Running head: Improving Outcomes with Newborn Screening
Improved Outcomes with Newborn Screening
Alishia Pecks
Christina Perry
Lynda Stephenson
Liane Towle
Auburn University of Montgomery
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Running head: Improving Outcomes with Newborn Screening
2
Improving Outcomes with Newborn Screening
Of the 4 million infants who are screened each year, approximately 12,500 are diagnosed
with one of the 29 core conditions of the uniform screening panel (CDC, 2012). Newborn
screening is a key factor in early detection of an array of heritable conditions. It has dramatically
decreased morbity and mortality rates worldwide. Nurses at Sweet Baby hospital have been
charged to convince the healthcare providers to use more comprehensive newborn screenings.
Screenings are used for early detection of hearing, developmental, genetic, and metabolic
disorders. Regulations for screenings vary from state to state. All states are required to test for
congenital hypothyroidism, galactosemia, and phenylketonuria. The American College of
Medical Genetics organized a group of experts to address the variation of disorders screened for
in each state. The experts then developed a recommended screening panel of 29 core conditions
to be included in the newborn screening process (DeLuca, 2013). There is still much information
needed to determine if newborn screening is an appropriate tool to decrease morbity and
mortality in newborns versus waiting to see if the newborns exhibit symptoms before screening
is more appropriate. It will need to be known which screenings are already implemented in the
hospital. Does the hospital have the capabilities and finances for the testing itself and the experts
that will be needed to determine diagnosis and management of the conditions detected? Are
some of the screenings specific for certain races or genders? What comprehensive screening
programs are being used in other hospitals? Which specific diseases should be screened for? Will
the screening program be cost effective?
Situation Focused Question
The purpose of the query is to compare data on the benefits of intense screening
programs for newborns. The goal for the query is to assure that a comprehensive newborn
Running head: Improving Outcomes with Newborn Screening
3
screening is appropriate for the Sweet Baby hospital. The focused question is what is the highest
level of evidence available to determine if comprehensive screenings are more effective in
detecting heritable conditions in newborns versus state regulated screenings.
Target Resources
After some discussion and experimentation, the evidence based practice team decided to
search for the best evidence related to the focused question in PubMed, Cochrane, and CINAHL.
The team determined that these databases provided the most current and highest level of
information pertaining to the focused question. The databases provided a feasible means of
narrowing results to ensure the information gathered is up-to-date and all-inclusive.
The Search
Once the team decided which databases would be used in the search for the best
evidence, a focused question was established to guide the research. This question was developed
using the PPAARE method (see Table 1). This method breaks the situation into small pieces
making it easier to identify the vital elements to search for relevant evidence. The situation is
broken down into the problem, the patient or population, the action that will be taken, an
alternative if appropriate, the result of the action, and the level of evidence being achieved
(Howlett, 2013). The focused query question is what is the highest level of evidence available to
determine if comprehensive screenings are more effective in detecting heritable conditions in
newborns versus state regulated screenings.
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Running head: Improving Outcomes with Newborn Screening
Table 1
Newborn Screening
PPAARE Component
Case Example
Problem
Patient
Need for more comprehensive newborn
screenings to detect heritable conditions
Newborns
Action
Implement a new screening program
Alternative
Watchful waiting; State regulated screenings
Patient Results
Reduce infant morbidity and mortality rates
Level of Evidence
Highest available
Relevant Evidence
The evidence based practice team found relevant evidence from various sources (see
Table 2). These articles showed that with expanded newborn screening, diseases are caught early
on. With early diagnoses, the newborns have a greater prognosis. There are additional expenses,
but expanded newborn screening is shown to be cost effective when compared to unexpanded
screening. The benefits outweigh the programmatic costs. Overall, more comprehensive
screening for newborns will reduce mortality.
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Running head: Improving Outcomes with Newborn Screening
Table 2
Relevant Evidence
Evidence Citation (APA)
Level of
Evidence
1. Lipstein, E.A., Vorono, S.,
Highest
Browning, M.F., Green, N.S.,
Kemper, A.R., Knapp, A.A. &
Perrin, J.M.. (2010, May).
Systematic evidence review of
newborn screening and treatment
of severe combined
immunodeficiency. Pediatrics,
Research
Design
Purpose/Question(s)/Hypothesis
Population/Sample
/Inclusion and
exclusion criteria
described
Data Collection
Method(s)
Data Analysis
Method(s)
Findings and Conclusions
Qualitative
Newborn screening for severe
Children with SCID
combined immunodeficiency could
be beneficial in preventing childhood
death
Analyzing Data
Systematic review
Evidence indicates the benefits of
early treatment of SCID
2. Lund, A.M., Hougaard, D.M.,
Highest
Simonsen, H., Andresen,
B.S., Christensen,
M.(2012). Biochemical
screening of 504,049
newborns in Denmark, the
Faroe Islands, and Greenlandexperience and development of a
routine program for expanded
newborn screening. Elsevier.10
9(3).281-293.
Quantitative
Expanded newborn screenings should 504,049 newborns in
be standard of care
Denmark, Faroe
Islands,and Greenland
Observation
Meta-analysis
Early clinical management is
beneficial for metabolic diseases
discovered during expanded
newborn screening
3. Oerton, J. Khalid, J. Besley, G.,
Dalton, R.N., Downing, M.
(2011). Newborn screening for
medium chain acyl-CoA
dehydrogenase deficiency in
England. Journal of medical
screening. (18). 173-181.
Quantitative
125(5): e1226-35. Doi:
10.1542/peds.2009-1567.
Highest
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Running head: Improving Outcomes with Newborn Screening
3. Porter, H., Neely, S., & Gorga,
Highest
M. (2009, August). Using
benefitcost ratio to select universal
newborn hearing screening
test criteria. Ear Hear,
30(4): 447-457.
doi: 10.1097/AUD.0b013e318
1a26f11
Qualitative
Benefit-cost ratio of newborn hearing Existing data from 1200
screening
ears
Analyzing data
Meta-analysis
The monetary benefits of both
one step and two step programs
outweigh the programmatic costs
4. Tiwana, S.K., Rascati, K.L.,
Highest
Park, H., (2012). Cost
effectiveness of expanded
newborn screening in
Texas. Elsevier. P. 613-621.
http://www.ispor.org/ValueInHealth/Sho
wValueInHealth.aspx?issue=a6b67316065b-43e2-b8f3-01eb959f181f
Qualitative
How do the costs of expanded
Newborns in Texas
newborn screening compare to those
of the standard screening?
Analyzing data
Meta-analysis
Expanded newborn screening
improves patient outcomes by
preventing avoidable mortality
and morbidity.
5..Waisbren, S.E., Landau, Y., Wilson, J., Highest
& Vockley, J. (2012).
Neuropsychological outcomes
in fatty acid oxidation
disorders: 85 cases detected
by newborn screening.
Developmental Disabilities
Research Reviews, 17(3/4),
260-268.
Doi:10.1002/ddrr.1119
Quantitative
Will mortality and morbidity rates
Review of medical records Analyzing data
improve due to newborn screening of of 85 children with FAOD
fatty acid?
Meta analysis
Although expanded newborn
screening dramatically changes
the health and developmental
outcomes in many children with
fatty acid oxidation disorders, it
also complicates the
interpretation of biochemical and
molecular findings and raises
questions about the effectiveness
or necessity of treatment
Running head: Improving Outcomes with Newborn Screening
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Evidence Appraisal
One relevant qualitative and quantitative study was appraised for trustworthiness (see
Tables 2.1 & 2.2). After appraising both studies using a systematic process, both studies were
deemed to be trustworthy. The qualitative study findings suggested that screening for severe
combined immunodeficiency (SCID) is possible. Evidence indicates that early stem-cell
transplant has improved outcomes compared to later treatment. Unfortunately the findings from
this study has not led to any immediate implementations in practice (Lipstein, 2010), The
quantitative study findings show that quality assured screening and diagnostic protocols allow
early identification of children with clinically important diseases, resulting in favorable outcomes
(Oerton, 2011).
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Running head: Improving Outcomes with Newborn Screening
Table 2.1
Appraisal of Qualitative Evidence
Content
Questions
Appraisal
Ellen Lipstein, MD, Center for Child and Adolescent
Health Policy, Sienna Vorono, BA, Center for Human
Genetic Research, Mass General Hospital for Children
Marsha Browning, MD, MPH, MMSC, Department of
Pediatrics, Harvard Medical Schol, Nancy Green, MD,
Department of Pediatrics, Columbia University, Alex
Kemper, MD, MPH, MS, Duke Clinical Research
Institute and Department of Pediatrics, A.Knapp, MS,
Center for Child and Adolescent Health Policy, Lisa
Prosser, PhD, Child Health Evaluation and Research
Unit, James M. Perrin, MD, Department of Pediatrics,
Harvest Medical School
Funding Source: Supported by the US Department of
Health and Human Services, Health Resources and
Services Administration, Mass General Hospital for
Children
The authors have indicated they have no financial
relationships relevant to this article.
Purpose: To conduct a systematic review of the evidence
for newborn screening for SCID
-Are the authors` credentials and educational background
appropriate to conduct this type of study? Yes
-Are the authors affiliated with an educational program,
health institution, or practice setting? Yes
-Do the authors report a conflict of interest? No
Strength
Does the funding source have a vested interest in a
beneficial outcome of the study? No
Strength
-Is the intent of the study clearly stated? Yes
-Is the phenomenon being investigated? Yes
-Is the population identifiable?
No
-Are the research questions in alignment with the intended
purpose? Yes
-Is the phenomenon under study identifiable in a broad
research question? Yes
Strength
Research Questions:
1. What methods exist to detect SCID through
newborn screening? What is known about the
sensitivity and specificity of screening tests? Has
population based testing been shown to be
Strength
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Running head: Improving Outcomes with Newborn Screening
feasible?
2. Does earlier treatment of SCID improve
outcomes?
3. Under what circumstances would universal
newborn screening for SCID be cost effective?
Qualitative approach
Sample: Multiple methods used to gain samples.
Searched multiple databases, limited to human studies
published in English, researched studies on SCID,
Interviews, Multiple reviewers
Data Collection Protocol: Interviews, Reviews, Limited
searches to human studies in English, reviewed
references, consulted SCID , specific articles rather than
broad
Sample Results: Several small studies suggested that it is
possible to screen for SCID. Evidence from large case
series indicates early stem cell transplants improve
-Is the rationale for using a qualitative approach explained?
No
-Is the qualitative approach in alignment with the intended
purpose? Yes
-Was a sampling method or multiple methods used to
identify participants who could inform the study? Yes
-How did the researchers attempt to gain variation within
the sample? Searched multiple databases, sough specifically
addressed SCID articles
-Were the inclusion and exclusion criteria clearly described
and were they appropriate for the purpose of the study? Yes
-Were data collection methods appropriate for the intended
purpose of the study? Yes
-Was the protocol for conducting the study described
thoroughly and in enough detail? No, not enough detail
-Were data collection procedures consistently applied to the
participants of the study? No
-Did the data collector have sufficient qualifications and
training? Yes
-Were data collected long enough to have saturation? N/A
-Was the protocol ethical and approved by an Institutional
Review Board? Yes
-What steps were taken to ensure the confidentiality and
anonymity of the participants? N/A
Limitation
-Were the participants characteristics described in enough
detail to understand how they contributed to the data? Yes
-Were the participants experiences with the phenomenon
Strength
Strength
Limitation
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Running head: Improving Outcomes with Newborn Screening
outcomes.
varied? Yes
Data Analysis
-What steps were taken to ensure that the interview or focus
group data were transcribed verbatim? 2 reviewers used
standardized tools, memos
-How were the data coded? N/A
-How were categories and themes constructed? According
the key questions
What steps were taken to ensure credibility during data
analysis? Referencing
Limitation
Findings:
-Are the themes or theories presented in an understandable
manner? Yes
-Are the finding supported by quotations from the
participants to facilitate transferability? No
-Are finding s presented relative to the intended purpose
and each research question? Yes
-Did the researches thoroughly explain their interpretation
of the findings? Yes
-Were the explanations logical? Yes
-Did the researchers describe the contribution of their study
to understanding the phenomenon? Yes
-Did the researchers discuss how their findings are related
to previous studies? Yes
-What are the implications for practice? Implementation of
SCID screening
What future research recommendations are made? Does a
sufficient public health infrastructure exist to support the
test? More research on cost effectiveness
Are the conclusions in alignment with the intended purpose
of the study? Yes
-Do the conclusions logically follow from the findings? Yes
Strength
Discussion:
This review has provided key evidence regarding
newborn screening for SCID. Data from the reviews
indicate that children who receive early treatment
consistently do better than those that receive later
treatment. The morbidity of SCID mean that randomize,
controlled trials of early versus late treatment lack
clinical justification.
Conclusions
Strength
Strength
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Running head: Improving Outcomes with Newborn Screening
Table 2.2
Appraisal of Quantitative Evidence
Content
Questions
-Juliet Oerton, MRC Centre of epidemiology for Child Health
-Javaria Khalid, MRC Centre of Epidemiology for Child Health
-Guy Besley, Royal Manchester Children’s Hospital
-R. Neil Dalton, Evelina Children’s Hospital
-Melanie Downing, Sheffield Children’s Hospital
-Anne Green, Birmingham Children’s Hospital
-Mick Henderson, St. James University Hospital
- Are the authors credentials and education appropriate Strength
to conduct this type of study? Yes
-Are the authors affiliated with an educational
program, health institution, or practice setting? Yes
-Do the authors report a conflict of interest? No
Funded by the Department of Health, commissioned by the UK
Screening Committee.
The MRC Centre of Epidemiology for Child Health
benefits from funding from the Medical Research
Council.
-Is the intent of the study clearly stated? Yes
-Are the variables being investigated identifiable? Yes
-Are the outcomes of the study identifiable?
Yes
-Is the population under study identifiable?
Yes
Limitation
-Are the hypotheses in alignment with the intended
purpose? Yes
-Are the variables under study identifiable in the
hypotheses? Yes
Limitation
Purpose: To estimate the overall prevalence of MCADD
diagnosis with early newborn screening
Hypotheses and research questions:
-Early diagnosis by screening asymptomatic newborns may
improve outcome.
-Do all those detected benefit from screening?
Appraisal
Strength
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Running head: Improving Outcomes with Newborn Screening
-Does ethnicity play a role in MCADD?
Research Design: Quantitative
Sample: Babies 5-8 days old in areas served by six newborn
screening laboratories in areas of high minority ethnic
prevalence
Research protocol:
Heel prick blood sample was collected on to filter paper cards as
four dried blood spots. Laboratories analyzed a single 3 mm
punch. A presumptive positive screening result for MCADD was
defined as an average triplicate C8 value > 0.50 mol/L. A full
acylcarnitine profile was performed on presumptive positive
samples.
-Is one hypotheses written for each dependent
variable? No
-Is one question written for each variable under study?
No
-Is the design selected in alignment with the purpose?
Yes
-Is the design appropriate to reach the stated outcome?
Yes
-Are the researchers blind to the assignment of
participants? No
-Does the design limit the number of extraneous
variables? No
-Did the authors describe the population that the
sample is intended to represent? Yes
-Was the sampling frame used appropriate for the
purpose of the study? Yes
-Was the inclusion and exclusion criteria clearly
described, and was it appropriate for the intended
outcome? No
-Was the assignment of participants to treatment
and control/comparison groups random or non
random, and was the method appropriate?
Nonrandom
-Was the protocol for conducting the study described
thoroughly and in enough detail? Yes
-Was the protocol followed appropriate for the
purpose? Yes
-Did the study continue long enough to have valid
outcomes? Yes
-Was the protocol consistently administered to the
participants in each group? Yes
-Did the researchers take steps to control for
extraneous variables? Yes
Strength
Limitation
Strength
Running head: Improving Outcomes with Newborn Screening
Data Collection:
Specimens were circulated and results were analyzed and
reported back to all participating laboratories. Pediatricians
notified all newly diagnosed children with MCADD.
Notifications were followed up with questionnaires.
Sample Results: 1,568,445 babies were screened and 199
presumptive positive children referred. 147 of these were
confirmed with MCADD. Most commonly found in Asian
babies .
Data analysis results: The prevalence of disease detected through
screening was 0.94 per 10,000 babies screened.
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-Was the protocol ethical and approved by an
Institutional Review Board? Yes, approved by the
London Great Ormond Street Hospital for Children
NHS Trust Committee and Patient Information
Advisory Group
-Were the data collection methods appropriate for the Limitation
intended purpose of the study? Yes
-Were the data collection procedures consistently
applied to the participants? Yes
-Was the validity and reliability of the data collection
instrument established at a high enough level? Yes
-Was the reliability of the data collectors established
at a high enough level? Yes
-Were important demographics of the intervention and Limitation
control/comparison group similar and, if not, did it
impact the results? Yes
-Were the treatment and control groups similar at the
baseline measurement of the outcome variables? Yes
-How were eligible participants accounted for
throughout the study? Presumptive positive babies
sent for further testing
-What did the power analysis indicate?
Strength
-Were data analyzed using an on-protocol or intentionto-treat analysis or both? Both
-If intention to treat analysis was used, what method
was used to input missing data? Referral
-Were the statistical analyses appropriate for the level
of data?
Yes
-Were the statistical analyses appropriate to test the
hypotheses and answer the research questions? Yes
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Running head: Improving Outcomes with Newborn Screening
Findings: 1.5 million babies were screened. MCADD was
confirmed in 147 of 190 babies with a positive screening result.
Discussion: Findings were reported from a large-scale
prospective study of newborn screening conducted in a multiethnic population. Approximately 1 in 10,000 babies were
diagnosed with MCADD, 60 a year. The numbers of false
positives were minimal. High specificity and overall PPV were
achieved. Strengths include a large scale, adherence to common
protocols and high completeness of data. A limitation of the
study is that clinical significance, outcome, and benefit for
babies assigned as MCADD of uncertain phenotype is not
known. Mutations through screening remain difficult to assess.
Conclusions: Newborn screening identifies MCADD in 1/10000
babies born in England. Features indicate a phenotype of definite
clinical importance. Ethnic variations in genotype and phenotype
were noted. This study supplied evidence for a high-quality and
rapidly implemented screening program.
-Are findings presented relative to each hypotheses
and research question? No
-Are finding reported as statistically significant or not
significant?
-Do the findings have practical or clinical
significance? Clinical significance
-Did the researchers thoroughly explain their
interpretation of the findings? Yes
-Were the explanation s logical?
Yes
-Did the researchers compare their findings to the
findings of previous studies and provide a rationale on
why they differ? Yes
-Did the researchers thoroughly identify and discuss
the limitations? Yes
-What are the implications for practice? A marker for
measuring clinical validity of the screening program
was established.
-What future recommendations are made? MCADD
referrals will only be made if C8 > 0.5 and C8/C10 >
1.0 to minimize unnecessary anxiety for families.
-Are the conclusions in alignment with the
intended purpose of the study? Yes
-Do the conclusions logically follow from the
findings and interpretation? Yes
Strength
Strength
Strength
Running head: Improving Outcomes with Newborn Screening
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References
Centers for Disease Control and Prevention (CDC). (2012, June 1). CDC Grand Rounds:
Newborn Screening and Improved Outcomes. Morbidity and Mortality Weekly Report
(MMWR). Retrieved from
http://www.cdc.gov/about/grandrounds/archives/2011/august2011.htm
Deluca, J., Zanni, K., Bonhomme, N., & Kemper, A. (2013). Implications of newborn screening
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Lipstein, E.A., Vorono, S., Browning, M.F., Green, N.S., Kemper, A.R., Knapp, A.A., … &
Perrin, J.M.. (2010, May). Systematic evidence review of newborn screening and
treatment of severe combined immunodeficiency. Pediatrics, 125(5): e1226-35. Doi:
10.1542/peds.2009-1567.
Lund, A.M., Hougaard, D.M., Simonsen, H., Andresen, B.S., & Christensen, M. (2012,
November). Biochemical screening of 504,049 newborns in Denmark, the Faroe Islands,
and Greenland-experience and development of routine program for expanded newborn
screening. Molecular Genetics and Metabolism. 107(3), 281-293.
Mahle, W.T., Newburger, J.W., Matherne, G.P., Smith, F.C., Hoke, T.R., Koppel, R., … &
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Oerton, J. Khalid, J. Besley, G., Dalton, R.N., Downing, M. (2011). Newborn screening for
medium chain acyl-CoA dehydrogenase deficiency in England. Journal of medical
screening. (18). 173-181.
Running head: Improving Outcomes with Newborn Screening
16
Porter, H., Neely, S., & Gorga, M. (2009, August). Using benefit-cost ratio to select universal
newborn hearing screening test criteria. Ear Hear, 30(4): 447-457.
doi: 10.1097/AUD.0b013e3181a26f11
Tiwana, S.K., Rascati, K.L., & Park, H., (2012, July). Cost effectiveness of expanded newborn
screening in Texas. Value in Health 15(5), 613-621.
Trikalinos, T.A., Chung, M., Lau, J., & Ip S. (2009, October). Systematic review of screening for
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Waisbren, S.E., Landau, Y., Wilson, J., & Vockley, J. (2012). Neuropsychological outcomes in
fatty acid oxidation disorders: 85 cases detected by newborn screening. Developmental
Disabilities Research Reviews, 17(3/4), 260-268. Doi:10.1002/ddrr.1119
Zwahlen, M., Low, N., Borisch, B., Egger, M., Kunzli, N., Obrist, R., … & Probst-Hensch, N.M.
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