Choline Supplementation for Fetal Alcohol Syndrome in School Children

This dissertation aims to evaluate the effectiveness of choline supplementation as a nutritional intervention for treating the symptoms of Fetal Alcohol Syndrome (FAS) in school children. The research will also explore alternative interventions for managing FAS in school age children.

Running head: HEALTHCARE DISSERTATION
HEALTHCARE DISSERTATION
Name of the Student:
Name of the University:
Author Note:

1
HEALTHCARE DISSERTATION
Table of Contents
Chapter 1: Introduction....................................................................................................................5
1.0: Background:..........................................................................................................................5
1.1: Problem Statement:...............................................................................................................5
1.2: Research Rationale:..............................................................................................................6
1.3: Research Question:...............................................................................................................6
1.4: Research Aim:......................................................................................................................7
1.5: Research Objectives:............................................................................................................7
1.6: Literature Review:................................................................................................................8
1.7: Results and Discussion:........................................................................................................8
Chapter 2: Literature Review...........................................................................................................9
2.0: Introduction:.........................................................................................................................9
2.1: Literature Review:................................................................................................................9
Literature Gap:...........................................................................................................................20
Chapter 3: Methodology................................................................................................................22
3:0: Methodology:.....................................................................................................................22
3.1: Summary of the Literature Findings:..................................................................................22
3.2: Search Strategy:..................................................................................................................23
3.3: Exclusion Criteria:..............................................................................................................25
3.4: Inclusion Criteria:...............................................................................................................25
3.5: Key Terms:.........................................................................................................................25
3.6: PICO Questions:.................................................................................................................26
Research Study Design and Justification:..................................................................................27
Chapter 4: Results and Discussion................................................................................................28
4.0: Literature Findings:............................................................................................................28
4.1: Thematic Analysis:.............................................................................................................28
4.2: Critical Analysis:................................................................................................................33
4.3: Discussion:..........................................................................................................................33
4.4: Summary:............................................................................................................................34
4.5: Limitations:.........................................................................................................................35
4.6: Level of evidence:..............................................................................................................36

2
HEALTHCARE DISSERTATION
Chapter 5: Conclusion and Recommendations..............................................................................38
5.0: Conclusion:.........................................................................................................................38
5.1: Recommendation:...............................................................................................................38

3
HEALTHCARE DISSERTATION
Abstract:
Background: According to a report published by the Institute of Alcohol Studies (2019), it has
been mentioned that UK ranks among the top five nations with the highest prevalence of Fetal
Alcohol Syndrome. The research report further suggested that Britain has the highest prevalence
percentage of FASD on a global context. The estimated cases diagnosed within Britain
comprises of 61.3 cases out of 10,000 live births. In addition to this, the disease burden
associated with FASD results in problems such as learning difficulties, hearing and vision
impairment, poor growth and development and behavioral difficulties which diminish the quality
of life of the child as well as the parents who are responsible for bringing up the child. The
rationale for conducting the research can be explained as evaluating the evidence base to
determine if choline supplementation could help in improving cognitive functioning in school
children so as to support them through the developmental process and improve their coping
skills.
Research Study Design: A systematic review research design was adapted to address the
research. Relevant literatures were scanned on the electronic databases of CINAHL and Google
Scholar. Appropriate key terms were used and papers that qualified inclusion criteria were
included in the research study.
Results and Discussion: Choline supplementation intervention can help in improving cognitive
functions and memory in FASD children. In addition to this a combination of pharamacological
interventions and support systems such as special education and occupational therapy can help in
supporting the child through developmental stages

4
HEALTHCARE DISSERTATION
Conclusion and Recommendation: More research is required in order to validate the genetic
precision pharamacological interventions and validate the positive effect of choline
supplementation on the children suffering from FASD.

5
HEALTHCARE DISSERTATION
Chapter 1: Introduction
1.0: Background:
Fetal Alcohol Syndrome abbreviated as FAS can be defined as a condition that manifests
when the mother is exposed to alcohol during the pregnancy term. Fetal alcohol syndrome results
in brain damage and significant growth and developmental problems (Rasmussen et al. 2013). It
is important to note here that the defect caused by fetal alcohol syndrome is irreversible but the
intensity of the effect varies from one child to other. Consumption of alcohol during pregnancy is
unsafe and increases the risk of developing Fetal Alcohol Syndrome in babies. Research studies
suggest that early diagnosis could help in implementing effective interventions to treat learning
difficulties and behavioral problems (Fuglestad et al. 2013; Tsang et al. 2016). Research studies
further state that the sign and symptoms of FAS span across a combination of physical, cognitive
and intellectual defects (Fuglestad et al. 2015). It is crucial to note here that there is no specific
recommended treatment routine that can treat FASD in infants and children. However, the
associated symptoms of the disorder can be controlled so as to improve the coping skills of the
child. A number of research studies suggest that nutritional intervention with the inclusion of
Choline-supplementation could help in improving cognitive functioning in FASD children
(Tsang et al. 2016; Murawski et al. 2015).
1.1: Problem Statement:
According to a report published by the Institute of Alcohol Studies (2019), it has been
mentioned that UK ranks among the top five nations with the highest prevalence of Fetal
Alcohol Syndrome. The research report further suggested that Britain has the highest prevalence

6
HEALTHCARE DISSERTATION
percentage of FASD on a global context. The estimated cases diagnosed within Britain
comprises of 61.3 cases out of 10,000 live births. In addition to this, the disease burden
associated with FASD results in problems such as learning difficulties, hearing and vision
impairment, poor growth and development and behavioral difficulties which diminish the quality
of life of the child as well as the parents who are responsible for bringing up the child.
1.2: Research Rationale:
It is important to note that there is no specific treatment available for the cure of FASD,
however, the evidence base reveals about a number of interventions which could help in
symptom management. Particularly, in this regard, administering nutritional intervention in the
form of Choline supplementation has been studied to improve cognitive functioning in children.
Choline is an important nutrient that is responsible for the development of brain and behavior
(Coriale et al. 2013). A number of animal trials have been successfully conducted that reveal
prenatal and post natal choline supplementation was responsible for enhancing cognitive
functions. Also, research studies have suggested that choline supplementation improved
cognitive outcomes in rats that were exposed to alcohol during the development process
(Murawski et al. 2015). Therefore, the rationale for conducting the research can be explained as
evaluating the evidence base to determine if choline supplementation could help in improving
cognitive functioning in school children so as to support them through the developmental process
and improve their coping skills.
1.3: Research Question:

7
HEALTHCARE DISSERTATION
Thus, based on the available background information about fetal alcohol syndrome and
its impact on the quality of life of the affected children and their care providers, the following
research questions can be formulated:
RQ1: What does the evidence base suggest about the use of choline supplementation as a
potential nutritional intervention for treating FASD symptoms in school age children?
RQ2: What are the positive effects of using choline supplementation in school age children
suffering from FASD?
RQ3: What are the evidence-based interventions that can be used for treating FASD in school
age children?
1.4: Research Aim:
The aim of the research is to conduct a thorough search on the electronic databases so as
to evaluate the effectiveness of using choline supplementation as a nutritional intervention for
treating the symptoms of FASD in relation to intellectual and cognitive impairment in school
children. The research also intends to evaluate the evidence based intervention strategies that
could be used to treat FASD in school age children.
1.5: Research Objectives:
The research objectives for the research study include the following:
 To determine whether choline supplementation could be used as an effective intervention
to treat the symptoms of FASD in school children
 To determine the impact of using choline supplementation in school children

8
HEALTHCARE DISSERTATION
 To determine alternative interventions which could be used to manage the symptoms of
FASD in school children

9
HEALTHCARE DISSERTATION
1.6: Literature Review:
According to Murawski et al. (2015), it has been stated that diagnosis of FASD is
challenging but recent advances in the form of recognition of facial characteristics, identification
of biomarkers as well as estimating relation between face, brain and behavior has sped up the
diagnosis process. However, the researchers have mentioned that to a great extent the
pharmacological therapies and nutritional intervention has been used in animal models which has
yielded successful outcome and the same set of interventions can be implemented on humans to
improve outcomes of impairment. Another research study conducted by Wozniak et al. (2013),
made use of a pilot study to evaluate the feasibility, tolerability and adverse effects of choline
supplementation in children who were diagnosed with Fetal Alcohol Syndrome Disorder. The
study comprised of 20 children who were aged between 2.9 years to 4.9 years and were
diagnosed with FASD. The participants were randomly administered 500mg Choline for 9
months. The results revealed no serious adverse effect on the children apart from a fishy body
odor. The results further suggested that choline supplementation intervention was feasible and
had high tolerability in children aged 2 to 5 years (Wozinak et al. 2013). However, the
effectiveness of choline supplementation is yet to be evaluated.
1.7: Results and Discussion:
Therefore, it can be mentioned that FASD in children causes a number of issues in terms
of developmental delay and cognitive functioning impairment. Research studies have majorly
focused on testing the effectiveness of choline supplementation to treat FASD in animal models,
but the effectiveness is yet to be tested completely in humans (Murawski et al. 2015; Coriale et

10
HEALTHCARE DISSERTATION
al. 2013). However, the evidence base suggests that choline supplementation in children is
feasible and does not cause any adverse effects (Wozinak et al. 2013).
Chapter 2: Literature Review
2.0: Introduction:
According to Stringer (2013), literature review can be defined as an important aspect of a
dissertation that sheds light on the research done previously so as to ensure that researchers can
obtain an overview about the research conducted so far and add to the evidence base. In addition
to this, it should also be noted that a literature review helps in assessing the current state of
research on a concerned research topic. It further helps in the identification of key research
questions in relation to a research topic and identification of research gap that requires further
investigation. The rationale for conducting a literature review can be explained as determination
of methodologies used in the previous research studies that were aligned to the devised research
question. Therefore, the literature review would be conducted in order to evaluate the evidence
base so as to determine that whether or not choline supplementation is an effective intervention
measure for treating Fetal Alcohol Syndrome in school going children.
2.1: Literature Review:
As per Nguyen et al. (2016), Fetal alcohol syndrome is defined as a health condition that
arises in children due to alcohol exposure during the period of pregnancy. Research studies state
that the syndrome leads to brain damage and developmental issues. Further it should also be
noted that the impact of fetal alcohol syndrome varies from one child to another and that the

11
HEALTHCARE DISSERTATION
effect of the disorder is not reversible. According to Nguyen et al. (2016), it has been mentioned
that nutrition forms an important factor that impact the brain development process. As reported
to Nguyen et al. (2016), it has been stated that nutritional deficiencies can potentially enhance
the damaging effects of alcohol. In addition to this, it has further been mentioned that nutritional
supplementation plays an important role against the damage caused due to alcohol and serves as
an optimal intervention strategy that yield positive outcome against fetal alcohol disorder. The
research study critically evaluated the dietary intake of the school going children whose parents
were heavily inclined to alcohol exposure during the prenatal period. The research study
intended to evaluate the nutritional intake of the school children so as to estimate their nutritional
status with reference to the dietary reference intake of a national-sample of the normally
developing children. The researchers collected the dietary intake data from the children that
possessed permanent histories of increased prenatal-alcohol exposure. It should further be noted
that the data was collected by making use of the Automated Self-Administered 24 Hour Dietary
Recall (ASA24). The observed and recorded nutrient level from the dietary status was critically
compared to the Dietary Reference Intakes in order to establish the appropriateness of the
nutritional-intake against the standard national average of the children who belonged to the same
age group. The findings of the research study stated that children that were predominately
exposed to alcohol during the pre-natal period displayed poor nutritional-status in comparison to
the healthy and developing children who were considered in accordance to the NHANES sample.
Typically, it was found that the children that were suffering from Fetal-Alcohol-Syndrome were
suffering from a deficiency of proportionate amount of protein, Magnesium, omega-3 fatty acids,
Zinc, Potassium, Niacin, Choline as well as Vitamin K and Vitamin C. In addition to this, the
overall findings of the research-study also stated that the dietary intake of the school going
children were deprived of the recommended dietary level of essential-nutrients such as

12
HEALTHCARE DISSERTATION
Potassium, dietary fiber, Vitamin E, Vitamin K, Omega-3 Fatty acids as well as Choline. In
addition to this, further it can be concluded that the cumulative findings of the research-study
were aligned to the previous studies and indicated that children suffering from Fetal-Alcohol-
Syndrome were vulnerable to nutritional deficiencies. In addition to this, the overall findings of
the research also suggest that there is an increased need to incorporate a percentage of
proportionate nutrients within the school children so as to ensure proper cognitive development
across the developmental stages.
As stated by Willhoit, Scott and Simecka (2017), it has been mentioned that Fetal-
Alcohol-Syndrome includes a continuation of disorder that manifests itself in children on
account of mother’s increased alcohol consumption and dependence during the period of
pregnancy. The research study further reveals that potentially there is no specific cure for Fetal-
Alcohol-Syndrome and that the impact of the syndrome varies from one individual to another. In
addition to this, the research also suggests that the Fetal Alcohol Syndrome leads to behavioral
and intellectual impairment and that early intervention and lifetime support could help in
positively dealing with the disorder. The research study further mentions that pre and post
choline supplementation in affected children can help in the process of recovery. It is crucial to
note in this context that Fetal Alcohol Syndrome in children is not curable, however the
symptoms can be managed with the use of accessory interventions that help with cognitive
treatment. The research study also mentions that FASD has been identified as one of the thirteen
disabilities that has been recognized under the Disabilities Education Act. The research further
reveals that recovery options such as making use of ADHD treatment facilities can help in
assisting symptom recovery. Also, the use of speech therapy as well as occupational therapy can
help in improving intellectual perception as well as induce behavior modification that can yield
positive outcome in terms of verbal memory, phonological processing as well as arithmetic

13
HEALTHCARE DISSERTATION
comprehension ability. The research study further suggests that schools play an integral role in
supporting the developmental process of the children that are reported to suffer from Fetal-
Alcohol-Syndrome. The use of a combination of individualized special-education plan along
with person-centred counselling can help in the overall development of the children and ensure a
stable education outcome. Overall, the findings of the research suggests that FASD causes a
cumulative of medical, cognitive, behavioral as well as social defects in children that make it
difficult to cope with the daily activities of life which might not be a problem for children of
similar age who are normal and are not affected with the disorder. The research study in this
context critically makes use of the evidence base to discuss plausible interventions and family-
centred practice measures which could help in promoting a positive outcome for the children and
support the children cope with the different development stages across life.
Another research study carried out by Dearman et al. (2015), evaluated the evidence
based interventions that could be used by primary healthcare providers in order to support
healthcare providers to treat FASD in children. The researchers make use of the evidence based
practices that are closely aligned with the practice guidelines that were developed by the
American Academy of Pediatrics-Clinical practice. The findings of the research study mentioned
that in most of the cases there is a need to administer a combination of pharmacotherapies in
combination with behavior and learning therapies as well as social and environmental modifiers
in order to ensure appropriate support and recovery from the syndrome. In this context, it should
be mentioned that the first line of pharmacotherapeutic medications that are ideally used to treat
FASD are similar to the medication used for treating ADHD and comprise of stimulant
medications. These medications comprise of short or long acting formulations such as
methylphenidate that is also used in the Multimodal Treatment of ADHD. The common side
effects of the medication comprise of appetite loss and sleep abnormalities. In addition to

14
HEALTHCARE DISSERTATION
methylphenidate, another non-stimulant medication that is used for the treatment of FASD
comprises of Atomoxetine which is basically a norepinephrine transport inhibitor that has been
rendered effective for types of ADHD and Anxiety. The medication requires regular dosing as
well as more than four weeks of the administration in order to determine the degree of
effectiveness. In addition to this, administration of Alpha 2 andergenic agonists acting clonidine
and long-acting guanfacine that are effective in the release of norephinephrine and dopamine
neurotransmission can be considered beneficial for the medical management of FASD in
children. Further, the use of antipsychotic medications as well as stimulants can help in
improving symptoms of anxiety in FASD children. Research studies have also revealed that
nutritional deficiencies in combination with alcohol exposure serve as the major causative factors
that lead to FASD among the children. The researchers in this regard suggest that the use of
micronutrient supplementation such as choline supplementation can help in improving cognitive
functions post-parental alcohol-exposure. Overall the research findings reveal that there is an
increasing need to engage the family members of the affected patient in the treatment routine so
as to ensure recovery. In addition to this, there is also a need to incorporate pharmacotherapuetic
interventions along with accessory interventions such as cognitive behavioral therapy, speech
therapy as well as occupational therapy so as to promote positive recovery across the
development stages of the affected child.
According to Koren (2015), FASD has been stated as the most prevalent cause that leads
to developmental disability and affects more than 1% of the total population based within North
America. Lack of attention, hyperactivity and impulsivity affects more than 50% to 90% of the
children who are affected with Fetal-Alcohol-Disorder and are 3 to 9 times common within the
common population. It should be noted in this context that a large proportion of the affected
children generally suffer from conduct disorder or defiant disorder which comprises of

15
HEALTHCARE DISSERTATION
deprivation of social judgment as well as failure to learn from every day life experiences. The
researchers conducted a review of literatures in order to evaluate the evidence base in order to
retrieve relevant pharmacological therapies which would be beneficial for the cure of Fetal-
Alcohol-Syndrome in children. The study results suggested that the use of methyl phenidate and
other such stimulants which are majorly used for the treatment of ADHD are used for the
pharmacological treatment measured for FASD. The research study further discusses the
experimental findings of Synder and his colleagues who conducted a randomized controlled
atrail with 12 children who were aged between 6 to 16 years of age and were affected with FAD
and ADHD. Eight children received methylphenidate, 2 children received Pemoline and 1 of the
children received Dexedrine in a crossover study design. The children received the drug for 3
days which was followed by a 1 day washout before each intervention. In between the two-sets
of interventions, it was found that the use of the drugs did not improve the attention scores but a
stark improvement was motive in the levels of hyperactivity as well as impulsivity. In addition to
this, the research study also significantly stated that the use of antipsychotic drugs for the
treatment of disruptive behavior was widely used for treating children who were suffering from
FASD. The study further revealed that at present only a handful of drugs have acquired approval
which are feasible for the use in children. A large number of the children are treated with
neuroleptics that include the use of risperidone which is the most prevalent drug that is used for
the treatment of FASD in children. It should be noted in this context that the combines use of
stimulants along with children friendship training revealed improvement in symptoms compared
to the individual use of medications in the children. The overall findings of the research-study
indicated that there is extensive need to conduct intervention studies using stimulants in FAS
patients so as to determine the effectiveness of cumulative treatment outcome of the holistic
recovery of the children suffering from FAS.

16
HEALTHCARE DISSERTATION
Another research conducted by Petrenko and Alto (2017) suggested that Fetal Alcohol
Disorder are present across nations and the prevalence proportion of the disorder is rising on an
exponential basis over the years. In order to support children as well as their families who are
dealing with FASD, it is extremely important for the healthcare researchers to make use of the
evidence base and implement the best practice to ensure effective management of the symptoms
and promote positive recovery. The research suggests that making use of a number of therapies
such as parent Education and Training as well as Parent Child Assistance program can help in
improving the cognitive functions of the children. In addition this, Breaking the Cycle which
comprises of Relationship focused dyadic intervention in infancy and during the early childhood
can help improving symptoms of anxiety and other psychological symptoms and neuro-
behavioral symptoms. It should further be noted in this regard that parent training workshops that
comprises of psycho-education for the families can help in effective behavior management
strategies and at the same time can also help in advocating in the best interest of the child.
Further, other family-centred programs such as coaching families programs, parent-child
interaction therapy, parent- child moving forward as well as parent child assistance program for
the adults can help in improving the cognitive functions and behavioral outcome in the children
that are suffering from FASD. In addition to this, the research study also builds upon the
available evidence based research studies and recommends that that effective use of nutritional
supplements such as choline supplements as well as pharamacotherapeutics such as stimulants
and neuroleptics can help in improving the behavioral outcome among children suffering from
FASD. It is crucial to note in this context that there has been increasing research that involves
animal trials and evaluate the effectiveness if choline supplementation on the overall cognitive as
well as motor functioning after the pre as well as post administration of choline supplementation.
The research study further reports the findings of Kable et al. 2015 that tested the effectiveness

17
HEALTHCARE DISSERTATION
of micro-nutrient choline supplementation of the cognitive as well as the motor development of
6-month old Infants in Ukraine. The results, revealed that there was a considerable improvement
in the cognitive functioning, but the motor functioning did not improve. In addition to this, the
post-natal supplementation of Choline was tested in two trials, the first included children who
were aged between 2 to 5 years and were administered a dose of 500 mg choline in a powdered
form which was mixed with a fruit flavored drink and was administered for a period of 9 months.
The primary outcomes revealed that choline supplementation helped in improving explicit
memory in the younger children. The second trail was conducted with older children who were
aged between 5 to 10 years and were administered the similar dose, however the impact was not
significant. Researchers are of the opinion that adjusting the dose in accordance to the body
weight can help in acquiring better memory outcome.
Another research-study that was conducted by Nguyen et al. (2016), mentions that the
prenatal-alcohol exposure during the period of pregnancy leads to widespread cognitive as well
as behavioral impairments. On account of the devastating impact of the Fetal Alcohol Disorder,
it is extremely important to scan the evidence-base so as to devise effective measures which
could help in the symptom management of FASDS. The researchers emphasizes on the fact that
preclinical animal studies have revealed that choline supplementation could help in the effective
management of the symptoms related to Fetal Alcohol Disorder in the children. The researchers
in this paper argue that choline is an important nutrient that possessed the capacity to neutralize
or attenuate the severe impact of alcohol and its related cognitive impairments. The researchers
conducted a randomized, double-blind, placebo controlled trial in order to investigate that
whether or not choline supplementation could help in improving the symptoms of memory,
executive function as well as attention deficits in children that were suffering from Fetal-
Alcohol-Syndrome. The researchers investigated the impact of Choline supplementation in fifty

18
HEALTHCARE DISSERTATION
five children who were aged between 5 to 10 years. The researchers administered 625 mg
Choline per day for 6 weeks to the choline group against the other group that received an
inactive placebo treatment. The primary outcomes in terms of neuropsychological measures o
memory, executive function, attention as well as hyperactivity was evaluated at baseline and
after the intervention. The results revealed did not reveal a significant improvement of the school
children across any cognitive domain within the school children. The key findings of the
research study stresses upon the evaluation of effective evidence based interventions in
combination with choline supplementation so as to improve the cumulative behavioral and
cognitive outcome among the children suffering from Fetal Alcohol Syndrome.
Another study conducted by Wozniak et al. (2015), based their research objective upon
the success rate of choline supplementation as an intervention in an animal model and
determined that whether or not post natal choline supplementation in children could improve
memory and cognitive functions. The research study design adapted by the researchers was a
double-blind, randomized, placebo-controlled pilot trail in children who were aged between 2.5
years to 5 years at the time of enrolment. A total of 60 children were recruited for the research
that were suffering from FASD and were administered 500 mg of Choline supplementation every
day for a period of 9 months. The outcome were evaluated using the elicited memory paradigm
for secondary outcome and Mullen Scaled of Early Learning for primary outcome. Overall the
administration suggested that choline was tolerated well by the group of the participants. Overall
the findings suggested that choline supplementation improved memory functioning in children
however, the side effect was evaluated to be fishy body odor that was emitted from the children
who were treated with choline supplementation. It should be noted that future trails in relation to
choline supplementation could help in determining the impact on the level of cognitive
functioning of the children affected with FAS.

19
HEALTHCARE DISSERTATION
Another research-study by Wozinak et al. (2013), suggested that Choline supplement is
well tolerated by children who are suffering from FASD. The researchers conducted a double-
blind, randomized controlled trail that comprised of 20 children who were aged between 2.5
years to 4.9 years of age. The participants were randomly administered 500 mg choline or
placebo for a period of 9 months. The primary outcome measure evaluated the feasibility,
adverse effects, tolerability and the serum choline levels. A total of 17 participants had been
included in the research study and the compliance level was measured to be approximately 82%
to 87% as evidenced by the log sheets filled up by the parents. The overall effects suggested that
the adverse impacts were minimal and only constituted a pungent fishy odor within the active
group. In addition to this, the phase 1 pilot study results suggested that the choline
supplementation at 500 mg dose for 9 months was feasible and tolerable among the children that
were aged in between 2 to 5 years.
Another research study conducted by Lussier et al. (2017), suggests that early
identification of FASD can help in implementation of appropriate interventions which can
effectively help in ensuring symptom management and supporting recovery. Implementation of
molecular medicine in relation to genomic editing can help unravel dimensions of therapeutic
intervention which can help in acquiring a major breakthrough in the treatment of FASD in
children.
According to Murawski et al. (2015), it was reported that FASD symptoms can be
managed with the implementation of a combination of interventions that comprise of
pharmacotherapies, exercise interventions as well as nutritional therapies. The researchers have
further suggested that the implementation of interventions have resulted in positive outcome in
the animal trials, however the research is yet to be tested for effectiveness in human studies.

20
HEALTHCARE DISSERTATION
Animal models have been playing an important role in evaluating and continuing the research on
FASD. The researchers have made use of a number of animal-models in order to test the physical
and behavioral alterations in cases of FASD as seen in human subjects. The models were used in
order to control the factors such as alcohol exposure, nutritional status as well as maternal factors
and genetics which has been studied to affect clinical outcomes in patients suffering from FASD.
The research study further highlights that on account of alcohol exposure, pregnant mothers are
often deprived of a number of essential micronutrients that comprise of Choline, Vitamin A, C,
D,E, B6 as well as Iron, Calcium, Zinc and Omega-3 fatty acids. It has been evaluated in animal
models that the deficiency of these micronutrients leads to detrimental effect on the brain
development. A number of research studies showed that a combination of alcohol exposure and
deficiency of iron led to cerebellar apoptosis as well as reduced myelin content and increased
impairments in cerebellar-dependent classical eye-blink conditioning (Nguyen et al. 2016). A
wide number of research studies also suggest that nutritional supplementation during the period
of pregnancy can help in neutralizing the teratogenic impact of ethanol. The review includes a
research study where two groups of pregnant mothers in Ukraine who were exposed to alcohol
were treated differentially in order to evaluate the impact of nutritional supplements on the
infants and to estimate the prevalence of FASD. It was observed that the group of mothers who
were administered micronutrient supplementation during the period of pregnancy were less
likely to give birth to a baby with Fetal Alcohol Spectrum Disorder. In addition to this, it was
also seen in animal models that administration of antioxidant nutritional supplements such as
Vitamin C, Vitamin E and Omega-3 Fatty acids led to reduced oxidative stress and reduced the
impact of behavioral impairment in rodents that were exposed to alcohol (Hanlon-Dearman et al.
2015). The effectiveness of the antioxidant supplementation revealed positive impact in animal

21
HEALTHCARE DISSERTATION
models, however the same does not hold true for human subjects as research studies conducted in
human subjects have not yielded significant positive clinical outcomes (Murawski et al. 2015).
Research studies also suggest that there is a potential relationship between nutrient
supplements on gene transcription (Koren 2015; Petrenko and Alto 2017). A number of research
trials on animal models suggests that alcohol exposure in parents significantly affects the quality
of genetic transcription. Alcohol exposure is said to have induced changes in terms of DNA
methylation, histone modification as well as non-coding RNAs that affect the expression of the
multiple genes that are involved in the determination of behavior as well as neurodevelopment
patterns. Nutrient supplements such as choline, betaine, Zinc, methionine as well as folic acid
can help in attenuating alcohol-induced changes within the epigenome (Lussier et al. 2017). The
effect of choline- supplementation was tested in rats where it was observed that supplemental
choline in rats that were pre-exposed to alcohol during the developmental process exhibited
alcohol-related changes within the global DNA methylation in the hippocampal region as well as
the prefrontal cortex (Wilhoit et al. 2017) This subsequently led to ethanol-induced methylation
of the genes within the hypothalamus. The nutrient induced changes within the rat led to
significant improvement in terms of behavioral outcome and cognitive functions. A number of
research studies have also indicated that nutritional supplementation such as omega-3 fatty acids,
Vitamin D and Choline can help in improving cognitive and behavioral functions in FASD
infants (Lussier et al. 2017). However, on account of lack of adequate sample size and
appropriate human trials the results can be treated as ambiguous and cannot be generalized. This
invites further research in order to devise appropriate nutritional supplementation intervention
for improved clinical outcome among children suffering from FASD.
Literature Gap:

22
HEALTHCARE DISSERTATION
On the basis of the extensive and elaborate review of the scholarly-literatures, it can be
mentioned that a number of research-studies have investigated the impact of suitable
interventions for the treatment of FASD in children. It is important to note in this context that
most of the research studies focus on animal trials. It should also be noted in this case that a
number of research-studies focus on the implementation of nutritional supplementation as an
intervention to ensure improvement in terms of behavioral as well as cognitive functions in the
children suffering from FASD (Nguyen et al. 2016; Wozniak et al. 2015). However, the trials
evaluating the impact of choline supplementation is substantially low which does not permit the
generalization of the treatment intervention. However, it is also important to note in this context,
that a combination of nutritional intervention, pharmacological therapy and family-centred
practice along with counselling can help in acquiring positive-outcome and improvement in
behavioral outcome for the children suffering from Fetal Alcohol Spectrum Disorder (Petrenko
and Alta 2017; Nguyen et al. 2016). It is important to note in this context that the evidence-base
suggests that symptom management in school age children would require a combination of
pharmacological and cognitive behavioral therapy approach throughout the life span so as to
ensure positive recovery through the span of the syndrome (Koren 2015; Hanlon-Dearman et al.
2015). This suggests that there is a need to conduct further research so as to test the efficacy of
Choline supplementation therapy in order to evaluate its impact on the treatment intervention
outcome of FASD.

23
HEALTHCARE DISSERTATION
Chapter 3: Methodology
3:0: Methodology:
Methodology forms a significant part of a dissertation or a thesis that deals with the
scanning of the evidence base in order to choose an appropriate method that would ideally
answer the articulated research objectives. The feasibility and appropriateness of the data-
collection method is broadly based upon the correct selection of the methodological framework
(Petrenko and Alto 2017). In this section, the exhaustive literature findings from the evidence
base would be summarized followed by making use of a search strategy in order to discuss the
research papers that are closely aligned with the articulated research questions.
3.1: Summary of the Literature Findings:
On the basis of the evidence based research studies, it can be stated that a number of
animal trials have successfully evaluated the effectiveness of choline supplementation in rodents
that were stimulated with FASD. It is important to note here that a few research studies have
successfully established improved tolerance of choline supplementation in children aged two to
five years. Research studies further reveal that choline supplementation in school going children
improves memory and cognitive functions (Murawski et al. 2015; Wilhoit et al. 2017). However,
on account of the poor sample size, the results cannot be generalized. In addition to this, the
evidence base also suggested that a single intervention was not sufficient for the symptom
management of FASD (Wilhoit et al. 2017; Nguyen et al. 2016). In other words a combination of
family-centered practice, counselling, pharaco-therapeutic intervention as well as nutritional
supplementation can help in improving cognitive and behavioral outcome among the affected

24
HEALTHCARE DISSERTATION
patients. Overall, the evidence base suggests that more research is required in order to ensure that
choline supplementation is the single most effective measure that helps in improving the holistic
outcome and symptom management in children suffering from FASD (Hanlon-Dearman et al.
2015; Koren 2015).
3.2: Search Strategy:
The search strategy for conducting the systematic interview comprised of conducting a
thorough search on the popular electronic databases that comprised of Google Scholar and
CINAHL. The electronic databases comprise of a gamut of scholarly literatures that provide an
overview about what has been done so far in the research topic so as to retrieve a guideline about
the research studies and conduct further research to add to the evidence base (Stringer 2013). The
search strategy typically comprised of using specific key terms that were aligned with the
research question and conducting a search on the two electronic databases so as to retrieve
relevant research papers. The search-terms were used in combination with the BOOLEAN
operators that included OR/AND so as to retrieve papers that were most closely linked to the
articulated objectives of the research- study.

25
HEALTHCARE DISSERTATION
Fig: PRISMA Flow Diagram

26
HEALTHCARE DISSERTATION
3.3: Exclusion Criteria:
As per Marshall and Rossman (2014), exclusion criteria can be defined as the specific
characteristics that help in excluding literatures that are not aligned with the research question
and the articulated research objectives. The exclusion criteria in this case, comprised of
characteristics such as consideration of research papers that were published before 2013. In
addition to this, the exclusion criteria also included papers that were published in foreign
languages other than English language. Further, the exclusion criteria also comprised of papers
that were not full-text accessible and only contained abstracts.
3.4: Inclusion Criteria:
According to Tesch (2013), inclusion criteria can be defined as the specific set of
characteristics that are included while conducting a research on the evidence base. The inclusion
criteria included while conducting the search comprised of factors such as consideration of
research papers that were published 2013 to 2017. In addition to this, the inclusion criteria also
comprised of papers that were published in English language. Also, the papers that were included
comprised of qualitative studies, quantitative studies, randomized controlled trails as well as
experimental studies. The papers that were included were full-text accessible and focused on
interventions that are used for the management and treatment of symptoms related to FASD.
3.5: Key Terms:
As mentioned by Whitley and Kite (2013), key terms can be defined as short scientific
phrases or terms that are closely linked to the research-question and aid in recovering appropriate

27
HEALTHCARE DISSERTATION
research studies from the evidence base. The key terms help in filtering the evidence base to
extract research articles that are specifically relate with the research topic. The key terms that
were used to conduct the search on the electronic database comprised of the following:
Intervention, FASD, Choline Supplementation, nutritional supplementation, pharmacological
intervention, clinical outcome, school-aged children, symptom management, evidence-based
practice outcome
The BOOLEAN operators that were used to conduct the research study comprised of OR/ AND.
According to Crano et al. (2014), Boolean operators are used to align two scientific key terms in
order to extract the relevant research study articles. The Boolean Operators were used in
combination with two scientific terms to yield relevant research articles. The following table
represents the usage of the key-terms in combination with the Boolean operators.
Key-Term 1 Boolean Operators Key-Term 2
FASD OR/AND Intervention
Choline supplementation OR/AND Nutritional Intervention
Pharmacological intervention OR/AND Clinical Outcome
School aged children OR/AND Symptom management
Evidence-based practice OR/AND outcome
FASD OR/AND School-aged children
Pharmacological intervention OR/AND Symptom management
Choline supplementation OR/AND FASD
FASD OR/AND Pharmacological intervention
3.6: PICO Questions:
PICO questions help in organizing the key words in order to articulate a proper research
question. As stated by Parahoo (2014), evidence based models make use of an appropriate
process for framing a research question and locating, assessing, evaluating as well as repeating
the process as and when required. The PICO elements comprise of problem/patient/population,

28
HEALTHCARE DISSERTATION
intervention or indicator, comparison and outcome (McNiff 2013). On the basis of the articulated
background information, the PICO questions that can be deduced includes the following:
P: Population Does choline supplementation in FASD
children improve symptom management?
I: Intervention Is choline supplementation an effective
nutritional intervention that helps in
improving clinical outcome in FASD
children?
C: Comparison What are the effects of choline
supplementation in school going children
affected with FASD against normal children
who are not treated with choline
supplementation?
O: Outcome What are the cumulative outcome of the
implementation of evidence-based
intervention for improving clinical outcome in
FASD children?
Therefore, on the basis of the articulated PICO elements, the research questions that can
be framed would comprise of the following:
RQ1: what are the evidence based interventions that help in symptom management in FASD
children?
RQ2: What does the evidence base suggest about the effectiveness of choline supplementation in
improving the clinical outcome of FASD patients?
Research Study Design and Justification:
Therefore, the research study design that would be followed to address the articulated
research questions would comprise of a systematic review of literatures. The rationale for the
same can be explained as evaluation of the evidence base in order to retrieve relevant papers that
are closely aligned with the research question and the research objectives of the concerned
research.

29
HEALTHCARE DISSERTATION
Chapter 4: Results and Discussion
4.0: Literature Findings:
On the basis of the review it can be stated that literature included in the review provide an
insight into what has been researched as promising interventions for the treatment of FASD.
Overall, the literature findings suggest that FASD is a progressive disorder and that it manifests
itself on account of exposure to alcohol during the period of pregnancy. The evidence base
suggests a number of intervention strategies can be used for symptom management so as to
foster support to the children affected with FASD throughout the stages of development.
4.1: Thematic Analysis:
In this section of the dissertation, the findings from the evidence base would be discussed
under themes so as to derive a better understanding about what the review of literatures state
about the intervention practices that are implemented for the treatment and cure of Feta; Alcohol
Spectrum Syndrome.
Choline supplementation as an effective nutritional intervention for the symptom
management of FASD:
Nguyen et al. (2016), conducted a research study in order to evaluate that whether or not
children suffering from FASD suffered from nutritional deficiencies. The research study suggests
that nutritional deficiencies in children can amplify the damaging teratogenic impact of alcohol.
The research study compared and contrasted the nutritional status of school going children
whose parents were exposed to alcohol against children who were subjected to normal dietary

30
HEALTHCARE DISSERTATION
intake. The researchers collected the data of children who were aged in between 5 to 10 years
and had a history of excessive parental alcohol exposure. The data was collected using the
automated self-administered 24 hour dietary recall and the observed nutrient level was contrasted
to the Dietary-Reference Intake in order to assess the appropriateness of the nutrient intake to the
national mean for the normal children who were of the same age. The findings of the research
study suggested that the children that were exposed to heavy amount of alcohol intake shower
poor nutritional status when compared to the children of the similar age group whose parents
were not exposed to alcohol. In addition to this, the results further revealed that children
suffering from FASD were deprived of essential micronutrients such as protein, Omega 3 fatty
acid, Vitamin, C, Vitamin K, Niacin as well as Choline. Also the nutritional intake of these
children were not aligned to the recommended dietary allowance or intake for potassium,
Vitamin E and K, Omega-3 fatty acids, Choline and Dietary fiber. The overall findings of the
research indicated that children suffering from FASD are deprived of essential nutrients. In
addition to this, a number of research studies have also mentioned that the essential nutrients
such as Zinc, Choline, Vitamin E and K as well as Omega-3 fatty acids are extremely important
for the maintenance of normal brain and cognitive functions and that nutritional deficiencies of
these essential nutrients could lead to deterioration in cognitive functioning.
Another research study conducted by Nguyen et al. (2016), focused on investigating that
whether or not choline supplementation can neutralize the severity of loss of memory, executive
function and attention deficits in those children that are suffering from FASD. The research
design comprised of a randomized, double-blind, placebo-controlled clinical trial that evaluated
the effectiveness of choline intervention in children who were aged between 5 to 10 years and
were suffering from Fetal Alcohol Spectrum Disorder. The researchers compared a sample size
of 55 participants that had histories of alcohol exposure. The participants were divided into two

31
HEALTHCARE DISSERTATION
groups that were either treated with choline supplementation (n=29) or placebo (n=26) treatment
arms. The participants in the choline group were administered a dose of 625 mg choline for a
span of 6 weeks (Nguyen et al. 2016). On the other hand, the placebo treatment group received
an equivalent dose of inactive placebo treatment. The primary outcome suggested that the
neuropsychological measures of the memory, executive function as well as attention outcome
and hyperactivity significantly improved post choline supplementation intervention.
Wozinak et al. (2015) conducted a similar research study in order to determine that
whether or not postnatal choline supplementation could potentially improve neurocognitive
functioning with regard to hippocampal-dependent memory in children that were suffering from
Fetal Alcohol Spectrum Disorder. The researchers conducted a double-blind, randomized,
placebo-controlled pilot trial in children that were aged 2.5 to 5 years during the time of
enrolment and were suffering from FASD. A total of 60 children were recruited who received a
dose of 500 mg Choline or a placebo for a span of 9 months. The clinical outcomes were
evaluated with the help of Mullen Scaled of Early Learning and the elicited imitation memory
paradigm. The research results showed that Choline was tolerated well with the participants who
received a medication dose over 88% of the enrollment days. In addition to this, the research
results also stated that a fishy body odor was the only side effect that was linked to treatment
with choline supplementation. The treatment effect on the elicited imitation memory paradigm
was improved in the younger children who were aged 2.5 years to 4 years old. In addition to this,
it was also observed that the group of participants that was treated with choline intervention
exhibited an increase of 12 t0 14 percentage points that was more than the younger placebo
group on delayed recall-measures during the process of treatment process. It should further be
noted that there was a marginal baseline difference in the delayed item recall which contributed
to the exhibited treatment effect. A negative effect of choline supplementation was observed on

32
HEALTHCARE DISSERTATION
the immediate elicited imitation recall criteria of the ordered pairs. The placebo group of the
young group exhibited that there was a 8 to 17 percent increase in terms of memory and
executive function in the group that was given choline supplementation intervention. Further an
inverse relationship was observed between the choline dose (in mg/kg) and level of improvement
in terms of memory (P=0.041). Overall the research suggested that weight adjusted doses of
Choline supplementation yielded better clinical outcome (Wozinak et al. 2015). The overall
findings of the research study support the validity of the intervention that choline
supplementation is an effective treatment measure to improve cognitive functions and memory
outcome in children (Wozinak et al. 2015).
Evidence-based intervention strategies for the treatment of FASD in school children:
According to Willhoit, Scottt and Simecka (2017), fetal alcohol spectrum disorder is a
progressive disorder that manifests in children due to increased alcohol consumption of the
mothers during the period of pregnancy. It should further be noted that Fetal Alcohol Syndrome
manifests differentially in different children. It should further be noted that extending life-long
support to the affected children can help in coping with the neurological and behavioral
impairment. Dearman et al. (2015) stated that FASD is a broad disease term that leads to a wide
range of complications that includes neurological and behavioral impairment in children. The
research recommends a set of evidence based practices which could be used by healthcare
professionals in order to support the children suffering from FASD. The research stated that
referral for diagnosis made by the Physician with regard to screening, prevention and sub-
speciality referrals can help in improving outcome of the patient and their families (Dearman et
al. 2015). Another research study conducted by Petrenko and Alto (2017), suggested that support
interventions including parenting and education, attention and self-regulation, adaptive

33
HEALTHCARE DISSERTATION
functioning as well as nutrition and medication can help in improving clinical outcome in
children suffering from Fetal Alcohol Syndrome Disorder. Research studies state that special
education and social service in association with a nurturing environment can help in promoting a
sound development and management of the symptoms (Koren 2015; Schneider and Thomas
2016). In addition to this, a number of research studies also stated that implementation of
antipsychotic medication could help in managing symptoms related to hyperactivity and anxiety
in children affected with FASD (Koren 2015; Bearer et al. 2015).
Advanced medication for the treatment of FASD in school children:
Lussier, Weinberg and Kobor (2017) stated in their research paper that parental exposure
to alcohol could potentially lead to complicated physiological systems that could give rise to
neuro-developmental deficits. Research data in this regard has shown that alcohol exposure
could reprogram the interrelated neurobiological systems which could subsequently alter the
health, behavioral as well as health outcomes. It is crucial to note in this regard that the evidence
base suggests that epigenetic mechanism governs the process of environmental and genomic
interplay that subsequently determines neuro-developmental outcome. The findings of the
research state that research studies that evaluate DNA methylation patterns, ncRNA expression
levels and chromatin states can help in medication designing that could subsequently help in
unraveling the potential targets of the therapeutics (Lussier et al. 2017). In addition to this,
research studies further predict that identification of FASD biomarkers can help in devising
appropriate pharmacological treatment interventions for children affected with FASD (Lussier et
al. 2017). However, research studies discussing the recent genetic advances of the
pharmacological interventions are limited and required further research.

34
HEALTHCARE DISSERTATION
4.2: Critical Analysis:
On critically accessing the quality of the evidence base, it can be stated that the included
papers do not comprise of sufficient sample size which could help in generalizing the results and
findings. In addition to this, the evidence base lacks ample amount of research papers that could
validate choline supplementation as an effective intervention for the treatment of FASD. More
research is required in order to validate the same. A number of research studies suggest the
effectiveness of the intervention in animal trials but the same needs validation in human studies
(Muralidharan et al. 2013; Balaraman et al. 2017; Scheinder and Thomas 2016). In addition to
this, the evidence based practices that suggested choline supplementation in combination with
pharmaco-therapeutic intervention and additional support can be explained as effective symptom
management support options (Fuglestad et al. 2017; Idrus et al. 2017). It is also important to note
here that the papers included in the review are recent and are published between 2013 to 2017,
which suggests that the review provides a recent overview about the treatment advances made in
the research area. Also, the research papers included comprise of primary research articles,
randomized control trails and systematic review which suggests that the most relevant and
reliable piece of information from the evidence base has been considered in the research study.
4.3: Discussion:
Therefore, on the basis of the analysis of the scholarly research papers, it can be
mentioned that choline supplementation is one of the nutritional interventions that has been used
in order to manage and treat the symptoms of fetal alcohol disorder. A number of research
studies had investigated the dosage tolerance level of choline supplementation. Typically, the
evidence base states that choline supplementation is tolerated effectively among the children

35
HEALTHCARE DISSERTATION
aged 2 to 5 years. In addition to this, it was also found that the side effects of the intervention led
to fishy body odor. It was also found that choline supplementation improved memory and
cognitive functions on the group of participants. However, it should be critically noted in this
context, that most of the papers that discussed the impact of choline supplementation were
restricted to animal trails and only a few papers focused on evaluating the impact of choline
supplementation in school going children. In this regard, it should also be stated that two of the
reviewed papers focused on the use of antipsychotic medication to control symptoms of anxiety
and hyperactivity in children affected with FASD. In addition to this, occupational therapy,
special education as well as improved parent education and counseling were some of the
methods that evidence based therapeutic interventions that could help in improving the holistic
clinical outcome among the suffering patient (Koren 2015; Wozinak 2015). One of the papers
talked about genetic precision medication that could potentially help in treating the symptoms of
FASD, however there is a need of increased research to validate the same (Liyanage et al. 2017;
Lussier et al. 2017).
4.4: Summary:
Therefore, to summarize the key findings from the reviewed papers, it can be mentioned
that FASD is a life-long and progressive disorder that manifests itself in the fetus on account of
maternal exposure to alcohol during the time of pregnancy. In addition to this, the evidence base
further suggests that the disease is not curable but the symptoms can be managed with the
implementation of nutritional and pharmacological intervention that include choline
supplementation and administration of antipsychotic medication (Koren 2015). It has been
validated by the research studies that choline supplementation intervention in school children as
well as during the prenatal period leads to improved cognitive functions and memory capacity

36
HEALTHCARE DISSERTATION
(Wozinak et al. 2013; Wozinak et al. 2015; Nguyen et al. 2016). In addition to this, research
studies also state that additional support interventions such as special education and occupational
therapy can help affected children cope with the symptoms better (Koren 2015). Also, future
medical studies such as implementation of genetic precision medication therapies can help in
improving holistic clinical outcome among the children affected with FASD (Lussier et al.
2017).
4.5: Limitations:
The limitations of the systematic review majorly comprise of the lack of proper evidence
aligned to the research topic. In addition to this, the research papers included in the study contain
poor sample size that restricts the ability to generalize the results. However, on account of the
stipulated time-frame, it can be said that the systematic review of the scholarly literatures has
justified the purpose and significance of the research.

37
HEALTHCARE DISSERTATION
4.6: Level of evidence:
Authors Research Title Level of evidence Key findings
Nguyen et al. 2016 Dietary Nutrient
Intake in School‐Aged
Children With Heavy
Prenatal Alcohol
Exposure
Medium Children affected with
FASD are deprived of
essential
micronutrients that
play an integral role in
the brain development
process
Willhoit et al. 2017 Fetal Alcohol
Spectrum Disorders:
Characteristics,
Complications, and
Treatment
High Early intervention and
long-support
management can help
in promoting positive
outcome through the
developmental
processes
Dearman et al. 2015 Anticipatory
Guidance fo Children
and Adolescents with
Fetal Alcohol
Spectrum Disorder
(FASD): Practice
Points for Primary
Health Care Providers
Medium parent education and
counseling along with
support interventions
can help in effective
symptom
management through
developmental
processes
Koren 2015 Pharmacological
Treatment of
Disruptive Behavior
in Children with Fetal
Alcohol Spectrum
Disorder
Medium Administration of
anti-psychotic
medication and
support interventions
such as special
education and
occupational therapy
can help in improving
clinical outcome
among patients
Petrenko and Alto
2017
Interventions in fetal
alcohol spectrum
disorders: An
international
perspective
Medium Support strategies
such as parent
counseling and
education and help in
providing support to
the children through
the developmental
process
Nguyen et al. 2016 Randomized, double-
blind, placebo-
High Choline
supplementation

38
HEALTHCARE DISSERTATION
controlled clinical
trial of choline
supplementation in
school-aged children
with fetal alcohol
spectrum disorders
improves cognitive
function and memory
in children suffering
from FASD
Wozinak et al. 2015 Choline
supplementation in
children with fetal
alcohol spectrum
disorders: a
randomized, double-
blind, placebo-
controlled trial
High Choline
supplementation is
well tolerated by
children suffering
from FASD and has
no adverse outcomes
except for fishy body
odor.
Lussier et al. 2017 Epigenetics studies of
fetal alcohol spectrum
disorder: where are
we now?
High Genetic precision
medication can help
in improving clinical
outcome in children
suffering from FASD

39
HEALTHCARE DISSERTATION
Chapter 5: Conclusion and Recommendations
5.0: Conclusion:
Therefore, to conclude, it can be mentioned that the research study has primarily focused
on investigating the evidence base in order to evaluate the evidence based interventions for the
treatment and symptom management of FASD. In addition to this, the research study also
intended to investigate that whether or not choline supplementation is an effective method for
symptom management among FASD school going children. The review was conducted after
scanning the two electronic databases of CINHAL and Google Scholar. On the basis of the
literature findings, it can be established that choline supplementation is effectively tolerated and
improves outcome in relation to memory function and cognitive functioning. Further, it was also
found that choline supplementation was majorly linked with fishy body odor as a potential
adverse effect. Also, studies suggested that a combination of family-centred practice that
involved parent education and counseling, special education, nutritional and pharmacological
intervention as well as occupational therapy could help the affected child throughout lifespan in
effectively manage his symptoms. In addition to this, advanced medication therapies such as
genetic precision medicine was also included and discussed, however, it needs further research in
order to validate the effectiveness of the treatment measures.
5.1: Recommendation:
The recommendations would majorly comprise of encouraging and inclusion of future
research in order to test the effectiveness of choline supplementation on the cognitive and
neurological functions of the children suffering from FASD. In addition to this, inclusion of
studies that focus on evaluation of an equivalent to choline supplementation would also help in

40
HEALTHCARE DISSERTATION
improving outcome. Further, more promising research on genetic precision therapeutic
medication can help in improving holistic outcome and help in supporting affected FASD
patients throughout their life span.

41
HEALTHCARE DISSERTATION
References:
Balaraman, S., Idrus, N.M., Miranda, R.C. and Thomas, J.D., 2017. Postnatal choline
supplementation selectively attenuates hippocampal microRNA alterations associated with
developmental alcohol exposure. Alcohol, 60, pp.159-167.
Bearer, C.F., Wellmann, K.A., Tang, N., He, M. and Mooney, S.M., 2015. Choline ameliorates
deficits in balance caused by acute neonatal ethanol exposure. The Cerebellum, 14(4), pp.413-
420.
Coriale, G., Fiorentino, D., Di Lauro, F., Marchitelli, R., Scalese, B., Fiore, M., Maviglia, M. and
Ceccanti, M., 2013. Fetal Alcohol Spectrum Disorder (FASD): neurobehavioral profile,
indications for diagnosis and treatment. Rivista di psichiatria, 48(5), pp.359-369.
Crano, W.D., Brewer, M.B. and Lac, A., 2014. Principles and methods of social research.
Routledge.P.63
Fuglestad, A.J., Fink, B.A., Eckerle, J.K., Boys, C.J., Hoecker, H.L., Kroupina, M.G., Zeisel,
S.H., Georgieff, M.K. and Wozniak, J.R., 2013. Inadequate intake of nutrients essential for
neurodevelopment in children with fetal alcohol spectrum disorders (FASD). Neurotoxicology
and teratology, 39, pp.128-132.
Fuglestad, A.J., Fink, B.A., Eckerle, J.K., Boys, C.J., Hoecker, H.L., Kroupina, M.G., Zeisel,
S.H., Georgieff, M.K. and Wozniak, J.R., 2013. Inadequate intake of nutrients essential for
neurodevelopment in children with fetal alcohol spectrum disorders (FASD). Neurotoxicology
and teratology, 39, pp.128-132.

42
HEALTHCARE DISSERTATION
Fuglestad, A.J., Whitley, M.L., Carlson, S.M., Boys, C.J., Eckerle, J.K., Fink, B.A. and
Wozniak, J.R., 2015. Executive functioning deficits in preschool children with Fetal Alcohol
Spectrum Disorders. Child Neuropsychology, 21(6), pp.716-731.
Hanlon-Dearman, A., Green, C.R., Andrew, G., LeBlanc, N. and Cook, J.L., 2015. Anticipatory
Guidance fo Children and Adolescents with Fetal Alcohol Spectrum Disorder (FASD): Practice
Points for Primary Health Care Providers. Journal of Population Therapeutics and Clinical
Pharmacology, 22(1).
Ias.org.uk (2019). UK foetal alcohol rates among highest in the world - IAS. [online] Ias.org.uk.
Available at: http://www.ias.org.uk/What-we-do/Alcohol-Alert/January-2017/UK-foetal-alcohol-
rates-among-highest-in-the-world.aspx [Accessed 11 Jun. 2019].
Idrus, N.M., Breit, K.R. and Thomas, J.D., 2017. Dietary choline levels modify the effects of
prenatal alcohol exposure in rats. Neurotoxicology and teratology, 59, pp.43-52.
Kable, J. A., Coles, C. D., Keen, C. L., Uriu-Adams, J. Y., Jones, K. L., Yevtushok, L., ... &
CIFASD. (2015). The impact of micronutrient supplementation in alcohol-exposed pregnancies
on information processing skills in Ukrainian infants. Alcohol, 49(7), 647- 656.
Koren, G., 2015. Pharmacological treatment of disruptive behavior in children with fetal alcohol
spectrum disorder. Pediatric Drugs, 17(3), pp.179-184.
Lussier, A.A., Weinberg, J. and Kobor, M.S., 2017. Epigenetics studies of fetal alcohol spectrum
disorder: where are we now?. Epigenomics, 9(3), pp.291-311.
Marshall, C. and Rossman, G.B., 2014. Designing qualitative research. Sage publications.P.22-
27

43
HEALTHCARE DISSERTATION
McNiff, J., 2013. Action research: Principles and practice. Routledge.P.88
Muralidharan, P., Sarmah, S., Zhou, F. and Marrs, J., 2013. Fetal alcohol spectrum disorder
(FASD) associated neural defects: complex mechanisms and potential therapeutic targets. Brain
sciences, 3(2), pp.964-991.
Murawski, N.J., Moore, E.M., Thomas, J.D. and Riley, E.P., 2015. Advances in diagnosis and
treatment of fetal alcohol spectrum disorders: from animal models to human studies. Alcohol
research: current reviews, 37(1), p.97.
Nguyen, T. T. (2015). Choline intervention in children with fetal alcohol spectrum disorders.
Retreived from ProQuest Dissertation & Theses International (3712754)
Nguyen, T.T., Risbud, R.D., Chambers, C.D. and Thomas, J.D., 2016. Dietary Nutrient Intake in
School‐Aged Children With Heavy Prenatal Alcohol Exposure. Alcoholism: Clinical and
Experimental Research, 40(5), pp.1075-1082.
Nguyen, T.T., Risbud, R.D., Mattson, S.N., Chambers, C.D. and Thomas, J.D., 2016.
Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in
school-aged children with fetal alcohol spectrum disorders. The American journal of clinical
nutrition, 104(6), pp.1683-1692.
Parahoo, K., 2014. Nursing research: principles, process and issues. Macmillan International
Higher Education.P.76
Petrenko, C.L. and Alto, M.E., 2017. Interventions in fetal alcohol spectrum disorders: An
international perspective. European journal of medical genetics, 60(1), pp.79-91.

44
HEALTHCARE DISSERTATION
Rasmussen, C., Tamana, S., Baugh, L., Andrew, G., Tough, S. and Zwaigenbaum, L., 2013.
Neuropsychological impairments on the NEPSY-II among children with FASD. Child
Neuropsychology, 19(4), pp.337-349.
RB Liyanage, V., Curtis, K., M Zachariah, R., E Chudley, A. and Rastegar, M., 2017. Overview
of the genetic basis and epigenetic mechanisms that contribute to FASD pathobiology. Current
topics in medicinal chemistry, 17(7), pp.808-828.
Schneider, R.D. and Thomas, J.D., 2016. Adolescent choline supplementation attenuates
working memory deficits in rats exposed to alcohol during the third trimester
equivalent. Alcoholism: Clinical and Experimental Research, 40(4), pp.897-905.
Stringer, E.T., 2013. Action research. Sage publications.P.90-92
Tesch, R., 2013. Qualitative research: Analysis types and software. Routledge.P.11-113
Tsang, T.W., Lucas, B.R., Olson, H.C., Pinto, R.Z. and Elliott, E.J., 2016. Prenatal alcohol
exposure, FASD, and child behavior: A meta-analysis. Pediatrics, 137(3), p.e20152542.
Whitley, B.E. and Kite, M.E., 2013. Principles of research in behavioral science.
Routledge.P.50-52
Wilhoit, L.F., Scott, D.A. and Simecka, B.A., 2017. Fetal alcohol spectrum disorders:
characteristics, complications, and treatment. Community mental health journal, 53(6), pp.711-
718.
Wozniak, J. R., Fuglestad, A. J., Eckerle, J. K., Kroupina, M. G., Miller, N. C., Boys, C. J., ...
and Georgieff, M. K. 2013. Choline supplementation in children with fetal alcohol spectrum
disorders has high feasibility and tolerability. Nutrition research, 33(11), 897-904.

45
HEALTHCARE DISSERTATION
Wozniak, J.R., Fuglestad, A.J., Eckerle, J.K., Fink, B.A., Hoecker, H.L., Boys, C.J., Radke, J.P.,
Kroupina, M.G., Miller, N.C., Brearley, A.M. and Zeisel, S.H., 2015. Choline supplementation
in children with fetal alcohol spectrum disorders: a randomized, double-blind, placebo-controlled
trial. The American journal of clinical nutrition, 102(5), pp.1113-1125.
Wozniak, J.R., Fuglestad, A.J., Eckerle, J.K., Kroupina, M.G., Miller, N.C., Boys, C.J., Brearley,
A.M., Fink, B.A., Hoecker, H.L., Zeisel, S.H. and Georgieff, M.K., 2013. Choline
supplementation in children with fetal alcohol spectrum disorders has high feasibility and
tolerability. Nutrition research, 33(11), pp.897-904.