcohol syndrome can help provide insight into their putative developmental origins. © The Author(s) 2014.

Focus on: epigenetics and fetal alcohol spectrum disorders.

PubMed

Kobor, Michael S; Weinberg, Joanne

2011-01-01

Epigenetic changes-stable but potentially reversible alterations in a cell's genetic information that result in changes in gene expression but do not involve changes in the underlying DNA sequence-may mediate some of the detrimental effects of prenatal alcohol exposure and contribute to the deficits and abnormalities associated with fetal alcohol spectrum disorders. These epigenetic processes are linked to the chromatin (i.e., DNA, histone proteins, and other associated proteins) and commonly involve chemical modifications (e.g., methylation) of these molecules, which may result in altered expression of the affected genes. Even alcohol exposure prior to conception appears to be able to induce epigenetic changes in the parental genetic material that can be passed on to the offspring and affect offspring outcome. Similarly, epigenetic processes may occur as a result of maternal alcohol consumption during the period between fertilization of the egg and implantation in the uterus. The period most sensitive to alcohol's adverse effects appears to be gastrulation, which corresponds to prenatal weeks 3 to 8 in the human and prenatal days 7 to 14 in the mouse, when cells are differentiating to form organs. One way in which alcohol exposure may induce epigenetic changes, particularly abnormal DNA methylation, is by affecting a set of biochemical reactions called the methionine-homocysteine cycle.

Identifying Risk and Promoting Resilience in Infants and Toddlers with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Shah, Prachi; Milgrom, Tedi; Munzer, Tiffany; Hoyme, H. Eugene

2015-01-01

Fetal alcohol spectrum disorders (FASDs) is an umbrella term that describes a variety of conditions characterized by a pattern of atypical facial features, growth restriction, structural physical abnormalities, and brain dysfunction resulting from prenatal alcohol exposure. Studies suggest that the prevalence of FASDs ranges between 2-5% (of the…

Intervention for Individuals with Fetal Alcohol Spectrum Disorders: Treatment Approaches and Case Management

ERIC Educational Resources Information Center

Paley, Blair; O'Connor, Mary J.

2009-01-01

Exposure to alcohol in utero is considered to be the leading cause of developmental disabilities of known etiology. The most severe consequence of such exposure, fetal alcohol syndrome (FAS), is characterized by a distinct constellation of characteristic facial anomalies, growth retardation, and central nervous system (CNS) dysfunction. Some…

Brain single-photon emission computed tomography in fetal alcohol syndrome: a case report and study implications.

PubMed

Codreanu, Ion; Yang, JiGang; Zhuang, Hongming

2012-12-01

The indications of brain single-photon emission computed tomography (SPECT) in fetal alcohol syndrome are not clearly defined, even though the condition is recognized as one of the most common causes of mental retardation. This article reports a case of a 9-year-old adopted girl with developmental delay, mildly dysmorphic facial features, and behavioral and cognitive abnormalities. Extensive investigations including genetic studies and brain magnetic resonance imaging (MRI) revealed no abnormalities, and a diagnosis of fetal alcohol syndrome was considered since official diagnostic criteria were met. A brain SPECT was requested and showed severely decreased tracer activity in the thalami, basal ganglia, and temporal lobes on both sides, the overall findings being consistent with the established diagnosis of fetal alcohol syndrome. With increasing availability of functional brain imaging, the study indications and possible ethical implications in suspected prenatal alcohol exposure or even before adoption need further consideration. In this patient, SPECT was the only test to yield positive results.

Epigenetics studies of fetal alcohol spectrum disorder: where are we now?

PubMed

Lussier, Alexandre A; Weinberg, Joanne; Kobor, Michael S

2017-03-01

Adverse in utero events can alter the development and function of numerous physiological systems, giving rise to lasting neurodevelopmental deficits. In particular, data have shown that prenatal alcohol exposure can reprogram neurobiological systems, altering developmental trajectories and resulting in increased vulnerability to adverse neurobiological, behavioral and health outcomes. Increasing evidence suggests that epigenetic mechanisms are potential mediators for the reprogramming of neurobiological systems, as they may provide a link between the genome, environmental conditions and neurodevelopmental outcomes. This review outlines the current state of epigenetic research in fetal alcohol spectrum disorder, highlighting the role of epigenetic mechanisms in the reprogramming of neurobiological systems by alcohol and as potential diagnostic tools for fetal alcohol spectrum disorder. We also present an assessment of the current limitations in studies of prenatal alcohol exposure, and highlight the future steps needed in the field.

Prenatal Alcohol Exposure Alters Fetal Iron Distribution and Elevates Hepatic Hepcidin in a Rat Model of Fetal Alcohol Spectrum Disorders123

PubMed Central

Huebner, Shane M; Blohowiak, Sharon E; Kling, Pamela J; Smith, Susan M

2016-01-01

Background: Prenatal alcohol exposure (PAE) causes neurodevelopmental disabilities, and gestational iron deficiency (ID) selectively worsens learning and neuroanatomical and growth impairments in PAE. It is unknown why ID worsens outcomes in alcohol-exposed offspring. Objective: We hypothesized that PAE alters maternal-fetal iron distribution or its regulation. Methods: Nulliparous, 10-wk-old, Long-Evans rats were mated and then fed iron-sufficient (100 mg Fe/kg) or iron-deficient (≤4 mg Fe/kg) diets. On gestational days 13.5–19.5, dams received either 5.0 g ethanol/kg body weight (PAE) or isocaloric maltodextrin by oral gavage. On gestational day 20.5, maternal and fetal clinical blood counts, tissue mineral and iron transport protein concentrations, and hepatic hepcidin mRNA expression were determined. Results: In fetal brain and liver (P < 0.001) and in maternal liver (P < 0.005), ID decreased iron (total and nonheme) and ferritin content by nearly 200%. PAE reduced fetal bodyweight (P < 0.001) and interacted with ID (P < 0.001) to reduce it by an additional 20%. Independent of maternal iron status, PAE increased fetal liver iron (30–60%, P < 0.001) and decreased brain iron content (total and nonheme, 15–20%, P ≤ 0.050). ID-PAE brains had lower ferritin, transferrin, and transferrin receptor content (P ≤ 0.002) than ID-maltodextrin brains. PAE reduced fetal hematocrit, hemoglobin, and red blood cell numbers (P < 0.003) independently of iron status. Unexpectedly, and also independent of iron status, PAE increased maternal and fetal hepatic hepcidin mRNA expression >300% (P < 0.001). Conclusions: PAE altered fetal iron distribution independent of maternal iron status in rats. The elevated iron content of fetal liver suggests that PAE may have limited iron availability for fetal erythropoiesis and brain development. Altered fetal iron distribution may partly explain why maternal ID substantially worsens growth and behavioral outcomes in PAE. PMID:27146918

Identifying the Characteristics of Fetal Alcohol Spectrum Disorders (FASD) among Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Someki, Fumio

2011-01-01

Fetal alcohol spectrum disorder (FASD), characterized by various levels of dysmorphia and behavioral and cognitive dysfunctions, is the result of prenatal alcohol exposure. FASD characteristics can be masked by many other conditions. As a result, early identification of FASD is often difficult, leading to a delay of children with FASD receiving…

Evidence-Based Practice Guidelines for Fetal Alcohol Spectrum Disorder and Literacy and Learning

ERIC Educational Resources Information Center

Mitten, H. Rae

2013-01-01

Evidence-based Practice Guidelines for Fetal Alcohol Spectrum Disorder (FASD) and Literacy and Learning are derived from an inductive analysis of qualitative data collected in field research. FASD is the umbrella term for a spectrum of neurocognitive and physical disabilities caused by prenatal exposure to alcohol. Data from a sample of N=150 was…

Evidence-Based Practice Guidelines for Fetal Alcohol Spectrum Disorder and Literacy and Learning

ERIC Educational Resources Information Center

Mitten, H. Rae

2013-01-01

Evidence-based Practice Guidelines for Fetal Alcohol Spectrum Disorder (FASD) and Literacy and Learning are derived from an inductive analysis of qualitative data collected in field research. FASD is the umbrella term for a spectrum of neurocognitive and physical disabilities caused by prenatal exposure to alcohol. Data from a sample of N =150 was…

Fetal Alcohol Effects in Children: Cognitive, Educational, and Behavioral Considerations.

ERIC Educational Resources Information Center

Horowitz, Sheldon

The effects of alcohol on the developing fetus are examined. Noted is the existence of both structural problems (such as microcephaly and cardiac anomalies) and behavioral problems (such as mental retardation and speech and language deficits). The potential damage of alcohol at a very early stage of fetal development is discussed. It is thought…

Infant Symbolic Play as an Early Indicator of Fetal Alcohol-Related Deficit

ERIC Educational Resources Information Center

Molteno, Christopher D.; Jacobson, Sandra W.; Carter, R. Colin; Jacobson, Joseph L.

2010-01-01

Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. A total of 107 Cape-Colored, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of…

Correlation between morphological MRI findings and specific diagnostic categories in fetal alcohol spectrum disorders.

PubMed

Boronat, S; Sánchez-Montañez, A; Gómez-Barros, N; Jacas, C; Martínez-Ribot, L; Vázquez, E; Del Campo, M

2017-01-01

Fetal alcohol spectrum disorders (FASD) include physical and neurodevelopmental abnormalities related to prenatal alcohol exposure. Some neuroimaging findings have been clearly related to FASD, including corpus callosum and cerebellar anomalies. However, detailed studies correlating with specific FASD categories, that is, the fetal alcohol syndrome (FAS), partial FAS (pFAS) and alcohol related neurodevelopmental disorders (ARND), are lacking. We prospectively performed clinical assessment and brain MR imaging to 72 patients with suspected FASD, and diagnosis was confirmed in 62. The most frequent findings were hypoplasia of the corpus callosum and/or of the cerebellar vermis. Additional findings were vascular anomalies, gliosis, prominent perivascular spaces, occipito-cervical junction and cervical vertebral anomalies, pituitary hypoplasia, arachnoid cysts, and cavum septum pellucidum. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Lifelong Impacts of Moderate Prenatal Alcohol Exposure on Neuroimmune Function

PubMed Central

Noor, Shahani; Milligan, Erin D.

2018-01-01

In utero alcohol exposure is emerging as a major risk factor for lifelong aberrant neuroimmune function. Fetal alcohol spectrum disorder encompasses a range of behavioral and physiological sequelae that may occur throughout life and includes cognitive developmental disabilities as well as disease susceptibility related to aberrant immune and neuroimmune actions. Emerging data from clinical studies and findings from animal models support that very low to moderate levels of fetal alcohol exposure may reprogram the developing central nervous system leading to altered neuroimmune and neuroglial signaling during adulthood. In this review, we will focus on the consequences of low to moderate prenatal alcohol exposure (PAE) on neuroimmune interactions during early life and at different stages of adulthood. Data discussed here will include recent studies suggesting that while abnormal immune function is generally minimal under basal conditions, following pathogenic stimuli or trauma, significant alterations in the neuroimmune axis occur. Evidence from published reports will be discussed with a focus on observations that PAE may bias later-life peripheral immune responses toward a proinflammatory phenotype. The propensity for proinflammatory responses to challenges in adulthood may ultimately shape neuron–glial-immune processes suspected to underlie various neuropathological outcomes including chronic pain and cognitive impairment.

Human alcohol-related neuropathology

PubMed Central

Kril, Jillian J.

2015-01-01

Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions. PMID:24370929

Population differences in dysmorphic features among children with fetal alcohol spectrum disorders.

PubMed

May, Philip A; Gossage, J Phillip; Smith, Matthew; Tabachnick, Barbara G; Robinson, Luther K; Manning, Melanie; Cecanti, Mauro; Jones, Kenneth Lyons; Khaole, Nathaniel; Buckley, David; Kalberg, Wendy O; Trujillo, Phyllis M; Hoyme, H Eugene

2010-05-01

To examine the variation in significant dysmorphic features in children from 3 different populations with the most dysmorphic forms of fetal alcohol spectrum disorders, fetal alcohol syndrome (FAS), and partial fetal alcohol syndrome (PFAS). Advanced multiple regression techniques are used to determine the discriminating physical features in the diagnosis of FAS and PFAS among children from Northern Plains Indian communities, South Africa, and Italy. Within the range of physical features used to identify children with fetal alcohol spectrum disorders, specifically FAS and PFAS, there is some significant variation in salient diagnostic features from one population to the next. Intraclass correlations in diagnostic features between these 3 populations is 0.20, indicating that about 20% of the variability in dysmorphology core features is associated with location and, therefore, specific racial/ethnic population. The highly significant diagnostic indicators present in each population are identified for the full samples of FAS, PFAS, and normals and also among children with FAS only. A multilevel model for these populations combined indicates that these variables predict dysmorphology unambiguously: small palpebral fissures, narrow vermillion, smooth philtrum, flat nasal bridge, and fifth finger clinodactyly. Long philtrum varies substantially as a predictor in the 3 populations. Predictors not significantly related to fetal alcohol spectrum disorders dysmorphology across the 3 populations are centile of height (except in Italy) strabismus, interpupilary distance, intercanthal distance, and heart murmurs. The dysmorphology associated with FAS and PFAS vary across populations, yet a particular array of common features occurs in each population, which permits a consistent diagnosis across populations.

Epigenetics studies of fetal alcohol spectrum disorder: where are we now?

PubMed Central

Lussier, Alexandre A; Weinberg, Joanne; Kobor, Michael S

2017-01-01

Adverse in utero events can alter the development and function of numerous physiological systems, giving rise to lasting neurodevelopmental deficits. In particular, data have shown that prenatal alcohol exposure can reprogram neurobiological systems, altering developmental trajectories and resulting in increased vulnerability to adverse neurobiological, behavioral and health outcomes. Increasing evidence suggests that epigenetic mechanisms are potential mediators for the reprogramming of neurobiological systems, as they may provide a link between the genome, environmental conditions and neurodevelopmental outcomes. This review outlines the current state of epigenetic research in fetal alcohol spectrum disorder, highlighting the role of epigenetic mechanisms in the reprogramming of neurobiological systems by alcohol and as potential diagnostic tools for fetal alcohol spectrum disorder. We also present an assessment of the current limitations in studies of prenatal alcohol exposure, and highlight the future steps needed in the field. PMID:28234026

Focus On: Epigenetics and Fetal Alcohol Spectrum Disorders

PubMed Central

Kobor, Michael S.; Weinberg, Joanne

2011-01-01

Epigenetic changes—stable but potentially reversible alterations in a cell’s genetic information that result in changes in gene expression but do not involve changes in the underlying DNA sequence—may mediate some of the detrimental effects of prenatal alcohol exposure and contribute to the deficits and abnormalities associated with fetal alcohol spectrum disorders. These epigenetic processes are linked to the chromatin (i.e., DNA, histone proteins, and other associated proteins) and commonly involve chemical modifications (e.g., methylation) of these molecules, which may result in altered expression of the affected genes. Even alcohol exposure prior to conception appears to be able to induce epigenetic changes in the parental genetic material that can be passed on to the offspring and affect offspring outcome. Similarly, epigenetic processes may occur as a result of maternal alcohol consumption during the period between fertilization of the egg and implantation in the uterus. The period most sensitive to alcohol’s adverse effects appears to be gastrulation, which corresponds to prenatal weeks 3 to 8 in the human and prenatal days 7 to 14 in the mouse, when cells are differentiating to form organs. One way in which alcohol exposure may induce epigenetic changes, particularly abnormal DNA methylation, is by affecting a set of biochemical reactions called the methionine–homocysteine cycle. PMID:23580038

Prevalence of fetal alcohol spectrum disorders in child care settings: a meta-analysis.

PubMed

Lange, Shannon; Shield, Kevin; Rehm, Jürgen; Popova, Svetlana

2013-10-01

Children often enter a child-care system (eg, orphanage, foster care, child welfare system) because of unfavorable circumstances (eg, maternal alcohol and/or drug problems, child abuse/neglect). Such circumstances increase the odds of prenatal alcohol exposure, and thus this population can be regarded as high risk for fetal alcohol spectrum disorders (FASD). The primary objective was to estimate a pooled prevalence for fetal alcohol syndrome (FAS) and FASD in various child-care systems based on data from existing studies that used an active case ascertainment method. A systematic literature review, using multiple electronic bibliographic databases, and meta-analysis of internationally published and unpublished studies that reported the prevalence of FAS and/or FASD in all types of child-care systems were conducted. The pooled prevalence estimates and 95% confidence intervals (CIs) were calculated by using the Mantel-Haenszel method, assuming a random effects model. Sensitivity analyses were performed for studies that used either passive surveillance or mixed methods. On the basis of studies that used active case ascertainment, the overall pooled prevalence of FAS and FASD among children and youth in the care of a child-care system was calculated to be 6.0% (60 per 1000; 95% CI: 38 to 85 per 1000) and 16.9% (169 per 1000; 95% CI: 109 to 238 per 1000), respectively. The results confirm that children and youth housed in or under the guardianship of the wide range of child-care systems constitute a population that is high-risk for FASD. It is imperative that screening be implemented in these at-risk populations.

Profiling ethanol-targeted transcription factors in human carcinoma cell-derived embryoid bodies.

PubMed

Mandal, Chanchal; Halder, Debasish; Chai, Jin Choul; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

2016-01-15

Fetal alcohol spectrum disorder is a collective term that represents fetal abnormalities associated with maternal alcohol consumption. Prenatal alcohol exposure and related anomalies are well characterized, but the molecular mechanism behind this phenomenon is not yet understood. Few insights have been gained from genetic and epigenetic studies of fetal alcohol spectrum disorder. Our aim was to profile the important molecular regulators of ethanol-related alterations of the genome. For this purpose, we have analyzed the gene expression pattern of human carcinoma cell-derived embryoid bodies in the absence or presence of ethanol. A cDNA microarray analysis was used to profile mRNA expression in embryoid bodies at day 7 with or without ethanol treatment. A total of 493 differentially expressed genes were identified in response to 50 mM ethanol exposure. Of these, 111 genes were up-regulated, and 382 were down-regulated. Gene ontology term enrichment analysis revealed that these genes are involved in important biological processes: neurological system processes, cognition, behavior, sensory perception of smell, taste and chemical stimuli and synaptic transmission. Similarly, the enrichment of disease-related genes included relevant categories such as neurological diseases, developmental disorders, skeletal and muscular disorders, and connective tissue disorders. Furthermore, we have identified a group of 26 genes that encode transcription factors. We validated the relative gene expression of several transcription factors using quantitative real time PCR. We hope that our study substantially contributes to the understanding of the molecular mechanisms underlying the pathology of alcohol-mediated anomalies and facilitates further research. Copyright © 2015 Elsevier B.V. All rights reserved.

Factors Predisposing, Enabling and Reinforcing Routine Screening of Patients for Preventing Fetal Alcohol Syndrome: A Survey of New Jersey Physicians.

ERIC Educational Resources Information Center

Donovan, Carole L.

1991-01-01

Survey of 58 physicians revealed that they did not routinely ask their pregnant patients about alcohol consumption for several reasons: physician bias resulting from own abuse, lack of training, poor awareness of problem and effects, denial that Fetal Alcohol Syndrome occurs in private practice, time limitations, disinterest, fear of offending…

Regulatory Behaviors and Stress Reactivity among Infants at High Risk for Fetal Alcohol Spectrum Disorders: An Exploratory Study

ERIC Educational Resources Information Center

Jirikowic, Tracy; Chen, Maida; Nash, Jennifer; Gendler, Beth; Olson, Heather Carmichael

2016-01-01

Introduction: This article examines regulatory behaviors and physiological stress reactivity among 6-15 month-old infants with moderate to heavy prenatal alcohol exposure (PAE), a group at very high risk for fetal alcohol spectrum disorders and self-regulation impairments, compared to low risk infants with no/low exposure. Participants: Eighteen…

The Feasibility of Screening for Fetal Alcohol Spectrum Disorders Risk in Early Intervention Settings: A Pilot Study of Systems Change

ERIC Educational Resources Information Center

Watson, Enid; Finkelstein, Norma; Gurewich, Deborah; Morse, Barbara

2011-01-01

Prenatal alcohol exposure can result in fetal alcohol spectrum disorders (FASD), which can include physical and neurobehavioral disorders, including cognitive, social, language, and motor impairments that can persist throughout life. In order for children with FASD to receive the full benefit of services, recognition of their disability needs to…

Executive Function Deficits in Children with Fetal Alcohol Spectrum Disorders (FASD) Measured Using the Cambridge Neuropsychological Tests Automated Battery (CANTAB)

ERIC Educational Resources Information Center

Green, C. R.; Mihic, A. M.; Nikkel, S. M.; Stade, B. C.; Rasmussen, C.; Munoz, D. P.; Reynolds, J. N.

2009-01-01

Background: Chronic prenatal alcohol exposure causes a spectrum of deleterious effects in offspring, collectively termed fetal alcohol spectrum disorders (FASD), and deficits in executive function are prevalent in FASD. The goal of this research was to test the hypothesis that children with FASD exhibit performance deficits in tasks that assess…

Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis

PubMed Central

Chudley, Albert E.; Conry, Julianne; Cook, Jocelynn L.; Loock, Christine; Rosales, Ted; LeBlanc, Nicole

2005-01-01

THE DIAGNOSIS OF FETAL ALCOHOL SPECTRUM DISORDER (FASD) is complex and guidelines are warranted. A subcommittee of the Public Health Agency of Canada's National Advisory Committee on Fetal Alcohol Spectrum Disorder reviewed, analysed and integrated current approaches to diagnosis to reach agreement on a standard in Canada. The purpose of this paper is to review and clarify the use of current diagnostic systems and make recommendations on their application for diagnosis of FASD-related disabilities in people of all ages. The guidelines are based on widespread consultation of expert practitioners and partners in the field. The guidelines have been organized into 7 categories: screening and referral; the physical examination and differential diagnosis; the neurobehavioural assessment; and treatment and follow-up; maternal alcohol history in pregnancy; diagnostic criteria for fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorder; and harmonization of Institute of Medicine and 4-Digit Diagnostic Code approaches. The diagnosis requires a comprehensive history and physical and neurobehavioural assessments; a multidisciplinary approach is necessary. These are the first Canadian guidelines for the diagnosis of FAS and its related disabilities, developed by broad-based consultation among experts in diagnosis. PMID:15738468

A Practical Clinical Approach to Diagnosis of Fetal Alcohol Spectrum Disorders: Clarification of the 1996 Institute of Medicine Criteria

PubMed Central

Eugene Hoyme, H.; May, Philip A.; Kalberg, Wendy O.; Kodituwakku, Piyadasa; Phillip Gossage, J.; Trujillo, Phyllis M.; Buckley, David G.; Miller, Joseph H.; Aragon, Alfredo S.; Khaole, Nathaniel; Viljoen, Denis L.; Jones, Kenneth Lyons; Robinson, Luther K.

2006-01-01

Background. The adverse effects of alcohol on the developing human represent a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). The first descriptions in the modern medical literature of a distinctly recognizable pattern of malformations associated with maternal alcohol abuse were reported in 1968 and 1973. Since that time, substantial progress has been made in developing specific criteria for defining and diagnosing this condition. Two sets of diagnostic criteria are now used most widely for evaluation of children with potential diagnoses in the FASD continuum, ie, the 1996 Institute of Medicine (IOM) criteria and the Washington criteria. Although both approaches have improved the clinical delineation of FASD, both suffer from significant drawbacks in their practical application in pediatric practice. Objective. The purpose of this report is to present specific clarifications of the 1996 IOM criteria for the diagnosis of FASD, to facilitate their practical application in clinical pediatric practice. Methods. A large cohort of children who were prenatally exposed to alcohol were identified, through active case-ascertainment methods, in 6 Native American communities in the United States and 1 community in the Western Cape Province of South Africa. The children and their families underwent standardized multidisciplinary evaluations, including a dysmorphology examination, developmental and neuropsychologic testing, and a structured maternal interview, which gathered data about prenatal drinking practices and other demographic and family information. Data for these subjects were analyzed, and revisions and clarifications of the existing IOM FASD diagnostic categories were formulated on the basis of the results. Results. The revised IOM method defined accurately and completely the spectrum of disabilities among the children in our study. On the basis of this experience, we propose specific diagnostic criteria for fetal alcohol syndrome and partial fetal alcohol syndrome. We also define alcohol-related birth defects and alcohol-related neurodevelopmental disorder from a practical standpoint. Conclusions. The 1996 IOM criteria remain the most appropriate diagnostic approach for children prenatally exposed to alcohol. The proposed revisions presented here make these criteria applicable in clinical pediatric practice. Pediatrics 2005;115:39–47; fetal alcohol syndrome, fetal alcohol spectrum disorders, diagnostic criteria, mental retardation, developmental disabilities. PMID:15629980

A report on the Fetal Alcohol Spectrum Disorders Study Group meeting of 2012, Theme title, “Biomarkers for FASD”

PubMed Central

Miranda, Rajesh C.; Kable, Julie; Reynolds, James N.; Valenzuela, C. Fernando

2013-01-01

The 2012 meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) focused on the development and ethics of biomarkers for fetal alcohol exposure. This one-day international conference brought students and trainees together with clinicians and researchers to discuss the latest research on FASD. One keynote speaker discussed the value of profiling epigenetic modifications in readily available fetal tissues to diagnose fetal exposure to environmental agents, while the second speaker discussed the ethics of biomarker development within the context of core principles of justice, autonomy, beneficence and non-maleficence. Three sessions of short data talks informed the audience of research advances with particular emphasis on the diagnosis of FASD. Other activities included updates on FASD-related activities by representatives of government agencies, a report on the implementation FASD-related diagnostic criteria in the fifth edition of the Diagnostic and Statistical Manual (DSM-5) of the American Psychiatric Association and a networking lunch, and the presentation of the “Merit Award” to Dr. Nathan Muraski for his work on behavioural outcomes of fetal alcohol exposure. The capstone of the meeting was the presentation of the “Henri Rosett” award to Dr. Denis Viljoen, in recognition of his role in raising awareness about the incidence of FASD in South Africa and in promoting FASD prevention and treatment programs as chairperson and chief executive officer of the Foundation for Alcohol Related Research (FARR). PMID:24183101

Fetal Alcohol Syndrome: Research Review and Implications.

ERIC Educational Resources Information Center

Griesbach, Linda Sue; Polloway, Edward A.

Research on fetal alcohol syndrome is reviewed, with particular emphasis on the implications of the syndrome for the development of mental retardation and other handicapping conditions. Attention is given to historical aspects; epidemiology; physiological and behavioral characteristics; and concerns related to diagnosis, prevention, and…

RNA Sequencing Reveals the Alteration of the Expression of Novel Genes in Ethanol-Treated Embryoid Bodies.

PubMed

Mandal, Chanchal; Kim, Sun Hwa; Chai, Jin Choul; Oh, Seon Mi; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

2016-01-01

Fetal alcohol spectrum disorder is a collective term representing fetal abnormalities associated with maternal alcohol consumption. Prenatal alcohol exposure and related anomalies are well characterized, but the molecular mechanism behind this phenomenon is not well characterized. In this present study, our aim is to profile important genes that regulate cellular development during fetal development. Human embryonic carcinoma cells (NCCIT) are cultured to form embryoid bodies and then treated in the presence and absence of ethanol (50 mM). We employed RNA sequencing to profile differentially expressed genes in the ethanol-treated embryoid bodies from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH data sets. A total of 632, 205 and 517 differentially expressed genes were identified from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH, respectively. Functional annotation using bioinformatics tools reveal significant enrichment of differential cellular development and developmental disorders. Furthermore, a group of 42, 15 and 35 transcription factor-encoding genes are screened from all of the differentially expressed genes obtained from NCCIT vs. EB, NCCIT vs. EB+EtOH and EB vs. EB+EtOH, respectively. We validated relative gene expression levels of several transcription factors from these lists by quantitative real-time PCR. We hope that our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of alcohol-mediated anomalies and ease further research.

Evaluating changes in brain vasculature of murine embryos in utero due to maternal alcohol consumption using optical coherence tomography

NASA Astrophysics Data System (ADS)

Raghunathan, Raksha; Wu, Chen; Singh, Manmohan; Liu, Chih-Hao; Miranda, Rajesh C.; Larin, Kirill V.

2017-04-01

Fetal Alcohol Syndrome (FAS) refers to the broad spectrum of developmental and behavioral effects caused due to prenatal alcohol exposure (PAE). Wide range of abnormalities vary depending on the amount of alcohol consumed and the period of consumption during gestation. PAE during early stages of pregnancy is very common. However a large number of women continue to consume alcohol even during the second trimester, a critical period for fetal neurogenesis and angiogenesis. Optical coherence tomography (OCT) has shown to be extremely useful in embryonic imaging. Our previous work showed that OCT is capable of quantitative assessment of ventriculomegaly caused by maternal alcohol consumption. Although structural changes and changes in blood flow in the fetal brain after maternal alcohol consumption have been studied, acute vasculature changes are not well documented. Speckle variance OCT (SVOCT), is a functional extension of OCT that has been used to study vasculature development in embryos. We use SVOCT, to detect vasculature changes in the embryonic brain in utero, minutes after maternal alcohol consumption.

A State of Double Jeopardy: Impact of Prenatal Alcohol Exposure and Adverse Environments on the Social Communicative Abilities of School-Age Children with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Coggins, Truman E.; Timler, Geralyn R.; Olswang, Lesley B.

2007-01-01

Purpose: This article is a retrospective examination of environmental risk, language performance, and narrative discourse data from a clinical database of school-age children with fetal alcohol spectrum disorder (FASD). Method: A case-defined diagnostic approach for measuring and reporting the full spectrum of disabilities in children with…

Canadian Children and Youth in Care: The Cost of Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Popova, Svetlana; Lange, Shannon; Burd, Larry; Rehm, Jürgen

2014-01-01

Background: A high prevalence of prenatal alcohol exposure has been reported among children in care and thus, the risk of fetal alcohol spectrum disorder (FASD) in this population is high. Objective: The purpose of the current study was to estimate the number of children (0-18 years) in care with FASD and to determine the associated cost by age…

Preventing Fetal Alcohol Spectrum Disorders: An Evidence-Based Prevention Program for Adolescent and Adult Hispanic Females in the South Texas Border Region

ERIC Educational Resources Information Center

Russell, Todd T.; Craddock, Christopher S.; Kodatt, Stephanie A.; Ramirez, Dora Maria

2017-01-01

Fetal Alcohol Spectrum Disorders (FASD) present serious problems for the twenty-first century. These disorders describe a variety of neurological and behavioral deficits that result from exposure of an unborn child to alcohol during pregnancy. While thousands of children are diagnosed with FASD annually, FASD is completely preventable if women…

HIV/AIDS and Alcohol

MedlinePlus

... Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special Populations & Co-occurring Disorders Publications & Multimedia Brochures & ...

Fetal alcohol spectrum disorders: an overview.

PubMed

Riley, Edward P; Infante, M Alejandra; Warren, Kenneth R

2011-06-01

When fetal alcohol syndrome (FAS) was initially described, diagnosis was based upon physical parameters including facial anomalies and growth retardation, with evidence of developmental delay or mental deficiency. Forty years of research has shown that FAS lies towards the extreme end of what are now termed fetal alcohol spectrum disorders (FASD). The most profound effects of prenatal alcohol exposure are on the developing brain and the cognitive and behavioral effects that ensue. Alcohol exposure affects brain development via numerous pathways at all stages from neurogenesis to myelination. For example, the same processes that give rise to the facial characteristics of FAS also cause abnormal brain development. Behaviors as diverse as executive functioning to motor control are affected. This special issue of Neuropsychology Review addresses these changes in brain and behavior highlighting the relationship between the two. A diagnostic goal is to recognize FAS as a disorder of brain rather than one of physical characteristics.

Proceedings of the 2009 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group

PubMed Central

Zhou, Feng C.; Kane, Cynthia J.M.; Smith, Susan M.

2013-01-01

The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was held on June 20, 2009 in San Diego, CA, as a satellite of the Research Society on Alcoholism Meeting. The FASDSG membership includes clinical, basic, and social scientists who meet to discuss recent advances and issues in Fetal Alcohol Spectrum Disorders research. The main theme of the meeting was “Epigenetics and Development.” Two keynote speakers, Dr. Randy Jirtle and Dr. Michael Skinner, addressed the role of epigenetics and environmental inputs, including alcohol, during critical stages of development and their potential critical and long-lasting effects. Members of the FASDSG provided new findings through brief “FASt” data reports, and national agency representatives provided updates on activities and funding priorities. Scientific presentations were made by recipients of the Student Research Merit Award and Rosett Award. PMID:21621368

The effectiveness of a multimedia program to prevent fetal alcohol syndrome.

PubMed

Lachausse, Robert G

2008-07-01

Fetal alcohol syndrome (FAS) continues to be the leading preventable cause of mental retardation in the United States. Because abstaining from alcohol prior to and throughout pregnancy is the only way to prevent FAS, some prevention programs try to target women before they become pregnant. The Fetal Alcohol Spectrum Teaching and Research Awareness Campaign (FASTRAC) is a multimedia, peer-delivered educational presentation designed to reduce the incidence of FAS. Results from an ethnically diverse sample of high school students indicate that the program increased participants' knowledge regarding FAS but had no significant effect on participants' attitudes, beliefs about the dangers of FAS or intention to use alcohol during pregnancy. The FASTRAC program failed partly because of its didactic approach and the lack of health education principles that have been shown to be effective in changing other substance use behaviors. Suggestions for improving FAS prevention education programs are offered.

Postsecondary Educational Experiences of Adults with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Duquette, Cheryll; Orders, Shari

2013-01-01

The postsecondary experiences of adults diagnosed with Fetal Alcohol Spectrum Disorder (FASD) were examined in this qualitative research. Tinto's Student Integration Model (SIM) (1975, 1997) provided the theoretical framework that guided the study. Tinto posits that the interplay of background characteristics, academic integration, and social…

Fetal Alcohol Spectrum Disorders and the Criminal Justice System

ERIC Educational Resources Information Center

Fast, Diane K.; Conry, Julianne

2009-01-01

The life-long neurological impairments found in people with fetal alcohol spectrum disorders (FASDs), including learning disabilities, impulsivity, hyperactivity, social ineptness, and poor judgment, can increase susceptibility to victimization and involvement in the criminal justice system (CJS). Individuals with FASDs become involved in the CJS…

Effective Teaching for FAS & FAE Children.

ERIC Educational Resources Information Center

Root, Pam

This paper discusses the importance of teaching social skills to children with Fetal Alcohol Syndrome (FAS) or Fetal Alcohol Effect (FAE) and the interrelationship between social skills and academic improvement. Goals and techniques for teaching social skills are identified, including: (1) improving the skill of compliance by setting reasonable…

Goal-directed arm movements in children with fetal alcohol syndrome: a kinematic approach.

PubMed

Domellöf, E; Fagard, J; Jacquet, A-Y; Rönnqvist, L

2011-02-01

Although many studies have documented deficits in general motor functioning in children with fetal alcohol syndrome (FAS), few have employed detailed measurements to explore the specific nature of such disabilities. This pilot study explores whether three-dimensional (3D) kinematic analysis may generate increased knowledge of the effect of intrauterine alcohol exposure on motor control processes by detecting atypical upper-limb movement pattern specificity in children with FAS relative to typically developing (TD) children. Left and right arm and head movements during a sequential unimanual goal-directed precision task in a sample of children with FAS and in TD children were registered by an optoelectronic tracking system (ProReflex, Qualisys Inc.). Children with FAS demonstrated evidently poorer task performance compared with TD children. Additionally, analyses of arm movement kinematics revealed atypical spatio-temporal organization in the children with FAS. In general, they exhibited longer arm movement trajectories at both the proximal and distal level, faster velocities at the proximal level but slower at the distal level, and more segmented distal movements. Children with FAS also showed atypically augmented and fast head movements during the task performance. Findings indicate neuromotor deficits and developmental delay in goal-directed arm movements because of prenatal alcohol exposure. It is suggested that 3D kinematic analysis is a valid technique for furthering the understanding of motor control processes in children with FAS/fetal alcohol spectrum disorders. A combination with relevant neuroimaging techniques in future studies would enable a more clear-cut interpretation of how atypical movement patterns relate to underlying brain abnormalities. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

Adaptation of the Children's Friendship Training Program for Children with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Laugeson, Elizabeth A.; Paley, Blair; Schonfeld, Amy M.; Carpenter, Erika M.; Frankel, Fred; O'Connor, Mary J.

2007-01-01

Previous research attests to the marked impairments in social functioning exhibited by children with Fetal Alcohol Spectrum Disorders (FASD), suggesting that such children are in need of social skills intervention. Recently, an existing evidence-based manualized behavioral treatment for improving children's friendships was implemented and…

Supporting Individuals with Fetal Alcohol Spectrum Disorders:a Summary of Effective Practices

ERIC Educational Resources Information Center

Riggie, Jennifer; Xu, Tingting

2013-01-01

Fetal alcohol spectrum disorder (FASD) is a lifelong condition that significantly affects the individual's learning, development, behavior, family, and quality of life. Diagnosing children with this condition and providing effective supports is challenging for professionals because little intervention research has been performed with the…

Alaska Native Education: Issues in the Nineties. Alaska Native Policy Papers.

ERIC Educational Resources Information Center

Kleinfeld, Judith

This booklet identifies several crucial problems in Alaska Native education, for example: (1) Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) occur in Alaska Native populations at relatively high rates and can produce mental retardation, hyperactivity, attention deficits, and learning disabilities; (2) while many Native rural school…

Fetal Alcohol Syndrome Resource Guide.

ERIC Educational Resources Information Center

All Indian Pueblo Council, Albuquerque, NM.

The guide was developed to assist professionals working with American Indian people as a resource in obtaining printed and non-printed materials on Fetal Alcohol Syndrome. The resource guide is divided into the following sections: films (4), books (5), bibliographies (2), pamphlets (16), posters (5), slides (2), training curriculum (3), and…

Fetal Alcohol Syndrome and the Developing Socio-Emotional Brain

ERIC Educational Resources Information Center

Niccols, Alison

2007-01-01

Fetal alcohol syndrome (FAS) is currently recognized as the most common known cause of mental retardation, affecting from 1 to 7 per 1000 live-born infants. Individuals with FAS suffer from changes in brain structure, cognitive impairments, and behavior problems. Researchers investigating neuropsychological functioning have identified deficits in…

Fetal Alcohol Syndrome Resource Guide.

ERIC Educational Resources Information Center

Snyder, Lisa

This resource guide provides information on programs, publications, organizations, and other resources related to prevention of fetal alcohol syndrome (FAS). The purpose of this guide is to assist health care providers to comply with Indian Health Service (IHS) FAS goals and objectives. It gives examples of community approaches to FAS prevention,…

Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain.

PubMed

Creeley, Catherine E; Dikranian, Krikor T; Johnson, Stephen A; Farber, Nuri B; Olney, John W

2013-06-12

In utero exposure of the fetal non-human primate (NHP) brain to alcohol on a single occasion during early or late third-trimester gestation triggers widespread acute apoptotic death of cells in both gray and white matter (WM) regions of the fetal brain. In a prior publication, we documented that the dying gray matter cells are neurons, and described the regional distribution and magnitude of this cell death response. Here, we present new findings regarding the magnitude, identity and maturational status of the dying WM cells in these alcohol-exposed fetal NHP brains. Our findings document that the dying WM cells belong to the oligodendrocyte (OL) lineage. OLs become vulnerable when they are just beginning to generate myelin basic protein in preparation for myelinating axons, and they remain vulnerable throughout later stages of myelination. We found no evidence linking astrocytes, microglia or OL progenitors to this WM cell death response. The mean density (profiles per mm3) of dying WM cells in alcohol-exposed brains was 12.7 times higher than the mean density of WM cells dying by natural apoptosis in drug-naive control brains. In utero exposure of the fetal NHP brain to alcohol on a single occasion triggers widespread acute apoptotic death of neurons (previous study) and of OLs (present study) throughout WM regions of the developing brain. The rate of OL apoptosis in alcohol-exposed brains was 12.7 times higher than the natural OL apoptosis rate. OLs become sensitive to the apoptogenic action of alcohol when they are just beginning to generate constituents of myelin in their cytoplasm, and they remain vulnerable throughout later stages of myelination. There is growing evidence for a similar apoptotic response of both neurons and OLs following exposure of the developing brain to anesthetic and anticonvulsant drugs. Collectively, this body of evidence raises important questions regarding the role that neuro and oligo apoptosis may play in the human condition known as fetal alcohol spectrum disorder (FASD), and also poses a question whether other apoptogenic drugs, although long considered safe for pediatric/obstetric use, may have the potential to cause iatrogenic FASD-like developmental disability syndromes.

Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets

PubMed Central

Krahe, Thomas E.; Filgueiras, Claudio C.; Medina, Alexandre E.

2017-01-01

Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively. Altered social behavior is a hallmark of both these conditions and there is ample evidence showing that developmental exposure to alcohol and VPA affect social behavior in rodents. However, results from rodent models are somewhat difficult to translate to humans owing to the substantial differences in brain development, morphology, and connectivity. Since the cortex folding pattern is closely related to its specialization and that social behavior is strongly influenced by cortical structures, here we studied the effects of developmental alcohol and VPA exposure on the play behavior of the ferret, a gyrencephalic animal known for its playful nature. Animals were injected with alcohol (3.5 g/kg, i.p.), VPA (200 mg/kg, i.p.) or saline (i.p) every other day during the brain growth spurt period, between postnatal days 10 and 30. The play behavior of pairs of the same experimental group was evaluated 3 weeks later. Both treatments induced significant behavioral differences compared to controls. Alcohol and VPA exposed ferrets played less than saline treated ones, but while animals from the alcohol group displayed a delay in start playing with each other, VPA treated ones spent most of the time close to one another without playing. These findings not only extend previous results on the effects of developmental exposure to alcohol and VPA on social behavior, but make the ferret a great model to study the underlying mechanisms of social interaction. PMID:27208641

Fetal alcohol effects in alcoholic veteran patients.

PubMed

Tishler, P V; Henschel, C E; Ngo, T A; Walters, E E; Worobec, T G

1998-11-01

Fetal alcohol syndrome is often associated with severe physical and neuropsychiatric maldevelopment. On the other hand, some offspring of women who drank during pregnancy appear to be affected in minimal ways and function relatively well within society. We questioned whether this effect of prenatal alcohol in the adult is generally minimal. To bear on this, we determined whether we could distinguish alcohol-exposed from nonexposed individuals in a population of male veterans, selected because of both their accepted level of function within society (e.g., honorable discharge from the military) and their admission to an alcohol treatment unit (thus, a greater likelihood of parental alcoholism, because of its familial aggregation). Consecutively admitted alcoholics (cases; n = 77) with likely maternal alcohol ingestion during their pregnancy or the first 10 years of life were matched with alcoholics with no maternal alcohol exposure during these periods (controls; n = 161). Each subject completed questionnaires regarding personal birthweight, alcohol, drug, educational and work histories, and family (including parental) alcohol and drug histories. We measured height, weight, and head circumference; checked for facial and hand anomalies; and took a frontal facial photograph, from which measurements of features were made. Data were analyzed by univariate statistics and stepwise logistic regression. No case had bona fide fetal alcohol syndrome. With univariate statistical analyses, the cases differed from the controls in 10 variables, including duration of drinking, width of alae nasae, being hyperactive or having a short attention span, and being small at birth. By stepwise logistic regression, the variables marital status, small size at birth, duration of drinking, and the presence of a smooth philtrum were marginally (the first two) or definitely (the last two) significant predictors of case status. Analysis of only the 37 cases in whom maternal prenatal drinking was the most likely yielded a marginal association for small size at birth (odds ratio = 3.1, p = 0.08) and a significant association for the presence of a smooth philtrum (odds ratio = 11.9, p = 0.005). Predictability was poor in all regression models. Based on the presence of this single physical finding (smooth philtrum), we estimate that the prevalence of manifestations of fetal alcohol exposure (fetal alcohol effects) is 6 to 13% in adult male veteran children (not necessarily nonveteran offspring) of women who drank alcohol during pregnancy. Thus, in our study of adult veterans, most individuals who were born to women who drank during pregnancy could not be differentiated from normal individuals, and those who were affected were distinguished by a single, nonspecific physical finding.

Fantastic Antone Succeeds! Experiences in Educating Children with Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Kleinfeld, Judith, Ed.; Wescott, Siobhan, Ed.

Three themes run through the accounts of parents and teachers as they relate their experiences rearing and teaching children with fetal alcohol syndrome (FAS): (1) Children with FAS can achieve far more than current negative stereotypes suggest; (2) Early intervention and excellent family care make an enormous difference to the success and…

Children and Youth with Fetal Alcohol Spectrum Disorders: Summary of Intervention Recommendations after Clinical Diagnosis

ERIC Educational Resources Information Center

Jirikowic, Tracy; Gelo, Julie; Astley, Susan

2010-01-01

Children with fetal alcohol spectrum disorders (FASDs) present with a wide range of developmental disabilities; however, clinical standards of care after a diagnosis are not well established. This retrospective review summarizes the types of intervention recommendations generated by an interdisciplinary FASD diagnostic team for 120 children ages…

Is There Evidence To Show That Fetal Alcohol Syndrome Can Be Prevented?

ERIC Educational Resources Information Center

Murphy-Brennan, Majella G.; Oei, Tian P. S.

1999-01-01

Reviews the effectiveness of prevention programs in reducing Fetal Alcohol Syndrome (FAS). Results reveal that prevention programs, to date, have been successful in raising awareness of FAS; however this awareness has not been translated into behavioral changes in high-risk drinkers as consumption levels in this group have increased. (Author/MKA)

Educators' Relational Experiences with Learners Identified with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Van Schalkwyk, Izanette; Marais, Sandra

2017-01-01

The focus of this research is educators' relational experiences with learners presumed to have Fetal Alcohol Spectrum Disorder (FASD) in a South African school community. Although relational interaction (usually seen as trusting and caring) is an integral aspect of the learning environment, relational functioning within this context is seriously…

Support for Native Americans with Developmental Disabilities.

ERIC Educational Resources Information Center

Goodman, Wylie; Rife, Christine

This report addresses the high incidence of fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE) among Native Americans and suggests that there is a lack of comprehensive effort to provide outreach services to the Native American population in Illinois. The report begins with an overview of American Indian history and the migration of…

Students with Fetal Alcohol Syndrome Participating in Recess

ERIC Educational Resources Information Center

Scheel, Rebecca; Lucas, Matthew D.

2011-01-01

For the student with Fetal Alcohol Syndrome (FAS), participation in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with FAS and present basic solutions to improve the experience of these students in the recess setting. Initially, the definition and…

Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2007

2007-01-01

"Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

Diagnosing moral disorder: the discovery and evolution of fetal alcohol syndrome.

PubMed

Armstrong, E M

1998-12-01

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.

Use of chaos theory and complex systems modeling to study alcohol effects on fetal condition.

PubMed

Mehl, L E; Manchanda, S

1993-10-01

A systems dynamics computer model to predict birth complications for individual pregnant woman was developed from prospectively conducted data on a database of 125 pregnant women. The model is based upon nonlinear mathematics derived from the study of chaos and complex systems. The model was then tested prospectively on 27 additional pregnant women, making predictions on their level of obstetrical risk. The model was refined until it correctly predicted the outcomes of all 125 cases in the development database. Prediction was made with an accuracy of 25/27 cases for the prospective test cases. Predictions were made for fetal condition at birth, presence or absence of operative delivery, and presence or absence of uterine dysfunction. Then the model was used to explore alcohol use during pregnancy. A reasonable spread of alcohol use existed among subjects, allowing consideration of alcohol effects. Alcohol was found to have differential effects on fetal condition at birth depending upon the presence or absence of high levels of psychosocial stress and the use of other substances. In all cases, the effect of alcohol was only evident after the 10 drinks per week level was reached. For the high-stress/one other substance group, there could be an 18-fold effect on fetal condition at birth. For the low-stress/one other substance group, the effect was only 3-fold, and for the alcohol alone group, the effect was negligible.

Toxicology screen

MedlinePlus

... Analgesics - screen; Antidepressants - screen; Narcotics - screen; Phenothiazines - screen; Drug abuse screen; Blood alcohol test ... poisoning) Complicated alcohol abstinence (delirium tremens) Delirium ... Fetal alcohol syndrome Intentional overdose Seizures Stroke ...

Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro-RNA (miR-26b) in a mouse model of fetal alcohol spectrum disorders.

PubMed

Stringer, Randa L; Laufer, Benjamin I; Kleiber, Morgan L; Singh, Shiva M

2013-08-02

Prenatal alcohol exposure is known to result in fetal alcohol spectrum disorders, a continuum of physiological, behavioural, and cognitive phenotypes that include increased risk for anxiety and learning-associated disorders. Prenatal alcohol exposure results in life-long disorders that may manifest in part through the induction of long-term gene expression changes, potentially maintained through epigenetic mechanisms. Here we report a decrease in the expression of Canabinoid receptor 1 (Cnr1) and an increase in the expression of the regulatory microRNA miR-26b in the brains of adult mice exposed to ethanol during neurodevelopment. Furthermore, we show that miR-26b has significant complementarity to the 3'-UTR of the Cnr1 transcript, giving it the potential to bind and reduce the level of Cnr1 expression. These findings elucidate a mechanism through which some genes show long-term altered expression following prenatal alcohol exposure, leading to persistent alterations to cognitive function and behavioural phenotypes observed in fetal alcohol spectrum disorders.

National Institute on Alcohol Abuse and Alcoholism and the study of fetal alcohol spectrum disorders. The International Consortium.

PubMed

Calhoun, Faye; Attilia, Maria Luisa; Spagnolo, Primavera Alessandra; Rotondo, Claudia; Mancinelli, Rosanna; Ceccanti, Mauro

2006-01-01

Fetal alcohol syndrome (FAS) is a large and rapidly increasing public health problem worldwide. Aside the full-blown FAS, multiple terms are used to describe the continuum of effects that result from prenatal exposure to alcohol, including the whole fetal alcohol spectrum disorders (FASD). The revised Institute of Medicine (IOM) Diagnostic Classification System and the diagnostic criteria for FAS and FASD are reported, as well as the formation of the four-state FAS International Consortium and its aims, as the development of an information base that systematizes data collection that helps to determine at-high-risk populations, and to implement and test a scientific-based prevention/intervention model for at risk women. The Consortium was further enlarged, with the inclusion of some more states (including Italy), leading to the formation of the International Consortium for the Investigation of FASD. The objectives of the Consortium are reported, as well as its previous activities, the South Africa and Italy Projects (active case ascertainment initiatives), and its future activities.

Male germline transmits fetal alcohol epigenetic marks for multiple generations: a review.

PubMed

Sarkar, Dipak K

2016-01-01

Alcohol exposure during fetal and early postnatal development can lead to an increased incidence of later life adult-onset diseases. Examples include central nervous system dysfunction, depression, anxiety, hyperactivity, and an inability to deal with stressful situations, increased infection and cancer. Direct effects of alcohol leading to developmental abnormalities often involve epigenetic modifications of genes that regulate cellular functions. Epigenetic marks carried over from the parents are known to undergo molecular programming events that happen early in embryonic development by a wave of DNA demethylation, which leaves the embryo with a fresh genomic composition. The proopiomelanocortin (Pomc) gene controls neuroendocrine-immune functions and is imprinted by fetal alcohol exposure. Recently, this gene has been shown to be hypermethylated through three generations. Additionally, the alcohol epigenetic marks on the Pomc gene are maintained in the male but not in the female germline during this transgenerational transmission. These data suggest that the male-specific chromosome might be involved in transmitting alcohol epigenetic marks through multiple generations. © 2015 Society for the Study of Addiction.

Nutrition Implications for Fetal Alcohol Spectrum Disorder12

PubMed Central

Young, Jennifer K.; Giesbrecht, Heather E.; Eskin, Michael N.; Aliani, Michel; Suh, Miyoung

2014-01-01

Prenatal alcohol exposure produces a multitude of detrimental alcohol-induced defects in children collectively known as fetal alcohol spectrum disorder (FASD). Children with FASD often exhibit delayed or abnormal mental, neural, and physical growth. Socioeconomic status, race, genetics, parity, gravidity, age, smoking, and alcohol consumption patterns are all factors that may influence FASD. Optimal maternal nutritional status is of utmost importance for proper fetal development, yet is often altered with alcohol consumption. It is critical to determine a means to resolve and reduce the physical and neurological malformations that develop in the fetus as a result of prenatal alcohol exposure. Because there is a lack of information on the role of nutrients and prenatal nutrition interventions for FASD, the focus of this review is to provide an overview of nutrients (vitamin A, docosahexaenoic acid, folic acid, zinc, choline, vitamin E, and selenium) that may prevent or alleviate the development of FASD. Results from various nutrient supplementation studies in animal models and FASD-related research conducted in humans provide insight into the plausibility of prenatal nutrition interventions for FASD. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of multiple-nutrient supplementation. PMID:25398731

Proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group

PubMed Central

Bonthius, Daniel J.; Olson, Heather Carmichael; Thomas, Jennifer D.

2007-01-01

This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005–2006 FASDSG officers, Daniel J. Bonthius (president), Heather Carmichael Olson (vice-president), and Jennifer Thomas (secretary-treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology. PMID:17157721

Biobehavioral Markers of Adverse Effect in Fetal Alcohol Spectrum Disorders

PubMed Central

Jacobson, Sandra W.; Jacobson, Joseph L.; Stanton, Mark E.; Meintjes, Ernesta M.; Molteno, Christopher D.

2011-01-01

Identification of children with fetal alcohol spectrum disorders (FASD) is difficult because information regarding prenatal exposure is often lacking, a large proportion of affected children do not exhibit facial anomalies, and no distinctive behavioral phenotype has been identified. Castellanos and Tannock have advocated going beyond descriptive symptom-based approaches to diagnosis to identify biomarkers derived from cognitive neuroscience. Classical eyeblink conditioning and magnitude comparison are particularly promising biobehavioral markers of FASD—eyeblink conditioning because a deficit in this elemental form of learning characterizes a very large proportion of alcohol-exposed children; magnitude comparison because it is a domain of higher order cognitive function that is among the most sensitive to fetal alcohol exposure. Because the neural circuitry mediating both these biobehavioral markers is well understood, they have considerable potential for advancing understanding of the pathophysiology of FASD, which can contribute to development of treatments targeted to the specific deficits that characterize this disorder. PMID:21541763

Fetal and infantile alcohol-mediated associative learning in the rat.

PubMed

Abate, P; Spear And, N E; Molina, J C

2001-07-01

Infant rats express conditioned responses to an odor experienced prenatally as a chemosensory cue associated with moderate alcohol intoxication. This study examined postnatal intake of a chemosensory cue (cineole) that had been paired with alcohol's unconditioned effects. It also tested the interaction between prenatal association and postnatal conditioning with cineole and alcohol. Pregnant female rats intubated with cineole were given ethanol (EtOH).25 or 4.0 hr later. Other groups received only water or water paired with ethanol. During postnatal day 15 (PD15), infant consumption of cineole solution was assessed. After the cineole drinking test, pups were intubated with EtOH or water to assess infant conditioning. On PD16, all pups were tested for mouthing to milk alone or to a milk-cineole solution. Statistical analysis confirmed fetal associative conditioning attributable to the unconditioned effects of prenatal alcohol. Fetuses given explicit pairings of cineole and alcohol ingested less cineole on PD15 than control fetuses given a 4-hr interval between cineole and alcohol. On PD16, consumption of cineole was significantly increased by prenatal exposure to cineole. Teratogenic effects of this dose of prenatal alcohol did not affect postnatal associative or nonassociative behavior. Prenatal associative learning can be established through temporal contiguity between fetal chemosensory stimulation and alcohol's unconditioned properties. This associative memory survives to infancy and modulates intake patterns and behavioral reactivity to substances that were prenatally paired with alcohol intoxication.

Instructional Tips: Supporting the Educational Needs of Students with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Ryan, Susan Marie

2006-01-01

The Center on Disease Control, Substance Abuse and Mental Health Administration (2005) identified the prevalence of Fetal Alcohol Spectrum Disorders (FASD) as being 10 per 1,000. The Substance Abuse and Mental Health Services Administration (SAMHSA) has further explained (2005) that FASD now outranks autism and Down syndrome in prevalence.…

Intervention Strategies for School Age Children.

ERIC Educational Resources Information Center

D'Entremont, Denise Morel

Fetal Alcohol Syndrome (FAS) is a relatively new diagnostic label. As more physicians become familiar with the diagnosis of this syndrome, schools will begin to see children with the label FAS and Fetal Alcohol Effects (FAE). Children with FAS often do not pick up skills from their environment as easily as some of their peers. They often need to…

Educating Children and Young People with Fetal Alcohol Spectrum Disorders: Constructing Personalised Pathways to Learning

ERIC Educational Resources Information Center

Blackburn, Carolyn; Carpenter, Barry; Egerton, Jo

2012-01-01

The range of learning difficulties associated with children and young people who have Fetal Alcohol Spectrum Disorders (FASD) has been highlighted as an emerging but little understood area of Special Educational Needs. This engaging, timely and highly practical book will raise awareness about FASD and its associated difficulties across the entire…

Exploring the Utility of Narrative Analysis in Diagnostic Decision Making: Picture-Bound Reference, Elaboration, and Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Thorne, John C.; Coggins, Truman E.; Olson, Heather Carmichael; Astley, Susan J.

2007-01-01

Purpose: To evaluate classification accuracy and clinical feasibility of a narrative analysis tool for identifying children with a fetal alcohol spectrum disorder (FASD). Method: Picture-elicited narratives generated by 16 age-matched pairs of school-aged children (FASD vs. typical development [TD]) were coded for semantic elaboration and…

Educational Advocacy among Adoptive Parents of Adolescents with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Duquette, Cheryll Ann; Stodel, Emma J.; Fullarton, Stephanie; Hagglund, Karras

2012-01-01

The purpose of this qualitative study was to examine the educational advocacy experiences of 36 adoptive parents of adolescents and young adults with fetal alcohol spectrum disorder (FASD). The participants responded to a questionnaire and 29 of them also engaged in an in-depth individual interview. Data were analysed inductively. Emerging from…

The Relation between Mathematics and Working Memory in Young Children with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Rasmussen, Carmen; Bisanz, Jeffrey

2011-01-01

The goal of this study was to examine the relation between mathematics and working memory in young children with Fetal Alcohol Spectrum Disorders (FASD). Children with FASD and comparison children (4 to 6 years old) completed standardized tests of mathematics and working memory. Children with FASD showed impairments on mathematics (applied…

Special Education of Children with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Popova, Svetlana; Lange, Shannon; Burd, Larry; Nam, Seungree; Rehm, Jürgen

2016-01-01

The current study aimed to estimate the cost associated with special education among children (5 to 14 years) with Fetal Alcohol Spectrum Disorder (FASD) in elementary and middle school by sex, age group, and province and territory in Canada. It was estimated that there were 6,520 students with FASD receiving special education in Canada in…

Inclusion for Students with Fetal Alcohol Syndrome: Classroom Teachers Talk about Practice

ERIC Educational Resources Information Center

Dybdahl, Claudia S.; Ryan, Susan

2009-01-01

The authors aimed to investigate the perceptions and experiences of regular education classroom teachers whose students included at least 1 child diagnosed with fetal alcohol spectrum (FAS) disorders. The authors collected data over a 3-year period in 3 school districts in the Pacific Northwest. Data included interviews with classroom teachers,…

A Sourcebook of Successful School-based Strategies for Fetal Alcohol and Drug-Affected Students.

ERIC Educational Resources Information Center

Osborne, Jan, Comp.

This publication's instructional strategies were collected over a three-year period from participants in a series of workshops which dealt with fetal alcohol and other drug-affected children in the educational setting. These strategies are not intended to be all inclusive; rather, they are intended to celebrate the "wisdom of practice."…

Resilience in the Face of Adversity: Stories from Adults with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Knorr, Lyndsay; McIntyre, Laureen J.

2016-01-01

This study explored the school and life experiences of four adults diagnosed with a fetal alcohol spectrum disorder (FASD) from an urban area in western Canada. Semi-structured interviews provided insight into the lives of these adults, including their experiences with this disorder as it related to their social interactions and peer relationships…

[Caregiver Stress in Foster and Adoptive Parents of Children with Fetal Alcohol Spectrum Disorders].

PubMed

Sarimski, Klaus

2014-01-01

Caregiver Stress in Foster and Adoptive Parents of Children with Fetal Alcohol Spectrum Disorders. Foster and adoptive parents of 71 children with fetal alcohol syndrome (FAS) report on developmental and behavioral characteristics, family stress, coping resources and their satisfaction with support. The data reveal an elevated rate of social and emotional problems in the children. In spite positive individual and social resources, the foster and adoptive parents feel a high level of caregiver stress. 30 % of them rate the support they receive from pediatric, therapeutic or educational services as lower than expected. Specifically, they miss early information on the diagnosis, professional knowledge and support for the special challenges of education and managing behavioral problems in their collaboration with social support agencies.

Animal Models of Fetal Alcohol Spectrum Disorders: Impact of the Social Environment

PubMed Central

Kelly, Sandra J.; Goodlett, Charles R.; Hannigan, John H.

2013-01-01

Animal models of fetal alcohol spectrum disorder (FASD) have been used to demonstrate the specificity of alcohol’s teratogenic effects and some of the underlying changes in the central nervous system (CNS) and, more recently, to explore ways to ameliorate the effects of alcohol. The main point of this review is to highlight research findings from the animal literature which point to the impact of the social context or social behavior on the effect(s) of alcohol exposure during development, and also to point to research questions about the social environment and effects of prenatal alcohol exposure that remain to be answered. Alcohol exposure during early development alters maternal responding to the exposed pup in a variety of ways and the alteration in maternal responding could alter later stress responsivity and adult maternal and social behavior of the exposed offspring. Environmental enrichment and voluntary exercise have been shown to ameliorate some of alcohol’s impact during development, but the roles of enhanced social interactions in the case of enrichment and of social housing during voluntary exercise need to be more fully delineated. Similarly, the role of social context across the lifespan, such as social housing, social experiences, and contact with siblings, needs further study. Because of findings that alcohol during development alters DNA methylation patterns and that there are alterations in the maternal care of the alcohol-exposed offspring, epigenetic effects and their relationship to social behavior in animal models of FASD are likely to become a fruitful area of research. Because of the simpler social behavior and the short lifespan of rodents, animal models of FASD can be useful in determining how the social context impacts the effects of alcohol exposure during development. PMID:19731387

CDC Vital Signs: Alcohol and Pregnancy

MedlinePlus

... prematurity, and sudden infant death syndrome (SIDS). Doctors, nurses, or other health professionals can help prevent alcohol ... Fetal Alcohol Spectrum Disorders Toolkit American College of Nurse-Midwives – Alcohol and Pregnancy The Arc’s FASD Prevention ...

Alcohol Use During Pregnancy in a South African Community: Reconciling Knowledge, Norms, and Personal Experience.

PubMed

Watt, Melissa H; Eaton, Lisa A; Dennis, Alexis C; Choi, Karmel W; Kalichman, Seth C; Skinner, Donald; Sikkema, Kathleen J

2016-01-01

Due to high rates of fetal alcohol spectrum disorder (FASD) in South Africa, reducing alcohol use during pregnancy is a pressing public health priority. The aim of this study was to qualitatively explore knowledge and attitudes about maternal alcohol consumption among women who reported alcohol use during pregnancy. The study was conducted in Cape Town, South Africa. Participants were pregnant or within 1 year postpartum and self-reported alcohol use during pregnancy. In-depth interviews explored personal experiences with drinking during pregnancy, community norms and attitudes towards maternal drinking, and knowledge about FASD. Transcripts were analyzed using a content analytic approach, including narrative memos and data display matrices. Interviews revealed competing attitudes. Women received anti-drinking messages from several sources, but these sources were not highly valued and the messages often contradicted social norms. Women were largely unfamiliar with FASD, and their knowledge of impacts of fetal alcohol exposure was often inaccurate. Participants' personal experiences influenced their attitudes about the effects of alcohol during pregnancy, which led to internalization of misinformation. The data revealed a moral conflict that confronted women in this setting, leaving women feeling judged, ambivalent, or defensive about their behaviors, and ultimately creating uncertainty about their alcohol use behaviors. Data revealed the need to deliver accurate information about the harms of fetal alcohol exposure through sources perceived as trusted and reliable. Individual-level interventions to help women reconcile competing attitudes and identify motivations for reducing alcohol use during pregnancy would be beneficial.

A Review of the History of Attitudes Toward Drinking in Pregnancy.

PubMed

Warren, Kenneth R

2015-07-01

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. Historical review of events primarily in the U.S. federal government, found in referenced documents. 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. 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. Copyright © 2015 by the Research Society on Alcoholism.

Neuroimaging effects of prenatal alcohol exposure on the developing human brain: a magnetic resonance imaging review.

PubMed

Donald, Kirsten Ann; Eastman, Emma; Howells, Fleur Margaret; Adnams, Colleen; Riley, Edward Patrick; Woods, Roger Paul; Narr, Katherine Louise; Stein, Dan Joseph

2015-10-01

This paper reviews the magnetic resonance imaging (MRI) literature on the effects of prenatal alcohol exposure on the developing human brain. A literature search was conducted through the following databases: PubMed, PsycINFO and Google Scholar. Combinations of the following search terms and keywords were used to identify relevant studies: 'alcohol', 'fetal alcohol spectrum disorders', 'fetal alcohol syndrome', 'FAS', 'FASD', 'MRI', 'DTI', 'MRS', 'neuroimaging', 'children' and 'infants'. A total of 64 relevant articles were identified across all modalities. Overall, studies reported smaller total brain volume as well as smaller volume of both the white and grey matter in specific cortical regions. The most consistently reported structural MRI findings were alterations in the shape and volume of the corpus callosum, as well as smaller volume in the basal ganglia and hippocampi. The most consistent finding from diffusion tensor imaging studies was lower fractional anisotropy in the corpus callosum. Proton magnetic resonance spectroscopy studies are few to date, but showed altered neurometabolic profiles in the frontal and parietal cortex, thalamus and dentate nuclei. Resting-state functional MRI studies reported reduced functional connectivity between cortical and deep grey matter structures. Discussion There is a critical gap in the literature of MRI studies in alcohol-exposed children under 5 years of age across all MRI modalities. The dynamic nature of brain maturation and appreciation of the effects of alcohol exposure on the developing trajectory of the structural and functional network argue for the prioritisation of studies that include a longitudinal approach to understanding this spectrum of effects and potential therapeutic time points.

Fetal Alcohol Spectrum Disorders (FASDs): Alcohol Use Quiz

MedlinePlus

... Data & Statistics State-Level Estimates 2016 Research & Tracking Monitoring Alcohol Use International Research Training & Education Online Training Past Activities Articles & Key Findings Materials & Multimedia Fact Sheets & Brochures ...

Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder. Part I: A Comparison of Parenting Stress

ERIC Educational Resources Information Center

Watson, Shelley L.; Coons, Kelly D.; Hayes, Stephanie A.

2013-01-01

Background: There is a long history of research on parents of children with disabilities, but to the authors' knowledge, no study has compared the stress of parents of children with fetal alcohol spectrum disorder (FASD) to parents of children with autism spectrum disorder (ASD). Method: Twenty-five parents of children with ASD and 25 parents of…

Enhancing Learning Environments for Students Affected by Fetal Alcohol Spectrum Disorders: An Exploratory Study of Canadian Pre-Service Teacher Knowledge and Conceptions

ERIC Educational Resources Information Center

Pei, Jacqueline; Job, Jenelle; Poth, Cheryl; O'Brien-Langer, Anna; Tang, Wei

2015-01-01

There is a pressing need for enhancing the learning environment for students affected by Fetal Alcohol Spectrum Disorders (FASDs). To develop relevant professional learning opportunities for teachers, a logical initial step is to explore the extent to which pre-service teachers accurately understand the unique neuropsychological functioning…

Integrating Case Topics in Medical School Curriculum to Enhance Multiple Skill Learning: Using Fetal Alcohol Spectrum Disorders as an Exemplary Case

ERIC Educational Resources Information Center

Paley, Blair; O'Connor, Mary J.; Baillie, Susan J.; Guiton, Gretchen; Stuber, Margaret L.

2009-01-01

Objectives: This article describes the use of fetal alcohol spectrum disorders (FASDs) as a theme to connect the learning of basic neurosciences with clinical applications across the age span within a systems-based, integrated curricular structure that emphasizes problem-based learning. Methods: In collaboration with the Centers for Disease…

An Evolution of Virtual Reality Training Designs for Children with Autism and Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Strickland, Dorothy C.; McAllister, David; Coles, Claire D.; Osborne, Susan

2007-01-01

This article describes an evolution of training programs to use first-person interaction in virtual reality (VR) situations to teach safety skills to children with autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD). Multiple VR programs for children aged 2 to 9 were built and tested between 1992 and 2007. Based on these…

Fetal Alcohol Syndrome: A Training Manual To Aid in Vocational Rehabilitation and Other Non-Medical Services.

ERIC Educational Resources Information Center

LaDue, Robin A.; Schacht, Robert M.; Tanner-Halverson, Patricia; McGowan, Mark

This training manual provides vocational rehabilitation and school counselors with background information and practical tools related to fetal alcohol syndrome (FAS), with particular reference to the needs of Native Americans. The most recent reliable data (1990) for American Indians and Alaska Natives show a rate of FAS over 10 times the national…

The Effect of Rehearsal Training on Working Memory Span of Children with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Loomes, Carly; Rasmussen, Carmen; Pei, Jacqueline; Manji, Shazeen; Andrew, Gail

2008-01-01

A key area of weakness in individuals with fetal alcohol spectrum disorder (FASD) is working memory, thus the goal of this study was to determine whether teaching children (aged 4-11) with FASD verbal rehearsal would increase their memory. Rehearsal training has been effective in other populations with working memory difficulties, so we…

Gene-specific of endocannabinoid receptor 1 (cnr1a) by ethanol probably leads to the development of fetal alcohol spectrum disorder (FASD) phenotypes in Japanese rice fish (Oryzias latipes) embryogenesis

USDA-ARS?s Scientific Manuscript database

Developmental ethanol exposure is able to induce Fetal Alcohol Spectrum Disorder (FASD) phenotypes in Japanese rice fish (Oryzias latipes). This study investigated possible differential expression of cannabinoid receptor (cnr) mRNAs during Japanese rice fish embryogenesis and variability to ethanol-...

Variability in Classroom Social Communication: Performance of Children with Fetal Alcohol Spectrum Disorders and Typically Developing Peers

ERIC Educational Resources Information Center

Kjellmer, Liselotte; Olswang, Lesley B.

2013-01-01

Purpose: In this study, the authors examined how variability in classroom social communication performance differed between children with fetal alcohol spectrum disorders (FASD) and pair-matched, typically developing peers. Method: Twelve pairs of children were observed in their classrooms, 40 min per day (20 min per child) for 4 days over a…

Observation of Classroom Social Communication: Do Children with Fetal Alcohol Spectrum Disorders Spend Their Time Differently than Their Typically Developing Peers?

ERIC Educational Resources Information Center

Olswang, Lesley B.; Svensson, Liselotte; Astley, Susan

2010-01-01

Purpose: In this research, the authors examined how social communication profiles during classroom activities differed between children with fetal alcohol spectrum disorders (FASD) and typically developing pair-matched peers. Method: Twelve pairs of children were observed in their classrooms 20 min a day for 4 days across 2 weeks. Coders…

Neuropharmacology of drugs and alcohol in mother and fetus.

PubMed

Pollard, Irina

2007-04-01

Epidemiological evidence suggests that an adverse prenatal environment can have profound long-term health consequences throughout postnatal life. This chapter discusses the underlying mechanisms implicated in the consumption of mood-altering recreational drugs and teratogenicity in the fetus. The way metabolic parameters in pregnancy influence the pharmacokinetic characteristics of drugs and alcohol and the developmental stage of neurotoxicity are reviewed. The general underlying mechanisms that link multifaceted interactions between drug characteristics, gene polymorphisms, dietary deficiencies, changed endocrine indices and fetal programming are outlined, with specific examples throughout the text. As developmental injury is of significant social concern, the final section questions whether society provides adequate support for making appropriate and informed lifestyle choices to alleviate preventable transgenerational harm.

Computer-Aided Recognition of Facial Attributes for Fetal Alcohol Spectrum Disorders.

PubMed

Valentine, Matthew; Bihm, Dustin C J; Wolf, Lior; Hoyme, H Eugene; May, Philip A; Buckley, David; Kalberg, Wendy; Abdul-Rahman, Omar A

2017-12-01

To compare the detection of facial attributes by computer-based facial recognition software of 2-D images against standard, manual examination in fetal alcohol spectrum disorders (FASD). Participants were gathered from the Fetal Alcohol Syndrome Epidemiology Research database. Standard frontal and oblique photographs of children were obtained during a manual, in-person dysmorphology assessment. Images were submitted for facial analysis conducted by the facial dysmorphology novel analysis technology (an automated system), which assesses ratios of measurements between various facial landmarks to determine the presence of dysmorphic features. Manual blinded dysmorphology assessments were compared with those obtained via the computer-aided system. Areas under the curve values for individual receiver-operating characteristic curves revealed the computer-aided system (0.88 ± 0.02) to be comparable to the manual method (0.86 ± 0.03) in detecting patients with FASD. Interestingly, cases of alcohol-related neurodevelopmental disorder (ARND) were identified more efficiently by the computer-aided system (0.84 ± 0.07) in comparison to the manual method (0.74 ± 0.04). A facial gestalt analysis of patients with ARND also identified more generalized facial findings compared to the cardinal facial features seen in more severe forms of FASD. We found there was an increased diagnostic accuracy for ARND via our computer-aided method. As this category has been historically difficult to diagnose, we believe our experiment demonstrates that facial dysmorphology novel analysis technology can potentially improve ARND diagnosis by introducing a standardized metric for recognizing FASD-associated facial anomalies. Earlier recognition of these patients will lead to earlier intervention with improved patient outcomes. Copyright © 2017 by the American Academy of Pediatrics.

Fetal alcohol spectrum disorders: from research to policy.

PubMed

Thomas, Jennifer D; Warren, Kenneth R; Hewitt, Brenda G

2010-01-01

Forty years ago, alcohol was not commonly recognized as a teratogen, an agent that can disrupt the development of a fetus. Today, we understand that prenatal alcohol exposure induces a variety of adverse effects on physical, neurological, and behavioral development. Research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has contributed to the identification of the range and prevalence of fetal alcohol spectrum disorders (FASD), as well as methods for prevention and treatment of FASD. The worldwide prevalence and high personal and societal costs of FASD speak to the importance of this research. This article briefly examines some of the ways that NIAAA has contributed to our understanding of FASD, the challenges that we still face, and how this research is translated into changes in public policy.

Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro-RNA (miR-26b) in a mouse model of fetal alcohol spectrum disorders

PubMed Central

2013-01-01

Background Prenatal alcohol exposure is known to result in fetal alcohol spectrum disorders, a continuum of physiological, behavioural, and cognitive phenotypes that include increased risk for anxiety and learning-associated disorders. Prenatal alcohol exposure results in life-long disorders that may manifest in part through the induction of long-term gene expression changes, potentially maintained through epigenetic mechanisms. Findings Here we report a decrease in the expression of Canabinoid receptor 1 (Cnr1) and an increase in the expression of the regulatory microRNA miR-26b in the brains of adult mice exposed to ethanol during neurodevelopment. Furthermore, we show that miR-26b has significant complementarity to the 3’-UTR of the Cnr1 transcript, giving it the potential to bind and reduce the level of Cnr1 expression. Conclusions These findings elucidate a mechanism through which some genes show long-term altered expression following prenatal alcohol exposure, leading to persistent alterations to cognitive function and behavioural phenotypes observed in fetal alcohol spectrum disorders. PMID:23915435

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

PubMed

Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

2016-07-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by the Research Society on Alcoholism.

Diffusion Tensor Imaging in Children with Fetal Alcohol Spectrum Disorders

PubMed Central

Wozniak, Jeffrey R.; Mueller, Bryon A.; Chang, Pi-Nian; Muetzel, Ryan L.; Caros, Lydia; Lim, Kelvin O.

2010-01-01

Background Prenatal alcohol exposure, which is associated with macrostructural brain abnormalities, neurocognitive deficits, and behavioral disturbances, is characterized as fetal alcohol syndrome (FAS) in severe cases. The only published study thus far using diffusion tensor imaging (DTI) showed microstructural abnormalities in patients with FAS. The current study investigated whether similar abnormalities are present in less severely affected, prenatally exposed patients who did not display all of the typical FAS physical stigmata. Methods Subjects included 14 children, ages 10 to 13, with fetal alcohol spectrum disorders (FASD) and 13 matched controls. Cases with full-criteria FAS, mental retardation, or microcephaly were excluded. Subjects underwent MRI scans including DTI. Results Although cases with microcephaly were excluded, there was a trend toward smaller total cerebral volume in the FASD group (p = 0.057, Cohen’s d effect size = 0.73). Subjects with FASD had greater mean diffusivity (MD) in the isthmus of the corpus callosum than controls (p = 0.013, effect size = 1.05), suggesting microstructural abnormalities in this region. There were no group differences in 5 other regions of the corpus callosum. Correlations between MD in the isthmus and facial dysmorphology were nonsignificant. Conclusions These results suggest that even relatively mild forms of fetal alcohol exposure may be associated with microstructural abnormalities in the posterior corpus callosum that are detectable with DTI. PMID:17010147

Fetal alcohol syndrome

MedlinePlus

... a baby when a mother drinks alcohol during pregnancy. Causes Using alcohol during pregnancy can cause the same risks as using alcohol in general. But it poses extra risks to the unborn baby. When a pregnant woman drinks ... use during pregnancy. Larger amounts of alcohol appear to increase the ...

Fetal Alcohol Spectrum Disorders and Abnormal Neuronal Plasticity

PubMed Central

Medina, Alexandre E.

2012-01-01

The ingestion of alcohol during pregnancy can result in a group of neurobehavioral abnormalities collectively known as fetal alcohol spectrum disorders (FASD). During the past decade, studies using animal models indicated that early alcohol exposure can dramatically affect neuronal plasticity, an essential property of the central nervous system responsible for the normal wiring of the brain and involved in processes such as learning and memory. The abnormalities in neuronal plasticity caused by alcohol can explain many of the neurobehavioral deficits observed in FASD. Conversely, improving neuronal plasticity may have important therapeutic benefits. In this review, the author discuss the mechanisms that lead to these abnormalities and comment on recent pharmacological approaches that have been showing promising results in improving neuronal plasticity in FASD. PMID:21383101

Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

PubMed Central

Li, Yong; Gonzalez, Pablo; Zhang, Lubo

2012-01-01

Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

Fetal alcohol programming of hypothalamic proopiomelanocortin system by epigenetic mechanisms and later life vulnerability to stress.

PubMed

Bekdash, Rola; Zhang, Changqing; Sarkar, Dipak

2014-09-01

Hypothalamic proopiomelanocortin (POMC) neurons, one of the major regulators of the hypothalamic-pituitary-adrenal (HPA) axis, immune functions, and energy homeostasis, are vulnerable to the adverse effects of fetal alcohol exposure (FAE). These effects are manifested in POMC neurons by a decrease in Pomc gene expression, a decrement in the levels of its derived peptide β-endorphin and a dysregulation of the stress response in the adult offspring. The HPA axis is a major neuroendocrine system with pivotal physiological functions and mode of regulation. This system has been shown to be perturbed by prenatal alcohol exposure. It has been demonstrated that the perturbation of the HPA axis by FAE is long-lasting and is linked to molecular, neurophysiological, and behavioral changes in exposed individuals. Recently, we showed that the dysregulation of the POMC system function by FAE is induced by epigenetic mechanisms such as hypermethylation of Pomc gene promoter and an alteration in histone marks in POMC neurons. This developmental programming of the POMC system by FAE altered the transcriptome in POMC neurons and induced a hyperresponse to stress in adulthood. These long-lasting epigenetic changes influenced subsequent generations via the male germline. We also demonstrated that the epigenetic programming of the POMC system by FAE was reversed in adulthood with the application of the inhibitors of DNA methylation or histone modifications. Thus, prenatal environmental influences, such as alcohol exposure, could epigenetically modulate POMC neuronal circuits and function to shape adult behavioral patterns. Identifying specific epigenetic factors in hypothalamic POMC neurons that are modulated by fetal alcohol and target Pomc gene could be potentially useful for the development of new therapeutic approaches to treat stress-related diseases in patients with fetal alcohol spectrum disorders. Copyright © 2014 by the Research Society on Alcoholism.

Genetic and epigenetic insights into fetal alcohol spectrum disorders

PubMed Central

2010-01-01

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. PMID:20423530

75 FR 8726 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-25

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel, Review of Applications on Case Ascertainment to Estimate the U.S. Prevalence of Fetal Alcohol Spectrum Disorders in Young Children (U01), RFA AA-10-005...

Alcohol exposure during development: Impact on the epigenome.

PubMed

Perkins, Amy; Lehmann, Claudia; Lawrence, R Charles; Kelly, Sandra J

2013-10-01

Fetal alcohol spectrum disorders represent a wide range of symptoms associated with in utero alcohol exposure. Animal models of FASD have been useful in determining the specific neurological consequences of developmental alcohol exposure, but the mechanisms of those consequences are unclear. Long-lasting changes to the epigenome are proposed as a mechanism of alcohol-induced teratogenesis in the hippocampus. The current study utilized a three-trimester rodent model of FASD to examine changes to some of the enzymatic regulators of the epigenome in adolescence. Combined pre- and post-natal alcohol exposureresulted in a significant increase in DNA methyltransferase activity (DNMT), without affecting histone deacetylase activity (HDAC). Developmental alcohol exposure also caused a change in gene expression of regulators of the epigenome, in particular, DNMT1, DNMT3a, and methyl CpG binding protein 2 (MeCP2). The modifications of the activity and expression of epigenetic regulators in the hippocampus of rodents perinatally exposed to alcohol suggest that alcohol's impact on the epigenome and its regulators may be one of the underlying mechanisms of alcohol teratogenesis. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Oculomotor control in children with fetal alcohol spectrum disorders assessed using a mobile eye-tracking laboratory.

PubMed

Green, C R; Mihic, A M; Brien, D C; Armstrong, I T; Nikkel, S M; Stade, B C; Rasmussen, C; Munoz, D P; Reynolds, J N

2009-03-01

Prenatal exposure to alcohol can result in a spectrum of adverse developmental outcomes, collectively termed fetal alcohol spectrum disorders (FASDs). This study evaluated deficits in sensory, motor and cognitive processing in children with FASD that can be identified using eye movement testing. Our study group was composed of 89 children aged 8-15 years with a diagnosis within the FASD spectrum [i.e. fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), and alcohol-related neurodevelopmental disorder (ARND)], and 92 controls. Subjects looked either towards (prosaccade) or away from (antisaccade) a peripheral target that appeared on a computer monitor, and eye movements were recorded with a mobile, video-based eye tracker. We hypothesized that: (i) differences in the magnitude of deficits in eye movement control exist across the three diagnostic subgroups; and (ii) children with FASD display a developmental delay in oculomotor control. Children with FASD had increased saccadic reaction times (SRTs), increased intra-subject variability in SRTs, and increased direction errors in both the prosaccade and antisaccade tasks. Although development was associated with improvements across tasks, children with FASD failed to achieve age-matched control levels of performance at any of the ages tested. Moreover, children with ARND had faster SRTs and made fewer direction errors in the antisaccade task than children with pFAS or FAS, although all subgroups were different from controls. Our results demonstrate that eye tracking can be used as an objective measure of brain injury in FASD, revealing behavioral deficits in all three diagnostic subgroups independent of facial dysmorphology.

Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

PubMed

Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

2017-09-01

Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders.

PubMed

Boronat, S; Vicente, M; Lainez, E; Sánchez-Montañez, A; Vázquez, E; Mangado, L; Martínez-Ribot, L; Del Campo, M

2017-01-01

Fetal alcohol spectrum disorders (FASD) cause neurodevelopmental abnormalities. However, publications about epilepsy and electroencephalographic features are scarce. In this study, we prospectively performed electroencephalography (EEG) and brain magnetic resonance (MR) imaging in 61 patients with diagnosis of FASD. One patient had multiple febrile seizures with normal EEGs. Fourteen children showed EEG anomalies, including slow background activity and interictal epileptiform discharges, focal and/or generalized, and 3 of them had epilepsy. In one patient, seizures were first detected during the EEG recording and one case had an encephalopathy with electrical status epilepticus during slow sleep (ESES). Focal interictal discharges in our patients did not imply the presence of underlying visible focal brain lesions in the neuroimaging studies, such as cortical dysplasia or polymicrogyria. However, they had nonspecific brain MR abnormalities, including corpus callosum hypoplasia, vermis hypoplasia or cavum septum pellucidum. The latter was significantly more frequent in the group with EEG abnormal findings (p < 0.01). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Accentuate the Negative: Grammatical Errors during Narrative Production as a Clinical Marker of Central Nervous System Abnormality in School-Aged Children with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Thorne, John C.

2017-01-01

Purpose: The purpose of this study was to examine (a) whether increased grammatical error rates during a standardized narrative task are a more clinically useful marker of central nervous system abnormality in Fetal Alcohol Spectrum Disorders (FASD) than common measures of productivity or grammatical complexity and (b) whether combining the rate…

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

PubMed Central

Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth

2016-01-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

Alcohol exposure during development: Impact on the epigenome

PubMed Central

Perkins, Amy; Lehmann, Claudia; Lawrence, R. Charles; Kelly, Sandra J.

2013-01-01

Fetal Alcohol Spectrum Disorders represent a wide range of symptoms associated with in utero alcohol exposure. Animal models of FASD have been useful in determining the specific neurological consequences of developmental alcohol exposure, but the mechanisms of those consequences are unclear. Long-lasting changes to the epigenome are proposed as a mechanism of alcohol-induced teratogenesis in the hippocampus. The current study utilized a three-trimester rodent model of FASD to examine changes to some of the enzymatic regulators of the epigenome in adolescence. Combined pre- and post-natal alcohol exposure resulted in a significant increase in DNA methyltransferase activity (DNMT), without affecting histone deacetylase activity (HDAC). Developmental alcohol exposure also caused a change in gene expression of regulators of the epigenome, in particular, DNMT1, DNMT3a, and methyl CpG binding protein 2 (MeCP2). The modifications of the activity and expression of epigenetic regulators in the hippocampus of rodents perinatally exposed to alcohol suggest that alcohol’s impact on the epigenome and its regulators may be one of the underlying mechanisms of alcohol teratogenesis. PMID:23542005

Human Brain Abnormalities Associated With Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder

PubMed Central

Jarmasz, Jessica S.; Basalah, Duaa A.; Chudley, Albert E.; Del Bigio, Marc R.

2017-01-01

Abstract Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental problem, but neuropathologic descriptions are rare and focused on the extreme abnormalities. We conducted a retrospective survey (1980–2016) of autopsies on 174 individuals with prenatal alcohol exposure or an FASD diagnosis. Epidemiologic details and neuropathologic findings were categorized into 5 age groups. Alcohol exposure was difficult to quantify. When documented, almost all mothers smoked tobacco, many abused other substances, and prenatal care was poor or nonexistent. Placental abnormalities were common (68%) in fetal cases. We identified micrencephaly (brain weight <5th percentile) in 31, neural tube defects in 5, isolated hydrocephalus in 6, corpus callosum defects in 6 (including some with complex anomalies), probable prenatal ischemic lesions in 5 (excluding complications of prematurity), minor subarachnoid heterotopias in 4, holoprosencephaly in 1, lissencephaly in 1, and cardiac anomalies in 26 cases. The brain abnormalities associated with prenatal alcohol exposure are varied; cause–effect relationships cannot be determined. FASD is likely not a monotoxic disorder. The animal experimental literature, which emphasizes controlled exposure to ethanol alone, is therefore inadequate. Prevention must be the main societal goal, however, a clear understanding of the neuropathology is necessary for provision of care to individuals already affected. PMID:28859338

Fetal Alcohol Spectrum Disorders (FASDs)

MedlinePlus

... other research. DATA & STATISTICS Data and statistics highlights. Interventions CHOICES program and alcohol screening and brief intervention (SBI). EDUCATION & TRAINING Tools, training centers, & educational resources. ...

Neuropsychological comparison of alcohol-exposed children with or without physical features of fetal alcohol syndrome.

PubMed

Mattson, S N; Riley, E P; Gramling, L; Delis, D C; Jones, K L

1998-01-01

Fetal alcohol syndrome (FAS) is associated with behavioral and cognitive deficits. However, the majority of children born to alcohol-abusing women do not meet the formal criteria for FAS and it is not known if the cognitive abilities of these children differ from those of children with FAS. Using a set of neuropsychological tests, 3 groups were compared: (a) children with FAS, (b) children without FAS who were born to alcohol-abusing women (the PEA group), and (c) normal controls. The results indicated that, relative to controls, both the FAS and the PEA groups were impaired on tests of language, verbal learning and memory, academic skills, fine-motor speed, and visual-motor integration. These data suggest that heavy prenatal alcohol exposure is related to a consistent pattern of neuropsychological deficits and the degree of these deficits may be independent of the presence of physical features associated with FAS.

Native American adolescents' views of fetal alcohol syndrome prevention in schools.

PubMed

Ma, G X; Toubbeh, J; Cline, J; Chisholm, A

1998-04-01

Alcohol is the most commonly abused substance among adolescents in the United States. Adolescent females are recognized as one group at risk for giving birth to babies with fetal alcohol syndrome (FAS). Sixth through eighth grade Native Americans were surveyed about their attitudes toward and knowledge of FAS risk factors and prevention strategies. Data revealed that 52% of students drank alcohol prior to the survey. Though sexually active, students lacked knowledge about the relationship between alcohol and FAS. The study revealed 1) limited prevention programs in middle schools and 2) the most influential factor in determining attitudes and decisions about alcohol use was the immediate family. Students felt FAS prevention is an important topic in school health education, noting the important role peers play in teaching and role modeling. Various strategies incorporating music and communication technology such as videotape and computer-assisted interactive tools into prevention materials are discussed.

Mechanisms of influence: Alcohol industry submissions to the inquiry into fetal alcohol spectrum disorders.

PubMed

Avery, Michelle Rose; Droste, Nicolas; Giorgi, Caterina; Ferguson, Amy; Martino, Florentine; Coomber, Kerri; Miller, Peter

2016-11-01

Industry groups with vested interests in policy regularly work to protect their profits via the endorsement of ineffective voluntary regulation and interventions, extensive lobbying activity and minimising the health impact of consumption behaviours. This study aims to examine all alcohol industry submissions to the Australian House of Representatives Standing Committee on Social Policy and Legal Affairs into Fetal Alcohol Spectrum Disorders (FASD), to assist in understanding how those with vested interests contribute to policy development. The analysis aims to document the strategies and arguments used by alcohol industry bodies in their submissions and to compare these with known strategies of vested-interest groups. All 92 submissions to the Inquiry were screened to include only those submitted by alcohol industry bodies (five submissions). Content domains were derived based on the major themes emerging from the industry submissions and on common vested-interest behaviours identified in previous literature. The following content categories were identified: Concerns about FASD; Current industry activities and FASD prevention; Value of mandatory warning labels; and Credibility of independent public health researchers and organisations. Alcohol industry submissions sought to undermine community concern, debate the evidence, promote ineffective measure which are no threat to the profit margins and attack independent health professionals and researchers. In doing so, their behaviour is entirely consistent with their responses to other issues, such as violence and chronic health, and copies the tactics employed by the tobacco industry. [Avery MR, Droste N, Giorgi C, Ferguson A, Martino F, Coomber K, Miller P. Mechanisms of influence: Alcohol industry submissions to the inquiry into fetal alcohol spectrum disorders. Drug Alcohol Rev 2016;35:665-672]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Postnatal growth restriction and gene expression changes in a mouse model of fetal alcohol syndrome.

PubMed

Kaminen-Ahola, Nina; Ahola, Arttu; Flatscher-Bader, Traute; Wilkins, Sarah J; Anderson, Greg J; Whitelaw, Emma; Chong, Suyinn

2010-10-01

Growth restriction, craniofacial dysmorphology, and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal or postnatal, but the underlying mechanisms remain unknown.We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome (e.g., craniofacial changes and growth restriction in adolescent mice). In this study, we characterize in detail the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and by extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of nonfostered, ethanol-exposed and control mice at postnatal day 28.We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This finding suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiologic result of ethanol exposure in utero. We also find that, despite some catch-up growth after 5 weeks of age, the effect extends into adulthood, which is consistent with longitudinal studies in humans.Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis, and lipid metabolism. © 2010 Wiley-Liss, Inc.

Psychiatric Conditions Associated with Prenatal Alcohol Exposure

ERIC Educational Resources Information Center

O'Connor, Mary J.; Paley, Blair

2009-01-01

Since the identification of fetal alcohol syndrome (FAS) over 35 years ago, mounting evidence about the impact of maternal alcohol consumption during pregnancy has prompted increased attention to the link between prenatal alcohol exposure (PAE) and a constellation of developmental disabilities that are characterized by physical, cognitive, and…

Postnatal nutritional treatment of neurocognitive deficits in fetal alcohol spectrum disorder.

PubMed

Bastons-Compta, A; Astals, M; Andreu-Fernandez, V; Navarro-Tapia, E; Garcia-Algar, O

2018-04-01

Ethanol is the most important teratogen agent in humans. Prenatal alcohol exposure can lead to a wide range of adverse effects, which are broadly termed as fetal alcohol spectrum disorder (FASD). The most severe consequence of maternal alcohol abuse is the development of fetal alcohol syndrome, defined by growth retardation, facial malformations, and central nervous system impairment expressed as microcephaly and neurodevelopment abnormalities. These alterations generate a broad range of cognitive abnormalities such as learning disabilities and hyperactivity and behavioural problems. Socioeconomic status, ethnicity, differences in genetic susceptibility related to ethanol metabolism, alcohol consumption patterns, obstetric problems, and environmental influences like maternal nutrition, stress, and other co-administered drugs are all factors that may influence FASD manifestations. Recently, much attention has been paid to the role of nutrition as a protective factor against alcohol teratogenicity. There are a great number of papers related to nutritional treatment of nutritional deficits due to several factors associated with maternal consumption of alcohol and with eating and social disorders in FASD children. Although research showed the clinical benefits of nutritional interventions, most of work was in animal models, in a preclinical phase, or in the prenatal period. However, a minimum number of studies refer to postnatal nutrition treatment of neurodevelopmental deficits. Nutritional supplementation in children with FASD has a dual objective: to overcome nutritional deficiencies and to reverse or improve the cognitive deleterious effects of prenatal alcohol exposure. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of simultaneous multiple-nutrient supplementation.

Fetal Alcohol Programming of Hypothalamic Proopiomelanocortin System by Epigenetic Mechanisms and Later Life Vulnerability to Stress

PubMed Central

Bekdash, Rola; Zhang, Changqing; Sarkar, Dipak

2014-01-01

Hypothalamic proopiomelanocortin (POMC) neurons, one of the major regulators of the HPA axis, immune functions, and energy homeostasis, are vulnerable to the adverse effects of fetal alcohol exposure (FAE). These effects are manifested in POMC neurons by a decrease in Pomc gene expression, a decrement in the levels of its derived peptide β-endorphin (β-EP) and a dysregulation of the stress response in the adult offspring. The HPA axis is a major neuroendocrine system with pivotal physiological functions and mode of regulation. This system has been shown to be perturbed by prenatal alcohol exposure. It has been demonstrated that the perturbation of the HPA axis by FAE is long-lasting and is linked to molecular, neurophysiological and behavioral changes in exposed individuals. Recently, we showed that the dysregulation of the POMC system function by FAE is induced by epigenetic mechanisms such as hypermethylation of POMC gene promoter and an alteration in histone marks in POMC neurons. This developmental programming of the POMC system by FAE altered the transcriptome in POMC neurons and induced a hyperresponse to stress in adulthood. These long-lasting epigenetic changes influenced subsequent generations via the male germline. We also demonstrated that the epigenetic programming of the POMC system by FAE was reversed in adulthood with the application of the inhibitors of DNA methylation or histone modifications. Thus, prenatal environmental influences such as alcohol exposure could epigenetically modulate POMC neuronal circuits and function to shape adult behavioral patterns. Identifying specific epigenetic factors in hypothalamic POMC neurons that are modulated by fetal alcohol and target Pomc gene could be potentially useful for the development of new therapeutic approaches to treat stress-related diseases in patients with Fetal Alcohol Spectrum Disorders. PMID:25069392

Breastfeeding and maternal alcohol use: Prevalence and effects on child outcomes and fetal alcohol spectrum disorders.

PubMed

May, Philip A; Hasken, Julie M; Blankenship, Jason; Marais, Anna-Susan; Joubert, Belinda; Cloete, Marise; de Vries, Marlene M; Barnard, Ronel; Botha, Isobel; Roux, Sumien; Doms, Cate; Gossage, J Phillip; Kalberg, Wendy O; Buckley, David; Robinson, Luther K; Adnams, Colleen M; Manning, Melanie A; Parry, Charles D H; Hoyme, H Eugene; Tabachnick, Barbara; Seedat, Soraya

2016-08-01

Determine any effects that maternal alcohol consumption during the breastfeeding period has on child outcomes. Population-based samples of children with fetal alcohol spectrum disorders (FASD), normally-developing children, and their mothers were analyzed for differences in child outcomes. Ninety percent (90%) of mothers breastfed for an average of 19.9 months. Of mothers who drank postpartum and breastfed (MDPB), 47% breastfed for 12 months or more. In case control analyses, children of MDPB were significantly lighter, had lower verbal IQ scores, and more anomalies in comparisons controlling for prenatal alcohol exposure and final FASD diagnosis. Utilizing a stepwise logistic regression model adjusting for nine confounders of prenatal drinking and other maternal risks, MDPB were 6.4 times more likely to have a child with FASD than breastfeeding mothers who abstained from alcohol while breastfeeding. Alcohol use during the period of breastfeeding was found to significantly compromise a child's development. Copyright © 2016 Elsevier Inc. All rights reserved.

BREASTFEEDING AND MATERNAL ALCOHOL USE: PREVALENCE AND EFFECTS ON CHILD OUTCOMES AND FETAL ALCOHOL SPECTRUM DISORDERS

PubMed Central

May, Philip A.; Hasken, Julie M.; Blankenship, Jason; Marais, Anna-Susan; Joubert, Belinda; Cloete, Marise; de Vries, Marlene M.; Barnard, Ronel; Botha, Isobel; Roux, Sumien; Doms, Cate; Gossage, J. Phillip; Kalberg, Wendy O.; Buckley, David; Robinson, Luther K.; Adnams, Colleen M.; Manning, Melanie A.; Parry, Charles D.H.; Hoyme, H. Eugene; Tabachnick, Barbara; Seedat, Soraya

2016-01-01

Objective Determine any effects that maternal alcohol consumption during the breastfeeding period has on child outcomes. Methods Population-based samples of children with fetal alcohol spectrum disorders (FASD), normally-developing children, and their mothers were analyzed for differences in child outcomes. Results Ninety percent (90%) of mothers breastfed for an average of 19.9 months. Of mothers who drank postpartum and breastfed (MDPB), 47% breastfed for 12 months or more. In case control analyses, children of MDPB were significantly lighter, had lower verbal IQ scores, and more anomalies in comparisons controlling for prenatal alcohol exposure and final FASD diagnosis. Utilizing a stepwise logistic regression model adjusting for nine confounders of prenatal drinking and other maternal risks, MDPB were 6.4 times more likely to have a child with FASD than breastfeeding mothers who abstained from alcohol while breastfeeding. Conclusions Alcohol use during the period of breastfeeding was found to significantly compromise a child’s development. PMID:27174445

Prevalence of Fetal Alcohol Syndrome and Maternal Characteristics in a Sample of Schoolchildren from a Rural Province of Croatia

PubMed Central

Petković, Giorgie; Barišić, Ingeborg

2013-01-01

Fetal alcohol syndrome (FAS) is a congenital syndrome caused by maternal alcohol consumption during pregnancy and is entirely preventable by abstinence from alcohol drinking during this time. Little is known about the prevalence of FAS and maternal alcohol consumption during pregnancy in Western countries. We present the results of FAS/partial fetal alcohol syndrome (PFAS) prevalence study and maternal characteristics in a sample of schoolchildren from a rural province of Croatia. This study involved seven elementary schools with 1,110 enrolled children attending 1st to 4th grade and their mothers. We used an active case ascertainment method with passive parental consent and Clarified IOM criteria. The investigation protocol involved maternal data collection and clinical examination of children. Out of 1,110 mothers, 917 (82.6%) answered the questionnaire. Alcohol exposure during pregnancy was admitted by 11.5%, regular drinking by 4.0% and binge drinking by 1.4% of questioned mothers. Clinical examination involved 824 (74.2%) schoolchildren and disclosed 14 (1.7%) with clinical signs of FAS and 41 (5.0%) of PFAS. The observed FAS prevalence, based on 74.2% participation rate, was 16.9, PFAS 49.7 and combined prevalence was 66.7/1,000 examined schoolchildren. This is the first FAS prevalence study based on active ascertainment among schoolchildren and pregnancy alcohol drinking analysis performed in a rural community of Croatia and Europe. High prevalence of FAS/PFAS and pregnancy alcohol consumption observed in this study revealed that FAS is serious health problem in rural regions as well as a need to develop future studies and preventive measures for pregnancy alcohol drinking and FASD. PMID:23591786

Towards a Neurobehavioral Profile of Fetal Alcohol Spectrum Disorders

PubMed Central

Mattson, Sarah N.; Roesch, Scott C.; Fagerlund, Åse; Autti-Rämö, Ilona; Jones, Kenneth Lyons; May, Philip A.; Adnams, Colleen M.; Konovalova, Valentina; Riley, Edward P.

2010-01-01

Background A primary goal of recent research is the development of neurobehavioral profiles that specifically define fetal alcohol spectrum disorders (FASD), which may assist differential diagnosis or improve treatment. In the current study we define a preliminary profile using neuropsychological data from a multisite study. Methods Data were collected using a broad neurobehavioral protocol from two sites of a multisite study of FASD. Subjects were children with heavy prenatal alcohol exposure and unexposed controls. The alcohol-exposed group included children with and with out fetal alcohol syndrome (FAS). From 547 neuropsychological, 22 variables were selected for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure from nonexposed controls. These data were analyzed using latent profile analysis (LPA). Results The results indicated that a 2-class model best fit the data. The resulting profile was successful at distinguishing subjects with FAS from nonexposed controls without FAS with 92% overall accuracy; 87.8% of FAS cases and 95.7% of controls were correctly classified. The same analysis was repeated with children with heavy prenatal alcohol exposure but without FAS and non-exposed controls with similar results. The overall accuracy was 84.7%; 68.4% of alcohol-exposed cases and 95% of controls were correctly classified. In both analyses, the profile based on neuropsychological variables was more successful at distinguishing the groups than was IQ alone. Conclusions We used data from two sites of a multisite study and a broad neuropsychological test battery to determine a profile that could be used to accurately identify children affected by prenatal alcohol exposure. Results indicated that measures of executive function and spatial processing are especially sensitive to prenatal alcohol exposure. PMID:20569243

Preventing fetal alcohol spectrum disorders: the role of protection motivation theory.

PubMed

Cismaru, Magdalena; Deshpande, Sameer; Thurmeier, Robin; Lavack, Anne M; Agrey, Noreen

2010-01-01

This article examines health communication campaigns aimed at preventing alcohol consumption among women who are pregnant or attempting to become pregnant. Relevant communication materials were gathered and a qualitative review was conducted. A majority of the campaigns followed the tenets of protection motivation theory by focusing on the threat variables of severity and vulnerability, as well as emphasizing response efficacy. Few campaigns focused on costs or self-efficacy. Future fetal alcohol spectrum disorders prevention initiatives should attempt to reduce perceived costs, as well as include self-efficacy messages in order to increase women's confidence that they can carry out the recommended actions.

DNA methylation signature of human fetal alcohol spectrum disorder.

PubMed

Portales-Casamar, Elodie; Lussier, Alexandre A; Jones, Meaghan J; MacIsaac, Julia L; Edgar, Rachel D; Mah, Sarah M; Barhdadi, Amina; Provost, Sylvie; Lemieux-Perreault, Louis-Philippe; Cynader, Max S; Chudley, Albert E; Dubé, Marie-Pierre; Reynolds, James N; Pavlidis, Paul; Kobor, Michael S

2016-01-01

Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol's effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with fetal alcohol spectrum disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Genome-wide DNA methylation patterns of buccal epithelial cells (BECs) were analyzed using the Illumina HumanMethylation450 array in a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. After correcting for the effects of genetic background, we found 658 significantly differentially methylated sites between FASD cases and controls, with 41 displaying differences in percent methylation change >5 %. Furthermore, 101 differentially methylated regions containing two or more CpGs were also identified, overlapping with 95 different genes. The majority of differentially methylated genes were highly expressed at the level of mRNA in brain samples from the Allen Brain Atlas, and independent DNA methylation data from cortical brain samples showed high correlations with BEC DNA methylation patterns. Finally, overrepresentation analysis of genes with up-methylated CpGs revealed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. These findings suggested that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.

The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders

PubMed Central

Tran, Tuan D.; Amin, Aenia; Jones, Keith G.; Sheffer, Ellen M.; Ortega, Lidia; Dolman, Keith

2017-01-01

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain undergoes rapid organizational change and is similar to accelerated brain changes that occur during the third trimester in humans. This model of fetal alcohol spectrum disorders (FASDs) produces severe brain damage, mimicking the amount and pattern of binge-drinking that occurs in some pregnant alcoholic mothers. We describe the use of trace eyeblink classical conditioning (ECC), a higher-order variant of associative learning, to assess long-term hippocampal dysfunction that is typically seen in alcohol-exposed adult offspring. At 90 days of age, rodents were surgically prepared with recording and stimulating electrodes, which measured electromyographic (EMG) blink activity from the left eyelid muscle and delivered mild shock posterior to the left eye, respectively. After a 5 day recovery period, they underwent 6 sessions of trace ECC to determine associative learning differences between alcohol-exposed and control rats. Trace ECC is one of many possible ECC procedures that can be easily modified using the same equipment and software, so that different neural systems can be assessed. ECC procedures in general, can be used as diagnostic tools for detecting neural pathology in different brain systems and different conditions that insult the brain. PMID:28809846

Fetal alcohol-spectrum disorders: identifying at-risk mothers

PubMed Central

Montag, Annika C

2016-01-01

Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children. PMID:27499649

Facts about Alcohol and Other Drug Use during Pregnancy. ARC Facts.

ERIC Educational Resources Information Center

Association for Retarded Citizens, Arlington, TX.

The fact sheet provides basic information about how alcohol and drug use during pregnancy can lead to Fetal Alcohol Syndrome (FAS) and Alcohol Related Birth Defects (ARBD), resulting in such problems as mental retardation, sleep disturbances, learning disabilities, muscle problems, heart defects, and small head size. The question and answer format…

RE-AIM evaluation of the Alcohol and Pregnancy Project: educational resources to inform health professionals about prenatal alcohol exposure and fetal alcohol spectrum disorder.

PubMed

Payne, Janet M; France, Kathryn E; Henley, Nadine; D'Antoine, Heather A; Bartu, Anne E; O'Leary, Colleen M; Elliott, Elizabeth J; Bower, Carol; Geelhoed, Elizabeth

2011-03-01

The objective was to evaluate the Alcohol and Pregnancy Project that provided health professionals in Western Australia (WA) with educational resources to inform them about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder (FASD). The authors developed, produced, and distributed educational resources to 3,348 health professionals in WA. Six months later, they surveyed 1,483 of these health professionals. The authors used the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate the project. The educational resources were effective in producing a 31% increase in the proportion of health professionals who routinely provided pregnant women with information about the consequences of drinking alcohol during pregnancy. One hundred percent of the settings adopted the project, it reached 96.3% of the target population, it was implemented as intended, and the resources were maintained (http://www.ichr.uwa.edu.au/alcoholandpregnancy). The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

"A tempest in a cocktail glass": mothers, alcohol, and television, 1977-1996.

PubMed

Golden, J

2000-06-01

This article examines the portrayal of pregnancy and alcohol in thirty-six national network evening news broadcasts (ABC, CBS, NBC). Early coverage focused on white, middle-class women, as scientific authorities and government officials warned against drinking during pregnancy. After 1987, however, women who drank during pregnancy were depicted as members of minority groups and as a danger to society. The thematic transition began before warning labels appeared on alcoholic beverages and gained strength from official government efforts to prevent fetal alcohol syndrome. The greatest impetus for the revised discourse, however, was the eruption of a "moral panic" over crack cocaine use. By linking fetal harm to substance abuse, the panic suggested it was in the public's interest to control the behavior of pregnant women.

Epigenetic mechanisms: A possible link between autism spectrum disorders and fetal alcohol spectrum disorders.

PubMed

Varadinova, Miroslava; Boyadjieva, Nadka

2015-12-01

The etiology of autism spectrum disorders (ASDs) still remains unclear and seems to involve a considerable overlap between polygenic, epigenetic and environmental factors. We have summarized the current understanding of the interplay between gene expression dysregulation via epigenetic modifications and the potential epigenetic impact of environmental factors in neurodevelopmental deficits. Furthermore, we discuss the scientific controversies of the relationship between prenatal exposure to alcohol and alcohol-induced epigenetic dysregulations, and gene expression alterations which are associated with disrupted neural plasticity and causal pathways for ASDs. The review of the literature suggests that a better understanding of developmental epigenetics should contribute to furthering our comprehension of the etiology and pathogenesis of ASDs and fetal alcohol spectrum disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurobehavioral consequences of prenatal alcohol exposure: an international perspective.

PubMed

Riley, Edward P; Mattson, Sarah N; Li, Ting-Kai; Jacobson, Sandra W; Coles, Claire D; Kodituwakku, P W; Adnams, Colleen M; Korkman, Marit I

2003-02-01

This article represents the proceedings of a symposium at the 2002 Research Society on Alcoholism/International Society for Biomedical Research on Alcoholism meeting in San Francisco, CA. The organizers were Edward P. Riley and Sarah N. Mattson, and the chairperson was Edward P. Riley. The presentations were (1) Neurobehavioral deficits in alcohol-exposed South African infants: preliminary findings, by Sandra W. Jacobson, Christopher D. Molteno, Denis Viljoen, and Joseph L. Jacobson; (2) A pilot study of classroom intervention for learners with fetal alcohol syndrome in South Africa, by Colleen Adnams, M. W. Rossouw, M. D. Perold, P. W. Kodituwakku, and W. Kalberg; (3) Differential effects of prenatal alcohol exposure on fluid versus crystallized intelligence, by P. W. Kodituwakku, W. Kalberg, L. Robinson, and P. A. May; (4) Neurobehavioral outcomes of prenatal alcohol exposure: early identification of alcohol effects, by Claire D. Coles; (5) Fetal alcohol syndrome in Moscow, Russia: neuropsychology test performance, by Sarah N. Mattson, E. P. Riley, A. Matveeva, and G. Marintcheva; and (6) Long-term follow-up of Finnish children exposed to alcohol in utero in various durations, by Marit I. Korkman and I. Autti-Rämö. The discussant was Ting-Kai Li.

Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats.

PubMed

Thomas, Jennifer D; Abou, Elizabeth J; Dominguez, Hector D

2009-01-01

Prenatal alcohol exposure can lead to a range of physical, neurological, and behavioral alterations referred to as fetal alcohol spectrum disorders (FASD). Variability in outcome observed among children with FASD is likely related to various pre- and postnatal factors, including nutritional variables. Choline is an essential nutrient that influences brain and behavioral development. Recent animal research indicates that prenatal choline supplementation leads to long-lasting cognitive enhancement, as well as changes in brain morphology, electrophysiology and neurochemistry. The present study examined whether choline supplementation during ethanol exposure effectively reduces fetal alcohol effects. Pregnant dams were exposed to 6.0g/kg/day ethanol via intubation from gestational days (GD) 5-20; pair-fed and lab chow controls were included. During treatment, subjects from each group received choline chloride (250mg/kg/day) or vehicle. Physical development and behavioral development (righting reflex, geotactic reflex, cliff avoidance, reflex suspension and hindlimb coordination) were examined. Subjects prenatally exposed to alcohol exhibited reduced birth weight and brain weight, delays in eye opening and incisor emergence, and alterations in the development of all behaviors. Choline supplementation significantly attenuated ethanol's effects on birth and brain weight, incisor emergence, and most behavioral measures. In fact, behavioral performance of ethanol-exposed subjects treated with choline did not differ from that of controls. Importantly, choline supplementation did not influence peak blood alcohol level or metabolism, indicating that choline's effects were not due to differential alcohol exposure. These data indicate early dietary supplements may reduce the severity of some fetal alcohol effects, findings with important implications for children of women who drink alcohol during pregnancy.

Exploring the complexity of intellectual disability in fetal alcohol spectrum disorders.

PubMed

Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M

2014-01-01

Brain development in mammals is long lasting. It begins early during embryonic growth and is finalized in early adulthood. This progression represents a delicate choreography of molecular, cellular, and physiological processes initiated and directed by the fetal genotype in close interaction with environment. Not surprisingly, most aberrations in brain functioning including intellectual disability (ID) are attributed to either gene(s), or environment or the interaction of the two. The ensuing complexity has made the assessment of this choreography, ever challenging. A model to assess this complexity has used a mouse model (C57BL/6J or B6) that is subjected to prenatal alcohol exposure. The resulting pups show learning and memory deficits similar to patients with fetal alcohol spectrum disorder (FASD), which is associated with life-long changes in gene expression. Interestingly, this change in gene expression underlies epigenetic processes including DNA methylation and miRNAs. This paradigm is applicable to ethanol exposure at different developmental times (binge at trimesters 1, 2, and 3 as well as continuous preference drinking (70%) of 10% alcohol by B6 females during pregnancy). The exposure leads to life-long changes in neural epigenetic marks, gene expression, and a variety of defects in neurodevelopment and CNS function. We argue that this cascade may be reversed postnatally via drugs, chemicals, and environment including maternal care. Such conclusions are supported by two sets of results. First, antipsychotic drugs that are used to treat ID including psychosis function via changes in DNA methylation, a major epigenetic mark. Second, post-natal environment may improve (with enriched environments) or worsen (with negative and maternal separation stress) the cognitive ability of pups that were prenatally exposed to ethanol as well as their matched controls. In this review, we will discuss operational epigenetic mechanisms involved in the development of intellectual ability/disability in response to alcohol during prenatal or post-natal development. In doing so, we will explore the potential of epigenetic manipulation in the treatment of FASD and related disorders implicated in ID.

Exploring the Complexity of Intellectual Disability in Fetal Alcohol Spectrum Disorders

PubMed Central

Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M.

2014-01-01

Brain development in mammals is long lasting. It begins early during embryonic growth and is finalized in early adulthood. This progression represents a delicate choreography of molecular, cellular, and physiological processes initiated and directed by the fetal genotype in close interaction with environment. Not surprisingly, most aberrations in brain functioning including intellectual disability (ID) are attributed to either gene(s), or environment or the interaction of the two. The ensuing complexity has made the assessment of this choreography, ever challenging. A model to assess this complexity has used a mouse model (C57BL/6J or B6) that is subjected to prenatal alcohol exposure. The resulting pups show learning and memory deficits similar to patients with fetal alcohol spectrum disorder (FASD), which is associated with life-long changes in gene expression. Interestingly, this change in gene expression underlies epigenetic processes including DNA methylation and miRNAs. This paradigm is applicable to ethanol exposure at different developmental times (binge at trimesters 1, 2, and 3 as well as continuous preference drinking (70%) of 10% alcohol by B6 females during pregnancy). The exposure leads to life-long changes in neural epigenetic marks, gene expression, and a variety of defects in neurodevelopment and CNS function. We argue that this cascade may be reversed postnatally via drugs, chemicals, and environment including maternal care. Such conclusions are supported by two sets of results. First, antipsychotic drugs that are used to treat ID including psychosis function via changes in DNA methylation, a major epigenetic mark. Second, post-natal environment may improve (with enriched environments) or worsen (with negative and maternal separation stress) the cognitive ability of pups that were prenatally exposed to ethanol as well as their matched controls. In this review, we will discuss operational epigenetic mechanisms involved in the development of intellectual ability/disability in response to alcohol during prenatal or post-natal development. In doing so, we will explore the potential of epigenetic manipulation in the treatment of FASD and related disorders implicated in ID. PMID:25207264

Substance use in the perinatal period

PubMed Central

Forray, Ariadna; Foster, Dawn

2015-01-01

Perinatal substance use remains a major public health problem and is associated with a number of deleterious maternal and fetal effects. Polysubstance use in pregnancy is common, and can potentiate adverse maternal and fetal outcomes. Tobacco is the most commonly used substance in pregnancy, followed by alcohol and illicit substances. The treatments for perinatal substance use are limited and consist mostly of behavioral and psychosocial interventions. Of these contingency management has shown the most efficacy. More recently, novel interventions such as progesterone for postpartum cocaine use have shown promise. The purpose of this review is to examine the recent literature on the use of tobacco, alcohol, cannabis, stimulants, and opioids in the perinatal period, their effects on maternal and fetal health and current treatments. PMID:26386836

Fetal Alcohol Syndrome

MedlinePlus

... Infants and Toddlers Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management ... Categories: Family Health, Infants and Toddlers, Pregnancy and Childbirth, WomenTags: alcohol abuse, female, Obstetrical, Pregnant Women, prenatal ...

Impaired delay and trace eyeblink conditioning in school-age children with fetal alcohol syndrome.

PubMed

Jacobson, Sandra W; Stanton, Mark E; Dodge, Neil C; Pienaar, Mariska; Fuller, Douglas S; Molteno, Christopher D; Meintjes, Ernesta M; Hoyme, H Eugene; Robinson, Luther K; Khaole, Nathaniel; Jacobson, Joseph L

2011-02-01

Classical eyeblink conditioning (EBC) involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Impairment of EBC has been demonstrated in studies of alcohol-exposed animals and in children exposed prenatally at heavy levels. Fetal alcohol syndrome (FAS) was diagnosed by expert dysmorphologists in a large sample of Cape Coloured, South African children. Delay EBC was examined in a new sample of 63 children at 11.3 years, and trace conditioning in 32 of the same children at 12.8 years. At each age, 2 sessions of 50 trials each were administered on the same day; 2 more sessions the next day, for children not meeting criterion for conditioning. Six of 34 (17.6%) children born to heavy drinkers were diagnosed with FAS, 28 were heavily exposed nonsyndromal (HE), and 29 were nonexposed controls. Only 33.3% with FAS and 42.9% of HE met criterion for delay conditioning, compared with 79.3% of controls. The more difficult trace conditioning task was also highly sensitive to fetal alcohol exposure. Only 16.7% of the FAS and 21.4% of HE met criterion for trace conditioning, compared with 66.7% of controls. The magnitude of the effect of diagnostic group on trace conditioning was not greater than the effect on short delay conditioning, findings consistent with recent rat studies. Longer latency to onset and peak eyeblink CR in exposed children indicated poor timing and failure to blink in anticipation of the puff. Extended training resulted in some but not all of the children reaching criterion. These data showing alcohol-related delay and trace conditioning deficits extend our earlier findings of impaired EBC in 5-year-olds to school-age. Alcohol-related impairment in the cerebellar circuitry required for both forms of conditioning may be sufficient to account for the deficit in both tasks. Extended training was beneficial for some exposed children. EBC provides a well-characterized model system for assessment of degree of cerebellar-related learning and memory dysfunction in fetal alcohol exposed children. Copyright © 2010 by the Research Society on Alcoholism.

First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

PubMed

Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

2017-03-01

Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T 2 * and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T 2 * and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T 2 * values vary throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 *throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal risk factors predicting child physical characteristics and dysmorphology in fetal alcohol syndrome and partial fetal alcohol syndrome.

PubMed

May, Philip A; Tabachnick, Barbara G; Gossage, J Phillip; Kalberg, Wendy O; Marais, Anna-Susan; Robinson, Luther K; Manning, Melanie; Buckley, David; Hoyme, H Eugene

2011-12-01

Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46-89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child's physical anomalies (R² = .30, p < .001), followed by maternal demographics (R² = .24, p < .001), maternal physical characteristics (R²=.15, p < .001), and childbearing variables (R² = .06, p < .001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (β = 0.61, p < .001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome

PubMed Central

SOGUT, IBRAHIM; OGLAKCI, AYSEGUL; KARTKAYA, KAZIM; OL, KEVSER KUSAT; SOGUT, MELIS SAVASAN; KANBAK, GUNGOR; INAL, MINE ERDEN

2015-01-01

To the best of our knowledge, this is the first study concerning the effect of boric acid (BA) administration on fetal alcohol syndrome (FAS). In this study, the aim was to investigate prenatal alcohol-induced oxidative stress on the cerebral cortex of newborn rat pups and assess the protective and beneficial effects of BA supplementation on rats with FAS. Pregnant rats were divided into three groups, namely the control, alcohol and alcohol + boric acid groups. As markers of alcohol-induced oxidative stress in the cerebral cortex of the newborn pups, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were measured. Although the MDA levels in the alcohol group were significantly increased compared with those in the control group (P<0.05), the MDA level in the alcohol + boric acid group was shown to be significantly decreased compared with that in the alcohol group (P<0.01). The CAT activity of the alcohol + boric acid group was significantly higher than that in the alcohol group (P<0.05). The GPx activity in the alcohol group was decreased compared with that in the control group (P<0.05). These results demonstrate that alcohol is capable of triggering damage to membranes of the cerebral cortex of rat pups and BA could be influential in antioxidant mechanisms against oxidative stress resulting from prenatal alcohol exposure. PMID:25667671

Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome.

PubMed

Sogut, Ibrahim; Oglakci, Aysegul; Kartkaya, Kazim; Ol, Kevser Kusat; Sogut, Melis Savasan; Kanbak, Gungor; Inal, Mine Erden

2015-03-01

To the best of our knowledge, this is the first study concerning the effect of boric acid (BA) administration on fetal alcohol syndrome (FAS). In this study, the aim was to investigate prenatal alcohol-induced oxidative stress on the cerebral cortex of newborn rat pups and assess the protective and beneficial effects of BA supplementation on rats with FAS. Pregnant rats were divided into three groups, namely the control, alcohol and alcohol + boric acid groups. As markers of alcohol-induced oxidative stress in the cerebral cortex of the newborn pups, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were measured. Although the MDA levels in the alcohol group were significantly increased compared with those in the control group (P<0.05), the MDA level in the alcohol + boric acid group was shown to be significantly decreased compared with that in the alcohol group (P<0.01). The CAT activity of the alcohol + boric acid group was significantly higher than that in the alcohol group (P<0.05). The GPx activity in the alcohol group was decreased compared with that in the control group (P<0.05). These results demonstrate that alcohol is capable of triggering damage to membranes of the cerebral cortex of rat pups and BA could be influential in antioxidant mechanisms against oxidative stress resulting from prenatal alcohol exposure.

An animal model of fetal alcohol spectrum disorder: Trace conditioning as a window to inform memory deficits and intervention tactics.

PubMed

Hunt, Pamela S; Barnet, Robert C

2015-09-01

Animal models of Fetal Alcohol Spectrum Disorders (FASD) afford the unique capacity to precisely control timing of alcohol exposure and alcohol exposure amounts in the developing animal. These models have powerfully informed neurophysiological alterations associated with fetal and perinatal alcohol. In two experiments presented here we expand use of the Pavlovian Trace Conditioning procedure to examine cognitive deficits and intervention strategies in a rat model of FASD. Rat pups were exposed to 5g/kg/day ethanol on postnatal days (PD) 4-9, simulating alcohol exposure in the third trimester in humans. During early adolescence, approximately PD 30, the rats were trained in the trace conditioning task in which a light conditioned stimulus (CS) and shock unconditioned stimulus (US) were paired but separated by a 10-s stimulus free trace interval. Learning was assessed in freezing behavior during shock-free tests. Experiment 1 revealed that neonatal ethanol exposure significantly impaired hippocampus-dependent trace conditioning relative to controls. In Experiment 2 a serial compound conditioning procedure known as 'gap filling' completely reversed the ethanol-induced deficit in trace conditioning. We also discuss prior data regarding the beneficial effects of supplemental choline and novel preliminary data regarding the pharmacological cognitive enhancer physostigmine, both of which mitigate the alcohol-induced cognitive deficit otherwise seen in trace conditioning controls. We suggest trace conditioning as a useful tool for characterizing some of the core cognitive deficits seen in FASD, and as a model for developing effective environmental as well as nutritional and pharmacological interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

PubMed

Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

2015-01-01

Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

An Animal Model of Fetal Alcohol Spectrum Disorder: Trace Conditioning as a Window to Inform Memory Deficits and Intervention Tactics

PubMed Central

Hunt, Pamela S.; Barnet, Robert C.

2014-01-01

Animal models of Fetal Alcohol Spectrum Disorders (FASD) afford the unique capacity to precisely control timing of alcohol exposure and alcohol exposure amounts in the developing animal. These models have powerfully informed neurophysiological alterations associated with fetal and perinatal alcohol. In two experiments presented here we expand use of the Pavlovian Trace Conditioning procedure to examine cognitive deficits and intervention strategies in a rat model of FASD. Rat pups were exposed to 5 g/kg/day ethanol on postnatal days (PD) 4–9, simulating alcohol exposure in the third trimester in humans. During early adolescence, approximately PD 30, the rats were trained in the trace conditioning task in which a light conditioned stimulus (CS) and shock unconditioned stimulus (US) were paired but separated by a 10-s stimulus free trace interval. Learning was assessed in freezing behavior during shock-free tests. Experiment 1 revealed that neonatal ethanol exposure significantly impaired hippocampus-dependent trace conditioning relative to controls. In Experiment 2 a serial compound conditioning procedure known as ‘gap filling’ completely reversed the ethanol-induced deficit in trace conditioning. We also discuss prior data regarding the beneficial effects of supplemental choline and novel preliminary data regarding the pharmacological cognitive enhancer physostigmine, both of which mitigate the alcohol-induced cognitive deficit otherwise seen in trace conditioning controls. We suggest trace conditioning as a useful tool for characterizing some of the core cognitive deficits seen in FASD, and as a model for developing effective environmental as well as nutritional and pharmacological interventions. PMID:25477227

Facts About Fetal Alcohol Spectrum Disorders (FASDs)

MedlinePlus

... attention Poor memory Difficulty in school (especially with math) Learning disabilities Speech and language delays Intellectual disability ... do poorly in school and have difficulties with math, memory, attention, judgment, and poor impulse control. Alcohol- ...

Pregnancy and Substance Abuse

MedlinePlus

... baby. If you smoke, use alcohol or take illegal drugs, so does your unborn baby. First, don't ... children, including fetal alcohol syndrome. Don't use illegal drugs. Using illegal drugs may cause underweight babies, birth ...

"Mummy beerest": a study of fetal alcohol spectrum disorder, a mother's duty of care and strategies for intervention.

PubMed

Nolan, Elise Jane

2011-09-01

Fetal alcohol spectrum disorder can occur in children when a mother consumes alcohol while pregnant. It can manifest in a range of both physical and mental impairments and in varying degrees of seriousness. The act of consuming alcohol while pregnant arguably constitutes a breach of the duty of care that a mother owes to her unborn child and may lead to an award of damages for children with the disorder. However, to conclude that a duty is owed to an unborn child may be legally problematic. Further, an award of compensation may be of little utility to the child. It is therefore suggested that intervention strategies should instead be implemented which target relevant population groups and which prevent and assist in the management of the disorder.

Differential correlations between maternal hair levels of tobacco and alcohol with fetal growth restriction clinical subtypes.

PubMed

Sabra, Sally; Malmqvist, Ebba; Almeida, Laura; Gratacos, Eduard; Gomez Roig, Maria Dolores

2018-08-01

Maternal exposure to tobacco and alcohol is a known cause, among others, for fetal growth restriction (FGR). Clinically, FGR can be subclassified into two forms: intrauterine growth restriction (IUGR) and small for gestational age (SGA), based on the severity of the growth retardation, and abnormal uterine artery Doppler or cerebro-placental ratio. This study aimed at investigating any differential correlation between maternal exposures to these toxins with the two clinical forms of FGR. Therefore, a case-control study was conducted in Barcelona, Spain. Sixty-four FGR subjects, who were further subclassified into IUGR (n = 36) and SGA (n = 28), and 89 subjects matched appropriate-for-gestational age (AGA), were included. The levels of nicotine (NIC) and ethyl glucuronide (EtG), biomarkers of tobacco and alcohol exposure, respectively, were assessed in the maternal hair in the third trimester. Our analysis showed 65% of the pregnant women consumed alcohol, 25% smoked, and 19% did both. The odds ratios (ORs) of IUGR were 21 times versus 14 times for being SGA with maternal heavy smoking, while with alcohol consumption the ORs for IUGR were 22 times versus 37 times for the SGA group. The differential correlations between these toxins with the two subtypes of FGR suggest different mechanisms influencing fetal weight. Our alarming data of alcohol consumption during pregnancy should be considered for further confirmation among Spanish women. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal Alcohol and Cocaine Exposure: Influences on Cognition, Speech, Language, and Hearing

ERIC Educational Resources Information Center

Cone-Wesson, B.

2005-01-01

This paper reviews research on the consequences of prenatal exposure to alcohol and cocaine on children's speech, language, hearing, and cognitive development. The review shows that cognitive impairment, learning disabilities, and behavioral disorders are the central nervous system manifestations of fetal alcohol syndrome (FAS), and cranio-facial…

Fetal Alcohol Syndrome & Effects: A Continuing Education Offering

DTIC Science & Technology

1988-01-01

feeble, and distempered children" (Robe, 1982). Cheap gin had flooded the country, permitting alcohol to be used heavily by many who previously had not had...cause of weak, feeble,- and distempered children." 1787 America Dr. Benjamin Rush spoke out against alcohol use by pregnant women because he feared

Prevention of Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Floyd, R. Louise; Weber, Mary Kate; Denny, Clark; O'Connor, Mary J.

2009-01-01

Alcohol use among women of childbearing age is a leading, preventable cause of birth defects and developmental disabilities in the United States. Although most women reduce their alcohol use upon pregnancy recognition, some women report drinking during pregnancy and others may continue to drink prior to realizing they are pregnant. These findings…

Vitamin A, folate, and choline as a possible preventive intervention to fetal alcohol syndrome.

PubMed

Ballard, Mark S; Sun, Muxin; Ko, Jenny

2012-04-01

It is recognized that alcohol consumption during pregnancy is associated with fetal alcohol syndrome (FAS). Alcohol can trigger a pattern of neurodegeneration in rat brains similar to other known gamma-aminobutyric acid (GABA) specific agonists. However this does not seem to explain FAS entirely, as impoverished care-giving environments have been shown to increase the risk of FAS. Individuals living under the poverty level are at risk for micronutrient deficiencies due to insufficient intake. In particular, three nutrients commonly found to be deficient are folate, choline and vitamin A. There is evidence to suggest that ethanol alone may not explain the entire spectrum of anomalies seen in individuals with FAS. It is hypothesized that FAS may be caused more by the nutritional deficiencies that are exacerbated by alcohol than by direct alcoholic neurotoxicity. It is known that ethanol inhibits folate, choline, and vitamin A/retinoic acid metabolism at multiple steps. Additionally, mice exposed to ethanol demonstrated epigenetic changes, or variations in the methylation of DNA to control gene expression. Folate is important in the production of methyl groups, which are subsequently used to create and methylate DNA. Choline (which is metabolized to acetylcholine) is important in neurotransmission and neurodevelopment. It is also involved in an alternative pathway in the production of methyl groups. In fact a study by Thomas et al. in 2009 found that nutritional supplementation with choline in rats exposed to ethanol in utero almost completely mitigated the degenerative effects of ethanol on development and behaviour. Lastly, vitamin A and retinoic acid metabolism is associated with the regulation of one sixth of the entire proteome. Thus supplementation of folate, choline and vitamin A to mothers may mitigate the effects of the alcohol and reduce the severity or prevalence of FAS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Special Education of Children with Fetal Alcohol Spectrum Disorder

PubMed Central

Popova, Svetlana; Lange, Shannon; Burd, Larry; Nam, Seungree; Rehm, Jürgen

2016-01-01

Abstract The current study aimed to estimate the cost associated with special education among children (5 to 14 years) with Fetal Alcohol Spectrum Disorder (FASD) in elementary and middle school by sex, age group, and province and territory in Canada. It was estimated that there were 6,520 students with FASD receiving special education in Canada in 2011–2012. The cost of special education among these students was 53.5 million Canadian dollars. Implications for decision- and policymakers, educational systems and school staff are discussed. PMID:27695197

Fetal Alcohol Spectrum Disorders (FASDs): Data and Statistics

MedlinePlus

... alcohol screening and counseling for all women Data & Statistics Recommend on Facebook Tweet Share Compartir Prevalence of ... conducted annually by the National Center for Health Statistics (NCHS), CDC, to produce national estimates for a ...

What Research Is Being Done on Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorders in the Russian Research Community?

PubMed Central

Popova, Svetlana; Yaltonskaya, Aleksandra; Yaltonsky, Vladimir; Kolpakov, Yaroslav; Abrosimov, Ilya; Pervakov, Kristina; Tanner, Valeria; Rehm, Jürgen

2014-01-01

Aims: Although Russia has one of the highest rates of alcohol consumption and alcohol-attributable burden of disease, little is known about the existing research on prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders (FASDs) in this country. The objective of this study was to locate and review published and unpublished studies related to any aspect of PAE and FASD conducted in or using study populations from Russia. Methods: A systematic literature search was conducted in multiple English and Russian electronic bibliographic databases. In addition, a manual search was conducted in several major libraries in Moscow. Results: The search revealed a small pool of existing research studies related to PAE and/or FASD in Russia (126: 22 in English and 104 in Russian). Existing epidemiological data indicate a high prevalence of PAE and FASD, which underlines the strong negative impact that alcohol has on mortality, morbidity and disability in Russia. High levels of alcohol consumption by women of childbearing age, low levels of contraception use, and low levels of knowledge by health and other professionals regarding the harmful effects of PAE put this country at great risk of further alcohol-affected pregnancies. Conclusions: Alcohol preventive measures in Russia warrant immediate attention. More research focused on alcohol prevention and policy is needed in order to reduce alcohol-related harm, especially in the field of FASD. PMID:24158024

Epigenetic medicine and fetal alcohol spectrum disorders

PubMed Central

Resendiz, Marisol; Chen, Yuanyuan; Öztürk, Nail C; Zhou, Feng C

2013-01-01

Epigenetic medicine is still in its infancy. To date, only a handful of diseases have documented epigenetic correlates upstream of gene regulation including cancer, developmental syndromes and late-onset diseases. The finding that epigenetic markers are dynamic and heterogeneous at tissue and cellular levels, combined with recent identification of a new form of functionally distinct DNA methylation has opened a wider window for investigators to pry into the epigenetic world. It is anticipated that many diseases will be elucidated through this epigenetic inquiry. In this review, we discuss the normal course of DNA methylation during development, taking alcohol as a demonstrator of the epigenetic impact of environmental factors in disease etiology, particularly the growth retardation and neurodevelopmental deficits of fetal alcohol spectrum disorders. PMID:23414322

Impaired delay and trace eyeblink conditioning in school-age children with fetal alcohol syndrome

PubMed Central

Jacobson, Sandra W.; Stanton, Mark E.; Dodge, Neil C.; Pienaar, Mariska; Fuller, Douglas S.; Molteno, Christopher D.; Meintjes, Ernesta M.; Hoyme, H. Eugene; Robinson, Luther K.; Khaole, Nathaniel; Jacobson, Joseph L.

2013-01-01

Background Classical eyeblink conditioning (EBC) involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Impairment of EBC has been demonstrated in studies of alcohol-exposed animals and in children exposed prenatally at heavy levels. Methods Fetal alcohol syndrome (FAS) was diagnosed by expert dysmorphologists in a large sample of Cape Coloured, South African children. Delay EBC was examined in a new sample of 63 children at 11.3 years, and trace conditioning in 32 of the same children at 12.8 years. At each age, two sessions of 50 trials each were administered on the same day; two more sessions the next day, for children not meeting criterion for conditioning. Results 6 of 34 (17.6%) children born to heavy drinkers were diagnosed with FAS, 28 were heavily exposed nonsyndromal (HE), and 29 were non-exposed controls. Only 33.3% with FAS and 42.9% of HE met criterion for delay conditioning, compared with 79.3% of controls. The more difficult trace conditioning task was also highly sensitive to fetal alcohol exposure. Only 16.7% of the FAS and 21.4% of HE met criterion for trace conditioning, compared with 66.7% of controls. The magnitude of the effect of diagnostic group on trace conditioning was not greater than the effect on short delay conditioning, findings consistent with recent rat studies. Longer latency to onset and peak eyeblink CR in exposed children indicated poor timing and failure to blink in anticipation of the puff. Extended training resulted in some but not all of the children reaching criterion. Conclusions These data showing alcohol-related delay and trace conditioning deficits extend our earlier findings of impaired EBC in 5-year-olds to school-age. Alcohol-related impairment in the cerebellar circuitry required for both forms of conditioning may be sufficient to account for the deficit in both tasks. Extended training was beneficial for some exposed children. EBC provides a well-characterized model system for assessment of degree of cerebellar-related learning and memory dysfunction in fetal alcohol exposed children. PMID:21073484

Diving into the world of alcohol teratogenesis: a review of zebrafish models of fetal alcohol spectrum disorder.

PubMed

Fernandes, Yohaan; Buckley, Desire M; Eberhart, Johann K

2018-04-01

The term fetal alcohol spectrum disorder (FASD) refers to the entire suite of deleterious outcomes resulting from embryonic exposure to alcohol. Along with other reviews in this special issue, we provide insight into how animal models, specifically the zebrafish, have informed our understanding of FASD. We first provide a brief introduction to FASD. We discuss the zebrafish as a model organism and its strengths for alcohol research. We detail how zebrafish has been used to model some of the major defects present in FASD. These include behavioral defects, such as social behavior as well as learning and memory, and structural defects, disrupting organs such as the brain, sensory organs, heart, and craniofacial skeleton. We provide insights into how zebrafish research has aided in our understanding of the mechanisms of ethanol teratogenesis. We end by providing some relatively recent advances that zebrafish has provided in characterizing gene-ethanol interactions that may underlie FASD.

MATERNAL NUTRITIONAL STATUS AS A CONTRIBUTING FACTOR FOR THE RISK OF FETAL ALCOHOL SPECTRUM DISORDERS

PubMed Central

May, Philip A.; Hamrick, Kari J.; Corbin, Karen D.; Hasken, Julie M.; Marais, Anna-Susan; Blankenship, Jason; Hoyme, H. Eugene; Gossage, J. Phillip

2016-01-01

Objective Compare nutritional status of 57 South African mothers of children with fetal alcohol spectrum disorders (FASD) with 148 mothers of controls. Methods Dietary data were analyzed for macronutrients, micronutrients, and fats via Estimated Average Requirements (EAR) and Adequate Intakes (AI) for pregnant women. Results Virtually all mothers were likely deficient on most micronutrients by either EAR (<50%) or AI values. Mothers of FASD children consumed more of 13 of 25 micronutrients. For percentage below EAR, only vitamin D was significantly higher for FASD mothers. Despite no difference in total food intake, control mothers had a higher mean body mass index (BMI) than FASD mothers. Maternal BMI is more significant for positive child outcomes than any individual nutrient. Conclusions Most mothers have inadequate dietary intake. Minor advantages in nutrient intake are overpowered by teratogenic effects of alcohol. Further study is needed of the interaction of alcohol, maternal nutrition, and metabolism. PMID:26656914

Drugs of abuse that cause developing neurons to commit suicide.

PubMed

Farber, Nuri B; Olney, John W

2003-12-30

When neuronal activity is abnormally suppressed during the developmental period of synaptogenesis, the timing and sequence of synaptic connections is disrupted, and this causes nerve cells to receive an internal signal to commit suicide, a form of cell death known as "apoptosis". By altering glutamate and GABA transmission alcohol suppresses neuronal activity, causing millions of nerve cells to commit suicide in the developing brain. This proapoptotic effect of alcohol provides a likely explanation for the diminished brain size and lifelong neurobehavioral disturbances associated with the human fetal alcohol syndrome. These findings have public health significance, not only in relation to fetal alcohol syndrome, but also in relation to several other drugs of abuse and various drugs used in obstetric and pediatric medicine, because these additional drugs (e.g. phencyclidine, ketamine, benzodiazepines, barbiturates) also suppress neuronal activity and drive developing neurons to commit suicide.

Public Attitudes to and Awareness of Fetal Alcohol Syndrome in Young Adults.

ERIC Educational Resources Information Center

Oei, Tian P. S.; And Others

1986-01-01

Assessed public attitude toward, and awareness of possible problems and risks associated with, the consumption of alcohol during pregnancy. Results indicated a high awareness of the problem, knowledge of the specific effects to the offspring, and of quantities and frequency of consumption of alcohol which would have teratogenic effects were…

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.

PubMed

Reynolds, James N; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2011-03-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes

PubMed Central

Reynolds, James N.; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2016-01-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. PMID:21575841

Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium.

PubMed

Sanvisens, Arantza; Robert, Neus; Hernández, José María; Zuluaga, Paola; Farré, Magí; Coroleu, Wifredo; Serra, Montserrat; Tor, Jordi; Muga, Robert

2016-03-22

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26-34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0-110.6 ng/g). With respect to EtS, it was undetectable (<0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health.

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure.

PubMed

Gavin, David P; Grayson, Dennis R; Varghese, Sajoy P; Guizzetti, Marina

2017-05-11

Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced differentiation changes with developmental alterations in chromatin structure remain to be elucidated. In the first part of this review, we discuss the sequence of chromatin structural changes involved in neural cell differentiation during normal development. We then discuss the effects of prenatal alcohol on developmental histone modifications and DNA methylation in the context of neurogenesis and astrogliogenesis. We attempt to synthesize the developmental literature with the FASD literature, proposing that alcohol-induced changes to chromatin structure account for altered neurogenesis and astrogliogenesis as well as altered neuron and astrocyte differentiation. Together these changes may contribute to the cognitive and behavioral abnormalities in FASD. Future studies using standardized alcohol exposure paradigms at specific developmental stages will advance the understanding of how chromatin structural changes impact neural cell fate and maturation in FASD.

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure

PubMed Central

Gavin, David P.; Grayson, Dennis R.; Varghese, Sajoy P.; Guizzetti, Marina

2017-01-01

Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced differentiation changes with developmental alterations in chromatin structure remain to be elucidated. In the first part of this review, we discuss the sequence of chromatin structural changes involved in neural cell differentiation during normal development. We then discuss the effects of prenatal alcohol on developmental histone modifications and DNA methylation in the context of neurogenesis and astrogliogenesis. We attempt to synthesize the developmental literature with the FASD literature, proposing that alcohol-induced changes to chromatin structure account for altered neurogenesis and astrogliogenesis as well as altered neuron and astrocyte differentiation. Together these changes may contribute to the cognitive and behavioral abnormalities in FASD. Future studies using standardized alcohol exposure paradigms at specific developmental stages will advance the understanding of how chromatin structural changes impact neural cell fate and maturation in FASD. PMID:28492482

Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder.

PubMed

Camargo Moreno, Maria; Mooney, Sandra M; Middleton, Frank A

2017-01-01

Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure. In the present study we examined the effect of ethanol-induced cellular and molecular responses in primary somatosensory cortex (SI) and hippocampus of 7-day-old wild-type (WT) and p53-knockout (KO) mice. We quantified apoptosis by active caspase-3 immunohistochemistry and ApopTag™ labeling, then determined total RNA expression levels in laminae of SI and hippocampal subregions. Immunohistochemical results confirmed increased incidence of apoptotic cells in both regions in WT and KO mice following ethanol exposure. The lack of p53 was not protective in these brain regions. Molecular analyses revealed a heterogeneous response to ethanol exposure that varied depending on the subregion, and which may go undetected using a global approach. Gene network analyses suggest that the presence or absence of p53 alters neuronal function and synaptic modifications following ethanol exposure, in addition to playing a classic role in cell cycle signaling. Thus, p53 may function in a way that underlies the intellectual and behavioral deficits observed in FASD.

Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child Characteristics, and Maternal Risk Factors in a Second Sample of Rural Communities in South Africa.

PubMed

May, Philip A; De Vries, Marlene M; Marais, Anna-Susan; Kalberg, Wendy O; Buckley, David; Adnams, Colleen M; Hasken, Julie M; Tabachnick, Barbara; Robinson, Luther K; Manning, Melanie A; Bezuidenhout, Heidre; Adam, Margaret P; Jones, Kenneth L; Seedat, Soraya; Parry, Charles D H; Hoyme, H Eugene

2017-05-12

Background : Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods : Active case ascertainment focused on children with height, weight and/or head circumference ≤25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results : Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 9-129 per 1000 children. Total FASD affect 196-276 per 1000 or 20-28% of the children in these communities. Conclusions : Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions.

Prevalence of fetal alcohol syndrome in a population-based sample of children living in remote Australia: the Lililwan Project.

PubMed

Fitzpatrick, James P; Latimer, Jane; Carter, Maureen; Oscar, June; Ferreira, Manuela L; Carmichael Olson, Heather; Lucas, Barbara R; Doney, Robyn; Salter, Claire; Try, Julianne; Hawkes, Genevieve; Fitzpatrick, Emily; Hand, Marmingee; Watkins, Rochelle E; Martiniuk, Alexandra L C; Bower, Carol; Boulton, John; Elliott, Elizabeth J

2015-04-01

Aboriginal leaders concerned about high rates of alcohol use in pregnancy invited researchers to determine the prevalence of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (pFAS) in their communities. Population-based prevalence study using active case ascertainment in children born in 2002/2003 and living in the Fitzroy Valley, in Western Australia (April 2010-November 2011) (n = 134). Socio-demographic and antenatal data, including alcohol use in pregnancy, were collected by interview with 127/134 (95%) consenting parents/care givers. Maternal/child medical records were reviewed. Interdisciplinary assessments were conducted for 108/134 (81%) children. FAS/pFAS prevalence was determined using modified Canadian diagnostic guidelines. In 127 pregnancies, alcohol was used in 55%. FAS or pFAS was diagnosed in 13/108 children, a prevalence of 120 per 1000 (95% confidence interval 70-196). Prenatal alcohol exposure was confirmed for all children with FAS/pFAS, 80% in the first trimester and 50% throughout pregnancy. Ten of 13 mothers had Alcohol Use Disorders Identification Test scores and all drank at a high-risk level. Of children with FAS/pFAS, 69% had microcephaly, 85% had weight deficiency and all had facial dysmorphology and central nervous system abnormality/impairment in three to eight domains. The population prevalence of FAS/pFAS in remote Aboriginal communities of the Fitzroy Valley is the highest reported in Australia and similar to that reported in high-risk populations internationally. Results are likely to be generalisable to other age groups in the Fitzroy Valley and other remote Australian communities with high-risk alcohol use during pregnancy. Prevention of FAS/pFAS is an urgent public health challenge. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Neural correlates of cerebellar-mediated timing during finger tapping in children with fetal alcohol spectrum disorders.

PubMed

du Plessis, Lindie; Jacobson, Sandra W; Molteno, Christopher D; Robertson, Frances C; Peterson, Bradley S; Jacobson, Joseph L; Meintjes, Ernesta M

2015-01-01

Classical eyeblink conditioning (EBC), an elemental form of learning, is among the most sensitive indicators of fetal alcohol spectrum disorders. The cerebellum plays a key role in maintaining timed movements with millisecond accuracy required for EBC. Functional MRI (fMRI) was used to identify cerebellar regions that mediate timing in healthy controls and the degree to which these areas are also recruited in children with prenatal alcohol exposure. fMRI data were acquired during an auditory rhythmic/non-rhythmic finger tapping task. We present results for 17 children with fetal alcohol syndrome (FAS) or partial FAS, 17 heavily exposed (HE) nonsyndromal children and 16 non- or minimally exposed controls. Controls showed greater cerebellar blood oxygen level dependent (BOLD) activation in right crus I, vermis IV-VI, and right lobule VI during rhythmic than non-rhythmic finger tapping. The alcohol-exposed children showed smaller activation increases during rhythmic tapping in right crus I than the control children and the most severely affected children with either FAS or PFAS showed smaller increases in vermis IV-V. Higher levels of maternal alcohol intake per occasion during pregnancy were associated with reduced activation increases during rhythmic tapping in all four regions associated with rhythmic tapping in controls. The four cerebellar areas activated by the controls more during rhythmic than non-rhythmic tapping have been implicated in the production of timed responses in several previous studies. These data provide evidence linking binge-like drinking during pregnancy to poorer function in cerebellar regions involved in timing and somatosensory processing needed for complex tasks requiring precise timing.

A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: profiles, mechanisms, and interventions.

PubMed

Kully-Martens, Katrina; Denys, Kennedy; Treit, Sarah; Tamana, Sukhpreet; Rasmussen, Carmen

2012-04-01

Individuals gestationally exposed to alcohol experience a multitude of sociobehavioral impairments, including deficits in adaptive behaviors such as social skills. The goal of this report is to critically review research on social skills deficits in individuals with prenatal alcohol exposure, including individuals with and without fetal alcohol spectrum disorders (FASD). Social deficits are found in alcohol-exposed children, adults, and adolescents with and without a clinical presentation. These deficits tend to persist across the lifespan and may even worsen with age. Social deficits in this population appear to be independent of facial dysmorphology and IQ and are worse than can be predicted based on atypical behaviors alone. Abnormalities in neurobiology, executive function, sensory processing, and communication likely interact with contextual influences to produce the range of social deficits observed in FASD. Future investigations should strive to reconcile the relationship between social skills deficits in FASD and variables such as gender, age, cognitive profile, and structural and functional brain impairments to enable better characterization of the deficits observed in this population, which will enhance diagnosis and improve remediation. Copyright © 2011 by the Research Society on Alcoholism.

Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective.

PubMed

Wilhelm, Clare J; Guizzetti, Marina

2015-01-01

Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.

Fetal Programming and Cardiovascular Pathology

PubMed Central

Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

2016-01-01

Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation

PubMed Central

Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P.; Zhou, Feng C.

2009-01-01

Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88 mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10 and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p < 0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in gene expression, which together may contribute to the observed abnormal fetal development. PMID:20009564

Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

PubMed

Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

2009-10-01

Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in gene expression, which together may contribute to the observed abnormal fetal development.

Deep serotonergic and dopaminergic structures in fetal alcoholic syndrome: a study with nor-beta-CIT-single-photon emission computed tomography and magnetic resonance imaging volumetry.

PubMed

Riikonen, Raili S; Nokelainen, Pekka; Valkonen, Kirsi; Kolehmainen, Anni I; Kumpulainen, Kirsti I; Könönen, Mervi; Vanninen, Ritva-Liisa S; Kuikka, Jyrki T

2005-06-15

In prenatally alcohol exposed children, the relationship between brain structure and function is highlighted to be important to study. We studied 12 children with fetal alcoholic syndrome (FAS) and fetal alcoholic effects (FAE) by magnetic resonance imaging volumetry and by single-photon emission computed tomography with iodine-123 labeled 2beta-carbomethoxy-3beta-(4-iodophenyl) ([123I]nor-beta-CIT) and related these findings to those from neuropsychological and psychiatric tests. The absolute volumes of studied nuclei, including the brain volume, were significantly smaller in FAS/FAE children than in control patients. After normalization of volumes, significant differences were not found. Left hippocampus was smaller than the right (p<.003) but did not significantly differ from the control subjects. The children with FAS/FAE showed reduced serotonin (p=.02) in the medial frontal cortex and slightly increased striatal dopamine transporter binding. All FAS/FAE children had attention-deficit/hyperkinetic disorder (ADHD). None had depression. The internalization scores correlated with dopamine transporter binding (r=-.65; p=.03). The results indicate that the serotonin (5-HT) system may be vulnerable to the effects of ethanol in utero. The high dopamine transporter levels may correlate with the ADHD findings. Reduced serotonin and increased binding of dopamine transporter are also seen in type 2 alcoholism. Some behavioral problems of FAS/FAE might be preventable by early intervention and treatment.

Maternal factors predicting cognitive and behavioral characteristics of children with fetal alcohol spectrum disorders.

PubMed

May, Philip A; Tabachnick, Barbara G; Gossage, J Phillip; Kalberg, Wendy O; Marais, Anna-Susan; Robinson, Luther K; Manning, Melanie A; Blankenship, Jason; Buckley, David; Hoyme, H Eugene; Adnams, Colleen M

2013-06-01

To provide an analysis of multiple predictors of cognitive and behavioral traits for children with fetal alcohol spectrum disorders (FASDs). Multivariate correlation techniques were used with maternal and child data from epidemiologic studies in a community in South Africa. Data on 561 first-grade children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and not FASD and their mothers were analyzed by grouping 19 maternal variables into categories (physical, demographic, childbearing, and drinking) and used in structural equation models (SEMs) to assess correlates of child intelligence (verbal and nonverbal) and behavior. A first SEM using only 7 maternal alcohol use variables to predict cognitive/behavioral traits was statistically significant (B = 3.10, p < .05) but explained only 17.3% of the variance. The second model incorporated multiple maternal variables and was statistically significant explaining 55.3% of the variance. Significantly correlated with low intelligence and problem behavior were demographic (B = 3.83, p < .05) (low maternal education, low socioeconomic status [SES], and rural residence) and maternal physical characteristics (B = 2.70, p < .05) (short stature, small head circumference, and low weight). Childbearing history and alcohol use composites were not statistically significant in the final complex model and were overpowered by SES and maternal physical traits. Although other analytic techniques have amply demonstrated the negative effects of maternal drinking on intelligence and behavior, this highly controlled analysis of multiple maternal influences reveals that maternal demographics and physical traits make a significant enabling or disabling contribution to child functioning in FASD.

Fetal alcohol syndrome: the origins of a moral panic.

PubMed

Armstrong, E M; Abel, E L

2000-01-01

Since its discovery almost 30 years ago, the fetal alcohol syndrome (FAS) has been characterized in the USA, as a major threat to public health. In part because FAS resonated with broader social concerns in the 1970s and 1980s about alcohol's deleterious effect on American society and about a perceived increase in child abuse and neglect, it quickly achieved prominence as a social problem. In this paper, we demonstrate that, as concern about this social problem escalated beyond the level warranted by the existing evidence, FAS took on the status of a moral panic. Through examples taken from both the biomedical literature and the media about drinking during pregnancy, we illustrate the evolution of this development, and we describe its implications, particularly how it has contributed to a vapid public policy response.

Fatty acid ethyl esters (FAEEs) as markers for alcohol in meconium: method validation and implementation of a screening program for prenatal drug exposure.

PubMed

Hastedt, Martin; Krumbiegel, Franziska; Gapert, René; Tsokos, Michael; Hartwig, Sven

2013-09-01

Alcohol consumption during pregnancy is a widespread problem and can cause severe fetal damage. As the diagnosis of fetal alcohol syndrome is difficult, the implementation of a reliable marker for alcohol consumption during pregnancy into meconium drug screening programs would be invaluable. A previously published gas chromatography mass spectrometry method for the detection of fatty acid ethyl esters (FAEEs) as alcohol markers in meconium was optimized and newly validated for a sample size of 50 mg. This method was applied to 122 cases from a drug-using population. The meconium samples were also tested for common drugs of abuse. In 73 % of the cases, one or more drugs were found. Twenty percent of the samples tested positive for FAEEs at levels indicating significant alcohol exposure. Consequently, alcohol was found to be the third most frequently abused substance within the study group. This re-validated method provides an increase in testing sensitivity, is reliable and easily applicable as part of a drug screening program. It can be used as a non-invasive tool to detect high alcohol consumption in the last trimester of pregnancy. The introduction of FAEEs testing in meconium screening was found to be of particular use in a drug-using population.

Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

PubMed

Petrelli, Berardino; Weinberg, Joanne; Hicks, Geoffrey G

2018-04-01

The potential impact of prenatal alcohol exposure (PAE) varies considerably among exposed individuals, with some displaying serious alcohol-related effects and many others showing few or no overt signs of fetal alcohol spectrum disorder (FASD). In animal models, variables such as nutrition, genetic background, health, other drugs, and stress, as well as dosage, duration, and gestational timing of exposure to alcohol can all be controlled in a way that is not possible in a clinical situation. In this review we examine mouse models of PAE and focus on those with demonstrated craniofacial malformations, abnormal brain development, or behavioral phenotypes that may be considered FASD-like outcomes. Analysis of these data should provide a valuable tool for researchers wishing to choose the PAE model best suited to their research questions or to investigate established PAE models for FASD comorbidities. It should also allow recognition of patterns linking gestational timing, dosage, and duration of PAE, such as recognizing that binge alcohol exposure(s) during early gestation can lead to severe FASD outcomes. Identified patterns could be particularly insightful and lead to a better understanding of the molecular mechanisms underlying FASD.

In Utero Alcohol Exposure, Epigenetic Changes, and Their Consequences

PubMed Central

Ungerer, Michelle; Knezovich, Jaysen; Ramsay, Michele

2013-01-01

Exposure to alcohol has serious consequences for the developing fetus, leading to a range of conditions collectively known as fetal alcohol spectrum disorders (FASD). Most importantly, alcohol exposure affects the development of the brain during critical periods of differentiation and growth, leading to cognitive and behavioral deficits. The molecular mechanisms and processes underlying the teratogenic effects of alcohol exposure remain poorly understood and are complex, because the specific effects depend on the timing, amount, and duration of exposure as well as genetic susceptibility. Accumulating evidence from studies on DNA methylation and histone modification that affect chromatin structure, as well as on the role of microRNAs in regulating mRNA levels supports the contribution of epigenetic mechanisms to the development of FASD. These epigenetic effects are difficult to study, however, because they often are cell-type specific and transient in nature. Rodent models play an important role in FASD research. Although recent studies using these models have yielded some insight into epigenetic mechanisms affecting brain development, they have generated more questions than they have provided definitive answers. Researchers are just beginning to explore the intertwined roles of different epigenetic mechanisms in neurogenesis and how this process is affected by exposure to alcohol, causing FASD. PMID:24313163

Dose-dependent alcohol-induced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects.

PubMed

Veazey, Kylee J; Parnell, Scott E; Miranda, Rajesh C; Golding, Michael C

2015-01-01

In recent years, we have come to recognize that a multitude of in utero exposures have the capacity to induce the development of congenital and metabolic defects. As most of these encounters manifest their effects beyond the window of exposure, deciphering the mechanisms of teratogenesis is incredibly difficult. For many agents, altered epigenetic programming has become suspect in transmitting the lasting signature of exposure leading to dysgenesis. However, while several chemicals can perturb chromatin structure acutely, for many agents (particularly alcohol) it remains unclear if these modifications represent transient responses to exposure or heritable lesions leading to pathology. Here, we report that mice encountering an acute exposure to alcohol on gestational Day-7 exhibit significant alterations in chromatin structure (histone 3 lysine 9 dimethylation, lysine 9 acetylation, and lysine 27 trimethylation) at Day-17, and that these changes strongly correlate with the development of craniofacial and central nervous system defects. Using a neural cortical stem cell model, we find that the epigenetic changes arising as a consequence of alcohol exposure are heavily dependent on the gene under investigation, the dose of alcohol encountered, and that the signatures arising acutely differ significantly from those observed after a 4-day recovery period. Importantly, the changes observed post-recovery are consistent with those modeled in vivo, and associate with alterations in transcripts encoding multiple homeobox genes directing neurogenesis. Unexpectedly, we do not observe a correlation between alcohol-induced changes in chromatin structure and alterations in transcription. Interestingly, the majority of epigenetic changes observed occur in marks associated with repressive chromatin structure, and we identify correlative disruptions in transcripts encoding Dnmt1, Eed, Ehmt2 (G9a), EzH2, Kdm1a, Kdm4c, Setdb1, Sod3, Tet1 and Uhrf1. These observations suggest that the immediate and long-term impacts of alcohol exposure on chromatin structure are distinct, and hint at the existence of a possible coordinated epigenetic response to ethanol during development. Collectively, our results indicate that alcohol-induced modifications to chromatin structure persist beyond the window of exposure, and likely contribute to the development of fetal alcohol syndrome-associated congenital abnormalities.

Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

PubMed

Glendinning, John I; Tang, Joyce; Morales Allende, Ana Paula; Bryant, Bruce P; Youngentob, Lisa; Youngentob, Steven L

2017-08-01

Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes. NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal chemosensory neurons. We found that FAE substantially reduced taste and trigeminal responsiveness to ethanol and its flavor components. Copyright © 2017 the American Physiological Society.

Magnetic resonance imaging (MRI) findings among children with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS) and alcohol related neurodevelopmental disorders (ARND).

PubMed

Anna Dyląg, Katarzyna; Sikora-Sporek, Aleksanda; Bańdo, Bożena; Boroń-Zyss, Joanna; Drożdż, Dorota; Dumnicka, Paulina; Przybyszewska, Katarzyna; Sporek, Mateusz; Walocha, Jerzy W; Wojciechowski, Wadim; Urbanik, Andrzej

The aim of the study was to analyze the findings in MRI (magnetic resonance imaging) of the brain amongst children diagnosed with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS) or alcohol related neurodevelopmental disorders (ARND). The issue has been studied in several researches previously but the experts agree that there is still few data on the MRI results in the group of younger children. MRI results of 121 patients with either FAS or pFAS or ARND diagnosed with Canadian criteria were analyzed regarding the presence of abnormalities. The group consisted of 71 patients diagnosed with FAS, 33 diagnosed with pFAS and 17 diagnosed with ARND. The mean age of the patients was 8.03 years (standard deviation 4.07). In the total group of FASD patients 61.98% of the patients’ MRI results were abnormal. The most common abnormality in MRI of the patients were demyelination plaques (incidence 23.1%) and corpus callosum narrowing (20.7%) as well as ventricular asymmetry (18.8%).The demyelination plaques and corpus callosum narrowing were more frequent among children ≤4 years old (41.7% vs 18.6%; p=0.016 and 50.0% vs.13.4%; p<0.001, respectively). Age ≤4 years predicted the presence of demyelination plaques and corpus callosum narrowing independently of FAS diagnosis. Among younger children, multiple central nervous system abnormalities were observed more often than in the older age group (54.2% vs. 14.4%; p<0.001). Odds ratio for multiple changes was 0.84 per one-year increase in age (95% CI 0.73-0.97), p=0.016. Furthermore, in the analysis according to the specific diagnosis, among the patients diagnosed with FAS, multiple anomalies were more common than in pFAS and ARND. Both age ≤4 years and FAS diagnosis were independent predictors for multiple anomalies in multiple logistic regression. In structural brain MRI of younger children, multiple anomalies were found more frequently than among older children. Demyelination plaques and corpus callosum narrowing were more common in younger FASD patients than in older ones.

Fetal Substance Exposure and Cumulative Environmental Risk in an African American Cohort

ERIC Educational Resources Information Center

Yumoto, Chie; Jacobson, Sandra W.; Jacobson, Joseph L.

2008-01-01

Two models of vulnerability to socioenvironmental risk were examined in 337 African American children (M = 7.8 years) recruited to overrepresent prenatal alcohol or cocaine exposure: The cumulative risk model predicted synergistic effects from exposure to multiple risk factors, and the fetal patterning of disease model predicted that prenatal…

Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice

PubMed Central

Laufer, Benjamin I.; Mantha, Katarzyna; Kleiber, Morgan L.; Diehl, Eric J.; Addison, Sean M. F.; Singh, Shiva M.

2013-01-01

SUMMARY Fetal alcohol spectrum disorders (FASDs) are characterized by life-long changes in gene expression, neurodevelopment and behavior. What mechanisms initiate and maintain these changes are not known, but current research suggests a role for alcohol-induced epigenetic changes. In this study we assessed alterations to adult mouse brain tissue by assaying DNA cytosine methylation and small noncoding RNA (ncRNA) expression, specifically the microRNA (miRNA) and small nucleolar RNA (snoRNA) subtypes. We found long-lasting alterations in DNA methylation as a result of fetal alcohol exposure, specifically in the imprinted regions of the genome harboring ncRNAs and sequences interacting with regulatory proteins. A large number of major nodes from the identified networks, such as Pten signaling, contained transcriptional repressor CTCF-binding sites in their promoters, illustrating the functional consequences of alcohol-induced changes to DNA methylation. Next, we assessed ncRNA expression using two independent array platforms and quantitative PCR. The results identified 34 genes that are targeted by the deregulated miRNAs. Of these, four (Pten, Nmnat1, Slitrk2 and Otx2) were viewed as being crucial in the context of FASDs given their roles in the brain. Furthermore, ∼20% of the altered ncRNAs mapped to three imprinted regions (Snrpn-Ube3a, Dlk1-Dio3 and Sfmbt2) that showed differential methylation and have been previously implicated in neurodevelopmental disorders. The findings of this study help to expand on the mechanisms behind the long-lasting changes in the brain transcriptome of FASD individuals. The observed changes could contribute to the initiation and maintenance of the long-lasting effect of alcohol. PMID:23580197

Drugs, Alcohol and Pregnancy: Parents and Children At Risk. Emerging Issues. A Report.

ERIC Educational Resources Information Center

Fallon, Stacie Alexander

The effects of drug and alcohol use by pregnant women which concern state policymakers are discussed in this booklet. Topics discussed include: (1) the effects of fetal alcohol syndrome on infants and children, as well as the effects on children of drug use by mothers during pregnancy; (2) initiatives aimed at helping these children; (3) women…

Skeletal muscle and fetal alcohol spectrum disorder.

PubMed

Myrie, Semone B; Pinder, Mark A

2018-04-01

Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol ("prenatal alcohol exposure"; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE.

Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child Characteristics, and Maternal Risk Factors in a Second Sample of Rural Communities in South Africa

PubMed Central

May, Philip A.; De Vries, Marlene M.; Marais, Anna-Susan; Kalberg, Wendy O.; Buckley, David; Adnams, Colleen M.; Hasken, Julie M.; Tabachnick, Barbara; Robinson, Luther K.; Manning, Melanie A.; Bezuidenhout, Heidre; Adam, Margaret P.; Jones, Kenneth L.; Seedat, Soraya; Parry, Charles D.H.; Hoyme, H. Eugene

2017-01-01

Background: Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods: Active case ascertainment focused on children with height, weight and/or head circumference ≤25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results: Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 89–129 per 1000 children. Total FASD affect 196–276 per 1000 or 20–28% of the children in these communities. Conclusions: Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions. PMID:28498341

Time to Address a Preventable Tragedy.

ERIC Educational Resources Information Center

Wescott, Siobhan M.

1990-01-01

Discusses the epidemic of fetal alcohol syndrome (FAS) affecting Native American communities, the lifetime costs associated with an FAS birth, behavioral aberrations of FAS children that affect classroom performance, and federal and state legislation and funding aimed at FAS prevention through treatment of pregnant alcoholics. (SV)

Phosphodiesterase Inhibition Increases CREB Phosphorylation and Restores Orientation Selectivity in a Model of Fetal Alcohol Spectrum Disorders

PubMed Central

Krahe, Thomas E.; Wang, Weili; Medina, Alexandre E.

2009-01-01

Background Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity. Methodology/Principal Findings Here we show that the primary visual cortex of ferrets exposed to alcohol during the third trimester equivalent of human gestation have decreased CREB phosphorylation and poor orientation selectivity revealed by western blotting, optical imaging of intrinsic signals and single-unit extracellular recording techniques. Treating animals several days after the period of alcohol exposure with a phosphodiesterase type 1 inhibitor (Vinpocetine) increased CREB phosphorylation and restored orientation selectivity columns and neuronal orientation tuning. Conclusions/Significance These findings suggest that CREB function is important for the maturation of orientation selectivity and that plasticity enhancement by vinpocetine may play a role in the treatment of sensory problems in FASD. PMID:19680548

Automated diagnosis of fetal alcohol syndrome using 3D facial image analysis

PubMed Central

Fang, Shiaofen; McLaughlin, Jason; Fang, Jiandong; Huang, Jeffrey; Autti-Rämö, Ilona; Fagerlund, Åse; Jacobson, Sandra W.; Robinson, Luther K.; Hoyme, H. Eugene; Mattson, Sarah N.; Riley, Edward; Zhou, Feng; Ward, Richard; Moore, Elizabeth S.; Foroud, Tatiana

2012-01-01

Objectives Use three-dimensional (3D) facial laser scanned images from children with fetal alcohol syndrome (FAS) and controls to develop an automated diagnosis technique that can reliably and accurately identify individuals prenatally exposed to alcohol. Methods A detailed dysmorphology evaluation, history of prenatal alcohol exposure, and 3D facial laser scans were obtained from 149 individuals (86 FAS; 63 Control) recruited from two study sites (Cape Town, South Africa and Helsinki, Finland). Computer graphics, machine learning, and pattern recognition techniques were used to automatically identify a set of facial features that best discriminated individuals with FAS from controls in each sample. Results An automated feature detection and analysis technique was developed and applied to the two study populations. A unique set of facial regions and features were identified for each population that accurately discriminated FAS and control faces without any human intervention. Conclusion Our results demonstrate that computer algorithms can be used to automatically detect facial features that can discriminate FAS and control faces. PMID:18713153

Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders

PubMed Central

Murawski, Nathen J.; Moore, Eileen M.; Thomas, Jennifer D.; Riley, Edward P.

2015-01-01

Prenatal alcohol exposure can cause a number of physical, behavioral, cognitive, and neural impairments, collectively known as fetal alcohol spectrum disorders (FASD). This article examines basic research that has been or could be translated into practical applications for the diagnosis or treatment of FASD. Diagnosing FASD continues to be a challenge, but advances are being made at both basic science and clinical levels. These include identification of biomarkers, recognition of subtle facial characteristics of exposure, and examination of the relation between face, brain, and behavior. Basic research also is pointing toward potential new interventions for FASD involving pharmacotherapies, nutritional therapies, and exercise interventions. Although researchers have assessed the majority of these treatments in animal models of FASD, a limited number of recent clinical studies exist. An assessment of this literature suggests that targeted interventions can improve some impairments resulting from developmental alcohol exposure. However, combining interventions may prove more efficacious. Ultimately, advances in basic and clinical sciences may translate to clinical care, improving both diagnosis and treatment. PMID:26259091

Maternal nutritional status as a contributing factor for the risk of fetal alcohol spectrum disorders.

PubMed

May, Philip A; Hamrick, Kari J; Corbin, Karen D; Hasken, Julie M; Marais, Anna-Susan; Blankenship, Jason; Hoyme, H Eugene; Gossage, J Phillip

2016-01-01

Compare nutritional status of 57 South African mothers of children with fetal alcohol spectrum disorders (FASD) with 148 mothers of controls. Dietary data were analyzed for macronutrients, micronutrients, and fats via estimated average requirements (EAR) and adequate intakes (AI) for pregnant women. Virtually all mothers were likely deficient on most micronutrients by either EAR (<50%) or AI values. Mothers of FASD children consumed more of 13 of 25 micronutrients. For percentage below EAR, only vitamin D was significantly higher for FASD mothers. Despite no difference in total food intake, control mothers had a higher mean body mass index (BMI) than FASD mothers. Maternal BMI is more significant for positive child outcomes than any individual nutrient. Most mothers have inadequate dietary intake. Minor advantages in nutrient intake are overpowered by teratogenic effects of alcohol. Further study is needed of the interaction of alcohol, maternal nutrition, and metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurocognitive habilitation therapy for children with fetal alcohol spectrum disorders: an adaptation of the Alert Program®.

PubMed

Wells, Anne M; Chasnoff, Ira J; Schmidt, Christine A; Telford, Erin; Schwartz, Linda D

2012-01-01

This study evaluated the effectiveness of neurocognitive habilitation, a group therapy intervention for foster and adoptive caregivers and their children who were prenatally exposed to alcohol. Participants were recruited from clients seeking evaluation for fetal alcohol syndrome (FAS) and alcohol-related neurodevelopmental disorder (ARND) and were randomly assigned to treatment and no-treatment control groups. Forty children participated in the treatment program and were compared with 38 control participants using the Behavior Rating Inventory of Executive Function (BRIEF) and the Roberts Apperception Test for Children (RATC). Significant differences between the treatment and control groups were demonstrated on the BRIEF and on the RATC, suggesting that the intervention improved executive functioning and emotional problem-solving skills. These findings yield promising evidence of the effectiveness of the neurocognitive habilitation intervention in improving executive functioning and emotional problem solving in children with FAS or ARND. Copyright © 2012 by the American Occupational Therapy Association, Inc.

Fetal Alcohol Spectrum Disorders (FASD) and competency to stand trial (CST): Suggestions for a 'best practices' approach to forensic evaluation.

PubMed

Brown, Jerrod M; Haun, Jeffrey; Zapf, Patricia A; Brown, Natalie Novick

Fetal Alcohol Spectrum Disorders (FASD), an umbrella term for neurodevelopmental conditions caused by prenatal alcohol exposure, is overrepresented in the U.S. juvenile and adult criminal justice systems. The brain damage in FASD manifests in a combination of cognitive and adaptive impairments that potentially reduce ability to function adequately during the criminal justice process, including capacity to stand trial (CST). Despite the high risk of arrest and conviction in this population, relatively little research guides CST assessment for defendants who have or may have FASD. Therefore, the purpose of this article is to describe how FASD may affect CST and suggest ways forensic professionals might modify assessment protocols to address possible effects of FASD-associated impairments on adjudicative capacity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder

PubMed Central

Mooney, Sandra M.; Middleton, Frank A.

2017-01-01

Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure. In the present study we examined the effect of ethanol-induced cellular and molecular responses in primary somatosensory cortex (SI) and hippocampus of 7-day-old wild-type (WT) and p53-knockout (KO) mice. We quantified apoptosis by active caspase-3 immunohistochemistry and ApopTag™ labeling, then determined total RNA expression levels in laminae of SI and hippocampal subregions. Immunohistochemical results confirmed increased incidence of apoptotic cells in both regions in WT and KO mice following ethanol exposure. The lack of p53 was not protective in these brain regions. Molecular analyses revealed a heterogeneous response to ethanol exposure that varied depending on the subregion, and which may go undetected using a global approach. Gene network analyses suggest that the presence or absence of p53 alters neuronal function and synaptic modifications following ethanol exposure, in addition to playing a classic role in cell cycle signaling. Thus, p53 may function in a way that underlies the intellectual and behavioral deficits observed in FASD. PMID:28723918

Long-term genomic and epigenomic dysregulation as a consequence of prenatal alcohol exposure: a model for fetal alcohol spectrum disorders.

PubMed

Kleiber, Morgan L; Diehl, Eric J; Laufer, Benjamin I; Mantha, Katarzyna; Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M

2014-01-01

There is abundant evidence that prenatal alcohol exposure leads to a range of behavioral and cognitive impairments, categorized under the term fetal alcohol spectrum disorders (FASDs). These disorders are pervasive in Western cultures and represent the most common preventable source of neurodevelopmental disabilities. The genetic and epigenetic etiology of these phenotypes, including those factors that may maintain these phenotypes throughout the lifetime of an affected individual, has become a recent topic of investigation. This review integrates recent data that has progressed our understanding FASD as a continuum of molecular events, beginning with cellular stress response and ending with a long-term "footprint" of epigenetic dysregulation across the genome. It reports on data from multiple ethanol-treatment paradigms in mouse models that identify changes in gene expression that occur with respect to neurodevelopmental timing of exposure and ethanol dose. These studies have identified patterns of genomic alteration that are dependent on the biological processes occurring at the time of ethanol exposure. This review also adds to evidence that epigenetic processes such as DNA methylation, histone modifications, and non-coding RNA regulation may underlie long-term changes to gene expression patterns. These may be initiated by ethanol-induced alterations to DNA and histone methylation, particularly in imprinted regions of the genome, affecting transcription which is further fine-tuned by altered microRNA expression. These processes are likely complex, genome-wide, and interrelated. The proposed model suggests a potential for intervention, given that epigenetic changes are malleable and may be altered by postnatal environment. This review accentuates the value of mouse models in deciphering the molecular etiology of FASD, including those processes that may provide a target for the ammelioration of this common yet entirely preventable disorder.

Long-term genomic and epigenomic dysregulation as a consequence of prenatal alcohol exposure: a model for fetal alcohol spectrum disorders

PubMed Central

Kleiber, Morgan L.; Diehl, Eric J.; Laufer, Benjamin I.; Mantha, Katarzyna; Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M.

2014-01-01

There is abundant evidence that prenatal alcohol exposure leads to a range of behavioral and cognitive impairments, categorized under the term fetal alcohol spectrum disorders (FASDs). These disorders are pervasive in Western cultures and represent the most common preventable source of neurodevelopmental disabilities. The genetic and epigenetic etiology of these phenotypes, including those factors that may maintain these phenotypes throughout the lifetime of an affected individual, has become a recent topic of investigation. This review integrates recent data that has progressed our understanding FASD as a continuum of molecular events, beginning with cellular stress response and ending with a long-term “footprint” of epigenetic dysregulation across the genome. It reports on data from multiple ethanol-treatment paradigms in mouse models that identify changes in gene expression that occur with respect to neurodevelopmental timing of exposure and ethanol dose. These studies have identified patterns of genomic alteration that are dependent on the biological processes occurring at the time of ethanol exposure. This review also adds to evidence that epigenetic processes such as DNA methylation, histone modifications, and non-coding RNA regulation may underlie long-term changes to gene expression patterns. These may be initiated by ethanol-induced alterations to DNA and histone methylation, particularly in imprinted regions of the genome, affecting transcription which is further fine-tuned by altered microRNA expression. These processes are likely complex, genome-wide, and interrelated. The proposed model suggests a potential for intervention, given that epigenetic changes are malleable and may be altered by postnatal environment. This review accentuates the value of mouse models in deciphering the molecular etiology of FASD, including those processes that may provide a target for the ammelioration of this common yet entirely preventable disorder. PMID:24917881

Fetal Alcohol Spectrum Disorders: Using Knowledge, Attitudes and Practice of Justice Professionals to Support their Educational Needs.

PubMed

Mutch, Raewyn C; Jones, Heather M; Bower, Carol; Watkins, Rochelle E

2016-01-01

People with Fetal Alcohol Spectrum Disorders (FASD) can be involved in high risk, socially unacceptable and harmful behaviours and are at high risk of engaging with the justice system. To obtain baseline data on Western Australian justice professionals' knowledge, attitudes and practice relating to FASD to inform the development of FASD resources. Cross sectional study using on-line survey methods, descriptive analysis of quantitative data and content analysis methods for qualitative data. 1873 people were invited to complete the survey. A total of 427 (23%) judicial officers, lawyers, corrective services personnel and police completed the survey. The majority had heard of Fetal Alcohol Syndrome (85%) but were less familiar with FASD (60%). Only 16% of respondents identified the key features of FASD as permanent and only 48.4% considered psychological difficulties as important. The majority of legal and judicial officers and approximately half the police officers considered that knowledge about FASD was very relevant to their work. There was widespread agreement of the need for more information and training about FASD to optimise outcomes for people with, or suspected of having a FASD, engaging with the justice system.

Construction of vapor chambers used to expose mice to alcohol during the equivalent of all three trimesters of human development.

PubMed

Morton, Russell A; Diaz, Marvin R; Topper, Lauren A; Valenzuela, C Fernando

2014-07-13

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal Alcohol Spectrum Disorders (FASDs). At the most severe end of the spectrum is Fetal Alcohol Syndrome (FAS), characterized by growth retardation, craniofacial dysmorphology, and neurobehavioral deficits. Studies with animal models, including rodents, have elucidated many molecular and cellular mechanisms involved in the pathophysiology of FASDs. Ethanol administration to pregnant rodents has been used to model human exposure during the first and second trimesters of pregnancy. Third trimester ethanol consumption in humans has been modeled using neonatal rodents. However, few rodent studies have characterized the effect of ethanol exposure during the equivalent to all three trimesters of human pregnancy, a pattern of exposure that is common in pregnant women. Here, we show how to build vapor chambers from readily obtainable materials that can each accommodate up to six standard mouse cages. We describe a vapor chamber paradigm that can be used to model exposure to ethanol, with minimal handling, during all three trimesters. Our studies demonstrate that pregnant dams developed significant metabolic tolerance to ethanol. However, neonatal mice did not develop metabolic tolerance and the number of fetuses, fetus weight, placenta weight, number of pups/litter, number of dead pups/litter, and pup weight were not significantly affected by ethanol exposure. An important advantage of this paradigm is its applicability to studies with genetically-modified mice. Additionally, this paradigm minimizes handling of animals, a major confound in fetal alcohol research.

Maternal Factors Predicting Cognitive and Behavioral Characteristics of Children with Fetal Alcohol Spectrum Disorders

PubMed Central

May, Philip A.; Tabachnick, Barbara G.; Gossage, J. Phillip; Kalberg, Wendy O.; Marais, Anna-Susan; Robinson, Luther K.; Manning, Melanie A.; Blankenship, Jason; Buckley, David; Hoyme, H. Eugene; Adnams, Colleen M.

2013-01-01

Objective To provide an analysis of multiple predictors of cognitive and behavioral traits for children with fetal alcohol spectrum disorders (FASD). Method Multivariate correlation techniques were employed with maternal and child data from epidemiologic studies in a community in South Africa. Data on 561 first grade children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and not FASD and their mothers were analyzed by grouping 19 maternal variables into categories (physical, demographic, childbearing, and drinking) and employed in structural equation models (SEM) to assess correlates of child intelligence (verbal and non-verbal) and behavior. Results A first SEM utilizing only seven maternal alcohol use variables to predict cognitive/behavioral traits was statistically significant (B = 3.10, p < .05), but explained only 17.3% of the variance. The second model incorporated multiple maternal variables and was statistically significant explaining 55.3% of the variance. Significantly correlated with low intelligence and problem behavior were demographic (B = 3.83, p < .05) (low maternal education, low socioeconomic status (SES), and rural residence) and maternal physical characteristics (B = 2.70, p < .05) (short stature, small head circumference, and low weight). Childbearing history and alcohol use composites were not statistically significant in the final complex model, and were overpowered by SES and maternal physical traits. Conclusions While other analytic techniques have amply demonstrated the negative effects of maternal drinking on intelligence and behavior, this highly-controlled analysis of multiple maternal influences reveals that maternal demographics and physical traits make a significant enabling or disabling contribution to child functioning in FASD. PMID:23751886

Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine.

PubMed

Wells, Peter G; Bhatia, Shama; Drake, Danielle M; Miller-Pinsler, Lutfiya

2016-06-01

In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms. Antioxidative enzymes, like catalase in the fetal brain, while low, provide critical protection. Oxidatively damaged DNA is normally rapidly repaired, and fetal deficiencies in several DNA repair proteins, including oxoguanine glycosylase 1 (OGG1) and breast cancer protein 1 (BRCA1), enhance the risk of drug-initiated postnatal neurodevelopmental deficits, and in some cases deficits in untreated progeny, the latter of which may be relevant to conditions like autism spectrum disorders (ASD). Risk is further regulated by fetal nuclear factor erythroid 2-related factor 2 (Nrf2), a ROS-sensing protein that upregulates an array of proteins, including antioxidative enzymes and DNA repair proteins. Imbalances between conceptal pathways for ROS formation, versus those for ROS detoxification and DNA repair, are important determinants of risk. Birth Defects Research (Part C) 108:108-130, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Even Low Levels of Alcohol during Pregnancy Can Affect Fetal Brain Development. Science Briefs

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2008

2008-01-01

"Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Effects of Prenatal Alcohol Exposure on GABAergic Neurons" (V. C. Cuzone; P. W. L. Yeh; Y. Yanagawa; K. Obata; and H. H. Yeh). Study results indicate that even exposure to low levels of alcohol during…

Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure.

PubMed

Kalberg, Wendy O; Provost, Beth; Tollison, Sean J; Tabachnick, Barbara G; Robinson, Luther K; Eugene Hoyme, H; Trujillo, Phyllis M; Buckley, David; Aragon, Alfredo S; May, Philip A

2006-12-01

Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor delays in children with FAS may be related to specific neurobehavioral deficits that affect fine motor skills. The findings support the concept of an FASD continuum in some areas of motor development.

MARKERS OF OXIDATIVE STRESS AND SYSTEMIC VASOCONSTRICTION IN PREGNANT WOMEN DRINKING ≥ 48 GRAMS OF ALCOHOL PER DAY

PubMed Central

Signore, Caroline; Aros, Sofía; Morrow, Jason D.; Troendle, James; Conley, Mary R.; Flanigan, Elizabeth Y.; Cassorla, Fernando; Mills, James L.

2008-01-01

Background The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders (FASD) is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy. Methods Pregnant women consuming ≥ 48g alcohol/day (n=29) on average and pregnant women who abstained from alcohol use (n=39) were identified using detailed interviews and home visits. Random maternal urine specimens were collected. Urinary levels of the oxidative stress marker, 8-isoprostane F2α, and of the vasoactive prostaglandin metabolites, 2,3-dinor-6-keto-prostaglandin F1α (a vasodilator) and 11-dehydro-thromboxane B2 (a vasoconstrictor), were measured using mass spectrometric methods. All analyte levels were corrected for urinary creatinine. Results In crude analyses, there was no significant difference in 8-isoprostane F2α between pregnant drinkers and nondrinkers (2.16 vs. 2.08 ng/mg creatinine respectively, P=.87). There were no significant differences between the drinking and non-drinking groups in levels of 2,3-dinor-6-keto-prostaglandin F1α (1.03 vs. 1.17 ng/mg creatinine repectively, P=.50), 11-dehydro-thromboxane B2 (0.72 vs. 0.59 ng/mg creatinine respectively, P=.21), or the ratio of vasodilatory metabolite to vasoconstrictive metabolite (1.73 vs. 2.72 respectively, P=.14). Adjusting for maternal age, marital status, smoking, and gestational age at sampling did not substantially alter the results. Conclusion Our results show no difference in levels of urinary eicosanoid markers of oxidative stress and systemic vasoconstriction between pregnant women who drink heavily and pregnant women who abstain. These findings speak against a role for maternal oxidative stress or systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus. PMID:18715278

INFANT EMOTIONAL WITHDRAWAL: A PRECURSOR OF AFFECTIVE AND COGNITIVE DISTURBANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

PubMed Central

Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Dodge, Neil C.; Jacobson, Sandra W.

2013-01-01

Objectives To test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. Methods The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Socio-demographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years; cognitive and affective function, at 5 and 9 years. Results Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all four infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. Conclusions This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother-infant interaction, infant temperament, or other socioemotional aspects of the infant’s environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS. PMID:24033350

Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study.

PubMed

2008-11-03

To examine the association of maternal caffeine intake with fetal growth restriction. Prospective longitudinal observational study. Two large UK hospital maternity units. 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy. Investigations Quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Smoking and alcohol were assessed by self reported status and by measuring salivary cotinine concentrations. Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations. Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction (odds ratios 1.2 (95% CI 0.9 to 1.6) for 100-199 mg/day, 1.5 (1.1 to 2.1) for 200-299 mg/day, and 1.4 (1.0 to 2.0) for >300 mg/day compared with <100 mg/day; test for trend P<0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster compared to a slower caffeine clearance (test for interaction, P=0.06). Caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy.

Magnetic resonance imaging findings in substance abuse: alcohol and alcoholism and syndromes associated with alcohol abuse.

PubMed

Spampinato, M Vittoria; Castillo, Mauricio; Rojas, Rafael; Palacios, Enrique; Frascheri, Laura; Descartes, Fernando

2005-06-01

Alcohol abuse is common among the population and results in significant diseases that shorten life span. Ethanol may result in chronic brain changes such as atrophy but may also result in neurologic disease that may be acute or chronic and sometimes life threatening. Accompanying vitamin deficiencies may lead to Wernicke's encephalopathy and changes in serum osmosis may lead to several acute demyelinating disorders. In addition, pregnant women who consume alcohol place their babies at high risk for the fetal alcohol syndrome. In this article we review these disorders and emphasize their imaging features.

PERFLUOROOCTANOIC ACID AND PERFLUORONONANOIC ACID IN FETAL AND NEONATAL MICE FOLLOWING IN UTERO EXPOSURE TO 8-2 FLUOROTELOMER ALCOHOL

EPA Science Inventory

8-2 fluorotelomer alcohol (FTOH) and its metabolites, perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), are developmental toxicants, but metabolism and distribution during pregnancy is not known. To examine this, timed-pregnant mice received a single gavage dose (...

FASD Prevalence among Schoolchildren in Poland.

PubMed

Okulicz-Kozaryn, Katarzyna; Borkowska, Magdalena; Brzózka, Krzysztof

2017-01-01

Prenatal Alcohol Exposure is a major cause of brain damage and developmental delay, known as Fetal Alcohol Spectrum Disorders (FASD) but in Poland is rarely diagnosed and the scale of problem is not known. An active case ascertainment approach was applied to estimate the prevalence of FASD among 7-9 years olds. Pre-screening was conducted in 113 randomly selected regular and special schools. In the screening phase participated 280 children (54% from the risk group, 60% boys). The entire number of eligible students (N = 2500) was taken as a denominator. The prevalence of FASD is not lower than 2%, including 0.4% of Fetal Alcohol Syndrome. Neurodevelopmental disorders associated with PAE are a serious challenge for the public health system. Development of procedures and services to diagnose and to support individuals affected by PAE and their families is an urgent need in Poland. © 2015 John Wiley & Sons Ltd.

Proceedings of the 2017 annual meeting of the Fetal Alcohol Spectrum Disorders study group.

PubMed

Wozniak, Jeffrey R; Klintsova, Anna Y; Hamilton, Derek A; Mooney, Sandra M

2018-06-01

The 2017 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was titled "Prenatal alcohol exposure in the context of multiple factors affecting brain development." The theme was reflected in the interactions between members of the Teratology Society and the FASDSG this year. The first keynote speaker, Elaine Faustman, Ph.D., was a liaison between the societies and spoke about systems biology and the multiple genetic and environmental influences on development. The second keynote speaker, Rebecca Knickmeyer, Ph.D., discussed population neuroscience and multiple influences on brain development. The conference presented updates from three government agencies and short presentations by junior and senior investigators showcasing late-breaking FASD research. The conference was capped by Dr. John Hannigan, Ph.D., the recipient of the 2017 Henry Rosett award for career-long contributions to the field. Copyright © 2017 Elsevier Inc. All rights reserved.

Understanding and managing sleep disruption in children with fetal alcohol spectrum disorder.

PubMed

Hanlon-Dearman, Ana; Chen, Maida Lynn; Olson, Heather Carmichael

2018-04-01

Accumulating evidence has revealed high rates of sleep disruption among children with fetal alcohol spectrum disorder (FASD). Multiple animal and clinical studies have found a clear association between sleep problems and prenatal alcohol exposure, and recent research is beginning to characterize the types and extent of sleep disruption in FASD. Nevertheless, sleep disruption in children with FASD often goes unrecognized or is treated without referring to an evidence base. Children's disrupted sleep interferes with parental sleep and increases caregiver burden, which is of particular importance for families raising children with FASD, a group with very high levels of caregiving stress. The literature supporting an association between sleep problems and deficits in emotional, behavioral, and cognitive function in children is compelling, but needs further investigation in children with FASD. This paper will review the current state of knowledge on sleep in FASD and recommend a rational approach to sleep interventions for affected children and their families.

Parenting skills and family support programs for drug-abusing mothers.

PubMed

Kumpfer, Karol L; Fowler, Melissa A

2007-04-01

Children born to drug-using mothers can suffer from fetal alcohol or drug syndrome (FAS/FDS) or fetal alcohol or drug effect (FAE/FDE). Such children have a greater likelihood of developing acute or chronic physical, cognitive and behavioral problems. In-utero exposure to tobacco, alcohol or drugs impact on the developing fetus and, after birth, the family environment and family system exert effects on the infants and children of substance-abusing parents. Evidence-based prevention and maternal drug treatment programs focus on enhancing parental childcaring abilities, supporting parent-child attachment and encouraging family support systems to improve children's health and cognitive outcomes. FAS/FDS prevention programs, as well as selective and indicated prenatal and postnatal interventions, can improve the support given both to mother and to child, and evidence-based, in-home parenting and family-skills-training approaches are particularly useful.

[Alcohol and pregnancy].

PubMed

Seror, E; Chapelon, E; Bué, M; Garnier-Lengliné, H; Lebeaux-Legras, C; Loudenot, A; Lejeune, C

2009-10-01

Alcohol consumption during pregnancy is a major cause of mental retardation in Western countries. Fetal alcohol syndrome (FAS) is mainly characterized by pre- and postnatal stunted growth, neurocognitive disorders, and facial dysmorphism. It compromises the intellectual and behavioral prognosis of the child. Prevention tools exist, through better information of health professionals, for optimal care of high-risk women before, during, and after pregnancy, which would decrease the incidence of SAF in the future.

Sleep in infants and children with prenatal alcohol exposure.

PubMed

Inkelis, Sarah M; Thomas, Jennifer D

2018-05-31

Prenatal exposure to alcohol can result in a range of neurobehavioral impairments and physical abnormalities. The term fetal alcohol spectrum disorders (FASD) encompasses the outcomes of prenatal alcohol exposure (PAE), the most severe of which is fetal alcohol syndrome (FAS). These effects have lifelong consequences, placing a significant burden on affected individuals, caregivers, and communities. Caregivers of affected children often report that their child has sleep problems, and many symptoms of sleep deprivation overlap with the cognitive and behavioral deficits characteristic of FASD. Alcohol-exposed infants and children demonstrate poor sleep quality based on measures of electroencephalography (EEG), actigraphy, and questionnaires. These sleep studies indicate a common theme of disrupted sleep pattern, more frequent awakenings, and reduced total sleep time. However, relatively little is known about circadian rhythm disruption, and the neurobehavioral correlates of sleep disturbance in individuals with PAE. Furthermore, there is limited information available to healthcare providers about identification and treatment of sleep disorders in patients with FASD. This review consolidates the findings from studies of infant and pediatric sleep in this population, providing an overview of typical sleep characteristics, neurobehavioral correlates of sleep disruption, and potential avenues for intervention in the context of PAE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Exploring the utility of narrative analysis in diagnostic decision making: picture-bound reference, elaboration, and fetal alcohol spectrum disorders.

PubMed

Thorne, John C; Coggins, Truman E; Carmichael Olson, Heather; Astley, Susan J

2007-04-01

To evaluate classification accuracy and clinical feasibility of a narrative analysis tool for identifying children with a fetal alcohol spectrum disorder (FASD). Picture-elicited narratives generated by 16 age-matched pairs of school-aged children (FASD vs. typical development [TD]) were coded for semantic elaboration and reference strategy by judges who were unaware of age, gender, and group membership of the participants. Receiver operating characteristic (ROC) curves were used to examine the classification accuracy of the resulting set of narrative measures for making 2 classifications: (a) for the 16 children diagnosed with FASD, low performance (n = 7) versus average performance (n = 9) on a standardized expressive language task and (b) FASD (n = 16) versus TD (n = 16). Combining the rates of semantic elaboration and pragmatically inappropriate reference perfectly matched a classification based on performance on the standardized language task. More importantly, the rate of ambiguous nominal reference was highly accurate in classifying children with an FASD regardless of their performance on the standardized language task (area under the ROC curve = .863, confidence interval = .736-.991). Results support further study of the diagnostic utility of narrative analysis using discourse level measures of elaboration and children's strategic use of reference.

Fetal Alcohol Syndrome

MedlinePlus

American Association for Pediatric Ophthalmology and Strabismus Home About AAPOS Patient Info Resources Allied Health News & Events Meetings J AAPOS American Association for Pediatric Ophthalmology ...

Costs of Fetal Alcohol Spectrum Disorder in the Canadian Criminal Justice System.

PubMed

Thanh, Nguyen Xuan; Jonsson, Egon

2015-01-01

We reviewed literature to estimate the costs of Fetal Alcohol Spectrum Disorder (FASD) in the Canadian Criminal Justice System (CJS), and to update the total costs of FASD in Canada. The results suggest FASD is costlier than previous estimates. The costs of FASD associated with the CJS are estimated at $3.9 billion a year, with $1.2 billion for police, $0.4 billion for court, $0.5 billion for correctional services, $1.6 billion for victims, and $0.2 billion for third-party. The updated total costs of FASD in Canada are $9.7 billion a year, of which CJS accounts for 40%, healthcare 21%, education 17%, social services 13%, and others 9%.

Comparing Attentional Networks in fetal alcohol spectrum disorder and the inattentive and combined subtypes of attention deficit hyperactivity disorder.

PubMed

Kooistra, Libbe; Crawford, Susan; Gibbard, Ben; Kaplan, Bonnie J; Fan, Jin

2011-01-01

The Attention Network Test (ANT) was used to examine alerting, orienting, and executive control in fetal alcohol spectrum disorder (FASD) versus attention deficit hyperactivity disorder (ADHD). Participants were 113 children aged 7 to 10 years (31 ADHD-Combined, 16 ADHD-Primarily Inattentive, 28 FASD, 38 controls). Incongruent flanker trials triggered slower responses in both the ADHD-Combined and the FASD groups. Abnormal conflict scores in these same two groups provided additional evidence for the presence of executive function deficits. The ADHD-Primarily Inattentive group was indistinguishable from the controls on all three ANT indices, which highlights the possibility that this group constitutes a pathologically distinct entity.

Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

NASA Astrophysics Data System (ADS)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2013-02-01

The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

Infant emotional withdrawal: a precursor of affective and cognitive disturbance in fetal alcohol spectrum disorders.

PubMed

Molteno, Christopher D; Jacobson, Joseph L; Carter, R Colin; Dodge, Neil C; Jacobson, Sandra W

2014-02-01

Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years, cognitive and affective function at 5 and 9 years. Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother-infant interaction, infant temperament, or other socioemotional aspects of the infant's environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS. Copyright © 2013 by the Research Society on Alcoholism.

A multinational deployment of 3D laser scanning to study craniofacial dysmorphology in fetal alcohol spectrum disorders

NASA Astrophysics Data System (ADS)

Rogers, Jeff; Wernert, Eric; Moore, Elizabeth; Ward, Richard; Wetherill, Leah F.; Foroud, Tatiana

2007-01-01

Craniofacial anthropometry (the measurement and analysis of head and face dimensions) has been used to assess and describe abnormal craniofacial variation (dysmorphology) and the facial phenotype in many medical syndromes. Traditionally, anthropometry measurements have been collected by the direct application of calipers and tape measures to the subject's head and face, and can suffer from inaccuracies due to restless subjects, erroneous landmark identification, clinician variability, and other forms of human error. Three-dimensional imaging technologies promise a more effective alternative that separates the acquisition and measurement phases to reduce these variabilities while also enabling novel measurements and longitudinal analysis of subjects. Indiana University (IU) is part of an international consortium of researchers studying fetal alcohol spectrum disorders (FASD). Fetal alcohol exposure results in predictable craniofacial dysmorphologies, and anthropometry has been proven to be an effective diagnosis tool for the condition. IU is leading a project to study the use of 3D surface scanning to acquire anthropometry data in order to more accurately diagnose FASD, especially in its milder forms. This paper describes our experiences in selecting, verifying, supporting, and coordinating a set of 3D scanning systems for use in collecting facial scans and anthropometric data from around the world.

FASD Prevalence among Schoolchildren in Poland

ERIC Educational Resources Information Center

Okulicz-Kozaryn, Katarzyna; Borkowska, Magdalena; Brzózka, Krzysztof

2017-01-01

Background: Prenatal Alcohol Exposure is a major cause of brain damage and developmental delay, known as Fetal Alcohol Spectrum Disorders (FASD) but in Poland is rarely diagnosed and the scale of problem is not known. Methods: An active case ascertainment approach was applied to estimate the prevalence of FASD among 7-9 years olds. Pre-screening…

Alcohol Use and Sudden Infant Death Syndrome

ERIC Educational Resources Information Center

Friend, Karen B.; Goodwin, Matthew S.; Lipsitt, Lewis P.

2004-01-01

Despite general evidence of fetal toxicities associated with sudden infant death syndrome (SIDS), there has been limited research focusing on the effects of parental alcohol use on SIDS occurrence, either directly or in interaction with other risk conditions. The purpose of this paper is to review the literature on parental, especially maternal,…

[Consumption of medications, alcohol and smoking in pregnancy and assessment of teratogenic risks].

PubMed

Rocha, Rebeca Silveira; Bezerra, Samara Cavalcante; Lima, José Welington de Oliveira; Costa, Fabrício da Silva

2013-06-01

Medications, alcohol and smoking can cause fetal damage. A cross-sectional study was conducted with 326 mothers of the Fortaleza General Hospital to evaluate the use of drugs, alcohol and smoking during pregnancy and its relation to teratogenic potential in different population characteristics, between 2006 and 2007. Postpartum women who had their babies in the research site were included and those whose babies were not admitted as hospital inpatients were excluded. Chi-square tests and t-tests were used in the analysis, with a p value <0.05 considered significant. 96.6% of the mothers took medications (2.8 drugs/ pregnancy) and self-medication occurred in 11.3% of the cases. Single women took more drugs with high teratogenic potential (p=0.037). 11 cases of fetal malformation were observed, five of them were exposed to high teratogenic risks. Smoking occurred in 11.3% and alcohol use in 16%. Being single was found to be a risk factor for exposure to high teratogenic potential. Quality of prenatal care and other sociodemographic variables weren't related to exposure to teratogenic risks.

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C.; Marrs, James A.

2013-01-01

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection. PMID:24961433

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C; Marrs, James A

2013-06-19

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester

PubMed Central

Birch, Sharla M.; Lenox, Mark W.; Kornegay, Joe N.; Shen, Li; Ai, Huisi; Ren, Xiaowei; Goodlett, Charles R.; Cudd, Tim A.; Washburn, Shannon E.

2015-01-01

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4–41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD. PMID:26496796

THEORY OF MIND IN CHILDREN WITH FETAL ALCOHOL SPECTRUM DISORDERS

PubMed Central

Lindinger, Nadine M.; Malcolm-Smith, Susan; Dodge, Neil C.; Molteno, Christopher D.; Thomas, Kevin G. F.; Meintjes, Ernesta M.; Jacobson, Joseph L.; Jacobson, Sandra W.

2015-01-01

Background Theory of mind (ToM) refers to the ability to understand and make inferences about other people’s intentions, feelings, and beliefs. Although children with fetal alcohol spectrum disorders (FASD) are known to have deficits in social-cognitive function, little is known about ToM in FASD. Methods ToM ability was assessed using a developmentally sensitive ToM battery, including the Reading the Mind in the Eyes (RME) test, a measure of mental inferential ability that has been found to be impaired in other clinical populations. IQ and executive function (EF) were assessed as potential mediating variables. The battery was administered to 63 children (aged 9–11 years) from Cape Town, South Africa, whose mothers had been prospectively recruited during pregnancy. Children with fetal alcohol syndrome (FAS; n=8) and partial FAS (PFAS; n=19), as well as nonsyndromal heavily exposed children (HE; n=17), were compared to children born to abstaining or light drinkers (n=19) from the same community. Results No FASD group differences were found on the less challenging ToM tasks. By contrast, children with FAS and PFAS performed more poorly than controls on a more challenging ToM task, the RME test. A continuous measure of prenatal alcohol exposure was more sensitive than FASD diagnosis in that it was related to four higher-order ToM measures, particularly the ability to attribute mental states assessed on RME. IQ only partially mediated the effect of exposure on RME performance, and these effects were not mediated by EF. Hence, the data suggest that these ToM measures tap into a specific alcohol-related social-cognitive deficit that does not merely reflect poorer EF. FASD diagnosis and prenatal alcohol exposure were each also related to RME after control for Attention Deficit/Hyperactivity Disorder. Conclusions These findings suggest that deficits in higher-order ToM function may play a significant role in the social-cognitive behavioural impairment in FASD. PMID:26842255

MATERNAL ALCOHOL CONSUMPTION PRODUCING FETAL ALCOHOL SPECTRUM DISORDERS (FASD): QUANTITY, FREQUENCY, AND TIMING OF DRINKING

PubMed Central

May, Philip A.; Blankenship, Jason; Marais, Anna-Susan; Gossage, J. Phillip; Kalberg, Wendy O.; Joubert, Belinda; Cloete, Marise; Barnard, Ronel; De Vries, Marlene; Hasken, Julie; Robinson, Luther K.; Adnams, Colleen M.; Buckley, David; Manning, Melanie; Parry, Charles; Hoyme, H. Eugene; Tabachnick, Barbara; Seedat, Soraya

2013-01-01

Background Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). Methods Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. Results Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p<.001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p=.008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. Conclusions There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy. PMID:23932841

Maternal alcohol consumption producing fetal alcohol spectrum disorders (FASD): quantity, frequency, and timing of drinking.

PubMed

May, Philip A; Blankenship, Jason; Marais, Anna-Susan; Gossage, J Phillip; Kalberg, Wendy O; Joubert, Belinda; Cloete, Marise; Barnard, Ronel; De Vries, Marlene; Hasken, Julie; Robinson, Luther K; Adnams, Colleen M; Buckley, David; Manning, Melanie; Parry, Charles D H; Hoyme, H Eugene; Tabachnick, Barbara; Seedat, Soraya

2013-12-01

Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p<.001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p=.008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

What Is a Pediatric Geneticist?

MedlinePlus

... or achondroplasia) Conditions that can cause disabilities (fetal alcohol syndrome, or fragile X syndrome) Inborn errors of metabolism (cystic fibrosis, phenylketonuria, or sickle cell disease) Familial ...

Prevalence of alcohol consumption during pregnancy and Fetal Alcohol Spectrum Disorders among the general and Aboriginal populations in Canada and the United States.

PubMed

Popova, Svetlana; Lange, Shannon; Probst, Charlotte; Parunashvili, Nino; Rehm, Jürgen

2017-01-01

Prenatal alcohol exposure may cause a number of health complications for the mother and developing fetus, including Fetal Alcohol Spectrum Disorders (FASD). This study aimed to estimate the pooled prevalence of i) alcohol use (any amount) and binge drinking (4 or more standard drinks on a single occasion) during pregnancy, and ii) Fetal Alcohol Syndrome (FAS) and FASD among the general and Aboriginal populations in Canada and the United States, based on the available literature. Comprehensive systematic literature searches and meta-analyses, assuming a random-effects model, were conducted. It was revealed that about 10% and 15% of pregnant women in the general population consume alcohol in Canada and the United States, respectively, and that about 3% of women engage in binge drinking during pregnancy in both countries. However, the prevalence of alcohol use during pregnancy in the Aboriginal populations of the United States and Canada were found to be approximately 3-4 times higher, respectively, compared to the general population. Even more alarmingly, it was estimated that approximately one in five women in the Aboriginal populations in both countries engage in binge drinking during pregnancy. Further, among the general population of Canada, the pooled prevalence was estimated to be about 1 per 1000 for FAS and 5 per 1000 for FASD. However, compared to the general population, the prevalence of FAS and FASD among the Aboriginal population in Canada was estimated to be 38 times and 16 times higher, respectively. With respect to the United States, the pooled prevalence of FAS and FASD was estimated to be about 2 per 1000 and 15 per 1,000, respectively, among the general population, and 4 per 1000 and 10 per 1,000, respectively, among the Aboriginal population. The FAS and FASD pooled prevalence estimates presented here should be used with caution due to the limited number of existing studies and their methodological limitations. Based on the results of the current study, it is evident that there is an urgent need for implementing more effective national prevention and surveillance strategies to monitor and lower the prevalence of alcohol consumption during pregnancy and FASD. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Fetal Alcohol Spectrum Disorders (FASDs): Treatments

MedlinePlus

... out by mental health providers with specialized training. Math Interactive Learning Experience (MILE) program to help with mathematics difficulty 3 Deficits in mathematical functioning have been ...

Women’s receptivity to Fetal Alcohol Spectrum Disorders prevention approaches: A case study of two regions in Russia

PubMed Central

Balachova, Tatiana; Bonner, Barbara; Bard, David; Chaffin, Mark; Isurina, Galina; Owora, Arthur; Tsvetkova, Larissa; Volkova, Elena

2017-01-01

Aims This study obtained data to inform the development of programs for prevention of Fetal Alcohol Spectrum Disorders (FASD) by examining Russian women’s perceptions about the determinants of their decisions regarding alcohol consumption during pregnancy; the importance of educating professionals and community about FASD; and the credibility of various sources of information. Design Cross-sectional survey. Setting Seven women’s clinics in St. Petersburg and the Nizhny Novgorod region in Russia. Participants Six hundred and forty-eight pregnant and non-pregnant women of childbearing age. Measures A face-to-face structured interview assessed demographic characteristics, pregnancy status, alcohol consumption, and level of trust in and receptivity to FASD prevention messages. Findings The most influential contributor to women’s decisions regarding alcohol consumption during pregnancy was their own knowledge, followed by information from an obstetrician/gynecologist or nurse. It was most important to women that obstetrics and gynecology professionals and husbands or partners were knowledgeable about the effects of drinking during pregnancy. Physicians’ recommendations and research data were regarded by the women as the most credible sources of information. There were significant variations in responses by socio-demographic characteristics and alcohol consumption levels. Younger women were more likely to report the contributions of husbands, mothers, and friends or coworkers to their decisions about alcohol consumption and indicated the importance of educating these people. Women at risk for alcohol use during pregnancy reported greater influence of husbands or partners and warning labels on containers on their alcohol consumption. Conclusions This study emphasizes the importance of broadly disseminating information about FASD, particularly research data, through education of health professionals and the general public in Russia. Women’s socio-demographic characteristics and alcohol consumption levels should be considered in designing prevention programs. PMID:28936273

Is Prenatal Alcohol Exposure Related to Inattention and Hyperactivity Symptoms in Children? Disentangling the Effects of Social Adversity

ERIC Educational Resources Information Center

Rodriguez, A.; Olsen, J.; Kotimaa, A. J.; Kaakinen, M.; Moilanen, I.; Henriksen, T. B.; Linnet, K. M.; Miettunen, J.; Obel, C.; Taanila, A.; Ebeling, H.; Jarvelin, M. R.

2009-01-01

Background: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting…

"Helping Communities To Help Themselves." Twenty 1989 Exemplary Prevention Programs for Preventing Alcohol and Other Drug Abuse. Project Summaries.

ERIC Educational Resources Information Center

National Association of State Alcohol and Drug Abuse Directors, Inc.

Twenty exemplary substance abuse prevention programs are presented in this document. These programs are included: (1) Tuba City, Arizona, Fetal Alcohol Syndrome (FAS) Prevention Program; (2) Chemical Addiction Course, University of Arkansas; (3) "Teens Are Concerned" of Arkansas; (4) "Dare to be You of Colorado"; (5) Winyan…

Developmental regulation of neuroligin genes in Japanese rice fish (oryzias latipes) embryogenesis maintains the rhythym during ethanol-in

USDA-ARS?s Scientific Manuscript database

Although prenatal alcohol exposure is the potential cause of fetal alcohol spectrum disorder (FASD) in humans, the molecular mechanism(s) of FASD is yet unknown. We have used Japanese rice fish (Oryzias latipes) embryogenesis as an animal model of FASD and reported that this model has effectively ge...

THE EPIDEMIOLOGY OF FETAL ALCOHOL SYNDROME AND PARTIAL FAS IN A SOUTH AFRICAN COMMUNITY

PubMed Central

May, Philip A.; Gossage, J. Phillip; Marais, Anna-Susan; Adnams, Colleen M.; Hoyme, H. Eugene; Jones, Kenneth L.; Robinson, Luther K.; Khaole, Nathaniel C.O.; Snell, Cudore; Kalberg, Wendy O.; Hendricks, Loretta; Brooke, Lesley; Stellavato, Chandra; Viljoen, Denis L.

2007-01-01

OBJECTIVES The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) were determined in a third primary school cohort in a community in South Africa (S.A.). METHODS An active case ascertainment, two-tier screening methodology, and the revised Institute of Medicine diagnostic criteria were employed among 818 first grade pupils. Characteristics of children with FAS and PFAS are contrasted with a randomly-selected control group. Data were collected and analyzed for children in the study regarding: 1.) physical growth and development, including dysmorphology, 2.) intelligence and behavioral characteristics, and 3.) their mother’s social, behavioral, and physical characteristics. RESULTS The rate of FAS and PFAS in this area continues as the highest reported in any overall community and is much higher than rates elsewhere. In this cohort it is 68.0 to 89.2 per 1,000. Severe episodic drinking on weekends among mothers of children with FAS and PFAS accounts for 96% of all alcohol consumed. Various measures of maternal drinking are significantly correlated with negative outcomes of children in the areas of non-verbal intelligence (-0.26), verbal intelligence (-0.28), problem behavior (0.31), and overall dysmorphology score (0.59). Significantly more FAS and PFAS exists among children of rural residents (OR = 3.79). CONCLUSIONS A high rate of FAS and PFAS was again documented in this community, and it has increased. Given population similarities, we suspect that other communities in the Western Cape Province of South Africa also have high rates. Programs for prevention are needed. PMID:17127017

Visual defects in a mouse model of fetal alcohol spectrum disorder.

PubMed

Lantz, Crystal L; Pulimood, Nisha S; Rodrigues-Junior, Wandilson S; Chen, Ching-Kang; Manhaes, Alex C; Kalatsky, Valery A; Medina, Alexandre Esteves

2014-01-01

Alcohol consumption during pregnancy can lead to a multitude of neurological problems in offspring, varying from subtle behavioral changes to severe mental retardation. These alterations are collectively referred to as Fetal Alcohol Spectrum Disorders (FASD). Early alcohol exposure can strongly affect the visual system and children with FASD can exhibit an amblyopia-like pattern of visual acuity deficits even in the absence of optical and oculomotor disruption. Here, we test whether early alcohol exposure can lead to a disruption in visual acuity, using a model of FASD to mimic alcohol consumption in the last months of human gestation. To accomplish this, mice were exposed to ethanol (5 g/kg i.p.) or saline on postnatal days (P) 5, 7, and 9. Two to three weeks later we recorded visually evoked potentials to assess spatial frequency detection and contrast sensitivity, conducted electroretinography (ERG) to further assess visual function and imaged retinotopy using optical imaging of intrinsic signals. We observed that animals exposed to ethanol displayed spatial frequency acuity curves similar to controls. However, ethanol-treated animals showed a significant deficit in contrast sensitivity. Moreover, ERGs revealed a market decrease in both a- and b-waves amplitudes, and optical imaging suggest that both elevation and azimuth maps in ethanol-treated animals have a 10-20° greater map tilt compared to saline-treated controls. Overall, our findings suggest that binge alcohol drinking restricted to the last months of gestation in humans can lead to marked deficits in visual function.

Guidelines for pregnancy: what's an acceptable risk, and how is the evidence (finally) shaping up?

PubMed

O'Leary, Colleen M; Bower, Carol

2012-03-01

The lack of consensus about whether low to moderate levels of prenatal alcohol exposure are a risk factor for fetal development has generated considerable debate about what advice policies and guidelines should provide. This paper reviews the evidence from systematic reviews and meta-analyses examining the risk from low and moderate levels of prenatal alcohol exposure, along with the results of articles published 2009-2010, after the reviews. The reported significant effects from low levels of prenatal alcohol exposure are likely due to methodological issues such as confounding and/or misclassification of exposure or outcome and there is no strong research evidence of fetal effects from low levels of alcohol exposure. However, harm is well-documented with heavy exposure and moderate levels of exposure, 30-40 g per occasion and no more than 70 g per week, have been demonstrated to increase the risk of child behaviour problems. With such a small margin before there is increased risk to the fetus, it would be morally and ethically unacceptable for policies and guidelines to condone consumption of alcohol during pregnancy. Not all women will follow this advice and some women will inadvertently consume alcohol prior to pregnancy awareness requiring non-judgmental counselling and the provision of rational advice about the likelihood of risk to the fetus. The policy advice that 'the safest choice for pregnant women is to abstain from alcohol during pregnancy' should be maintained. However, the abstinence message needs to be presented in a balanced and rational manner to prevent unintended negative consequences. © 2011 Australasian Professional Society on Alcohol and other Drugs.

DNA Methylation program in normal and alcohol-induced thinning cortex

PubMed Central

Öztürk, Nail Can; Resendiz, Marisol; Öztürk, Hakan; Zhou, Feng C.

2017-01-01

While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6) mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7–16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls. Cortical neuroanatomy, neural phenotypes, and epigenetic markers of methylation were assessed using immunohistochemistry, Western blot, and methyl-DNA assays. We report that cortical thickness, neuroepithelial proliferation, and neuronal migration and maturity were found to be deterred by alcohol at E17. Simultaneously, DNA methylation, including 5-methylcytosine (5mC) and 5-hydroxcylmethylcytosine (5hmC), which progresses as an intrinsic program guiding normal embryonic cortical development, was severely affected by in utero alcohol exposure. The intricate relationship between cortical thinning and this DNA methylation program disruption is detailed and illustrated. DNA methylation, dynamic across the multiple cortical layers during the late embryonic stage, is highly disrupted by fetal alcohol exposure; this disruption occurs in tandem with characteristic developmental abnormalities, ranging from structural to molecular. Finally, our findings point to a significant question for future exploration: whether epigenetics guides neurodevelopment or whether developmental conditions dictate epigenetic dynamics in the context of alcohol-induced cortical teratogenesis. PMID:28433420

White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning

PubMed Central

Fan, Jia; Meintjes, Ernesta M.; Molteno, Christopher D.; Spottiswoode, Bruce S.; Dodge, Neil C.; Alhamud, Alkathafi A.; Stanton, Mark E.; Peterson, Bradley S.; Jacobson, Joseph L.; Jacobson, Sandra W.

2015-01-01

Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1±1.0 yrs, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles. PMID:25783559

Fetal Alcohol Spectrum Disorders

MedlinePlus

... between the nose and upper lip Small head size Shorter-than-average height Low body weight Poor coordination Hyperactive behavior Difficulty with attention and memory Learning disabilities and difficulty in school ...

Fetal Alcohol Spectrum Disorders: When Science, Medicine, Public Policy, and Laws Collide

ERIC Educational Resources Information Center

Warren, Kenneth R.; Hewitt, Brenda G.

2009-01-01

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,…

The Prevalence of Fetal Alcohol Syndrome and Its Impact on a Child's Classroom Performance: A Case Study of a Rural South African School.

PubMed

Lubbe, Melissa; van Walbeek, Corné; Vellios, Nicole

2017-08-09

Alcohol consumption is high among farm labourers in the Western and Northern Cape of South Africa. Excessive alcohol consumption during pregnancy is common, resulting in a high prevalence of Fetal Alcohol Syndrome (FAS) among children. FAS causes intellectual and behavioural problems, which create considerable obstacles to a child's education. The aim of this study is to provide a prevalence estimate of FAS in a rural school and to examine the effects of FAS on learners' educational outcomes. The study was conducted at a farm school near Clanwilliam in the Western Cape of South Africa. The sample comprises 166 learners from Grades 1 to 4. Educational outcomes include class scores (Afrikaans Home Language and Mathematics), reading ability, and classroom behaviour. A physician diagnosed FAS using a three-stage process. We find FAS prevalence of 127 per 1000 (12.7%). Children with FAS score significantly lower (at the 10% level) for home language and behaviour than children who do not have FAS. Large-scale interventions in rural areas of the Western and Northern Cape that specifically target females of child-bearing age, as well aschildren with FAS, are necessary.

Indicated Prevention of Fetal Alcohol Spectrum Disorders in South Africa: Effectiveness of Case Management

PubMed Central

de Vries, Marlene M.; Joubert, Belinda; Cloete, Marise; Roux, Sumien; Baca, Beth A.; Hasken, Julie M.; Barnard, Ronel; Buckley, David; Kalberg, Wendy O.; Snell, Cudore L.; Marais, Anna-Susan; Seedat, Soraya; Parry, Charles D. H.; May, Philip A.

2015-01-01

In the Western Cape Province of South Africa (ZA) a subculture of binge drinking produces the highest global documented prevalence of fetal alcohol spectrum disorders (FASD). FASD prevention research activities in ZA use the Comprehensive Prevention approach from the United States Institute of Medicine. Case management (CM) was delivered as a method of indicated prevention to empower heavy drinking pregnant women to achieve cessation or a reduction in drinking. CM activities incorporated life management, Motivational Interviewing (MI) techniques and the Community Reinforcement Approach (CRA). Data were collected at baseline, 6, 12 and 18 months. Mean drinking decreases 6 months into CM; but overall alcohol consumption rose significantly over time to levels higher than baseline at 12 and 18 months. Alcohol consumption drops significantly from before pregnancy to the second and third trimesters. AUDIT scores indicate that problematic drinking decreases significantly even after the vulnerable fetus/baby was born. CM significantly increases client happiness, which correlates with reduced weekend drinking. CM was successful for women with high-risk drinking behaviour, and was effective in helping women stop drinking, or drink less, while pregnant, reducing the risk of FASD. PMID:26703708

The Prevalence of Fetal Alcohol Syndrome and Its Impact on a Child’s Classroom Performance: A Case Study of a Rural South African School

PubMed Central

Lubbe, Melissa; van Walbeek, Corné

2017-01-01

Alcohol consumption is high among farm labourers in the Western and Northern Cape of South Africa. Excessive alcohol consumption during pregnancy is common, resulting in a high prevalence of Fetal Alcohol Syndrome (FAS) among children. FAS causes intellectual and behavioural problems, which create considerable obstacles to a child’s education. The aim of this study is to provide a prevalence estimate of FAS in a rural school and to examine the effects of FAS on learners’ educational outcomes. The study was conducted at a farm school near Clanwilliam in the Western Cape of South Africa. The sample comprises 166 learners from Grades 1 to 4. Educational outcomes include class scores (Afrikaans home language and mathematics), reading ability, and classroom behaviour. A physician diagnosed FAS using a three-stage process. We find FAS prevalence of 127 per 1000 (12.7%). Children with FAS score significantly lower (at the 10% level) for home language and behaviour than children who do not have FAS. Large-scale interventions in rural areas of the Western and Northern Cape that specifically target females of child-bearing age, as well as children with FAS, are necessary. PMID:28792446

Antimicrobial activity of a new intact skin antisepsis formulation.

PubMed

Russo, Antonello; Viotti, Pier Luigi; Vitali, Matteo; Clementi, Massimo

2003-04-01

Different antiseptic formulations have shown limitations when applied to disinfecting intact skin, notably short-term tolerability and/or efficacy. The purpose of this study was optimizing a new antiseptic formulation specifically targeted at intact skin disinfection and evaluating its in vitro microbicidal activity and in vivo efficacy. The biocidal properties of the antiseptic solution containing 0.5% chloramine-T diluted in 50% isopropyl alcohol (Cloral; Eurospital SpA Trieste, Italy) were measured in vitro versus gram-positive-, gram-negative-, and acid-alcohol-resistant germs and fungi with standard suspension tests in the presence of fetal bovine serum. Virus-inhibiting activity was evaluated in vitro against human cytomegalovirus, herpes simplex virus, poliovirus, hepatitis B virus, and hepatitis C virus. Tests used different methods for the different biologic and in vitro replication capacity of these human viruses. Lastly, Cloral tolerability and skin colonization retardation efficacy after disinfection were studied in vivo. The antiseptic under review showed fast and sustained antimicrobial activity. The efficacy of Cloral against clinically important bacterial and viral pathogens and fungi was highlighted under the experimental conditions described in this article. Finally, microbial regrowth lag and no side effects were documented in vivo after disinfection of 11 volunteers. A stable chloramine-T solution in isopropyl alcohol may be suggested for intact skin antisepsis.

A review of experimental evidences that could warn of possible dangers of alcohol consumption by pregnant mothers.

PubMed

Chaudhuri, J D

2000-12-01

Most of the features of fetal alcohol syndrome (FAS) have been replicated in experimental models. They provide an insight into the effects of alcohol on the developing embryo, however, satisfactory explanations for these effects are still not available. Certain maternal characteristics of children with FAS have been identified. However, it is not absolute as at times the most unlikely women are susceptible to problems of maternal alcoholism. The levels of awareness of FAS among the general public and health workers are inadequate. Measures need to be taken to remedy this condition.

Fetal Alcohol Spectrum Disorders (FASDs): Diagnosis

MedlinePlus

... reactions. Executive functioning deficits These deficits involve the thinking processes that help a person manage life tasks. Such deficits include poor organization and planning, lack of inhibition, difficulty grasping cause ...

Communicating the risks of fetal alcohol spectrum disorder: effects of message framing and exemplification.

PubMed

Yu, Nan; Ahern, Lee A; Connolly-Ahern, Colleen; Shen, Fuyuan

2010-12-01

Health messages can be either informative or descriptive, and can emphasize either potential losses or gains. This study, guided by message framing theory and exemplification theory, specifically investigated the combined effects of messages with loss-gain frames mixed with statistics or exemplar appeals. The findings revealed a series of main effects and interactions for loss-gain frames and statistics-exemplar appeals on fetal alcohol spectrum disorder (FASD) prevention intention, intention to know more, perceived severity, perceived fear, perceived external efficacy, and perceived internal efficacy. The gain-statistics appeal showed an advantage in promoting perceived efficacy toward FASD, while the loss-exemplar appeal revealed an advantage in increasing prevention intention, perceived severity, and perceived fear toward FASD. Limitations and implications for future research are discussed.

Recognized spontaneous abortion in mid-pregnancy and patterns of pregnancy alcohol use.

PubMed

Chiodo, Lisa M; Bailey, Beth A; Sokol, Robert J; Janisse, James; Delaney-Black, Virginia; Hannigan, John H

2012-05-01

Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking was significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African-American sample. Some drinking measures averaged across pregnancy may have under-estimated consumption and overestimated risk of SAb, but other risk drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk level alcohol consumption and protect from pregnancy loss. Copyright © 2012 Elsevier Inc. All rights reserved.

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester.

PubMed

Birch, Sharla M; Lenox, Mark W; Kornegay, Joe N; Shen, Li; Ai, Huisi; Ren, Xiaowei; Goodlett, Charles R; Cudd, Tim A; Washburn, Shannon E

2015-11-01

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD. Copyright © 2015 Elsevier Inc. All rights reserved.

Environmental Enrichment Alters Neurotrophin Levels After Fetal Alcohol Exposure in Rats

PubMed Central

Parks, Elizabeth A.; McMechan, Andrew P.; Hannigan, John H.; Berman, Robert F.

2014-01-01

Background Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats. Methods Pregnant rats received alcohol by gavage, 0, 4, or 6 g / kg / d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis. Results Prenatal alcohol exposure increased NGF levels in frontal cortex (High-dose group) and cerebellar vermis (High- and Low-dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low-dose groups), and increased NT-3 in hippocampus and cerebellar vermis (High-dose). Environmental enrichment resulted in lower NGF, BDNF, and NT-3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT-3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions. Conclusions Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats. PMID:18652597

Executive functioning deficits in preschool children with Fetal Alcohol Spectrum Disorders

PubMed Central

Fuglestad, Anita J.; Whitley, Marisa L.; Carlson, Stephanie M.; Boys, Christopher J.; Eckerle, Judith K.; Fink, Birgit A.; Wozniak, Jeffrey R.

2014-01-01

Executive function (EF) deficit is a hallmark of Fetal Alcohol Spectrum Disorders (FASD), but the vast majority of available evidence comes from school-age children and adolescents. Very little is known about EF during the critical developmental period prior to 6 years of age in FASD. We evaluated EF in 39 children with FASD (3.0 – 5.5 years) and a comparison group of 50 age-matched, non-exposed controls. Measures included the EF Scale for Early Childhood and a Delay of Gratification task. Compared to age-matched controls, pre-school children with FASD had impairments on the EF Scale and showed more impulsivity on the Delay of Gratification task. To confirm the EF Scale finding, FASD group performance was compared to a separate normative dataset (N=1,400). Those with FASD performed below normal (M= −0.57, SD=0.92). Within the FASD group, IQ was correlated with the EF Scale (partial r=.60, p=.001) and Delay of Gratification (partial r=.58, p=.005). EF Scale performance did not differ significantly across levels of FASD severity [fetal alcohol syndrome (FAS), partial FAS, or alcohol-related neurobehavioral disorder (ARND)]. However, compared to normative data, those with FAS had the largest deficits (M= −0.91 SD, SE=0.23), followed by partial FAS (M= −0.66 SD, SE=0.26), then ARND (M= −0.36 SD, SE=0.20). These novel data show that EF deficits manifest well before the age of 6 years in children with FASD, that they occur across the spectrum, and that EF may be most impaired in children with more severe forms of FASD and/or lower IQs. PMID:25011516

Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine.

PubMed

Sogut, Ibrahim; Uysal, Onur; Oglakci, Aysegul; Yucel, Ferruh; Kartkaya, Kazim; Kanbak, Gungor

2017-03-01

Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy. Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei. Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments. We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.

Dietary Choline Levels Modify the Effects of Prenatal Alcohol Exposure in Rats

PubMed Central

Idrus, Nirelia M.; Breit, Kristen R.; Thomas, Jennifer D.

2018-01-01

Prenatal alcohol exposure can cause a range of physical and behavioral alterations; however, the outcome among children exposed to alcohol during pregnancy varies widely. Some of this variation may be due to nutritional factors. Indeed, higher rates of fetal alcohol spectrum disorders (FASD) are observed in countries where malnutrition is prevalent. Epidemiological studies have shown that many pregnant women throughout the world may not be consuming adequate levels of choline, an essential nutrient critical for brain development, and a methyl donor. In this study, we examined the influence of dietary choline deficiency on the severity of fetal alcohol effects. Pregnant Sprague-Dawley rats were randomly assigned to receive diets containing 40, 70, or 100% recommended choline levels. A group from each diet condition was exposed to ethanol (6.0 g/kg/day) from gestational day 5 to 20 via intubation. Pair-fed and ad lib lab chow control groups were also included. Physical and behavioral development was measured in the offspring. Prenatal alcohol exposure delayed motor development, and 40% choline altered performance on the cliff avoidance task, independent of one another. However, the combination of low choline and prenatal alcohol produced the most severe impairments in development. Subjects exposed to ethanol and fed the 40% choline diet exhibited delayed eye openings, significantly fewer successes in hind limb coordination, and were significantly overactive compared to all other groups. These data suggest that suboptimal intake of a single nutrient can exacerbate some of ethanol’s teratogenic effects, a finding with important implications for the prevention of FASD. PMID:27888055

Dietary choline levels modify the effects of prenatal alcohol exposure in rats.

PubMed

Idrus, Nirelia M; Breit, Kristen R; Thomas, Jennifer D

Prenatal alcohol exposure can cause a range of physical and behavioral alterations; however, the outcome among children exposed to alcohol during pregnancy varies widely. Some of this variation may be due to nutritional factors. Indeed, higher rates of fetal alcohol spectrum disorders (FASD) are observed in countries where malnutrition is prevalent. Epidemiological studies have shown that many pregnant women throughout the world may not be consuming adequate levels of choline, an essential nutrient critical for brain development, and a methyl donor. In this study, we examined the influence of dietary choline deficiency on the severity of fetal alcohol effects. Pregnant Sprague-Dawley rats were randomly assigned to receive diets containing 40, 70, or 100% recommended choline levels. A group from each diet condition was exposed to ethanol (6.0g/kg/day) from gestational day 5 to 20 via intubation. Pair-fed and ad lib lab chow control groups were also included. Physical and behavioral development was measured in the offspring. Prenatal alcohol exposure delayed motor development, and 40% choline altered performance on the cliff avoidance task, independent of one another. However, the combination of low choline and prenatal alcohol produced the most severe impairments in development. Subjects exposed to ethanol and fed the 40% choline diet exhibited delayed eye openings, significantly fewer successes in hindlimb coordination, and were significantly overactive compared to all other groups. These data suggest that suboptimal intake of a single nutrient can exacerbate some of ethanol's teratogenic effects, a finding with important implications for the prevention of FASD. Copyright © 2016. Published by Elsevier Inc.

Maternal Risk Factors for Fetal Alcohol Spectrum Disorders in a Province in Italy*

PubMed Central

Ceccanti, Mauro; Fiorentino, Daniela; Coriale, Giovanna; Kalberg, Wendy O.; Buckley, David; Hoyme, H. Eugene; Gossage, J. Phillip; Robinson, Luther K.; Manning, Melanie; Romeo, Marina; Hasken, Julie M.; Tabachnick, Barbara; Blankenship, Jason

2016-01-01

Background Maternal risk factors for fetal alcohol spectrum disorders (FASD) in Italy and Mediterranean cultures need clarification, as there are few studies and most are plagued by inaccurate reporting of antenatal alcohol use. Methods Maternal interviews (n=905) were carried out in a population-based study of the prevalence and characteristics of FASD in the Lazio region of Italy which provided data for multivariate case control comparisons and multiple correlation models. Results Case control findings from interviews seven years post-partum indicate that mothers of children with FASD are significantly more likely than randomly-selected controls or community mothers to: be shorter; have higher body mass indexes (BMI); be married to a man with legal problems; report more drinking three months pre-pregnancy; engage in more current drinking and drinking alone; and have alcohol problems in her family. Logistic regression analysis of multiple candidate predictors of a FASD diagnosis indicates that alcohol problems in the child’s family is the most significant risk factor, making a diagnosis within the continuum of FASD 9 times more likely (95% C.I. = 1.6 to 50.7). Sequential multiple regression analysis of the child’s neuropsychological performance also identifies alcohol problems in the child’s family as the only significant maternal risk variable (p<.001) when controlling for other potential risk factors. Conclusions Underreporting of prenatal alcohol use has been demonstrated among Italian and other Mediterranean antenatal samples, and it was suspected in this sample. Nevertheless, several significant maternal risk factors for FASD have been identified. PMID:25456331

Maternal risk factors for fetal alcohol spectrum disorders in a province in Italy.

PubMed

Ceccanti, Mauro; Fiorentino, Daniela; Coriale, Giovanna; Kalberg, Wendy O; Buckley, David; Hoyme, H Eugene; Gossage, J Phillip; Robinson, Luther K; Manning, Melanie; Romeo, Marina; Hasken, Julie M; Tabachnick, Barbara; Blankenship, Jason; May, Philip A

2014-12-01

Maternal risk factors for fetal alcohol spectrum disorders (FASD) in Italy and Mediterranean cultures need clarification, as there are few studies and most are plagued by inaccurate reporting of antenatal alcohol use. Maternal interviews (n = 905) were carried out in a population-based study of the prevalence and characteristics of FASD in the Lazio region of Italy which provided data for multivariate case control comparisons and multiple correlation models. Case control findings from interviews seven years post-partum indicate that mothers of children with FASD are significantly more likely than randomly-selected controls or community mothers to: be shorter; have higher body mass indexes (BMI); be married to a man with legal problems; report more drinking three months pre-pregnancy; engage in more current drinking and drinking alone; and have alcohol problems in her family. Logistic regression analysis of multiple candidate predictors of a FASD diagnosis indicates that alcohol problems in the child's family is the most significant risk factor, making a diagnosis within the continuum of FASD 9 times more likely (95%C.I. = 1.6 to 50.7). Sequential multiple regression analysis of the child's neuropsychological performance also identifies alcohol problems in the child's family as the only significant maternal risk variable (p < .001) when controlling for other potential risk factors. Underreporting of prenatal alcohol use has been demonstrated among Italian and other Mediterranean antenatal samples, and it was suspected in this sample. Nevertheless, several significant maternal risk factors for FASD have been identified. Copyright © 2014. Published by Elsevier Ireland Ltd.

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Early alcohol exposure impairs ocular dominance plasticity throughout the critical period.

PubMed

Medina, Alexandre E; Ramoa, Ary S

2005-06-09

Animal models of fetal alcohol syndrome (FAS) have revealed an impairment of sensory neocortex plasticity. Here, we examine whether early alcohol exposure leads to a permanent impairment of ocular dominance plasticity (OD) or to an alteration in the timing of the critical period. Ferrets were exposed to alcohol during a brief period of development prior to eye opening and effects of monocular deprivation examined during early, mid and late critical period. Single-unit electrophysiology revealed markedly reduced OD plasticity at every age examined. This finding provides evidence that early alcohol exposure does not affect the timing or duration of the critical period of OD plasticity and suggests an enduring impairment of neural plasticity in FAS.

A Proposal for a Prevalence Study of the Use of Alcohol among Women Attending Selected United States Air Force Prenatal Clinics.

DTIC Science & Technology

1985-06-01

and ptosis 7. epicanthal folds 8. cleft lip or cleft palate 9. hirsuitism APPENDIX 2 PROCESSION PLAN Stage Activit Time Required Phase I step 1 Select...thin upper lip , and/or flattening of the maxillary area II. FETAL ALCOHOL EFFECTS: Any congenital abnormality seen in children as a result of maternal

Impairment of motor skills in children with fetal alcohol spectrum disorders in remote Australia: The Lililwan Project.

PubMed

Lucas, Barbara R; Doney, Robyn; Latimer, Jane; Watkins, Rochelle E; Tsang, Tracey W; Hawkes, Genevieve; Fitzpatrick, James P; Oscar, June; Carter, Maureen; Elliott, Elizabeth J

2016-11-01

We aimed to characterise motor performance in predominantly Aboriginal children living in very remote Australia, where rates of prenatal alcohol exposure (PAE) are high. Motor performance was assessed, and the relationship between motor skills, fetal alcohol spectrum disorders (FASD) and PAE was explored. Motor performance was assessed using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition Complete Form, in a population-based study of children born in 2002 or 2003 living in the Fitzroy Valley, Western Australia. Composite scores ≥2SD (2nd percentile) and ≥1SD (16th percentile) below the mean were used respectively for FASD diagnosis and referral for treatment. FASD diagnoses were assigned using modified Canadian Guidelines. A total of 108 children (Aboriginal: 98.1%; male: 53%) with a mean age of 8.7 years was assessed. The cohort's mean total motor composite score (mean ± SD 47.2 ± 7.6) approached the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition normative mean (50 ± 10). Motor performance was lower in children with FASD diagnosis than without (mean difference (MD) ± SD: -5.0 ± 1.8; confidence interval: -8.6 to -1.5). There was no difference between children with PAE than without (MD ± SE: -2.2 ± 1.5; confidence interval: -5.1 to 0.80). The prevalence of motor impairment (≥-2SD) was 1.9% in the entire cohort, 9.5% in children with FASD, 3.3% in children with PAE and 0.0% both in children without PAE or FASD. Almost of 10% of children with FASD has significant motor impairment. Evaluation of motor function should routinely be included in assessments for FASD, to document impairment and enable targeted early intervention.[Lucas BR, Doney R, Latimer J, Watkins RE, Tsang TW, Hawkes G, Fitzpatrick JP, Oscar J, Carter M, Elliott EJ. Impairment of motor skills in children with fetal alcohol spectrum disorders in remote Australia: The Lililwan Project. Drug Alcohol Rev 2016;35:719-727]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Theory of Mind in Children with Fetal Alcohol Spectrum Disorders.

PubMed

Lindinger, Nadine M; Malcolm-Smith, Susan; Dodge, Neil C; Molteno, Christopher D; Thomas, Kevin G F; Meintjes, Ernesta M; Jacobson, Joseph L; Jacobson, Sandra W

2016-02-01

Theory of mind (ToM) refers to the ability to understand and make inferences about other people's intentions, feelings, and beliefs. Although children with fetal alcohol spectrum disorders (FASD) are known to have deficits in social-cognitive function, little is known about ToM in FASD. ToM ability was assessed using a developmentally sensitive ToM battery, including the reading the mind in the eyes (RME) test, a measure of mental inferential ability that has been found to be impaired in other clinical populations. IQ and executive function (EF) were assessed as potential mediating variables. The battery was administered to 63 children (aged 9 to 11 years) from Cape Town, South Africa, whose mothers had been prospectively recruited during pregnancy. Children with fetal alcohol syndrome (FAS; n = 8) and partial FAS (PFAS; n = 19), as well as nonsyndromal heavily exposed children (n = 17), were compared to children born to abstaining or light drinkers (n = 19) from the same community. No FASD group differences were found on the less challenging ToM tasks. By contrast, children with FAS and PFAS performed more poorly than controls on a more challenging ToM task, the RME test. A continuous measure of prenatal alcohol exposure (PAE) was more sensitive than FASD diagnosis in that it was related to 4 higher-order ToM measures, particularly the ability to attribute mental states assessed on RME. IQ only partially mediated the effect of exposure on RME performance, and these effects were not mediated by EF. Hence, the data suggest that these ToM measures tap into a specific alcohol-related social-cognitive deficit that does not merely reflect poorer EF. FASD diagnosis and PAE were each also related to RME after control for attention deficit/hyperactivity disorder. These findings suggest that deficits in higher-order ToM function may play a significant role in the social-cognitive behavioral impairment in FASD. Copyright © 2016 by the Research Society on Alcoholism.

Effects of third trimester-equivalent ethanol exposure on Cl(-) co-transporter expression, network activity, and GABAergic transmission in the CA3 hippocampal region of neonatal rats.

PubMed

Everett, Julie C; Licón-Muñoz, Yamhilette; Valenzuela, C Fernando

2012-09-01

Fetal alcohol spectrum disorders are often associated with structural and functional hippocampal abnormalities, leading to long-lasting learning and memory deficits. The mechanisms underlying these abnormalities are not fully understood. Here, we investigated whether ethanol exposure during the 3rd trimester-equivalent period alters spontaneous network activity that is involved in neuronal circuit development in the CA3 hippocampal region. This activity is driven by GABA(A) receptors, which can have excitatory actions in developing neurons as a consequence of greater expression of the Cl(-) importer, NKCC1, with respect to expression of the Cl(-) exporter, KCC2, resulting in high [Cl(-)](i). Rat pups were exposed to ethanol vapor from postnatal day (P) 2-16 (4 h/day). Weight gain was significantly reduced in pups exposed to ethanol compared to control at P15 and 16. Brain slices were prepared immediately after the end of the 4-h exposure on P4-16 and experiments were also performed under ethanol-free conditions at the end of the exposure paradigm (P17-22). Ethanol exposure did not significantly affect expression of KCC2 or NKCC1, nor did it affect network activity in the CA3 hippocampal region. Ethanol exposure significantly decreased the frequency (at P9-11) and increased the amplitude (at P5-8 and P17-21) of GABA(A) receptor-mediated miniature postsynaptic currents. These data suggest that repeated in vivo exposure to ethanol during the 3rd trimester-equivalent period alters GABAergic transmission in the CA3 hippocampal region, an effect that could lead to abnormal circuit maturation and perhaps contribute to the pathophysiology of fetal alcohol spectrum disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of spatial working memory in children with prenatal alcohol exposure and those diagnosed with ADHD; A functional magnetic resonance imaging study

PubMed Central

2012-01-01

Background Alcohol related neurodevelopmental disorder (ARND) falls under the umbrella of fetal alcohol spectrum disorder (FASD), but individuals do not demonstrate the facial characteristics associated with fetal alcohol syndrome (FAS), making diagnosis difficult. While attentional problems in ARND are similar to those found in attention-deficit/hyperactivity disorder (ADHD), the underlying impairment in attention pathways may be different. Methods Functional magnetic resonance imaging (fMRI) of a working memory (1-back) task of 63 children, 10 to 14 years old, diagnosed with ARND and ADHD, as well as typically developing (TD) controls, was conducted at 3 T. Diffusion tensor imaging (DTI) data were also acquired. Results Activations were observed in posterior parietal and occipital regions in the TD group and in dorsolateral prefrontal and posterior parietal regions in the ARND group, whereas the ADHD group activated only dorsolateral prefrontal regions, during the working memory component of the task (1-back minus 0-back contrast). The increases in frontal and parietal activity were significantly greater in the ARND group compared to the other groups. This increased activity was associated with reduced accuracy and increased response time variability, suggesting that ARND subjects exert greater effort to manage short-term memory load. Significantly greater intra-subject variability, demonstrated by fMRI region-of-interest analysis, in the ADHD and ARND groups compared to the TD group suggests that moment-to-moment lapses in attention contributed to their poorer task performance. Differences in functional activity in ARND subjects with and without a diagnosis of ADHD resulted primarily from reduced activation by the ARND/ADHD + group during the 0-back task. In contrast, children with ADHD alone clearly showed reduced activations during the 1-back task. DTI analysis revealed that the TD group had significantly higher total tract volume and number of fibers than the ARND group. These measures were negatively correlated with errors on the 1-back task, suggesting a link between white matter integrity and task performance. Conclusions fMRI activations suggest that the similar behavior of children with ARND and ADHD on a spatial working memory task is the result of different cognitive events. The nature of ADHD in children with ARND appears to differ from that of children with ADHD alone. PMID:22958510

Visual search for feature conjunctions: an fMRI study comparing alcohol-related neurodevelopmental disorder (ARND) to ADHD.

PubMed

O'Conaill, Carrie R; Malisza, Krisztina L; Buss, Joan L; Bolster, R Bruce; Clancy, Christine; de Gervai, Patricia Dreessen; Chudley, Albert E; Longstaffe, Sally

2015-01-01

Alcohol-related neurodevelopmental disorder (ARND) falls under the umbrella of fetal alcohol spectrum disorder (FASD). Diagnosis of ARND is difficult because individuals do not demonstrate the characteristic facial features associated with fetal alcohol syndrome (FAS). While attentional problems in ARND are similar to those found in attention-deficit/hyperactivity disorder (ADHD), the underlying impairment in attention pathways may be different. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was conducted at 3 T. Sixty-three children aged 10 to 14 years diagnosed with ARND, ADHD, and typically developing (TD) controls performed a single-feature and a feature-conjunction visual search task. Dorsal and ventral attention pathways were activated during both attention tasks in all groups. Significantly greater activation was observed in ARND subjects during a single-feature search as compared to TD and ADHD groups, suggesting ARND subjects require greater neural recruitment to perform this simple task. ARND subjects appear unable to effectively use the very efficient automatic perceptual 'pop-out' mechanism employed by TD and ADHD groups during presentation of the disjunction array. By comparison, activation was lower in ARND compared to TD and ADHD subjects during the more difficult conjunction search task as compared to the single-feature search. Analysis of DTI data using tract-based spatial statistics (TBSS) showed areas of significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the right inferior longitudinal fasciculus (ILF) in ARND compared to TD subjects. Damage to the white matter of the ILF may compromise the ventral attention pathway and may require subjects to use the dorsal attention pathway, which is associated with effortful top-down processing, for tasks that should be automatic. Decreased functional activity in the right temporoparietal junction (TPJ) of ARND subjects may be due to a reduction in the white matter tract's ability to efficiently convey information critical to performance of the attention tasks. Limited activation patterns in ARND suggest problems in information processing along the ventral frontoparietal attention pathway. Poor integrity of the ILF, which connects the functional components of the ventral attention network, in ARND subjects may contribute to the attention deficits characteristic of the disorder.

Palpebral slant - eye

MedlinePlus

... and syndromes. The most common of these is Down syndrome. People with Down syndrome often also have an epicanthal fold in the ... in some cases, it may be due to: Down syndrome Fetal alcohol syndrome Certain genetic disorders

Recognition of clinical characteristics for population-based surveillance of fetal alcohol syndrome.

PubMed

Andrews, Jennifer G; Galindo, Maureen K; Meaney, F John; Benavides, Argelia; Mayate, Linnette; Fox, Deborah; Pettygrove, Sydney; O'Leary, Leslie; Cunniff, Christopher

2018-06-01

The diagnosis of fetal alcohol syndrome (FAS) rests on identification of characteristic facial, growth, and central nervous system (CNS) features. Public health surveillance of FAS depends on documentation of these characteristics. We evaluated if reporting of FAS characteristics is associated with the type of provider examining the child. We analyzed cases aged 7-9 years from the Fetal Alcohol Syndrome Surveillance Network II (FASSNetII). We included cases whose surveillance records included the type of provider (qualifying provider: developmental pediatrician, geneticist, neonatologist; other physician; or other provider) who evaluated the child as well as the FAS diagnostic characteristics (facial dysmorphology, CNS impairment, and/or growth deficiency) reported by the provider. A total of 345 cases were eligible for this analysis. Of these, 188 (54.5%) had adequate information on type of provider. Qualifying physicians averaged more than six reported FAS characteristics while other providers averaged less than five. Qualifying physicians reported on facial characteristics and developmental delay more frequently than other providers. Also, qualifying physicians reported on all three domains of characteristics (facial, CNS, and growth) in 97% of cases while others reported all three characteristics on two thirds of cases. Documentation in medical records during clinical evaluations for FAS is lower than optimal for cross-provider communication and surveillance purposes. Lack of documentation limits the quality and quantity of information in records that serve as a major source of data for public health surveillance systems. © 2018 Wiley Periodicals, Inc.

Prevalence and Predictors of Maternal Alcohol Consumption in Two Regions of Ukraine

PubMed Central

Chambers, Christina D.; Yevtushok, Lyubov; Zymak-Zakutnya, Natalya; Korzhynskyy, Yuriy; Ostapchuk, Lyubov; Akhmedzhanova, Diana; Chan, Priscilla H.; Xu, Ronghui; Wertelecki, Wladimir

2014-01-01

Background Fetal Alcohol Spectrum Disorders (FASD) are thought to be a leading cause of developmental disabilities worldwide. However, data are lacking on alcohol use among pregnant women in many countries.. The purpose of this study was to evaluate the prevalence and predictors of alcohol consumption by pregnant women in Ukraine. Methods Cross sectional screening of pregnant women was conducted in two regions of Ukraine during the recruitment phase of an ongoing clinical study that is part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD). Women attending a routine prenatal visit at one of two participating regional centers were asked about alcohol consumption. Quantity and frequency of alcoholic beverages consumed in the month around conception and in the most recent month of pregnancy were measured using a standard interview instrument. Results Between 2007 and 2012, 11,909 pregnant women were screened on average in the second trimester of pregnancy. Of these, 92.7% reported being ever-drinkers. Among ever-drinkers, 54.8% reported drinking alcohol in the month around conception, and 12.9% consumed at least three drinks on at least one day in that time period. In the most recent month of pregnancy, 46.3% continued to report alcohol use and 9.2% consumed at least three drinks per day. Significant predictors of average number of drinks or heavier drinking per day in either time period in pregnancy included lower gravidity, being single, unmarried/living with a partner, or separated, lower maternal education, smoking, younger age at initiation of drinking and higher score on the TWEAK screening test for harmful drinking. Conclusions These findings support the need for education/intervention in women of childbearing age in Ukraine, and can help inform targeted interventions for women at risk of an alcohol exposed pregnancy. The initiation of a standard screening protocol in pregnancy is a step in the right direction. PMID:24834525

Prenatal alcohol exposure among Alaska Native/American Indian infants.

PubMed

Khan, Burhan A; Robinson, Renee F; Smith, Julia J; Dillard, Denise A

2013-01-01

Recent reports indicate a decline in rates of Fetal Alcohol Syndrome (FAS) among Alaska Native and American Indian (AN/AI) infants. Nevertheless, AN/AI infants remain disproportionately impacted by the effects of prenatal alcohol exposure. AN/AI pregnant women in their 3rd trimester completed a questionnaire on demographic data and the amount and frequency of their alcohol consumption in the month prior to conception and during pregnancy. Differences across demographics and trimesters were tested with the Chi-square, Fisher's exact or McNemar's test as appropriate. Of the 125 participants, 56% (n = 71) reported no alcohol consumption in the 1st through 3rd trimesters of pregnancy; 30% (n = 38) of the 125 participants also reported no alcohol consumption in the month before pregnancy. Of the 43% (n = 54) who reported consuming alcohol during pregnancy (1st, 2nd and/or 3rd trimester), most (35%) reported alcohol use only in the 1st trimester. Binge drinking in the 1st or 2nd trimester was reported amongst 20% (n = 25) of participants with an additional 18% (n = 29) reporting binge drinking in the month prior to pregnancy. Women who reported pre-conception binge drinking were significantly more likely to report binge drinking during their 1st trimester (p < 0.0001) and 2nd trimester (p < 0.0001). A history of tobacco use (p = 0.0403) and cigarette smoking during pregnancy (p < 0.0001) were also associated with binge drinking during pregnancy. Among study participants, reported use of alcohol was primarily limited to pre-conception and the 1st trimester, with a dramatic decrease in the 2nd and 3rd trimesters. Prevention programmes, such as the Alaska FAS Prevention Project, may have contributed to observed decreases in the 2nd and 3rd trimesters. Additional study and focus on pre-conception, the 1st trimester and binge drinking, as well as tobacco use might augment Fetal Alcohol Spectrum Disorder prevention efforts.

The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

PubMed

Hogg, Kirsten; Wood, Charlotte; McNeilly, Alan S; Duncan, W Colin

2011-01-01

Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62-102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05) and the histological presence of fatty liver (P<0.05) independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05), glucocorticoid receptor (GR; P<0.05), UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05) and IGF1 (P<0.01) expression were upregulated. The direct fetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (P<0.05) and this was opposed by fetal TP (P<0.05). Hepatic estrogen receptor (ERα; P<0.05) and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05) were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.

Disruption of adherens junction and alterations in YAP-related proliferation behavior as part of the underlying cell transformation process of alcohol-induced oral carcinogenesis.

PubMed

Husari, Ayman; Hülter-Hassler, Diana; Steinberg, Thorsten; Schulz, Simon Daniel; Tomakidi, Pascal

2018-01-01

Accumulating evidences indicate that alcohol might play a causative in oral cancer. Unfortunately, in vitro cell systems, uncovering the molecular background of the underlying cell transformation process, are rare. Therefore, this study was conducted, to identify molecular changes and characterize their putative cell behavioral consequences in epitheloid (EPI) and fibroblastoid (FIB) oral keratinocyte phenotypes, arising from chronical alcohol treatment. Concerning adherens junctions (AJs), both EPI and FIB showed membrane-bound β-catenin, but exhibited differences for E-cadherin and zyxin. While EPI revealed E-cadherin/β-catenin membrane co-localization, which in parts also applied for zyxin, FIB membranes were devoid of E-cadherin and exhibited marginal zyxin expression. Fetal calf serum (FCS) administration in starved cells promoted proliferation in both keratinocyte phenotypes, whereat EPI and FIB yielded a strikingly modified FCS sensitivity on the temporal scale. Impedance measurement-based cell index detection yielded proliferation stimulation occurring much earlier in FIB (<20h) compared to EPI (>45h). Nuclear preference of the proliferation-associated YAP co-transcription factor in FIB was FCS independent, while it required FCS in EPI. Taken together, the lack of membrane-inherent E-cadherin/β-catenin co-localization together with low zyxin - reveals perturbation of AJ integrity in FIB. Regarding cell behavior, perturbed AJs in FIB correlate with temporal proliferation sensitivity towards FCS. CYF of 5.6 strongly suggests involvement of chromatin-bound YAP in FIB's proliferation temperosensitivity. These molecular differences detected for EPI and FIB are part of the underlying cell transformation process of alcohol-induced oral carcinogenesis, and indicate FIB being in a more advanced transformation stage. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of prenatal alcohol exposure on testosterone and pubertal development

PubMed Central

Carter, R.C.; Jacobson, J.L.; Dodge, N.C.; Granger, D.A.; Jacobson, S.W.

2014-01-01

Background Animal models have demonstrated fetal alcohol-related disruptions in neuroendocrine function in the hypothalamic-pituitary-gonadal (HPG) axis and downstream effects on pubertal development and sexual behavior in males and females, but little is known about these effects in humans. This study examined whether prenatal alcohol exposure is associated with alterations in testosterone during adolescence and whether it affects timing of pubertal development. Methods The sample consisted of 265 African American adolescents from the Detroit Longitudinal Cohort Study for whom testosterone and/or pubertal development data were available. Subjects were offspring of women recruited at their first prenatal clinic visit to over-represent moderate-to-heavy alcohol use, including a 5% random sample of low-level drinkers/abstainers. Mothers were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach and about their smoking and drug use and sociodemographic factors. At age 14 years, adolescents provided salivary samples, which were analyzed for testosterone (pg/mL), self-reported Tanner stages for pubertal development, and age at menarche (females). Results Prenatal alcohol exposure was related to elevated testosterone concentrations for males and females but not to changes in Tanner stages or age at menarche, after controlling for confounders. In regression models stratified by alcohol exposure, the expected relation between testosterone and pubic hair development was seen among males with light-to-no prenatal alcohol exposure but not among those with moderate-to-heavy prenatal alcohol exposure. This interaction between testosterone and prenatal alcohol exposure was confirmed in multivariable models including an alcohol exposure group X testosterone interaction term and potential confounders. Conclusions This study was the first to show a relation between prenatal alcohol exposure and increased testosterone during adolescence and evidence of decreased testosterone responsiveness in tissues related to pubertal development. Further studies examining androgen receptor expression and other hormonal and cellular factors affecting pubertal development may reveal important mechanisms underlying these teratogenic effects of alcohol exposure. PMID:24717169

Creating a Culturally Appropriate Web-Based Behavioral Intervention for American Indian/Alaska Native Women in Southern California: The Healthy Women Healthy Native Nation Study

ERIC Educational Resources Information Center

Gorman, Jessica R.; Clapp, John D.; Calac, Daniel; Kolander, Chelsea; Nyquist, Corinna; Chambers, Christina D.

2013-01-01

Health disparities in fetal alcohol spectrum disorders (FASD) are of high importance to American Indian/Alaska Native (AI/AN) communities. We conducted focus groups and interviews with 21 AI/AN women and key informants in Southern California to modify a brief, Web-based program for screening and prevention of prenatal alcohol use. This process…

Low Birth Weight: A Descriptive Study of Risk Factors

DTIC Science & Technology

1999-01-07

abruption Dx on admit MT Placenta previa Yes Placenta previa Dx complete/partial MT Smoking Yes Tobacco use this pregnancy MT Heavy alcohol use Yes...Multiple Gestation MT Urinary tract infection MT *Anemia MT Fetal anomalies MT Abruptio placentae MT Placenta previa MT Smoking MT Alcohol use...categories: (a) problems with the placenta , (b) problems with the pregnant woman herself, (c) problems with the fetus itself, or (d) any

Evaluating PTSD on Reproductive Outcomes: Women Deployed in Iraq and Afghanistan

DTIC Science & Technology

2010-04-14

more likely to smoke, abuse alcohol and drugs , and have peer prenatal care but the study did not have sufficient power to identify pregnancy outcomes...fetal wt Yes (ect preg, spon AB, Ptcont, macro, hyperem; no (GDM, pre-ec, labor diff) Drug abuse sig more w/PTSD (p<.001); spont AB, excess...Prenatal Complications gestational diabetes hypertension preeclampsia infections drug /alcohol use hyperemesis Postpartum Complications

Fetal alcohol spectrum disorder in Africa.

PubMed

Adnams, Colleen M

2017-03-01

This review aims to summarize data published in the scientific literature and available on official websites on fetal alcohol spectrum disorder (FASD) in Africa. There is a paucity of published literature and evidence-based information on prenatal exposure to alcohol in the African continent and the majority of the continent's literature on FASD emanates from South Africa. A small number of scientific publications document FASD and drinking in pregnancy in other Sub-Saharan African countries and these findings provide evidence that FASD occurs across the continent. Further evidence shows that the world's highest reported rates of FASD occur in South Africa and that this confers a significant public health and neurodevelopmental disability burden on the region. There is an established body of epidemiological, diagnostic, neurobehavioral and neuroscientific knowledge from studies in South Africa. Universal and indicated case method preventions are effective in reducing maternal alcohol consumption in high-risk areas. Throughout Africa, a policy and service implementation gap exists that impedes translation of generated knowledge into effective prevention and intervention strategies. FASD is likely a widely occurring and largely unrecognized neurodevelopmental disability in Africa. A key future direction for global agencies and research partnerships is to collaboratively address evidence gaps and knowledge translation through scalable approaches and strategies that aim to ameliorate the burden of FASD in African and other countries.

Games that "work": using computer games to teach alcohol-affected children about fire and street safety.

PubMed

Coles, Claire D; Strickland, Dorothy C; Padgett, Lynne; Bellmoff, Lynnae

2007-01-01

Unintentional injuries are a leading cause of death and disability for children. Those with developmental disabilities, including children affected by prenatal alcohol exposure, are at highest risk for injuries. Although teaching safety skills is recommended to prevent injury, cognitive limitations and behavioral problems characteristic of children with fetal alcohol spectrum disorder make teaching these skills challenging for parents and teachers. In the current study, 32 children, ages 4-10, diagnosed with fetal alcohol syndrome (FAS) and partial FAS, learned fire and street safety through computer games that employed "virtual worlds" to teach recommended safety skills. Children were pretested on verbal knowledge of four safety elements for both fire and street safety conditions and then randomly assigned to one condition. After playing the game until mastery, children were retested verbally and asked to "generalize" their newly acquired skills in a behavioral context. They were retested after 1 week follow-up. Children showed significantly better knowledge of the game to which they were exposed, immediately and at follow-up, and the majority (72%) was able to generalize all four steps within a behavioral setting. Results suggested that this is a highly effective method for teaching safety skills to high-risk children who have learning difficulties.

[Polythelia in alcoholics. Preliminary report].

PubMed

König, P; Haller, R; Dünser, H

1985-09-30

We present a study comparing 650 alcoholics with 1074 patients with miscellaneous other psychiatric (665) and medical (409) diagnoses for the frequency of supernumerary nipples (SN). Also 716 adolescents and school-children in a general medical screening were investigated for this phenomenon. In alcoholics SN were found in over 6%, in the non-alcoholic group in approximately 1%. The latter figure correlates well with other findings in literature, 6% being significantly higher. In the group of adolescents/children (1,8-3,2%) polythelia correlates with familial alcoholism, albeit of the father. As polythelia may be part of fetal alcohol-syndrome, the addiction should be expected on the mother's side, the more so, as the local rate of female/male alcoholism is approximately 1:3 (administrative incidence). We suggest that polythelia may be more frequent among alcoholics. Apart from SN occurring in alcoholic embryopathy, alcoholism of the father may be an additional factor for their development. Polythelia may in certain cases offer a diagnostic clue not only for mammo-renal syndromes but also for individual or familial alcoholism.

A survey of physicians knowledge regarding awareness of maternal alcohol use and the diagnosis of FAS.

PubMed Central

Nevin, Alexandra C; Parshuram, Christopher; Nulman, Irena; Koren, Gideon; Einarson, Adrienne

2002-01-01

Background Alcohol is the most widely used drug in the world that is a human teratogen whose use among women of childbearing age has been steadily increasing. It is also probable that Fetal Alcohol Syndrome is under diagnosed by physicians. The objectives of this study were twofold: 1) to evaluate the experience, knowledge and confidence of family physicians with respect to the diagnosis of FAS and 2) to evaluate physicians awareness of maternal drinking patterns. Methods and Participants A multiple choice anonymous questionnaire was sent to a randomly selected group of family physicians in the Metropolitan Toronto area. Results There was a 73% (75/103) total response rate; Overall, 6/75 (8%) of family physicians reported that they had actually diagnosed a child with FAS. 17.9% had suspicions but did not make a diagnosis and 12.7% reported making a referral to confirm the diagnosis. Physician rated confidence in the ability to diagnosis FAS was low, with 49% feeling they had very little confidence. 75% reported counselling pregnant women and 60.8% reported counselling childbearing women in general on the use of alcohol. When asked what screening test they used to detect the use of alcohol, 75% described frequency/quantity. Not a single respondent identified using the current accepted screening method for alcohol use (TWEAK) which is recommended by The Centre for Addiction and Mental Health. Conclusions Family physicians do not feel confident about diagnosing FAS. None of the physicians were aware of the current screening methods to accurately gage alcohol use in pregnant and childbearing women PMID:11860607

Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

PubMed

Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

2015-08-01

Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD).

Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum

PubMed Central

Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A.; Handshoe, Jonathan W.; Cui, Jiajun; Xu, Wenhua

2015-01-01

Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR−/− mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR−/− mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR−/− mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD). PMID:25592072

Sympathy, shame, and few solutions: News media portrayals of fetal alcohol spectrum disorders.

PubMed

Eguiagaray, Ines; Scholz, Brett; Giorgi, Caterina

2016-09-01

there is a lack of public understanding about fetal alcohol spectrum disorders (FASD), and many countries lack policies to deal with FASD concerns. Given the role of news media in disseminating a range of health information, the aim of the current study was to explore the media coverage on alcohol use during pregnancy and FASD, and to identify ways to improve associated health messages. the current study uses a framing analysis of news media reports about FASD over a 1-year period. Framing analysis seeks to better understand how media messages serve to shape the thoughts, feelings, and decisions of readers. two frames dominated the media coverage of FASD: a frame of sympathy, and a frame of shame. Some news media encouraged feelings of sympathy for children with FASD, while others encouraged sympathy towards mothers of these children. At the same time, mothers were also portrayed as deserving of shame. the interrelated frames of sympathy and shame may confuse readers, as they inconsistently hold different parties responsible for the impact of FASD. Media portrayals that encourage women to refrain from alcohol consumption during pregnancy might be more useful than stigmatising and isolating those who do. practitioners should be aware that conflicting messages about alcohol consumption during pregnancy might lead to shame and confusion, and should encourage openness with mothers to challenge stigma. Guidelines for media reporting should discourage stigmatising frames, and media articles should also consider the role that government, non-government organisations, and the alcohol industry could play for improving FASD shame. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling Fetal Alcohol Spectrum Disorder: validating an ex vivo primary hippocampal cell culture system

PubMed Central

Tunc-Ozcan, Elif; Ferreira, Adriana B.; Redei, Eva E.

2016-01-01

Background Fetal Alcohol Spectrum Disorder (FASD) is the leading non-genetic cause of mental retardation. There are no treatments for FASD to date. Preclinical in vivo and in vitro studies could help in identifying novel drug targets as for other diseases. Here, we describe an ex vivo model that combines the physiological advantages of prenatal ethanol (E) exposure in vivo with the uniformity of primary fetal hippocampal culture to characterize the effects of prenatal E. The insulin signaling pathways are known to be involved in hippocampal functions. Therefore, we compared the expression of insulin signaling pathway genes between fetal hippocampi (in vivo) and primary hippocampal culture (ex vivo). The similarity of prenatal E effects in these two paradigms would deem the ex vivo culture acceptable to screen possible treatments for FASD. Methods Pregnant Sprague-Dawley rats received one of three diets: ad libitum standard lab chow (control-C), isocaloric pair-fed (PF, nutritional control), and E containing liquid diets from gestational day (GD) 8. Fetal male and female hippocampi were collected either on GD21 (in vivo) or on GD18 for primary culture (ex vivo). Transcript levels of Igf2, Igf2r, Insr, Grb10, Rasgrf1 and Zac1 were measured by RT-qPCR. Results Hippocampal transcript levels differed by prenatal treatment in both males and females with sex differences observed in the expression of Igf2 and Insr. The effect of prenatal E on the hippocampal expression of the insulin pathway genes was parallel in the in vivo and the ex vivo conditions. Conclusions The similarity of gene expression changes in response to prenatal E between the in vivo and the ex vivo conditions ascertain that these effects are already set in the fetal hippocampus at GD18. This strengthens the feasibility of the ex vivo primary hippocampal culture as a tool to test and screen candidate drug targets for FASD. PMID:27162054

Psychometric Properties of Brief Screening Tests for Alcohol Use Disorders during Pregnancy in Argentina.

PubMed

López, Mariana Beatriz; Lichtenberger, Aldana; Conde, Karina; Cremonte, Mariana

2017-07-01

Background  Considering the physical, mental and behavioral problems related to fetal alcohol exposure, prenatal clinical guides suggest a brief evaluation of alcohol consumption during pregnancy to detect alcohol intake and to adjust interventions, if required. Even if any alcohol use should be considered risky during pregnancy, identifying women with alcohol use disorders is important because they could need a more specific intervention than simple advice to abstain. Most screening tests have been developed and validated in male populations and focused on the long-term consequences of heavy alcohol use, so they might be inappropriate to assess consumption in pregnant women. Objective  To analyze the internal reliability and validity of the alcohol screening instruments Alcohol Use Disorders Identification Test (AUDIT), Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), Tolerance, Worried, Eye-Opener, Amnesia and Cut-Down (TWEAK), Rapid Alcohol Problems Screen - Quantity Frequency (RAPS-QF) and Tolerance, Annoyed, Cut-Down and Eye-Opener (T-ACE) to identify alcohol use disorders in pregnant women. Methods  A total of 641 puerperal women were personally interviewed during the 48 hours after delivery. The receiver operating characteristics (ROC) curves and the sensitivity and specificity of each instrument using different cut-off points were analyzed. Results  All instruments showed areas under the ROC curves above 0.80. Larger areas were found for the TWEAK and the AUDIT. The TWEAK, the T-ACE and the AUDIT-C showed higher sensitivity, while the AUDIT and the RAPS-QF showed higher specificity. Reliability (internal consistency) was low for all instruments, improving when optimal cut-off points were used, especially for the AUDIT, the AUDIT-C and the RAPS-QF. Conclusions  In other cultural contexts, studies have concluded that T-ACE and TWEAK are the best instruments to assess pregnant women. In contrast, our results evidenced the low reliability of those instruments and a better performance of the AUDIT in this population. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Adolescent Choline Supplementation Attenuates Working Memory Deficits in Rats Exposed to Alcohol During the Third Trimester Equivalent

PubMed Central

Schneider, Ronald D.; Thomas, Jennifer D.

2018-01-01

Background Children exposed to alcohol prenatally may suffer from behavioral and cognitive alterations that adversely affect their quality of life. Animal studies have shown that perinatal supplementation with the nutrient choline can attenuate ethanol’s adverse effects on development; however, it is not clear how late in development choline can be administered and still effectively reduce the consequences of prenatal alcohol exposure. Using a rodent model, this study examined whether choline supplementation is effective in mitigating alcohol’s teratogenic effects when administered during adolescence/young adulthood. Methods Sprague–Dawley rats were exposed to alcohol (5.25 g/kg/d) during the third trimester equivalent brain growth spurt, which occurs from postnatal day (PD) 4 to 9, via oral intubation. Sham-intubated and nontreated controls were included. Subjects were treated with 100 mg/kg/d choline chloride or vehicle from PD 40 to 60, a period equivalent to young adulthood in the rat. After the choline treatment had ceased, subjects were tested on a series of behavioral tasks: open field activity (PD 61 to 64), Morris water maze spatial learning (PD 65 to 73), and spatial working memory (PD 87 to 91). Results Ethanol-exposed subjects were overactive in the activity chambers and impaired on both the spatial and the working memory versions of the Morris water maze. Choline treatment failed to attenuate alcohol-related overactivity in the open field and deficits in Morris water maze performance. In contrast, choline supplementation significantly mitigated alcohol-related deficits in working memory, which may suggest that choline administration at this later developmental time affects functioning of the prefrontal cortex. Conclusions The results indicate that adolescent choline supplementation can attenuate some, but not all, of the behavioral deficits associated with early developmental alcohol exposure. The results of this study indicate that dietary intervention may reduce some fetal alcohol effects, even when administered later in life, findings with important implications for adolescents and young adults with fetal alcohol spectrum disorders. PMID:27038598

Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits

PubMed Central

Bonthius, Daniel J.; Winters, Zachary; Karacay, Bahri; Bousquet, Samantha Larimer; Bonthius, Daniel J.

2014-01-01

The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS−/− mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS−/− mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS−/− mice and their wild type controls received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days 4–9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS−/− and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS−/− mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS−/− mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS−/− mice, but not in wild type. Thus, homozygous mutation of the nNOS gene increases vulnerability to alcohol-induced cerebellar dysfunction and neuronal loss. nNOS is the first gene identified whose mutation worsens alcohol-induced cerebellar behavioral deficits. PMID:25511929

Recognized Spontaneous Abortion in Mid-Pregnancy and Patterns of Pregnancy Alcohol Use

PubMed Central

Chiodo, Lisa M.; Bailey, Beth; Sokol, Robert J.; Janisse, James; Delaney-Black, Virginia; Hannigan, John H.

2012-01-01

Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking were significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African American sample. Some drinking measures averaged across pregnancy may have underestimated consumption and overestimated risk of SAb, but others risk-drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk-level alcohol consumption and protect from pregnancy loss. PMID:22440690

CB1-receptor knockout neonatal mice are protected against ethanol-induced impairments of DNMT1, DNMT3A, and DNA methylation.

PubMed

Nagre, Nagaraja N; Subbanna, Shivakumar; Shivakumar, Madhu; Psychoyos, Delphine; Basavarajappa, Balapal S

2015-02-01

The significant consequences of ethanol use during pregnancy are neurobehavioral abnormalities involving hippocampal and neocortex malfunctions that cause learning and memory deficits collectively named fetal alcohol spectrum disorder. However, the molecular mechanisms underlying these abnormalities are still poorly understood and therefore warrant systematic research. Here, we document novel epigenetic abnormalities in the mouse model of fetal alcohol spectrum disorder. Ethanol treatment of P7 mice, which induces activation of caspase 3, impaired DNA methylation through reduced DNA methyltransferases (DNMT1 and DNMT3A) levels. Inhibition of caspase 3 activity, before ethanol treatment, rescued DNMT1, DNMT3A proteins as well as DNA methylation levels. Blockade of histone methyltransferase (G9a) activity or cannabinoid receptor type-1 (CB1R), prior to ethanol treatment, which, respectively, inhibits or prevents activation of caspase 3, rescued the DNMT1 and DNMT3A proteins and DNA methylation. No reduction of DNMT1 and DNMT3A proteins and DNA methylation was found in P7 CB1R null mice, which exhibit no ethanol-induced activation of caspase 3. Together, these data demonstrate that ethanol-induced activation of caspase 3 impairs DNA methylation through DNMT1 and DNMT3A in the neonatal mouse brain, and such impairments are absent in CB1R null mice. Epigenetic events mediated by DNA methylation may be one of the essential mechanisms of ethanol teratogenesis. Schematic mechanism of action by which ethanol impairs DNA methylation. Studies have demonstrated that ethanol has the capacity to bring epigenetic changes to contribute to the development of fetal alcohol spectrum disorder (FASD). However, the mechanisms are not well studied. P7 ethanol induces the activation of caspase 3 and impairs DNA methylation through reduced DNA methyltransferases (DNMT1 and DNMT3A) proteins (→). The inhibition or genetic ablation of cannabinoid receptor type-1 or inhibition of histone methyltransferase (G9a) by Bix (-----) or inhibition of caspase 3 activation by Q- quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh) () rescue loss of DNMT1, DNMT3A as well as DNA methylation. Hence, the putative DNMT1/DNMT3A/DNA methylation mechanism may have a potential regulatory role in FASD. © 2014 International Society for Neurochemistry.

Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol syndrome in South Africa: a third study.

PubMed

May, Philip A; Gossage, J Phillip; Marais, Anna-Susan; Hendricks, Loretta S; Snell, Cudore L; Tabachnick, Barbara G; Stellavato, Chandra; Buckley, David G; Brooke, Lesley E; Viljoen, Denis L

2008-05-01

This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. Significant differences were found between the mothers of FASD children and controls in socio-economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS-producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is different between groups, 16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking controls. Mothers of FAS and PFAS children were significantly smaller in height and weight than controls at time of interview. The child's total dysmorphology score correlates significantly with mother's weight (-0.46) and BMI (-0.39). Bivariate correlations are significant between the child's dysmorphology and known independent demographic and behavioral maternal risk factors for FASD: higher gravidity and parity; lower education and income; rural residence; drinks consumed daily, weekly, and bingeing during pregnancy; drinking in all trimesters; partner's alcohol consumption during pregnancy; and use of tobacco during pregnancy. Similar significant correlations were also found for most of the above independent maternal risk variables and the child's verbal IQ, non-verbal IQ and behavioral problems. Maternal data in this population are generally consistent with a spectrum of effects exhibited in the children. Variation within the spectrum links greater alcohol doses with a greater severity of effects among children of older and smaller mothers of lower socio economic status in their later pregnancies. Prevention is needed to address known maternal risk factors for FASD in this population.

Adopting and Fostering Children with Fetal Alcohol Spectrum Disorders

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... is best for everyone so that placements are successful, parents are prepared, and children get the help ... how to reduce the impact of the child’s biological risks by providing a nurturing, responsive, and healthy ...

MOLECULAR AND MORPHOLOGICAL CHANGES IN ZEBRAFISH FOLLOWING TRANSIENT ETHANOL EXPOSURE DURING DEFINED DEVELOPMENTAL STAGES

PubMed Central

Zhang, Chengjin; Frazier, Jared M.; Chen, Hao; Liu, Yao; Lee, Ju-Ahng; Cole, Gregory J.

2014-01-01

Alcohol is a teratogen that has diverse effects on brain and craniofacial development, leading to a constellation of developmental disorders referred to as fetal alcohol spectrum disorder (FASD). The molecular basis of ethanol insult remains poorly understood, as does the relationship between molecular and behavioral changes as a consequence of prenatal ethanol exposure. Zebrafish embryos were exposed to a range of ethanol concentrations (0.5–5.0%) during defined developmental stages, and examined for morphological phenotypes characteristic of FASD. Embryos were also analyzed by in situ hybridization for changes in expression of defined cell markers for neural cell types that are sonic hedgehog-dependent. We show that transient binge-like ethanol exposures during defined developmental stages, such as early gastrulation and early neurulation, result in a range of phenotypes and changes in expression of Shh-dependent genes. The severity of fetal alcohol syndrome (FAS) morphological phenotypes, such as microphthalmia, depends on the embryonic stage and concentration of alcohol exposure, as does diminution of retinal Pax6a or forebrain and hindbrain GAD1 gene expression. We also show that changes in eye and brain morphology correlate with changes in Pax6a and GAD1 gene expression. Our results therefore show that transient binge-like ethanol exposures in zebrafish embryos produce the stereotypical morphological phenotypes of FAS, with the severity of phenotypes depending on the developmental stage and alcohol concentration of exposure. PMID:24929233

Virtual Sensorimotor Training for Balance: Pilot Study Results for Children With Fetal Alcohol Spectrum Disorders.

PubMed

Jirikowic, Tracy; Westcott McCoy, Sarah; Price, Robert; Ciol, Marcia A; Hsu, Lin-Ya; Kartin, Deborah

2016-01-01

To examine the effects of Sensorimotor Training to Affect Balance, Engagement, and Learning (STABEL), a virtual reality system to train sensory adaptation for balance control, for children with fetal alcohol spectrum disorders (FASDs). Twenty-three children with FASDs received STABEL training in a university laboratory, or home, or were controls. The Movement Assessment Battery for Children-2nd edition (MABC-2) and Pediatric Clinical Test of Sensory Interaction for Balance-2 (P-CTSIB-2) were analyzed by group (lab, home, and control), session (pre-STABEL, 1 week post-STABEL, and 1 month post-STABEL), and group-by-session interaction. Significant effects were group and session for MABC-2 Balance and interaction for MABC-2 Total Motor and P-CTSIB-2. Preliminary results support improved sensory adaptation, balance, and motor performance post-STABEL, which warrant further study with a larger, randomized sample.

Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in Drosophila

PubMed Central

Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L.

2014-01-01

Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

Adolescent Choline Supplementation Attenuates Working Memory Deficits in Rats Exposed to Alcohol During the Third Trimester Equivalent.

PubMed

Schneider, Ronald D; Thomas, Jennifer D

2016-04-01

Children exposed to alcohol prenatally may suffer from behavioral and cognitive alterations that adversely affect their quality of life. Animal studies have shown that perinatal supplementation with the nutrient choline can attenuate ethanol's adverse effects on development; however, it is not clear how late in development choline can be administered and still effectively reduce the consequences of prenatal alcohol exposure. Using a rodent model, this study examined whether choline supplementation is effective in mitigating alcohol's teratogenic effects when administered during adolescence/young adulthood. Sprague-Dawley rats were exposed to alcohol (5.25 g/kg/d) during the third trimester equivalent brain growth spurt, which occurs from postnatal day (PD) 4 to 9, via oral intubation. Sham-intubated and nontreated controls were included. Subjects were treated with 100 mg/kg/d choline chloride or vehicle from PD 40 to 60, a period equivalent to young adulthood in the rat. After the choline treatment had ceased, subjects were tested on a series of behavioral tasks: open field activity (PD 61 to 64), Morris water maze spatial learning (PD 65 to 73), and spatial working memory (PD 87 to 91). Ethanol-exposed subjects were overactive in the activity chambers and impaired on both the spatial and the working memory versions of the Morris water maze. Choline treatment failed to attenuate alcohol-related overactivity in the open field and deficits in Morris water maze performance. In contrast, choline supplementation significantly mitigated alcohol-related deficits in working memory, which may suggest that choline administration at this later developmental time affects functioning of the prefrontal cortex. The results indicate that adolescent choline supplementation can attenuate some, but not all, of the behavioral deficits associated with early developmental alcohol exposure. The results of this study indicate that dietary intervention may reduce some fetal alcohol effects, even when administered later in life, findings with important implications for adolescents and young adults with fetal alcohol spectrum disorders. Copyright © 2016 by the Research Society on Alcoholism.

Prevalence and characteristics of fetal alcohol syndrome and partial fetal alcohol syndrome in a Rocky Mountain Region City.

PubMed

May, Philip A; Keaster, Carol; Bozeman, Rosemary; Goodover, Joelene; Blankenship, Jason; Kalberg, Wendy O; Buckley, David; Brooks, Marita; Hasken, Julie; Gossage, J Phillip; Robinson, Luther K; Manning, Melanie; Hoyme, H Eugene

2015-10-01

The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial FAS (PFAS) in the United States (US) are not well known. This active case ascertainment study in a Rocky Mountain Region City assessed the prevalence and traits of children with FAS and PFAS and linked them to maternal risk factors. Diagnoses made by expert clinical dysmorphologists in multidisciplinary case conferences utilized all components of the study: dysmorphology and physical growth, neurobehavior, and maternal risk interviews. Direct parental (active) consent was obtained for 1278 children. Averages for key physical diagnostic traits and several other minor anomalies were significantly different among FAS, PFAS, and randomly-selected, normal controls. Cognitive tests and behavioral checklists discriminated the diagnostic groups from controls on 12 of 14 instruments. Mothers of children with FAS and PFAS were significantly lower in educational attainment, shorter, later in pregnancy recognition, and suffered more depression, and used marijuana and methamphetamine during their pregnancy. Most pre-pregnancy and pregnancy drinking measures were worse for mothers of FAS and PFAS. Excluding a significant difference in simply admitting drinking during the index pregnancy (FAS and PFAS=75% vs. 39.4% for controls), most quantitative intergroup differences merely approached significance. This community's prevalence of FAS is 2.9-7.5 per 1000, PFAS is 7.9-17.7 per 1000, and combined prevalence is 10.9-25.2 per 1000 or 1.1-2.5%. Comprehensive, active case ascertainment methods produced rates of FAS and PFAS higher than predicted by long-standing, popular estimates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi; Medical Research Center, Oulu University Hospital, Oulu; Alhonen, Leena

Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism andmore » uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this stage is so vulnerable to the development of neural tube defect, and growth restriction, the findings previously observed in fetal alcohol syndrome.« less

Neuropsychological study of FASD in a sample of American Indian children: processing simple versus complex information.

PubMed

Aragón, Alfredo S; Kalberg, Wendy O; Buckley, David; Barela-Scott, Lindsey M; Tabachnick, Barbara G; May, Philip A

2008-12-01

Although a large body of literature exists on cognitive functioning in alcohol-exposed children, it is unclear if there is a signature neuropsychological profile in children with Fetal Alcohol Spectrum Disorders (FASD). This study assesses cognitive functioning in children with FASD from several American Indian reservations in the Northern Plains States, and it applies a hierarchical model of simple versus complex information processing to further examine cognitive function. We hypothesized that complex tests would discriminate between children with FASD and culturally similar controls, while children with FASD would perform similar to controls on relatively simple tests. Our sample includes 32 control children and 24 children with a form of FASD [fetal alcohol syndrome (FAS) = 10, partial fetal alcohol syndrome (PFAS) = 14]. The test battery measures general cognitive ability, verbal fluency, executive functioning, memory, and fine-motor skills. Many of the neuropsychological tests produced results consistent with a hierarchical model of simple versus complex processing. The complexity of the tests was determined "a priori" based on the number of cognitive processes involved in them. Multidimensional scaling was used to statistically analyze the accuracy of classifying the neurocognitive tests into a simple versus complex dichotomy. Hierarchical logistic regression models were then used to define the contribution made by complex versus simple tests in predicting the significant differences between children with FASD and controls. Complex test items discriminated better than simple test items. The tests that conformed well to the model were the Verbal Fluency, Progressive Planning Test (PPT), the Lhermitte memory tasks, and the Grooved Pegboard Test (GPT). The FASD-grouped children, when compared with controls, demonstrated impaired performance on letter fluency, while their performance was similar on category fluency. On the more complex PPT trials (problems 5 to 8), as well as the Lhermitte logical tasks, the FASD group performed the worst. The differential performance between children with FASD and controls was evident across various neuropsychological measures. The children with FASD performed significantly more poorly on the complex tasks than did the controls. The identification of a neurobehavioral profile in children with prenatal alcohol exposure will help clinicians identify and diagnose children with FASD.

Alcohol and the developing fetus--a review.

PubMed

Chaudhuri, J D

2000-01-01

Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in some children exposed to alcohol in the prenatal period. It is characterized mainly by physical and mental retardation, craniofacial anomalies and minor joint abnormalities. However, with the increasing incidence of FAS, there is a great variation in the clinical features of FAS. This article describes in detail these clinical features. Due to ethical reasons it is not possible to perform experiments on pregnant women. Hence to study the effects of alcohol, various animal and avian experimental models have been chosen. The various experimental findings and human correlation are described. The exact mechanism by which alcohol induces its teratogenic effects is not known. The possible mechanisms are discussed. Measures to prevent the occurrence of FAS have been suggested.

Sex differences in associations between white matter microstructure and gonadal hormones in children and adolescents with prenatal alcohol exposure.

PubMed

Uban, K A; Herting, M M; Wozniak, J R; Sowell, E R

2017-09-01

Despite accumulating evidence from animal models demonstrating that prenatal alcohol exposure (PAE) results in life-long neuroendocrine dysregulation, very little is known on this topic among humans with fetal alcohol spectrum disorders (FASD). We expected that alterations in gonadal hormones might interfere with the typical development of white matter (WM) myelination, and in a sex-dependent manner, in human adolescents with FASD. In order to investigate this hypothesis, we used diffusion tensor imaging (DTI) to assess: 1) whether or not sex moderates the impact of PAE on WM microstructure; and 2) how gonadal hormones relate to alterations in WM microstructure in children and adolescents affected by PAE. 61 youth (9 to 16 yrs.; 49% girls; 50% PAE) participated as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD). DTI scans and passive drool samples were obtained to examine neurodevelopmental associations with testosterone (T) and dehydroepiandrosterone (DHEA) levels in boys and girls, and estradiol (E2) and progesterone (P) levels in girls. Tract-based spatial statistics were utilized to generate fractional anisotropy (FA) and mean diffusivity (MD) for 9 a priori WM regions of interest (ROIs). As predicted, alterations in FA were observed in adolescents with PAE relative to controls, and these differences varied by sex. Girls with PAE exhibited lower FA (Inferior fronto-occipital and Uncinate fasciculi) while boys with PAE exhibited higher FA (Callosal body, Cingulum, Corticospinal tract, Optic radiation, Superior longitudinal fasciculus) relative to age-matched controls. When gonadal hormone levels were examined in relation to DTI measures, additional group differences in FA were revealed, demonstrating that neuroendocrine factors are associated with PAE-related brain alterations. These findings provide human evidence that PAE relates to sex-specific differences in WM microstructure, and underlying alterations in gonadal hormone function may, in part, contribute to these effects. Determining PAE-effects on neuroendocrine function among humans is an essential first step towards developing novel clinical (e.g., assessment or intervention) tools that target hormone systems to improve on-going brain development among children and adolescents with FASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

The burden of prenatal exposure to alcohol: revised measurement of cost.

PubMed

Stade, Brenda; Ali, Alaa; Bennett, Dainel; Campbell, Douglas; Johnston, Mary; Lens, Cynthia; Tran, Sofia; Koren, Gideon

2009-01-01

In Canada the incidence of Fetal Alcohol Spectrum Disorder (FASD) is estimated to be 1 in 100 live births. FASD is the leading cause of developmental and cognitive disabilities in Canada. Only one study has examined the cost of FASD in Canada. In that study we did not include prospective data for infants under the age of one year, costs for adults beyond 21 years or costs for individuals living in institutions. To calculate a revised estimate of direct and indirect costs associated with FASD at the patient level. Cross-sectional study design was used. Two-hundred and fifty (250) participants completed the study tool. Participants included caregivers of children, youth and adults, with FASD, from day of birth to 53 years, living in urban and rural communities throughout Canada participated. Participants completed the Health Services Utilization Inventory (HSUI). Key cost components were elicited: direct costs: medical, education, social services, out-of-pocket costs; and indirect costs: productivity losses. Total average costs per individual with FASD were calculated by summing the costs for each in each cost component, and dividing by the sample size. Costs were extrapolated to one year. A stepwise multiple regression analysis was used to identify significant determinants of costs and to calculate the adjusted annual costs associated with FASD. Total adjusted annual costs associated with FASD at the individual level was $21,642 (95% CI, $19,842; $24,041), compared to $14,342 (95% CI, $12,986; $15,698) in the first study. Severity of the individual's condition, age, and relationship of the individual to the caregiver (biological, adoptive, foster) were significant determinants of costs (p < 0.001). Cost of FASD annually to Canada of those from day of birth to 53 years old, was $5.3 billion (95% CI, $4.12 billion; $6.4 billion). Study results demonstrated the cost burden of FASD in Canada was profound. Inclusion of infants aged 0 to 1 years, adults beyond the age of 21 years and costs associated with residing in institutions provided a more accurate estimate of the costs of FASD. Implications for practice, policy, and research are discussed. Key words: Alcohol, pregnancy, cost, economic burden, fetal alcohol spectrum disorder.

Maternal-fetal transfer of selenium in the mouse.

PubMed

Burk, Raymond F; Olson, Gary E; Hill, Kristina E; Winfrey, Virginia P; Motley, Amy K; Kurokawa, Suguru

2013-08-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.

Molecular changes during neurodevelopment following second-trimester binge ethanol exposure in a mouse model of fetal alcohol spectrum disorder: from immediate effects to long-term adaptation.

PubMed

Mantha, Katarzyna; Laufer, Benjamin I; Singh, Shiva M

2014-01-01

Fetal alcohol spectrum disorder (FASD) is an umbrella term that refers to a wide range of behavioral and cognitive deficits resulting from prenatal alcohol exposure. It involves changes in brain gene expression that underlie lifelong FASD symptoms. How these changes are achieved from immediate to long-term effects, and how they are maintained, is unknown. We have used the C57BL/6J mouse to assess the dynamics of genomic alterations following binge alcohol exposure. Ethanol-exposed fetal (short-term effect) and adult (long-term effect) brains were assessed for gene expression and microRNA (miRNA) changes using Affymetrix mouse arrays. We identified 48 and 68 differentially expressed genes in short- and long-term groups, respectively. No gene was common between the 2 groups. Short-term (immediate) genes were involved in cellular compromise and apoptosis, which represent ethanol's toxic effects. Long-term genes were involved in various cellular functions, including epigenetics. Using quantitative RT-PCR, we confirmed the downregulation of long-term genes: Camk1g, Ccdc6, Egr3, Hspa5, and Xbp1. miRNA arrays identified 20 differentially expressed miRNAs, one of which (miR-302c) was confirmed. miR-302c was involved in an inverse relationship with Ccdc6. A network-based model involving altered genes illustrates the importance of cellular redox, stress and inflammation in FASD. Our results also support a critical role of apoptosis in FASD, and the potential involvement of miRNAs in the adaptation of gene expression following prenatal ethanol exposure. The ultimate molecular footprint involves inflammatory disease, neurological disease and skeletal and muscular disorders as major alterations in FASD. At the cellular level, these processes represent abnormalities in redox, stress and inflammation, with potential underpinnings to anxiety. © 2014 S. Karger AG, Basel.

Ethanol impairs activation of retinoic acid receptors in cerebellar granule cells in a rodent model of fetal alcohol spectrum disorders.

PubMed

Kumar, Ambrish; Singh, Chandra K; DiPette, Donald D; Singh, Ugra S

2010-05-01

Ethanol is the main addictive and neurotoxic constituent of alcohol. Ethanol exposure during embryonic development causes dysfunction of the central nervous system (CNS) and leads to fetal alcohol spectrum disorders. The cerebellum is one of the CNS regions that are particularly vulnerable to ethanol toxic effects. Retinoic acid (RA) is a physiologically active metabolite of vitamin A that is locally synthesized in the cerebellum. Studies have shown that RA is required for neuronal development, but it remains unknown if ethanol impairs RA signaling and thus induces neuronal malformations. In this study, we tested the hypothesis that ethanol impairs the expression and activation of RA receptors in cerebellum and in cerebellar granule cells. The cerebellum of ethanol unexposed and exposed pups was used to study the expression of retinoic acid receptors (RARs or RXRs) by immunohistochemistry and by Western blot analysis. We also studied the effect of ethanol on expression of RA receptors in the cerebellar granule cells. Activation of RA receptors (DNA-binding activities) in response to high-dose ethanol was determined by electrophoretic mobility shift and supershift assays. Findings from these studies demonstrated that ethanol exposure reduced the expression of RARalpha/gamma while it increased the expression of RXRalpha/gamma in the cerebellum and in cerebellar granule neurons. Immuno-histological studies further strengthened the expression pattern of RA receptors in response to ethanol. The DNA-binding activity of RARs was reduced, while DNA-binding activity of RXRs was increased in response to ethanol exposure. For the first time, our studies have demonstrated that high-dose ethanol affects the expression and activation of RA receptors, which could impair the signaling events and induce harmful effects on the survival and differentiation of cerebellar granule cells. Taken together, these findings could provide insight into the treatment options for brain defects caused by excessive ethanol exposure, such as in Fetal Alcohol Spectrum Disorders.

Mathematics intervention for children with fetal alcohol spectrum disorder: A replication and extension of the math interactive learning experience (MILE) program.

PubMed

Kully-Martens, Katrina; Pei, Jacqueline; Kable, Julie; Coles, Claire D; Andrew, Gail; Rasmussen, Carmen

2018-07-01

Individuals with fetal alcohol spectrum disorders (FASD) experience deficits in behavior, cognition, and academic functioning resulting from prenatal alcohol exposure (PAE). Although receiving intervention for developmental disabilities is a strong protective factor against negative outcomes in FASD, intervention research in this population is in its infancy. The purpose of this study was to replicate and extend a mathematics intervention, the Math Interactive Learning Experience (MILE) program, which was developed in the USA specifically for children with FASD. Twenty-eight Canadian children aged 4-10 years with confirmed PAE or an FASD diagnosis were assigned to either the MILE intervention or a contrast intervention. Following a relatively brief, individualized, one-on-one intervention, children in the MILE group demonstrated significantly greater changes in math achievement compared to the contrast group. Significant changes in other cognitive functions were not observed. Older age, lower IQ, and confirmed PAE but no FASD diagnosis were associated with greater math achievement change in the MILE group. The replication and extension of the math intervention appears to have significant, positive impact on mathematics achievement scores of children with PAE and FASD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Overexpression of Serum Response Factor in Neurons Restores Ocular Dominance Plasticity in a Model of Fetal Alcohol Spectrum Disorders

PubMed Central

Foxworthy, W. Alex; Medina, Alexandre E.

2015-01-01

Background Deficits in neuronal plasticity underlie many neurobehavioral and cognitive problems presented in Fetal Alcohol Spectrum Disorders (FASD). Our lab has developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. For instance, a few days of monocular deprivation results in a robust reduction of visual cortex neurons’ responsiveness to stimulation of the deprived eye in normal animals, but not in ferrets with early alcohol exposure. Previously our lab demonstrated that overexpression of serum response factor (SRF) exclusively in astrocytes can improve neuronal plasticity in FASD. Here we test whether neuronal overexpression of SRF can achieve similar effects. Methods Ferrets received 3.5 g/kg alcohol i.p. (25% in saline) or saline as control every other day between postnatal day (P) 10 to 30, which is roughly equivalent to the third trimester of human gestation. Animals were given intracortical injections of a Herpes viral vector to express either GFP or a constitutively active form of SRF in infected neurons. They were then monocularly deprived by eyelid suture for 4–5 d after which single-unit recordings were conducted to determine if changes in ocular dominance had occurred. Results Overexpression of a constitutively active form of SRF by neurons restored OD plasticity in alcohol-treated animals. This effect was observed only in areas near the site of viral infection. Conclusions Overexpression of SRF in neurons can restore plasticity in the ferret model of FASD, but only in areas near the site of infection. This contrasts with SRF overexpression in astrocytes which restored plasticity throughout the visual cortex. PMID:26342644

The Source for Syndromes.

ERIC Educational Resources Information Center

Richard, Gail J.; Hoge, Debra Reichert

Designed for practicing speech-language pathologists, this book discusses different syndrome disabilities, pertinent speech-language characteristics, and goals and strategies to begin intervention efforts at a preschool level. Chapters address: (1) Angelman syndrome; (2) Asperger syndrome; (3) Down syndrome; (4) fetal alcohol syndrome; (5) fetal…

Fetal alcohol spectrum disorders in Australia--the future is prevention.

PubMed

Elliott, Elizabeth J

2015-03-30

Fetal alcohol spectrum disorders (FASD) are increasingly recognised throughout Australia as important, but preventable, disorders that result in lifelong problems with health and learning, mental health, behaviour and substance misuse. The role of this article is to highlight current efforts, which are in their infancy, to recognise and prevent FASD in Australia. A federal parliamentary inquiry into FASD (2011), development of an Australian Government 'action plan' to prevent FASD (2013) and the announcement in June 2014 of government funding to progress the plan and appoint a National FASD Technical Network have focused attention on the need for FASD prevention in Australia. Other welcome developments include the formation of Parliamentarians for the Prevention of FASD (2011), revision of guidelines regarding alcohol use in pregnancy by the National Health and Medical Research Council (NHMRC; 2009) and provision of targeted funding for FASD research by the NHMRC (2013). Initiatives by Indigenous communities to restrict access to alcohol and diagnose and prevent FASD have had a significant impact in high-risk communities. The National Organisation for FASD has an important ongoing advocacy and educational remit. Nongovernment organisations such as the Foundation for Alcohol Research and Education have contributed to prevention by developing resources to assist health professionals to advise women about the harms of alcohol use in pregnancy; encouraging men to abstain from alcohol during the pregnancy; drafting a national plan; and advocating for pregnancy warning labels on alcohol. Internationally, in 2014, a charter on prevention of FASD was published in The Lancet Global Health, and the World Health Organization released guidelines for identification and management of substance use in pregnancy. Early recognition and support for individuals with FASD is crucial to prevent adverse secondary outcomes; however, primary prevention of alcohol use in pregnancy, and hence FASD, should be our future goal. The causal pathway to drinking in pregnancy is complex and requires a broad social ecological approach. Prevention will take time, must involve all government sectors and should incorporate primary, secondary and tertiary strategies to target both the broader community and populations at high risk of alcohol use during pregnancy.

A Prospective Cohort Study of the Prevalence of Growth, Facial, and Central Nervous System Abnormalities in Children with Heavy Prenatal Alcohol Exposure

PubMed Central

Kuehn, Devon; Aros, Sofía; Cassorla, Fernando; Avaria, Maria; Unanue, Nancy; Henriquez, Cecilia; Kleinsteuber, Karin; Conca, Barbara; Avila, Alejandra; Carter, Tonia C.; Conley, Mary R.; Troendle, James; Mills, James L.

2014-01-01

Background Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited. Methods This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status. Results One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome. Conclusions After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and may be the only sign to alert physicians to prenatal alcohol exposure. PMID:22823161

Effect of alcohol consumption on CpG methylation in the differentially methylated regions of H19 and IG-DMR in male gametes: implications for fetal alcohol spectrum disorders.

PubMed

Ouko, Lillian A; Shantikumar, Katpaham; Knezovich, Jaysen; Haycock, Philip; Schnugh, Desmond J; Ramsay, Michèle

2009-09-01

Exposure to alcohol in utero is the main attributable cause of fetal alcohol spectrum disorders (FASD) which in its most severe form is characterized by irreversible behavioral and cognitive disability. Paternal preconception drinking is not considered to be a significant risk factor, even though animal studies have demonstrated that chronic paternal alcohol consumption has a detrimental effect on the physical and mental development of offspring even in the absence of in utero alcohol exposure. It has been documented that alcohol can reduce the levels and activity of DNA methyltransferases resulting in DNA hypomethylation and that reduced methyltransferase activity can cause activation of normally silenced genes. The aim of this study was to establish a link between alcohol use in men and hypomethylation of paternally imprinted loci in sperm DNA in genomic regions critical for embryonic development, thus providing a mechanism for paternal effects in the aetiology of FASD. Sperm DNA from male volunteers was bisulfite treated and the methylation patterns of 2 differentially methylated regions (DMRs), H19 and IG-DMR, analyzed following sequencing of individual clones. The methylation patterns were correlated with the alcohol consumption levels of the volunteer males. There was a pattern of increased demethylation with alcohol consumption at the 2 imprinted loci with a significant difference observed at the IG-DMR between the nondrinking and heavy alcohol consuming groups. Greater inter-individual variation in average methylation was observed at the H19 DMR and individual clones were more extensively demethylated than those of the IG-DMR. CpG site #4 in the IG-DMR was preferentially demethylated among all individuals and along with the H19 DMR CpG site #7 located within the CTCF binding site 6 showed significant demethylation in the alcohol consuming groups compared with the control group. This study demonstrates a correlation between chronic alcohol use and demethylation of normally hypermethylated imprinted regions in sperm DNA. We hypothesize that, should these epigenetic changes in imprinted genes be transmitted through fertilization, they would alter the critical gene expression dosages required for normal prenatal development resulting in offspring with features of FASD.

A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway

PubMed Central

McClure, Kimberly D.; French, Rachael L.; Heberlein, Ulrike

2011-01-01

SUMMARY Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. Additionally, we show that, as in mammals, flies reared on ethanol have altered responses to ethanol vapor exposure as adults, including increased locomotor activation, resistance to the sedating effects of the drug and reduced tolerance development upon repeated ethanol exposure. We have found that the developmental and behavioral defects are largely due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression. Transgenic expression of Dilp proteins in the larval brain suppressed both the developmental and behavioral abnormalities displayed by ethanol-reared adult flies. Our results thus establish Drosophila as a useful model system to uncover the complex etiology of fetal alcohol syndrome. PMID:21303840

Maternal-fetal transfer of selenium in the mouse

PubMed Central

Burk, Raymond F.; Olson, Gary E.; Hill, Kristina E.; Winfrey, Virginia P.; Motley, Amy K.; Kurokawa, Suguru

2013-01-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.—Burk, R. F., Olson, G. E., Hill, K. E., Winfrey, V. P., Motley, A. K., and Kurokawa, S. Maternal-fetal transfer of selenium in the mouse. PMID:23651543

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD).

PubMed

Wozniak, Jeffrey R; Mueller, Bryon A; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Sowell, Elizabeth R

2017-10-01

Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

Epidermal growth factor-like growth factors prevent apoptosis of alcohol-exposed human placental cytotrophoblast cells.

PubMed

Wolff, Garen S; Chiang, Po Jen; Smith, Susan M; Romero, Roberto; Armant, D Randall

2007-07-01

Maternal alcohol abuse during pregnancy can produce an array of birth defects comprising fetal alcohol syndrome. A hallmark of fetal alcohol syndrome is intrauterine growth retardation, which is associated with elevated apoptosis of placental cytotrophoblast cells. Using a human first trimester cytotrophoblast cell line, we examined the relationship between exposure to ethanol and cytotrophoblast survival, as well as the ameliorating effects of epidermal growth factor (EGF)-like growth factors produced by human cytotrophoblast cells. After exposure to 0-100 mM ethanol, cell death was quantified by the TUNEL method, and expression of the nuclear proliferation marker, Ki67, was measured by immunohistochemistry. The mode of cell death was determined by assessing annexin V binding, caspase 3 activation, pyknotic nuclear morphology, reduction of TUNEL by caspase inhibition, and cellular release of lactate dehydrogenase. Ethanol significantly reduced proliferation and increased cell death approximately 2.5-fold through the apoptotic pathway within 1-2 h of exposure to 50 mM alcohol. Exposure to 25-50 mM ethanol significantly increased transforming growth factor alpha (TGFA) and heparin-binding EGF-like growth factor (HBEGF), but not EGF or amphiregulin (AREG). When cytotrophoblasts were exposed concurrently to 100 mM ethanol and 1 nM HBEGF or TGFA, the increase in apoptosis was prevented, while EGF ameliorated at 10 nM and AREG was weakly effective. HBEGF survival-promoting activity required ligation of either of its cognate receptors, HER1 or HER4. These findings reveal the potential for ethanol to rapidly induce cytotrophoblast apoptosis. However, survival factor induction could provide cytotrophoblasts with an endogenous cytoprotective mechanism.

Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

PubMed

Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

2011-12-01

Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Alcohol--woman, pregnancy and a newborn child].

PubMed

Jagielska, Iwona; Kazdepka-Ziemińska, Anita; Stankiewicz, Martyna; Kaźmierczak, Jolanta

2012-01-01

According to the World Health Organization, alcohol is the third most dangerous factor following smoking of tobacco and hypertension of risks impacting health of the population. 50 % of men and 10 % of women suffer from diseases caused by alcohol drinking. Chronic consumption of alcohol damages the nervous system, causes adverse changes in the circulatory system and intestine, increases the risk of cancers. Comparing the impact of alcohol on the health of women and men, in case of women, even similar levels of consumption cause stronger action. Alcohol is the cause of endocrine diseases and among others- reduces fertility. It is the risk factor of premature deliveries, abortions, and placenta- associated pathologies. Disorders of children with prenatal exposure to alcohol are described as fetal alcohol syndrome, alcohol related neurodevelopmental disorders and alcohol related birth defects. It is recommended to impose a total ban on alcohol consumption by pregnant women. Moreover one should emphasize that the minimum safe dose of alcohol for the foetus cannot be specified. In order to resolve alcohol drinking problems a cooperation of representatives of many professions such as: doctors, psychologists, educators and employees of care facilities is necessary. It is also obligatory to obtain support and assistance from the nearest surroundings of the patient.

Evaluating Innovations in Transition From Pediatric to Adult Care - The Transition Navigator Trial

ClinicalTrials.gov

2018-06-06

Diabetes; Endocrine System Diseases; Gastro-Intestinal Disorder; Neuro-Degenerative Disease; Epilepsy; Autoimmune Diseases; Renal Disease; Cardiac Disease; Metabolic Disease; Genetic Diseases, Inborn; Respiratory Disease; Hematologic Diseases; Autism Spectrum Disorder; Fetal Alcohol Spectrum Disorders; Traumatic Brain Injury; Stroke

All Our Children: Handicapped and Normal.

ERIC Educational Resources Information Center

Johnson, Marilyn J.; Scruggs, Thomas E.

The two part presentation presents information on specific conditions of developmental delay and suggests intervention approaches. Three causes of mental retardation (Down's syndrome, Fetal Alcohol Syndrome, and cerebral palsy) are identified and described in terms of definition, incidence, characteristics, and educational implications. Part II is…

Cost of fetal alcohol spectrum disorder diagnosis in Canada.

PubMed

Popova, Svetlana; Lange, Shannon; Burd, Larry; Chudley, Albert E; Clarren, Sterling K; Rehm, Jürgen

2013-01-01

Fetal Alcohol Spectrum Disorder (FASD) is underdiagnosed in Canada. The diagnosis of FASD is not simple and currently, the recommendation is that a comprehensive, multidisciplinary assessment of the individual be done. The purpose of this study was to estimate the annual cost of FASD diagnosis on Canadian society. The diagnostic process breakdown was based on recommendations from the Fetal Alcohol Spectrum Disorder Canadian Guidelines for Diagnosis. The per person cost of diagnosis was calculated based on the number of hours (estimated based on expert opinion) required by each specialist involved in the diagnostic process. The average rate per hour for each respective specialist was estimated based on hourly costs across Canada. Based on the existing clinical capacity of all FASD multidisciplinary clinics in Canada, obtained from the 2005 and 2011 surveys conducted by the Canada Northwest FASD Research Network, the number of FASD cases diagnosed per year in Canada was estimated. The per person cost of FASD diagnosis was then applied to the number of cases diagnosed per year in Canada in order to calculated the overall annual cost. Using the most conservative approach, it was estimated that an FASD evaluation requires 32 to 47 hours for one individual to be screened, referred, admitted, and diagnosed with an FASD diagnosis, which results in a total cost of $3,110 to $4,570 per person. The total cost of FASD diagnostic services in Canada ranges from $3.6 to $5.2 million (lower estimate), up to $5.0 to $7.3 million (upper estimate) per year. As a result of using the most conservative approach, the cost of FASD diagnostic services presented in the current study is most likely underestimated. The reasons for this likelihood and the limitations of the study are discussed.

Prevalence and Characteristics of Fetal Alcohol Syndrome and Partial Fetal Alcohol Syndrome in a Rocky Mountain Region City

PubMed Central

Keaster, Carol; Bozeman, Rosemary; Goodover, Joelene; Blankenship, Jason; Kalberg, Wendy O.; Buckley, David; Brooks, Marita; Hasken, Julie; Gossage, J. Phillip; Robinson, Luther K.; Manning, Melanie; Hoyme, H. Eugene

2015-01-01

Background The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial FAS (PFAS) in the United States (US) are not well known. Methods This active case ascertainment study in a Rocky Mountain Region City assessed the prevalence and traits of children with FAS and PFAS and linked them to maternal risk factors. Diagnoses made by expert clinical dysmorphologists in multidisciplinary case conferences utilized all components of the study: dysmorphology and physical growth; neurobehavior; and maternal risk interviews. Results Direct parental (active) consent was obtained for 1,278 children. Averages for key physical diagnostic traits and several other minor anomalies were significantly different among FAS, PFAS, and randomly-selected, normal controls. Cognitive tests and behavioral checklists discriminated the diagnostic groups from controls on 12 of 14 instruments. Mothers of children with FAS and PFAS were significantly lower in educational attainment, shorter, later in pregnancy recognition, and suffered more depression, and used marijuana and methamphetamine during their pregnancy. Most pre-pregnancy and pregnancy drinking measures were worse for mothers of FAS and PFAS. Excluding a significant difference in simply admitting drinking during the index pregnancy (FAS and PFAS = 75% vs. 39.4% for controls), most quantitative intergroup differences merely approached significance. This community’s prevalence of FAS is 2.9 to 7.5 per 1,000, PFAS is 7.9 to 17.7 per 1,000, and combined prevalence is 10.9 to 25.2 per 1,000 or 1.1% to 2.5%. Conclusions Comprehensive, active case ascertainment methods produced rates of FAS and PFAS higher than predicted by long-standing, popular estimates. PMID:26321671

An analysis of the teratagenic effects that could possibly be due to alcohol consumption by pregnant mothers.

PubMed

Chaudhuri, J D

2000-10-01

It can be concluded that alcohol is definitely harmful to the developing fetus. The effect can manifest in various ways, the most extreme of which is a condition called Fetal Alcohol Syndrome (FAS). The diagnosis of maternal alcoholism leading onto cases of FAS is difficult due to absence of accurate diagnostic tests. The diagnosis of FAS in a child is easier by a proper examination. There is no specific treatment of FAS in a child. The only management is by institution of corrective and rehabilitative measures. The exact mechanism of the teratogenic action of alcohol is not known. It is probably due to the harmful effect of alcohol on the epiblast layer of the bilaminar germ disc. In the absence of adequate knowledge regarding FAS, not much can be done to remedy the deleterious effects of alcohol. Hence, a word of advice to all pregnant women is to avoid drinking during pregnancy.

Health Care Students’ Attitudes About Alcohol Consumption During Pregnancy: Responses to Narrative Vignettes

PubMed Central

Coons, Kelly D.; Watson, Shelley L.; Yantzi, Nicole M.; Lightfoot, Nancy E.; Larocque, Sylvie

2017-01-01

This article explores medical, midwifery, and nurse practitioner students’ attitudes about women who may consume alcohol throughout their pregnancies. Twenty-one health care students responded to a scenario-based vignette addressing alcohol consumption during pregnancy, as well as a semistructured interview, which were analyzed using Braun and Clarke’s thematic analysis approach. Two primary themes related to students’ attitudes concerning alcohol consumption during pregnancy were identified: (a) divergent recommendations for different women, based on perceptions of their level of education, culture/ethnicity, and ability to stop drinking; and (b) understanding the social determinants of health, including the normalization of women’s alcohol consumption and potential partner violence. Health care professionals in training need further education about the risks of alcohol consumption during pregnancy and fetal alcohol spectrum disorder (FASD). In addition, health care students need training in how to engage in reflective practice to identify their own stereotypical beliefs and attitudes and how these attitudes may affect their practice. PMID:29164171

Study protocol: Asking QUestions about Alcohol in pregnancy (AQUA): a longitudinal cohort study of fetal effects of low to moderate alcohol exposure.

PubMed

Muggli, Evelyne; O'Leary, Colleen; Forster, Della; Anderson, Peter; Lewis, Sharon; Nagle, Cate; Craig, Jeffrey M; Donath, Susan; Elliott, Elizabeth; Halliday, Jane

2014-09-03

Despite extensive research, a direct correlation between low to moderate prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders has been elusive. Conflicting results are attributed to a lack of accurate and detailed data on PAE and incomplete information on contributing factors. The public health effectiveness of policies recommending complete abstinence from alcohol during pregnancy is challenged by the high frequency of unplanned pregnancies, where many women consumed some alcohol prior to pregnancy recognition. There is a need for research evidence emphasizing timing and dosage of PAE and its effects on child development. Asking QUestions about Alcohol (AQUA) is a longitudinal cohort aiming to clarify the complex effects of low to moderate PAE using specifically developed and tested questions incorporating dose, pattern and timing of exposure. From 2011, 2146 pregnant women completed a questionnaire at 8-18 weeks of pregnancy. Further prenatal data collection took place via a questionnaire at 26-28 weeks and 35 weeks gestation. Extensive information was obtained on a large number of risk factors to assist in understanding the heterogeneous nature of PAE effects. 1571 women (73%) completed all three pregnancy questionnaires. A biobank of DNA from maternal and infant buccal cells, placental biopsies and cord blood mononuclear cells will be used to examine epigenetic state at birth as well as genetic factors in the mother and child. Participants will be followed up at 12 and 24 months after birth to assess child health and measure infant behavioural and sensory difficulties, as well as family environment and parenting styles. A subgroup of the cohort will have 3D facial photography of their child at 12 months and a comprehensive developmental assessment (Bayley Scales of Infant & Toddler Development, Bayley-III) at two years of age. Using detailed, prospective methods of data collection, the AQUA study will comprehensively examine the effects of low to moderate alcohol consumption throughout pregnancy on child health and development, including the role of key mediators and confounders. These data will ultimately contribute to policy review and development, health professional education and information about alcohol consumption for pregnant women in the future.

Fetal alcohol syndrome (FAS) primary prevention through fas diagnosis: II. A comprehensive profile of 80 birth mothers of children with FAS.

PubMed

Astley, S J; Bailey, D; Talbot, C; Clarren, S K

2000-01-01

A 5-year, fetal alcohol syndrome (FAS) primary prevention study was conducted in Washington State to: (1) assess the feasibility of using a FAS diagnostic and prevention clinic as a centre for identifying and targeting primary prevention intervention to high-risk women; (2) generate a comprehensive, lifetime profile of these women; (3) identify factors that have enhanced and/or hindered their ability to achieve abstinence. The results of this study are presented in two parts. Objective 1 is summarized in the preceding paper and objectives 2 and 3 are summarized here. Comprehensive interviews were conducted with 80 women, who had given birth to a child diagnosed with FAS, to document their sociodemographics, reproductive and family planning history, social and healthcare utilization patterns, adverse social experiences, social support network, alcohol use and treatment history, mental health, and intelligence quotient (IQ). These high-risk women were diverse in racial, educational and economic backgrounds, were often victims of abuse, and challenged by mental health issues. Despite their rather harsh psychosocial profile, many demonstrated the ability to overcome their alcohol dependence over time. Relative to the women who had not achieved abstinence, the women who had achieved abstinence had significantly higher IQs, higher household incomes, larger more satisfactory social support networks, were more likely to report a religious affiliation, and were more likely to be receiving mental health treatment for their mental health disorders. The rate of unintended pregnancies and alcohol-exposed pregnancies was substantial. Key barriers to achieving effective family planning were maternal alcohol and drug use, lack of access to birth control and lack of support by their partner to use birth control. A FAS diagnostic and prevention clinic can be used to identify women at high risk for producing children damaged by prenatal alcohol exposure. Primary prevention programmes targeted to this population could lead to measurable reductions in the incidence of FAS.

"They silently live in terror…" why sleep problems and night-time related quality-of-life are missed in children with a fetal alcohol spectrum disorder.

PubMed

Ipsiroglu, Osman S; McKellin, William H; Carey, Norma; Loock, Christine

2013-02-01

Children and adolescents with a Fetal Alcohol Spectrum Disorder (FASD) are at high-risk for developing sleep problems (SPs) triggering daytime behavioral co-morbidities such as inattention, hyperactivity, and cognitive and emotional impairments. However, symptoms of sleep deprivation are solely associated with typical daytime diagnosis, such as attention deficit hyperactivity disorder (ADHD) and treated with psychotropic medications. To understand how and why SPs are missed, we conducted qualitative interviews (QIs) with six parents and seven health care professionals (HCPs), and performed comprehensive clinical sleep assessments (CCSAs) in 27 patients together with their caregivers referred to our clinic for unresolved SPs. We used narrative schema and therapeutic emplotment in conjunction with analyzes of medical records to appropriately diagnose SPs and develop treatment strategies. The research was conducted at British Columbia Children's Hospital in Vancouver (Canada) between 2008 and 2011. In the QIs, parents and HCPs exhibited awareness of the significance of SPs and the effects of an SP on the daytime behaviors of the child and the associated burdens on the parents. HCPs' systemic inattention to the sequelae of SPs and the affected family's wellbeing appears due to an insufficient understanding of the various factors that contribute to nighttime SPs and their daytime sequelae. In the CCSAs, we found that the diagnostic recognition of chronic SPs in children and adolescents was impaired by the exclusive focus on daytime presentations. Daytime behavioral and emotional problems were targets of pharmacological treatment rather than the underlying SP. Consequently, SPs were also targeted with medications, without investigating the underlying problem. Our study highlights deficits in the diagnostic recognition of chronic SPs among children with chronic neurodevelopmental disorders/disabilities and proposes a clinical practice strategy, based on therapeutic emplotment that incorporates patients and parents' contributions in recognizing SPs and related sequelae in designing appropriate treatment and care. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

What Is Fetal Alcohol Spectrum Disorders (FASDs) and Why Is It Important That I Know about It?

MedlinePlus

... often get worse. Return to Steps World-Wide Web Search KidsHealth Organization: What Kids say about drinking ... outside this website We provide links to other web pages if you want to learn more about ...

Caregivers' management of schooling for their children with fetal alcohol spectrum disorder.

PubMed

Swart, Suretha; Hall, Wendy A; McKee, William T; Ford, Laurie

2014-11-01

In this article we describe a grounded theory study of how caregivers of school-aged children with fetal alcohol spectrum disorder (FASD) managed their children's schooling. We completed 30 interviews with 17 caregivers residing in a western Canadian province, as well as document analysis and 25 hours of participant observation. We used constant comparative analysis to construct our substantive theory: intertwining to fit in. The core variable is an iterative cycle caregivers used to resolve their main concerns: preventing their children from failing academically and in social interactions and preventing themselves from being regarded as unacceptable parents. To intertwine to fit in, caregivers used two strategies: orchestrating schooling and keeping up appearances. They also regulated their relationships with their children. "Intertwining to fit in" contributes to the literature on attachment and parenting and extends explanations about caregivers' advocacy for their children with FASD. The theory has implications for school personnel and practitioners, as well as researchers. © The Author(s) 2014.

Functional handwriting performance in school-age children with fetal alcohol spectrum disorders.

PubMed

Duval-White, Cherie J; Jirikowic, Tracy; Rios, Dianne; Deitz, Jean; Olson, Heather Carmichael

2013-01-01

Handwriting is a critical skill for school success. Children with fetal alcohol spectrum disorders (FASD) often present with fine motor and visual-motor impairments that can affect handwriting performance, yet handwriting skills have not been systematically investigated in this clinical group. This study aimed to comprehensively describe handwriting skills in 20 school-age children with FASD. Children were tested with the Process Assessment of the Learner, 2nd Edition (PAL-II), and the Visuomotor Precision subtest of NEPSY, a developmental neuropsychological assessment. Participants performed below average on PAL-II measures of handwriting legibility and speed and on NEPSY visual-motor precision tasks. In contrast, PAL-II measures of sensorimotor skills were broadly within the average range. Results provide evidence of functional handwriting challenges for children with FASD and suggest diminished visual-motor skills and increased difficulty as task complexity increases. Future research is needed to further describe the prevalence and nature of handwriting challenges in this population. Copyright © 2013 by the American Occupational Therapy Association, Inc.

Functional Handwriting Performance in School-Age Children With Fetal Alcohol Spectrum Disorders

PubMed Central

Duval-White, Cherie J.; Rios, Dianne; Deitz, Jean; Olson, Heather Carmichael

2013-01-01

Handwriting is a critical skill for school success. Children with fetal alcohol spectrum disorders (FASD) often present with fine motor and visual–motor impairments that can affect handwriting performance, yet handwriting skills have not been systematically investigated in this clinical group. This study aimed to comprehensively describe handwriting skills in 20 school-age children with FASD. Children were tested with the Process Assessment of the Learner, 2nd Edition (PAL–II), and the Visuomotor Precision subtest of NEPSY, a developmental neuropsychological assessment. Participants performed below average on PAL–II measures of handwriting legibility and speed and on NEPSY visual–motor precision tasks. In contrast, PAL–II measures of sensorimotor skills were broadly within the average range. Results provide evidence of functional handwriting challenges for children with FASD and suggest diminished visual–motor skills and increased difficulty as task complexity increases. Future research is needed to further describe the prevalence and nature of handwriting challenges in this population. PMID:23968791

Emotional Understanding in School-Aged Children with Fetal Alcohol Spectrum Disorders: A Promising Target for Intervention

PubMed Central

Petrenko, Christie L. M.; Pandolfino, Mary E.; Quamma, Julie; Olson, Heather Carmichael

2017-01-01

Background Children with fetal alcohol spectrum disorders (FASD) are at high risk for secondary conditions, including mental health difficulties. Data on both children with typical development and other clinical conditions suggest that limited emotional understanding (EU) raises risk for psychopathology, but little is known about EU in FASD. Objective Determine if EU is a reasonable treatment target for children with FASD. Methods 56 children (6–13 years) with FASD completed the Kusche Affective Interview-Revised, a verbal interview measure of EU. Results Children showed striking delays in EU (2–5 years delay) relative to published normative data, despite mean IQ (IQ=94.56) within normal limits. Individual variability was considerable even after accounting for age and verbal IQ. Conclusions Despite variability in individual differences, treatments targeting EU may benefit children with FASD as components within a comprehensive, tailored intervention focused on child self-regulation and caregiver behavior management. PMID:28594481

Meconium indicators of maternal alcohol abuse during pregnancy and association with patient characteristics.

PubMed

Goecke, Tamme W; Burger, Pascal; Fasching, Peter A; Bakdash, Abdulsallam; Engel, Anne; Häberle, Lothar; Voigt, Franziska; Faschingbauer, Florian; Raabe, Eva; Maass, Nicolai; Rothe, Michael; Beckmann, Matthias W; Pragst, Fritz; Kornhuber, Johannes

2014-01-01

Identification of women with moderate alcohol abuse during pregnancy is difficult. We correlated self-reported alcohol consumption during pregnancy and patient characteristics with objective alcohol indicators measured in fetal meconium. A total of 557 women singleton births and available psychological tests, obstetric data and meconium samples were included in statistical analysis. Alcohol metabolites (fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG)), were determined from meconium and correlated with patient characteristics. We found that 21.2% of the 557 participants admitted low-to-moderate alcohol consumption during pregnancy. Of the parameters analyzed from meconium, only EtG showed an association with alcohol history (P < 0.01). This association was inverse in cases with EtG value above 120 ng/g. These values indicate women with most severe alcohol consumption, who obviously denied having consumed alcohol during pregnancy. No other associations between socioeconomic or psychological characteristics and the drinking status (via meconium alcohol metabolites) could be found. Women who drink higher doses of ethanol during pregnancy, according to metabolite measures in meconium, might be less likely to admit alcohol consumption. No profile of socioeconomic or psychological characteristics of those women positively tested via meconium could be established.

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability.

PubMed

Wozniak, Jeffrey R; Fuglestad, Anita J; Eckerle, Judith K; Kroupina, Maria G; Miller, Neely C; Boys, Christopher J; Brearley, Ann M; Fink, Birgit A; Hoecker, Heather L; Zeisel, Steven H; Georgieff, Michael K

2013-11-01

There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway. © 2013.

Education, safe drinking practices and fetal alcohol spectrum disorder in the Kimberley region of Western Australia.

PubMed

Kavanagh, Phillip S; Payne, Jennifer S

2014-09-01

There are alarming rates of fetal alcohol spectrum disorder (FASD) in the Kimberley region of Western Australia despite numerous international studies demonstrating the links between alcohol consumption during pregnancy and FASD. The aim of this research was to help determine factors that may be associated with correct knowledge about safe drinking practices during pregnancy, with these factors used to help inform future interventions. Ninety-nine residents (40 males, 59 females, 39% of which self-identified as Indigenous) from the Kimberley region (Broome and smaller remote communities) completed a survey examining knowledge of currently recommended safe drinking practices during pregnancy and knowledge of the outcomes for children with FASD over a period of approximately 2 months. The results revealed that education level (i.e. not completing high school through to completing university) is the biggest predictor (β = 0.44, P < 0.01) of knowledge of safe drinking practices during pregnancy, and having heard of FASD (β = 0.67, P < 0.001) was the biggest predictor of knowledge of outcomes for children with FASD. Other variables such as age, sex, Indigenous status and income level were not as important. These findings suggest that early education regarding the consequences of alcohol consumption for women of childbearing age should be paramount in this or similar communities. Suggestions for targeted interventions are discussed in light of these findings. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Fine motor skills in children with prenatal alcohol exposure or fetal alcohol spectrum disorder.

PubMed

Doney, Robyn; Lucas, Barbara R; Jones, Taryn; Howat, Peter; Sauer, Kay; Elliott, Elizabeth J

2014-01-01

Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD) and associated neurodevelopmental impairments. It is uncertain which types of fine motor skills are most likely to be affected after PAE or which assessment tools are most appropriate to use in FASD diagnostic assessments. This systematic review examined which types of fine motor skills are impaired in children with PAE or FASD; which fine motor assessments are appropriate for FASD diagnosis; and whether fine motor impairments are evident at both "low" and "high" PAE levels. A systematic review of relevant databases was undertaken using key terms. Relevant studies were extracted using a standardized form, and methodological quality was rated using a critical appraisal tool. Twenty-four studies met inclusion criteria. Complex fine motor skills, such as visual-motor integration, were more frequently impaired than basic fine motor skills, such as grip strength. Assessment tools that specifically assessed fine motor skills more consistently identified impairments than those which assessed fine motor skills as part of a generalized neurodevelopmental assessment. Fine motor impairments were associated with "moderate" to "high" PAE levels. Few studies reported fine motor skills of children with "low" PAE levels, so the effect of lower PAE levels on fine motor skills remains uncertain. Comprehensive assessment of a range of fine motor skills in children with PAE is important to ensure an accurate FASD diagnosis and develop appropriate therapeutic interventions for children with PAE-related fine motor impairments.

Choline supplementation in children with Fetal Alcohol Spectrum Disorders (FASD) has high feasibility and tolerability

PubMed Central

Wozniak, Jeffrey R.; Fuglestad, Anita J.; Eckerle, Judith K.; Kroupina, Maria G.; Miller, Neely C.; Boys, Christopher J.; Brearley, Ann M.; Fink, Birgit A.; Hoecker, Heather L.; Zeisel, Steven H.; Georgieff, Michael K.

2013-01-01

There are no biological treatments for fetal alcohol spectrum disorders (FASD), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In pre-clinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This Phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well-tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children, ages 2.5–4.9y, with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg. choline or placebo daily for nine months (10 active; 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82–87% as evidenced by parent-completed logsheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This Phase I pilot study demonstrates that choline supplementation at 500 mg per day for nine months in children ages 2–5 is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway. PMID:24176229

Prenatal alcohol exposure and long-term developmental consequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spohr, H.L.; Willms, J.; Steinhausen, H.C.

Fetal alcohol syndrome (FAS) is a leading cause of congenital mental retardation but little is known about the long-term development and adolescent outcome of children with FAS. In a 10-year follow-up study of 60 patients diagnosed as having FAS in infancy and childhood, the authors investigated the long-term sequelae of intrauterine alcohol exposure. The authors found that the characteristic craniofacial malformations of FAS diminish with time, but microcephaly and, to a lesser degree, short stature and underweight (in boys) persist; in female adolescents body weight normalizes. Persistent mental retardation is the major sequela of intrauterine alcohol exposure in many cases,more » and environmental and educational factors do not have strong compensatory effects on the intellectual development of affected children.« less

Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence.

PubMed

Akison, Lisa K; Nitert, Marloes Dekker; Clifton, Vicki L; Moritz, Karen M; Simmons, David G

2017-06-01

Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta as glycogen. However, the function of this glycogen deposition remains a matter of debate: It could be a source of fuel for the placenta itself or a storage reservoir for later use by the fetus in times of need. While the significance of placental glycogen remains elusive, mounting evidence indicates that altered glycogen metabolism and/or deposition accompanies many pregnancy complications that adversely affect fetal development. This review will summarize histological, biochemical and molecular evidence that glycogen accumulates in a) placentas from a variety of experimental rodent models of perturbed pregnancy, including maternal alcohol exposure, glucocorticoid exposure, dietary deficiencies and hypoxia and b) placentas from human pregnancies with complications including preeclampsia, gestational diabetes mellitus and intrauterine growth restriction (IUGR). These pregnancies typically result in altered fetal growth, developmental abnormalities and/or disease outcomes in offspring. Collectively, this evidence suggests that changes in placental glycogen deposition is a common feature of pregnancy complications, particularly those associated with altered fetal growth. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Fetal alcohol spectrum disorders and the criminal justice system.

PubMed

Fast, Diane K; Conry, Julianne

2009-01-01

The life-long neurological impairments found in people with fetal alcohol spectrum disorders (FASDs), including learning disabilities, impulsivity, hyperactivity, social ineptness, and poor judgment, can increase susceptibility to victimization and involvement in the criminal justice system (CJS). Individuals with FASDs become involved in the CJS as complainants, witnesses, and accused. Their disabilities, resulting from the prenatal alcohol exposure, must be considered at all stages in the legal process. Adverse experiences, such as having a dysfunctional family background, mental health problems, and substance use disorders, are compounding factors. Experiencing physical, sexual, and emotional abuse also increases the risk that these individuals will become involved in the CJS. It is critical that everyone involved in the CJS receives education and training to understand FASD and the implications for the individual offender. A comprehensive medical-legal report, prepared by professionals experienced with FASD, can help judges and lawyers understand the complex interactions among brain damage, genetics and the environment. Corrections workers and probation officers need to comprehend the significance of FASD and how it affects the offender's abilities to understand and follow rules and probation orders. Caregivers and parents need to be involved whenever possible. Early recognition of the disabilities associated with FASDs may help reduce the over-representation of this group in the CJS. (c) 2009 Wiley-Liss, Inc.

Long-term Reductions in the Population of GABAergic Interneurons in the Mouse Hippocampus following Developmental Ethanol Exposure.

PubMed

Bird, Clark W; Taylor, Devin H; Pinkowski, Natalie J; Chavez, G Jill; Valenzuela, C Fernando

2018-07-15

Developmental exposure to ethanol leads to a constellation of cognitive and behavioral abnormalities known as Fetal Alcohol Spectrum Disorders (FASDs). Many cell types throughout the central nervous system are negatively impacted by gestational alcohol exposure, including inhibitory, GABAergic interneurons. Little evidence exists, however, describing the long-term impact of fetal alcohol exposure on survival of interneurons within the hippocampal formation, which is critical for learning and memory processes that are impaired in individuals with FASDs. Mice expressing Venus yellow fluorescent protein in inhibitory interneurons were exposed to vaporized ethanol during the third trimester equivalent of human gestation (postnatal days 2-9), and the long-term effects on interneuron numbers were measured using unbiased stereology at P90. In adulthood, interneuron populations were reduced in every hippocampal region examined. Moreover, we found that a single exposure to ethanol at P7 caused robust activation of apoptotic neurodegeneration of interneurons in the hilus, granule cell layer, CA1 and CA3 regions of the hippocampus. These studies demonstrate that developmental ethanol exposure has a long-term impact on hippocampal interneuron survivability, and may provide a mechanism partially explaining deficits in hippocampal function and hippocampus-dependent behaviors in those afflicted with FASDs. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Prenatal Alcohol Exposure and Cellular Differentiation

PubMed Central

Veazey, Kylee J.; Muller, Daria; Golding, Michael C.

2013-01-01

Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell–cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell’s identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes—the Polycomb and Trithorax proteins—are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder. PMID:24313167

The Marulu Strategy 2008-2012: overcoming Fetal Alcohol Spectrum Disorder (FASD) in the Fitzroy Valley.

PubMed

Fitzpatrick, James P; Oscar, June; Carter, Maureen; Elliott, Elizabeth J; Latimer, Jane; Wright, Edie; Boulton, John

2017-10-01

Aboriginal leaders concerned about high rates of Fetal Alcohol Spectrum Disorder (FASD) in the Fitzroy Valley, remote north-western Australia, introduced restrictions on access to take-away full-strength alcohol. Following this, Aboriginal leaders engaged strategic partners in a broader strategy to address FASD in the region. The aim of this study was to develop and implement a community-led, researcher-supported, FASD strategy. A review of literature focusing on community-led FASD strategies identified key components that informed the Marulu FASD strategy. These included strategy ownership, leadership, and governance by participating communities, and a research framework. Community meetings and workshops led to the development of The Marulu FASD Strategy (2008). Feasibility and community consent to conduct a FASD prevalence study (the Lililwan Project) was confirmed, and implementation was progressed (2010-2013). Concurrent FASD prevention activities were conducted. In 2012, the Marulu FASD Unit was established within a local Aboriginal organisation to sustain and coordinate ongoing strategy activities. Community control of public health initiatives can be achieved when Aboriginal communities prioritise issues of significant concern, and engage strategic partners to overcome them. Implications for public health: The Marulu Strategy forms a template for action to address FASD and other public health issues in Aboriginal communities in Australia and internationally. © 2017 The Authors.

A resolution designating September 9, 2010, as "National Fetal Alcohol Spectrum Disorders Awareness Day".

THOMAS, 111th Congress

Sen. Murkowski, Lisa [R-AK

2010-08-05

Senate - 08/05/2010 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

A resolution designating September 9, 2009, as "National Fetal Alcohol Spectrum Disorders Awareness Day".

THOMAS, 111th Congress

Sen. Murkowski, Lisa [R-AK

2009-08-04

Senate - 08/04/2009 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

A resolution designating September 9, 2012, as "National Fetal Alcohol Spectrum Disorders Awareness Day".

THOMAS, 112th Congress

Sen. Murkowski, Lisa [R-AK

2012-08-01

Senate - 08/01/2012 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

A resolution designating September 9, 2011, as "National Fetal Alcohol Spectrum Disorders Awareness Day".

THOMAS, 112th Congress

Sen. Murkowski, Lisa [R-AK

2011-09-08

Senate - 09/08/2011 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

Early life programming and the risk of non-alcoholic fatty liver disease.

PubMed

Lynch, C; Chan, C S; Drake, A J

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

Socio-cognitive habilitation using the math interactive learning experience program for alcohol-affected children.

PubMed

Kable, Julie A; Coles, Claire D; Taddeo, Elles

2007-08-01

Fetal alcohol syndrome (FAS) has been recognized as a disabling condition with a significant impact on the neurobehavioral functioning of affected individuals, including cognition, behavior, and academic functioning, but little research has been performed on targeted interventions for these children. A socio-cognitive habilitative program focused on improving behavior and math functioning in children 3 to 10 years of age (n=61) was developed and evaluated. The intervention provided parental instruction on FAS, advocacy, and behavioral regulation via workshops and interactive math tutoring with children. All families received parental instruction and were then randomly assigned to either the math instruction or standard psychoeducational care groups. Satisfaction with workshops was very high, with over 90% agreeing that trainers were knowledgeable and materials easy to understand and helpful. Significant gains in knowledge were found for information provided in the instructional groups. At posttesting, caregivers reported fewer problem behaviors on the Achenbach Child Behavior Checklist, Internalizing Problem Behavior, Externalizing Problem Behavior, and Total Problem Behavior summary scales. After 5 months, both groups of children demonstrated gains in math knowledge but significantly higher gains were found in the group receiving direct math instruction. The math treatment group was also more likely to demonstrate a gain of over 1 standard deviation on any of the 4 math outcome measures used. These findings suggest that parents of children with fetal alcohol spectrum disorders (FAS(D)) benefit from instruction in understanding their child's alcohol-related neurological damage and strategies to provide positive behavioral supports and that targeted psychoeducational programs may be able to remediate some of the math deficits associated with prenatal alcohol exposure.

Acute administration of vinpocetine, a phosphodiesterase type 1 inhibitor, ameliorates hyperactivity in a mice model of fetal alcohol spectrum disorder.

PubMed

Nunes, Fernanda; Ferreira-Rosa, Kélvia; Pereira, Maurício Dos S; Kubrusly, Regina C; Manhães, Alex C; Abreu-Villaça, Yael; Filgueiras, Cláudio C

2011-12-01

Maternal alcohol use during pregnancy causes a continuum of long-lasting disabilities in the offspring, commonly referred to as fetal alcohol spectrum disorder (FASD). Attention-deficit/hyperactivity disorder (ADHD) is possibly the most common behavioral problem in children with FASD and devising strategies that ameliorate this condition has great clinical relevance. Studies in rodent models of ADHD and FASD suggest that impairments in the cAMP signaling cascade contribute to the hyperactivity phenotype. In this work, we investigated whether the cAMP levels are affected in a long-lasting manner by ethanol exposure during the third trimester equivalent period of human gestation and whether the acute administration of the PDE1 inhibitor vinpocetine ameliorates the ethanol-induced hyperactivity. From postnatal day (P) 2 to P8, Swiss mice either received ethanol (5g/kg i.p.) or saline every other day. At P30, the animals either received vinpocetine (20mg/kg or 10mg/kg i.p.) or vehicle 4h before being tested in the open field. After the test, frontal cerebral cortices and hippocampi were dissected and collected for assessment of cAMP levels. Early alcohol exposure significantly increased locomotor activity in the open field and reduced cAMP levels in the hippocampus. The acute treatment of ethanol-exposed animals with 20mg/kg of vinpocetine restored both their locomotor activity and cAMP levels to control levels. These data lend support to the idea that cAMP signaling system contribute to the hyperactivity induced by developmental alcohol exposure and provide evidence for the potential therapeutic use of vinpocetine in FASD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Maternal ethanol consumption reduces Se antioxidant function in placenta and liver of embryos and breastfeeding pups.

PubMed

Nogales, Fátima; Ojeda, M Luisa; Jotty, Karick; Murillo, M Luisa; Carreras, Olimpia

2017-12-01

The fetal alcohol exposition during pregnancy leads to different disorders in offspring, related to the oxidative stress generated by alcohol. It is well-documented that there is an impairment of the antioxidant selenoprotein Glutathione peroxidase (GPx) activity in ethanol offspring during the embryo period, although no-one has described Selenium (Se) status. The aim is to analyze for the first time Se deposits in vivo and Se's biological implication in embryos and placenta after alcohol exposure and in offspring whose mothers continued to drink ethanol during lactation. Se deposits, GPx and glutathione reductase (GR) activity, lipid and protein oxidation and the expression of GPx1 were measured in placenta and liver of both embryos (E-19) and breastfeeding pups (L-21) in control and ethanol groups (20% v/v). Ethanol consumption decreased Se deposits, GPx activity and GPx1 expression, while increasing biomolecular oxidation in placenta and in the liver of E-19 and L-21. The GR/GPx ratio decreased in placenta and in E-19, together with an increase in lipid oxidation, while increased in the liver of L-21 pups with protein oxidation. Ethanol also decreased the GPx1 expression/GPx activity ratio in the liver of E-19 and L-21, indicating that alcohol decreases GPx activity by both depleting Se deposits and promoting GPx inactivation. In placenta GPx activity is proportional to the GPx1 expression found, so the ethanol affects GPx activity in offspring more than in dams. Therefore, Se supplementation therapy in dams could contribute as an interesting antioxidant that prevents fetal alcohol syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

PubMed

Ibrahim, Z M; Sayed Ahmed, W A; El-Hamid, S A; Hagras, A M

2015-01-01

To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

A Review of Psychological and Educational Assessment of Northern American Indian/Alaska Native Children.

ERIC Educational Resources Information Center

Amos, Terese Lipinski

1997-01-01

Reviews the literature on psychological and educational assessment of American Indian and Alaska Native children, including the background psychological factors of biological deprivation, motivation, attitudes toward self, and traditional nonformal education. Discusses brain hemispheres, visuospatial skills, otitis media, fetal alcohol syndrome,…

75 FR 29551 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance Abuse and Mental Health Services Administration... Substance Abuse and Mental Health Services Administration (SAMHSA) will publish a summary of information... Excellence--New Since 2001, SAMHSA's Center for Substance Abuse Prevention has been operating a Fetal Alcohol...

DNA methylation as a predictor of fetal alcohol spectrum disorder.

PubMed

Lussier, Alexandre A; Morin, Alexander M; MacIsaac, Julia L; Salmon, Jenny; Weinberg, Joanne; Reynolds, James N; Pavlidis, Paul; Chudley, Albert E; Kobor, Michael S

2018-01-01

Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2-5%, FASD has proven difficult to identify in the absence of the overt physical features characteristic of fetal alcohol syndrome. As interventions may have the greatest impact at an early age, accurate biomarkers are needed to identify children at risk for FASD. Building on our previous work identifying distinct DNA methylation patterns in children and adolescents with FASD, we have attempted to validate these associations in a different clinical cohort and to use our DNA methylation signature to develop a possible epigenetic predictor of FASD. Genome-wide DNA methylation patterns were analyzed using the Illumina HumanMethylation450 array in the buccal epithelial cells of a cohort of 48 individuals aged 3.5-18 (24 FASD cases, 24 controls). The DNA methylation predictor of FASD was built using a stochastic gradient boosting model on our previously published dataset FASD cases and controls (GSE80261). The predictor was tested on the current dataset and an independent dataset of 48 autism spectrum disorder cases and 48 controls (GSE50759). We validated findings from our previous study that identified a DNA methylation signature of FASD, replicating the altered DNA methylation levels of 161/648 CpGs in this independent cohort, which may represent a robust signature of FASD in the epigenome. We also generated a predictive model of FASD using machine learning in a subset of our previously published cohort of 179 samples (83 FASD cases, 96 controls), which was tested in this novel cohort of 48 samples and resulted in a moderately accurate predictor of FASD status. Upon testing the algorithm in an independent cohort of individuals with autism spectrum disorder, we did not detect any bias towards autism, sex, age, or ethnicity. These findings further support the association of FASD with distinct DNA methylation patterns, while providing a possible entry point towards the development of epigenetic biomarkers of FASD.

Prevalence of fetal alcohol syndrome in a South African city with a predominantly Black African population.

PubMed

Urban, Michael F; Olivier, Leana; Viljoen, Denis; Lombard, Chanelle; Louw, Jacobus G; Drotsky, Lian-Marie; Temmerman, Marleen; Chersich, Matthew F

2015-06-01

Fetal alcohol spectrum disorder (FASD) and fetal alcohol syndrome (FAS) are common in some South African populations, notably those of mixed ancestry descent in rural areas and small towns. Little is known about FAS/FASD prevalence in the majority of South Africans: city dwellers of Black African ethnicity. This study describes the prevalence of FAS in a South African city, comparing 2 suburbs with predominantly mixed ancestry (Roodepan) and Black African (Galeshewe) populations that house over 60% of the city population. We conducted a tiered, active case ascertainment study for the prevalence of FAS and also detected some less clinically specific FASD cases. All first-grade learners in the 2 suburbs were eligible for anthropometric screening, and screen-positive learners were assessed for dysmorphic features of FAS. Those with suggestive clinical features received neurocognitive assessment, and maternal or collateral interview. Final diagnosis was made following a case conference. Complete ascertainment of FAS status was made in 1,503 (94.7%) of 1,587 eligible learners (435 in Roodepan and 1,152 in Galeshewe). Overall, FAS was diagnosed in 83 (5.5%, 95% confidence interval [CI] = 4.4 to 6.8) learners and FASD in 96 (6.4%, 95% CI = 5.2 to 7.7). Levels of FAS were high in both areas: 26 (6.3%, 95% CI = 4.2 to 9.2) learners from Roodepan, compared to 57 (5.2%, 95% CI = 4.0 to 6.7) from Galeshewe (p = 0.39). No cases were previously diagnosed. The mortality rate for mothers of FASD children from Galeshewe was 19 of 65 (29%), compared to 3 of 31 (9.7%; p = 0.03) for Roodepan. Interviewed mothers in Galeshewe were older and had higher body mass index. Prevalence of FAS is high in both Galeshewe and Roodepan, and the lack of prior diagnoses indicates that awareness remains low. The maternal mortality rate was especially high in Galeshewe. The unexpectedly high burden of FAS in an urban area with predominantly Black African population mandates extension of surveillance and intervention measures in southern Africa. Copyright © 2015 by the Research Society on Alcoholism.

Alcohol-induced epigenetic alterations to developmentally crucial genes regulating neural stemness and differentiation.

PubMed

Veazey, Kylee J; Carnahan, Mindy N; Muller, Daria; Miranda, Rajesh C; Golding, Michael C

2013-07-01

From studies using a diverse range of model organisms, we now acknowledge that epigenetic changes to chromatin structure provide a plausible link between environmental teratogens and alterations in gene expression leading to disease. Observations from a number of independent laboratories indicate that ethanol (EtOH) has the capacity to act as a powerful epigenetic disruptor and potentially derail the coordinated processes of cellular differentiation. In this study, we sought to examine whether primary neurospheres cultured under conditions maintaining stemness were susceptible to alcohol-induced alterations in the histone code. We focused our studies on trimethylated histone 3 lysine 4 and trimethylated histone 3 lysine 27, as these are 2 of the most prominent posttranslational histone modifications regulating stem cell maintenance and neural differentiation. Primary neurosphere cultures were maintained under conditions promoting the stem cell state and treated with EtOH for 5 days. Control and EtOH-treated cellular extracts were examined using a combination of quantitative RT-PCR and chromatin immunoprecipitation techniques. We find that the regulatory regions of genes controlling both neural precursor cell identity and processes of differentiation exhibited significant declines in the enrichment of the chromatin marks examined. Despite these widespread changes in chromatin structure, only a small subset of genes including Dlx2, Fabp7, Nestin, Olig2, and Pax6 displayed EtOH-induced alterations in transcription. Unexpectedly, the majority of chromatin-modifying enzymes examined including members of the Polycomb Repressive Complex displayed minimal changes in expression and localization. Only transcripts encoding Dnmt1, Uhrf1, Ehmt1, Ash2 l, Wdr5, and Kdm1b exhibited significant differences. Our results indicate that primary neurospheres maintained as stem cells in vitro are susceptible to alcohol-induced perturbation of the histone code and errors in the epigenetic program. These observations indicate that alterations to chromatin structure may represent a crucial component of alcohol teratogenesis and progress toward a better understanding of the developmental origins of fetal alcohol spectrum disorders. Copyright © 2013 by the Research Society on Alcoholism.

Systematic review of interventions for children with Fetal Alcohol Spectrum Disorders

PubMed Central

Peadon, Elizabeth; Rhys-Jones, Biarta; Bower, Carol; Elliott, Elizabeth J

2009-01-01

Background Children with Fetal Alcohol Spectrum Disorders (FASD) may have significant neurobehavioural problems persisting into adulthood. Early diagnosis may decrease the risk of adverse life outcomes. However, little is known about effective interventions for children with FASD. Our aim is to conduct a systematic review of the literature to identify and evaluate the evidence for pharmacological and non-pharmacological interventions for children with FASD. Methods We did an electronic search of the Cochrane Library, MEDLINE, EMBASE, PsychINFO, CINAHL and ERIC for clinical studies (Randomized controlled trials (RCT), quasi RCT, controlled trials and pre- and post-intervention studies) which evaluated pharmacological, behavioural, speech therapy, occupational therapy, physiotherapy, psychosocial and educational interventions and early intervention programs. Participants were aged under 18 years with a diagnosis of a FASD. Selection of studies for inclusion and assessment of study quality was undertaken independently by two reviewers. Meta-analysis was not possible due to diversity in the interventions and outcome measures. Results Twelve studies met the inclusion criteria. Methodological weaknesses were common, including small sample sizes; inadequate study design and short term follow up. Pharmacological interventions, evaluated in two studies (both RCT) showed some benefit from stimulant medications. Educational and learning strategies (three RCT) were evaluated in seven studies. There was some evidence to suggest that virtual reality training, cognitive control therapy, language and literacy therapy, mathematics intervention and rehearsal training for memory may be beneficial strategies. Three studies evaluating social communication and behavioural strategies (two RCT) suggested that social skills training may improve social skills and behaviour at home and Attention Process Training may improve attention. Conclusion There is limited good quality evidence for specific interventions for managing FASD, however seven randomized controlled trials that address specific functional deficits of children with FASD are underway or recently completed. PMID:19463198

Growth curve analysis of placental and fetal growth influenced by adjacent fetal sex status under crowded uterine conditions in pigs

USDA-ARS?s Scientific Manuscript database

Intrauterine position and sex of adjacent fetuses in litter bearing species have been implicated in physiological and behavioral differences in males and females. Our objective was to establish growth curves for fetal and placental weight gain as influenced by sex status of flanking fetuses under cr...

Alcohol effects on the epigenome in the germline: role in the inheritance of alcohol-related pathology

PubMed Central

Chastain, Lucy G.; Sarkar, Dipak K.

2017-01-01

Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. Recent studies in animal models have suggested that epigenetic factors are also responsible for the transmission of alcohol-related pathologies across generations. Alcohol exposure has been shown to induce changes in the epigenome of sperm of exposed male animals, and these epimutations are inherited in the offspring. This paper reviews evidence for multigenerational and transgenerational epigenetic inheritance of alcohol-related pathology through the germline. We also review the literature on the epigenetic effects of alcohol exposure on somatic cells in brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this field, such as the lack of clinical studies in human populations and the lack of data on epigenetic inheritance via the female germline, and we suggest future research directions. PMID:28431793

Sex-related differences in auditory processing in adolescents with fetal alcohol spectrum disorder: A magnetoencephalographic study.

PubMed

Tesche, Claudia D; Kodituwakku, Piyadasa W; Garcia, Christopher M; Houck, Jon M

2015-01-01

Children exposed to substantial amounts of alcohol in utero display a broad range of morphological and behavioral outcomes, which are collectively referred to as fetal alcohol spectrum disorders (FASDs). Common to all children on the spectrum are cognitive and behavioral problems that reflect central nervous system dysfunction. Little is known, however, about the potential effects of variables such as sex on alcohol-induced brain damage. The goal of the current research was to utilize magnetoencephalography (MEG) to examine the effect of sex on brain dynamics in adolescents and young adults with FASD during the performance of an auditory oddball task. The stimuli were short trains of 1 kHz "standard" tone bursts (80%) randomly interleaved with 1.5 kHz "target" tone bursts (10%) and "novel" digital sounds (10%). Participants made motor responses to the target tones. Results are reported for 44 individuals (18 males and 26 females) ages 12 through 22 years. Nine males and 13 females had a diagnosis of FASD and the remainder were typically-developing age- and sex-matched controls. The main finding was widespread sex-specific differential activation of the frontal, medial and temporal cortex in adolescents with FASD compared to typically developing controls. Significant differences in evoked-response and time-frequency measures of brain dynamics were observed for all stimulus types in the auditory cortex, inferior frontal sulcus and hippocampus. These results underscore the importance of considering the influence of sex when analyzing neurophysiological data in children with FASD.

Cost of specialized addiction treatment of clients with fetal alcohol spectrum disorder in Canada.

PubMed

Popova, Svetlana; Lange, Shannon; Burd, Larry; Urbanoski, Karen; Rehm, Jürgen

2013-06-11

Individuals with Fetal Alcohol Spectrum Disorder (FASD) constitute a special population that may be at particularly high risk for substance use. The purpose of the current study was to estimate the utilization of specialized addiction treatment services (SATS) and the associated cost, as a part of the total cost of health care associated with FASD in Canada. The current study was a modeling study. Data on SATS by lifetime mental disorder status were obtained from the Drug and Alcohol Treatment Information System (DATIS) in Ontario, Canada for 2010/11. The number of clients with FASD who received SATS in Ontario in 2010/11 was estimated, assuming that approximately 37% (confidence interval: 21.6%-54.5%) of individuals with FASD abuse or are addicted to alcohol and/or drugs and that their utilization rate of SATS is the same as those for people with a lifetime mental disorder. The data from DATIS was then extrapolated to the total Canadian population. The cost of SATS for clients with FASD in Canada in 2010/11 ranged from $1.65 million Canadian dollars (CND) to $3.59 million CND, based on 5,526 outpatient visits and 9,529 resident days. When the sensitivity analysis was performed the cost of SATS ranged from $979 thousand CND to $5.34 million CND. Special attention must be paid to at-risk groups of individuals such as those with FASD, in order to reduce the likelihood of the development of co-morbid substance abuse problems, and thus, reducing the overall burden on Canadian society.

Eye movements reveal sexually dimorphic deficits in children with fetal alcohol spectrum disorder

PubMed Central

Paolozza, Angelina; Munn, Rebecca; Munoz, Douglas P.; Reynolds, James N.

2015-01-01

Background: We examined the accuracy and characteristics of saccadic eye movements in children with fetal alcohol spectrum disorder (FASD) compared with typically developing control children. Previous studies have found that children with FASD produce saccades that are quantifiably different from controls. Additionally, animal studies have found sex-based differences for behavioral effects after prenatal alcohol exposure. Therefore, we hypothesized that eye movement measures will show sexually dimorphic results. Methods: Children (aged 5–18 years) with FASD (n = 71) and typically developing controls (n = 113) performed a visually-guided saccade task. Saccade metrics and behavior were analyzed for sex and group differences. Results: Female control participants had greater amplitude saccades than control males or females with FASD. Accuracy was significantly poorer in the FASD group, especially in males, which introduced significantly greater variability in the data. Therefore, we conducted additional analyses including only those trials in which the first saccade successfully reached the target within a ± 1° window. In this restricted amplitude dataset, the females with FASD made saccades with significantly lower velocity and longer duration, whereas the males with FASD did not differ from the control group. Additionally, the mean and peak deceleration were selectively decreased in the females with FASD. Conclusions: These data support the hypothesis that children with FASD exhibit specific deficits in eye movement control and sensory-motor integration associated with cerebellar and/or brain stem circuits. Moreover, prenatal alcohol exposure may have a sexually dimorphic impact on eye movement metrics, with males and females exhibiting differential patterns of deficit. PMID:25814922

Aging and Intellectual Disability: Insights from Mouse Models of Down Syndrome

ERIC Educational Resources Information Center

Ruparelia, Aarti; Pearn, Matthew L.; Mobley, William C.

2013-01-01

Down syndrome (DS) is one of many causes of intellectual disability (ID), others including but not limited to, fetal alcohol syndrome, Fragile X syndrome, Rett syndrome, Williams syndrome, hypoxia, and infection. Down syndrome is characterized by a number of neurobiological problems resulting in learning and memory deficits and early onset…

Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder. Part II: A Qualitative Comparison of Parenting Stress

ERIC Educational Resources Information Center

Watson, Shelley L.; Hayes, Stephanie A.; Coons, Kelly D.; Radford-Paz, Elisa

2013-01-01

Background: Researchers investigating the impact of parenting children with disabilities suggest that regardless of the specific diagnosis, parents experience increased levels of stress. However, particular disabilities may be associated with distinct stressors and strains. Method: Parents of children with autism spectrum disorder (ASD) and…

Hippity Hops Velcroed to the Floor and Other Strategies to Educate Kids with FAS or FAE.

ERIC Educational Resources Information Center

Wescott, Siobhan

1991-01-01

Children with fetal alcohol syndrome may exhibit hyperactivity, hypersensitivity to touch, attention deficit disorder, stimulus overload, or an overtrusting nature. Educational strategies include consistent routines, multisensory cues to prompt memory, problem-solving training to recognize options, and emphasis on social skills and daily living…

Toward Intentional, Reflective, and Assimilative Classroom Practices with Students with FASD

ERIC Educational Resources Information Center

Poth, Cheryl; Pei, Jacqueline; Job, Jenelle M.; Wyper, Katherine

2014-01-01

The value of research-informed classroom practices is well recognized and thus this qualitative study was designed to explore, from multiple perspectives, the experiences and influences of classroom practices for students with Fetal Alcohol Spectrum Disorders (FASD). The inductive analysis of 11 focus groups and three interviews involving 60…

Drugs in the Womb: College Student Perceptions of Maternal v. Fetal Rights.

ERIC Educational Resources Information Center

Vener, Arthur M.; And Others

1992-01-01

Surveyed 523 undergraduates regarding drug use during pregnancy. Rank order of relative safety of drugs existed for respondents. Tobacco, alcohol, and aspirin were perceived as similar in their consequences to fetus. Cocaine was considered most deleterious and Accutane was considered least deleterious. Seventy-five percent would imprison pregnant…

Online training on fetal alcohol spectrum disorders for court-appointed special advocates volunteers.

PubMed

Pomeroy, Elizabeth C; Parrish, Danielle E

2013-08-01

Fetal alcohol spectrum disorders (FASDs) are a leading cause of developmental disabilities. Children within the child welfare system are five to 10 times more likely than other children to experience these symptoms. Court Appointed Special Advocates (CASA) volunteers are uniquely positioned to identify these children and refer them for assessment and services. This study used a one-group pretest-posttest design to assess the impact of a three-hour online FASDs training on CASA workers' knowledge of FASDs and their comfort and confidence in identifying children with FASDs for referral, advocating for them, and linking them to services. The training and assessment measures were completed by 338 CASA volunteers and staff from 55 CASA locations in Texas. Wilcoxon matched-pairs tests and paired t tests were used to assess change in each of the dependent measures. All comfort and confidence items showed significant improvement from pretest to posttest; there was also a significant improvement in knowledge. These results support the potential of this online training to enhance CASA volunteers' ability to help children with FASDs.

Investigating a theatre-based intervention for Indigenous youth with fetal alcohol spectrum disorder: Exploration d'une intervention basée sur le théâtre auprès de jeunes Autochtones atteints du syndrome d'alcoolisme fœtal.

PubMed

Keightley, Michelle; Agnihotri, Sabrina; Subramaniapillai, Sivaniya; Gray, Julia; Keresztesi, Jennifer; Colantonio, Angela; Polatajko, Helene J; Cameron, Debra; Wiseman-Hakes, Catherine

2018-04-01

Theatre-based interventions use artistic media to facilitate social and emotional awareness and have therapeutic benefits for persons with developmental disabilities and mental health problems. The role of these interventions with Indigenous youth who have emotional, behavioural, and cognitive sequelae related to fetal alcohol spectrum disorder (FASD) has not been explored. The purpose of this study was to explore the experiences and acceptability of a theatre-based approach for facilitating social communication and engagement in youth with FASD. Participants were three Indigenous youth with FASD. A qualitative exploration of the experiences and acceptability of the intervention was conducted via focus groups held 2 weeks post-program participation with the participants, their caregivers, and program facilitators. The transcripts were analyzed using an inductive thematic approach. Our results identified perceived postintervention improvements in participants' development of self-esteem, social skills, and emotional awareness. A theatre-based arts intervention has the potential to support improvements in social skills for youth with FASD.

Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.

PubMed

Wijayawardhane, Nayana; Shonesy, Brian C; Vaithianathan, Thirumalini; Pandiella, Noemi; Vaglenova, Julia; Breese, Charles R; Dityatev, Alexander; Suppiramaniam, Vishnu

2008-01-01

Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational approach for the treatment of alcohol-related cognitive deficits using aniracetam, an allosteric AMPAR modulator. In the present study, 28 to 34-day-old rats exposed to ethanol in utero were treated with aniracetam, and subsequently exhibited persistent improvement in mEPSC amplitude, frequency, and decay time. Furthermore, these animals expressed positive changes in synaptic single channel properties, suggesting that aniracetam ameliorates prenatal ethanol-induced deficits through modifications at the single channel level. Specifically, single channel open probability, conductance, mean open and closed times, and the number and burst duration were positively affected. Our findings emphasize the utility of compounds which slow the rate of deactivation and desensitization of AMPARs such as aniracetam.

Fetal alcohol spectrum disorders and their transmission through genetic and epigenetic mechanisms

PubMed Central

Mead, Edward A.; Sarkar, Dipak K.

2014-01-01

Fetal alcohol spectrum disorders (FASD) are a group of related conditions that arise from prenatal exposure to maternal consumption of the teratogen, ethanol. It has been estimated that roughly 1% of children in the US suffer from FASD (Sampson etal., 1997), though in some world populations, such as inhabitants of some poorer regions of South Africa, the rate can climb to as high as 20% (May etal., 2013). FASD are the largest cause of mental retardation in U.S. neonates, and ironically, are entirely preventable. FASD have been linked to major changes in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in lifelong impairments through mental disorders, retardation, and sensitivity to stress. FASD are linked to an impaired immune system which consequently leads to an elevated risk of cancer and other diseases. FASD arise from a complex interplay of genetic and epigenetic factors. Here, we review current literature on the topic to tease apart what is known in these areas particularly emphasizing HPA axis dysfunction and how this ties into new studies of transgenerational inheritance in FASD. PMID:24917878

Fishing for Fetal Alcohol Spectrum Disorders: Zebrafish as a Model for Ethanol Teratogenesis.

PubMed

Lovely, Charles Ben; Fernandes, Yohaan; Eberhart, Johann K

2016-10-01

Fetal Alcohol Spectrum Disorders (FASD) describes a wide array of ethanol-induced developmental defects, including craniofacial dysmorphology and cognitive impairments. It affects ∼1 in 100 children born in the United States each year. Due to the pleiotropic effects of ethanol, animal models have proven critical in characterizing the mechanisms of ethanol teratogenesis. In this review, we focus on the utility of zebrafish in characterizing ethanol-induced developmental defects. A growing number of laboratories have focused on using zebrafish to examine ethanol-induced defects in craniofacial, cardiac, ocular, and neural development, as well as cognitive and behavioral impairments. Growing evidence supports that genetic predisposition plays a role in these ethanol-induced defects, yet little is understood about these gene-ethanol interactions. With a high degree of genetic amenability, zebrafish is at the forefront of identifying and characterizing the gene-ethanol interactions that underlie FASD. Because of the conservation of gene function between zebrafish and humans, these studies will directly translate to studies of candidate genes in human populations and allow for better diagnosis and treatment of FASD.

Neonatal Ethanol Exposure Causes Behavioral Deficits in Young Mice.

PubMed

Xu, Wenhua; Hawkey, Andrew B; Li, Hui; Dai, Lu; Brim, Howard H; Frank, Jacqueline A; Luo, Jia; Barron, Susan; Chen, Gang

2018-04-01

Fetal ethanol (EtOH) exposure can damage the developing central nervous system and lead to cognitive and behavioral deficits, known as fetal alcohol spectrum disorders (FASD). EtOH exposure to mouse pups during early neonatal development was used as a model of EtOH exposure that overlaps the human third-trimester "brain growth spurt"-a model that has been widely used to study FASD in rats. C57BL/6 male and female mice were exposed to EtOH (4 g/kg/d) on postnatal days (PD) 4 to 10 by oral intubation. Intubated and nontreated controls were also included. Behavioral testing of the offspring, including open field, elevated plus maze, and Morris water maze, was performed on PD 20 to 45. EtOH exposure during PD 4 to 10 resulted in hyperactivity and deficits in learning and memory in young mice with no apparent sex differences. Based on these data, this neonatal intubation mouse model may be useful for future mechanistic and genetic studies of FASD and for screening of novel therapeutic agents. Copyright © 2018 by the Research Society on Alcoholism.

Prenatal alcohol exposure and cellular differentiation: a role for Polycomb and Trithorax group proteins in FAS phenotypes?

PubMed

Veazey, Kylee J; Muller, Daria; Golding, Michael C

2013-01-01

Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell-cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell's identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes--the Polycomb and Trithorax proteins--are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder.

The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis.

PubMed

Perkins, Amy E; Fadel, Jim R; Kelly, Sandra J

2015-05-01

Fetal alcohol spectrum disorders (FASD) are characterized by damage to multiple brain regions, including the hippocampus, which is involved in learning and memory. The acetylcholine neurotransmitter system provides major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intubation to male rat pups (postnatal day [PD] 2-10; ethanol-treated [ET]). Controls received a sham intubation (IC) or no treatment (NC). Acetylcholine efflux was measured using in vivo microdialysis (PD 32-35). ET animals were not different at baseline, but had decreased K(+)/Ca(2+)-induced acetylcholine efflux compared to NC animals and an enhanced acetylcholine response to galantamine (acetylcholinesterase inhibitor; 2.0 mg/kg) compared to both control groups. A separate cohort of animals was tested in the context pre-exposure facilitation effect task (CPFE; PD 30-32) following postnatal alcohol exposure and administration of galantamine (2.0 mg/kg; PD 11-30). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Using immunohistochemistry, we found that neither alcohol exposure nor behavioral testing significantly altered the density of vesicular acetylcholine transporter or alpha7 nicotinic acetylcholine receptor in the ventral hippocampus (CA1). In the medial septum, the average number of choline acetyltransferase (ChAT+) cells was increased in ET animals that displayed the context-shock association; there were no changes in IC and NC animals that learned the context-shock association or in any animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up‑regulated in ET animals that learned the CPFE, which may account for their ability to perform this task. In sum, developmental alcohol exposure may disrupt learning and memory in adolescence via a cholinergic mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in rats.

PubMed

Roberts, Linda G; Gray, Thomas M; Trimmer, Gary W; Parker, Robert M; Murray, F Jay; Schreiner, Ceinwen A; Clark, Charles R

2014-11-01

Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (<1-7mg/m(3), 5min). Dose responsive maternal effects were reduced maternal body weight and/or weight change, and/or reduced food consumption. No significant malformations were seen in any study. Developmental effects occurred at 20,000mg/m(3) of G/TAME (reduced fetal body weight, increased incidence of stunted fetuses), G/TBA (reduced fetal body weight, increased skeletal variants) and G/DIPE (reduced fetal weight) resulting in developmental NOAEL of 10,000mg/m(3) for these materials. Developmental NOAELs for other materials were 20,000mg/m(3) as no developmental toxicity was induced in those studies. Developmental NOAELs were equal to or greater than the concurrent maternal NOAELs which ranged from 2000 to 20,000mg/m(3). There were no clear cut differences in developmental toxicity between vapors of gasoline and gasoline blended with the ether or alcohol oxygenates. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of alcohol exposure on fetal brain development

NASA Astrophysics Data System (ADS)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2013-02-01

Alcohol consumption during pregnancy can be severely damage to the brain development in fetuses. This study investigates the effects of maternal ethanol consumption on brain development in mice embryos. Pregnant mice at gestational day 12.5 were intragastrically gavaged with ethanol (3g/Kg bwt) twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde and imaged using a swept-source optical coherence tomography (SSOCT) system. 3D images of the mice embryo brain were obtained and the volumes of the left and right ventricles of the brain were measured. The average volumes of the left and the right volumes of 5 embryos each alcohol-exposed and control embryos were measured to be 0.35 and 0.15 mm3, respectively. The results suggest that the left and right ventricle volumes of brain are much larger in the alcohol-exposed embryos as compared to control embryos indicating alcohol-induced developmental delay.

Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

PubMed

Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

2014-12-14

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

PubMed

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2014-01-01

The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). Copyright © 2013 by the Research Society on Alcoholism.

Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats.

PubMed

Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, Ilknur; Yürüker, Sinan

2017-10-01

Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6±40.9mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). During postnatal development, the temporal pattern of morphometric changes was shown to be region-dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons at PD1. Full recovery from these effects took place within the first 10 postnatal days. This study showed regional and temporal differences in the development of different morphometric features of principal hippocampal neurons in intact subjects over a protracted 2-months postnatal period. It also demonstrated an overlap in the effects of a moderate fetal ethanol intoxication and a mild maternal stress produced by the intragastric intubation, a commonly used method of ethanol administration to the pregnant dams. Fast recovery from the adverse effects on the soma size, dendritic arborization and spines density observed at birth indicates towards the fetal ethanol/stress induced developmental retardation. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Auditory Brainstem Response (ABR) Abnormalities across the Life Span of Rats Prenatally Exposed to Alcohol

PubMed Central

Church, Michael W.; Hotra, John W.; Holmes, Pamela A.; Anumba, Jennifer I.; Jackson, Desmond A.; Adams, Brittany R.

2011-01-01

Background Fetal Alcohol Syndrome is a leading cause of neurodevelopmental impairments (NDI) in developed countries. Sensory deficits can play a major role in NDI, yet few studies have investigated the effects of prenatal alcohol exposure on sensory function. In addition, there is a paucity of information on the life-long effects of prenatal alcohol exposure. Thus, we sought to investigate the effects of prenatal alcohol exposure on auditory function across the life span in an animal model. Based on prior findings with prenatal alcohol exposure and other forms of adverse prenatal environments, we hypothesized that animals prenatally exposed to alcohol would show an age-dependent pattern of (A) hearing and neurological abnormalities as post-weanling pups, (B) a substantial dissipation of such abnormalities in young adulthood, and (C) a resurgence of such abnormalities in middle-aged adulthood. Method Pregnant rats were randomly assigned to an untreated control (CON), a pair-fed control (PFC) or an alcohol treated group (ALC). The ALC dams were gavaged with 6 mg/kg alcohol daily from gestation day (GD) 6 to 21. The PFC dams were gavaged daily from GD6-21 with an isocaloric and isovolumetric water-based solution of Maltose-Dextrins and pair-fed to the ALC dams. The CON dams were the untreated group to which the ALC and CON groups were compared. Hearing and neurological functions in the offspring were assessed with the Auditory Brainstem Response (ABR) at the postnatal ages of 22, 220 and 520 days of age. Results & Conclusions In accord with our hypothesis, ABR abnormalities were first observed in the post-weanling pups, largely dissipated in young adulthood, and then resurged in middle-aged adulthood. This age-related pattern suggests that the ALC pups had a developmental delay that dissipated in young adulthood and an enhanced age-related deterioration that occurred in middle-aged adulthood. Such a pattern is consistent with the fetal programming hypothesis of adult-onset diseases (the Barker Hypothesis). Our findings have important clinical implications for the assessment and management of (A) childhood hearing disorders and their co-morbidities (i.e., speech-and-language, learning, and attention deficit disorders) and (B) enhanced age-related hearing and neurological degeneration in middle-aged adulthood that can result from prenatal alcohol exposure. We recommend hearing evaluation be a part of any long-term follow-up for FAS patients and patients exposed to any adverse prenatal environment. PMID:21815896

Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

PubMed Central

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2013-01-01

The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52). PMID:24033426

Effects of Ethanol on the Cerebellum: Advances and Prospects.

PubMed

Luo, Jia

2015-08-01

Alcohol abuse causes cerebellar dysfunction and cerebellar ataxia is a common feature in alcoholics. Alcohol exposure during development also impacts the cerebellum. Children with fetal alcohol spectrum disorder (FASD) show many symptoms associated specifically with cerebellar deficits. However, the cellular and molecular mechanisms are unclear. This special issue discusses the most recent advances in the study of mechanisms underlying alcoholinduced cerebellar deficits. The alteration in GABAA receptor-dependent neurotransmission is a potential mechanism for ethanol-induced cerebellar dysfunction. Recent advances indicate ethanol-induced increases in GABA release are not only in Purkinje cells (PCs), but also in molecular layer interneurons and granule cells. Ethanol is shown to disrupt the molecular events at the mossy fiber - granule cell - Golgi cell (MGG) synaptic site and granule cell parallel fibers - PCs (GPP) synaptic site, which may be responsible for ethanol-induced cerebellar ataxia. Aging and ethanol may affect the smooth endoplasmic reticulum (SER) of PC dendrites and cause dendritic regression. Ethanol withdrawal causes mitochondrial damage and aberrant gene modifications in the cerebellum. The interaction between these events may result in neuronal degeneration, thereby contributing to motoric deficit. Ethanol activates doublestranded RNA (dsRNA)-activated protein kinase (PKR) and PKR activation is involved ethanolinduced neuroinflammation and neurotoxicity in the developing cerebellum. Ethanol alters the development of cerebellar circuitry following the loss of PCs, which could result in modifications of the structure and function of other brain regions that receive cerebellar inputs. Lastly, choline, an essential nutrient is evaluated for its potential protection against ethanol-induced cerebellar damages. Choline is shown to ameliorate ethanol-induced cerebellar dysfunction when given before ethanol exposure.

Long-term behavioral change as a result of acute ethanol exposure in zebrafish: Evidence for a role for sonic hedgehog but not retinoic acid signaling.

PubMed

Burton, Derek F; Zhang, Chengjin; Boa-Amponsem, Oswald; Mackinnon, Shanta; Cole, Gregory J

2017-05-01

Developmental exposure to ethanol is recognized to produce long-term neurobehavioral impairment in multiple animal models. However, the molecular mechanisms underlying these deficits remain poorly understood. The present study was undertaken to ascertain whether two well-characterized targets of prenatal alcohol exposure, sonic hedgehog (Shh) and retinoic acid (RA), that induce the hallmark morphological phenotypes of fetal alcohol spectrum disorders (FASD), are involved in the generation of behavioral alterations as a result of alcohol exposure. Zebrafish embryos were exposed to ethanol (0%, 1%, 3%) at either 8-10 or 24-27h post-fertilization (hpf) and then evaluated during adolescence in the novel tank dive test to assess anxiety and risk-taking behavior. Overt signs of dysmorphogenesis were also scored and behavioral and morphological changes were compared for embryos treated with alcohol alone or in combination with subthreshold doses of shh or alhh1a3 morpholinos (MOs). Ethanol treated fish displayed altered tank diving behavior that was not exacerbated by combined MO treatment. While treatment of embryos with either shha mRNA or RA prior to ethanol exposure only ameliorated the altered tank diving response in the case of shha mRNA overexpression, dysmorphogenesis was rescued by both treatments. These results suggest that the effects of ethanol exposure on changes in anxiety and risk-taking behavior in adolescent zebrafish is manifested by a blunting of Shh, but not RA, signaling during early development. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes to histone modifications following prenatal alcohol exposure: An emerging picture.

PubMed

Chater-Diehl, Eric J; Laufer, Benjamin I; Singh, Shiva M

2017-05-01

Epigenetic mechanisms are important for facilitating gene-environment interactions in many disease etiologies, including Fetal Alcohol Spectrum Disorders (FASD). Extensive research into the role of DNA methylation and miRNAs in animal models has illuminated the complex role of these mechanisms in FASD. In contrast, histone modifications have not been as well researched, due in part to being less stable than DNA methylation and less well-characterized in disease. It is now apparent that even changes in transient marks can have profound effects if they alter developmental trajectories. In addition, many histone methylations are now known to be relatively stable and can propagate themselves. As technologies and knowledge have advanced, a small group has investigated the role of histone modifications in FASD. Here, we synthesize the data on the effects of prenatal alcohol exposure (PAE) on histone modifications. Several key points are evident. AS with most alcohol-induced outcomes, timing and dosage differences yield variable effects. Nevertheless, these studies consistently find enrichment of H3K9ac, H3K27me2,3, and H3K9me2, and increased expression of histone acetyltransferases and methyltransferases. The consistency of these alterations may implicate them as key mechanisms underlying FASD. Histone modification changes do not often correlate with gene expression changes, though some important examples exist. Encouragingly, attempts to reproduce specific histone modification changes are very often successful. We comment on possible directions for future studies, focusing on further exploration of current trends, expansion of time-point and dosage regimes, and evaluation of biomarker potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional capacity and cryopreservation of fetal rat pancreas in streptozotocin-diabetes. [Effectiveness of transplantation of fetal pancreas for control of diabetes in adult rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.; Clark, W.; Molnar, I.G.

1976-01-01

The fetal rat pancreas has a marked capacity for growth and maturation in glucose responsivity after transplantation under the kidney capsules of adult rats. The optimal conditions for function of the organ are a 3-week period of growth in a normal rat before transfer to a diabetic animal. Under these conditions diabetes is completely reversed by one fetal pancreas, and glucose disappearance rate and plasma insulin response to glucose are normal. Shunting of the venous drainage into the liver from fetal pancreases placed beneath the kidney capsule results in a marked improvement in diabetes control, and this technique may provemore » useful in experimental or human applications. Cryopreservation of the fetal pancreas has been successfully accomplished and will serve as a useful adjuvant to this method of reversing experimental diabetes.« less

Educating Students with FASD: Linking Policy, Research and Practice

ERIC Educational Resources Information Center

Millar, Julie A.; Thompson, Janet; Schwab, Dorothy; Hanlon-Dearman, Ana; Goodman, Deborah; Koren, Gal; Masotti, Paul

2017-01-01

Fetal alcohol spectrum disorder (FASD) is a prevalent neurodevelopmental disability with significant implications for learning and behaviour. International research suggests that the prevalence of FASD in school-aged children is 2.3-6.3%. In this paper, we address the questions: (1) what is FASD; (2) what is the prevalence of FASD in schools; (3)…

Assessment of Cognitive Processing in Persons with FASD: A Promising Alternative to Traditional IQ Measures

ERIC Educational Resources Information Center

Odishaw, Janine; Snart, Fern

2005-01-01

Previous challenges to the usefulness of traditional IQ measures in capturing the full range and magnitude of cognitive abilities have particular relevance for the assessment of persons with Fetal Alcohol Spectrum Disorder (FASD). How the construct of intelligence is operationalized can be critical for these persons since IQ scores typically…

Finding Ways to Teach to Students with FASD: A Research Study

ERIC Educational Resources Information Center

Edmonds, Kelly; Crichton, Susan

2008-01-01

This study examines a unique educational program designed for youth with Fetal Alcohol Spectrum Disorder [FASD] in Alberta, Canada. Care was taken to include the participants' voice in this case study resulting in key insights and strategies for working with youth and/or students struggling with FASD. Using observation notes, survey and interview…

Modulation of DNA methylation machineries in japanese rice fish (Oryzias latipes) embryogenesis by ethanol and 5-azacytidine

USDA-ARS?s Scientific Manuscript database

As a sequel of our investigations on the impact of epigenome in inducing fetal alcohol spectrum disorder (FASD) phenotypes in Japanese rice fish, we investigated on several DNA methylation machinery genes including DNA methyl transferase 3ba (dnmt3ba) and methyl binding proteins (MBPs), namely, mbdl...

DNA methyltransferase expressions in Japanese rice fish (Oryzias latipes) embryogenesis is developmentally regulated and modulated by ethanol and 5-azacytidine

USDA-ARS?s Scientific Manuscript database

We aimed to investigate the impact of the epigenome in inducting fetal alcohol spectrum disorder (FASD) phenotypes in Japanese rice fish embryogenesis. One of the significant events in epigenome is DNA methylation which is catalyzed by DNA methyl transferase (DNMT) enzymes. We analyzed DNMT enzyme m...

Re: Defining Success. A Team Approach to Supporting Students with FASD

ERIC Educational Resources Information Center

Alberta Education, 2009

2009-01-01

This strategy guide is for mentors, support workers and coaches who are working with school-aged children and youth who are affected by Fetal Alcohol Spectrum Disorder (FASD). In addition to supporting these children and youth at home and in the community, mentors may be involved in advocating for and supporting them at school. This guide…

Fetal Endoscopic Tracheal Intubation: A New Fetoscopic Procedure to Ensure Extrauterine Tracheal Permeability in a Case with Congenital Cervical Teratoma.

PubMed

Cruz-Martinez, Rogelio; Moreno-Alvarez, Oscar; Garcia, Maritza; Méndez, Antonio; Pineda, Hugo; Cruz-Martinez, Miriam Alejandra; Cruz, Miriam A; Martinez-Morales, Cecilia

2015-01-01

Congenital neck masses are associated with high perinatal mortality and morbidity secondary to airway obstruction due to a mass effect of the tumor with subsequent neonatal asphyxia and/or neonatal death. Currently, the only technique designed to establish a secure neonatal airway is the ex utero intrapartum treatment (EXIT) procedure, which involves neonatal tracheal intubation while fetal oxygenation is maintained by the uteroplacental circulation in a partial fetal delivery under maternal general anesthesia. We present a case with a giant cervical teratoma and huge displacement and compression of the fetal trachea that was treated successfully at 35 weeks of gestation with a novel fetoscopic procedure to ensure extrauterine tracheal permeability by means of a fetal endoscopic tracheal intubation (FETI) before delivery. The procedure consisted of a percutaneous fetal tracheoscopy under maternal epidural anesthesia using an 11-Fr exchange catheter covering the fetoscope that allowed a conduit to introduce a 3.0-mm intrauterine orotracheal cannula under ultrasound guidance. After FETI, a conventional cesarean section was performed uneventfully with no need for an EXIT procedure. This report is the first to illustrate that in cases with large neck tumors involving fetal airways, FETI is feasible and could potentially replace an EXIT procedure by allowing prenatal airway control.

Associative DNA methylation changes in children with prenatal alcohol exposure.

PubMed

Laufer, Benjamin I; Kapalanga, Joachim; Castellani, Christina A; Diehl, Eric J; Yan, Liying; Singh, Shiva M

2015-01-01

Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD). Previously, we assessed PAE in brain tissue from mouse models, however whether these changes are present in humans remains unknown. In this report, we show some identical changes in DNA methylation in the buccal swabs of six children with FASD using the 450K array. The changes occur in genes related to protocadherins, glutamatergic synapses, and hippo signaling. The results were found to be similar in another heterogeneous replication group of six FASD children. The replicated results suggest that children born with FASD have unique DNA methylation defects that can be influenced by sex and medication exposure. Ultimately, with future clinical development, assessment of DNA methylation from buccal swabs can provide a novel strategy for the diagnosis of FASD.

Altered Neural Oscillations During Multisensory Integration in Adolescents with Fetal Alcohol Spectrum Disorder.

PubMed

Bolaños, Alfredo D; Coffman, Brian A; Candelaria-Cook, Felicha T; Kodituwakku, Piyadasa; Stephen, Julia M

2017-12-01

Children with fetal alcohol spectrum disorder (FASD), who were exposed to alcohol in utero, display a broad range of sensory, cognitive, and behavioral deficits, which are broadly theorized to be rooted in altered brain function and structure. Based on the role of neural oscillations in multisensory integration from past studies, we hypothesized that adolescents with FASD would show a decrease in oscillatory power during event-related gamma oscillatory activity (30 to 100 Hz), when compared to typically developing healthy controls (HC), and that such decrease in oscillatory power would predict behavioral performance. We measured sensory neurophysiology using magnetoencephalography (MEG) during passive auditory, somatosensory, and multisensory (synchronous) stimulation in 19 adolescents (12 to 21 years) with FASD and 23 age- and gender-matched HC. We employed a cross-hemisphere multisensory paradigm to assess interhemispheric connectivity deficits in children with FASD. Time-frequency analysis of MEG data revealed a significant decrease in gamma oscillatory power for both unisensory and multisensory conditions in the FASD group relative to HC, based on permutation testing of significant group differences. Greater beta oscillatory power (15 to 30 Hz) was also noted in the FASD group compared to HC in both unisensory and multisensory conditions. Regression analysis revealed greater predictive power of multisensory oscillations from unisensory oscillations in the FASD group compared to the HC group. Furthermore, multisensory oscillatory power, for both groups, predicted performance on the Intra-Extradimensional Set Shift Task and the Cambridge Gambling Task. Altered oscillatory power in the FASD group may reflect a restricted ability to process somatosensory and multisensory stimuli during day-to-day interactions. These alterations in neural oscillations may be associated with the neurobehavioral deficits experienced by adolescents with FASD and may carry over to adulthood. Copyright © 2017 by the Research Society on Alcoholism.

Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model.

PubMed

Kaminen-Ahola, Nina; Ahola, Arttu; Maga, Murat; Mallitt, Kylie-Ann; Fahey, Paul; Cox, Timothy C; Whitelaw, Emma; Chong, Suyinn

2010-01-15

Recent studies have shown that exposure to some nutritional supplements and chemicals in utero can affect the epigenome of the developing mouse embryo, resulting in adult disease. Our hypothesis is that epigenetics is also involved in the gestational programming of adult phenotype by alcohol. We have developed a model of gestational ethanol exposure in the mouse based on maternal ad libitum ingestion of 10% (v/v) ethanol between gestational days 0.5-8.5 and observed changes in the expression of an epigenetically-sensitive allele, Agouti viable yellow (A(vy)), in the offspring. We found that exposure to ethanol increases the probability of transcriptional silencing at this locus, resulting in more mice with an agouti-colored coat. As expected, transcriptional silencing correlated with hypermethylation at A(vy). This demonstrates, for the first time, that ethanol can affect adult phenotype by altering the epigenotype of the early embryo. Interestingly, we also detected postnatal growth restriction and craniofacial dysmorphology reminiscent of fetal alcohol syndrome, in congenic a/a siblings of the A(vy) mice. These findings suggest that moderate ethanol exposure in utero is capable of inducing changes in the expression of genes other than A(vy), a conclusion supported by our genome-wide analysis of gene expression in these mice. In addition, offspring of female mice given free access to 10% (v/v) ethanol for four days per week for ten weeks prior to conception also showed increased transcriptional silencing of the A(vy) allele. Our work raises the possibility of a role for epigenetics in the etiology of fetal alcohol spectrum disorders, and it provides a mouse model that will be a useful resource in the continued efforts to understand the consequences of gestational alcohol exposure at the molecular level.

Long-term alterations to DNA methylation as a biomarker of prenatal alcohol exposure: From mouse models to human children with fetal alcohol spectrum disorders.

PubMed

Laufer, Benjamin I; Chater-Diehl, Eric J; Kapalanga, Joachim; Singh, Shiva M

2017-05-01

Rodent models of Fetal Alcohol Spectrum Disorders (FASD) have revealed that prenatal alcohol exposure (PAE) results in differential DNA cytosine methylation in the developing brain. The resulting genome-wide methylation changes are enriched in genes with neurodevelopmental functions. The profile of differential methylation is dynamic and present in some form for life. The methylation changes are transmitted across subsequent mitotic divisions, where they are maintained and further modified over time. More recent follow up has identified a profile of the differential methylation in the buccal swabs of young children born with FASD. While distinct from the profile observed in brain tissue from rodent models, there are similarities. These include changes in genes belonging to a number of neurodevelopmental and behavioral pathways. Specifically, there is increased methylation at the clustered protocadherin genes and deregulation of genomically imprinted genes, even though no single gene is affected in all patients studied to date. These novel results suggest further development of a methylation based strategy could enable early and accurate diagnostics and therapeutics, which have remained a challenge in FASD research. There are two aspects of this challenge that must be addressed in the immediate future: First, the long-term differential methylomics observed in rodent models must be functionally confirmed. Second, the similarities in differential methylation must be further established in humans at a methylomic level and overcome a number of technical limitations. While a cure for FASD is challenging, there is an opportunity for the development of early diagnostics and attenuations towards a higher quality of life. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Maternal And Neonatal Plasma MicroRNA Biomarkers For Fetal Alcohol Exposure In An Ovine Model

PubMed Central

Balaraman, Sridevi; Lunde, E. Raine; Sawant, Onkar; Cudd, Timothy A.; Washburn, Shannon E.; Miranda, Rajesh C.

2014-01-01

Background Plasma or circulating miRNAs (cirmiRNAs) have potential diagnostic value as biomarkers for a range of diseases. Based on observations that ethanol altered intracellular miRNAs during development, we tested the hypothesis that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in utero exposure, in the neonate. Methods Pregnant sheep were exposed to a binge model of ethanol consumption resulting in an average peak blood alcohol content of 243 mg/dl, for a three-trimester equivalent period from gestational day (GD) 4 to GD 132. MiRNA profiles were assessed by quantitative PCR analysis in plasma, erythrocyte and leukocytes obtained from non-pregnant ewes, and plasma from pregnant ewes 24 hours following the last binge ethanol episode, and from newborn lambs, at birth on ~GD 147. Results Pregnant ewe and newborn lamb cirmiRNA profiles were similar to each other and different from non-pregnant female plasma, erythrocyte or leukocyte miRNAs. Significant changes in cirmiRNA profiles were observed in the ethanol-exposed ewe, and at birth, in the in utero, ethanol-exposed lamb. CirmiRNAs including miR-9, -15b, -19b and -20a were sensitive and specific measures of ethanol exposure in both pregnant ewe and newborn lamb. Additionally, ethanol exposure altered guide to passenger strand cirmiRNA ratios in the pregnant ewe, but not in the lamb. Conclusion Shared profiles between pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. CirmiRNAs are biomarkers for alcohol exposure during pregnancy, in both mother and neonate, and may constitute an important shared endocrine biomarker that is vulnerable to the maternal environment. PMID:24588274

Fetal alcohol spectrum disorders (FASD) - What we know and what we should know - The knowledge of German health professionals and parents.

PubMed

Landgraf, Mirjam N; Albers, Lucia; Rahmsdorf, Birte; Vill, Katharina; Gerstl, Lucia; Lippert, Michaela; Heinen, Florian

2018-05-01

The objective of our study was to evaluate the knowledge about fetal alcohol spectrum disorders (FASD) and the implementation of the German guideline for FASD among different professionals in the health and social system and among parents with children with FASD. A questionnaire about FASD, containing 20 items, was sent by post to all children's hospitals (n = 287), all hospitals for child and adolescent psychiatry (n = 173), all social paediatric centres (n = 162), all neuropaediatricians (n = 129) and all youth welfare offices (n = 672) in Germany. Furthermore a link to the questionnaire as online version was put in the member's newsletter by 14 relevant professional societies. Besides, the questionnaire was distributed personally to the attendees of the annual national FASD conference (n = 363). Altogether 428 persons took part in the survey. 273 participants were professionals and 155 parents of children with FASD. More than 95% of the professionals and parents knew that alcohol consumption during pregnancy constitutes a risk for the child. The prevalence of maternal alcohol consumption and of FASD was underestimated. Although approx. 70% of the professionals knew which disorders belong to FASD just a few could tell their specific deficits. Questions regarding effective intervention for children with FASD and the long-term outcome were only partially answered correctly. Professionals in the German health and social system are aware of FASD but underestimate the level of damage and the impact on every day functioning of the affected people. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Food insecurity and alcohol use among pregnant women at alcohol-serving establishments in South Africa.

PubMed

Eaton, Lisa A; Pitpitan, Eileen V; Kalichman, Seth C; Sikkema, Kathleen J; Skinner, Donald; Watt, Melissa H; Pieterse, Desiree; Cain, Demetria N

2014-06-01

South Africa has the highest rate of fetal alcohol syndrome (FAS) in the world. While efforts have been made to curb the high rate of FAS, little is known about situational factors that may contribute to alcohol use during pregnancy. In the current paper, we focus on the role of food insecurity and its relationship to alcohol use among pregnant women. Women completed computer-assisted interviews. Generalized linear modeling was used in all analyses. Women attending alcohol-serving establishments in a township in Cape Town, South Africa were recruited for the study. Five hundred sixty women were sampled and 95 women reported being pregnant. High levels of alcohol use were reported among pregnant women: 65 % of women consumed alcohol at least every month and 29 % consumed alcohol as often as two to three times per week. Thirty-four percent of the women reported having six or more drinks per occasion on at least a weekly basis. The majority (87 %) of pregnant women reported experiencing some form of food insecurity (e.g., food unavailable, eating less) in the past month. Alcohol use was significantly associated with food insecurity, even when controlling for relevant demographic variables. Intervention with pregnant women who consume alcohol is urgently needed. Future research should focus on understanding the intersection of food insecurity and alcohol, and how the experience of food insecurity may contribute to greater rates of alcohol use and abuse among pregnant women.

Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

PubMed

Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

2017-02-01

Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

The Stillbirth Classification System for the Safe Passage Study: Incorporating Mechanism, Etiology, and Recurrence

PubMed Central

Boyd, Theonia K.; Wright, Colleen A.; Odendaal, Hein J.; Elliott, Amy J.; Sens, Mary Ann; Folkerth, Rebecca D.; Roberts, Drucilla J.; Kinney, Hannah C.

2017-01-01

OBJECTIVE Describe the classification system for the assignment of the cause of death for stillbirth in the Safe Passage Study, an international, multi-institutional, prospective analysis conducted by the NIAAA/NICHD funded PASS Network (The Prenatal Alcohol in SIDS and Stillbirth (PASS) Research Network). The study mission is to determine the role of prenatal alcohol and/or cigarette smoke exposure in adverse pregnancy outcomes, including stillbirth, in a high-risk cohort of 12,000 maternal/fetal dyads. METHODS The PASS Network classification system is based upon 5 ‘sites of origin’ for cause of stillbirth (Fetal, Placental, Maternal, External/Environmental, or Undetermined), further subdivided into mechanism subcategories (e.g., Placental Perfusion Failure). Both site of origin and mechanism stratification are employed to assign an ultimate cause of death. Each PASS stillbirth (n=19) in the feasibility study was assigned a cause of death, and status of sporadic versus recurrent. Adjudication involved review of the maternal and obstetrical records, and fetal autopsy and placental findings, with complete consensus in each case. Two published classification systems, i.e., INCODE and ReCoDe, were used for comparison. RESULTS Causes of stillbirth classified were: fetal (n=5, 26%), placental (n=10, 53%), external (n=1, 5%), and undetermined (n=3, 16%). Nine cases (47%) had placental causes of death due to maternal disorders that carry recurrence risks. There was complete agreement for the cause of death across the three classification systems in 26% of cases, and a combination of partial or complete agreement in 68% of cases. Complete vs. partial agreements were predicated upon the classification schemes used for comparison. CONCLUSIONS The proposed PASS system is a user-friendly classification system that provides comparable information to previously published systems. Advantages include its simplicity, mechanistic formulations, tight clinicopathologic integration, provision for an undetermined category, and its wide applicability for use by perinatal mortality review boards with access to information routinely collected during clinicopathologic evaluations. PMID:27116324

Near-term fetal response to maternal spoken voice

PubMed Central

Voegtline, Kristin M.; Costigan, Kathleen A.; Pater, Heather A.; DiPietro, Janet A.

2013-01-01

Knowledge about prenatal learning has been largely predicated on the observation that newborns appear to recognize the maternal voice. Few studies have examined the process underlying this phenomenon; that is, whether and how the fetus responds to maternal voice in situ. Fetal heart rate and motor activity were recorded at 36 weeks gestation (n = 69) while pregnant women read aloud from a neutral passage. Compared to a baseline period, fetuses responded with a decrease in motor activity in the 10-seconds following onset of maternal speech and a trend level decelerative heart rate response, consistent with an orienting response. Subsequent analyses revealed that the fetal response was modified by both maternal and fetal factors. Fetuses of women who were previously awake and talking (n = 40) showed an orienting response to onset of maternal reading aloud, while fetuses of mothers who had previously been resting and silent (n = 29) responded with elevated heart rate and increased movement. The magnitude of the fetal response was further dependent on baseline fetal heart rate variability such that largest response was demonstrated by fetuses with low variability of mothers who were previously resting and silent. Results indicate that fetal responsivity is affected by both maternal and fetal state and have implications for understanding fetal learning of the maternal voice under naturalistic conditions. PMID:23748167

Computational and Organotypic Modeling of Microcephaly ...

EPA Pesticide Factsheets

Microcephaly is associated with reduced cortical surface area and ventricular dilations. Many genetic and environmental factors precipitate this malformation, including prenatal alcohol exposure and maternal Zika infection. This complexity motivates the engineering of computational and experimental models to probe the underlying molecular targets, cellular consequences, and biological processes. We describe an Adverse Outcome Pathway (AOP) framework for microcephaly derived from literature on all gene-, chemical-, or viral- effects and brain development. Overlap with NTDs is likely, although the AOP connections identified here focused on microcephaly as the adverse outcome. A query of the Mammalian Phenotype Browser database for ‘microcephaly’ (MP:0000433) returned 85 gene associations; several function in microtubule assembly and centrosome cycle regulated by (microcephalin, MCPH1), a gene for primary microcephaly in humans. The developing ventricular zone is the likely target. In this zone, neuroprogenitor cells (NPCs) self-replicate during the 1st trimester setting brain size, followed by neural differentiation of the neocortex. Recent studies with human NPCs confirmed infectivity with Zika virions invoking critical cell loss (apoptosis) of precursor NPCs; similar findings have been shown with fetal alcohol or methylmercury exposure in rodent studies, leading to mathematical models of NPC dynamics in size determination of the ventricular zone. A key event