Parents' experiences of newborn screening for genetic susceptibility to type 1 diabetes

Advances in genomic medicine have lead to debate about the potential inclusion of genetic tests for susceptibility to common complex disorders in newborn screening programmes. Empirical evidence concerning psychosocial reactions to genetic testing is a crucial component of both ethical debate and policy development, but while there has been much speculation concerning the possible psychosocial impact of screening newborns for genetic susceptibilities, there remains a paucity of data. The aim of the study reported here is to provide some of this missing empirical evidence, using type 1 diabetes as an example of a common disorder with multiple significant genetic contributors to its aetiology. Semi-structured interviews were conducted with 11 parents of babies who had received increased risk results in a study that involved newborn screening for genetic susceptibility to type 1 diabetes. Interpretative phenomenological analysis was used to evaluate the data. The interview data suggest that the probabilistic nature of results of genetic susceptibility tests impacts upon all aspects of parents' psychosocial reactions, resulting in a complex and dynamic process quite different to that described in relation to current newborn screening programmes. While parents generally reported fairly minor levels of concern in response to news of their child's increased genetic risk, these worries frequently recurred, and perception of risk also varied and fluctuated over time. Both individual and contextual factors appeared to interact with the inherent uncertainty of the test result to contribute to the dynamic nature of parental reactions, and their behavioural responses. The implications of these findings for future research and for the debate concerning potential expansion of newborn screening are discussed.     

Proceduralisation, choice and parental reflections on decisions to accept newborn bloodspot screening

Newborn screening is the programme through which newborn babies are screened for a variety of conditions shortly after birth. Programmes such as this are individually oriented but resemble traditional public health programmes because they are targeted at large groups of the population and they are offered as preventive interventions to a population considered healthy. As such, an ethical tension exists between the goals of promoting the high uptake of supposedly 'effective' population-oriented programmes and the goal of promoting genuinely informed decision-making. There is, however, a lack of understanding with regard to how parents experience the tension between promoting uptake and facilitating informed choice. This paper addresses this issue, and data are presented to show how aspects of the timing, presentation of information and procedural routinisation of newborn screening serves to impact on the decisions made by parents.     

Risk factors for coronary heart disease in a self-referred population compared with a general population

Screening programmes for community coronary heart disease risk factors aim to identify persons who are at a high risk of the development of coronary heart disease by screening the population for the prevalence of smoking, obesity, high blood pressure and high blood cholesterol concentrations. The effectiveness of such screening programmes is dependent on a number of factors. The characteristics of individuals who attend such screening programmes voluntarily, and the prevalence of abnormal coronary heart disease risk factors that is detected, give a strong indication of the population reach and the potential benefits of the preventive strategy. In this study, persons who attended a self-referred risk-factor screening programme for coronary heart disease were compared with a random sample of the Australian urban population. A disproportionately high number of older persons and of women presented for the self-referred screening programme while smokers were underrepresented. In general, the risk-factor levels of those in the older age-groups who attended the screening programme were lower than were the corresponding measurements that were found in the random sample; the opposite was true for those in the younger age-groups. These results suggest that coronary heart disease risk-factor screening programmes in the community appeal more to those in the health-conscious older age-groups and to women. For heart disease prevention programmes to be more effective, it will be necessary to design screening programmes to attract more men, those in younger age-groups and smokers.     

Newborn screening in North Carolina: the evolution of policy and practice

Newborn screening policies in North Carolina are due to the efforts of skilled and knowledgeable state officials, clinicians, and scientists who are able to develop effective newborn screening procedures. A newborn screening that was developed in North Carolina is the first automated method for diagnosing phenylketonuria. This process was later adopted in many other states. The use of tandem mass spectrometry in newborn screening was also pioneered in North Carolina, and it is being used in an increasing number of states. Newborn screening is more than testing, however; follow-up and specialized care are essential. State-level policies should recognize the multiple links necessary to make newborn screening effective and efficient.     

The "new genetics" and clinical practice

A "new genetics" has emerged driven by knowledge gained at the DNA level. In clinical practice, a practical application of the new genetics is DNA testing, which can be expected to expand with the completion of the Human Genome Project as the functions of new genes are discovered. Genetic DNA testing scenarios include diagnostic DNA testing, prenatal DNA testing, predictive (presymptomatic) DNA testing and screening DNA testing. The challenge for genetic DNA testing and clinical practice will be to define the roles to be played by the general practitioner, the specialist, and other healthcare professionals. From the patients' and families' perspective, the new genetics will best be implemented if a planned approach is adopted in the ordering of DNA tests and the associated counselling and support processes.     

新生儿听力与聋病易感基因联合筛查的临床实践研究

目的 探讨新生儿听力和聋病易感基因联合筛查的临床实践的可行性.方法选择从2012年9月-2013年7月在该市出生的6 057例新生儿进行听力和聋病易感基因的联合筛查,同时进行动态筛查及基因检测,新生儿听力动态筛查分初筛和复筛,初筛以快速脑干诱发电位（AABR）为主要筛查方式,如果不通过,30~42 d复筛,复筛不通过转诊该院耳鼻喉科诊断,采用如畸变产物耳声发射（DPOAE）,脑干听觉诱发电位（ABR）,声导抗、多频稳态反应（ASSR）、CT等检查进行综合评估;同时对新生儿进行基因筛查,采取6 057例新生儿脐带（或足跟血）以检测常见易感基因（线粒体12S rRNA、SLC26A4（PDS）、GJB2）的突变情况.结果 动态听力筛查未通过新生儿375例,所占比例6.19%;耳鼻喉科诊断有120例中度听力损失、131例重度听力损失、80例极重度听力损失、44例听力正常.对6 057例新生儿行基因检测显示193例新生儿基因异常,其中1例为1494C〉T纯合突变、2例1555A〉G杂合突变、16例1555A〉G纯合突变、7例2168A〉G杂合突变、46例IVS7-2A〉G杂合突变、1例IVS7-2A〉G纯合突变、101例235delC杂合突变、4例235delC纯合突变、11例299_300delAT杂合突变、4例176_191del16杂合突变,阳性率为3.19%.结论新生儿听力和聋病的易感基因联合筛查作用显著,可以发现新生儿中存在和聋病相关的遗传基因,从而弥补其他筛查不能发现聋病新生儿的不足.     

Predictive Genetic Testing, Autonomy and Responsibility for Future Health

Individual autonomy is a concept highly appreciated in modern Western societies. Its significance is reflected by the central importance and broad use of the model of informed consent in all fields of medicine. In predictive genetic testing, individual autonomy gains particular importance, for what is in focus here is not so much a concrete medical treatment but rather options for taking preventive measures and the influence that the test results have on long-term lifestyle and preferences. Based on an analysis of autonomy-related issues in predictive genetic diagnosis and genetic screening programmes, this contribution stresses the central relevance of a broad notion of autonomy for the discussion of ethical issues raised in connection with predictive genetic testing and genetic screening programmes. Only against the background of such a broad notion of autonomy, which stresses not only free and informed decision-making but also the relevance of long-term prospects for leading a self-determined life in familial and social contexts, can the manifold autonomy-related issues linked to predictive genetic testing be given adequate consideration.     

Ethical issues in preconception genetic carrier screening

Population-based preconception genetic carrier screening programmes (PCS) with expanded panels are currently being developed in the Netherlands. This form of genetic screening for recessive traits differs from other forms of genetic testing and screening in that it is offered to persons not known to have an increased risk of being carriers of genetic traits for severe recessive diseases and in that they include tests for a large number of traits, potentially several hundred. This raises several ethical issues around justice, consequences, and autonomy. It will be argued that most of these ethical problems call for cautious reflection when setting up PCS and similar programmes within preconception care. It is moreover argued that it is ethically problematic to have an official aim and failing to mention possibly legitimate public aims that actually drive the development of PCS.     

美国的医学遗传检测

Genetic tests for about1000health conditions have been developed,of which more than600are currently a-vailable for clinical testing[1].Many genetic tests identify DNAvariants;others measure biochemical markers or an-alyze chromosomes.Most are used for dia…     

General practitioners and the provision of Papanicolaou smear-tests: current practice, knowledge and attitudes

General practitioners are the main providers of Papanicolaou smear-tests yet, given the current suboptimal rates of cervical screening, it is clear that their full potential as screening providers is not being realized. To date, no information has been available concerning the possible barriers to the provision of Papanicolaou smear-tests by general practitioners. The present study assessed the views of a random sample of NSW general practitioners regarding the value of smear-tests, the most appropriate providers, the recommended screening protocol, and factors that were thought to influence both practitioners' provision and women's utilization of screening. The results indicate a number of changes to the current system which could counter screening barriers such as educational programmes for general practitioners, more female providers and the investigation of alternative services, consensus screening guide-lines, and screening registers and recall systems.     

Screening for breast cancer: the role of mammography.

The early diagnosis of breast cancer by screening is a relatively new development in medical practice and its enthusiastic acceptance needs to be tempered by an appraisal of the costs, the risks and the potential benefits. No case can be made at present for screening well women under the age of 50 years, when such screening includes mammography. With the exception of women who have already had cancer in one breast, it is likely that those women under 50 with the associated "risk factors" are better managed by careful attention to breast self-examination and more frequent physical examinations. Provided that the radiation dose is less than one rad per examination, the benefits to women over 50 outweigh the risks of radiation-induced breast cancer. Against this must be placed the very large cost to the community of screening programmes and the relatively low additional benefits gained by incorporation of mammography into the screening process.     

History of medical screening: from concepts to action

The objective of medical screening is to identify disease in its preclinical, and therefore hopefully still curable, phase. This may have been an old quest in medicine but it became historically possible when at least four conditions were met: the availability of simple, valid and acceptable forms of tests, the discovery of effective treatments, the establishment of a theory of screening, and the wide access to health care. Five selected examples that illustrate the history of medical screening are reviewed: screening for psychiatric disorders in the United States army as it is one of the oldest screening programmes; screening for syphilis as it used one of the earliest screening tests; screening for diabetes as one of the first modern forms of mass screening; screening for cervical cancer using the Pap test as one of the greatest successes of screening; and screening for breast cancer by mammography as this offers a good opportunity to discuss the development of modern evaluation of screening programmes. The evaluation of the impact of screening on human health slowly progressed, from obvious changes in the vital statistics such as the decline in incidence of syphilis, to less obvious changes such as the decline in mortality of cancer of the uterus, to finally more subtle changes, such as the impact of mammographic screening on breast cancer mortality. Methods of evaluation had therefore to adapt, evolving from simple surveys to case-control studies and randomised trials. The history of screening is short, but very rich and mostly still to be written.     

Screening for hearing loss in childhood: a study of national practice

A questionnaire survey of all health districts in England and Wales was carried out at the end of 1984 to document screening programmes for identifying hearing loss in childhood. The response rate was 81.3%. All districts performed distraction testing, all but nine aiming at doing so at 7-9 months of age. All districts tested children's hearing at school, generally before 7 years of age. The number of times that children were screened both before school and at school varied considerably, from one to six times before school and one to six times at school. Few districts collected information that would allow them to make judgments about the efficiency of effectiveness of their screening programmes.     

宫颈病变筛查策略的效果分析

宫颈癌是妇科常见的恶性肿瘤之一,其发病率逐年升高,且发病年龄有年轻化的趋势。对宫颈癌的筛查是预防和控制宫颈癌的主要手段,也是极大限度防治宫颈癌的最好途径。宫颈癌筛查方法包括肉眼观察、宫颈细胞学、人类乳头瘤病毒检测及阴道镜检查等。世界各地学者做了许多努力来寻求适宜的宫颈癌筛查方案,包括各种方法的单独及联合使用。现就近年来国内外宫颈病变筛查策略的效果予以综述。     

新生儿遗传病基因筛查技术及相关疾病

新生儿遗传病筛查目前以代谢物生化指标检测为主,检测结果假阳性率较高,且有一定的假阴性,筛查的病种较少。近几年逐步开展的新生儿遗传病筛查基因检测技术包括定量聚合酶链反应技术和高通量测序。高通量测序又分为基因包测序、全外显子组测序和全基因组测序。但目前用于新生儿遗传病筛查的基因技术主要为定量聚合酶链反应技术和基因包测序。新生儿基因筛查病种由单病种筛查如耳聋、脊髓性肌萎缩及重症联合免疫缺陷病等向多病种筛查发展。新生儿基因筛查结果解读除遵循美国医学遗传学与基因组学学会联合分子病理协会在2015年提出的“序列变异解读标准和指南”外,还需要结合生化指标检测及其他检测结果综合分析。新生儿遗传病基因筛查的开展需要遵循伦理原则,包括将新生儿基因筛查作为公共卫生项目的伦理、新生儿及其家庭成员知情选择权和隐私权伦理等。新生儿遗传病基因筛查的开展将使更多的遗传病患者能够早期诊断,改善其预后,在新生儿遗传病筛查领域具有里程碑意义。     

Newborn Screening Healthcare Information System Based on Service-Oriented Architecture

In this paper, we established a newborn screening system under the HL7/Web Services frameworks. We rebuilt the NTUH Newborn Screening Laboratory’s original standalone architecture, having various heterogeneous systems operating individually, and restructured it into a Service-Oriented Architecture (SOA), distributed platform for further integrity and enhancements of sample collections, testing, diagnoses, evaluations, treatments or follow-up services, screening database management, as well as collaboration, communication among hospitals; decision supports and improving screening accuracy over the Taiwan neonatal systems are also addressed. In addition, the new system not only integrates the newborn screening procedures among phlebotomy clinics, referral hospitals, as well as the newborn screening center in Taiwan, but also introduces new models of screening procedures for the associated, medical practitioners. Furthermore, it reduces the burden of manual operations, especially the reporting services, those were heavily dependent upon previously. The new system can accelerate the whole procedures effectively and efficiently. It improves the accuracy and the reliability of the screening by ensuring the quality control during the processing as well.     

Public health explores expanding newborn screening for cystic fibrosis, congenital adrenal hyperplasia, and medium-chain acyl coenzyme A dehydrogenase deficiency (MCAD)

Advances in technology provide new challenges to public health to implement screening programs that are effective, cost-efficient, and available to all infants regardless of ability to pay. The Newborn Metabolic Disorder Screening Program (NMDSP) of the Oklahoma State Department of Health is evaluating the expansion of newborn screening for the disorders of cystic fibrosis, congenital adrenal hyperplasia, and medium-chain acyl coenzyme A dehydrogenase deficiency (MCAD) to the current screening battery of disorders (phenylketonuria, congenital hypothyroidism, galactosemia, and sickle cell disease). The challenge is to offer these new screening tests in a cost-efficient manner that ensures all newborns have access to screening and that an infrastructure exists to diagnose and provide the specialized comprehensive care affected infants will require to reduce the morbidity, mortality, and disability associated with these disorders. Essential components of an effective newborn screening system include the smooth integration of sample collection, laboratory testing, follow-up, diagnosis, timely treatment, and tracking components. The NMDSP has recommended that screening should be expanded, but issues of cost and the establishment of a sustainable infrastructure of comprehensive medical services must be addressed.     

微阵列基因芯片在新生儿遗传性耳聋筛查中的应用研究

背景　新生儿听力筛查在世界范围内广泛开展,在早期发现、诊断和干预方面发挥了重要作用。2012年1月北京市启动了新生儿听力和基因筛查同步工作,同时进行新生儿听力和基因筛查,将发挥重要作用。目的　应用微阵列基因芯片对新生儿进行遗传性耳聋筛查,评估新生儿中4个常见遗传性耳聋基因突变的频率、突变类型以及其与遗传性耳聋的相关性,为推广新生儿遗传性耳聋基因筛查提供临床研究证据。方法　选取2017年度北京大学第三医院妇产科生殖医学中心检测的17 824例新生儿,采集出生3 d后的足跟血,使用微阵列基因芯片进行4个常见遗传性耳聋基因9个突变位点的筛查,对阳性结果进行测序验证。结果　新生儿遗传性耳聋基因筛查17 824例,检出阳性890例,阳性率为4.99%。其中GJB2基因杂合突变型501例（2.81%）,SLC26A4基因杂合突变型290例（1.63%）,SLC26A4基因纯合突变型1例（0.01%）,线粒体DNA 12S rRNA突变型41例（0.23%）,GJB3基因杂合突变型41例（0.23%）,双杂合突变型16例（0.09%）。结论　新生儿常见遗传性耳聋基因突变以GJB2基因突变、SLC26A4基因突变为主,微阵列基因芯片可以及早有效地检出先天性耳聋、迟发性耳聋及药物性耳聋基因的携带情况。微阵列基因芯片筛查,快速、高效,对遗传性耳聋的早期诊断、早期干预及遗传咨询具有重要意义,提倡推广新生儿听力筛查联合基因筛查。     

Newborn screening for cystic fibrosis in Victoria: 10 years' experience (1989-1998)

OBJECTIVE: To review the effectiveness of statewide newborn screening for cystic fibrosis (CF) in Victoria over the first 10 years of the program (1989-1998). DESIGN: Population study involving screening of newborns by immunoreactive trypsinogen (IRT) testing on Day 3-5, followed by either repeat IRT testing (1989-1990) or delta F508 mutation analysis (1991-1998). PATIENTS AND SETTING: All babies screened for CF in a newborn screening program in Victoria in 1989-1998. MAIN OUTCOME MEASURE: The diagnosis of CF. RESULTS: Of 635,157 babies born in Victoria in the 10 years, 191 were diagnosed with CF. A further 30 cases were detected antenatally, giving an incidence of 1/2874 (95% CI, 1/2519-1/3294). CF was detected early in 182 babies (95.3% of affected babies in the screened cohort)--136 by screening, 35 because they had meconium ileus, and 11 because they were siblings of older children with CF. Nine cases of CF were missed by screening. Of these nine babies, four did not have an elevated neonatal IRT level, one had a normal IRT level at repeat testing at 4-6 weeks (1989-1990), three did not have a delta F508 mutation (1991-1998), and one had a false negative sweat test result. Six of the nine missed babies (67%) were diagnosed within four months of birth. CONCLUSION: Newborn screening for CF in Victoria has proven effective in detecting most babies with CF in the newborn period. However, a sweat test should be requested when the clinical features suggest the diagnosis of CF, even if the child has been screened.     

A Newborn Screening System Based on Service-Oriented Architecture Embedded Support Vector Machine

The clinical symptoms of metabolic disorders are rarely apparent during the neonatal period, and if they are not treated earlier, irreversible damages, such as mental retardation or even death, may occur. Therefore, the practice of newborn screening is essential to prevent permanent disabilities in newborns. In the paper, we design, implement a newborn screening system using Support Vector Machine (SVM) classifications. By evaluating metabolic substances data collected from tandem mass spectrometry (MS/MS), we can interpret and determine whether a newborn has a metabolic disorder. In addition, National Taiwan University Hospital Information System (NTUHIS) has been developed and implemented to integrate heterogeneous platforms, protocols, databases as well as applications. To expedite adapting the diversities, we deploy Service-Oriented Architecture (SOA) concepts to the newborn screening system based on web services. The system can be embedded seamlessly into NTUHIS.