1

Running head: INTEGRATIVE REVIEW

Integrative Review

Melanie Carlson

Arlene Holowaychuk, EdD, MSN, RN, CNE

NUR 4122

Bon Secours Memorial College of Nursing

October 29, 2019

“I pledge”
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INTEGRATIVE REVIEW

Abstract

The purpose of this integrative review is to examine research literature that evaluates the

interrelationship between immunizations against diseases and the risk for Autism Spectrum

Disorder (ASD). Past research illustrates an increase in worldwide concern pertaining to

vaccinations such as MMR and influenza and their connection to ASD. The sudden interest in

this issue has challenged the rates of immunizations. The PICO question under discussion is: For

fetuses and newborns, what is the association of vaccinations and Autism Spectrum Disorder

compared to newborns who do not receive vaccinations? The research design is an integrative

review. Articles were obtained using the database EBSCO Discovery Series located in the

openATHENS online library. Final results after filtration supplied fewer than 3,000 articles and

five met the inclusion criteria. All five articles pertained to vaccinations and autism and indicated

that there was no correlation between vaccination administration and an increase in ASD.

Limitations for this integrative review consisted of an inexperienced researcher, limited time to

complete assignment, and a limit of five articles for the review. Implications of this review

include education to prevent misinformation about vaccinations, targeting social media messages

about anti-vaccination beliefs, educating on the overall symptomatic disabilities of ASD, and

understanding the benefits and complication of vaccination during pregnancy. Future research

recommendations are comprised of utilization of subgroups or phenotypes to establish a more

reliable study and to moreover help identify unknown risk factors associated with ASD.
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Integrative Review

The purpose of this integrative review is to examine research literature that evaluates the

interrelationship between immunizations against diseases and the risk for Autism Spectrum

Disorder (ASD). ASD is characterized as a developmental disorder where social and

communicative interactions are underdeveloped and typically occur before the age of three

(Zerbo et al., 2018). The theoretical connection between vaccinations such as Measle, Mumps,

and Rubella (MMR) in correlation with risk for ASD has drawn an increase for concern and has

further challenged vaccine rates (Hviid, Hansen, Frisch, & Melbye, 2019). Beyond the

hypothetical connection between ASD and immunizations, further research was conducted to

include a decrease in caregivers not providing vaccinations to younger siblings who have older

siblings with ASD due to fear of the younger sibling developing the disorder (Zerbo et al., 2018).

Vaccinations are known to be a great achievement in decreasing major illnesses and researchers

have conducted multiple studies to configure the cause behind decreased vaccination rates. One

researcher developed a theory on the impact of social media on the decline in vaccinations to

consist of spreading anti-vaccination misinformation to social media sites such as Facebook

(Hoffman et al., 2018). Formulating a connection between ASD, immunizations, pregnancy, and

younger siblings will help determine if vaccinations provide the full benefits they portray or if

they include ASD risk factors. The importance and aim of this study are to examine past research

data in correlation to the researcher’s PICO question: For fetuses and newborns, what is the

association of vaccinations and Autism Spectrum Disorder compared to newborns who do not

receive vaccinations?
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Design and Research Methods

The research design is an integrative review. Research of the articles was applied using

one search engine, EBSCO Discovery Series on the openATHENS online library source. The

keywords used to search for the desired articles included ‘ASD’, ‘vaccinations’,

‘immunizations’, ‘pregnancy’, ‘MMR’, ‘ASD in children’, and ‘influenza’. Prior to the final

article research results, filters such as scholarly peer-reviewed, full text, academic articles,

English as the written language, and 2014-2019 publication years increased the acceptability of

the articles. After the filters were applied, the results decreased from over 9,000 articles to fewer

than 3,000. Out of the 3,000 articles, eight were applicable and five were accepted for the

integrative review.

The screening of each article was based on pertinence and how well it applied to the

PICO question: For fetuses and newborns, what is the association of vaccinations and Autism

Spectrum Disorder compared to newborns who do not receive vaccinations? Inclusion criteria for

the review included ASD and immunization variables, qualitative or quantitative research, and a

publishing date after 2014. Any article that did not meet the requirements for the search process

was excluded.

Findings and Results

The findings and results of the five reviewed studies illustrate that vaccinations such as

MMR and influenza are not associated with an increased risk for ASD in fetuses or newborns

compared to those that do not receive vaccinations (Anjali et al., 2015; Hoffman et al., 2019;

Hviid et al., 2019; Zerbo et al., 2018; Zerbo et al., 2017). A summary of the articles is attached

via Appendix 1. The overall structure of this integrative review is based on the following themes
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surrounding the concern about immunization and risk for ASD: health communication and

vaccinations, Autism Spectrum Disorder, and younger siblings of children with ASD.

Health Communication and Vaccinations

Two of the five articles pertain to the theme of health communication concerning

vaccines and the interrelationship with Autism. Hoffman et al. (2019) conducted a study that

characterized anti-vaccination positions on a social media network (Facebook) to determine the

themes and connections in each individual Facebook post. An analysis of public information was

coded using quantitative coding, descriptive analysis, social network analysis, and a qualitative

assessment. After determining the design for the study, the final sample included anti-vaccine

comments on a post promoting vaccinations that consisted of 197 individuals within a span of

eight days. The measurement tools to collect this data included the use of a hybrid process to

detect specific codes. The methods used in this research involve collection of comments in

response to a video in a span of 8 days, assessing the 40 comments by single coding them,

obtaining a random sampling of 197 profiles, and gathering demographic information to further

increase the validity of the study. Data analysis was portrayed by discussing sociodemographic

and antivaccination variables, anti-vaccination topics, and the development of subgroups who

posted public messages between 2015-2017 using a grounded theory approach. The results of the

study confirmed that the beliefs concerning anti-vaccinations were shared amidst four subgroups,

the most common being female and a parent. Researchers concluded that the anti-vaccine

movement is on the rise and could potentially cause major health concerns if changes are not

made.

The second quantitative article to touch upon the vaccination theme was conducted by

Zerbo et al. (2017). These researchers established a cohort study to detect a possible increased
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risk for ASD in pregnant women that received the influenza vaccine. Pregnant women are

encouraged to receive the influenza vaccine, but no past studies have explored this topic in

relation to ASD risk. The study collected a sample of 196,929 children born in Northern

California from January 1, 2000 to December 31, 2010 with a gestational age of at least 24

weeks. Collection of data for the influenza infection and vaccine were obtained from Kaiser

Permanente Northern California (KPNC) inpatient and outpatient directories, followed by

collection of ASD information from pediatric electronic medical records from birth to June 30,

2015. The data analysis of the cohort study comprised a Cox proportional hazards regression

model to interpret maternal influenza vaccine/infection and ASD risk. In addition to the

regression model, the use of separate analysis was implemented to evaluate exposure of

influenza during specific pregnancy trimester as well as a post hoc analysis to adjust for

comparisons. These increased the suitability of the study. Zerbo et al. (2017) found there to be no

link between maternal influenza during pregnancy or the influenza vaccination and the risk for

ASD. The study did establish limitations but found them to be insignificant due to the pregnancy

complications influenza brings forth without the use of the vaccination.

Autism Spectrum Disorder

Two of the five articles demonstrated in great detail pertaining to Autism Spectrum

Disorder. In a nationwide cohort study, Hviid et al. (2019) examined the association between the

Measle, Mumps, and Rubella (MMR) vaccination and an increased risk for autism in children,

subgroups of children, or the time periods after the vaccination. Within the study, researchers

utilized the Danish Civil Registration System to identify individuals living in Denmark along

with their demographic information. Using this method, a final sample was made of 657,461

children born in Denmark from 19999 through December 31, 2010 with follow-up appointment
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from 1 year of age through August 31, 2013 to measure the findings for the study. A Danish

childhood vaccination program was used to obtain MMR records that included MMR1 and

MMR2 vaccinations within the first year of life of the child. Additionally, diagnostic coding for

autism information was collected through the Danish Psychiatric Central Registry and factors

were obtained through the Denmark National Patient Registry. To include individuality in the

study, the researchers collected sibling information to identify subgroups within the investigation

which were derived from the Danish Civil Registration System. The use of survival and

statistical analysis was used to further detail the Cox regression model to develop hazard ratios

relative to the child. In conclusion, the researchers found no evidence to support the increased

risk for autism after an MMR vaccine. This study shows great significance by educating

healthcare facilities about the important use of vaccines and the lack of evidentiary support for

their risk for autism.

Furthermore, in the study completed by Zerbo et al. (2017), the connection between

vaccinations such as influenza and risk for ASD was examined. After finalizing the study,

researchers revealed that if there was a possibility of ASD risk following influenza exposure via

vaccine during pregnancy, it would occur in the first trimester with a ratio of four ASD cases per

every 1000 women. However, after statistical corrections and multiple comparisons such as

maternal allergy, hypertension, and gestational diabetes, the concern for ASD within the first

trimester after an influenza vaccine was termed insignificant.

Siblings of children with ASD

Two of the five articles acknowledged an interest in determining a link between

vaccinations and ASD in children who have a sibling with ASD. Anjali et al. (2015) conducted a

study that focused on the relationship between MMR and ASD occurrences to include U.S.
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children with or without siblings that have ASD. The overall design consisted of a retrospective

cohort study that used an administrative database that included large U.S. healthcare plans. A

sample was demonstrated to encompass children enrolled in the health plan from birth to five

years during 2001-2012 that also have enrolled siblings for at least 6 months between 1997-

2012. An Optum Research Database was used to examine the collection of data within the study

and contained commercially insured and Medicare enrolled individuals. Measurement tools used

to manage the data included a claim-based algorithm to determine ASD status and older sibling

existence, enrollment status during study period, and a CPT code to determine if the MMR

vaccine was given between birth and five years of age. The tests were appropriate based on the

study by applying a sensitivity analysis to explore MMR and ASD potential status and those with

missing data on any covariates. Results confirmed that out of the 95,727 children in the cohort

study, 1929 had an older sibling with ASD. In the group of children who has ASD, the

vaccination rates were lower than in those who did not have an older sibling with ASD. In

summary, there is no evidence to support a link between MMR and ASD risk for those who have

siblings with ASD. This study provides significance for future research as it portrays reliable

data to educate parents on the importance of vaccines to prevent future outbreaks.

Zerbo et al. (2018) created a study that primarily focused on a two-fold objective to

investigate an ASD diagnosis of children and whether the younger siblings of the child with

ASD would receive the recommended vaccinations compared to those who do not have a sibling

with ASD. Researchers employed this study by using a retrospective match cohort study to

integrate health care delivery systems within the Vaccine Safety Datalink (VSD). Children born

between January 1, 1995 and September 30, 2019 followed by their siblings born between

January 1, 1997 and September 30, 2014 was the primary sample used for this research.
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ASD data collection was gathered through an electronic health record from birth until either the

sixth birthday of the child or until the end of the follow-up. Among the children with and without

ASD, the younger sibling data collection were matched based on sex, VSD site, and month and

year of birth. Finally, vaccination data was compiled through VSD database that consisted of

immunization medical records of over ten million people. Conclusion of sample results from the

collected data resulted in 3729 children with ASD, 592907 children without ASD, and their

retrospective younger siblings (Zerbo et al. 2018). Data was analyzed using a statistical study to

compare fully vaccinated children with their corresponding controls, a secondary analysis to

evaluate individual vaccines, and an overall calculation of no more than two vaccination

injections or parental refusal of vaccinations to adjust for the ratio of children who did not

receive the recommended immunizations. Adjustment of the ratios was made using a log

binomial regression analysis. Zerbo et al. (2018) completed the research to conclude that overall

vaccine rates were high among children, but those with an ASD diagnosis were less likely to be

vaccinated compared to those without ASD. Researchers believe the significance of these results

is partly due to parents assuming there is a greater ASD risk at a young age, therefore parents

may be more willing to vaccinate their children as they get older.

Discussions and Implications

The extensive details of the selected articles offer awareness into the worldwide concern

of vaccinations and their link to an increased risk for Autism Spectrum Disorder. The PICO

question, for fetuses and newborns, what is the association of vaccinations and Autism Spectrum

Disorder compared to newborns who do not receive vaccinations, was clearly defined based on

the research findings. The research conducted by Anjali et al. (2015), Hoffman et al. (2019)

Hviid et al. (2019), Zerbo et al. (2017), and Zerbo et al. (2018) provides insight into this topic by
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applying subgroups, vaccinations during pregnancy, siblings of those with ASD, and many other

variables to increase the validity of their research. Autism, vaccinations, and siblings of children

with ASD were all found to be important correlations in vaccinations and the theoretical risk

factor for ASD. The research suggests social media may contribute to the misinformation

provided to individuals and could potentially cause a major health crisis if they are not educated

properly. Future research should consider the use of subgroups or phenotypes to establish a more

reliable study. Focusing on subgroups with future research will help identify unknown risk

factors associated with autism and establishing a link with the risk for autism. Implications for

the research findings include education regarding correct information on vaccination benefits and

how the complications of anti-vaccination approaches could cause a possible health crisis.

Limitations

As with most research studies, many limitations exist and should be characterized as a

part of this integrative review. Because the articles required a limited time frame of five years, it

is not recognized as an exhausted review. Limitations regarding the researcher’s inexperience,

inclusion of only five articles, and the integrative review as a class assignment should be

recognized.

Zerbo et al. (2018b) and Anjali et al. (2015) determined limitations of their study which

included small sample sizes and the possibility of children receiving vaccinations outside the

researcher’s data collection method. Zerbo et al. (2017) also noted a limitation regarding children

who did not receive medical treatment at all or who received treatment outside of the method of

data collection. The study conducted by Hviid et al. (2019) lacked in correctly identifying the

first diagnosis of autism and the misclassification of autism and vaccination rates, creating a
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possibility of bias. Lastly, Hoffman et al. (2019) confirmed that the results do not reflect a broad

discussion on the issue of anti-vaccination, which decreases the overall credibility of the study.

Conclusion

The findings of this integrative review highlight the broad discussion and relationship

among vaccinations and the hypothesis of an increased risk of autism which thoroughly relates to

the PICO question. The results of this worldwide topic indicate that the correlation between

vaccinations such as MMR and influenza do not reflect any risk factors associated with the

development for ASD. The findings in this integrative review portray importance to global health

by providing significant data to support the use of vaccination and how it does not equate to the

risk of ASD on multiple aspects. Benefits of vaccinations, such as prevention from deadly

illnesses outweigh the anti-vaccinations concerns that have given rise in the past couple of years;

complications of antivaccination approaches could lead to a worldwide health epidemic that has

been averted with the creation of vaccinations. Education on the consequences of non-

vaccination, studying common traits of those who do not believe in vaccines, disregarding

persona biases, and offering recommendations towards misinformation regarding vaccines are all

approaches that can used to incorporate a positive outcome to this worldwide concern.
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References

Anjali, J., Jaclyn, M., Ami, B., Tim, B., Jonathan P., K., & Craig J., N. (2015). Autism

occurrence by MMR vaccine status among US children with older siblings with and

Without Autism. Journal of the American Medical Association, (15), 1534.

https://doi.org/10.1001/jama.2015.3077

Hoffman, B. L., Felter, E. M., Chu, K.-H., Shensa, A., Hermann, C., Wolynn, T., … Primack, B.

A. (2019). It’s not all about autism: The emerging landscape of anti-vaccination

sentiment on Facebook. Vaccine, 37(16), 2216–2223.

https://doi.org/10.1016/j.vaccine.2019.03.003

Hviid, A., Hansen, J. V., Frisch, M., & Melbye, M. (2019). Measles, mumps, rubella vaccination

and autism: A nationwide cohort study.  Annals of Internal Medicine, 170(8), 513–520.

doi: 10.3726/M18-2101

Zerbo, O., Qian, Y., Yoshida, C., Fireman, B. H., Klein, N. P., & Croen, L. A. (2017).

Association between influenza infection and vaccination during pregnancy and risk of

autism spectrum disorder. Journal of the American Medical Association

Pediatrics, 171(1), e163609. https://doi.org/10.1001/jamapediatrics.2016.3609

Zerbo, O., Modaressi, S., Goddard, K., Lewis, E., Fireman, B. H., Daley, M. F., … Klein, N. P.

(2018). Vaccination patterns in children after autism spectrum disorder diagnosis and in

their younger siblings. Journal of the American Medical Association Pediatrics, 172(5),

469–475. https://doi.org/10.1001/jamapediatrics.2018.0082
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Appendix I: Summary of the Literature Tables

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Article Reference Anjali, J., Jaclyn, M., Ami, B., Tim, B., Jonathan P., K., &

Craig J., N. (2015). Autism Occurrence by MMR

Vaccine Status Among US Children with Older

Siblings with and Without Autism. JAMA, (15), 1534.

https://doi.org/10.1001/jama.2015.3077
Background/Problem Background: although there has been found no link between

Statement MMR and ASD (autism spectrum disorder) parents are still

refusing to vaccinate their children. Parents may also be

concerned with the link if they already have a child with

ASD.

Problem statement: Link between MMR and ASD

occurrence using a sample consisting of US children with or

without siblings that have ASD

Conceptual/theoretical NONE

Framework
Design/Method/Philosophical A retrospective cohort study that used an administrative

Underpinnings database which consisted of a large US health plan

Sample/ Setting/Ethical Sample: children enrolled in the health plan form birth to 5

Considerations years during 20001-2012 that also have an enrolled sibling at

least 6 months between 1997-2012.

Ethical: The New England Institutional Review Board

excused informed consent due to the study being free of

liability based on the existing deidentified data

Major Variables Studied Autism

(and their definition), if MMR vaccine

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appropriate Autism in siblings

Quantitative study
Measurement Tool/Data Date method: Optum Research Database  containing

Collection Method commercially insured and Medicare enrolled individuals

Measurement tools:

- A claims-based algorithm was used to determine

ASD status and older sibling  needed 2 or more

claims of ASD or other autistic disorder for diagnosis

code on two separate dates of service

- Index child and ASD sibling were determined by

their enrollment status in the study period

- CPT code determined MMR vaccine between birth

and 5 years

Measurements were valid and reliable

Data Analysis Sensitivity analysis to explore MMR and ASD potential

status and those with missing data on any covariates

Findings/Discussion - No associated between MMR and ASD risk

- No evidence of increased risk of MMR after 1-2

doses even if the child has an older sibling with ASD

- MMR immunization is lower in children that have

older siblings with ASD

- The claims database made the study free from bias

- The MMR and autism risk phenomenon is delaying

immunization decision making

- Those with poor healthcare may not benefit from this

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study

- Overall, the link between MMR and ASD is not

associated with any risk or those that have siblings

with ASD

The results were significant for the study

Appraisal/Worth to practice The belief that MMR can have the potential to put children at

risk for autism has been the leading cause of vaccination

decline. Educating parents about the importance of vaccines

and showing studies proving no correlation between MMR

and ASD risk can prevent future illness outbreaks.

The limitations of the study included diagnosis and

conditions eventually being ruled out and the possibility of

children who were claimed unvaccinated, may have possibly

received vaccines in a school or public clinic.

Article Reference Hoffman, B. L., Felter, E. M., Chu, K.-H., Shensa, A.,

Hermann, C., Wolynn, T., … Primack, B. A. (2019).

It’s not all about autism: The emerging landscape of

anti-vaccination sentiment on

Facebook. Vaccine, 37(16), 2216–2223.

https://doi.org/10.1016/j.vaccine.2019.03.003
Background/Problem Background: A decrease in vaccine rates could be due to anti-

Statement vaccine posts on social media.

Problem statement: To characterize anti-vaccine information

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on Facebook and how its related to Facebook posts and how

the content spreads.

Conceptual/theoretical none

Framework
Design/Method/Philosophica Analysis of public information coded using quantitative

l coding, descriptive analysis, social network analysis, and an

Underpinnings in-depth qualitative assessment.

Sample/ Setting/Ethical Sample: Anti-vaccine comments posted on a message

Considerations promoting vaccine that consisted of 197 individuals (in a

span of 8 days)

Ethical: The study was approved by the University of

Pittsburgh Institutional Review Board

Major Variables Studied Major variables:

(and their definition), if - Age

appropriate - Gender

- Location

- political affiliation

- marital status

- parental status

- employment

- whether or not post-secondary education was listed

Qualitative study
Measurement Tool/Data Specific codes were determined using a hybrid process

Collection Method Researchers examined public information that had been

posted in the past 2 years

1: collection of all comments posted in response to a video

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promoting vaccines in a span of 8 days

2: researchers assessed 40 comments and single-coded them

3: obtained a random sampling of 197 profiles to conduct a

qualitative assessment

4: after final sample was collected, demographic information

was gathered such as age and marital status

Measurements were valid and reliable

Data Analysis A descriptive analysis was used for sociodemographic and

anti-vaccine variables

A social network analysis was used to determine if

individuals spoke about different anti-vaccine topics and if

that led to subgroups being included and participating

together

Qualitative analysis was used with public messages posted

between 2015-2017 using a ground theory approach

Data analysis was appropriate for the study

Findings/Discussion Out of the randomized sample, the results concluded the most

common were those who were female, a parent, and spanned

the globe

Individuals tended to cluster in 4 subgroups and shared

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beliefs about anti-vaccinations

- 4 subgroups: trust (mistrust in science community),

alternative (use of home remedies alternative to

vaccines), safety (risks and concerns about vaccines),

and conspiracy (belief that the gov’t is hiding

information about vaccines)

- Common coded topics included: education material,

and the belief that pharmaceutical companies are

trying to cover up the adverse effects of the vaccine

- Overall, the anti-vaccine movement is growing and

could cause many health problems

The results were significant for the study

Appraisal/Worth to practice The growing number of individuals refusing vaccines for

themselves and their children could cause a major health

crisis. Individuals are gaining misinformation through social

media and education about the importance of vaccines should

be intervened. Targeting messages about anti-vaccination

beliefs could help the decline in vaccination rates.

The results were significant, and limitations included that the

results do not reflect broad discussion on the anti-vaccination

issue, credibility is at risk due to self-report data, and the

coding on public information only instead of included

information that Facebook friends were sharing privately.

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Article Reference Hviid, A., Hansen, J. V., Frisch, M., & Melbye, M. (2019).

Measles, Mumps, Rubella Vaccination and Autism: A

Nationwide Cohort Study. Annals of Internal

Medicine, 170(8), 513–520. doi: 10.3726/M18-2101

Background/Problem Background: The association between MMR and autism is an

Statement increasing concern and has begun to challenge vaccine acceptance

Problem statement: The objective for this study is to assess if the

MMR vaccine increases the risk for autism, subgroups of

children, or time periods after vaccinations.

Conceptual/theoretical None

Framework
Design/ Design: nationwide cohort study

Method/Philosophical Method: sourced from the Danish Civil Registration System that

Underpinnings identifies people living in Denmark and their demographic

information.
Sample/ Setting/Ethical Sample: 657461 children born in Denmark form 1999 through

Considerations December 31, 2010 with follow-ups from 1 yr of age and through

August 31, 2013

Setting: Denmark

Ethical Considerations: ethical approval is not necessary when

registries are being used for research. However, the Danish Data
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Protection Agency approved the study

Major Variables Major Variables:

Studied (and their o MMR vaccine

definition), if o Autism

appropriate Quantitative study

Measurement Tool/Data Measurement tool/data collection:

Collection Method o MMR vaccine  obtained individual data on MMR1 and

MMR2 vaccinations followed by other vaccines within the

first year of life.

o Autism  obtained from the Danish Psychiatric Central

Registry. The registry used diagnostic codes containing

information from psychiatric hospitals and wards.

o Identification of autism risk factors through the Danish

National Patient Registry

o Collection of sibling information to identify subgroups

was concluded through the Danish Civil Registration

System
Data Analysis - Analysis of the study was conducted using survival

analysis
Findings/Discussion - They found no support for an increased risk for autism

after an MMR vaccine

- MMR vaccine does not trigger those who have autism risk

factors

- No support for an increase in autism cases in a specific

time period after the MMR vaccine

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- Increase in study validity due to use of subgroups

according to environment and risks, autism phenotypes

associated with MMR (regressive autism), nationwide

cohort, and a large single study

- Overall, the study does not support that MMR increases

the chance of autism or triggers associated with autism.

The results were significant for the study

Appraisal/Worth to Education and valid evidence to increase the importance of

practice vaccines and how it does not increase the risk for autism. MMR is

not common currently, but if vaccines use reduced it could triple

measle outbreaks. The study offers reliable data to use in

healthcare settings and educate on the important use of vaccines

and no support for its increased risk for autism.

The results of this study were significant but had some limitations.

The limitations include the use of first diagnosis autism and the

misclassification with autism and vaccination rates.

Article Reference Zerbo, O., Qian, Y., Yoshida, C., Fireman, B. H., Klein, N.
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P., & Croen, L. A. (2017). Association Between

Influenza Infection and Vaccination During Pregnancy

and Risk of Autism Spectrum Disorder. JAMA

Pediatrics, 171(1), e163609.

https://doi.org/10.1001/jamapediatrics.2016.3609
Background/Problem Background: Pregnant women are encouraged to get the

Statement influenza vaccine due to increased risk of infection and future

complications. No study has investigated the correlation

between maternal influenza vaccine during pregnancy and

ASD risk.

Objective: To determine if there is an ASD risk for pregnant

women that receive the influenza vaccination

Conceptual/theoretical none

Framework
Design/Method/Philosophica Design: Cohort study

Underpinnings
Sample/ Setting/Ethical Sample: 196,929 children born at Kaiser Permanente

Considerations Northern California from January 1, 2000 to December 31,

2010 which a gestational age of at least 24 weeks

Setting: Metropolitan San Francisco and Sacramento

surrounding areas

Ethical considerations:

- The study was approved by the KPNC institutional

review board and the California State Committee for

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the Protection of Human subjects.

- The California Committee waived consent for the

participants because data was collected through

medical records and no direct contact with patients

were made.
Major Variables Studied Major Variables:

(and their definition), if Diagnosis of ASD (autism disorder)

appropriate Vaccinated

Not vaccinated

Influenza infection

Quantitative study
Measurement Tool/Data - KPNC medical record system was used to collect data

Collection Method on exposures to the mother during pregnancy

- Influenza infection and vaccination was collected

from KPNC inpatient and outpatient directories

- Autism spectrum disorder data was collected through

the Pediatric electronic medical records and had to

consists of two occasions from birth through June 30,

2015
Data Analysis - A Cox proportional hazards regression model was

used to determine the association between maternal

influenza infection/vaccine and risk for ASD

- Use of hazard ratios were utilized to interpreted ASD

risk adjusted on a Kaplan-Meier plot

- A separate analysis was used to distinguish the data

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by pregnancy trimesters and exposure of influenza

during pregnancy

- A post hoc analysis was used to accommodate for

multiple comparisons, as well as a sensitivity analysis

to test for potential unmeasured cofounders

Findings/Discussion Maternal influenza during pregnancy was found to have no

connection with the risk of autism spectrum disorder

Inclusion of inpatient and outpatient data of documented

influenza diagnosis by a physician made this study a more

reliable source

They concluded that if there were a possibility of ASD risk

during pregnancy after influenza exposure or vaccine, it

would occur in the first trimester with ratio of 4 ASD cases

every 1000 women vaccinated

Although there was an association, the study found it to be

insignificant due to the importance of the influenza vaccine

towards other pregnancy complications

The results were significant for this study

Appraisal/Worth to practice This study brings forth important information regarding the

importance of influenza vaccines and how it does not

associate with the risk for ASD.

The limitations of this significant study include use of

medical records instead of standardized clinical assessments,

inclusion of women who did not seek medical care, records

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outside of KPNC, and not a large enough ASD cases sample.

Article Reference Zerbo, O., Modaressi, S., Goddard, K., Lewis, E., Fireman, B. H.,

Daley, M. F., … Klein, N. P. (2018). Vaccination Patterns

in Children After Autism Spectrum Disorder Diagnosis and

in Their Younger Siblings. JAMA Pediatrics, 172(5), 469–

475. https://doi.org/10.1001/jamapediatrics.2018.0082
Background/Problem Background: Although studies have shown no significance

Statement between vaccinations and ASD risk, rates of vaccination among

children has declines. However, other studies have found a high

percentage of parents that have children with autism spectrum

disorder (ASD) tend to decline or delay immunizations for their

younger children due to the belief of ASD risk after vaccines

Objective: A two-fold objective that investigated if children with

an ASD diagnosis received remaining vaccines; followed by if the

younger sibling of the ASD diagnosed child recieved all of the

recommended vaccinations compared to those who do not have a

sibling with an ASD diagnosis.

Conceptual/theoretical NONE
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Framework
Design/ Design: retrospective matched cohort study

Method/Philosophical Method: Integrated health care delivery system within the Vaccine

Underpinnings Safety Datalink (VSD)

Sample/ Setting/Ethical Sample: children born between January 1, 1995 and September

Considerations 30, 2019 and their siblings born between January 1, 1997 and

September 30, 2014

Setting: 8 VSD sites across the US originating in North Carolina,

Colorado, Northwest, Washington, Marshfield Clinic, and

Southern California

Ethical: The study was approved by the institutional review board

for each VSD site and approved by CDC. Written informed

consent was waived due to no direct contact with the sample.

Major Variables Vaccination status

Studied (and their Autism Spectrum Disorder (ASD)

definition), if Younger siblings with and without older sibling that have ASD

appropriate Quantitative study

Measurement Tool/Data Collection of data for ASD was gathered through electronic health

Collection Method records and had to consist of 2 occasions form birth until either

the sixth birthday of the child or until the end of the follow-up.

Among the children with and without ASD, their younger sibling

data collection were matched based on sex, VSD site, and month

and year of birth.

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Vaccination patterns were compiled through the VSD/CDC

database that contains medical and immunization status for over

10 million people
Data Analysis In a statistical analysis study, they compared fully vaccinated

children with ASD, younger siblings with of those with ASD, and

the corresponding controls.

In a secondary analysis, individual vaccines were evaluated based

on the previous variables.

Calculation of no more than 2 vaccination shot or parental refusal

of vaccinations were used to adjust for the ratio of children who

did not receive the recommended immunizations.

Adjustment of ratios were calculated using a log binomial

regression analysis
Findings/Discussion Findings concluded that overall vaccine rates were high but those

with an ASD diagnosis were less likely to vaccinate compared to

those without ASD.

Rates for vaccinations amidst younger siblings of children with

ASD were significantly lower than those who did not have

siblings with ASD

The highest ratings for under-vaccination consisted of siblings of

children with ASD in the age range of 1-11months and 1-2 years.

Conclusions believe that some parents assume there is a greater

ASD risk when they are younger and may be willing to vaccinate

as the children become older.

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The results were significant for the study

Appraisal/Worth to Importance of this study is to educate parents of those with

practice children with and without ASD on the importance of vaccines and

the low risk they have for future ASD in younger siblings.

Healthcare professionals can use this data and the overall study to

increase the vaccine uptake in those who are under-vaccinated.

The study showed significant results. The limitations of the study

included the lack of medical records reviewed, small sample size

in siblings who were eleven to twelve years old, outside vaccines,

and the modification of vaccinations in younger siblings.