Fetal Alcohol Syndrome

Fetal Alcohol syndrome (FAS) is a disorder characterised by ethanol mediated interference of embryonic development leading to a wide range of physical and mental abnormalities. The introduction of ethanol in utero is believed to interfere with the embryo’s critical periods. Although the teratogenic mechanism of ethanol is not fully understood, it is suspected that there are both genetic and environmental factors that influence the incidence of FAS.[1] Current diagnosis of the condition relies on the detection of craniofacial dysmorphia and fatty acid ethyl esters.[2] Research into this disorder is providing greater insight into possible genetic and molecular biomarkers, molecular and neuronal mechanisms, structural abnormalities in the brain, detailed cognitive and behavioural characteristics, treatments and preventative measures.

Bibliography
1. Ismail, S., Buckley, S., Budacki, R., Jabbar, A., & Gallicano, G.I. (2010). Screening. Diagnosing and Prevention of Fetal Alcohol Syndrome: Is This Syndrome Treatable? Dev Neurosci, 32, 91-100
2. Pruett, D., Hubbard Waterman, E., Caughey, A.B. (2013). Fetal Alcohol Exposure: Consequences, Diagnosis, and Treatment. Obstetrical and Gynecological survey, 68(1), 62-69


Diagnosis

main article: Diagnosis
author: Jacky Ng

Cranial Facial Diagnostic test for FASD
Diagnostic test for FAS performed by Dr. David Wargowski MD
from The University of Wisconsin School of Medicine and Public Health

In order for an individual to be diagnosed with fetal alcohol syndrome (FAS), they must exhibit all of the four cardinal symptoms. These symptoms include the consumption of alcohol of the mother during pregnancy, deformities in facial structures, growth deficits and abnormal development of the central nervous system.[1]

The early diagnosis of FAS is important in implementing possible treatments and preventative measures that may inhibit the adverse effects of intrauterine consumption of ethanol. Although there are substantial advantages in early FAS detection, there are currently no definitive diagnostic techniques which can be implemented.[1] Current diagnosis of FAS relies mainly on post-natal examinations as well as testimonies of the mother, which can be altered through social desirability and recall bias.[1],[2] Researchers have been searching for a consistent assessment of FAS by investigating genetic prevalence, detectable changes in gene expression and molecular mechanisms associated with the disorder.

Bibliography
1. Pruett, D., Hubbard Waterman, E., Caughey, A.B. (2013). Fetal Alcohol Exposure: Consequences, Diagnosis, and Treatment. Obstetrical and Gynecological survey, 68(1), 62-69
2. Landgraf, M.N., Nothacker, M., Kopp, I.B., & Heinen, F. (2013). The Diagnosis of Fetal Alcohol syndrome. Dtsch Arztebl Int, 110(42), 703-10


Functional Deficits Often Observed in Fetal Alcohol Syndrome

main article: Functional Deficits Often Observed in Fetal Alcohol Syndrome
author: Yukiko Mihashi
Individuals with fetal alcohol syndrome exhibit a multitude of cognitive, behavioural, and social deficits[1,2]. Many of these impairments can be intuitively related to the structural abnormalties, and are probably functional correlates to them to a certain extent.

Bibliography
1. Mattson, S.N., Crocker, N., & Nguyen, T.T. Fetal alcohol spectrum disorders: Neuropsychological and behavioral features. Neuropsychology Review 2011; 21(1): 81-101.
2. Kully-Martens, K., Denys, K., Treit, S., Tamana, S., & Rasmussen, C. A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: Profiles, mechanisms, and interventions. Alcoholism: Clinical and Experimental Research 2011; 36(4): 568-576.


Neural Mechanisms

main article: Neural Mechanisms
author: Cheryl Tsui

Living with FAS

The fetal brain is most susceptible to the neurotoxic effects of ethanol during the third-trimester synaptogenesis, which is also known as the “brain growth spurt”[1]. Although the placenta is supposed to act as a barrier against certain substances for the protection of the fetus, it exceptionally allows the crossing of ethanol[2][3]. As the development of the fetus has yet to reach the stage at which ethanol detoxicating agents, such as ADH enzymes are expressed within the liver, the fetus will be subjected to lengthy intrauterine exposure to ethanol should the mother chooses to consume alcohol[3].

Growing evidence suggests that ephemeral exposure of the developing brain to ethanol potentially induces detrimental apoptosis of neurons, and thus dysmorphogenic anomalies and neurobehavioral dysfunctions observed in Fetal Alcohol Syndrome (FAS)[4]. Apoptotic neurodegeneration is widely distributed among the general brain mass, including the auditory and visual cortices[5]; it is however specifically localized at the cerebellum and hippocampus. The thorough destruction of neuronal and synaptic circuits therefore results in the interference of not only the integration of sensory information, but also fundamental behaviors and functions, such as memory and motor skills[4]. Despite the extensive research conducted on FAS, no candidate neuronal or biochemical pathway can be designated as the definitive mechanism underlying its development. Nevertheless, animal models, especially rat and mice models, have provided critical and fairly compelling clues as to how ethanol stimulates apoptosis and the impairment of synaptic plasticity[1][4]. It is essential to have continuous investigation on the neurodegenerative aspect of FAS, as further research may provide valuable insight on targeting specific molecular pathways for developing potential therapeutic strategies and treatments that are lacking today.

Bibliography
1. Medina, A.E. (2011). Fetal Alcohol Spectrum Disorders and abnormal neuronal plasticity. Neuroscientist, 17(3): 274-87.
2. Nava-Ocampo, A.A., Velazquez-Armenta, Y., Brien, J.F., & Koren, G. (2004). Elimination kinetics of ethanol in pregnant women. Reproductive Toxicology, 18: 613-7.
3. Zelner, I., & Koren, G. (2013). Pharmacokinetics of ethanol in the maternal-fetal unit. J Popul Ther Clin Pharmacol, 20(3): e259-65.
4. Ikonomidou, C., Bittigau, P., Ishimaru, M.J., Wozniak, D.F., Koch, C., Genz, K.,…Olney, J.W. (2000). Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science, 287: 1056-60.
5. Olney, J.W. (2004). Fetal alcohol syndrome at the cellular level. Addiction Biology, 9: 137-49.


Structural Brain Abnormalities

main article: Structural Brain Abnormalities
author: Yukiko Mihashi

Microcephaly in the FAS affected brain
Image Unavailable
FAS brain on right, compared to healthy brain on left
(from moondragon.org)

The fetal alcohol syndrome (FAS) affected brain shows a wide range of structural abnormalities. Most areas of the brain seem to be affected, including the cerebral cortex, subcortical white and gray matters, and the cerebellum[1]. Most of these structural changes seem to be a reduction in size or thickness, which is intuitive given the overall reduction in size of the FAS brain[1]. However, increased densities and shape variations are also observed[1].

Bibliography
1. Nunez, S.C., Rousette, F., & Sowell, E.R. Structural and Functional Brain Abnormalities in Fetal Alcohol Syndrome. Alcohol Research and Health 2011; 34(1): 121-131.


Treatment and Prevention of FAS

main article: Treatment and Prevention of FAS
author: Niroshan Jeyarajah
Due to the nature of FAS and the damage it inflicts to the Central Nervous System, it creates a permanent disability. Though there are measures of treatment available, there is no cure, nor does any single treatment work for everyone.[2] The treatment for FAS may occur prenatally or after the birth of the child. When providing treatment during in utero stages, it gives the opportunity to prevent, slow or reverse the damages that are associated with alcohol during the prenatal period. In order to provide treatment in prenatal stage, early recognition of alcohol exposure to the fetus is crucial.[3]

Alcohol is known to cause neurodegeneration in rat brain. It has the same effect as gamma-aminobutyric acid (GABA) specific agonists. The consumption of alcohol does not fully explain FAS. Factors such as malnutrition alongside exposure to alcohol increases susceptibility to FAS. It has been illustrated that 40% of infants born to mothers of the lower socioeconomic status were diagnosed with FAS compared to 2.7% of infants born to middle class alcoholics. Individuals that are living under poverty lines are at greater risk of developing micronutrients and macronutrients deficiencies. Health authorities have determined that alcoholism and malnutrition have a contributing factor to folic and cholic deficiencies. [1] Proteins, certain types of fats, iron, zinc, iodine, vitamin A, and choline are significant in fetal development especially with regards to brain and neurobehavioural functions.[2]

Bibliography
1. Ballard, M. S., Sun, M., & Ko, J. (2012). Vitamin A, folate, and choline as a possible preventive intervention to fetal alcohol syndrome. Medical hypotheses, 78(4), 489-493.
2. DeRegnier, R. A., & Desai, S. (2010). Fetal development. Wiley-Blackwell Handbook of Infant Development, 2 (2nd edition).
3. Pruett, D., Hubbard Waterman, E., Caughey, A.B. (2013) Fetal Alcohol Exposure: Consequences, Diagnosis, and Treatment. Obstetrical and Gynecological survey. 68(1): 62-69.



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