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Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders: From Animal Models to Human Studies.

Murawski NJ, Moore EM, Thomas JD, Riley EP - Alcohol Res (2015)

Bottom Line: Diagnosing FASD continues to be a challenge, but advances are being made at both basic science and clinical levels.However, combining interventions may prove more efficacious.Ultimately, advances in basic and clinical sciences may translate to clinical care, improving both diagnosis and treatment.

View Article: PubMed Central - PubMed

Affiliation: Center for Behavioral Teratology, San Diego State University, San Diego, California.

ABSTRACT
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.

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Related in: MedlinePlus

Magnetic resonance imaging (MRI) images showing the differential effect of different timing of exposure on face shape and brain morphology. (A) The left panel shows a control, whereas the two other panels show animals exposed on gestation day 7 and gestation day 8.5. The different timing produces differential effects on face and brain. (B) An illustration of how the shape analysis shown in figure 3 can be applied to the mouse images. The left panel shows the difference between an animal exposed on gestation day 7 versus a control. Red areas indicate a reduction in size. The middle panel shows gestation day 8 exposure versus control, note the absence of many red areas. The right panel shows the difference between the two exposure times. (C) Ethanol interacts synergistically with the PDGFRA gene. The two left most figures show an intact embryo and the dissected neurocranium of a stained PDGFRA heterozygote displaying normal morphology of the neurocranium. The right most panel shows how ethanol severely disrupts development of the anterior neurocranium and palate of the zebrafish. The homozygote, −/−, (not shown) is even more affected.SOURCE: Photos in A and B are courtesy of Dr. Kathleen Sulik, University of North Carolina at Chapel Hill.Photos in C are courtesy of Dr. Johann Eberhart, University of Texas at Austin.
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f4-arcr-37-1-97: Magnetic resonance imaging (MRI) images showing the differential effect of different timing of exposure on face shape and brain morphology. (A) The left panel shows a control, whereas the two other panels show animals exposed on gestation day 7 and gestation day 8.5. The different timing produces differential effects on face and brain. (B) An illustration of how the shape analysis shown in figure 3 can be applied to the mouse images. The left panel shows the difference between an animal exposed on gestation day 7 versus a control. Red areas indicate a reduction in size. The middle panel shows gestation day 8 exposure versus control, note the absence of many red areas. The right panel shows the difference between the two exposure times. (C) Ethanol interacts synergistically with the PDGFRA gene. The two left most figures show an intact embryo and the dissected neurocranium of a stained PDGFRA heterozygote displaying normal morphology of the neurocranium. The right most panel shows how ethanol severely disrupts development of the anterior neurocranium and palate of the zebrafish. The homozygote, −/−, (not shown) is even more affected.SOURCE: Photos in A and B are courtesy of Dr. Kathleen Sulik, University of North Carolina at Chapel Hill.Photos in C are courtesy of Dr. Johann Eberhart, University of Texas at Austin.

Mentions: Developing truly accurate and specific methods for identifying individuals with FASD requires an understanding of the full spectrum of alcohol-related consequences and clarification of the various factors, both protective and permissive, that influence outcome variability. Animal models have provided information on the mechanisms by which alcohol affects facial development and the factors that may make a fetus more susceptible to these facial changes (see figure 1B and C for examples of craniofacial defects in the mouse and zebrafish). In the mouse, for example, alcohol administration on gestational day (GD) 7, equivalent to approximately week 3 postfertilization in a human pregnancy, produces a constellation of facial malformations similar to those seen in FAS. Defects include severe midfacial hypoplasia, shortening of the palpebral fissures, an elongated upper lip, and deficient philtrum (Godin et al. 2010). However, alcohol exposure delayed a day and a half to GD 8.5 produces a distinctly different pattern of malformations, with mild hypoplasia and shortening of the palpebral fissures and upper lip but a preserved philtrum (Lipinski et al. 2012) (see figure 4A and B). These data suggest that maternal alcohol consumption, even before many women are aware that they are pregnant, can cause significant and selective facial alterations in their offspring. The distinctive facial phenotype of FAS depends on the timing of exposure, and other facial characteristics resulting from alcohol exposure during different critical periods are possible.


Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders: From Animal Models to Human Studies.

Murawski NJ, Moore EM, Thomas JD, Riley EP - Alcohol Res (2015)

Magnetic resonance imaging (MRI) images showing the differential effect of different timing of exposure on face shape and brain morphology. (A) The left panel shows a control, whereas the two other panels show animals exposed on gestation day 7 and gestation day 8.5. The different timing produces differential effects on face and brain. (B) An illustration of how the shape analysis shown in figure 3 can be applied to the mouse images. The left panel shows the difference between an animal exposed on gestation day 7 versus a control. Red areas indicate a reduction in size. The middle panel shows gestation day 8 exposure versus control, note the absence of many red areas. The right panel shows the difference between the two exposure times. (C) Ethanol interacts synergistically with the PDGFRA gene. The two left most figures show an intact embryo and the dissected neurocranium of a stained PDGFRA heterozygote displaying normal morphology of the neurocranium. The right most panel shows how ethanol severely disrupts development of the anterior neurocranium and palate of the zebrafish. The homozygote, −/−, (not shown) is even more affected.SOURCE: Photos in A and B are courtesy of Dr. Kathleen Sulik, University of North Carolina at Chapel Hill.Photos in C are courtesy of Dr. Johann Eberhart, University of Texas at Austin.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476607&req=5

f4-arcr-37-1-97: Magnetic resonance imaging (MRI) images showing the differential effect of different timing of exposure on face shape and brain morphology. (A) The left panel shows a control, whereas the two other panels show animals exposed on gestation day 7 and gestation day 8.5. The different timing produces differential effects on face and brain. (B) An illustration of how the shape analysis shown in figure 3 can be applied to the mouse images. The left panel shows the difference between an animal exposed on gestation day 7 versus a control. Red areas indicate a reduction in size. The middle panel shows gestation day 8 exposure versus control, note the absence of many red areas. The right panel shows the difference between the two exposure times. (C) Ethanol interacts synergistically with the PDGFRA gene. The two left most figures show an intact embryo and the dissected neurocranium of a stained PDGFRA heterozygote displaying normal morphology of the neurocranium. The right most panel shows how ethanol severely disrupts development of the anterior neurocranium and palate of the zebrafish. The homozygote, −/−, (not shown) is even more affected.SOURCE: Photos in A and B are courtesy of Dr. Kathleen Sulik, University of North Carolina at Chapel Hill.Photos in C are courtesy of Dr. Johann Eberhart, University of Texas at Austin.
Mentions: Developing truly accurate and specific methods for identifying individuals with FASD requires an understanding of the full spectrum of alcohol-related consequences and clarification of the various factors, both protective and permissive, that influence outcome variability. Animal models have provided information on the mechanisms by which alcohol affects facial development and the factors that may make a fetus more susceptible to these facial changes (see figure 1B and C for examples of craniofacial defects in the mouse and zebrafish). In the mouse, for example, alcohol administration on gestational day (GD) 7, equivalent to approximately week 3 postfertilization in a human pregnancy, produces a constellation of facial malformations similar to those seen in FAS. Defects include severe midfacial hypoplasia, shortening of the palpebral fissures, an elongated upper lip, and deficient philtrum (Godin et al. 2010). However, alcohol exposure delayed a day and a half to GD 8.5 produces a distinctly different pattern of malformations, with mild hypoplasia and shortening of the palpebral fissures and upper lip but a preserved philtrum (Lipinski et al. 2012) (see figure 4A and B). These data suggest that maternal alcohol consumption, even before many women are aware that they are pregnant, can cause significant and selective facial alterations in their offspring. The distinctive facial phenotype of FAS depends on the timing of exposure, and other facial characteristics resulting from alcohol exposure during different critical periods are possible.

Bottom Line: Diagnosing FASD continues to be a challenge, but advances are being made at both basic science and clinical levels.However, combining interventions may prove more efficacious.Ultimately, advances in basic and clinical sciences may translate to clinical care, improving both diagnosis and treatment.

View Article: PubMed Central - PubMed

Affiliation: Center for Behavioral Teratology, San Diego State University, San Diego, California.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus