Fetal Alcohol Spectrum Disorders Exam 1 Study Guide

Etiology of fetal alcohol spectrum disorders

• Caused by alcohol consumption during pregnancy

  • FAS (most severe condition)

  • Alcohol related birth disorder (ARBD)

  • Alcohol related neurodevelopmental disorder (ARND)

  • Neurodevelopmental disorder - prenatal alcohol exposure (ND-PAE)

FAS/FASD identification, diagnosis, and prevention

• identification

  • Facial features, physical abnormalities, growth retardation, CNS damages, and prenatal alcohol exposure

• Diagnosis

  • Facial dysmorphia: smooth philtrum, thin vermillion, small palpebral fissures

  • Growth problems or deficits: height or weight at or below the 10th percentile

  • CNS abnormalities: corpus callosum, cerebellum, basal ganglia, areas surrounding the inter-hemispheric fissure

  • Other possible associated physical features: limb abnormalities, crease differences in hands, cardia conditions, small genitalia, ocular problems, skeletal problems (small stature), auditory and sensory processing problems

• Issues with getting diagnosed

  • Discovering mothers use of alcohol during pregnancy 

  • Many receive misdiagnosis of ADHD 

  • Getting child needed services often results in receiving diagnoses other than FASD

• Prevention

  • No safe amount of alcohol to drink while pregnant so the best prevention technique is not drinking any alcohol

causes of FAS/FASD

Prenatal alcohol exposure 

consumption of alcohol 

• in 1999 - 12.8% of women continued to drink throughout pregnancy

• 3.3% were frequent drinkers, consuming more than 7 drinks/week

• 2.7% were binge drinkers, consuming more than 4 drinks in one occasion

• In 2019 it was reported that 1 in 9 women continue to drink after pregnancy confirmation

• 3 years later (2022), even more women (1 in 7) continue to drink after pregnancy confirmation

• From 2018-2020

  • 1 in 7 pregnant people in US reported drinking alcohol

  • 1 in 20 pregnant people reported binge drinking 

Differences between FASD and other birth disorders

• conditions similar to FASD

  • ELN deletion or Williams syndrome, Q22 deletion or velocardiofacial syndrome, PTPN deletion or Noonan syndrome, delange syndrome, dubowits syndrome, maternal PKU embryopathy, maternal toluene embryopathy 

costs of FAS/FASD

• estimated cost of $860,000/child in health costs, and $200,000/child in lost potential wages

  • Does not include long term services such as special education, foster care or incarceration

• Difficult to fully understand the true costs of this condition 

• Annual costs associated with FASDs in the US are estimated to be approx $5 billion 

• Estimated lifetime cost for one individual with an FASD is $1.5 million

Addiction and causes

• addiction: a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences

• Causes

  • To feel good, to feel better, to perform better, curiosity

  • Biological or genetic makeup factors

    • Stage of development and other medical conditions, such as mental disorders

    • Gender or ethnicity

  • Environmental factors

    • Parental use of alcohol or drugs, early use of drugs, access to or availability of drugs, drug experimentation, lack of paternal supervision/involvement, poor social skills/peer influences, community poverty, smoking a drug versus injection

Why drugs are so addictive

• drugs target the reward system of the brain with an overdose of dopamine

• Dopamine is the body’s natural chemical transmitter and regulates movement, emotion, motivation, and feelings of pleasure

• Flooding the body with dopamine (induced by drugs) results in euphoria and teaches the user to repeat 

• We are hard wired to repeat activities that are associated with pleasure or reward 

• The effects of that much dopamine in the body can last much longer than the “normal” reward systems & this results in motivating people to take the drugs again and again

Human brain and functions

• brain stem: controls based functions critical to life, such as heart rate, breathing, and sleeping

• The cerebral cortex: different areas process info from our senses, enabling us to see, feel, hear, and taste. The frontal cortex or forebrain is the thinking center; powers our ability to think, plan, solve problems, and make decisions

• Limbic system: brains reward circuit, controls and regulates our ability to feel pleasure; motivates us to repeat behaviors. Responsible for our perception of other emotions, both positive and negative, which explains the mood altering properties of many drugs

• Communication occurs:

  • Neuron to neuron: brain nerve cell sends and receives messages from other nerve cells

  • Neurotransmitters: message of the brain transmitted via chemical called neurotransmitters

  • Receptors: the chemical receivers of the brain

  • Transmitters: the brains chemical recyclers

Effects of drug use on the developing brain

• Babies: can be born premature, underweight, and have withdrawal symptoms at birth, in addition to poor intellectual development and behavior issues later in life

• Adolescents: poor academic performance, often drop out of school, and may become at risk for unplanned pregnancies, violence, and infectious diseases 

• Adults: problems thinking clearly, remembering and paying attention, in addition to having poor social skills, poor work performance, and poor relationships with families and others

• alcohol use during pregnancy can significantly alter the brain formation & development of the growing fetus

  • Cerebral cortex: responsible for higher brain function, problem solving, decision makink

  • Hippocampus: important for memory and learning

  • Cerebellum: important for movement coordination

• Early drug use (adolescent years) increases the likelihood of developing a serious drug problem

• Prefrontal cortex of the brain continues to mature well into the mid-20s

• Use of drugs during the adolescent period puts them at much higher risk for potentially profound & long lasting developmental consequences 

• Marijuana use during pregnancy can affect the developing fetus 

changes in brain function that are caused by the abuse of drugs

• brain response to the flood of dopamine is to reduce the “normal” production of dopamine or reduce the number of receptors that can receive signals

• People who abuse drugs begin to feel flat, lifeless, and depressed and lose the ability to enjoy the things that previously were pleasurable 

• Larger amounts of the drug are needed to produce what has become for them the familiar dopamine high - and this is known as tolerance 

research based programs impacting elimination or reduction of drug use among youth and young adults 

• combination of medical treatment with behavioral therapy is the most effective method of success

• Medications

  • To stop abusing drugs: meds needed to treat depression, anxiety as well as restlessness and sleepiness

  • To stay in treatment: meds are used to help the brain get used to the absence of the abused drugs

  • To prevent relapse: stress, cues to drug experience & exposure to drugs act as cues or triggers to want to use/abuse dugs again. Meds are used to interfere with these triggers

• Behavioral therapies 

  • Cognitive behavioral therapy: seeks to help patients recognize, avoid, and cope with situation in which they are most likely to abuse drugs

  • Motivational incentives: uses positive reinforcement such as providing rewards or privileges for remaining drug free, for attending and participating in counseling session, or for taking treatment medications as prescribed

  • Motivational interviewing: employs strategies to evoke rapid and internally motivated behavior change to stop drug use and facilitate treatment entry 

  • Group therapy: helps patients face their drug abuse realistically, come to terms with its harmful consequences, and boost their motivation to stay drug free. Patients learn effective ways to solve their emotional and interpersonal problems without resorting to drugs

  • Pharmacotherapy

  • Screening and brief intervention

  • 12 step facilitation (alcoholics anonymous)

purpose and impact of treatment programs for drug and alcohol use dependence

• addiction is treatable and can be managed successfully

• Relapse is common and expected due to the nature of addiction and its similarity to any chronic disease (diabetes, hypertension, asthma) 

• Long and complex process

• Person has to recover from the drugs impact on the brain as well as the impact on the persons day to day life

• Treatment must address the whole person

Basic underlying cause of alcohol use 

• immediate change in how they feel, genetics, and gene-environment interactions

• Interactions between alcohol use, genetic vulnerability, and particular environmental circumstances appear to determine eventual use

Health problems associated with risk and excessive alcohol use

• fetal alcohol spectrum disorders, hypertension, cardiovascular diseases, stroke, liver cirrhosis, several types of cancer and infections, type 2 diabetes, and various injuries 

• Typically, drug users have at least one or more medical issues

• Tobacco smoke causes cancers of the mouth, throat, larynx, blood, lungs, stomach, pancreas, kidney, bladder, & cervix

• Some drugs can damage or destroy nerve cells in the brain or in the peripheral nervous system

• Drug misuse and mental health disorders often co-exist 

  • Some mental health conditions precede drug use such as anxiety, depression, or schizophrenia

  • Other MHC are triggered or made worse by drug misuse & include ADHD, bipolar disorder, psychotic illness, borderline personality disorder, and antisocial personality disorder

ways alcohol impacts women differently from men

• women have lower body weight, smaller liver capacity to metabolize alcohol, and higher proportion of body fat

• Larger percentage of ingested alcohol reaches the blood and higher blood alcohol concentration levels for women

• Women progress quicker than men from first use to alcohol related problems and addiction

• Women absorb and metabolize alcohol differently than men sue to a lower level of the alcohol metabolizing enzyme alcohol dehydrogenase (ADH) in the stomach

• More likely to: die prematurely, experience serious cardiovascular disease, develop fatty liver, alcoholic hepatitis and cirrhosis, have hypertension, impaired immune function, and metabolic disturbances, show brain abnormalities and psychiatric disorders, gain weight and have nutrition disturbances, be diagnosed with diabetes, be affected by osteoporosis, and develop certain types of cancers (breast, lung, upper and lower digestive, genital, and urinary), risk of FASDs and other health problems in their newborns

stigma associated with having an AUD

• higher public stigma towards alcohol & other drug users compared to those with mental illness and physical disability

• 3 types of stigma

  • Perceived stigma: awareness of public stigma associated with poorer mental & physical health and lower quality of life

  • Experienced stigma: actual occurrences of discrimination attributed to a condition

  • Self stigma: negative evaluations associated with public stigma incorporated into ones sense of self

• To avoid further stigmatization, addicts may become secretive about their use

• Many health professionals have negative attitudes toward their patients with AUDs

• Can serve as a barrier to accessing treatment and be detrimental to achieving and sustaining recovery 

• Associated with poorer mental health, higher rates of depression, lower quality of life, and poorer physical health 

• High degree of embarrassment resulting in low expectations for treatment success which discourage them from seeking services 

basic elements of alcohol screening and brief intervention

• can help someone begin to recognize potential risks associated with their alcohol use patterns

• Begins with measuring both # of drinks consumed during the course of a week and also # of drinks consumed in a 2 hour timeframe (or binge drinking)

• 6 elements characterize key ingredients of brief intervention

  • Feedback of personal risk

  • Responsibility for personal control

  • Advice to change

  • Menu of ways to reduce or stop drinking

  • Empathetic counseling style 

  • Self efficacy or optimism about cutting down or stopping drinking 

• A key distinction is motivational enhancement - relies heavily on motivational interviewing techniques

• Interviewer characteristics

  • Supportive, non-judgmental techniques, focus on reducing alcohol use without criticism, thorough knowledge of the intervention technique, optimistic attitude about change, sincerity and respect for clients

elements of how to implement alcohol SBI in clinical settings

• important to ask about alcohol use on a regular basis

• Providers need to be comfortable in asking their patients about alcohol use 

• Need to consider levels of consumption and pattern of drinking

• Issues of under reporting of alcohol use, particularly for pregnant women

• Process begins with definition of standard drink

• Measurement of alcohol use (quantity and frequency)

  • Amount of drinking on average drinking days 

  • Average number of days on which alcohol is consumed

• Briefing screening instruments

  • DSM-5 criteria 

  • AUDIT 1-3

• Need to consider levels of understanding, terminology used, educational background, and other issues that may interfere with understanding 

special factors relating to alcohol use among women

• teens and college age women

  • Rates of alcohol use and sexual intercourse higher in early maturing girls, placing them at higher risk for adolescent pregnancies

  • Women who began drinking earlier in life are least likely to stop drinking upon becoming pregnant

• Women of childbearing age

  • Government surveys indicate that over half of non pregnant women report some alcohol use in the past 30 days

  • Increase in the % of pregnant women who report binge drinking in the past 30 days 

• Pregnant women

  • Women intending to become pregnant more likely than pregnant women to drink any amount of alcohol and to binge drinking 

  • Risky drinking has not decreased despite robust findings that prenatal drinking can affect fetal growth and child development 

  • PSAs have not changed public opinion, so its important to obtain accurate info regarding alcohol use during the preconception pregnancy

  • Nursing mothers: alcohol in mothers milk affects infant sleep-wake patterns and might also affect the child’s future reposes to alcohol 

Special factors relating to alcohol use among women cont

• race, ethnicity, and culture

  • Upon pregnancy recognition, white women are more likely to quit or reduce their drinking 

  • Asian American women more likely to abstain or consume less alcohol, possibly due to facial flushing while drinking

  • High rates of alcohol use and misuse among Native American populations 

• Socioeconomic status

  • Men and women in lower SES were more likely to abstain from alcohol and less likely to consume heavy amount of alcohol 

  • Those amongst the lowest SES position consumed alcohol even less

• Genetic influences

  • Genetic variation in ethanol metabolism

  • Women with ADH2*2 and the ADH2*3 alleles are less likely to become alcohol dependent

  • Women with these alleles metabolize alcohol more quickly and efficiently and expose the fetus to lower blood alcohol concentrations

• Depression

  • Evidence of link between alcohol use disorders and major depression

  • Presence of either condition doubles the risk of the other

  • Postpartum mothers who drink at risky levels respond well to the brief alcohol intervention 

    • The BI reduced both alcohol consumption & symptoms of postpartum depression

Alcohol metabolism (maternal & fetal)

• maternal

  • Liver, MEOS

• Fetal

  • Diffusion back to the mother

  • The placenta does not metabolize ethanol well; the capacity for ethanol metabolism by the embryo/fetus increases with gestational age

  • An embryo or early fetus lacks the enzymes for metabolism, thus the mother must metabolize most of the alcohol. Removal of the alcohol in the embryo/fetus occurs by simple diffusion back to the mother

  • Embryonic alcohol levels might be higher in the embryo than in the mother and be present for a more prolonged, variable time due to limited embryonic metabolism

Pharmacology (absorption, distribution, metabolism and elimination)

• absorption

  • Woman takes a drink, alcohol introduced into the stomach, the absorption/metabolism of the molecule (C2H5OH) occurs rapidly

  • Peak BAC is attained approx one hour after consumption

  • Women attain consistently higher blood ethanol concentrations than men following equivalent amounts of ethanol consumption

    • Smaller body water

    • Higher rate of alcohol absorption from the stomach

  • Distribution 

    • Compartmentalization

      • Because of alcohols rapid solubility in water, it can easily cross cell membranes into the cell (which is 98% water)

      • Alcohol is less soluble into lipids and compartments with substantial lipids 

    • Placental effects and fetal distribution

      • The placenta acts as a selective barrier

      • Alcohol is easily passed by diffusion from the maternal blood into the fetal blood

  • Metabolism and elimination

    • Alcohol is metabolized by enzymes as it is available by concentration

    • Most ethanol is metabolized in the liver via three pathways

      • Alcohol dehydrogenase (ADH)

      • Microsomal ethanol oxidizing system (MEOS)

      • Catalase (peroxisomal)

Birth defects associated with alcohol use

• result in morphological and functional changes to the brain

• Significant abnormalities in the cerebral cortex (no area of the brain is resistant to the effects of fetal alcohol exposure)

• Significant changes in the corpus callosum which is the major connecting pathway between the 2 halves of the cerebral cortex

• Alterations in brain structure may influence facial features, thus facial image analysis has been used to automate FAS diagnosis

• Craniofacial malformations

  • Short palpebral fissures

  • Smooth philtrum

  • Hypoplastic midface 

• Brain regions affected

  • The cerebral cortex

  • The hippocampus and cerebellum

  • The corpus callosum

Alcohol induced injuries on developing organ systems

• The loss or damage of even a few cells might result in global changes in the development of organs at a later phase

• nervous system (including eyes and ears)

  • Cognitive and/or behavioral impairments, problems with language and/or memory, difficulty with visual-spatial learning, attention disorders, reduced reaction times, and deficits in functioning, such as planning and organizing

• Myelination and synapse formation continue through the first year of life

  • Alcohol exposure can interfere with myelination resulting in alterations in motor movements

• Alcohol exposure during lactating

  • Damage to the nutritional intake

  • Effective suckling and nursing is reduced

  • Because of depressant effect, they nurse less effectively and sometimes fall asleep

Cellular responses to alcohol exposure

• neurogenesis

  • Neuron generation occurs rapidly in the developing embryo and fetus

  • Alcohol exposure during this process affects cell numbers, which might result in cognitive and behavioral deficits

• Growth and differentiation of neurons

  • Newly formed neurons undergo maturation or differentiation

    • Associated with differentiation is the genetic expression of appropriate neurotransmitters for synaptic function, growth, and migration of the processes (neurites) to their respective locations and migration of the cell to its appropriate location (brain nuclei) 

  • Each of these processes is vulnerable to the effects of ethanol exposure

• Migration

  • Cellular migration, and migration of the cell process, occurs to form nerve pathways

  • Migration of the processes occurs using molecules in the membrane that follow substrates in the tissue are supported by chemicals - nerve growth factors

  • Neurites are guided to their destinations following chemical substrates for which the neurites have an affinity 

  • Subsequent neurites follow using cell adhesion molecules (CAM) to co-locate to the appropriate destination forming a “nerve” 

• Synaptogenesis 

  • Once at its destination, the neurite must form a synapse

  • The connection between two nerves, or between nerve and another cell, allows communication between the nerves (or nerve and cell). This is a critical junction at which various components must be present for proper operation

  • Alcohol exposure during this period might disturb the mechanisms on which synaptogenesis depends

• Apoptosis

  • Refers to the process of programmed cell death

  • Alcohol exposure might enhance or modify apoptosis, resulting in more extensive cell death than what was biologically programmed

• Plasticity 

  • Refers to a nerve cell’s ability to grow back and re-establish meaningful connections after it is damaged, such as by trauma

  • Once maturation occurs, most neurons are post-mitotically static and less able to regenerate their function

  • Alcohol exposure during development seems to decrease the ability of the nervous system to regenerate 

putative biomedical mechanisms 

• neuromorphological effects

  • Cellular effects

    • Mechanisms such as neurogenesis, etc.

    • Membrane effects

  • Metabolic factors

    • Growth factors & adhesion molecules

    • Free radical generation

  • Gene expression

    • DNA/RNA regulation

• Alcohol has the following effects:

  • Alters neurogenesis and migration of neurons, by various mechanisms, including interruption of mitosis, alteration of glial proteins serving as guiding factors, and inhibition of trophic factors that provide substrates to migrating processes

  • Increases neuronal cell death and/or apoptosis by either the deleterious toxic effects of ethanol directly on the cell, or through programmed cell death

  • Alters dendritic growth, resulting in losses of functionality

  • Changes glial fibrillary acidic protein expression

  • Alters microvascular development, resulting in localized cellular loss

  • Decreases protein synthesis, causing a reduction in cell function

  • Enhances free radical toxicity, causing premature death of cells

  • Impairs DNA methylation, resulting in alteration of transcription in preparation for RNA expression

  • Alters mRNA translation of protein synthesis

  • Induces hypoxia and/or ischemia

Putative biomedical mechanisms cont. 

• effects of alcohol exposure during development on neurotransmitter receptors

  • Up-regulation (increased sensitivity) of NMDA receptors 

  • Altered GABA-mediated neurotransmisson

  • Excess nitric oxide (NO) formation leading to glutamate-mediated cell death

  • Specific apoptotic cell death in NMDA and GABA receptor systems

  • Abnormal serotonergic and/or catecholaminergic system development 

markers for susceptibility for FASD

• the ADH2*3 allele of the ADH gene, was demonstrated to protect against the adverse prenatal effects of alcohol among African Americans

  • Believed to be associated with rapid metabolism of alcohol to acetyaldehyde

  • Studies have found that women who lack this allele tend to report drinking more alcohol at the time of conception, twice as much overall, and almost twice as much per occasion than those who had the allele

• Genetic and epigenetic factors, in combination with the timing and amount of prenatal alcohol exposure

• Both the fetal and the maternal genome play a role in the susceptibility

• Many maternal nutritional factors have been suggested to play a role in the occurrence and severity

  • Overall protein calorie intake, zinc deficiency, cholesterol, vitamins, iron, and choline

• Prenatal alcohol exposure has been shown to alter multiple epigenetic processes, including DNA methylation, histone modifications, and ncRNA regulation

• Alcohol is a teratogen because it can cause structural or functional birth defects in a developing fetus