1

False Positive Newborn Screening for Cystic Fibrosis

Susan Powell-Proctor

NSG 4056

Dr. Griffin

South University

8/20/21

False Positive Newborn Screening for Cystic Fibrosis: Article Review

 2

Cystic Fibrosis (CF) is a hereditary disorder that damages organs of patients. The most

affected organs are lungs and the digestive system (Godfrey et al, 2020). Though previously

untreatable, with proper identification, most patients can now survive into adulthood (De Boeck,

2020). Being progressive, it does require daily care but quality of life improvements through

treatment allow patients to now live into their mid to late 30’s and 40’s (Mayo, 2021). Screening

for the disease is critical for early intervention. In the selected article for review, Hayeems et al.

(2017) examined the phenomenon of false positive newborn screenings for CF. According to the

researchers, evidence on the impact of false positive CF screening on healthcare systems is

ambiguous (Heyems, et al., 2017). Using negative binomial regression and a sampling of 7820

infants, the researchers sought to determine the impact of false positive NBS results on

healthcare outcomes of infants and the psychosocial effects on their parents (Heyems et al.,

2017). The research added to the current literature on the subject that newborns with FP

screening results experience increased hospital admission with no increase in health care

utilization among their mothers (parents) (Hayeems et al., 2017). Implications will be considered

with attention to evidence-based practice and results of other existing scholarship on the subject.

Methods

According to Hayeems et al. (2017), the study is best described as “a population-based,

retrospective, matched-cohort study” (p. e20170604). As previously articulated, the researchers

used a negative binomial regression and a sampling of 7820 infants. Of the sampling, false

positives accounted for 1564 and matched controls amounted to 6256 (Hayeems et al., 2017).

The data came from linked health administrative data collected between 2008 and 2012

(Hayeems et al., 2017). The outcomes that were established by the researchers were infant and

mother physicians, emergency room and inpatient visits from 3 months to 15 months of age
 3

(Hayeems et al., 2017). The data set was specific to Canadian data sources and approval for the

study came from a Canadian pediatric hospital based in Toronto (Hayeems et al., 2017). The

database employed was called the MOMBABY data set comprised of linked data that is

established by the Canadian government (Hayeems et al., 2017).

The researchers also employed a robust exclusionary process to ensure that the data

collected fit the parameters of what was being studied. The included study population were

newborns who had False Positive (FP) NBS results for cystic fibrosis (CF) or infants with

negative results on the rest of conditions that were screened (considered as unexposed controls)

but were deemed eligible. The study excluded cases where the infant has a length of stay of more

than 2 months after birth, either mother or infant deceased before the expiry of the follow-up

period

Results

The results indicated that a greater percentage of newborns with false positive (FP)

screening results had more than two outpatient visits, a rate that translated to 16.2% visits versus

13.2% visits for the control group. And more than two hospital admissions, a rate that translated

to 1.5 % admissions versus 0.7% admissions for the control group. This implies that FP CF

outcomes leads to increased utilization of healthcare services among infants. The results also

indicated that cystic fibrosis-related admissions as well as ED visits were not dissimilar from the

experimental controls..

Conclusions

Hayeems et al. (2017) stated that their research findings most closely mirrored those of

Karaceperet al. (2016). The reviewer, therefore, thought it would be prudent to look closer at the

Karaceper et al. (2016) study in order to better frame the work of Hayeemset al. (2017). Upon
 4

analysis of this earlier study, it made the work of Hayeems et al. (2017) more clear as the earlier

work did a better job as illustrated the present research gaps in scholarship and the implications

of those gaps. An examination of Karaceper et al. (2016) revealed that there is little consensus

present in medical academia related to the impact of false positive newborn screening results on

early health care utilization practices. As it stands, published evidence is in consisted regarding

FP newborn status and parental psychosocial experiences (Karacepter et al., 2016). Quite simply,

there is evidentiary disputes related to parental perspectives on health care emergencies and

visits that they deem necessary if they think their child is positive.

It would be reasonable to assume that a parent who though their child was positive for CF

would immediately connect any perceived medical issue to something more severe thereby

causing them to seek out additional help. Karacepter et al. (2016) felt that having strong data

related to this, if it was a proven phenomenon, could be used by medical

professionals/stakeholders to create better support and education programs for families.

According to both Karacepter et al. (2016) and Hayeems et al. (2017), newborn FP for CF

experienced considerably higher rates healthcare use in their first year of life than those with

negative results. Hayeems et al. (2017), however, also indicated that their results were

inconsistent with Tarini et al. (2017). Tarini et al. (2017), did suggestion that FB screenings and

increased visits may be attributed to underlying parental anxiety or chronic diseases. It is during

this reporting of data that the way in which Hayeems et al. (2017) discusses their data that it

becomes confusing. When referencing other studies, at times they seem to be saying one

conclusion and then shortly later they are saying something different. The reason for this is likely

due to the fact that they are discussing a number of complicated variables and within these

variables some are consistent with other studies and some deviate even though other elements
 5

they present may be congruent with other parts of these selected studies. As will be highlighted

in the student reflection portion, the complex nature of the study does make some elements

unclear. Despite the complex nature of the results and problems drawing conclusions from these

results, the researchers stated that further research is needed to produce a more holistic view of

the role of health status and false positive status (Hayeems et al., 2017). As it stands, there’s

research data supporting that infants with false positive screening outcomes for cystic fibrosis are

getting more care needlessly and contradicting data showing that they are getting care that’s

consistent with their actual health needs. This paper highlights the importance of continued

research on the topic.

Student Reflection

The study design, as noted in the methods portion of the overview, was extremely

complex. The advanced statistical design was such that some of the elements that were presented

were outside the full comprehension of the reviewer. It is important to note, however, that these

elements that were outside of the reviewer scope did not infringe on the usefulness of the study

or understanding the results and implications. The data collected could be useful to multiple

stakeholders relying on such healthcare delivery models. Understanding all of the elements that

went into making the study valid are not necessary for appreciating or applying the information

collected. Full comprehension, however, would be necessary if an individual or group wished to

replicate the results of the study or to examine if the same results would hold true in another data

set. For example, a research team could use the same study set up and employ a different data

base outside of the Canadian demographic to see if the data results stayed consistent. It would be

useful in the future, therefore, to use the same study set up and collect results from other

developed nations like the United States or the European Union. That data could be compared to
 6

the Canadian data to determine the if the results were consistent across all developed nations or if

they were specific to the Canadian health care system. Additionally, the same study could be

framed to examine less developed nations to see how the data sets compared. Overall, the scope

of the design is such that it could establish a framework for more complete understanding of the

subject across sophisticated health care systems and less sophisticated systems.

In terms of validity and reliability, the work had a robust sampling, consistent measures,

and a methods that can be replicated across other populations besides the one explored.

Additionally, the peer reviewed nature of the work and its relatively recent publication date of

2017 makes the material reliable, relevant, and useful to advancing the understanding of cystic

fibrosis. It was clear to the reviewer that the presence of false positive data had statistically

significant implications for evidence based practice. Examining this study was useful to the

reviewer for better understanding cystic fibrosis and what is known and unknown about the

disease. From a research standpoint, it also illustrated the potential complexity of research

studies. Elements like reliability, statistical analysis and ethical considerations were all apparent

and provided a greater sense of understanding the general attributes of academic research

pertaining to known information gaps that are present in current research.

Since the data presented is both supported and refuted by other research studies in the

field, this also highlights the imperfect nature of advancing medical knowledge. There is often

the misnomer present in academic literature that if a peer reviewed study says one thing, that is

scientific fact. This is not necessarily the case as it is an oversimplification of complicated

principles. According to Smith (2006), peer review is a process of all science. There are different

ways of interpreting data, flaws potentially present, confounding elements related to a specific

population or perhaps even an absence of knowledge necessary to properly understand the

 7

implications of a particular data set. It is, therefore, a flawed but necessary process (Smith,

2006). Hayeems et al. (2017) does not shy away from this phenomenon and makes it a point to

show where their data is congruent and divergent from other popular research in the field on the

same subject.

To further examine the variance present in the topic, a newer study was also sought out

by the reviewer. Lumertzet al. (2019) highlighted that FP and false negative can occur related to

chronic lung disease in children. The researchers stated that more research is present related to

FP than FN (Lumertzet al. 2019). According to Lumertz et al. (2019), there are important

psychosocial impacts related to false positive results on infants and their respective parents but

these show no consistent or persistent psychosocial impact beyond the immediate stresscaused

by information about a false positive result. This also shows that there is an element in Hayeems

et al. (2017), study, that of false positive, that was not explored and that could have profound

implications on the scholarship related to the study.

The study, though it did not specifically articulate this, also highlighted the importance of

electronic medical records. Without the advanced Canadian data system that collects information

about patients with various diseases and the progression of their health care related to the

respective disease(s), important information like this could not be accurately tracked. The

authors used several different official databases to find the necessary information. This

highlights how important innovation and data collection is important for medical research. It also

illustrates that in the future, a more singular electronic health record system could be put together

so all of the information is in one place that relates to specific topics. As it stands, electronic

health records are a relatively new phenomenon and with any new innovation, there are concerns

and fear related to how the data will be employed. Studies like this illustrate the profound
 8

importance of such record keeping and how those records can help shape and guide health care

delivery for better outcomes and a more healthy society. The reviewer, therefore, was reminded

of why record keeping in databases is so important for modern health care. If robust samplings of

over 7000 people were not available, such studies would be relegated to smaller samplings in

singular contexts of experimental research. While those types of studies are also useful, being

able to examine a broad scale population base across an entire nation for a relatively obscure

disease is of profound consequence. The entire scope of the research study analysis was useful

on multiple levels and has advanced the researchers knowledge of both cystic fibrosis and

medical research in general. The activity, therefore, was of tremendous value.

Strengths and Weaknesses

In my view, this study had a number of strengths and weaknesses. A critique of the paper

revealed several strengths. The first one is the use of recent and valid sources of literature. The

use if recent literature to support the study is important as it shows the relevancy of the study to

current practice. The sources and method used were also valid and credible as seen by the level

of concurrence or similarity of some of the findings to previous studies. The titles and the

abstract are also well-written. The paper also has a high level of logical consistency. In regards to

sampling, the author made a clear identification of the sample population and deployed a clear

method of sampling. An appropriate data analysis method was used by the authors, and this

added to the strength of the study. The authors also used proper method to highlight the sources

used in the reference section.

I believe that the study has some weaknesses. The main one includes lack of a proper

ethical strategy for seeking or gaining informed consent. There is a possibility that the author had

informed consent but failed to mention in the study. Nevertheless, such an ambiguity has a
 9

negative impact on the research process. The other weakness is the use of a complex statistical

process involving a stratified model. Stratified models do not represent the entire population and

may be skewed and full of errors.

Evidence-Based Practice

Evidence-based practice (EBP) is defined as a process involving the collection,

processing as well as implementation of research findings to achieve an improvement of clinical

practice, patient outcomes and state of or environment (Mackey, & Bassendowski et al, 2017).

The result of this study, event tough not based on randomized control trails (RCTs), can inform

clinical practice by using the evidence to support the need for optimizing infants with FP , CF

diagnoses. Several RCTs involving the False Positive for infants with suspected CF are in

existence. For instance, the advocacy role of nurses in championing for patient’s rights to

effective treatment using strategies like genetic counselling and associated improvement in

patient safety and health outcomes are based on evidence-based practice (Madlensky et al, 2017).

While handling FP cases, evidence-based practice suggests the use of proper communication

strategy to improve patient outcomes.

 10

References

De Boeck, K. (2020). Cystic fibrosis in the year 2020: A disease with a new face. Acta

Paediatrica, 109(5), 893-899.

Evridiki, K., Areti, S., Martha, K., Georgia, T., & Georgia, F. (2021). Critiquing a Grounded

Theory Research Paper: Αn Educational Guide for Nurses. Global Journal of Health

Science, 13(5), 1-92.\

Godfrey, N., Ganyam, M. M., Ibiang, G. O., Difa, C. A., & Christian, N. (2020). Defective Ion

Channel in Cystic Fibrosis: Current Development in Treatment of Cystic Fibrosis. Asian

Journal of Biochemistry, Genetics and Molecular Biology, 28-34

Hayeems, R. Z., Miller, F. A., Vermeulen, M., Potter, B. K., Chakraborty, P. Davies, C., Carroll,

J. C., Ratjen, F., & Guttmann, A. (2017). False positive newborn screening for cystic

fibrosis and health care use. Pediatrics, 140(5), e20170604.

Karaceper, M. D., Chakraborty, P., Coyle, D., Wilson, K., Kronick, J. B., Hawken, S., ... &

Potter, B. K. (2016). The health system impact of false positive newborn screening

results

for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study. Orphanet Journal

of Rare Diseases, 11(1), 1-9.

 11

Lumertz, M. S., Rispoli, T., Rosa, K. M. D., & Pinto, L. A. (2019). False-negative newborn

screening result for immunoreactive trypsinogen: a major problem in children with

chronic lung disease. Jornal Brasileiro de Pneumologia, 45.

Mackey, A., & Bassendowski, S. (2017). The history of evidence-based practice in nursing

education and practice. Journal of Professional Nursing, 33(1), 51-55.

Madlensky, L., Trepanier, A. M., Cragun, D., Lerner, B., Shannon, K. M., & Zierhut, H. (2017).

A rapid systematic review of outcomes studies in genetic counseling. Journal of genetic

counseling, 26(3), 361-378.

Mayo Clinic. (2020). Cystic Fibrosis. Mayo Clinic. Retrieved from https://www.mayoclinic.org/

diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700

Smith, R. (2006). Peer review: A flawed process at the heart of science and journals. Journal of

the Royal Society of Medicine, 99(4), 178-182.

Tarini, B. A., Clark, S., Pilli, S., Dombkowski, S., Korzeniewski, S., Gebremarian, A.,

Eisenhalder, J. & Grigorescu, V. (2011). False positive newborn screening result and

future health care use in a state medicaid cohort. Pediatrics, 128(4), 715-722.