Abstracts of Presentations Scheduled for the 10th ISNS-Asia Pacific Regional Meeting, Ulaanbataar, Mongolia, 24–26 August 2017

Abstract

first_page settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessMeeting Report Abstracts of Presentations Scheduled for the 10th ISNS-Asia Pacific Regional Meeting, Ulaanbataar, Mongolia, 24–26 August 2017 by J. Gerard Loeber ISNS Office, Bilthoven, The Netherlands Int. J. Neonatal Screen. 2017, 3(3), 20; https://doi.org/10.3390/ijns3030020 Received: 7 August 2017 / Revised: 13 August 2017 / Accepted: 15 August 2017 / Published: 15 August 2017 Download Download PDF Download PDF with Cover Download XML Download Epub Versions Notes Introduction......................................................................................................................1Invited Presentations......................................................................................................1Oral Presentations...........................................................................................................7Poster Presentations......................................................................................................16 1. IntroductionThe International Society for Neonatal Screening (ISNS) recognises six different geographical regions. Of these six, the Asia-Pacific region is probably the one encompassing countries with the largest mutual economical differences which have led to large discrepancies in the way health care, including neonatal screening, has been developed in each of those countries.ISNS aims to (co-)organise periodical conferences in the region and preferably in a less developed country to stimulate local professionals and policy makers to start or expand the neonatal screening programme. This 2017 conference has as theme “Racing to expand newborn screening in the Asia-Pacific region and Mongolia. 2. Invited Presentations Plenary 1. The Challenges of Adding Disorders to Screening Panels R. Rodney Howell M. D. Miller School of Medicine, University of Miami, Miami, FL, USA Newborn screening began with a single test, for a single condition, phenylketonuria. Such screening became virtually uniform more than 50 years ago in the USA. After this program was in place and quite successful other conditions were added to newborn screening panels which led to widespread variation across the regions, and growing need to establish careful plans for adding conditions to the newborn screening panels. The criteria originally presented by Wilson and Jungner for screening populations are widely used for choosing conditions to be added to newborn screening panels, and are being discussed elsewhere in this symposium.In this presentation, I will discuss the Committee that was established by the United States Congress to generate an evidence-based newborn screening panel. The criteria of Wilson and Jungner were used as background information, but considered in the context of the genomic era. The Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) was charged with reviewing conditions had been screened for in the newborn period and evaluating the data underlying these choices using the best data and science. From this work was developed the Recommended Uniform Screening Panel (RUSP) for all infants in the United States. The ACHDNC web-site (https://www.hrsa.gov/advisorycommittees/mchbadvisory/heritable disorders/) provides detailed information about their deliberations. For many conditions reviewed for inclusion to the RUSP detailed evidence reviews are made publically available for review and very costly to replicate.When a condition is considered for the RUSP, very large pilot studies are recommended, the Newborn Screening Translational Research Network (https://www.nbstrn.org/about) was established to assist with these studies and facilitate the development and assessment of new methods and technologies to improve early identification through newborn screening and other tasks for implementation. The costs of implementing newborn screening programs must always be considered (https://www.marchofdimes.org). Plenary 2. Newborn Screening in Europe J. Gerard Loeber ISNS, Office, 3721CK BILTHOVEN, The Netherlands Over the last 50 years almost all European countries have introduced neonatal screening as an important public health feature. Depending on health care structure, available funds, local politics, input from professional groups and the general public, this introduction has led to different approaches in the way the screening programmes have been set up, financed and governed. To get more information on these differences, in 2010 an online survey, commissioned by the EU, was compiled in which the whole screening programme was covered by a questionnaire. This survey covered the EU member states, (potential) candidate member states and EFTA countries, in total 38 countries. Results showed large variations in the panel of screened conditions, ranging from 0 to more than 30 conditions; specimen collection time after birth; screening methodology; and storage of residual specimens, varying from 1 to 1000 years. In addition, confirmatory diagnostics, treatment, and follow-up showed large discrepancies. In 2011 the project group provided a list of 60 recommendations to the EU Commission, but so far none of them have been taken up.Recently the same colleagues were asked to update their data. Over the last five years, in some, mostly smaller, countries considerable changes have been implemented, mainly concerning the number of ms/ms detectable conditions. In contrast, in other mainly larger, countries very little has changed, if at all. Screening for SCID and CCHD, very much promoted and implemented in the USA is getting attention but so far only in pilot programmes in a few countries. In contrast to the US, in Europe national public health policies are either not at all, or only marginally, influenced by developments in neighbouring countries. It is therefore unlikely that NBS programmes in Europe will converge in the years to come. Plenary 3. Newborn Screening in the Asia Pacific Region Carmencita Padilla MD Newborn Screening Reference Center, National Institutes of Health, MAHPS, University of the Philippines Manila Introduction: The boundaries of the Asia Pacific Region are Mongolia on the North, New Zealand in the South, Pakistan in the West and the region includes all the lands and islands in between until the Americas in the East. Of the 138 million babies born in the world, almost half (67 million) are born in the Asia Pacific Region. Countries in the region vary widely in size, economic development and geography. There are many different languages, cultural sensitivities, and religions, each creating its own challenges in implementing NBS. There are currently more developing programs than developed programs within the region. Despite these challenges, NBS continues to grow throughout the region.Purpose: This session will provide: (1) an overview of the development of newborn screening programs in Asia; (2) recent developments; and (3) continuing challenges on country implementation.Materials and Methods: Country newborn screening programs were reviewed in 2015 to identify developments in both developed and developing countries in terms of absence/presence of a program, screening coverage, conditions included (routine and pilot), challenges and plans.Results: There are 4 groups of countries: (1) some NBS programs within the region have included expanded newborn metabolic screening as a routine panel for all newborns; (2) some NBS programs offer expanded newborn metabolic screening as an option to families at an extra cost; (3) some NBS programs offer only CH plus another disorder; and (4) some have no NBS programs yet.Conclusions: Developed and developing countries have continuing challenges. Developed programs continue to look for new conditions to add to the panel and for some, increasing coverage of expanded newborn screening. The challenges for developing programs range from starting the program, strengthening the infrastructure, increasing conditions in the panel, introducing expanded newborn screening, laboratory QA issues, follow up and management of patients diagnosed by the program. Plenary 4. Newborn Screening Worldwide: Molecular Testing Is Becoming Part of Routine Newborn Screening Bradford L. Therrell U.S. National Newborn Screening and Global Resource Center, Austin, TX, USA Introduction: Newborn bloodspot screening (NBS) includes various tests that can occur within hours of birth and have the potential for preventing severe health problems, including death. NBS has evolved from a simple blood or urine screening test to a more comprehensive and complex screening system capable of detecting over 50 different conditions. Molecular testing using dried blood spot specimens was first demonstrated as a viable 2nd-tier NBS technique for both sickle cell diseases and cystic fibrosis in the 1980s. Since that time, molecular testing has slowly expanded in NBS programs until now it is routine in many screening programs including use as a primary screening method for SCID.Purpose: This presentation: (1) provides a brief overview of NBS activities worldwide; (2) reviews the origins of molecular testing as part of NBS; and (3) assesses molecular testing activities in NBS today.Materials and Methods: A series of reports described NBS activities in 5 regions of the world in 2007. These reports were updated in 2015 [Brad Therrell and John Adams (North America), Carmencita Padilla (Asia-Pacific), Gerard Loeber (Europe), Issam Khneisser and Amal Saadallah, Middle East/North Africa, Gustavo Borrajo (Latin America)]. These reports have been reviewed to assess trends in adding molecular testing.Results: NBS for one or more conditions now covers slightly more than one-third of the world’s newborns. In more developed programs, molecular testing protocols are included either as 2nd-tier (cystic fibrosis and sickle cell diseases) or as primary screening (SCID).Conclusions: Institutionalizing and sustaining NBS presents a formidable challenge, particularly in developing economies. While developing programs struggle to build infrastructure and implement screening for the basic screenable conditions, developed programs are moving forward with molecular testing strategies. Future expansion of NBS will continue to include molecular testing as a screening practice. Plenary 5. Screening, Diagnosis and Managemernt of Endocrine Disorders with Limited Resources Paul Hofman 1,2 1 Endocrinologist, Auckland, New Zealand 2 APPES Congenital hypothyroidism and congenital adrenal hyperplasia (CAH) are endocrine conditions that, if not recognised and treated appropriately, cause irreversible complications or death in early infancy. The case for neonatal screening for congenital hypothyroidism is irrefutable with progressive and permanent developmental delay resulting from delayed diagnosis. Most new born screening programs use TSH as the main or only marker to detect primary hypothyroidism. While there is currently debate as to the lower limit for TSH reporting in developed countries, the role of screening in developing countries is to identify cases that are likely to have clinically important hypothyroidism. Thus using higher reporting levels reduces false positives and ensures resources are focussed on the most severe cases. In situations where there is resource constraint other factors are relevant including the timing of the blood sample (for instance cord or a 2 day heel prick), the population being screened (e.g., whole population, larger cities or specific hospitals), the ability to contact families with potentially affected children and the availability of post natal testing and medications that can modify the later outcomes. These issues are discussed with relationship not only to congenital hypothyroidism but also the severer, salt wasting forms of CAH. With CAH there remains more controversy about the benefits of screening, both in terms of the diagnostic positive predictive value of the tests used (usually 17 hydroxy progesterone assays) and the need for therapy before symptoms occur. However over the past 20 years the majority of developed countries have opted for CAH screening. Paradigms for both CAH and congenital hypothyroidism will be discussed that have been used with varying success in other countries and a range of approaches will be suggested for developing countries. Notably for any program to succeed it must have local medical and nursing advocates as well as a commitment by the government to provide the necessary financial support needed to provide an ongoing program. Plenary 6. Reducing False Positive Results for Endocrine Disorders Toni Torresani Zürich, Switzerland The issue of false positive results in neonatal screening has always been a debated topic. The anxiety of the parents arising from such false positive results, has always been the driving reason for trying to find ways to effectively reduce them. Unfortunately, quite often in these discussions the notion that a neonatal screening test simply indicates that a baby might have a condition, is overlooked. Furthermore, when different programs compare their performances, the different conditions for sample collection, transport and analysis are not taken into consideration. Whether a neonatal screening result can be classified as within or outside limit, is not only dependent from the above-mentioned conditions, but also from several clinical conditions like maturity, time of sample collection, general health condition of the baby and sometimes also from the mother.Taking into account all or some of the above-mentioned conditions when interpreting neonatal screening results, will help in reducing substantially the number of false positives, in almost all tests performed. Particular measures that can be applied to neonatal screening of endocrine diseases, congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH), will be presented and discussed. Plenary 7. A New CLSI Guideline on Hemoglobinopathy Newborn Screening and the Results of Two Decades of Newborn Screening for Sickle Hemoglobinopathies in the United States Bradford L. Therrell U.S. National Newborn Screening and Global Resource Center, Austin, TX, USA Introduction: Hemoglobinopathy newborn screening (NBS) has existed since the 1970s, primarily for detection of sickle cell diseases (SCD) in the U.S. and the thalassemias in other regions of the world, including Asia. There is limited knowledge of the overall prevalence of SCD (SS-disease, SC-disease, S beta-thalassemia) and sickle carriers in the U.S., and thalassemias elsewhere. A source for international guidance for NBS programs does not exist.Purpose: The Clinical Laboratory Standards Institute (CLSI) is finalizing a new international guideline for hemoglobinopathy NBS that outlines laboratory and other system issues with appropriate recommendations for optimal NBS implementation. Additionally, the outcome of two decades of screening data for sickle hemoglobinopathies in the U.S. is now available for review.Materials and Methods: A defined proves for preparing CLSI guidelines was followed. U.S. SCD data were collected from program reports to the national data system from 1990 to 2010.Results: The CLSI Guideline is now in final review. The U.S. 20-years data revealed that there were 39,422 confirmed SCD cases among 76,527,627 newborns screened (1:1,941) and 1,107,875 laboratory reports of probable sickle carriers among 73,951,175 newborns screened (1:67). SCD was most prevalent in the District of Columbia (1:437) followed by Mississippi (1:683) and South Carolina (1:771). Likewise, sickle cell carrier prevalence was highest in the District of Columbia (1:22), Mississippi (1:26) and South Carolina (1:31).Conclusions: An international guideline on NBS hemoglobinopathy screening will be helpful as a resource for harmonizing and improving NBS activities worldwide. The U.S. data will assist in: (1) planning for health services delivery; (2) providing data for researchers; (3) aiding in tracking health outcome trends; and (4) assessing sickle gene prevalence in the newborn population. Plenary 8. Screening and Diagnosis of Metabolic Disorders Veronica Wiley NSW Newborn Screening Programme, SYDNEY, Australia Electrospray ionisation tandem mass spectrometry has been used in NSW since 1998 and has now been incorporated in many newborn screening programs worldwide. There have been many changes in methodology to prospectively screen newborns for inborn errors of amino acids, fatty acid oxidation and organic acidurias. However despite many attempts to harmonise its introduction, it remains the responsibility of each program to determine which disorders are screened, what sample to use, and what is acceptable performance.For each analyte tested there is sample, analytical and interpretative considerations. Sample aspects include the optimal time of collection after birth, the effect of feed status and gestational age. Analytical considerations include the instrumentation, sample preparation, establishing action limits, normal percentiles and expected results for proven positives as well as appropriate quality assurance protocols. To optimise the performance metrics of resample rate, sensitivity, specificity and positive predictive value further testing can be performed on the initial sample and this include ratios of analytes or second tier testing including DNA variant analysis.Sceening is however not diagnostic and further samples need to be requested from those suspected of having a disorder. The samples required depend on the suspected disorder including the urgency required to provide treatment. Samples required for diagnostic testing by biochemical genetics may be urine, plasma, CSF, skin or other biopsy specimens.Using various MSMS protocols since 1998, we have screened samples collected at 48–72 h of age from nearly 2 million babies, request further samples from 0.15%, and detect a disorder in 1:2691 babies with a sensitivity, specificity and positive predictive value which are currently 99%, 99.9% and 25% respectively.The use of tandem mass spectrometry in newborn screening is expanding to include many other disorders. The challenge remains how to optimise protocols for each specific disorder. Plenary 9. Deciding on Disorders for Inclusion in a Newborn Screening Programme J. Gerard Loeber ISNS, Office, 3721CK BILTHOVEN, The Netherlands This topic starts with the assumption that there is an infrastructure for newborn screening in place and that funding is available. The disorder of first choice is congenital hypothyroidism because it is very prevalent, irrespective of ethnicity, the screening and diagnostic methodology is relatively simple and the treatment is relatively cheap. For decision on further disorders the framework of the Wilson and Jungner criteria is very valuable, even after 50 years since its inception. Important considerations are: is the disorder in your jurisdiction an important health problem AND is the test acceptable for the population from cultural/ethical perspective (unintentional findings; carrier status; mild and late-onset forms).If the answer to both questions is affirmative, then the cost of the existing situation (detection by clinical symptoms) should be compared with the cost of screening; this is very much dependent on the prevalence of the disorder. If the cost-benefit ratio is positive then it should be checked if the existing facilities are adequate to also cover this disorder when added to the panel: adequate test method, clinical confirmation, follow-up and treatment, information and education of professionals and general public, informed consent especially when carriers will be detected.Disorders should NOT be added, just because the apparatus is capable of picking it up or because a clinician happens to have one patient in his practice and has become interested in that disorder or because a politician has a family member suffering from it.Reference in Plenary 9. Plenary 10. Strategies in Overcoming Geographic Obstacles Ma Elouisa Reyes Newborn Screening Reference Center, National Institutes of Health University of the Philippines Manila Introduction: The Philippine newborn screening program (NBS) started in 24 hospitals in Metro Manila in 1996. It was integrated in the public health delivery system with the passage of the Newborn Screening Law in 2004. Among the major challenges of the program at the beginning was the 7000+ islands of the country. The Philippines is made up of 3 groups of islands subdivided into 18 political regions and 81 provinces (a mix of rural and urban cities).Purpose: This session will provide: (1) challenges in the implementation of the program (2) strategies to overcoming geographic obstacles. Materials and Methods: Practices through existing IEC materials/Philippine Assessment Tools/Technical Reports since 2005 were reviewed to identify challenges and strategies made to resolve geographic concerns. Results: Among the challenges in implementation were: (1) initially, only the big cities were accessible; most rural areas are either island-based or mountainous, (2) home deliveries making NBS difficult; and (3) schedules of airports and ports initially limited prompt submission to laboratories; and (4) no available courier service in most rural areas. Among the strategies employed were: (1) strategic location of the 6 newborn screening laboratories; (2) engagement of health workers to go to houses for sample collection; (3) strategic location of 14 follow-up and management centers (continuity clinics); (4) coordination with the Department of Health (DOH) offices and the local government units for the hard-to-reach areas for transmission of samples and results, and follow up of positive cases; (5) engagement with the private sector (i.e., courier and transportation companies).Conclusions: The Philippine terrain is a continuing challenge to the program. It lessened through the years as more strategies in the national and local levels are developed and implemented; and a close coordination between NBS laboratories and DOH offices to resolve operations in geographically challenged areas. Plenary 11. Building National Qa Programs In China—Laboratory and Non-Laboratory Aspects Zhengyan Zhao Children’s Hospital of Zhejiang University School of medicine, Department of genetic and metabolism, Hangzhou, China, Peoples Republic The China Newborn Screening Program started in 1981 covering on average 17 million newborns annually. As a public health project, the screening rate has reached 97% in 2016. The newborn screening disorders started from the initial two diseases (CH, PKU) to G6PD and CAH and then expanded to 32 diseases by tandem mass spectrometry. Gradually, related laws and regulations are legislated and improved, quality control management systems are formed, guidelines are released, and affected babies in undeveloped areas are aided. The Chinese newborn screening quality control systems are manipulated in national, province, city and county levels. The NCCL organizes the quality assurance program, including PT, QC, information, quality index, on-site inspection and training summary. In recent years, information management promoted the connection with all related units of newborn screening to ensure the effectiveness of recall and follow-up, and achieve the integrated management of screening, diagnosis and treatment. 3. Oral Presentations O1. Screening for Hemoglobin Disorders: Philippine Experience Carmencita Padilla MD Newborn Screening Reference Center, National Institutes of Health, MAHPS, University of the Philippines Manila, Philippines Introduction: Newborn screening (NBS) in the Philippines began as a small pilot program in Manila in 1996 and became a nationwide program in 2004 by law requiring that NBS be offered to all newborns, supported by national health insurance. As screening for 6 conditions became routine in all hospitals, expansion to additional disorders was the next challenge. Purpose: This session will share the development of NBS for hemoglobin disorders: preparations, algorithms, initial data, and challenges in implementation.Methods and Methods: The Philippine program was fortunate to secure data on 110,000 Filipino newborns in the California Newborn Screening Program. The Philippine Department of Health accepted the data as basis of the expanded newborn screening (eNBS). Workshops with key players (NBS laboratory staff and follow up teams, geneticists, and pediatric hematologists) were conducted by Bradford Therrell of Newborn Screening and Genetics Resource Center, USA; David Millington, metabolic geneticist of Duke University (for metabolic disorders); and Carolyn Hoppe, pediatric hematologist of UCSF Benioff Children’s Hospital Oakland (for hemoglobin disorders). After preparations of the laboratory (screening and confirmatory), short term and long term follow-up teams, the Philippines started eNBS on December 2014. Patients now are given 2 options: Option 1 fully funded by the national health newborn screening—screening for 6 conditions such as congenital hypothyroidism, congenital adrenal hyperplasia, phenylketonuria, galactosemia, maple syrup urine disease and G6PD deficiency; and Option 2 partially funded eNBS for conditions detectable with tandem mass spectrometry, hemoglobinopathies, cystic fibrosis and biotinidase deficiency.Results: NBS results for hemoglobin disorders of the first 300,000 newborns will be presented.Conclusion: New challenges faced by the Philippine program with the inclusion of hemoglobin disorders are: training of teams, development of algorithms for both laboratory and clinical follow up, engagement of hematologists for long term care, and cost of treatment. O2. Pilot Newborn Screening in Nepal Arti Pandey Kathmandu Medical College and Teaching Hospital, Dept. Biochemistry, Kathmandu, Nepal Introduction: While newborn screening (NBS) has been established in many countries, already 50 years ago, there are still countries where no NBS is so far established. We report on the first preliminary results of a pilot NBS program in Nepal.Purpose: The main purpose of this pilot was to show the feasibility of NBS in Nepal, and probably get first positive results.Materials and Methods: The pilot study was established between, Kathmandu Medical College and Teaching Hospital, and the University Children’s Hospital in Zurich, which was approved by the Nepal Health Research Council (NHRC). 5000 dried blood samples (DBS) were collected in Nepal and sent to Zurich, where they were tested according to the Swiss NBS program.Results: Within these 5000 samples 1 child with congenital hypothyroidism, and 1 child with Cystic Fibrosis was detected. Median values and relevant percentiles were comparable to the values from Swiss NBS program for most analytes. However, enzyme activities (GALT and Biotinidase) were significantly lower, most probably due to the time delay and transportation.Conclusion: The pilot program showed the feasibility of NBS in Kathmandu region. Since the total number of samples was rather small, we are planning to extend this pilot to a further 10,000 samples, to gather more data on the more rare inborn errors of metabolism. O3. Pilot Scheme for the Establishment of a Neonatal Screening Program in the Democratic Republic of Laos Thomas Hoehn, Zoltan Lukacs and Saysanasongkham Bounnack University Hospital Duesseldorf, General Pediatrics, Neonatology and Pediatric Cardiology, Duesseldorf, Germany Background: Neonatal screening programs have been established and are in use in many countries worldwide. Countries without any established neonatal screening programs in 2009 included Nepal, Cambodia, Laos, and the Pacific Island nations.Aim: To show the feasibility of neonatal screening in the urban setting of Vientiane, capital of Laos. Furthermore to expand regular screening to other cities within Laos and to offer ongoing teaching to local pediatricians with respect to further follow-up of infants with diagnosed inborn errors of metabolism.Methods: Initial participants were the large maternity hospitals within the city of Vientiane (Mahosot Hospital (2.500 deliveries p.a.), Sethathirath Hospital (2.000 deliveries p.a.), Friendship Hospital (700 deliveries p.a.), and Mother and Child Health Hospital (3.500 deliveries p.a.)). Samples were taken immediately prior to hospital discharge and once weekly air-shipped to a German screening laboratory.Results: 11.362 samples of newborn infants have been examined. The rate of retests was above European average due to very early discharge policies in Laotian maternity hospitals. Confirmed cases of neonatal congenital diseases include two infants with hypothyroidism and one infant with congenital adrenal hyperplasia without salt-loss. All three infant received early therapy and are currently doing well.Conclusions: Even in a very low resource setting as in Laos the establishment of a neonatal screening program appears to be feasible. Further challenges include the expansion to the rest of the country and the on-site establishment of measurements within Laos. O4. 10 Years for the Neonatal Screening on Phenylketonuria in Kazakhstan D.N. Salimbayeva The Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan Background. Phenylketonuria (PKU; OMIM: #261,600) is an inborn error of phenylalanine metabolism. The effective method of the early diagnostics and prophylactics of PKU are a neonatal screening. Since 2007 year the national program of neonatal screening for phenylketonuria wa