Running head: ALCOHOL, PREGNANCY, AND FASD 1

“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

ALCOHOL, PREGNANCY, AND FASD 2

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 3

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 4

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

ALCOHOL, PREGNANCY, AND FASD 5

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).

ALCOHOL, PREGNANCY, AND FASD 6

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 7

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 8

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

ALCOHOL, PREGNANCY, AND FASD 9

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

ALCOHOL, PREGNANCY, AND FASD 10

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).

ALCOHOL, PREGNANCY, AND FASD 11

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

ALCOHOL, PREGNANCY, AND FASD 12

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.”

ALCOHOL, PREGNANCY, AND FASD 13

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ALCOHOL, PREGNANCY, AND FASD 16

APPENDIX

Diagnostic classification of fetal alcohol syndrome (FAS) and alcohol-related effects. CNS, central nervous system