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Competency I : History and Foundations in FAS

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1 Competency I : History and Foundations in FAS

2 “Those who cannot learn from history are doomed to repeat it”
- George Santayana

3 Alcohol is the oldest recorded and most widely used drug in the world.
Alcohol use in pregnancy has been considered a risk since at least 300 B.C. A wedding ritual forbade drinking of wine by the bridal couple so that a defective child would not be conceived (Ancient Carthage) It is in the Bible and Talmud

4 Behold, thou shall conceive and bear a son: and now drink no wine or strong drink Judges 13:4

5 Alcohol should be barred “to any man or woman who was intending to create children. Children should not be made in bodies saturated with drunkenness”. (Plato) “Parental drinking is a cause of weak, feeble, and distempered children” (College of Physicians to the British Parliament 1726) The Gin epidemic of raised concerns that maternal alcohol consumption produce weak and ill-tempered children. Sir Francis Bacon spoke of the dangers of alcohol and the need for a good diet Gin epidemic: death rate decreased; infant mortality increased, supposedly due to the distillation process Hogarth’s “Gin Lane” is a classic painting

6 Gin Lane - Hogarth Medical historians have searched for evidence that the characteristics of fetal alcohol syndrome (FAS) were recognized long before its modern description in This search has often focused on the ‘gin epidemic’ in 18th century London, and especially William Hogarth's Gin Lane, which some authors allege reflects an awareness of the facial characteristics of the syndrome. While the ‘gin epidemic’ undoubtedly resulted in the increased birth of weak and sickly children, claims about Hogarth's awareness of the stigmata of the FAS are unfounded. The birth of weak and sickly children, and the high infant mortality rates associated with this period, long preceded the ‘gin epidemic’ and were primarily due to disease, starvation, exposure, and deliberate infanticide.

7 First scientific study on fetal effects: Sullivan in 1899 who found women who drank had a 56% increase in stillbirths and infant death 2 ½ times higher than those did not drink. In 1942, after prohibition, a paper was published with the erroneous information that the fetus was protected in the womb. In late 1960s, Dr. C Ulleland noted failure to thrive in infants whose mothers consumed alcohol, during pregnancy, in spite of healthy post natal environment. Dr. Ulleland was the first modern Doc to discuss link between prenatal exposure and adverse effects

8 Modern concept of FAS was first identified in 1968 by the French (Lemoine et al).
The term FAS was coined by Smith and Jones in the U.S. in 1973 to describe a constellation of characteristics noted in children examined by Dr. Ulleland. In 1989, “The Broken Cord,” by Michael Dorris is published, a personal account by an adoptive father, was published. In 2000, Linda Belle LaFever wrote a first hand account of her child with FAS and her struggle with alcoholism in “ Cheers! Here’s To The Baby”

9 Epidemiology

10 Alcohol problems are increasing in adolescent girls and older women % of women age yrs used alcohol in the last month; 10.6% of them binged (FASD Center of Excellence,2004) Women have a greater mortality rate and greater sensitivity to effects of alcohol than men. Up to 80% of women with a substance abuse problem also have some form of psychiatric co-morbidity. In US alcohol use is as follows: highest –Caucasian, then African American, then Latinas, then Asians. Latinas are increasing rapidly in alcohol use Women are more likely to die or have complicaitons from alcohol use Women are less likely to be ID’d by health care provider NIDA study: 18.8% of women use alcohol and 20.4% use tobacco

11 From , CDC reported a 4-fold increase in frequent(7+ drinks per week) and binge(5+ on one occasion) drinking during pregnancy. 9-12% of pregnant women in US report consuming alcohol and 3% report drinking at levels that have consistently been associated with adverse effects on the fetus CDC. 2005). More than half of all women of childbearing age (18-44) report alcohol use; 1 in 8 report binge drinking within the last month. Binge drinking in young females is rising 15% of pregnant women drank in the last month (CDC,2005) 50 % of pregnancies are unplanned

12 Birth defects due to prenatal alcohol use can occur in the first 3-8 weeks of pregnancy, before most women know they are pregnant.

13 Animal Models and Prenatal Alcohol
Many studies cannot be done on humans Confounding factors can rarely be controlled in human studies Alcohol is rarely the only drug used Many abnormalities occur at low rates Epidemiological studies are time consuming and expensive Background Much of what we know about FAS and the effects of prenatal alcohol exposure is the result of work on animal models. After FAS was identified it became important to demonstrate that the effects were indeed the result of alcohol exposure and not due to factors such as other drugs, maternal conditions, or nutritional variables. The development of appropriate animal models was very important in this regard. Models were developed for assessing physical features of FAS as well as the behavioral, neuroanatomical, and neurochemical profiles of prenatal alcohol exposure. The ideal test animal would absorb, metabolize and eliminate alcohol similar to human, transport alcohol and metabolites across placenta similar to human, have embryos and fetuses with developmental and metabolic patterns similar to that of human, be easily bred with large litters and a short gestation length, be inexpensive to maintain under laboratory conditions, and importantly not bite, scratch, kick, howl or squeal. No one animal meets all these requirements and the vast amount of work has been done in rodents (e.g. rats and mice). However, models have been developed in primates, sheep, pigs, and dogs. There is a continued need for animal research to answer questions that simply cannot be answered in humans: including the identification of risk factors, the elucidations of mechanisms by which alcohol damages the brain, and brain behavior relationships. One can also mention the important reasons for conducting animal research and why it is done. Besides the ones listed on the slide the following factors could also be mentioned. We can assess mechanisms to help us understanding how alcohol does damage which might lead to ways to prevent or remediate this damage. We can also study genetic factors with the large number of selected lines or strains that are available. We can examine physiological outcomes not readily available for study in humans (e.g. anatomical or neurochemical changes). Finally, since the availability of FAS subjects for research is limited, these animal studies can act as a guide for studies on humans.

14 Animal Models – The Comparability of Effects
Growth retardation Facial characteristics Heart, skeletal defects Microcephaly Reductions in basal ganglia and cerebellar volumes Corpus callosum anomalies Hyperactivity, attentional problems Inhibitory deficits Impaired learning Perseveration errors Feeding difficulties Gait anomalies Hearing anomalies

15 Effects of Prenatal Exposure to Alcohol in Animals and Humans
In one study, of 72 mouse pups tested: 2 did not develop brains 30 presented with eye and oral malformations Several pups were not affected Regular use of alcohol was not necessary to alter brain development A defining feature of FAS is altered facial characteristics. These characteristics include a shortened eye openings and an altered upper lip. These features can be demonstrated across a wide range of species. The mouse pups above were exposed to alcohol on prenatal day 7, and thus a single exposure at a critical period is sufficient to produce FAS.

16 Animal Models of FAS Mice are not the only animals affected by prenatal exposure to alcohol: Note the substantial growth deficits observed in beagle pups and chicks. Overall facial features, head circumference, and size were smaller for alcohol-exposed animals. For the chicks, note malformations in the eyes and limbs.

17 Genetics May Be Involved in FAS
The fraternal twins pictured to the left are 17 months old. Identical twins are derived from a single egg, whereas fraternal twins are derived from two eggs. Thus, identical twins are more similar genetically. The child on the left is considerably more affected than his fraternal twin. Identical twins are more likely than fraternal twins to demonstrate similar FAS effects, suggesting a potential role for genetics in the expression of FAS.

18 Collaborative Initiative on Fetal Alcohol Spectrum Disorders (NIAAA)
FAS is the leading preventable cause of MR and DDs U.S.: 0.5-2/ Floyd, 2006 S. Africa: / Viljoen, 9/2005 Italy: / May, 9/2006 Sweden: 1-5/ Sampson, 1997 Russia: Phenotypic survey- 13% strong, 45% intermediate Miller, 2006 Finland: Dysmorphology in older Autti-Ramo, 2006 children The Challenge before the community today is to take a proactive, prevention oriented approach to issues relating to reproductive health. Faith-based organizations and other community groups can play an integral role in informing women and men of the dangers to the unborn child that consuming alcohol during pregnancy can cause. CIFASD is sponsored by NIAAA, has multiple arms.

19 Challenges in determining accurate prevalence:
No uniform, widely accepted diagnostic criteria (IOM, CDC, Seattle) FAS diagnosis is based on clinical examination of features, but not all children with FAS look or act the same Lack of knowledge and misconceptions among primary care providers.

20 Incidence Rates

21 An individual with FAS can incur a lifetime health cost of over $800,000 - $1.2 mil.
In 1998, the annual cost of FAS in the United States was estimated at $2.8 billion. In 2003, the estimated cost was $5.4 billion; direct costs were $3.9 billion and indirect costs were another $1.5 billion. FAS and related conditions are estimated to cost between $75 million and $9.7 billion annually in the United States.

22 What is FAS? Fetal Alcohol Syndrome (FAS) is a life long birth defect caused by maternal consumption of alcohol during pregnancy. Dad: sperm is off: quality, quantity, motility; milieu of drinking

23 FAS Diagnostic Criteria
Growth Restriction: Babies are born smaller than anticipated for the gestational age at birth, and usually remain so throughout life. Central Nervous System: Any or all of the following conditions may be present- mental retardation, developmental delays, short attention span, impulsivity, perceptual problems, hyperactivity, poor coordination & learning disabilities. Facial Anomalies: Babies have the following distinctive facial features-small widely spaced eyes; a short, upturned nose; a smooth philtrum (no notch between the nose and lips); abnormally thin upper lip; & small flat cheeks. Children who exhibit symptoms in less than 3 areas do not meet the criteria for FAS, however these children have been effected by alcohol while in utero and are therefore included in the FASD classification.




27 FAS – Only the tip of the Iceberg
Fetal Alcohol Spectrum Disorders ( FASD) refers to the broad spectrum of disorders caused by prenatal exposure to alcohol including: FAS (Fetal Alcohol Syndrome) FAE (Fetal Alcohol Effects) ARND (Alcohol Related Neuro-developmental Disorders) ARBD (Alcohol Related Birth Defects) Background This slide illustrates an extremely important point. Fetal alcohol syndrome only represents one point on what appears to be a continuum of effects from prenatal alcohol exposure. Towards one end may be fetal death and FAS. As one moves to the other end of the continuum, one may find isolated effects resulting from prenatal alcohol: maybe only some of the facial characteristics or maybe only behavioral problems. The point is that FAS represents only a small sampling of the effects of prenatal alcohol. Many more children are included when we consider those with FAE who might or might not have obvious signs of alcohol exposure, and those that do not manifest any physical features of FAS, but have behavioral problems. FAS is only the tip of the iceberg. Interestingly only 10 – 40% of children of chronic alcohol abusers can be diagnosed as having FAS. However, there is very good data suggesting that these non-FAS children are affected, most notably behavioral and cognitive deficits. Even in children with normal IQs who have been exposed to alcohol prenatally, there is evidence that they do not live up to their true potential.

28 FASD Fetal Alcohol Spectrum Disorders is an
umbrella term describing the range of effects that can occur in an individual whose mother drank during pregnancy. These effects may include physical, mental, behavioral, and /or learning disabilities with possible lifelong implications. The term FASD is not intended for use as a clinical diagnosis. CDC July 2004


30 POLICY STATEMENTS Since 1966, AMA and APA have recognized alcoholism as disease AMA, AAP, ACOG, CDC, NIAAA, March of Dimes, and NOFAS all have policies regarding drinking during pregnancy AMA urges physicians to be alert to possible alcohol related problems in women and to screen all patients for possible alcohol abuse and dependence. Surgeon general’s warning in 1981 and 2005 “0” tolerance: No safe time, amount or alcohol If pregnant don’t drink; if drink, don’t get pregnant

31 Be good to me... Stay alcohol free!
                                                               the message is: stop, think, and don’t drink when pregnant. In conclusion, I would like to read a poem. A few drinks can Last forever   No safe time No safe amount No safe alcohol Period…. NIAAA/NOFAS

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