Prenatal Alcohol Exposure and Neurodevelopmental Disorders

Neurodevelopmental Disorders
associated with Prenatal Exposure
to Alcohol
Carl C. Bell, M.D.
Staff Psychiatrist – Jackson Park Hospital Family Practice
Clinic
Staff Psychiatrist – St. Bernard Hospital Inpatient Psychiatry
Unit
Former Director of the Institute for Juvenile Research
(Birthplace of Child Psychiatry)
Professor Psychiatry and Public Health
Director of Public & Community Psychiatry – Department of
Psychiatry
University of Illinois at Chicago

Triadic Theory of Influence
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Sociological theories of social control and social bonding
(Akers et al., 1979; Elliott et al., 1985)
Peer clustering (Oetting & Beauvais, 1986)
Cultural identity (Oetting & Beauvais, 1990-91)
Psychological theories of attitude change & behavioral
prediction (Fishbein & Ajzen, 1975; Ajzen, 1985)
Personality development (Digman, 1990)
Social learning (Akers et al., 1979; Bandura, 1977, 1986)
Integrative theories (e.g., Jessor & Jessor's, Problem Behavior
Theory; Brook’s Family Interaction Theory, Hawkins’ Social
Development Theory)
See Petraitis, Flay and Miller (1995).

Cultural/
Attitudinal
Stream

Social/
Normative
Stream

Intrapersonal
Stream

Community Psychiatry Protective
Factor Field Principles
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Rebuilding the Village/Constructing Social Fabric
Access to Modern and Ancient Technology
Connectedness
Social and Emotional Skills
Self Esteem - Activities that create a sense of power;

Activities that create a sense of connectedness; Activities
that create a sense of models; Activities that create a sense
of uniqueness



Reestablish the Adult Protective Shield/Safety
Minimize the Effects of Trauma/Mastery

Risk Factor - Culture Destroys
Canada's monocultural ethnocentric culture
had little value for First Nation culture.
 Thus, First Nation children were removed from
their families and told them their culture was
not acceptable, resulting in First Nation people
having to give up their cultural protective
factors which ultimately led to many First
Native people engaging in the risky behaviors
of suicide and intra-group homicide.


Within these communities, alcoholism is
common and for every one child in Canadian
juvenile detention centers without fetal alcohol
syndrome there are 19 children with fetal
alcohol spectrum disorders (Popova et al,
2011).
 Bell (2012) has proposed many disruptive
behaviors leading to incarceration results from
fetal alcohol exposure (FAE).




Fetal Alcohol Exposure is the leading cause of
speech and language disorders, ADHD,
Specific Learning Disorders, & Mild Mental
Retardation which are often responsible for
affect dysregulation leading to disruptive
behaviors leading to incarceration.

Stratton et al. (1996). Fetal Alcohol Syndrome:
Diagnosis, Epidemiology, Prevention, and Treatment.
Washington, D.C. National Academy of Sciences,
Institute of Medicine.

ADHD on the Rise?
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

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In 2011, 11% of children/adolescents aged 4 to 17
years had ever received an ADHD diagnosis (6.4
million children).
Among those with a history of ADHD diagnosis, 83%
were reported as currently having ADHD (8.8%); 69%
of children with current ADHD were taking medication
for ADHD (6.1%, 3.5 million children).
A parent-reported history of ADHD increased by 42%
from 2003 to 2011. Prevalence of a history of ADHD,
current ADHD, medicated ADHD, & moderate/severe
ADHD increased significantly from 2007 estimates.
Prevalence of medicated ADHD increased by 28%
from 2007 to 2011.

ADHD on the Rise?






Conclusions: Approximately 2 million more U.S.
children/adolescents aged 4 to 17 years had been
diagnosed with ADHD in 2011, compared to 2003.
More than two-thirds of those with current ADHD were
taking medication for treatment in 2011.
Visser, et al. Trends in the Parent-Report of Health
Care Provider-Diagnosed and Medicated AttentionDeficit/Hyperactivity Disorder: United States, 2003–
2011. JOURNAL OF THE AMERICAN ACADEMY OF
CHILD & ADOLESCENT PSYCHIATRY, in press –
2013
http://www.jaacap.com/article/S0890-8567(13)00594-7/a

 Youth

Risk Behavior Surveillance
 The prevalence of having carried a
weapon in general was higher among
white males (27.2%) than among their
black counterparts (21%).
 The prevalence of having carried a
weapon onto school property was higher
among white males (7.8%) than black
males (6.7%).


The prevalence of having ever used cocaine
was higher among white males (7.6%) than
black males (4.2%).
 Yet, people of color make up a higher
proportion of children and young adults who
are incarcerated.
 In fact, in 2010, the imprisonment rate for
black non-Hispanic males (3,074/100,000 U.S.
black male residents) was almost seven times
higher than it was for white non-Hispanic
males (459/100,000) U.S. Bureau of Justice
Statistics


Protective Factor - Culture Protects
 While

doing HIV prevention work in
Durban, South Africa it was striking that
40 percent of the Zulu people were HIVpositive, 6 percent of the white South
African people were HIV-positive, but
only 1 percent of the Indian South African
people were HIV-positive.

The Critical Role of Self-Regulation




Neuroscience and behavioral
research are converging on the
importance of self-regulation for
successful development
Children who do not develop the
capacity to inhibit impulsive
behavior, to plan, and to regulate
their emotion are at high risk for
behavioral and emotional
difficulties

Bell CC & McBride DF. Affect Regulation and the Prevention of
Risky Behaviors. Journal of the American Medical Association,
Vol. 304, No. 5: 565 –566, August 4, 2010

Prevalence of FASD
 Fetal

Alcohol Syndrome (FAS) occurs far
more frequently than generally believed:
FAS: 1 per 1000 live births
 Although estimates vary widely, when
combined with the milder afflictions of
Fetal Alcohol Spectrum Disorders (FASD),
the Centers for Disease Control puts the
frequency of FAS/FASD as high as one in
100.

Prevalence of Drinking while Pregnant
In the US 13% knowingly drink while pregnant
 1% drink heavily while pregnant
 3-4% binge drink during pregnancy (SAMHSA)
 12% of pregnant women consume 5 or more
drinks per month
 50% of pregnancies are unplanned


Case History
A

31 year old Black male presented with a CC
of being handicapped all of his life and more
recently he has gotten out of control (per
mother’s report as patient was too intellectually
disabled and suffering from speech preservation
so he could not give a revealing HPI much less
any PH.
I had seen the patient last year and tried some
Sertraline and Benadryl but they did not help.
Mother reports that she recently picked up a
foster son and her 31-year old son is jealous (she
does not know why) and he is seriously choking

The

Case History

patient has previously been on Clonidine
0.1mg BID, Propranolol 10mg BID, Olanzapine
10mg BID, and Clonazepam 0.5mg BID without
any positive change in the patient’s behavior or
mentation.
He was groomed, cooperative but confused.
His mood was bland & his affect was flat. He had
perseveration, was easily distractible, & had
severe memory impairment.
DX – Pervasive Developmental Disorder and
Intellectual disability from fetal alcohol exposure.
Mother drank while pregnant.

Case History
The

mother called to report that her son had
really gotten violent & agitated – kicking over
chairs and choking the 14-year old
I told her to give him Omega – 3 twice a day;
she reported she knew what that was because
she and her husband were taking it for their
health.
Three months later the patient returned and
presented continuing to have poor insight, and
perseveration (the Miami Heath beat the Bulls) –
however he was no longer violent
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1979 – 55% (151) of the 274 children in Pupil Service
Center on Chicago’s Southside FAE
1985 – 20% of inmates in Texas Department of
Corrections were “mentally retarded.”
2011 - chart audit on 162 children in several nursebased school clinics estimates 39% (63) of those
children met the DSM-5 Condition for Further Study “Neurobehavioral Disorder Associated with Prenatal
Alcohol Exposure (NDA-PAE)
2012 prior to the closure of the Community Mental
Health Council, Inc. - chart audit of 330 randomly
selected patients revealed that 12% (39 of 330
patients) met criteria for NDA-PAE.



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2013 - work on an inpatient psychiatric unit at St.
Bernard Hospital (in the heart of Englewood - one
of the poorest African-American communities in
Chicago) reveals of 93 patients consecutively
admitted patients, 32% (30) meet the criteria for
NDA-PAE.
2013 - a random sample of 20% of consecutively
seen outpatients in Jackson Park Hospital's Family
Practice Clinic reveals that out of 100 patients,
29% (29) fit the criteria for NDA-PAE

Prenatal Choline
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Newborn rats prenatally exposed to alcohol exhibited
reduced birth weight and brain weight, delays in eye
opening and incisor emergence, and alterations in the
development of all behaviors.
Choline supplementation significantly attenuated
ethanol’s effects on birth and brain weight, incisor
emergence, and most behavioral measures.
In fact, behavioral performance of ethanol-exposed
subjects treated with choline did not differ from that of
controls.
Thomas et al. Prenatal choline supplementation mitigates the
adverse effects of prenatal alcohol exposure on development in
rats Neurotoxicol Teratol. 2009 ; 31(5): 303–311.

Postnatal Choline Animal Model
Thomas J et al. (2007). Choline
Supplementation Following Third-TrimesterEquivalent Alcohol Exposure Attenuates
Behavioral Alterations in Rats. Behavioral
Neuroscience
 Giving choline to infants who were exposed in
the womb to alcohol may mitigate some of the
resulting problems.


At San Diego State University, research led by
Jennifer Thomas, PhD, is using an animal
model to assess the potential therapeutic value
of choline.
 Because scientists have been unable to
determine a safe threshold for alcohol
consumption during human pregnancy,
abstention is the only sure means of
prevention.
 However, warnings about the dangers of
drinking during pregnancy either don’t reach or


As a result, researchers are seeking effective
remedies to give after birth, when health
professionals may be better able to intervene.
 Choline plays a number of roles in brain
development & is a precursor to acetylcholine,
a neurotransmitter involved in learning and
cognition, among other functions.
 Choline is available in many foods, such as
eggs and liver, and sold over the counter in
well-tolerated forms such as lecithin, choline
bitartrate or chloride, and phosphatidylcholine.


The current study of 170 rats found that giving
choline to rat pups exposed to alcohol during
the equivalent of the third trimester, when
there’s a spurt in brain growth, significantly
reduced the severity of alcohol-related overactivity and spatial learning deficits.
 The benefits lasted months after choline
treatment, suggesting that choline’s effects
are long-lasting, say the authors.


Various doses of choline were equally
effective, so the researchers think that at least
for the rat, as little as 10 mg/kg of weight per
day could be effective.
 Thomas and her colleagues would next like to
determine how choline helps and to assess
how late in development it can reduce fetal
alcohol effects.
 If choline is to be used clinically, it’s important
to know when treatment works best.


The current study demonstrates the benefits of
postnatal choline in rats, making it potentially
more useful given the realities of drinking
during pregnancy.
 Thomas and her colleagues are conducting
clinical studies of postnatal choline on humans
affected by prenatal alcohol exposure.
 If the current results with rats are replicated in
humans, then infants born to mothers who
drank when pregnant might benefit from
supplemental choline.


The authors conclude that extra choline "can
alter brain development following a
developmental insult.
 Early dietary interventions may reduce the
severity of some fetal alcohol effects, even
when administered after birth."
 Importantly, the animal data suggest that
although early postnatal choline can reduce
learning deficits and hyperactivity following
early alcohol exposure, it doesn’t help reduce
motor coordination deficits.


Thomas cautions, "Choline is not going to be
a panacea for all symptoms of fetal alcohol
spectrum disorders. Women need to be
continually reminded of the damaging effects
of alcohol on the developing fetus."
 Previous studies by other researchers have
shown that prenatal choline supplementation
in rats influences development of the nervous
system, especially the brain’s cortex and
hippocampus.


Due to choline’s beneficial effects on nervoussystem development, women are advised to
consume 450 mg a day while pregnant and 550
mg a day while breast feeding (the tolerable
upper limit has been set at 3.5 g per day).
 For infants, 125-150 mg/day is considered
adequate during the first year, rising as the
child grows older.
 Choline is added to some prenatal vitamins and
baby formulas, and is now added to some
children’s multivitamins and cereals.


Postnatal Choline
Wozniak et al. Post-Natal Choline
Supplementation in Children with FASD:
Preliminary Safety and Efficacy Results;
University of Minnesota
 Pilot study of 20 children with FASD, ages 2.5
to 5 years, who were randomly assigned
(double blind) to placebo or 500mg choline
supplementation per day for 9 months
 Plasma choline levels increased by 105% at
month 1 and remained elevated at 6 months
(105%) and 9 months (102)
 Tolerability was high with 17 participants
completing the study.


Postnatal Choline
By 6 months, the choline group showed a 9.9%
increase in delayed sequential memory (a
hippocampally dependent measure) compared
to the placebo group which showed only a
2.2% increase (effect size 0.42).
 In the choline group, earlier age at enrolment
was associated (non-significantly ) withy
greater improvement in memory.
 At 9 months, global cognitive functioning
(Mullen Scales) was increased by 8.6 points in
the choline group vs. 4.3 points in the placebo
group (effect size = 0.29).


Postnatal Choline


The greatest improvement on the Mullen was
in fine motor skill (7.1 points for the active
group vs 1 point for the placebo group, effect
sixe = 0.59).

Postnatal Choline

Thomas J, et al. Choline Supplementation in
Children With Fetal Alcohol Spectrum Disorders;
San Diego State University
 Randomized, Control Trial in 5 – 10 year olds
 Changes in cognitive function as measured by
performance on neuropsychological tasks of
learning/memory, executive functions, and
attention
 Children's Behavior Checklist (CBCL),
Behavioral Rating Inventory of Executive
Function (BRIEF) - Baseline and 6 weeks;
Parent questionnaires about children's
behavioral functioning will assess changes.


People with fetal alcohol exposure
(FAE) have several characteristics
Mild mental retardation, specific learning
disorders, speech and language deficits
and ADHD as evidenced by special
education in grammar and high school
(FAE is the leading cause of such
problems).
 Explosive emotionality - quick to get
frustrated and sometimes with an explosive
temper yet these affective outbursts do not
last long and are wrongfully referred to as
moods when the reality is their mood is


Most of the time such folk are very childlike
and naïve and they really want people to
like them because they have been
ostracized most of their lives because they
are "slow.“
 Patients have very poor judgment, planning
ability, capacity to foretell consequences of
their behavior, etc.
 Patients have difficulty doing simple math,
e.g. serial 7s - you know 100-7=; 93-7=; 867=; 79-7=; 72-7=; 65-7.


Patient often complains of being diagnosed as
bipolar, depressed, and schizophrenic.
 Patients are often on a wide variety of
medications that may or may not be helpful.
 Patients may continue to have the
characteristic facial characteristics of FAE wide apart set eyes, epicantal folds in their eye
lids, flat mid face, short palpebral fissures, no
philthrum or a very indistinct philthrum, small
chin, funny shaped ears, and a small head - of
course these features go away as the child


The range of fetal alcohol exposure varies
widely in people so that is why the growing way
of describing it as FASD (Fetal Alcohol
Spectrum Disorder).
 You have to remember that the fetal brain is
developing for 9 months so there are multiple
opportunities for the alcohol to denature the
choline, Vitamin A, and folate in the body that
causes the lack of these nutrients to damage
DNA, chromatin and RNA causing various
forms of brain damage.




There is growing evidence that by having a
good diet with choline bitartrate 650 ucg
BID (Puritan’s Pride 200 for $10.99),
Vitamin A 25,000 IU daily (Swanson 300 for
$5.69), and folate 800 mcg (Swanson Ultra
30 for $5.00), the effects of FAE may be
reversed in utero, possibly may also be
ameliorated post delivery, and may even
correct some of the problems in adults who
had FAE when fetuses.

DSM – 5: Neurobehavioral Disorder
Associated with Prenatal Alcohol Exposure


A. More than minimal exposure to alcohol during
gestation, including prior to pregnancy recognition
– Confirmation of gestational exposure to alcohol may be
obtained from maternal self-report of alcohol use in
pregnancy, medical or other records, or clinical
observation.



B. Impaired neurocognitive functioning as
manifested by one or more of the following:
1.Impairment in global intellectual performance (i.e. IQ of 70
or below)
2.Impairment in executive functioning (e.g. poor planning
and organization, inflexibility, difficulty with behavioral
inhibition)



B - Impaired neurocognitive functioning as
manifested by one or more of the following:
3. Impairment in learning (e.g. lower academic achievement
than expected for intellectual level; specific learning
disability)
4. Memory impairment (e.g. problems remembering
information learned recently; repeatedly making the
same mistakes; difficult remembering lengthy verbal
instructions)
5. Impairment in visual-spatial reasoning (e.g. disorganized
or poorly planned drawings or constructions; problems
differentiating left from right)



C. Impaired self-regulation manifested by one or
more of the following:
1. Impairment in mood or behavioral regulation (e.g. mood liability,;
negative affect or irritability ], frequent behavioral outbursts).
2. Attention deficit (e.g. difficulty shifting attention; difficulty sustaining
mental effort).
3. Impairment in impulse control (e.g. difficulty waiting turn; difficulty
complying with the rules).



D. Impairment in adaptive functioning as manifested by two
or more of the following, one of which must be (1) or (2):
1. Communication deficit (e.g. delayed acquisition of language;
difficulty understanding spoken language)
2. Impairment in social communication and interaction (e.g., overly
friendly with strangers, difficulty reading social cues; difficulty
understanding social consequences)



D. Impairment in adaptive functioning as manifested
by two or more of the following, one of which must be
(1) or (2):
3. Impairment in daily living skills (e.g. delayed toileting,
feeding, or bathing; difficulty managing daily schedule)
4. Impairment in motor skills (e.g., fine motor development;
delayed attainment of gross motor milestones or ongoing
deficits in gross motor function; deficits in coordination and
balance.



E. Onset of disorder (symptoms in Criteria B, C,
and D) occurs in childhood.





F. The disturbance causes clinically significant
distress or impairment in social, academic,
occupational or other important areas of
functioning.
G. The disorder is not better explained by the
direct physiological effects associated with
postnatal use of a substance (e.g. medication,
alcohol or other drugs); medical condition
(traumatic brain injury, delirium, dementia);

IDEAS TO COMBAT THE EFFECTS OF
FAE
Do public service announcements to
grandmothers who are care giving for
grandchildren who have learning disorders,
mild intellectual disability, ADHD, speech and
language disorders, explosive tempers and
who know their daughters or daughters-in-law
were drinking during pregnancy.
 Have correctional facilities who incarcerate
pregnant women screen those women for
drinking while pregnant before they knew they
were pregnant.


FAE
Psychiatric Services (11-15-13) “less than half
of American teens with mental health disorders
receive treatment, and those who do get help
rarely see a mental health specialist.”
 “analysis of data from more than 10,000 teens
aged 13 to 17 across the” US revealed that
“teens with ADHD, conduct disorder or
oppositional defiant disorder received mental
health care more than 70 percent of the time,
while those with phobias or anxiety disorders
were least likely to be treated.”


OTHER ROUTES OF TRANSMISSION?


I was talking to a woman who did not drink
when pregnant but who's son has all the signs
of fetal alcohol exposure (I am now asking
parents who are patients about their children to
see if they drank while pregnant) and she told
me that the father of her child (who is now
dead) also had all the symptoms that her son
has and how she learned that he was in special
education after they had had their son.

That sparked off a much more scary idea that it
is possible that if the father of her child had
fetal alcohol exposure and it damaged his DNA,
RNA and histones whether or not that acquired
biologic genetic damage might not be
transmitted from father to son in his sperm?
 If so then the question of the mother's drinking
while pregnant is important but there may be
another route of transmission.


Paternal alcohol consumption – expression of a
key enzyme catalyzing DNA methyelation –
called DNA methyltransferase 1 (DNMT1) was
reduced in the sperm of paternal rats after 9
weeks of chronic alcohol exposure.
 Analysis of methylation patterns of sperm DNA
from human volunteers showed a correlation
between chronic alcohol use and demethylation
of DNA regions that normally show particularly
high methylation..




Transmission of these epigenetic changes to
the offspring through fertilization possibly could
alter gene expression in the fetus, thus
affecting prenatal development.

– Kobor MS, Weinberg J. Epigenetics and Fetal
Alcohol Spectrum Disorders. Alcohol Research and
Health, Vol. 34 (No. 1):
http://pubs.niaaa.nih.gov/publications/arh341/29-37.h

– Ramsay M. Genetic and epigenetic insights into
FASD. Genome Medicine 2012, 2:27
http://www.biomedcentral.com/content/pdf/gm148.pdf

FAE
Educate Obstetricians about the damage FAE
can do and suggest to them that choline
supplements may decrease the outcome of
FAE exposed children (let them know that
prenatal vitamins do not have choline in them).
 Work with Chicago Public Schools to identify
children in special education who have the
characteristic histories of FAE, and have their
parents supplement those children’s nutrition
with choline, folate, and vitamin A.


FAE
Work with Cook County Detention Center to
identify children in their facility who have the
characteristic histories of FAE, and supplement
those children’s nutrition with choline, folate,
and vitamin A.
 Get in touch with the Illinois Department of
Children and Family Services and have them to
identify children in their facility who have the
characteristic histories of FAE, and supplement
those children’s nutrition with choline, folate,
and vitamin A.


FAE
Get vitamin companies to put choline in their
prenatal vitamins.
 Get Walgreens to supply choline supplements
in their stores.
 Get Phillip Jackson of the Black Star project on
it.
 Others?


Prenatal Alcohol Exposure and Neurodevelopmental Disorders

Prenatal Alcohol Exposure and Neurodevelopmental Disorders

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