Running head: ALCOHOL, PREGNANCY, AND FASD
“Alcohol, Pregnancy and Fetal Alcohol Spectrum Disorders (FASD)”
Maternal-Fetal Paper
Gabriela Olivas
University of Texas Medical Branch at Galveston School of Nursing
NNP 1
GNRS 5631
Leigh Ann Cates RN, NNP-BC, RRT-NPS, PhD. & Dr. Debra Armentrout RN, NNP-BC,PhD.
March 20th, 2014
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ALCOHOL, PREGNANCY, AND FASD
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Alcohol, Pregnancy and Fetal Alcohol Spectrum Disorders
Approximately 12% of women in the United States and over 20% worldwide drink
alcohol during pregnancy (Balachova et al., 2013). Most women stop drinking or at least
decrease their alcohol consumption upon learning that they are expecting (Balachova et al.,
2013). However, approximately half of all pregnancies are unplanned, and many women are not
aware they are pregnant until four to six weeks into pregnancy and continue using alcohol at
prepregnancy levels (Balachova et al., 2013). As a result, a significant proportion of women
consume alcohol during the early stages of pregnancy prior to knowing they are pregnant;
consequently, the fetus is exposed during the most critical time of development to the
detrimental effects of alcohol. Unfortunately, studies show that alcohol exposure early in
pregnancy may affect fetal development even if followed by later gestational abstinence
(Balachova et al., 2013).
Consumption of alcohol during any gestation of pregnancy equates into alcohol fetal
consumption, which can cause detrimental physical and neurological defects, which can be lead
to any one of the array of disorders which are described as Fetal Alcohol Spectrum Disorders
[FASD] (May & Gossage, 2011). FASD is an umbrella term for a range of physical, mental,
behavioral, and learning deficits that can occur in an individual whose mother drank alcohol
during pregnancy (Martin, Fanaroff, & Walsh, 2011). The most profound effects of prenatal
alcohol exposure are on the fetus’s brain development, which includes cognitive and behavioral
effects that follow (Riley, Infante, & Warren, 2011). The incidence of FASD is believed to range
from 0.2 to 2 per 1000 live births (Douzgou et al., 2012). Alcohol yields teratogenic effects in all
the gestations, with peculiar features in relationship to the trimester of pregnancy in which the
alcohol is consumed (Paoletti et al., 2013). Because there is no exact dose-response relationship
ALCOHOL, PREGNANCY, AND FASD
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between the amount of alcohol ingested during the prenatal period and the extent of damage
caused by alcohol in the fetus, abstinence from alcohol at conception and during pregnancy is
strongly recommended (Paoletti et al., 2013).
Pathophysiology
When alcohol is consumed by a pregnant woman, it crosses the placenta and rapidly
reaches the fetus(Vaux, 2012). Infants who were exposed to alcohol in utero are at increased risk
for a range of alcohol-related damage including any of the conditions in the FASD. There have
been many studies, which have shown equivalent fetal and maternal alcohol concentrations,
suggesting an unrestrained bidirectional movement of alcohol between the two compartments
(Vaux, 2012). The fetus appears to depend on maternal hepatic detoxification because the
activity of alcohol dehydrogenase (ADH) in the fetal liver is less than 10% of that seen in the
adult liver (Vaux, 2012). In addition, the amniotic fluid acts as a reservoir for alcohol,
prolonging fetal exposure (Vaux, 2012).
The mechanism for the spectrum of adverse effects on virtually all organ systems of the
developing fetus is unknown (Vaux, 2012). Ethanol and its metabolite acetyldehydrate (the
placenta deoxidizes ethanol to this substance), can alter fetal development by disrupting cellular
differentiation and growth, disrupting DNA and protein synthesis and inhibiting cell migration
due to the fact it reaches 50% of maternal levels. (Blackburn, 2012). Both ethanol and
acetyldehydrate modify the intermediary metabolism of carbohydrates, proteins, and fats (Vaux,
2012). Both also interfere and decrease the transfer of amino acids, glucose, folic acid, zinc, and
other nutrients across the placental barrier, indirectly disrupting fetal growth due to intrauterine
nutrient deprivation (Vaux, 2012). This also interferes with the incorporation of amino acids into
ALCOHOL, PREGNANCY, AND FASD
proteins. Acetyldehydrate affects cell membranes and cell migration altering embryonic tissue
organization with dysmorphic changes (Blackburn, 2013). This may limit the number of fetal
cells and lead to fetal growth restriction (Blackburn, 2013). Decreased placental transfer of
linoleic and docosahexanoic acid may also alter fetal growth and development (Blackburn,
2013).
The differential effects may be due in part to variations in the metabolism of alcohol in
the placenta by CYP2E1 and alcohol dehydrogenase (Blackburn, 2013). Elevated levels of
erythropoietin in the cord blood of newborns exposed to alcohol are reported and suggest a state
of chronic fetal hypoxia (Vaux, 2012).
Physiologic Impact
Women who range from alcoholics to mild social drinkers can have varying
physiological effects affect their fetus’s development depending on the time of gestation and
amount of consumption during pregnancy.
First Trimester
During the first trimester of human gestation, alcohol exposure can alter the normal
development of the neural tube and crest, leading to microcephaly, hydrocephaly, ocular
malformations and facial dysmorphology that characterize fetal alcohol syndrome (Medina,
2011). Alcohol fetal exposure induces a delay in the generation of cortical neurons, with a
reduction in their number and their distribution (Paoletti et al., 2013). Because many women
drink alcohol and are unaware they are pregnant, there has been a link between cardiac defects
and alcohol consumption within the first trimester (Paoletti et al., 2013). Unfortunately, if the
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ALCOHOL, PREGNANCY, AND FASD
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woman abstains from drinking after being informed she is pregnant, it may be too late
embryologically, and the heart might not have formed correctly (Sadler & Langman, 2012).
Second Trimester
During the second trimester, alcohol exposure reduces intrauterine and postnatal growth.
In addition, it also affects the proliferation of glial and neuronal precursors, with a strong
modification in the migration of cortical neurons (Paoletti et al., 2013). These abnormalities are
likely the cause of the agenesis, or malformation of the corpus callosum, or ventriculomegaly,
and of a small cerebellum (Paoletti et al., 2013). These have all been findings noted in autopsies
of newborns exposed to alcohol in the second trimester (Paoletti et al., 2013).
Third Trimester
During the third trimester, the brain goes through a period of quick growth often called
“brain growth spurt,” and the neurons are more prone to the apoptotic effects of alcohol (Medina,
2011). Through this mechanism, there is damage to the neuronal plasticity, which is the ability of
the brain to be changed in relationship to previous experiences (Paoletti et al., 2013). During
development, neuronal plasticity plays a key role in the processes of learning and memory
(Medina, 2011). The proposed oxidative stress alcohol induced can explain the mechanism
through which alcohol can exert harmful teratogenic effects on the brain during the third
trimester (Brocardo, Gil-Mohapel, & Christie, 2011).
Clinical Manifestations
The leading cause of intellectual disability is maternal alcohol abuse (Sadler, &
Langman, 2012). FASD is related to an extensive range of neurobehavioral deficits, including,
poorer verbal learning and memory, lower IQ, poorer attention and executive function and
slower cognitive processing speed (Jacobson, Jacobson, Stanton, Meintjes, & Molteno, 2011).
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These are key characteristics seen in individuals who have FASD. The clinical manifestations
post birth and within the first 36 hours after birth seen in these infants are discussed below.
Upon birth, there are certain disorders of the FASD that have a distinct set of facial anomalies
that can be seen upon birth alerting the health care provider that the patient was affected by
alcohol consumption in utero. FAS, the most severe form of FASD, is characterized by a
distinctive set of facial anomalies; the manifestations of this facies include short palpebral
fissures, flat midface, thin upper lip (vermilion border), flat or smooth philtrum, microcephaly
and pre- or postnatal growth retardation (Gomella, Cunningham, & Eyal, 2013). Associated
features also seen in infants with FASD include epicanthal folds, low nasal bridge, short nose,
and micrognathia (Warren, Hewitt, & Thomas, 2011). The infant may also have decreased
muscle tone, poor coordination and heart defects such as ventricular septal defect (VSD) or atrial
septal defect (ASD) (Vaux, 2012).
Central nervous symptoms can appear within 24 hours after delivery and includes
tremors, irritability, twitching, decreased tolerance to noise, or hyperacusis, hyperventilation,
hypertonicity, opisthotonos, and seizures (Gomella et al., 2013). These symptoms may be severe,
but they are usually of short duration. In premature infants of women who were heavy alcohol
users (> 7 drinks/wk), there is an increased risk of both intracranial hemorrhage and white matter
CNS damage (Gomella et al., 2013).
Diagnostic Approach
Diagnosis of FASD is difficult because information regarding prenatal exposure is often
lacking, a large proportion of affected children do not exhibit the distinctive facial anomalies,
and no distinctive behavioral phenotype has been identified (Jacobson et al., 2011). When a
diagnosis of FASD is considered, there are three major factors that must be addressed in the
ALCOHOL, PREGNANCY, AND FASD
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individual: (1) physical growth, development, and structural defects (for example,
dysmorphology); (2) cognitive and neurobehavioral function; and (3) maternal exposure and risk
(May & Gossage, 2011). In 1996, the Institute of Medicine published specific diagnostic criteria
for FAS with confirmed maternal alcohol exposure, FAS without confirmed maternal alcohol
exposure, partial FAS with confirmed alcohol exposure, alcohol related birth defects (ARBD),
and alcohol-related neurodevelopmental disorders [ARND] (Douzgou et al., 2012).
Fetal Alcohol Syndrome (FAS): FAS represents the most critical end of the FASD
spectrum. Strict criteria, including all of these following findings, define this diagnosis:

Three specific facial abnormalities (smooth philtrum, thin vermillion border, and small
palpebral fissures)

Growth deficits (e.g. lower‐than‐average height, weight, or both)

Central nervous system (CNS) abnormalities (structural, neurological, functional or a
combination) (Centers for Disease Control and Prevention, 2011).
Partial FAS: When a person does not meet the full diagnostic criteria for FAS but has a
history of prenatal alcohol exposure, some of the facial abnormalities as well as a growth
problem or CNS abnormalities (CDC, 2011).
Alcohol‐Related Neurodevelopmental Disorder (ARND): People with ARND might have
intellectual disabilities and problems with behavior and learning (CDC, 2011).
Alcohol‐Related Birth Defects (ARBD): People with ARBD might have problems with
the heart, kidneys, and/or bones, as well as with hearing and/or vision (CDC, 2011).
ALCOHOL, PREGNANCY, AND FASD
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A new test capable of detecting fetal fatty acid ethyl esters in the meconium of newborns
of heavy alcohol users may be useful for identification of infants in need of early health,
developmental and psychosocial intervention and may enhance clinical research involving
prenatal drug and alcohol exposure (Martin et al., 2011). See the appendix for the diagnostic
classification of fetal alcohol syndrome (FAS) and alcohol-related effects(Centers for Disease
Control and Prevention, 2011).
Therapeutic options
There is no cure for FASD. The main focus of treatment is ultimately prevention and
intervention. Prevention is key to keep these disorders from occurring. It is clear that FASD are
irreversible lifelong conditions that are entirely preventable if a woman does not drink alcohol
while she is pregnant (Martin et al., 2011). Intervention is vital to help the diagnosed person.
Prevention
The AAP recommends abstinence from alcohol preconceptionally and during pregnancy,
screening of al pregnant women for alcohol use, and referral of pregnant alcohol abusers for
assessment and treatment (Martin et al., 2011). Research has shown that the earlier the
intervention, the more successful the individuals with these developmental disabilities are.
Guidelines for screening and management of FASD include universal screening of pregnant
women for alcohol use, so that appropriate management can be provided (Martin et al., 2011). A
brief easily administered, standardized questionnaire such as the TWEAK (Tolerance of number
of drinks needed to feel high; Worry or concerns by family or friends about drinking behavior;
Eye opener in the morning; blackouts or Amnesia while drinking; self-perception of the need to
[K] cut-down on alcohol use) is applicable to nearly all obstetric settings for the identification of
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pregnant women at risk so that referrals can be made for further drug or alcohol abuse and
psychosocial assessment and treatment (Martin et al., 2011). Another key element to consider is
whether a woman has an alcohol dependence prior to conception. If so, contraception
consultation and services should be offered. It is recommended that pregnancy be delayed until it
can be an alcohol-free pregnancy (Floyd et al., 2008). Educating women prenatally is
fundamental to preventing FASD. Because of the adverse outcomes of alcohol on pregnancy,
The Department of Health and Human Services, Office of the Surgeon General, released an
updated Advisory on Drinking and Pregnancy in 2005 advising women who are pregnant,
planning to become pregnant, or at risk of becoming pregnant to abstain from alcohol use (Floyd
et al., 2008).
Intervention
It is imperative to identify the possible diagnosis of one of the FASD as soon as possible
because early recognition and intervention is associated with better outcomes (Schaefer & Deere,
2011). Once an FASD is identified in a specific patient, prompt referrals and enrollment in
indicated services are required to achieve the best outcomes (Schaefer & Deere, 2011). The key
to early diagnosis is to always keep the diagnostic possibility in the broad differential diagnoses
of growth and developmental disorders (Schaefer & Deere, 2011). No two people with an FASD
are exactly the same. Early diagnosis is important, so that the affected individuals can receive the
support they need in a protective setting. FASDs can include physical or intellectual disabilities,
as well as problems with behavior and learning. These symptoms can range from mild to severe
(CDC, 2011). Treatment services for people with FASDs should be different for each person
depending on the symptoms (CDC, 2011). There is no cure for FASDs, but early intervention
may improve primary effects (i.e., language, emotion dysregulation) and prevent secondary
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effects (i.e., academic, legal, psychiatric problems) related to FASDs (CDC, 2011). Patients
benefit from early diagnosis and aggressive intervention with physical, occupational, speech and
language, and educational therapies (CDC, 2011). The interventions need to be individualized,
multimodal, and precise to the individual and his/her family across the individual’s lifespan.
Economic, emotional and social implications
People affected with FASD often experience a wide range of health problems such as
birth defects, growth problems, cognitive delay, and speech and language difficulties. Infants
affected by FASD are also more susceptible to cardiac anomalies, urogenital defects, skeletal
abnormalities, and visual and hearing problems (Popova, Stade, Bekmuradov, Lange, & Rehm,
2011). The economic, emotional and social implications related to FASD are daunting, but
preventable.
Economic Implications
Due to the possibility of the wide array of disabilities, individuals who are affected with
FASD may have special needs that require lifelong help (Popova et al., 2011). Without the
crucial support, people affected by FASD are at a high risk of developing secondary disabilities
such as: mental health problems, trouble with the law, dropping out of school, becoming
unemployed, homeless and/or developing alcohol and drug problems (Popova et al., 2011). This
leads to tremendous costs over a lifetime period. FASD costs $6 billion annually in the United
States (NOFAS, n.d.). It costs $1.4 million to treat one person with FAS over their lifetime
(NOFAS, n.d.). The total lifetime cost per individual include estimates of medical treatment,
home and residential care, special educational services and productivity losses with patients with
FASD of all ages (Popova et al., 2011).
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Emotional/Social Implications
Children diagnosed with FAS or those affected by FASD often come from unstable
families and may be at greater risk for physical abuse, sexual abuse and neglect (NOFAS, n.d.).
As many as 85% of children with FASD are being raised by grandparents, other relatives, foster
parents, or adoptive parents (NOFAS, n.d.). As the provider, it is important to counsel the family
on the importance of caregiver attachment (NOFAS, n.d.). The time between birth and three
years old is particularly important for developing a stable and nurturing environment for the
infant. Children who may have FAS and are in the foster care system are at an increased risk for
negative attachment and reactive attachment disorder (RAD) (NOFAS, n.d.).
The other factor to consider is the guilt the mother may feel upon learning of the outcome
on the infant due to her consumption of alcohol. Counseling may be beneficial to foster a
positive relationship between the infant and mother and to educate the family on what
interventions are necessary to help the infant affected.
Many of these children have life-long behavioral and learning problems caused by
organic brain damage (NOFAS, n.d.). This is extremely stressful and can be overwhelming for
any parent or caregiver. These children may require a range of specialized medical, social,
educational, and legal services (NOFAS, n.d.).
As the 2004 CDC Fetal Alcohol Syndrome Guidelines for Referral and Diagnosis
correctly states, “Diagnosis is never an endpoint for any individual with a developmental
disability and his or her family.” Understanding a diagnosis can help families set realistic
expectations and facilitate appropriate treatment, intervention, and planning (NOFAS, n.d.).
Because the life skills affected by prenatal alcohol exposure vary greatly, the correct intervention
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ALCOHOL, PREGNANCY, AND FASD
is unique for each individual with FAS and their family (NOFAS, n.d.). The CDC has identified
specific services helpful to individuals with FAS that are age-specific (NOFAS, n.d.). The most
effective interventions are those that are geared towards an individual’s developmental level.
Conclusion
The worldwide rate of FAS has been estimated to be 1.9 per 1,000 live births (Balachova
et al., 2013). Recent studies show an elevated FAS rate of 2 to 7 per 1,000 in the US, and FASD
incidence is estimated to be 2%-5% among elementary school children in the US (Balachova et
al., 2013). Alcohol now is recognized as the leading preventable cause of birth defects and
developmental disorders in the United States (Warren et al., 2011). The severity of birth defects
resulting from exposure of the developing embryo or fetus to alcohol is determined by multiple
factors, including genetic background, timing and level of alcohol exposure, and nutritional
status (Warren et al., 2011). Infants diagnosed with FASD have serious, lifelong consequences
related to alcohol exposure in utero. Early diagnosis is important so that the affected children can
receive the support they need in a protective environment. The National Organization on Fetal
Alcohol Syndrome (n.d.) best sums up the relationship of alcohol and pregnancy by stating,
“Alcohol and Pregnancy. No safe amount. No safe time. No safe alcohol. Period.”
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ALCOHOL, PREGNANCY, AND FASD
References
Balachova, T., Bonner, B. L., Chaffin, M., Isurina, G., Shapkaitz, V., Tsvetkova, L., ... &
Knowlton, N. (2013). Brief FASD prevention intervention: physicians’ skills
demonstrated in a clinical trial in Russia. Addiction science & clinical practice, 8(1), 110.
Blackburn, S. T. (2013). Pharmacology and pharmacokinetics during the perinatal period.
Maternal, fetal, & neonatal physiology: a clinical perspective (4th ed., pp. 183-213).
Maryland Heights, MO: Elsevier Saunders.
Brocardo, P. S., Gil-Mohapel, J., & Christie, B. R. (2011). The role of oxidative stress in fetal
alcohol spectrum disorders. Brain research reviews, 67(1), 209-225. Centers for Disease
Control and Prevention (CDC). (2011). Fetal alcohol spectrum disorders. Retrieved from
http://www.cdc.gov/ncbddd/fasd/treatments.html
Douzgou, S., Breen, C., Crow, Y. J., Chandler, K., Metcalfe, K., Jones, E., ... & Clayton-Smith,
J. (2012). Diagnosing fetal alcohol syndrome: new insights from newer genetic
technologies. Archives of disease in childhood, 97(9), 812-817.
Floyd, R. L., Jack, B. W., Cefalo, R., Atrash, H., Mahoney, J., Herron, A., ... & Sokol, R. J.
(2008). The clinical content of preconception care: alcohol, tobacco, and illicit drug
exposures. American journal of obstetrics and gynecology, 199(6), S333-S339.
Gomella, T. L, Cunningham, M. D. & Eyal, F. G. (2013). Infant of a substance-abusing mother.
Neonatology: Management, procedures, on-call problems, diseases and drugs (7th Ed.,
pp. 715-724). New York: McGraw Hill Education.
Jacobson, S. W., Jacobson, J. L., Stanton, M. E., Meintjes, E. M., & Molteno, C. D. (2011).
ALCOHOL, PREGNANCY, AND FASD
14
Biobehavioral markers of adverse effect in fetal alcohol spectrum disorders.
Neuropsychology review, 21(2), 148-166.
Martin, R. J., Fanaroff, A. A., & Walsh, M. C. (2011). Pharmacology. Fanaroff and Martin's
neonatal-perinatal medicine: diseases of the fetus and infant (9th ed., pp. 708-757).
Philadelphia: Saunders/Elsevier.
May, P. A., & Gossage, J. P. (2011). Maternal risk factors for fetal alcohol spectrum disorders:
Not as simple as it might seem. Alcohol Research & Health, 34(1), 15.
Medina, A. E. (2011). Fetal alcohol spectrum disorders and abnormal neuronal plasticity. The
Neuroscientist, 17(3), 274-287.
National Organization on Fetal Alcohol Syndrome (NOFAS). (n.d.). Fetal alcohol spectrum
disorders. Retreived from http://www.nofas.org
Paoletti, A. M., Atzeni, I., Orrù, M., Pilloni, M., Loddo, A., Zirone, M., ... & Melis, G. B. (2013).
Alcohol and pregnancy. Journal of Pediatric and Neonatal Individualized Medicine
(JPNIM), 2(2), e020215.
Popova, S., Stade, B., Bekmuradov, D., Lange, S., & Rehm, J. (2011). What do we know about
the economic impact of fetal alcohol spectrum disorder? A systematic literature review.
Alcohol and Alcoholism, 46(4), 490-497.
Riley, E. P., Infante, M. A., & Warren, K. R. (2011). Fetal alcohol spectrum disorders: an
overview. Neuropsychology review, 21(2), 73-80.
Sadler, T. W., & Langman, J. (2012). Langman's medical embryology (12th ed.). Philadelphia:
Wolters Kluwer Health/Lippincott Williams & Wilkins.
Schaefer, G. B., & Deere, D. (2011). Recognition, diagnosis and treatment of fetal alcohol
syndrome. The Journal of the Arkansas Medical Society, 108(2), 38-40.
ALCOHOL, PREGNANCY, AND FASD
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Vaux, K. K. (2012). Fetal Alcohol Syndrome . Medscape. Retrieved from http://emedicine
.medscape.com/article/974016-overview
Warren, K. R., Hewitt, B. G., & Thomas, J. D. (2011). Fetal alcohol spectrum disorders: research
challenges and opportunities. Alcohol research & health: the journal of the National
Institute on Alcohol Abuse and Alcoholism, 34(1), 4.
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APPENDIX
Diagnostic classification of fetal alcohol syndrome (FAS) and alcohol-related effects. CNS,
central nervous system