Difference between revisions of "Talk:Abnormal Development - Fetal Alcohol Syndrome"

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==2019==
  
  
==10 Most Recent==
 
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===Fetal Alcohol Syndrome===
 
<pubmed limit=10>Fetal+Alcohol+Syndrome</pubmed>
 
  
 
==2018==
 
==2018==
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===The Early Developmental Outcomes of Prenatal Alcohol Exposure: A Review===
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Front Neurol. 2018 Dec 18;9:1108. doi: 10.3389/fneur.2018.01108. eCollection 2018.
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Subramoney S1, Eastman E1, Adnams C2, Stein DJ2,3, Donald KA1.
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Author information
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Abstract
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Aim: This paper systematically reviews the literature on the effects of prenatal alcohol exposure on early child development from birth to 5 years with the aim to synthesize the developmental outcomes associated with prenatal alcohol exposure, and inform further research to improve our knowledge of the manifestations of prenatal alcohol exposure. Methods: Electronic databases (MEDLINE, Psych INFO, and Psych ARTICLES) were searched to find papers on the developmental outcomes of prenatal alcohol exposure in neonates, infants and toddlers and pre-school aged children. Studies were selected based on participants self-reporting alcohol consumption during pregnancy (either prospectively or retrospectively) and/or children being diagnosed with FASD based on a standardized assessment that includes a dysmorphology examination. The search was limited to peer-reviewed, English language studies involving human subjects, up to 5.5 years old. Results: Out of the 1,684 titles screened, a total of 71 papers were identified as relevant and included in this review. The majority of studies were prospective longitudinal studies. A range of assessment modalities (or tools) was used to determine neurodevelopmental outcomes of prenatal exposure to alcohol in the age group under review, the most frequently described being the Bayley Scales of Infant and Toddler Development (BSID) (n = 19). Studies varied in terms of the dose, frequency, and timing of alcohol consumption during pregnancy and methodology used to assess alcohol consumption. Findings demonstrate extensive evidence for poor global developmental outcomes in children prenatally exposed to alcohol, particularly with moderate to severe levels of prenatal alcohol exposure. Conclusion: The outcomes related to lower levels of prenatal alcohol exposure as well as outcomes in specific developmental domains, are poorly understood. Further research should aim to clarify the more subtle or less easily measurable manifestations of prenatal alcohol exposure on early development when the potential for greatest impact of interventions is highest.
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KEYWORDS:
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developmental outcomes; early childhood; fetal alcohol spectrum disorders; neurodevelopment; prenatal alcohol exposure
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PMID: 30619064
  
 
===Maternal and partner prenatal alcohol use and infant cognitive development===
 
===Maternal and partner prenatal alcohol use and infant cognitive development===

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Cite this page: Hill, M.A. (2019, October 19) Embryology Abnormal Development - Fetal Alcohol Syndrome. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Fetal_Alcohol_Syndrome

2019

2018

The Early Developmental Outcomes of Prenatal Alcohol Exposure: A Review

Front Neurol. 2018 Dec 18;9:1108. doi: 10.3389/fneur.2018.01108. eCollection 2018.

Subramoney S1, Eastman E1, Adnams C2, Stein DJ2,3, Donald KA1. Author information Abstract Aim: This paper systematically reviews the literature on the effects of prenatal alcohol exposure on early child development from birth to 5 years with the aim to synthesize the developmental outcomes associated with prenatal alcohol exposure, and inform further research to improve our knowledge of the manifestations of prenatal alcohol exposure. Methods: Electronic databases (MEDLINE, Psych INFO, and Psych ARTICLES) were searched to find papers on the developmental outcomes of prenatal alcohol exposure in neonates, infants and toddlers and pre-school aged children. Studies were selected based on participants self-reporting alcohol consumption during pregnancy (either prospectively or retrospectively) and/or children being diagnosed with FASD based on a standardized assessment that includes a dysmorphology examination. The search was limited to peer-reviewed, English language studies involving human subjects, up to 5.5 years old. Results: Out of the 1,684 titles screened, a total of 71 papers were identified as relevant and included in this review. The majority of studies were prospective longitudinal studies. A range of assessment modalities (or tools) was used to determine neurodevelopmental outcomes of prenatal exposure to alcohol in the age group under review, the most frequently described being the Bayley Scales of Infant and Toddler Development (BSID) (n = 19). Studies varied in terms of the dose, frequency, and timing of alcohol consumption during pregnancy and methodology used to assess alcohol consumption. Findings demonstrate extensive evidence for poor global developmental outcomes in children prenatally exposed to alcohol, particularly with moderate to severe levels of prenatal alcohol exposure. Conclusion: The outcomes related to lower levels of prenatal alcohol exposure as well as outcomes in specific developmental domains, are poorly understood. Further research should aim to clarify the more subtle or less easily measurable manifestations of prenatal alcohol exposure on early development when the potential for greatest impact of interventions is highest. KEYWORDS: developmental outcomes; early childhood; fetal alcohol spectrum disorders; neurodevelopment; prenatal alcohol exposure PMID: 30619064

Maternal and partner prenatal alcohol use and infant cognitive development

Drug Alcohol Depend. 2018 Feb 23;185:330-338. doi: 10.1016/j.drugalcdep.2017.12.038. [Epub ahead of print]


McCormack C1, Hutchinson D2, Burns L3, Youssef G4, Wilson J3, Elliott E5, Allsop S6, Najman J7, Jacobs S8, Rossen L3, Olsson C9, Mattick R3. Author information Abstract BACKGROUND: Teratogenicity of heavy prenatal alcohol exposure is established, but uncertainty remains regarding the impact of moderate alcohol exposure on cognitive deficits in infants. Separating in utero effects from environmental confounding is a challenge for observational studies; consideration of alcohol use by partners as well as mothers may help clarify this. This study examined associations between prenatal alcohol use by both mothers and their partners and infant cognitive developmental outcomes at 12-months. METHODS: Pregnant women (n = 1331) and their partners (n = 699) were recruited from antenatal clinics of three metropolitan public hospitals in Australia, and completed detailed interviews about alcohol consumptions throughout pregnancy. Infants were assessed with the Bayley Scales of Infant Development - Third edition (Bayley) at 12-months of age. RESULTS: Alcohol use during pregnancy was reported by 65.7% of mothers and 84.1% of partners. Using multiple methods to adjust for confounding factors, no evidence for impaired cognitive ability associated with alcohol use by mothers or their partners was observed. Children born to women who drank low-levels of alcohol had slightly higher Bayley cognitive scores than those born to abstaining women. There was some evidence for an interaction between sociodemographic factors and prenatal alcohol exposure on infant cognitive outcomes. CONCLUSION: This finding corroborates existing evidence to suggest there are no detrimental effects to infant cognitive development at 12-months of age following low-level prenatal alcohol exposure. Future prospective studies involving families of a broad range of backgrounds would be informative to clarify interaction between alcohol exposure and environmental factors on developmental outcomes. Copyright © 2018 Elsevier B.V. All rights reserved. KEYWORDS: Alcohol; Cognition; Fetal alcohol syndrome; Infant development; Pregnancy; Prenatal alcohol exposure PMID: 29499553 DOI: 10.1016/j.drugalcdep.2017.12.038


Utility of Genetic Testing in Fetal Alcohol Spectrum Disorder

J Pediatr. 2018 Feb 2. pii: S0022-3476(17)31741-9. doi: 10.1016/j.jpeds.2017.12.046. [Epub ahead of print]

Jamuar SS1, Picker JD2, Stoler JM2.

Abstract

OBJECTIVE: To study the utility of genetic evaluation and testing in patients with suspected fetal alcohol spectrum disorder (FASD). STUDY DESIGN: We performed a retrospective chart review of all patients (n = 36) referred for evaluation for suspected FASD to the genetics clinic at Boston Children's Hospital between January 2006 and January 2013. Records of all patients were reviewed to obtain the medical history, family history, examination findings, and investigations, including genetic testing. RESULTS: Of the 36 patients, definite prenatal exposure was documented in 69%. Eight patients did not fulfill clinical criteria for FASD. Chromosomal microarray analysis (CMA) detected 19 copy number variants (CNVs) in 14 patients. Among patients who fulfilled criteria for FASD and underwent CMA, pathogenic CNVs were detected in 3 patients (2q37del, 22q11.22dup, and 4q31.21del syndromes), giving a yield of 14.3%. All 3 patients had overlapping features between FASD and the genetic syndrome. CONCLUSION: Genetic testing, especially CMA, should be considered in patients referred for evaluation of FASD, as a significant proportion have a clinically significant CNV even when they fulfill diagnostic criteria for FASD spectrum. Copyright © 2017 Elsevier Inc. All rights reserved. KEYWORDS: chromosomal microarray analysis; copy number variants; developmental delay; fetal alcohol spectrum disorder

PMID: 29398060 DOI: 10.1016/j.jpeds.2017.12.046

Page Change

Deleted - 26 August 2008 Draft Australian alcohol guidelines for low-risk drinking[1] "Following the initial consideration by the NHMRC Council, NHRMC is finalising the NHMRC Australian alcohol guidelines for low risk drinking, including the latest research. The Council is expected to consider them again in late 2008."


2017

Effects of Prenatal Alcohol Exposure on the Visual System of Monkeys Measured at Different Stages of Development

Invest Ophthalmol Vis Sci. 2017 Dec 1;58(14):6282-6291. doi: 10.1167/iovs.17-22181.

Harrar V1, Elkrief L1,2, Bouskila J1,3,4, Kucera R1, Fink-Jensen A5, Bouchard JF1, Palmour R3,4, Ptito M1,4,5.

Abstract

PURPOSE: Fetal alcohol spectrum disorder (FASD) is a developmental disease characterized by behavioral problems and physical defects including malformations of the eye and associated optical defects. How these malformations affect retinal functioning is not well known, although animal models have suggested that scotopic vision is particularly deficient. Age is also known to affect scotopic vision. Here, we determined the combined effects of age and fetal alcohol exposure (FAE) on retinal function using full-field electroretinograms (ERGs) in monkeys (Chlorocebus sabaeus). METHODS: ERGs were recorded in monkeys aged 3- to 12-years old, at multiple flash intensities under scotopic and photopic conditions, and functions were fit to the amplitudes of the a- and b-waves. RESULTS: We found that both age and alcohol exposure affected ERGs. In photopic ERGs, amplitudes increased with age, and were higher in FAEs than controls, for data related to the OFF- and ON-pathways. In scotopic ERGs, amplitudes were decreased in young FAE compared with age-matched controls but only for the rod-dominated responses, while at brighter flashes, alcohol exposure led to an increase in the amplitude of the a- and b-waves. CONCLUSIONS: The ERGs from the FAE animals closely resembled the data from the older sucrose-control monkeys. This suggests that the FAE monkey retina ages more quickly than the control monkeys. This large sample of nonhuman primates, with carefully monitored ethanol exposure, demonstrates the critical interplay between age and alcohol when assessing the integrity of the retina. We suggest that ERGs might be an important adjunct to diagnosing human FASD.

PMID: 29242902 DOI: 10.1167/iovs.17-22181


PLGF, a placental marker of fetal brain defects after in utero alcohol exposure

Acta Neuropathol Commun. 2017 Jun 6;5(1):44. doi: 10.1186/s40478-017-0444-6. Lecuyer M1, Laquerrière A1,2, Bekri S1,3, Lesueur C1,3, Ramdani Y1, Jégou S1, Uguen A4, Marcorelles P4, Marret S1,5, Gonzalez BJ6. Author information 1 UNIROUEN, Inserm U1245 and Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Normandie University, Rouen, France. 2 Department of Pathology, Rouen University Hospital, Rouen, France. 3 Department of Molecular Biochemistry, Rouen University Hospital, Rouen, France. 4 Department of Pathology, Brest University Hospital, Rouen, France. 5 Department of Neonatal Paediatrics and Intensive Care, Rouen University Hospital, Rouen, France. 6 UNIROUEN, Inserm U1245 and Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Normandie University, Rouen, France. bruno.gonzales@univ-rouen.fr. Abstract Most children with in utero alcohol exposure do not exhibit all features of fetal alcohol syndrome (FAS), and a challenge for clinicians is to make an early diagnosis of fetal alcohol spectrum disorders (FASD) to avoid lost opportunities for care. In brain, correct neurodevelopment requires proper angiogenesis. Since alcohol alters brain angiogenesis and the placenta is a major source of angiogenic factors, we hypothesized that it is involved in alcohol-induced brain vascular defects. In mouse, using in vivo repression and overexpression of PLGF, we investigated the contribution of placenta on fetal brain angiogenesis. In human, we performed a comparative molecular and morphological analysis of brain/placenta angiogenesis in alcohol-exposed fetuses. Results showed that prenatal alcohol exposure impairs placental angiogenesis, reduces PLGF levels and consequently alters fetal brain vasculature. Placental repression of PLGF altered brain VEGF-R1 expression and mimicked alcohol-induced vascular defects in the cortex. Over-expression of placental PGF rescued alcohol effects on fetal brain vessels. In human, alcohol exposure disrupted both placental and brain angiogenesis. PLGF expression was strongly decreased and angiogenesis defects observed in the fetal brain markedly correlated with placental vascular impairments. Placental PGF disruption impairs brain angiogenesis and likely predicts brain disabilities after in utero alcohol exposure. PLGF assay at birth could contribute to the early diagnosis of FASD. KEYWORDS: Angiogenesis; Cortex; Fetal alcohol exposure; Placenta PMID: 28587682 PMCID: PMC5461764 DOI: 10.1186/s40478-017-0444-6

Prenatal alcohol exposure impairs autophagy in neonatal brain cortical microvessels

Cell Death Dis. 2017 Feb 9;8(2):e2610. doi: 10.1038/cddis.2017.29.

Girault V1, Gilard V1,2, Marguet F1,3, Lesueur C1,4, Hauchecorne M1, Ramdani Y1, Laquerrière A1,3, Marret S1,5, Jégou S1, Gonzalez BJ1, Brasse-Lagnel C1, Bekri S1,4.

Abstract

Brain developmental lesions are a devastating consequence of prenatal alcohol exposure (PAE). We recently showed that PAE affects cortical vascular development with major effects on angiogenesis and endothelial cell survival. The underlying molecular mechanisms of these effects remain poorly understood. This study aimed at characterizing the ethanol exposure impact on the autophagic process in brain microvessels in human fetuses with fetal alcohol syndrome (FAS) and in a PAE mouse model. Our results indicate that PAE induces an increase of autophagic vacuole number in human fetal and neonatal mouse brain cortical microvessels. Subsequently, ex vivo studies using green fluorescent protein (GFP)-LC3 mouse microvessel preparations revealed that ethanol treatment alters autophagy in endothelial cells. Primary cultures of mouse brain microvascular endothelial cells were used to characterize the underlying molecular mechanisms. LC3 and p62 protein levels were significantly increased in endothelial cells treated with 50 mM ethanol. The increase of autophagic vacuole number may be due to excessive autophagosome formation associated with the partial inhibition of the mammalian target of rapamycin pathway upon ethanol exposure. In addition, the progression from autophagosomes to autolysosomes, which was monitored using autophagic flux inhibitors and mRFP-EGFP vector, showed a decrease in the autolysosome number. Besides, a decrease in the Rab7 protein level was observed that may underlie the impairment of autophagosome-lysosome fusion. In addition, our results showed that ethanol-induced cell death is likely to be mediated by decreased mitochondrial integrity and release of apoptosis-inducing factor. Interestingly, incubation of cultured cells with rapamycin prevented ethanol effects on autophagic flux, ethanol-induced cell death and vascular plasticity. Taken together, these results are consistent with autophagy dysregulation in cortical microvessels upon ethanol exposure, which could contribute to the defects in angiogenesis observed in patients with FAS. Moreover, our results suggest that rapamycin represents a potential therapeutic strategy to reduce PAE-related brain developmental disorders.

PMID 28182007 PMCID: PMC5386476 DOI: 10.1038/cddis.2017.29

Prenatal alcohol exposure impairs autophagy in neonatal brain cortical microvessels

Cell Death Dis. 2017 Feb 9;8(2):e2610. doi: 10.1038/cddis.2017.29.

Girault V1, Gilard V1,2, Marguet F1,3, Lesueur C1,4, Hauchecorne M1, Ramdani Y1, Laquerrière A1,3, Marret S1,5, Jégou S1, Gonzalez BJ1, Brasse-Lagnel C1, Bekri S1,4.

Abstract

Brain developmental lesions are a devastating consequence of prenatal alcohol exposure (PAE). We recently showed that PAE affects cortical vascular development with major effects on angiogenesis and endothelial cell survival. The underlying molecular mechanisms of these effects remain poorly understood. This study aimed at characterizing the ethanol exposure impact on the autophagic process in brain microvessels in human fetuses with fetal alcohol syndrome (FAS) and in a PAE mouse model. Our results indicate that PAE induces an increase of autophagic vacuole number in human fetal and neonatal mouse brain cortical microvessels. Subsequently, ex vivo studies using green fluorescent protein (GFP)-LC3 mouse microvessel preparations revealed that ethanol treatment alters autophagy in endothelial cells. Primary cultures of mouse brain microvascular endothelial cells were used to characterize the underlying molecular mechanisms. LC3 and p62 protein levels were significantly increased in endothelial cells treated with 50 mM ethanol. The increase of autophagic vacuole number may be due to excessive autophagosome formation associated with the partial inhibition of the mammalian target of rapamycin pathway upon ethanol exposure. In addition, the progression from autophagosomes to autolysosomes, which was monitored using autophagic flux inhibitors and mRFP-EGFP vector, showed a decrease in the autolysosome number. Besides, a decrease in the Rab7 protein level was observed that may underlie the impairment of autophagosome-lysosome fusion. In addition, our results showed that ethanol-induced cell death is likely to be mediated by decreased mitochondrial integrity and release of apoptosis-inducing factor. Interestingly, incubation of cultured cells with rapamycin prevented ethanol effects on autophagic flux, ethanol-induced cell death and vascular plasticity. Taken together, these results are consistent with autophagy dysregulation in cortical microvessels upon ethanol exposure, which could contribute to the defects in angiogenesis observed in patients with FAS. Moreover, our results suggest that rapamycin represents a potential therapeutic strategy to reduce PAE-related brain developmental disorders.

PMID 28182007 PMCID: PMC5386476 DOI: 10.1038/cddis.2017.29


2015

Proceedings of the 2014 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group

Alcohol. 2015 Aug;49(5):453-60. doi: 10.1016/j.alcohol.2015.02.009. Epub 2015 Apr 23.

Reynolds JN1, Valenzuela CF2, Medina AE3, Wozniak JR4.

Abstract

The 2014 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting focused on the dual themes of the risks associated with low to moderate alcohol exposure during pregnancy and knowledge translation practices to enhance the impact of scientific research. The meeting theme was titled "Low drinking versus no drinking: Matching science with policy and public perception." Despite decades of basic science and clinical evidence that has documented the risks associated with prenatal alcohol exposure, there still exists confusion and uncertainty on the part of health professionals and the public regarding the question of whether or not there is a "safe" level of alcohol consumption during pregnancy. The first keynote presentation reviewed the data obtained from large-scale epidemiological studies that have attempted to address the question of relative risk associated with low to moderate alcohol exposure during pregnancy. This presentation was followed by an expert panel discussion of the state of scientific evidence obtained from clinical and basic science investigations concerning this question, and strategies for moving research evidence into policy and practice. The second keynote presentation presented a framework for knowledge translation and mobilization to move research discoveries toward implementation. The conference also featured updates by government agencies, FASt data talks that highlighted new and innovative findings in FASD research, and award presentations, including a lifetime achievement award presented to Dr. Kenneth Warren to acknowledge his longstanding support for FASD research. A highlight of the meeting was the presentation of the 2014 Henry Rosett award to Dr. Philip May in recognition of his substantial contributions to epidemiological studies on FASD. Copyright © 2015 Elsevier Inc. All rights reserved. KEYWORDS: Epidemiology; Fetal alcohol spectrum disorders; Knowledge mobilization; Prenatal alcohol exposure; Rosett Award

PMID 25979530

Pioglitazone Blocks Ethanol Induction of Microglial Activation and Immune Responses in the Hippocampus, Cerebellum, and Cerebral Cortex in a Mouse Model of Fetal Alcohol Spectrum Disorders

Alcohol Clin Exp Res. 2015 Feb 19. doi: 10.1111/acer.12639. [Epub ahead of print]

Drew PD1, Johnson JW, Douglas JC, Phelan KD, Kane CJ.

Abstract

BACKGROUND: Fetal alcohol spectrum disorders (FASD) result from fetal exposure to alcohol and are the leading cause of mental retardation in the United States. There is currently no effective treatment that targets the causes of these disorders. Thus, novel therapies are critically needed to limit the neurodevelopmental and neurodegenerative pathologies associated with FASD. METHODS: A neonatal mouse FASD model was used to examine the role of the neuroimmune system in ethanol (EtOH)-induced neuropathology. Neonatal C57BL/6 mice were treated with EtOH, with or without pioglitazone, on postnatal days 4 through 9, and tissue was harvested 1 day post treatment. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits anti-inflammatory activity and is neuroprotective. We compared the effects of EtOH with or without pioglitazone on cytokine and chemokine expression and microglial morphology in the hippocampus, cerebellum, and cerebral cortex. RESULTS: In EtOH-treated animals compared with controls, cytokines interleukin-1β and tumor necrosis factor-α mRNA levels were increased significantly in the hippocampus, cerebellum, and cerebral cortex. Chemokine CCL2 mRNA was increased significantly in the hippocampus and cerebellum. Pioglitazone effectively blocked the EtOH-induced increase in the cytokines and chemokine in all tissues to the level expressed in handled-only and vehicle-treated control animals. EtOH also produced a change in microglial morphology in all brain regions that was indicative of microglial activation, and pioglitazone blocked this EtOH-induced morphological change. CONCLUSIONS: These studies indicate that EtOH activates microglia to a pro-inflammatory stage and also increases the expression of neuroinflammatory cytokines and chemokines in diverse regions of the developing brain. Further, the anti-inflammatory and neuroprotective PPAR-γ agonist pioglitazone blocked these effects. It is proposed that microglial activation and inflammatory molecules expressed as a result of EtOH treatment during brain development contribute to the sequelae associated with FASD. Thus, pioglitazone and anti-inflammatory pharmaceuticals more broadly have potential as novel therapeutics for FASD. Copyright © 2015 by the Research Society on Alcoholism. KEYWORDS: Brain; EtOH; Fetal Alcohol Spectrum Disorder; Microglia; Neuroinflammation PMID 25703036


2013

Prenatal Ethanol Exposure Disrupts Intraneocortical Circuitry, Cortical Gene Expression, and Behavior in a Mouse Model of FASD

J Neurosci. 2013 Nov 27;33(48):18893-905. doi: 10.1523/JNEUROSCI.3721-13.2013.

El Shawa H, Abbott CW 3rd, Huffman KJ. Source Department of Psychology and Interdepartmental Neuroscience Program, University of California, Riverside, Riverside, California 92521.

Abstract

In utero ethanol exposure from a mother's consumption of alcoholic beverages impacts brain and cognitive development, creating a range of deficits in the child (Levitt, 1998; Lebel et al., 2012). Children diagnosed with fetal alcohol spectrum disorders (FASD) are often born with facial dysmorphology and may exhibit cognitive, behavioral, and motor deficits from ethanol-related neurobiological damage in early development. Prenatal ethanol exposure (PrEE) is the number one cause of preventable mental and intellectual dysfunction globally, therefore the neurobiological underpinnings warrant systematic research. We document novel anatomical and gene expression abnormalities in the neocortex of newborn mice exposed to ethanol in utero. This is the first study to demonstrate large-scale changes in intraneocortical connections and disruption of normal patterns of neocortical gene expression in any prenatal ethanol exposure animal model. Neuroanatomical defects and abnormal neocortical RZRβ, Id2, and Cadherin8 expression patterns are observed in PrEE newborns, and abnormal behavior is present in 20-d-old PrEE mice. The vast network of neocortical connections is responsible for high-level sensory and motor processing as well as complex cognitive thought and behavior in humans. Disruptions to this network from PrEE-related changes in gene expression may underlie some of the cognitive-behavioral phenotypes observed in children with FASD.

PMID 24285895

A modified Delphi study of screening for fetal alcohol spectrum disorders in Australia

BMC Pediatr. 2013 Jan 25;13:13. doi: 10.1186/1471-2431-13-13.

Watkins RE, Elliott EJ, Halliday J, O'Leary CM, D'Antoine H, Russell E, Hayes L, Peadon E, Wilkins A, Jones HM, McKenzie A, Miers S, Burns L, Mutch RC, Payne JM, Fitzpatrick JP, Carter M, Latimer J, Bower C. Source Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Australia. rwatkins@ichr.uwa.edu.au

Abstract

BACKGROUND: There is little reliable information on the prevalence of fetal alcohol spectrum disorders (FASD) in Australia and no coordinated national approach to facilitate case detection. The aim of this study was to identify health professionals' perceptions about screening for FASD in Australia. METHOD: A modified Delphi process was used to assess perceptions of the need for, and the process of, screening for FASD in Australia. We recruited a panel of 130 Australian health professionals with experience or expertise in FASD screening or diagnosis. A systematic review of the literature was used to develop Likert statements on screening coverage, components and assessment methods which were administered using an online survey over two survey rounds. RESULTS: Of the panel members surveyed, 95 (73%) responded to the questions on screening in the first survey round and, of these, 81 (85%) responded to the second round. Following two rounds there was consensus agreement on the need for targeted screening at birth (76%) and in childhood (84%). Participants did not reach consensus agreement on the need for universal screening at birth (55%) or in childhood (40%). Support for targeted screening was linked to perceived constraints on service provision and the need to examine the performance, costs and benefits of screening.For targeted screening of high risk groups, we found highest agreement for siblings of known cases of FASD (96%) and children of mothers attending alcohol treatment services (93%). Participants agreed that screening for FASD primarily requires assessment of prenatal alcohol exposure at birth (86%) and in childhood (88%), and that a checklist is needed to identify the components of screening and criteria for referral at birth (84%) and in childhood (90%). CONCLUSIONS: There is an agreed need for targeted but not universal screening for FASD in Australia, and sufficient consensus among health professionals to warrant development and evaluation of standardised methods for targeted screening and referral in the Australian context. Participants emphasised the need for locally-appropriate, evidence-based approaches to facilitate case detection, and the importance of ensuring that screening and referral programs are supported by adequate diagnostic and management capacity.

PMID 23347677

Diagnosis of fetal alcohol syndrome (FAS): German guideline version 2013

Eur J Paediatr Neurol. 2013 Apr 22. pii: S1090-3798(13)00051-2. doi: 10.1016/j.ejpn.2013.03.008. [Epub ahead of print]

Landgraf MN, Nothacker M, Heinen F. Source Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians, University of Munich, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: mirjam.landgraf@med.uni-muenchen.de.

Abstract

BACKGROUND: Fetal alcohol syndrome (FAS) belongs to the umbrella of fetal alcohol spectrum disorders (FASD) and affects 0.02-0.8% of all annual births with a high number of undetected cases. FAS has severe and life determining consequences for the affected individual and his family. AIM: The aim of the German guideline version 2013 is to provide objectively evaluated, evidence-based, clinically relevant and easily applicable diagnostic criteria for the full picture FAS. METHODS: A systematic literature review (2001-2011), analysis of international guidelines and focused hand search were performed. Based on the evidence-assessed literature the multidisciplinary guideline group (14 German Professional Societies, the patient support group "FASD Germany" and 15 additional experts) consented recommendations for the diagnosis of FAS. RESULTS: The following diagnostic criteria for FAS resulted: at least one deficit of growth, three defined facial characteristics and one functional or structural anomaly of the central nervous system. Confirmation of intrauterine alcohol exposure is not considered as a prerequisite for FAS diagnosis. CONCLUSION: The German guideline presented here constitutes an unbiased evidence-based approach to the diagnosis of patients with fetal alcohol syndrome. It includes a practical pocket guide FAS for a quick overview of the diagnostic workup in everyday clinical work. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

PMID 23618613

Commonality in down and fetal alcohol syndromes

Birth Defects Res A Clin Mol Teratol. 2013 Apr 3. doi: 10.1002/bdra.23129. [Epub ahead of print]

Solzak JP, Liang Y, Zhou FC, Roper RJ. Source Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana.

Abstract

BACKGROUND: Down syndrome (DS) and Fetal Alcohol Syndrome (FAS) are two leading causes of birth defects with phenotypes ranging from craniofacial abnormalities to cognitive impairment. Despite different origins, we report that in addition to sharing many phenotypes, DS and FAS may have common underlying mechanisms of development. METHODS: Literature was surveyed for DS and FAS as well as mouse models. Gene expression and apoptosis were compared in embryonic mouse models of DS and FAS by qPCR, immunohistochemical and immunoflurorescence analyses. The craniometry was examined using MicroCT at postnatal day 21. RESULTS: A literature survey revealed over 20 comparable craniofacial and structural deficits in both humans with DS and FAS and corresponding mouse models. Similar phenotypes were experimentally found in pre- and postnatal craniofacial and neurological tissues of DS and FAS mice. Dysregulation of two genes, Dyrk1a and Rcan1, key to craniofacial and neurological precursors of DS, was shared in craniofacial precursors of DS and FAS embryos. Increased cleaved caspase 3 expression was also discovered in comparable regions of the craniofacial and brain precursors of DS and FAS embryos. Further mechanistic studies suggested overexpression of trisomic Ttc3 in DS embyros may influence nuclear pAkt localization and cell survival. CONCLUSIONS: This first and initial study indicates that DS and FAS share common dysmorphologies in humans and animal models. This work also suggests common mechanisms at cellular and molecular levels that are disrupted by trisomy or alcohol consumption during pregnancy and lead to craniofacial and neurological phenotypes associated with DS or FAS. Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

PMID 23554291

Alcohol-use disorders during and within one year of pregnancy: a population-based cohort study 1985-2006

BJOG. 2013 May;120(6):744-53. doi: 10.1111/1471-0528.12167. Epub 2013 Feb 19.

O'Leary C, Halliday J, Bartu A, D'Antoine H, Bower C. Source Centre for Population Health Research, Curtin University, Perth, WA, Australia; Division of Population Sciences Telethon Institute for Child Health Research Centre for Child Health Research, University of Western Australia, Perth, WA, Australia.

Abstract

OBJECTIVES: To examine alcohol-use disorders in pregnant women and the extent of under-reporting. DESIGN: Population-based cohort study. SETTING: Western Australia. POPULATION: Women with a birth recorded on the Western Australian Midwives Notification System (1985-2006). METHODS: Mothers with an International Classification of Diseases 9/10 alcohol-related diagnosis, indicating heavy alcohol consumption, recorded on population-based health datasets (non-Aboriginal n = 5839; Aboriginal n = 2583) were identified through the Western Australian data-linkage system. This 'exposed' cohort was frequency matched (on maternal age, year of birth of offspring, Aboriginal status) with comparison mothers without an alcohol-related diagnosis (non-Aboriginal n = 33 979; Aboriginal n = 8005). MAIN OUTCOME MEASURES: Trends in maternal alcohol diagnoses in relation to pregnancy for non-Aboriginal and Aboriginal women. The proportion of children diagnosed with fetal alcohol syndrome (FAS) who had a mother with an alcohol diagnosis recorded during pregnancy. RESULTS: The proportion of Aboriginal mothers in Western Australia with an alcohol diagnosis (23.1%) is ten times greater than for non-Aboriginal mothers (2.3%). There has been a six-fold increase in the percentage of non-Aboriginal births with a maternal alcohol diagnosis recorded during pregnancy and a 100-fold increase for Aboriginal births. Around 70% of the mothers of children diagnosed with FAS did not have an alcohol diagnosis recorded during pregnancy and 18% of the mothers had no record of an alcohol diagnosis. CONCLUSIONS: Maternal alcohol exposure during pregnancy is significantly under-ascertained. Given the severe risks to the fetus from heavy prenatal alcohol exposure, assessment and recording of alcohol use should be routinely undertaken in maternity and other health settings. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

PMID 23418853

Neuroprotective profile of pyruvate against ethanol-induced neurodegeneration in developing mice brain

Neurol Sci. 2013 Mar 15. [Epub ahead of print]

Ullah N, Naseer MI, Ullah I, Kim TH, Lee HY, Kim MO. Source Division of Life Science, College of Natural Sciences (RINS) and Applied Life Science, Gyeongsang National University, Chinju, 660-701, Republic of Korea.

Abstract

Exposure to ethanol during developmental stages leads to several types of neurological disorders. Apoptotic neurodegeneration due to ethanol exposure is a main feature in alcoholism. Exposure of developing animals to alcohol induces apoptotic neuronal death and causes fetal alcohol syndrome. In the present study, we observed the possible protective effect of pyruvate against ethanol-induced neurodegeneration. Exposure of developing mice to ethanol (2.5 g/kg) induces apoptotic neurodegeneration and widespread neuronal cell death in the cortex and thalamus. Co-treatment of pyruvate (500 mg/kg) protects neuronal cell against ethanol by the reduced expression of caspase-3 in these brain regions. Immunohistochemical analysis and TUNNEL at 24 h showed that apoptotic cell death induced by ethanol in the cortex and thalamus is reduced by pyruvate. Histomorphological analysis at 24 h with cresyl violet staining also proved that pyruvate reduced the number of neuronal cell loss in the cortex and thalamus. The results showed that ethanol increased the expression of caspase-3 and thus induced apoptotic neurodegeneration in the developing mice cortex and thalamus, while co-treatment of pyruvate inhibits the induction of caspase-3 and reduced the cell death in these brain regions. These findings, therefore, showed that treatment of pyruvate inhibits ethanol-induced neuronal cell loss in the postnatal seven (P7) developing mice brain and may appear as a safe neuroprotectant for treating neurodegenerative disorders in newborns and infants.

PMID 23494720


2012

Consensus diagnostic criteria for fetal alcohol spectrum disorders in Australia: a modified Delphi study

BMJ Open. 2012 Oct 25;2(5). pii: e001918. doi: 10.1136/bmjopen-2012-001918. Print 2012.


Watkins RE, Elliott EJ, Mutch RC, Payne JM, Jones HM, Latimer J, Russell E, Fitzpatrick JP, Hayes L, Burns L, Halliday J, D'Antoine HA, Wilkins A, Peadon E, Miers S, Carter M, O'Leary CM, McKenzie A, Bower C. Source Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.

Abstract

OBJECTIVE: To evaluate health professionals' agreement with components of published diagnostic criteria for fetal alcohol spectrum disorders (FASD) in order to guide the development of standard diagnostic guidelines for Australia.

DESIGN: A modified Delphi process was used to assess agreement among health professionals with expertise or experience in FASD screening or diagnosis. An online survey, which included 36 Likert statements on diagnostic methods, was administered over two survey rounds. For fetal alcohol syndrome (FAS), health professionals were presented with concepts from the Institute of Medicine (IOM), University of Washington (UW), Centers for Disease Control (CDC), revised IOM and Canadian diagnostic criteria. For partial FAS (PFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD), concepts based on the IOM and the Canadian diagnostic criteria were compared.

SETTING/PARTICIPANTS: 130 Australian and 9 international health professionals.

RESULTS: Of 139 health professionals invited to complete the survey, 103 (74.1%) responded, and 74 (53.2%) completed one or more questions on diagnostic criteria. We found consensus agreement among participants on the diagnostic criteria for FAS, with the UW criteria most commonly endorsed when compared with all other published criteria for FAS. When health professionals were presented with concepts based on the Canadian and IOM diagnostic criteria, we found consensus agreement but no clear preference for either the Canadian or IOM criteria for the diagnosis of PFAS, and no consensus agreement on diagnostic criteria for ARND. We also found no consensus on the IOM diagnostic criteria for ARBD.

CONCLUSIONS: Participants indicated clear support for use of the UW diagnostic criteria for FAS in Australia. These findings should be used to develop guidelines to facilitate improved awareness of, and address identified gaps in the infrastructure for, FASD diagnosis in Australia.

PMID 23100447 http://bmjopen.bmj.com/content/2/5/e001918.long

2011

Health initiatives by Indigenous people in Australia

Lancet. 2011 Jun 18;377(9783):2066-7.

Clark S. Source The Lancet, London NW1 7BY, UK. PMID 21684368 http://www.ncbi.nlm.nih.gov/pubmed/21684368 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60884-2/fulltext

Fetal Alcohol Spectrum Disorders: A Population Based Study of Premature Mortality Rates in the Mothers

Matern Child Health J. 2011 Jun 28. [Epub ahead of print]

Li Q, Fisher WW, Peng CZ, Williams AD, Burd L. Source North Dakota Fetal Alcohol Syndrome Center, University of North Dakota School of Medicine and Health Sciences, 501 N Columbia Road Stop 9037, Grand Forks, ND, 58202-9037, USA.

Abstract

Fetal alcohol spectrum disorders (FASD) are associated with an increase in risk for mortality for people with an FASD and their siblings. In this study we examine mortality rates of birth mothers of children with FASD, using a retrospective case control methodology. We utilized the North Dakota FASD Registry to locate birth certificates for children with FASD which we used to identify birth mothers. We then searched for mothers' death certificates. We then compared the mortality rates of the birth mothers with an age matched control group comprised of all North Dakota women who were born and died in the same year as the birth mother. The birth mothers of children with FASD had a mortality rate of 15/304 = 4.93%; (95% CI 2.44-7.43%). The mortality rate for control mothers born in same years as the FASD mothers was 126/114,714 = 0.11% (95% CI 0.09-0.13%). Mothers of children with an FASD had a 44.82 fold increase in mortality risk and 87% of the deaths occurred in women under the age of 50. Three causes of death (cancer, injuries, and alcohol related disease) accounted for 67% of the deaths in the mothers of children with FASD. A diagnosis of FASD is an important risk marker for premature death in the mothers of children diagnosed with an FASD. These women should be encouraged to enter substance abuse treatment.

PMID 21710184

Fetal alcohol syndrome: dashed hopes, damaged lives

Bull World Health Organ. 2011 Jun 1;89(6):398-9. [No authors listed] Abstract Since the term was coined about 40 years ago, fetal alcohol syndrome has slowly become recognized as a public health issue. Alicestine October reports from South Africa's Western Cape province, which has the highest reported rate in the world.

PMID 21673854

Fetal Alcohol Spectrum Disorders: An Overview

Neuropsychol Rev. 2011 Apr 16. [Epub ahead of print]

Riley EP, Infante MA, Warren KR. Source Department of Psychology, Center for Behavioral Teratology, San Diego State University, 6330 Alvarado Court, Suite 100, San Diego, CA, 92120, USA, eriley@mail.sdsu.edu.

Abstract

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.

PMID 21499711

The effects of alcohol on fetal development

Birth Defects Res C Embryo Today. 2011 Mar;93(1):3-11. doi: 10.1002/bdrc.20200.

Jones KL.

Department of Pediatrics, Division of Dysmorphology/Teratology, University of California, San Diego, California. klyons@ucsd.edu.

Abstract

Prenatal exposure to alcohol has profound effects on many aspects of fetal development. Although alterations of somatic growth and specific minor malformations of facial structure are most characteristic, the effects of alcohol on brain development are most significant in that they lead to substantial problems with neurobehavioral development. Since the initial recognition of the fetal alcohol syndrome (FAS), a number of important observations have been made from studies involving both humans and animals. Of particular importance, a number of maternal risk factors have been identified, which may well be of relevance relative to the development of strategies for prevention of the FAS as well as intervention for those who have been affected. These include maternal age >30 years, ethnic group, lower socioeconomic status, having had a previously affected child, maternal under-nutrition, and genetic background. The purpose of this review is to discuss these issues as well as to set forth a number of questions that have not adequately been addressed relative to alcohol's effect on fetal development. Of particular importance is the critical need to identify the full spectrum of structural defects associated with the prenatal effects of alcohol as well as to establish a neurobehavioral phenotype. Appreciation of both of these issues is necessary to understand the full impact of alcohol on fetal development. Birth Defects Research (Part C) 93:3-11, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID 21425437

Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure - retrospective cohort study in an urban obstetric population in Ireland

BMC Pregnancy Childbirth. 2011 Apr 11;11(1):27. [Epub ahead of print]

Mullally A, Cleary BJ, Barry J, Fahey TP, Murphy DJ. Abstract ABSTRACT:

BACKGROUND: Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption.

METHODS: A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (> 20 units per week).

RESULTS: Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80), Irish nationality OR 16.5 (95% CI 14.9 to 18.3), private health care OR 5.83 (95% CI 5.38 to 6.31) and smoking OR 1.86 (95% CI 1.73 to 2.01). Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91) and illicit drug use OR 6.46 (95% CI 3.32 to 12.60). High consumption was associated with very preterm birth (< 32 weeks gestation) even after controlling for socio-demographic factors adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups.

CONCLUSIONS: Public Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.

PMID 21481224

2010

Alcohol and other drug treatment services in Australia 2006–07

Around 143,000 alcohol and other drug treatment episodes were provided in Australia in 2008-09'

Australian Institute of Health and Welfare 2008. Alcohol and other drug treatment services in Australia 2006–07: report on the National Minimum Data Set. Drug treatment series no. 8. Cat. no. HSE 59. Canberra: AIHW.

"More episodes of this treatment were for alcohol than any other drug type, and this proportion has now risen four years in a row. ...As seen in previous years, most treatment episodes (66%) were provided to male clients."

Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

Cell Death Dis. 2010 May 27;1(5):e46.

Wang G, Bieberich E. Source Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, Augusta, GA 30912, USA.

Abstract

Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-β1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol.

PMID 21364652

2009

Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8

Alcohol Clin Exp Res. 2009 Jun;33(6):1001-11. Epub 2009 Mar 19.


Parnell SE, O'Leary-Moore SK, Godin EA, Dehart DB, Johnson BW, Allan Johnson G, Styner MA, Sulik KK.

The Bowles Center for Alcohol Studies, and Neurodevelopmental Disorders Research Center, University of North Carolina, Chapel Hill, NC 27599-7178, USA. sparnell@med.unc.edu

PMID 19302087 http://www3.interscience.wiley.com/journal/122268272/abstract

Integrating case topics in medical school curriculum to enhance multiple skill learning: using fetal alcohol spectrum disorders as an exemplary case

Acad Psychiatry. 2009 Mar-Apr;33(2):143-8.

Paley B, O'Connor MJ, Baillie SJ, Guiton G, Stuber ML. Source Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, CA 90024, USA. bpaley@mednet.ucla.edu

Abstract

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 Control and Prevention (CDC) and the National Organization on Fetal Alcohol Syndrome, the Western Regional Training Center for Fetal Alcohol Exposure at UCLA developed and integrated educational materials on FASDs into the curriculum for first-year medical students. RESULTS: Quantitative and qualitative evaluations suggested materials were effective in enhancing student knowledge and skills related to FASDs, as well as embryology, brain development, substance abuse, developmental psychopathology, and medical ethics. CONCLUSION: The use of a unifying theme integrating basic science and clinical information and skills is effective for medical student training in the prevention and treatment of common medical problems.


PMID 19398629

  1. NHMRC Website alcohol guidelines