Reconsidering reproductive benefit through newborn screening: a systematic review of guidelines on preconception,prenatal and newborn screening

The expansion of newborn screening (NBS) has been accompanied by debate about what benefits should be achieved and the role of parental discretion in their pursuit. The opportunity to inform parents of reproductive risks is among the most valued additional benefits gained through NBS, and assumes prominence where the primary goal of identifying a treatable condition is not assured. We reviewed 53 unique guidelines addressing prenatal, preconception and newborn screening to examine: (1) how generating reproductive risk information is construed as a benefit of screening; and (2) what conditions support the realization of this benefit. Most preconception and prenatal guidelines – where generating reproductive risk information is described as a primary benefit – required that individuals be given a ‘cascade of choices'', ensuring that each step in the decision-making process was well informed, from deciding to pursue information about reproductive risks to deciding how to manage them. With the exception of three guidelines, NBS policy infrequently attended to the potential for reproductive benefits; further, most guidelines that acknowledged such benefits construed voluntarism narrowly, without attention to the choices attendant on receiving reproductive risk information. This review suggests that prenatal and preconception guidance identifies a coherent framework to support the pursuit of reproductive benefits through population screening programmes. Interestingly, attention to reproductive benefits is increasing among NBS guidance, yet reflection on how such benefits ought to be pursued remains limited. Traditional norms for NBS may require reconsideration where the remit of screening exceeds the primary goal of clinical benefits for infants.     

Health-care providers' views on pursuing reproductive benefit through newborn screening: the case of sickle cell disorders

Newborn screening (NBS) programs aim to identify affected infants before the onset of treatable disorders. Historically, benefits to the family and society were considered secondary to this clinical benefit; yet, recent discourse defending expanded NBS has argued that screening can in part be justified by secondary benefits, such as learning reproductive risk information to support family planning ('reproductive benefit'). Despite increased attention to these secondary benefits of NBS, stakeholders' values remain unknown. We report a mixed methods study that included an examination of providers' views toward the pursuit of reproductive risk information through NBS, using sickle cell disorder carrier status as an example. We surveyed a stratified random sample of 1615 providers in Ontario, and interviewed 42 providers across 7 disciplines. A majority endorsed the identification of reproductive risks as a goal of NBS (74-77%). Providers' dominant rationale was that knowledge of carrier status is an important and inherent benefit of NBS as it allows people to make reproductive choices, which is consistent with the goals of disease prevention. However, some challenged its appropriateness, questioning its logic, timing and impact on disease prevention. Others were sensitive to intruding on individuals' choices or children's independent rights. While the dominant view is consistent with discourse defending expanded NBS, it deviates from the traditional screening principles that underpin most public health interventions. Broader discussion of the balance between benefits to screened individuals and those to families and societies, in the context of public health programs, is needed.     

The association between newborn screening analytes and childhood autism in a Texas Medicaid population, 2010–2012

Autism (or autism spectrum disorder [ASD]) is an often disabling childhood neurologic condition of mostly unknown cause. It is commonly diagnosed at 3 or 4 years of age. We explored whether there was an association of any analytes measured by newborn screening tests with a later diagnosis of ASD. A database was compiled of 3–5 year‐old patients with any ASD diagnosis in the Texas Medicaid system in 2010–2012. Two controls (without any ASD diagnosis) were matched to each case by infant sex and birth year/month. All study subjects were linked to their 2007–2009 birth and newborn screening laboratory records, including values for 36 analytes or analyte ratios. We examined the association of analytes/ratios with a later diagnosis of ASD. Among 3,258 cases and 6,838 controls, seven analytes (e.g., 17‐hydroxyprogesterone, acylcarnitines) were associated with a later ASD diagnosis. In this exploratory study, an ASD diagnosis was associated with 7 of 36 newborn screening analytes/ratios. These findings should be replicated in other population‐based datasets.     

Analyzing paths from online health information seeking to colorectal cancer screening using health literacy skills frame and cognitive mediation model

Objective

To test the hypothesized paths for Online Health Information Seeking (OHIS) behaviors in developing health literacy, leading to colorectal cancer (CRC) screening among Korean Americans (KAs) using Health Literacy Skills Frameworks (HLSF) and Cognitive Mediation Model (CMM).

Molecular analysis of CYP21A2 can optimize the follow‐up of positive results in newborn screening for congenital adrenal hyperplasia

Neonatal screening for congenital adrenal hyperplasia (CAH) is useful in diagnosing salt wasting form (SW). However, there are difficulties in interpreting positive results in asymptomatic newborns. The main objective is to analyze genotyping as a confirmatory test in children with neonatal positive results. Patients comprised 23 CAH children and 19 asymptomatic infants with persistently elevated 17‐hydroxyprogesterone (17OHP) levels. CYP21A2 gene was sequenced and genotypes were grouped according to the enzymatic activity of the less severe allele: A1 null, A2 < 2%, B 3–7%, C > 20%. Twenty‐one children with neonatal symptoms and/or 17OHP levels > 80 ng/ml carried A genotypes, except two virilized girls (17OHP < 50 ng/ml) without CAH genotypes. Patients carrying SW genotypes (A1, A2) and low serum sodium levels presented with neonatal 17OHP > 200 ng/ml. Three asymptomatic boys carried simple virilizing genotypes (A2 and B): in two, the symptoms began at 18 months; another two asymptomatic boys had nonclassical genotypes (C). The remaining 14 patients did not present CAH genotypes, and their 17OHP levels were normalized by 14 months of age. Molecular analysis is useful as a confirmatory test of CAH, mainly in boys. It can predict clinical course, identify false‐positives and help distinguish between clinical forms of CAH.     

Consumer health information technology in an adult public health primary care clinic: A heart health education feasibility study

Objective

To explore the feasibility and short term outcomes of using an interactive kiosk integrated into office flow to deliver health information in a primary care clinic.

Methods

Fifty-one adults with BMI ≥25 were randomly assigned to use a kiosk with attached devices to receive a six-week healthy eating/weight monitoring (intervention) or general health/BP monitoring (attention-control) program. Outcomes were measured at baseline, 8 weeks (post) and three month follow-up.

Results

Participants completed an average of 2.73 weekly sessions, with transportation and time given as limiting factors. They found the kiosk easy to use (97%), liked the touchscreen (94%), and would use the kiosk again (81%). Although there were no differences between groups, the 27 completing all assessments showed reduced weight (p = .02), and decreased systolic (p = .01) and diastolic BP (p < .001) at follow-up. Although healthy eating behaviors increased, the change was not statistically significant.

Conclusion

Using a kiosk within a clinic setting is a feasible method of providing health information and self-monitoring. Multi-session educational content can provide beneficial short-term outcomes in overweight adults.

Practice implications

A kiosk with attached peripherals in a clinic setting is a viable adjunct to provider education, particularly in medically underserved areas.     

Consumer health information technology in an adult public health primary care clinic: A heart health education feasibility study

ObjectiveTo explore the feasibility and short term outcomes of using an interactive kiosk integrated into office flow to deliver health information in a primary care clinic.MethodsFifty-one adults with BMI ≥25 were randomly assigned to use a kiosk with attached devices to receive a six-week healthy eating/weight monitoring (intervention) or general health/BP monitoring (attention-control) program. Outcomes were measured at baseline, 8 weeks (post) and three month follow-up.ResultsParticipants completed an average of 2.73 weekly sessions, with transportation and time given as limiting factors. They found the kiosk easy to use (97%), liked the touchscreen (94%), and would use the kiosk again (81%). Although there were no differences between groups, the 27 completing all assessments showed reduced weight (p = .02), and decreased systolic (p = .01) and diastolic BP (p < .001) at follow-up. Although healthy eating behaviors increased, the change was not statistically significant.ConclusionUsing a kiosk within a clinic setting is a feasible method of providing health information and self-monitoring. Multi-session educational content can provide beneficial short-term outcomes in overweight adults.Practice implicationsA kiosk with attached peripherals in a clinic setting is a viable adjunct to provider education, particularly in medically underserved areas.     

Newborn screening for severe combined immunodeficiency and T‐cell lymphopenia

The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots (DBS) made possible universal newborn screening (NBS) for severe combined immunodeficiency (SCID) as a public health measure. Upon being flagged by an abnormal screening test in a SCID screening program, an infant can receive further diagnostic testing for SCID in the neonatal period, prior to onset of infectious complications, to permit immediate institution of protective measures and definitive, life‐saving treatment to establish a functional immune system. SCID screening is now the accepted standard of care in state public health departments across the United States, and it is being adopted in many countries. It has proven effective, with infants having this otherwise inapparent but serious, rare disorder achieving survival and immune reconstitution. In addition to bringing to attention infants with the primary screening target diseases, typical SCID and leaky SCID (due to hypomorphic mutations in known SCID genes), the NBS assay for insufficient TRECs in DBS also reveals infants with non‐SCID T lymphopenic conditions. Experience has accumulated regarding the range and limitations of diagnoses of newborns with low TRECs and low T cells. Previously unknown immune defects have been discovered, as well as conditions not formerly recognized to have low T cells in the neonatal period.     

Retrospective review of Japanese sudden unexpected death in infancy: the importance of metabolic autopsy and expanded newborn screening

Sudden unexpected death in infancy is defined as sudden unexpected death occurring before 12 months of age. The common causes of sudden unexpected death in infancy are infection, cardiovascular anomaly, child abuse, and metabolic disorders. However, the many potential inherited metabolic disorders are difficult to diagnose at autopsy and may therefore be underdiagnosed as a cause of sudden unexpected death in infancy. In the present study we retrospectively reviewed 30 Japanese sudden unexpected death in infancy cases encountered between 2006 and 2009 at our institute. With postmortem blood acylcarnitine analysis and histological examination of the liver, we found two cases of long-chain fatty acid oxidation defects. Molecular analysis revealed that the one patient had a compound heterozygote for a novel mutation (p.L644S) and a disease-causing mutation (p.F383Y) in the carnitine palmitoyltransferase 2 gene. Furthermore, retrospective acylcarnitine analysis of the newborn screening card of this patient was consistent with carnitine palmitoyltransferase II deficiency. Metabolic autopsy and expanded newborn screening would be helpful for forensic scientists and pediatricians to diagnose fatty acid oxidation disorders and prevent sudden unexpected death in infancy.     

Junior physician's use of Web 2.0 for information seeking and medical education: A qualitative study

Background

Web 2.0 internet tools and methods have attracted considerable attention as a means to improve health care delivery. Despite evidence demonstrating their use by medical professionals, there is no detailed research describing how Web 2.0 influences physicians’ daily clinical practice. Hence this study examines Web 2.0 use by 35 junior physicians in clinical settings to further understand their impact on medical practice.

Method

Diaries and interviews encompassing 177 days of internet use or 444 search incidents, analyzed via thematic analysis.

Results

Results indicate that 53% of internet visits employed user-generated or Web 2.0 content, with Google and Wikipedia used by 80% and 70% of physicians, respectively. Despite awareness of information credibility risks with Web 2.0 content, it has a role in information seeking for both clinical decisions and medical education. This is enabled by the ability to cross check information and the diverse needs for background and non-verified information.

Conclusion

Web 2.0 use represents a profound departure from previous learning and decision processes which were normally controlled by senior medical staff or medical schools. There is widespread concern with the risk of poor quality information with Web 2.0 use, and the manner in which physicians are using it suggest effective use derives from the mitigating actions by the individual physician. Three alternative policy options are identified to manage this risk and improve efficiency in Web 2.0's use.     

Newborn screening for Fabry disease in Oregon: Approaching the iceberg of A143T and variants of uncertain significance

Fabry disease newborn screening (NBS) has been ongoing in Oregon for over 41 months by first-tier enzyme quantitation and second-tier DNA testing. During that period the majority of abnormal referrals received (34/60) were for the presence of the controversial c.427G > A (p.Ala143Thr) aka A143T and the majority of non-A143T referrals were for other variants of uncertain significance (17/60) resulting in at least 32 infants with an inconclusive case outcome even after clinical evaluation and/or diagnostic testing. To date there has been no significant family history or onset of symptoms in individuals with an inconclusive outcome. Based on our experience, we have developed a framework for approaching A143T and other variants of uncertain clinical significance in an attempt to balance sensitivity with the unnecessary medicalization of healthy infants.     

The use of video for patient information and education: A scoping review of the variability and effectiveness of interventions

ObjectiveTo provide an overview of video interventions used for patient information and education, and of the tools used to evaluate their effectiveness, in order to consider the feasibility of developing generic guidelines and appraisal tools for the use of video in patient care.MethodsA scoping review was carried out to describe and synthesise emerging knowledge, using thematic analysis of data. Studies focussed upon videos for health professional education were excluded, as were those which consider the impact of videos available via social media.ResultsA narrative overview of 65 identified papers provides insight into the range and scope of studies. Common themes emerge, notably the aim of reducing anxiety and the variety of instruments designed to measure this. The use of self-report questionnaires was common, but their design is variable.ConclusionTargeted video-based intervention can improve patient experience and outcomes. High utility guidelines and appraisal tools, transferable between contexts, are needed to facilitate deployments at scale for sustainable outcomes.Practice implicationsVideo production guidelines and appraisal tools will be of value to those engaged in video development and deployment. Guidance should be based upon emerging evidence of effectiveness and incorporate an emphasis on reusability.     

Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later‐onset GLA mutation c.936+919G>A (IVS4+919G>A)

Fabry disease (α‐galactosidase A (α‐Gal A, GLA) deficiency) is a panethnic inborn error of glycosphingolipid metabolism. Because optimal therapeutic outcomes depend on early intervention, a pilot program was designed to assess newborn screening for this disease in 171,977 consecutive Taiwanese newborns by measuring their dry blood spot (DBS) α‐Gal A activities and β‐galactosidase/α‐Gal A ratios. Of the 90,288 male screenees, 638 (0.7%) had DBS α‐Gal A activity <30% of normal mean and/or activity ratios >10. A second DBS assay reduced these to 91 (0.1%). Of these, 11 (including twins) had <5% (Group‐A), 64 had 5–30% (Group‐B), and 11 had >30% (Group‐C) of mean normal leukocyte α‐Gal A activity. All 11 Group‐A, 61 Group‐B, and 1 Group‐C males had GLA gene mutations. Surprisingly, 86% had the later‐onset cryptic splice mutation c.936+919G>A (also called IVS4+919G>A). In contrast, screening 81,689 females detected two heterozygotes. The novel mutations were expressed in vitro, predicting their classical or later‐onset phenotypes. Newborn screening identified a surprisingly high frequency of Taiwanese males with Fabry disease (∼1 in 1,250), 86% having the IVS4+919G>A mutation previously found in later‐onset cardiac phenotype patients. Further studies of the IVS4 later‐onset phenotype will determine its natural history and optimal timing for therapeutic intervention. Hum Mutat 30:1–9, 2009. © 2009 Wiley‐Liss, Inc.     

Efficient assessment of social problem‐solving abilities in medical and rehabilitation settings: a rasch analysis of the social problem‐solving inventory‐revised

The Social Problem Solving Inventory‐Revised Scale (SPSI‐R) has been shown to be a reliable and valid self‐report measure of social problem‐solving abilities. In busy medical and rehabilitation settings, a brief and efficient screening version with psychometric properties similar to the SPSI‐R would have numerous benefits including decreased patient and caregiver assessment burden and administration/scoring time. Thus, the aim of the current study was to identify items from the SPSI‐R that would provide for a more efficient assessment of global social problem‐solving abilities. This study consisted of three independent samples: 121 persons in low‐vision rehabilitation (M age=71 years old, SD=15.53), 301 persons living with diabetes mellitus (M age=58, and SD=14.85), and 131 family caregivers of persons with severe disabilities (M age=56 years old, SD=12.15). All persons completed a version of the SPSI‐R, Center for Epidemiological Studies Depression Scale (CES‐D), and the Satisfaction with Life Scale (SWLS). Using Rasch scaling of the SPSI‐R short‐form, we identified a subset of 10 items that reflected the five‐component model of social problem solving. The 10 items were separately validated on the sample of persons living with diabetes mellitus and the sample of family caregivers of persons with severe disabilities. Results indicate that the efficient 10‐item version, analyzed separately for all three samples, demonstrated good reliability and validity characteristics similar to the established SPSI‐R short form. The 10‐item version of the SPSI‐R represents a brief, effective way in which clinicians and researchers in busy health care settings can quickly assess global problem‐solving abilities and identify those persons at‐risk for complicated adjustment. Implications for the assessment of social problem‐solving abilities are discussed. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1–15, 2009.     

Health literacy and self-efficacy for participating in colorectal cancer screening: The role of information processing

Objective

This study aimed to document the association between health literacy and willingness and ability to seek information about the new colorectal cancer (CRC) screening program in the UK.¹ We also assessed self-efficacy for screening to determine the impact of health literacy on perceived confidence to take part in screening.

Methods

Ninety-six participants aged 50–69 years completed the British version of the Test of Functional Health Literacy in Adults (TOFHLA) (UK-TOFHLA) and used an interactive information menu to select information on why and how to participate in CRC screening. We derived a measure of reading effort by calculating the average amount of time spent reading individual information links. Each participant also completed a measure of comprehension, and self-efficacy for participating in screening.

Results

A multivariate analysis supported the hypothesis that lower health literacy would be associated with less information-seeking (b = .079, 95% confidence interval, .001–.157) greater effort in reading (b = −.965, 95% CI, −1.457 to −.473) and less self-efficacy for CRC screening (b = .61, 95% CI, .009–.131).

Conclusion

Lower health literacy had a direct impact on information-seeking. It was also independently associated with perceived confidence to participate in screening.

Practice implications

Reliance on printed communication when inviting low literate adults for screening can be problematic. The independent association between health literacy and self-efficacy further adds to the challenge of developing accessible and effective health promotion materials in this area.