A jump back in history gives us the following information: Alcohol was tagged as a teratogen in the 19th century. Pediatrician Paul Lemoine published a study in a French medical journal in 1968, describing distinctive features of children born to alcoholic mothers. In 1973, Dr Jones Kenneth Lyon labeled the dysmorphologic features seen in offsprings of alcoholic mothers as Fetal Alcohol Syndrome.Confirmation of alcohol as a teratogen was in 1978 following many animal studies.

Despite the well-documented teratogenic effects of alcohol, the incidence of fetal alcohol syndrome around the world is at a rate of 40-46 per 1000 births in South-Africa, 0.8 per 1000 births in Europe and 1 to 2 per 1000 births in the USA.

Mechanism:
a) Alcohol causes cells death by necrosis and apoptosis in the developing embryo and fetus. A more rapid cell death is experienced by the cells in the CNS as they have a lower threshold for alcohol.That is why some individuals may have significant CNS damage due to PAE but may not exhibit the facial characteristics of FAS. Oxidative stress is another contributing factor to Fetal Alcohol Syndrome. It occurs due to a combination of increased free-radical production and decreased free-radical elimination and these lead to mitochondrial dysfunction, cell damage and cell death.
b) Another adverse effect of alcohol is its ability to interfere with growth factors necessary for normal CNS development. Alcohol affects the IGF receptor site on neurons thus preventing cell division.
c) Alcohol also appears to affect the neurotransmitters serotonin and glutamate, which are important for fetal brain development.Without serotonin, growth-factor-releasing astrocytes are not stimulated and normal brain development does not occur. Glutamate being an excitatory neurotransmitter interacts with several receptors (one of them is N-methyl-D-asparate, NMDA) to control brain function. Alcohol exposure reduces the number and functionality of the NMDA receptors.
d) Glucose metabolism is imperative to brain development and growth. Alcohol exposure of the fetal cells affects glucose uptake, by decreasing the glucose transporter protein, GLUT 1, found in brain. This reduction in glucose uptake is a major contributor to CNS deficiencies.

Adverse effects in offspring:
1) increase in externalizing and aggressive behaviors;
2) delayed visual-perceptive ability, hyperactivity and distractibility,
3) teenagers with FASD have behavioral problems, decreased social competence, poor school performance, and display social and interpersonal relationship skills equivalent to a normal 6 year old child, independent of IQ.
4) children prenatally exposed to alcohol have an increased incidence of bacterial infections, such as meningitis, pneumonia, otitis media, gastroenteritis, and sepsis, as well as urinary tract and upper respiratory tract infection.

Researchers have evaluated a number of therapies for the prevention of alcohol-induced damage in model systems:
I) One of them being Nicotinamide. They used a dose of ethanol that achieved extremely high blood levels, and that were maintained for more than 12 hours, and yet they were able to reverse the neurobiological effects of ethanol. This study brings hope as nicotinamide is not regarded as a teratogenic substance and thus can be used in the treatment and prevention of the devastating sequelae of FAS.
II) Another study demonstrated that direct pharmacological blockade of TASK-1 and TASK-3 channels protects the most sensitive target of fetal alcohol exposure, cerebellar Purkinje cells.

What is new in this field of research? It is the study of the biomarkers.
What is needed in the future? A concrete association between a specific dose or threshold dose for prenatal alcohol use and its outcomes.

Thank you.