The complex promise of newborn screening.

Newborn screening has been practised as a form of preventive medicine since the 1960s, and has attracted increased attention in recent years as technological capacities expand. Like other emerging economies, India faces pressure to expand infant screening, though developments have been halting. The promise of newborn screening is the reduction of infant mortality and morbidity from a host of rare, typically genetic, disorders. Deciding what priority should be placed on the realisation of this promise, together with the practical challenge of coordinating the screening enterprise, requires the use of decision making frameworks that address both clinical criteria and values conflicts. Frameworks for public health ethics can aid sound policy development in India, and help to inform the larger international debate about the expansion and benefits of NBS.

Análise da implantação de programa de triagem auditiva neonatal em um hospital universitário / Newborn hearing screening program implantation analysis at a university hospital

A perda auditiva é mais prevalente que outros distúrbios já rastreados ao nascimento. Esforços têm sido feitos para identificação e tratamento precoces de perdas auditivas por meio de programas de triagem auditiva neonatal. OBJETIVO: Estudo prospectivo com objetivo caracterizar o processo de implantação do Programa de Triagem Auditiva Neonatal (PTAN) num Hospital Universitário. Analisar a investigação diagnóstica de perda auditiva em recém-nascidos. Apresentar propostas para aprimoramento do PTAN. MATERIAIS E MÉTODOS: Foram estudados recém-nascidos (RNs) submetidos à TAN por emissões otoacústicas transientes (EOAT), reflexo cócleo-palpebral (RCP) e Potencial Evocado Auditivo de Tronco Encefálico (PEATE). RESULTADOS: Foram testadas 625 crianças. Na primeira etapa passaram 458 RNs e falharam 155. Retornaram na segunda etapa 122 RNs, sendo que 8 o fizeram por apresentar fator de alto risco para PA. Encaminhados para investigação diagnóstica 12 RNs (1,9 por cento). Dos 5 que retornaram para PEATE, observou-se PA em dois RNs. CONCLUSÃO: O programa testou 81,7 por cento dos candidatos. O índice de adesão ao programa foi 68,2 por cento. Na primeira etapa falharam 26,7 por cento dos RNs. A implantação do programa está em andamento e necessita constantemente de análise das dificuldades, visando solucioná-las a fim de tornar a Triagem Auditiva Neonatal Universal uma realidade.

Hearing loss is more prevalent than other disorders found at birth. Efforts have been put up towards the early identification and treatment of hearing loss by means of neonatal hearing screening programs. AIM: prospective study with the goal of characterizing the process of implementing a Neonatal Auditory Screening Program (NASP) at a University Hospital. To analyze hearing loss diagnostic investigations in newborns, and to present proposals for NASP improvement. MATERIALS AND METHODS: we studied newborns (NB) submitted to Newborn Auditory Screening (NAS) by transient evoked otoacoustic emissions (TEOE), cochlear-eyelid reflex (CER) and Brainstem Evoked Auditory Potential (BEAP). RESULTS: we tested 625 children. In the first stage, 458 NBs passed and 155 failed. 122 NBs returned to the second stage, and 8 underwent it because they were positive for HL risk factors. 12 NBs (1.9 percent) were referred for diagnostic investigation. Of the 5 who returned for the BAEP, we observed HL in two NBs. CONCLUSIONS: the program tested 81.7 percent of the candidates. The program compliance rate was of 68.2 percent. In the first stage, 26.7 percent of the NBs failed. The program is being implemented and requires constant analyzes of its difficulties, aiming at solving them in order to turn the Universal Newborn Auditory Screening into reality.

Universal hearing screening.

OBJECTIVE: To determine the weighted incidence of hearing impairment in a standardized population of at risk and not at risk neonates seeking care at a tertiary level hospital in India. METHODS: A prospective study of a nonrandomized cohort of 1769 neonates (1490: Not at risk; 279: At risk) from a total of 8192 neonates (6509: Not at risk; 1683: At risk) who sought care at St John's medical College hospital from 1st September 2002 to 31st March 2006 were screened for hearing impairment using transient evoked otoacoustic emissions. Weighting was performed using the expected value of 10 % at risk and 90 % not at risk infants in a typical tertiary care level center in India derived from the National Neonatology and Perinatology database 2002-2003. Z test and 95 % confidence interval was used to determine the external validity of the results. P less than 0.05 was considered as statistically significant. The power of the study is 90 %. RESULTS: The incidence of hearing impairment in infants screened was 10 per 1769 infants screened (1490: Not at risk; 279: At risk) which is 5.65 per 1000 screened. 279 at risk infants were screened and 3 were detected to have hearing impairment which is an incidence of approximately 10.75 per 1000 screened. Of the 1490 not at risk infants screened 7 had hearing impairment that is 4.70 per 1000 screened. If this was extrapolated to a standardized population consisting of 10 % at risk and 90 % not at risk then the incidence would be 5.60 per 1000 screened with a 95 % confidence interval of 4.13-7.06. This narrow 95 % confidence interval with a p equal to 0.001 indicates that this value may be close to the caseload in a typical tertiary care center. CONCLUSION: In this study the incidence of hearing impairment is 3 per 279 in at risk infants screened and 7 per 1490 in not at risk infants screened. The weighted incidence in a standardized population of neonates seeking care at tertiary level center in India is 5.60 per 1000 as per this study. This high incidence calls for all pediatricians to consider incorporating a basic hearing screen for all the neonates using cost effective and appropriate technology. Initial screening may be performed using behavioral observation techniques and confirmation by otoacoustic emissions.

Newborn screening: experience of Bangladesh.

Newborn screening for early diagnosis of many preventable diseases is already an established program in developed countries as well as in some countries in Asia. With the control of infectious and communicable diseases, the Bangladesh government is now giving more attention to the preventive aspect of health. The country is now preparing to adopt newborn screening as part of the preventive aspect of health. Among the various activities are laboratory set up, expert visits, pilot studies on CH and training of personnel. A national project to screen newborns for congenital hypothyroidism is now under active consideration. A universal newborn screening program is a highly ambitious project for a country like Bangladesh. Funds to run such a program will be the main problem. The social pattern where still more than 80% of deliveries are done at home is another constraint. However, the enthusiasm of the professionals as well as of the government is a very encouraging thing. Now it needs the support of the international communities.

Storage and use of residual dried blood spots.

Newborn screening policy for Australia and New Zealand is developed by a committee of the Human Genetics Society of Australasia and the Royal Australasian College of Physicians Division of Pediatrics. Each program policy varies according to the local laws and customs. The residual dried blood spot policy recommends that each screening program develop its own policy taking into account the ownership of the material and the time of retention. Cards and associated records should be stored securely with regard to privacy issues. All uses of residual materials and access to stored material should be documented. Programs should state what permission and documentation is required for the use of samples in 1) investigation of cases missed by the screening program, 2) screening program development, method development and establishing normal ranges for new and existing tests, 3) requests from families for the return of samples, 4) requests from health professionals to use residual material for other health-related purposes, 5) research studies, and 6) coronial and forensic purposes. Storage of the samples must be appropriate to intended future uses and appropriate quality assurance material stored with the samples. Relevant privacy, legal and ethical issues should be considered when formulating storage and use policies. Use of dried blood spot samples for purposes other than newborn screening should also be covered.

Long term follow-up of patients with inborn errors of metabolism detected by the newborn screening program in Japan.

A newborn mass-screening program for the early detection of phenylketonuria, maple syrup urine disease, homocystinuria, galactosemia, congenital hypothyroidism, congenital adrenal hyperplasia, using filter paper blood specimens, was started throughout Japan in 1977. The total number of newborns screened by March 2000 reached 29,657,738; this represents 95% of the newborns during this period. A collaborative study group has performed a follow-up study of the cases detected by this program since the start of this screening program. The results we have obtained through this study to date include: hyperphenylalaninemia, 1:70,000; congenital hypothyroidism, 1:5,000; and, congenital adrenal hyperplasia, 1:20,000. The cases of maple syrup urine disease, homocystinuria, and galactosemia type 1 were too few for a reliable incidence. Accumulated data for PKU show that IQ is inversely related to blood phenylalanine level and stricter dietary control guidelines have resulted. We now have a number of adolescents with PKU and long-term follow-up data are being obtained.

Performance evaluation for screening laboratories of the Asia-Pacific region.

The Centers for Disease Control and Prevention (CDC) has a long history of involvement in quality assurance (QA) activities for support of newborn screening laboratories. Since 1978, CDC's Newborn Screening Quality Assurance Program (NSQAP), has distributed dried-blood spot (DBS) materials for external QA and has maintained related projects to serve newborn screening laboratories. The first DBS materials were distributed for congenital hypothyroidism screening in 1978 and by 2001, NSQAP had expanded to over 30 disorders and performance monitoring for all filter paper production lots from approved commercial sources. In 2001, there were 250 active NSQAP participants, 167 laboratories from 45 countries and 83 laboratories in the United States. Of these laboratories, 31 are from the Asia Pacific Region representing nine countries primarily for two disorders. In 1999, US laboratories had more errors for Performance Evaluation (PE) specimens than other laboratories; but in 2000, US laboratories had fewer errors. International laboratories reported 0.3% false-negative PE clinical assessments for congenital hypothyroidism and 0.5% for phenylketonuria (0.5%) in 2000. Paperless PE data-reporting operation using an Internet website has recently been implemented.

International developments in newborn screening quality assurance.

The five dimensions of quality are Accessibility, Acceptability, Effectiveness, Efficiency and Safety. A newborn screening program consists of a number of interlinked parts, not usually managed by the same individual, and the quality of the program is dependent on the quality of program planning, specimen collection, laboratory testing and follow up, diagnosis and treatment. Outcome assessment and feedback into program planning complete the loop. Use of the quality parameters can quantify ongoing improvements to our screening programs.

Newborn screening in the Philippines.

The Newborn Screening Study Group first introduced newborn screening in the Philippines in 1996. This group of pediatricians and obstetricians from 24 hospitals in the metropolitan Manila area developed a newborn screening program: (1) to establish the incidence of six metabolic conditions--congenital hypothyroidism, congenital adrenal hyperplasia, galactosemia, phenylketonuria, homocystinuria and glucose-6-phosphate dehydrogenase deficiency, and (2) to make recommendations for the adoption of newborn screening nationwide. Newborn screening developed in three phases: (1) routine screening for 5 disorders excluding G6PD deficiency in the 24 member hospitals in Metro Manila, (2) addition of screening for G6PD deficiency to the 5-disorder screening panel, and (3) program evaluation with subsequent reduction in the time of sample collection to 24 hrs of age or older (from the initial requirement of 48 hrs. or older) and discontinuation of screening for homocystinuria as a cost cutting measure (due to non-detection of cases). Data from 201 participating hospitals reported in September 2001 confirmed 48 cases of congenital hypothyroidism, 21 cases of congenital adrenal hyperplasia, 2 cases of galactosemia, 4 cases of hyperphenylalanemia and 1,495 cases of glucose-6-phosphate dehydrogenase deficiency. The Department of Health has recognized the significance of the initial data and efforts are now being undertaken to ensure the nationwide implementation of newborn screening.

Development of a newborn screening laboratory quality assurance system in Shandong, China.

Shandong is a large province in northeastern China with a population of over 80 million. There are over 800,000 births annually with newborn screening testing currently being performed in 15 laboratories in city maternity and child health care hospitals. Since 1996, the number of newborns screened has steadily increased until the number screened annually now exceeds 600,000 (over 70%). During the period from 1996--2000, there were 97 cases of classical PKU confirmed and 399 cases of congenital hypothyroidism giving incidences of 1:11,644 and 1:2,831 respectively. The large number of newborns screened and the relatively large number of screening laboratories presents a quality control challenge since ideally each newborn should receive identical newborn screening services and the laboratories should be of equal abilities. With assistance from the US Centers for Disease Control (CDC), a provincial laboratory quality control program has been established and provides oversight for a newborn screening system from blood collection through treatment of patients. The goal is to ensure that patients with the disorders of interest can be identified from within the normal newborn population with an acceptable minimum number of false positives while attempting to eliminate false negatives. External proficiency testing materials are provided quarterly by the CDC, repackaged by the Center for Newborn Screening Quality Control of Shandong (CNQCS), and distributed to the testing laboratories. Analytical results are reported within a specified period of time and then compared to CDC reported results. Laboratories unable to analyze the samples correctly are provided technical assistance. Additionally, the CNQCS oversees and provides educational assistance in training phlebotomists and other health workers associated with newborn screening. Brochures, posters, videotapes and parent support groups are also developed as a function of the CNQCS. Ultimately, control materials will be prepared for distribution with linkages to CDC for international comparability.

Information overload--new technologies, can we store the data?

Computerization within newborn screening programs is a developing issue. To date two basic approaches to data storage have been used: (1) a storage system for babies diagnosed with a disorder, (2) a comprehensive system with long-term details for all patient samples, tests performed, test results and interpretations. It usually provides efficient real-time reports for various clinical and quality control requirements and easy access to an inborn errors registry. Within the last decade there have been two new technologies adapted to routine use in newborn screening laboratories: (1) tandem mass spectrometry for selected amino acids and acyl carnitine, and (2) DNA mutational analysis of PCR products. Both technologies present data storage challenges. Both are capable of providing large files of information for a sample. Consideration must be given to how these data are stored, whether all results including a graphical representation or DNA sequence data are kept or whether only final results for specific analytes are stored. Many new analytical technologies can only be incorporated into routine programs as a result of advances in hardware and software allowing better access to, and storage of, data.

Challenges and opportunities in establishing and maintaining newborn screening systems.

Newborn screening began in the early 1960s and during the four decades it has existed, has become a recognized vital public health prevention program. It has evolved conceptually from a laboratory test for a single disorder, phenylketonuria, to a comprehensive 6-part public health system of education, screening, follow-up, diagnosis, management, and evaluation. Newborn screening in different countries has been successful because of the efforts of a single individual or group of individuals interested in improving the health of children. Newborn screening has been shown to successfully detect serious disorders before symptoms appear and to significantly reduce the morbidity and mortality that might result if left undetected and untreated, yet there have been (and continue to be) obstacles to implementing newborn screening programs. The obstacles are the same for developed or developing programs and include: (1) adequate financing, (2) technology implementation, (3) program logistics, (4) cultural sensitivity, (5) education, and (6) political support. All newborn screening programs must exist within the limitations of their local environment in this regard. Each program confronts these barriers in its own way and various examples of overcoming barriers are discussed including linkages to immunization programs, regional planning, program advocacy, and legislation.

Beyond screening: challenges in measuring outcomes.

There are several important messages for pediatricians concerned with what happens to patients after identification through newborn screening. Particularly important in many of the disorders are the developmental aspects of outcome. There are certain basic assumptions that are essential in improving developmental outcome as a result of newborn screening: 1) newborn screening leads to early case identification; 2) early diagnosis and intervention generally enhance developmental outcome; 3) sustained compliance is crucial for better developmental outcome; 4) increased awareness of other factors improves developmental outcome; 5) periodic developmental monitoring ensures quality follow-up. Even though the Philippine Newborn Screening Program is young, there are already experiences in these areas to draw from. Likewise, there are strategies that can be employed to overcome the challenges in a developing country, which can lead to better follow-up, characterized by desirable critical features of availability, accessibility, affordability, accuracy and adequacy.

Data integration and warehousing: coordination between newborn screening and related public health programs.

At birth, patient demographic and health information begin to accumulate in varied databases. There are often multiple sources of the same or similar data. New public health programs are often created without considering data linkages. Recently, newborn hearing screening (NHS) programs and immunization programs have virtually ignored the existence of newborn dried blood spot (DBS) newborn screening databases containing similar demographic data, creating data duplication in their 'new' systems. Some progressive public health departments are developing data warehouses of basic, recurrent patient information, and linking these databases to other health program databases where programs and services can benefit from such linkages. Demographic data warehousing saves time (and money) by eliminating duplicative data entry and reducing the chances of data errors. While newborn screening data are usually the first data available, they should not be the only data source considered for early data linkage or for populating a data warehouse. Birth certificate information should also be considered along with other data sources for infants that may not have received newborn screening or who may have been born outside of the jurisdiction and not have birth certificate information locally available. This newborn screening serial number provides a convenient identification number for use in the DBS program and for linking with other systems. As a minimum, data linkages should exist between newborn dried blood spot screening, newborn hearing screening, immunizations, birth certificates and birth defect registries.

Screening for congenital hypothyroidism in the Islamic Republic of Iran: strategies, obstacles and future perspectives

The operational feasibility of a congenital hypothyroidism [CH] screening programme was assessed. Cord blood spot specimens were collected at seven Teheran hospitals and within the Damavand District health network. Cord thyroid-stimulating hormone [TSH] levels > or = 20 mU/L were recalled and levothyroxine [L-T4] therapy was started immediately after diagnosis of CH. Of 20,107 acceptable specimens, 22 neonates had CH [1:914 births]. The recall rate was 1.3%. Screening coverage was 90% of live births. Of all cord samples, only 0.2% were unacceptable either because of delay in transportation or improper specimen collection. Median ages at the time of diagnosis and starting treatment were 12 and 8 days respectively. Screening for CH is feasible and a national screening programme is a necessity

A nationwide follow-up system is essential for a neonatal screening program.

A long-term follow-up study gives many benefits to patients detected by neonatal screening, their families, and all members who are involved in neonatal screening program. However, the follow-up system is not functioning satisfactorily enough in Japan. A nationwide long-term follow-up system needs to be established immediately to make the neonatal screening system complete in Japan.

Preventive aspects of genetic morbidity: experiences of the Canadian model

Genetic disorders are emerging as a major health problem in industrialized countries, especially with greater control of environmental diseases. Of total admissions to major paediatric hospitals, 50% are due to genetic disorders, and at least 10% of all adult admissions to hospitals involve major genetic contributions. Several programmes aimed at preventing or ameliorating these genetic disorders are being implemented. Identifying people at risk of genetic disease has helped decrease the burden of such diseases on families and society. Early recognition also leads to greater success of treatment and improves outcome and prognosis. In Arab populations, genetic disorders are still not perceived as a major health problem, even though they are widely prevalent. Applying similar programmes of early detection, maternal screening, neonatal screening, carrier testing and susceptibility testing will significantly help reduce the impact of these disorders in our populations

Manual de organizaçäo e normas técnicas para triagem neonatal: programa estadual de triagem neonatal Minas Gerais / Handbook of organization and technical standard for neonatal screening: government programs of neonatal screening state of Minas Gerais

Técnicas de triagem neonatal vêm sendo implantadas nos últimos anos em nosso País, como programas em saúde de responsabilidade pública e de caráter mandatório. O Programa Estadual de Triagem Neonatal em Minas Gerais ocupa, hoje, um importante papel no que se refere ao seu compromisso social, garantindo um atendimento integral e gratuito aos recém-nascidos submetidos ao rastreamento e àqueles cujos exames resultarem alterados. Visando o aprimoramento técnico e organizacional, a ediçäo deste manual se destina principalmente às diversas equipes de saúde que, nos atuais 703 municípios participantes, vêm superando com desenvoltura os problemas inerentes ao nosso período de implantaçäo. Procuramos sintetizar a experiência de três anos, onde mais de meio milhäo de recém-nascidos foram rastreados e, também fornecer alguns conceitos teóricos básicos sobre técnicas de triagem neonatal e sobre as doenças a serem detectadas. Introduzimos algumas modificaçöes importantes em relaçäo à coleta de sangue, alterando o formato do papel-filtro e o seu envelope, tornando mais fácil o preenchimento dos dados e adequando-a às recentes normas internacionais. Alteramos, ainda, valores de referência para as dosagens de TSH e T4, visando tornar mais sensível o rastreamento. Procuramos fornecer elementos para a organizaçäo adequada em nível local. Isto tem se mostrado essencial para se evitar repetiçöes desnecessárias de exames, reconvocaçöes de crianças e desgaste emocional dos familiares. Esperamos que as informaçöes aqui organizadas contribuam para que o Programa em nosso Estado mantenha os fundamentos de sua concepçäo: organizar näo apenas uma estrutura de diagnóstico, mas um sistema ágil e funcional, que atenda os usuários de maneira integral.