Exploring the potential to use data linkage for investigating the relationship between birth defects and prenatal alcohol exposure

2013 ◽  
Vol 97 (7) ◽  
pp. 497-504 ◽  
Author(s):  
Colleen M. O'Leary ◽  
Elizabeth J. Elliott ◽  
Natasha Nassar ◽  
Carol Bower
Keyword(s):  
Birth Defects ◽  
Data Linkage ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Prenatal Alcohol ◽  
The Relationship

Prenatal Alcohol Exposure and Risk of Birth Defects

PEDIATRICS ◽  
2010 ◽  
Vol 126 (4) ◽  
pp. e843-e850 ◽  
Author(s):  
C. M. O'Leary ◽  
N. Nassar ◽  
J. J. Kurinczuk ◽  
N. de Klerk ◽  
E. Geelhoed ◽  
...  
Keyword(s):  
Birth Defects ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Prenatal Alcohol

Alcohol Consumption During Pregnancy

2005 ◽  
Vol 23 (1) ◽  
pp. 101-134 ◽  
Author(s):  
Cara J. Krulewitch
Keyword(s):  
High Risk ◽  
Birth Defects ◽  
Prenatal Alcohol Exposure ◽  
Drinking Behavior ◽  
Genetic Research ◽  
Alcohol Exposure ◽  
Risk Groups ◽  
Screening Tools ◽  
Fetal Alcohol ◽  
Prenatal Alcohol

Alcohol is a potent teratogen in humans, and prenatal alcohol exposure is a leading preventable cause of birth defects and developmental disabilities. The term fetal alcohol syndrome (FAS) refers to a pattern of birth defects found in children of mothers who drank during pregnancy. FAS has four criteria: maternal drinking during pregnancy, a characteristic pattern of facial abnormalities, growth retardation, and brain damage (often manifested by intellectual difficulties or behavioral problems). As surveillance and research have progressed, it has become clear that FAS is but a rare example of a wide array of defects that can occur from exposure to alcohol in utero. At least 1 in 10 women will continue to consume alcohol during pregnancy, putting their fetuses at risk for the effects of alcohol exposure.Nurses are in a key position to provide care and conduct research that will contribute to the prevention of the adverse effects of prenatal alcohol exposure during the preconception and perinatal periods, as well as deal with the negative outcomes of exposure in the developing infant. Many areas have yet to be evaluated. Screening tools and interventions have been developed and tested, mostly in majority cultures. Culturally sensitive instruments must be generated and validated for high-risk groups such as Native Americans. Fetal alcohol biomarkers and genetic research are new and need considerably more work. Effective “no drinking during pregnancy” campaigns for high-risk groups must be created and tested. Nurses are well placed to conduct research that will describe the effects at social, behavioral, and biological levels; develop middle-range theories targeted at preventing the drinking behavior and optimizing care of affected children after birth; and generate and test effective interventions that enhance prevention strategies in the 21st century.

Prenatal Alcohol Exposure Patterns and Alcohol-Related Birth Defects and Growth Deficiencies: A Prospective Study

2012 ◽  
Vol 36 (4) ◽  
pp. 670-676 ◽  
Author(s):  
Haruna Sawada Feldman ◽  
Kenneth Lyons Jones ◽  
Suzanne Lindsay ◽  
Donald Slymen ◽  
Hillary Klonoff-Cohen ◽  
...  
Keyword(s):  
Prospective Study ◽  
Birth Defects ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Exposure Patterns ◽  
Prenatal Alcohol ◽  
A Prospective Study

scholarly journals Gene-environment interactions characterized by single embryo transcriptomics

2019 ◽  
Author(s):  
Alfire Sidik ◽  
Groves B. Dixon ◽  
Hannah G. Kirby ◽  
Johann K. Eberhart
Keyword(s):  
Cell Polarity ◽  
Birth Defects ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Convergent Extension ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Gene Environment ◽  
Midfacial Hypoplasia ◽  
Prenatal Alcohol

AbstractGene-environment interactions are likely to underlie most human birth defects. The most common environmental contributor to birth defects is likely prenatal alcohol exposure. Fetal Alcohol Spectrum Disorders (FASD) describes the full range of defects that result from prenatal alcohol exposure. Gene-ethanol interactions underlie susceptibility to FASD but we lack a mechanistic understanding of these interactions. Here, we leverage the genetic tractability of zebrafish to address this problem. We first show that vangl2, a member of the Wnt/planar cell polarity (Wnt/PCP) pathway that mediates convergent extension movements, strongly interacts with ethanol during late blastula and early gastrula stages. Embryos mutant or heterozygous for vangl2 are sensitized to ethanol- induced midfacial hypoplasia. We performed single-embryo RNA-Seq during early embryonic stages, to assess individual variation to the transcriptional response to ethanol and determine the mechanism of the vangl2-ethanol interaction. To identify the pathway(s) that are disrupted by ethanol we used these global changes in gene expression to identify small molecules that mimic the effects of ethanol via the Library of Integrated Network- based Cellular Signatures (LINCS L1000) dataset. Surprisingly, this dataset predicted that the Sonic Hedgehog (Shh) pathway inhibitor, cyclopamine, would mimic the effects of ethanol, despite the fact that ethanol did not alter the expression levels of direct targets of Shh signaling. Indeed, we found that ethanol and cyclopamine strongly interact to disrupt midfacial development. Collectively, these results suggest that the midfacial defects in ethanol-exposed vangl2 mutants are due to an indirect interaction between ethanol and the Shh pathway. Vangl2 functions as part of a signaling pathway that regulates coordinated cell movements during midfacial development. Consistent with an indirect model, a critical source of Shh signaling that separates the developing eye field into bilateral eyes, allowing the expansion of the midface, becomes mispositioned in ethanol-exposed vangl2 mutants. We demonstrate that ethanol also interacts with another Wnt/PCP pathway member, gpc4, and a chemical inhibitor, blebbistatin. By characterizing membrane protrusions, we demonstrate that ethanol synergistically interacts with the loss of vangl2 to disrupt cell polarity required for convergent extension movements. Collectively, our results shed light on the mechanism by which the most common teratogen can disrupt development.

Fetal Alcohol Syndrome

2003 ◽  
Vol 22 (3) ◽  
pp. 63-70 ◽  
Author(s):  
Martha Wilson Jones ◽  
W. Thomas Bass
Keyword(s):  
Mental Retardation ◽  
Public Education ◽  
Fetal Alcohol Syndrome ◽  
Birth Defects ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Fetal Alcohol ◽  
The World ◽  
Prenatal Alcohol ◽  
Pregnant Mothers

FETAL ALCOHOL SYNDROME (FAS) is the leading known cause of mental retardation and birth defects in the world.1,2 It is caused by in utero exposure to alcohol and is entirely preventable. Because alcohol is a known teratogen and the damage done to a fetus by alcohol exposure is permanent, public education about the dangers of prenatal alcohol exposure has been extensive. Nevertheless, alcohol is a widely accepted and legal social drug, and many pregnant mothers continue to drink it while pregnant. Other mothers drink before they are aware of their pregnancy. This column provides information regarding the incidence of FAS, its etiology, spectrum of effects, and diagnosis. We also discuss potential disabilities that these infants may face as they grow and suggest how to work effectively with the families.

scholarly journals Exposure to ethanol leads to midfacial hypoplasia in a zebrafish model of FASD via indirect interactions with the Shh pathway

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alfire Sidik ◽  
Groves Dixon ◽  
Desire M. Buckley ◽  
Hannah G. Kirby ◽  
Shuge Sun ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Birth Defects ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Global Changes ◽  
Convergent Extension ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Midfacial Hypoplasia ◽  
Prenatal Alcohol

Abstract Background Gene-environment interactions are likely to underlie most human birth defects. The most common known environmental contributor to birth defects is prenatal alcohol exposure. Fetal alcohol spectrum disorders (FASD) describe the full range of defects that result from prenatal alcohol exposure. Gene-ethanol interactions underlie susceptibility to FASD, but we lack a mechanistic understanding of these interactions. Here, we leverage the genetic tractability of zebrafish to address this problem. Results We first show that vangl2, a member of the Wnt/planar cell polarity (Wnt/PCP) pathway that mediates convergent extension movements, strongly interacts with ethanol during late blastula and early gastrula stages. Embryos mutant or heterozygous for vangl2 are sensitized to ethanol-induced midfacial hypoplasia. We performed single-embryo RNA-seq during early embryonic stages to assess individual variation in the transcriptional response to ethanol and determine the mechanism of the vangl2-ethanol interaction. To identify the pathway(s) that are disrupted by ethanol, we used these global changes in gene expression to identify small molecules that mimic the effects of ethanol via the Library of Integrated Network-based Cellular Signatures (LINCS L1000) dataset. Surprisingly, this dataset predicted that the Sonic Hedgehog (Shh) pathway inhibitor, cyclopamine, would mimic the effects of ethanol, despite ethanol not altering the expression levels of direct targets of Shh signaling. Indeed, we found that ethanol and cyclopamine strongly, but indirectly, interact to disrupt midfacial development. Ethanol also interacts with another Wnt/PCP pathway member, gpc4, and a chemical inhibitor of the Wnt/PCP pathway, blebbistatin, phenocopies the effect of ethanol. By characterizing membrane protrusions, we demonstrate that ethanol synergistically interacts with the loss of vangl2 to disrupt cell polarity required for convergent extension movements. Conclusions Our results show that the midfacial defects in ethanol-exposed vangl2 mutants are likely due to an indirect interaction between ethanol and the Shh pathway. Vangl2 functions as part of a signaling pathway that regulates coordinated cell movements during midfacial development. Ethanol exposure alters the position of a critical source of Shh signaling that separates the developing eye field into bilateral eyes, allowing the expansion of the midface. Collectively, our results shed light on the mechanism by which the most common teratogen can disrupt development.

scholarly journals Early School Years follow up of the Asking Questions in Alcohol Longitudinal Study in Melbourne, Australia (AQUA at 6): Cohort profile

2021 ◽  
Author(s):  
Evelyne Muggli ◽  
Jane Halliday ◽  
Elizabeth Elliott ◽  
Anthony Penington ◽  
Deanne K Thompson ◽  
...  
Keyword(s):  
Binge Drinking ◽  
Brain Structure ◽  
Prenatal Alcohol Exposure ◽  
Neuropsychological Functioning ◽  
Alcohol Exposure ◽  
Early School ◽  
Asking Questions ◽  
Prenatal Alcohol ◽  
The Relationship

Purpose The Asking Questions about Alcohol in Pregnancy (AQUA) study, established in 2011, is a pre-birth cohort of 1570 mother and child pairs designed to assess the effects of low to moderate prenatal alcohol exposure and sporadic binge drinking on long-term child development. The current follow-up of the children, now aged 6 to 8 years, aims to strengthen our understanding of the relationship between these levels of prenatal alcohol exposure and neuropsychological functioning, facial dysmorphology, and brain structure & function. Findings to date Over half (59%) of mothers consumed some alcohol during pregnancy, with one in five reporting at least one binge drinking episode prior to pregnancy recognition. Children's craniofacial shape was examined at 12 months of age, and low to moderate prenatal alcohol exposure was associated with subtle midface changes. At two years of age, formal developmental assessments showed no evidence that cognitive, language or motor outcome was associated with any of the prenatal alcohol exposures investigated. Participants Between June 2018 and April 2021, 802 of the 1342 eligible AQUA study families completed a parent-report questionnaire (60%). Restrictions associated with COVID-19 pandemic disrupted recruitment, but early school-age neuropsychological assessments were undertaken with 696 children (52%), and 482 (36%) craniofacial images were collected. A pre-planned, exposure-representative subset of 146 random children completed a brain MRI. The existing AQUA study biobank was extended through collection of 427 (32%) child buccal swabs. Future plans We will investigate the relationship between prenatal alcohol exposure and specific aspects of neurodevelopment at 6-8 years, including brain structure & function. We will also determine whether craniofacial changes identified at 12 months of age are predictive of later developmental impairments. The contribution of genetics and epigenetics to individual variations in outcomes will be examined in conjunction with established and future national and international collaborations.

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