Escolar Documentos
Profissional Documentos
Cultura Documentos
A Research Proposal
Submitted By:
Jimenez, Margaret Stephanie
Jimenez, Sarah Jane
Joaquino, John Marquis
Jordan, Stephanie Patricia
Preceptor:
Dr. Georgina Paredes
Department of Preventive and Community Medicine
College of Medicine, UERMMMCI
CHAPTER 1.
INTRODUCTION
B. HYPOTHESIS
Null Hypotheses:
a) There is no difference in the risk of developing autism among children of mothers who
smoke and children of mothers who do not smoke during prenatal period
b) There is no difference in the risk of developing autism among children of mothers who do
drink alcoholic beverages and children of mothers who drink alcoholic beverages during
the prenatal period
Alternative Hypotheses:
a) There is a difference in the risk of developing autism among children of mothers who
smoke and children of mothers who do not smoke during prenatal period
The odds of having a child with ASD is higher among mothers with a higher pack
years of smoking than those with lower pack years
b) There is a difference in the risk of developing autism among children of mothers who do
drink alcoholic beverages and children of mothers who drink alcoholic beverages during
the prenatal period
The odds of having a child with ASD is higher among mothers who are chronic
alcoholic drinkers than those who are not.
CHAPTER 2.
REVIEW OF RELATED LITERATURE
significantly associated with ASD are advanced maternal age, parity, and advanced paternal
age11. Although there is insufficient evidence to implicate any one factor in autism etiology,
exposure of a broad class of conditions that compromise perinatal and neonatal health may
increase the risk12. Exposure to smoking and alcohol intake during pregnancy are two common
risk factors for the development of neurodevelopmental disorders, and as such may be associated
with the pathogenesis of ASD13,14.
It must be emphasized that the exact etiology of ASD is not yet known, and studies agree
that an interplay between multiple genetic and environmental factors contribute to the
development of ASD. Thus, findings obtained from studies on ASD abroad might not be
applicable to the Filipino population. This further underscores the need for more research
regarding the disease in the Philippines.
sites in the United States. Results identified a higher prevalence of ASD for non-Hispanic white
children compared with non-Hispanic black children.
Results also showed showed an increase in prevalence of identified ASD among U.S
children aged 8 and underscore a need to regard ASD as an urgent public health concern 2. In the
United States an average of 1 child in every 150 has ADS and there is needed to improve early
identification of ADS2. There is a lack of awareness about autism among medical professionals 1.
Features of children with less than 2 years of age are subtle and difficult to define and the need to
be reassessed of ADS after the age of 2 is required1.
In a descriptive hospital based study with children with autism, the major clinical
symptoms observed and commonest complaints were delayed development of speech and being
lost in ones own world1. Children presented with difficulties in toilet training. ADS patients
showed no interest in play and used the toys inappropriately. Imaginative and pretend play was
absent. Children expressed behavioral problems like hyperactivity aggression and self-injury,
which is due to increase levels of endorphins1. Continued monitoring is needed to document and
understand changes over time, including the multiple ascertainments and potential risk factors2.
All professionals involved in the diagnosing ASD in children should consider either
LED-10 or DSM-IV-TR systems15. Professionals should aim to identify ASD early since it
provides opportunity for early referral and intervention so the child with ADS may have an
improved functioning later in life. Active monitoring by health care professionals is
recommended of 18 months and again at 24-36 months for key signs of ADS. Every pre-school
child diagnosed with ADS should have an individualized intervention plan that sets out goals,
types, frequency and intensity of intervention 15. Continued monitoring is varied according to the
childs changing need. No single language or communication intervention is appropriate for all
children; the optimal communication intervention for an individual child with ASD depends on
the need of a particular child.
ASD in the Philippines is not well characterized, both in terms of its prevalence and the
management of the disease. According to the Autism Society of the Philippines, the estimated
prevalence of Filipino children with autism in 2007 is 500,0003. However, there is no formal
figure due to the lack of funding towards researches on this disease.
A study by Dr. Alexis Reyes, a leading Filipino Developmental Pediatrician, extrapolated
that 0.5 million Filipinos exhibit neuro-behavioral disorder if the prevalence rate in the United
States will be the basis. Using this figure, only two percent of them will be given appropriate
care16. Data gathered from the Philippine General Hospital reveals that autism is ranked third in
the top 10 developmental disorders16, 17. However, it is important to note that no records from
private hospitals or clinics were obtained.
The study presents significant issues regarding the national outlook on Autism. It
emphasized a strong need for an appropriate national program that addresses the deficiencies
regarding the treatment and care regarding children with autism. Numerous deficiencies with
regards to patient care in the Philippine setting were identified: first, there is a lack of a national
center or institute for diagnostic and treatment procedures. Second, treatment is limited to
Western medical and behavioral approaches which are not always suitable for the cultural needs
of the patients. Third, the role of the non-medical professionals are not recognized. Creative
therapies used by psychologists and counselors are not put in the mainstream and are limited to
private practice. Fourth, the Autism Society of the Philippines, a non-profit organization founded
by parents of children with ASD is not incorporated with the medical professions systemically.
Lastly, the fundamental role of parents and family members with ASD, which is of fundamental
leading to metabolic deficiencies and even injury to major organs particularly the liver and even
the central nervous system. There are however certain situations such as pregnancy whereby
alcohol even in small amounts can have injurious effect18.
Ethanol consumption among pregnant women has found out to have damaging effect in
the central nervous system of the infant leading to impaired cognitive and behavioral function 19.
In another recent study where the researchers determined the frequencies of different
neurodevelopmental disorders using a cohort study found out that that 9% among 71 children
who have mothers with prenatal alcohol exposure exhibits autism20. Nonetheless, the study did
not determine if there is an association between prenatal alcohol exposure and developing
autism. Furthermore, in this study, autism was only classified as a co-morbid of FAS or fetal
alcohol syndrome.
A case-control study explored the relationship between FASD (fetal alcohol syndrome
disorder) and ASD (autism spectrum disorder) in individuals attending a specialist diagnostic
clinic. The study found out that 72% of the subjects have autism and that therefore there is an
association between FASD and having ASD21.
Nonetheless, for both studies, it must be noted that only a small population was used
which may indicate that samples may not be a representative of the total population.
Furthermore, the focus of both studies was FASD and not ASD per se. Indicating that both
studies did not clearly state whether ASD was due to prenatal alcohol exposure or just a comorbid or a manifestation of FASD.
A study on Autism families with a high incidence of alcoholism results also showed an
association between prenatal alcohol exposure and autism13. Nonetheless, the researchers also
pointed out that there are no literatures or studies that distinctly indicate that alcohol exposure
among mothers can be associated to ASD simply because the incidence of alcoholism is so much
greater than autism that the sample size of children with autism should be larger in order to have
a valid association.
With this, it must be clear that the association of prenatal alcohol exposure (whether in
low or high doses) in developing ASD alone is not yet fully established.
mothers23. The researchers concluded that intrauterine and neonatal factors related to deviant
intrauterine growth or fetal distress is important in the pathogenesis of autism.
Studies that focus on the mechanisms regarding the specific effects of smoking to
prenatal development are numerous. Tobacco contains over 2000 chemical constituents, all of
which may induce neurotoxic effects such as decreasing cerebral blood and causing brain
hypoxia resulting to production of high levels of carboxyhemoglobin and relative brain
hypoxia24. Nicotine may affect a broad spectrum of neurotransmitter receptors in the fetal brain
leading to abnormal cell proliferation and differentiation as well as abnormal up-regulation and
down-regulation of neurotransmitter receptors25. Post-mortem studies on autistic subjects have
exhibited a notable reduction in cortical nicotinic receptor binding 26. Moreover, other findings
have suggested that fetal nicotine exposure may affect brain development and 5HT synaptic
function linked with behavioral abnormalities27.
Hence, there is an evident need for additional studies that may provide more information
regarding the effects of maternal smoking on the development of autism among children owing
to the lack of sources.
CHAPTER 3.
METHODOLOGY
related to or have the same characteristics (such as age, occupation, and socioeconomic status) as
the mothers of children with ASD. Suggested participants in the control group are work mates
and neighbors of mothers with autistic children; so that the characteristics and the environmental
conditions of both mothers will be the same.
Inclusion criteria are mothers of children ages 4-11 years old who are diagnosed to have
ASD by a board-certified developmental pediatrician and who are members of the Autism
Society of the Philippines or regularly go to special education clinics in Metro Manila. Minimum
child age is set as 4 years old since it is the median age at which a child is diagnosed to have
ASP; maximum age is set at 11 years old to prevent recall bias on the part of the mother.
Exclusion criteria include mothers with comorbid conditions such as psychiatric
disorders, illicit drug intake, or any hereditary disease. Children with ASD symptoms who are
diagnosed with other comorbid diseases such as Fetal Alcohol Syndrome and Downs syndrome
will also be excluded.
Specification
p = 0.12
d = 2.4
(1.96)2(0.12)(0.88)
(2.4)2
=14 (for each control and
case group)
p = 0.09
d = 1.8
(1.96)2(0.09)(0.91)
(1.8)2
= 19 (for each control and
case group)
echolalia wherein they repeat words and phrases over and over again, they give unrelated
answers in response to questions, they get upset with minor changes, they have obsessive traits,
flap their hands and rock their bodies28.
Social skills are the most common symptoms in all types of ASD. Examples of social
issues related to ASDs are they do not share interests with others, only interacts to achieve
desired goals, has flat and inappropriate facial expression, does not understand personal space
boundaries, avoids and resists physical contact and is not comforted by others during distress.
Examples of communication issues related to ASDs are, delayed in speech and language skills,
they usually reverse pronouns (e.g they interchange me and I), uses no or a few gestures, talks in
a robot voice and does not understand jokes and sarcasm28.
People with ASD show unusual interests and behaviors. Examples of these are they like
lining up toys or other objects, they play with the same toys in the same way every time, they
like specific parts of objects, they are very well organized, follow certain routines. People with
ASDs repeat actions over and over again which may involve one or more body parts. Repetitive
activities are know as self-stimulation or stimming They thrive in routine, once their routine is
broken they usually lose control and have tantrums28.
Other symptoms related to ASD are hyperactivity, impulsivity, short attention span,
aggression, temper tantrums, unusual eating and sleeping habits, unusual moods or emotion
reactions and lack of fear or more fear than expected28.
Smoking: defined as a practice in which tobacco is inhaled through cigarettes, expressed
in pack years. Pack years is equal to the number of cigarettes smoked per day, multiplied by the
number of years smoked, divided by 20.
o Low pack years: defined as mothers with pack years less than 5
o High pack years: defined as mothers with pack years greater than or equal to 5.
o No exposure: defined as mothers who have never smoked (pack years = 0).
Alcohol intake: defined as the consumption of any beverage containing ethanol, and may
include beers, wines, and spirits.
o Chronic alcohol drinker: defined as people who have dependency on alcohol
which includes strong craving for alcohol and inability to limit drinking. For
women, mostly defined as consuming an average of more than 1 drink per day.
o Non-chronic alcohol drinker: Includes moderate drinking and binge drinking.
o Moderate drinking: Defined as having no more than 1 drink per day
o Binge drinking: Defined as 4 or more drinks on a single occasion for
women, generally within about 2 hours.
(+) smoking
(-) smoking
a
c
b
d
After computing the odds ratio, regression analysis will be done to determine which
among the maternal characteristics surveyed (such as age of pregnancy, number of children,
socioeconomic status, degree of alcohol intake, degree of smoking intake) contributed the most
to the development of autism among children.
H. Dummy Tables
Objective 1: To describe the socio-demographic characteristics of mothers of children (4-11
years old) with ASD according to:
Table 1. Socio-demographic characteristics of mothers of children with
ASD
Characteristic
Age of mothers when they
conceived their child with
ASD
Below 18 years old
18 25 years old
26 35 years old
35 40 years old
Above 40 years
old
Income Status
High
Middle
Low
Highest educational
attainment
Elementary
Frequency
Percentage
High School
College
Marital Status
Single
Married
Widowed
Objective 2, 3, 4 and 5: (2)To determine the prevalence of prenatal smoking exposure among
mothers with and without children with ASD. (3) To determine the prevalence of prenatal alcohol
exposure among mothers with and without children with ASD (4) To describe the association of
smoking before or during pregnancy in developing ASD among their children (5) To describe the
association of alcoholism before or during pregnancy in developing ASD among their children.
Table 2. Comparison of smoking and alcohol exposure between mothers with and without
children with ASD.
Mothers with autistic
children
Frequency
Percentage
Smoking
Without exposure:
With exposure:
- High pack years
- Low pack years
Alcohol
Without exposure:
With exposure:
- Chronic alcoholic
- Non-chronic alcoholic
CHAPTER 4.
TIMELINE AND BUDGET
A. Schedule of Activities
Weeks
1.
2.
3.
4.
5.
6.
7.
8.
9.
Coordinatin
g with
schools
KII
interviews
Selection of
participant
s for pretesting
FGD for
pre-testing
of
questionnai
re
Editing
questionnai
re
FGD for
final pretesting of
questionnai
re
Final
editing of
questionnai
re
Selecting
cases
Data
Collection
for cases
10. Selecting
Controls
11. Data
Collection
for controls
12. Data
Processing
13. Data
Analysis
14. Writing of
paper
1
0
1
1
1
2
1
3
1
4
1
5
1
6
1
7
1
8
1
9
2
0
B. Budget
Items
Printing
- Ink
- one ream of bond paper x 2
- photocopy and binding (proposal and thesis presentation)
- ball pens (2 boxes)
Subtotal
Transportation Fare
KII token
Food
- First FGD; Pre-testing (moderator and 10 participants)
- Second FGD; Pre-testing (moderator and 10 participants)
Subtotal
Total
C.
Amount (Pesos)
-
100
500
500
1200
1000
400
100
360
360
720
3320
REFERENCES
1. Juneja M, Mukherjee SB, Sharma S. A Descriptive Hospital Based Study of Children
with Autism. Indian Pediatrics 42: 453-458, 2005.
2. Rice C. Prevalence of Autism Spectrum Disorders. Center for Disease Control Autism
and Developmental Disabilities Monitoring Network. United States, 2006.
3. Early Signs of Autism. What is the Global Incidence of Autism? Accessed 2011 August
26 from <http://www.earlysignsofautism.com/what-is-the-global-incidence-of-autism/>
4. Reyes A. The Many Faces of Autism. Philippine Society of Developmental and
Behavioral Pediatrics, 2009.
5. Engel, SM. On the Complex Relationship Between Genes and Environment in the
Etiology of Autism. Epidemiology 22(4): 486-488, 2011.
6. American Psychiatric Association. Diagnostic and statistical manual of mental
disorders, 4th ed. Washington, DC, USA, 1994.
7. Corbett BA, Constantine LJ, Hendren R, Rocke D, Ozonoff S. Examining executive
functioning in children with autism spectrum disorder, attention deficit hyperactivity
disorder and typical development. Psychiatry Research 166(2-3): 210-222 (2009).
8. Muhle R, Trentacoste SV, Rapin I. The Genetics of Autism. Pediatrics 113(5): e472-e486,
2004.
9. Levitt P, Campbell DB. The genetic and neurobiologic compass points toward common
signaling dysfunctions in autism spectrum disorders. American Society for Clinical
Investigation 119(4): 747-754, 2009.
10. Geschwind DH. Autism: Many Genes, Common Pathways? Cell 135(3): 191-395, 2008.
11. Bilder D, Pinborough-Zimmerman J, Miller J, McMahon W. Prenatal, Perinatal, and
Neonatal Factors Associated With Autism Spectrum Disorders. Pediatrics 123(3): 12931300, 2009.
12. Gardener H, Spiegelman D, Buka SL. Perinatal and Neonatal Risk Factors for Autism: A
Comprehensive Meta-Analysis. Pediatrics, 2011. Accessed 22 August 2011 from
<http://pediatrics.aappublications.org/content/early/2011/07/06/peds.2010-1036.abstract>
13. Miles et. al., Autism Families with a High Incidence of Alcoholism. Journal of Autism
and Developmental Disorders, Vol. 33. No. 4. August 2003.
14. Hultman, C. (2002). Perinatal Risk Factors for Infantile Autism. Epidemiology 13(4):
417-423
15. Academy of Medicine, Singapore. Autism Spectrum Disorders in Preschool Children.
Ministry of Health, 2010.
16. Help sought as autism cases rise. Manila Bulletin 2009 Nov 8. Accessed 2011 August 26
from < http://findarticles.com/p/news-articles/manilabulletin/mi_7968/is_2009_Nov_8/sought-autism-cases-rise/ai_n42052711/
17. Carandang,. M (2011). A Report on Autism Spectrum Disorder in the Philippines.
Cardinal Santos Medical Center.
18. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of
Disease, 8th ed. Philadelphia, USA: Saunders Elsevier, 2010.
19. Chen et. al., Alcohol and the Developing Brain: Neuroanatomical Studies. NIAA
Newsletter. July 2014.
20. Landgrend et.al, Prenatal alcohol exposure and neurodevelopmental disorders in children
adopted from Eastern Europe. Pediatrics Volume 125, Number 5. May 2010.
21. Mukherjee et al., Autism anad autistic traits in people exposed to heavy prenatal alcohol:
data from a clinical series of 21 individuals and nested case control study. Advances in
Mental Health and Intellectual Disabilities Volume 5 Issue I. January 2011
22. Weitzman, M. . Gortmaker, S., Sobol, A. (1992). Maternal Smoking and Behavior
Problems of Children. Pediatrics, 90: 342-9
23. Brubakk, A. Indredavik, M. Romundstad , P., Vik, T. (2007). Prenatal Smoking
Exposure and Psychiatric Symptoms in Adolescence. Acta Pediatrics 96 (3): 377-382
24. Taylor, E. , Rogers, J. (2005). Practitioner review: Early Adversity and Developmental
Disorders. Journal of Child Psychology & Psychiatry, 46: 451-467.
25. Mendola, P., Selevan, S., Gutter, S., Rice, D. (2002). Environmental Factors Associated
with a Spectrum of Neurodevelopmental Deficits. Mental Retardation and Developmental
Disabilities Research Reviews, 8: 188-197.
26. Lam, T, Leung, G., Ho, L. (2001). The Effects of Environmental Tobacco Smoke on
Health Services Utilization in the First Eighteen Months of Life. Pediatrics, 107: E91.
27. Slotkin TA, Tate CA, Cousins MM, Seidler FJ. Prenatal Nicotine Exposure Alters the
Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence:
Serotonin Receptors and Cell Signaling. Neuropsychopharmacology 31: 2462-2475,
2006.
28. Center for Disease Control and Prevention (2010). Autism Spectrum Disorder. Signs and
Symptoms. Retreived on September 18, 2011 from http://www.cdc.gov/ncbddd/
autism/signs.html
APPENDIX A.
SAMPLE CONSENT FORM
You are being invited to participate in the study entitled A case-control study of smoking and
alcohol intake as prenatal risk factors of Autism Spectrum Disorder (ASD) among Filipino
children under the supervision of Dr. Ramon Jason Javier. The following have been explained well to
me and I fully understand them before I signed this consent form.
Ikaw ay inaanyayahan na lumahok sa pananaliksik na pinamagatang A case-control study of
smoking and alcohol intake as prenatal risk factors of Autism Spectrum Disorder (ASD) among
Filipino children sa pamamahala ni Dr. Georgina Paredes Ang mga sumusunod ay ipinaliwanag na
mabuti sa akin at lubos ang aking pang-unawa sa mga ito bago ko nilagdaan ang kasulatang ito.
The objective of the study is to determine the association of exposure to prenatal risk factors,
specifically smoking and alcohol intake, in developing Autism Spectrum Disorder among Filipino
children.
Ang layunin ng pananaliksik ay upang malaman kung meron bang relasyon ang paninigarilyo o
paginom ng alak sa panahon ng pagbubuntis sa pagkakaroon ng Autism Spectrum Disorder.
This study will be helpful to fill a gap in knowledge about the environmental causes of Autism, as
well as lays the foundation for future researches in the Philippines.
Ang pananaliksik na ito ay makakatulong ng malaki sa pagkontribyuta ng mga pangunahing
kaalaman sa kondisyon na Autism.
The number of study participants is 38.
Ang bilang ng mga sasali sa pag-aaral na ito ay 38.
The study will involve a one page survey questionnaire
Sa pag-aaral na ito, kinakailangang sumagot ng isang pahinang survey questionnaire or
katanungan
All your records or information about you will be kept strictly confidential.
Ang lahat ng iyong mga rekord o pangalan ay konpidensyal at hindi malalaman ng iba.
Your participation is voluntary and you can withdraw anytime for any reason.
Ang pagsali mo sa pag-aaral na ito ay sarili mong kusa at maaari kang tumiwalag anumang oras
sa anumang kadahilanan.
You can call or ask questions anytime regarding this study. The contact person for further
information or for consultation on diverse events is Sarah Jane A. Jimenez, 09052443580.
Maaari kang magtanong ng kahit anong oras hinggil sa pag-aaral na ito. Ang tatawagan at
kakausapin ay si Sarah Jane A. Jimenez, 09052443580.
I gave my consent subject to the conditions above.
Pumapayag akong sumali sa pag-aaral ayon sa mga nakasaad sa itaas.
Signature
Lagda
________________________________
Participant
Pastisipante
__________________________________
Witness
Saksi
______________________________
Witness
Saksi
__________________
Date Signed:
Petsa
Informed Consent obtained by: _______________________________________
Name and Signature
APPENDIX B.
SAMPLE QUESTIONNAIRE.
Control No._____
Birthday: _______
Occupation:_______
Marital Status:
Attainment:
Single____
Married ____
Widowed____
_____6-10 years
_____10-20 years
_____20 or more years
Age:___
7.
8.
9.
Highest Educational
Elementary _____
High school _____
College____
3.
4.
5.
children
was
___Wine
Per day, how many glasses do you
drinking
___ 1 to 2 glasses
___ 3-6 glasses
___ 7 or more
etc.)
___1 to 2 shots
___3 to 5 shots
___ 5 or more shots
If your answer to question number 1 is
NO; please disregard question 14 and 15.
14. Did you stop smoking when you were
pregnant with your child with ASD?
___ Yes completely stopped
___No, but smoked less than the usual
APPENDIX C.
SCREENING CHECKLIST FOR CONTROLS.