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Sample records for newborn screening linkage

  1. Newborn Screening

    PubMed Central

    Pitt, James J

    2010-01-01

    Early detection of many disorders, mainly inherited, is feasible with population-wide analysis of newborn dried blood spot samples. Phenylketonuria was the prototype disorder for newborn screening (NBS) and early dietary treatment has resulted in vastly improved outcomes for this disorder. Testing for primary hypothyroidism and cystic fibrosis (CF) was later added to NBS programs following the development of robust immunoassays and molecular testing. Current CF testing usually relies on a combined immunoreactive trypsin/mutation detection strategy. Multiplex testing for approximately 25 inborn errors of metabolism using tandem mass spectrometry is a relatively recent addition to NBS. The simultaneous introduction of many disorders has caused some re-evaluation of the traditional guidelines for NBS, because very rare disorders or disorders without good treatments can be included with minimal effort. NBS tests for many other disorders have been developed, but these are less uniformly applied or are currently considered developmental. This review focuses on Australasian NBS practices. PMID:20498829

  2. Hearing Loss: Screening Newborns

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table of ... of newborns in the U.S. are screened for hearing loss before they leave the hospital. Research improves the ...

  3. Newborn Screening

    MedlinePlus

    ... Pulse Oximetry Screening for CCHDs Sickle Cell Disease Laboratory SCID Quality Assurance Training and Resources For Lab Professionals Data and Reports Laboratory Reports National Birth Defects Prevention Network (NBDPN) Resources ...

  4. Newborn screening in Indonesia.

    PubMed

    Rustama, Diet S; Fadil, M Ryadi; Harahap, Elly R; Primadi, Aris

    2003-01-01

    In Indonesia, newborn screening is not yet a policy, and the incidence of preventable causes of mental retardation detected by newborn screening is not known. Congenital hypothyroidism (CH) is not infrequent. Without a screening program, unrecognized CH patients were neglected for years. Since May 1999, the International Atomic Energy Agency (IAEA) has assisted in starting a CH Newborn Screening Project to estimate the local incidence of CH and to evaluate the problems associated with the screening. In June 2000, a pilot study was conducted using primary TSH measurement, supplemented by T4 in infants with elevated TSH. The target was to screen 12,000 newborn infants, using cord blood serum taken at birth, or a heel prick between 2 to 6 days of age. Between June 2000 and February 2001, 3,534 neonates born in 4 hospitals were screened using cord blood serum taken at birth (recall rate 3.3%). From March 2001 onwards, the heel prick method was used and participating hospitals increased from 4 to 7. Using this approach, until August 2001, 3,309 samples were analysed and the recall rate was much lower (0.64%). The number of unsatisfactory samples was relatively high due to an unstable process of blood collection. Parental refusal and low acceptance of screening among policy makers resulted from lack of awareness of the dangers of CH, and the screening program was not considered a health priority. Recall of patients after screening was a major barrier, with problems in tracking patients arising from urbanization and a high rate of relocation. To advance the CH screening program nationwide, infrastructure must be improved along with the recall system, and education as well as information campaigns for parents and medical professionals must be intensified. The Department of Health must be persuaded to give a national mandate. PMID:15906701

  5. What's New with Newborn Screening

    ERIC Educational Resources Information Center

    Exceptional Parent, 2008

    2008-01-01

    Newborn screening is the process of testing and screening newborns shortly after birth for certain, potentially dangerous, conditions and/or impairments--conditions that include everything from inborn errors of metabolism and other genetic disorders to hearing impairment. Early detection through newborn screening is paramount, often allowing the…

  6. Screening Newborns' Hearing Now Standard

    MedlinePlus

    ... this page please turn Javascript on. Feature: Taste, Smell, Hearing, Language, Voice, Balance Screening Newborns' Hearing Now ... emailing NIDCDinfo@nidcd.nih.gov . Read More "Taste, Smell, Hearing, Language, Voice, Balance" Articles At Last: A ...

  7. How Are Newborn Screening Tests Done?

    MedlinePlus

    ... Clinical Trials Resources and Publications How are newborn screening tests done? Skip sharing on social media links Share this: Page Content Newborn screening typically consists of a blood test and a ...

  8. MedlinePlus: Newborn Screening

    MedlinePlus

    ... Phenylketonuria National Institutes of Health The primary NIH organization for research on Newborn Screening is the National Institute of Child Health and Human Development Languages Arabic (العربية) Bosnian (Bosanski) Chinese - Simplified (简体中文) ...

  9. Pilot Programs in Newborn Screening

    ERIC Educational Resources Information Center

    Pass, Kenneth; Green, Nancy S.; Lorey, Fred; Sherwin, John; Comeau, Anne Marie

    2006-01-01

    The term "pilot study" has been used over the years to describe the evaluation of the many elements involved in deciding whether a proposed condition should be added to a newborn screening (NBS) panel, and until recently, was unilaterally used to describe the evaluation of the assay to be used before the condition was officially adopted by a state…

  10. Newborn screening tests

    MedlinePlus

    ... at least 26 disorders on an expanded and standardized uniform panel. The most thorough screening panel checks ... diagnose illnesses. They show which babies need more testing to confirm or rule out illnesses. If follow- ...

  11. Newborn Screening for Biliary Atresia

    PubMed Central

    Wang, Kasper S.

    2016-01-01

    Biliary atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of biliary obstruction within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child’s native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has biliary atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for biliary atresia to improve outcomes. Herein, newborn screening for biliary atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for biliary atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of biliary atresia in the United States. PMID:26620065

  12. Newborn Screening: Characteristics of State Programs.

    ERIC Educational Resources Information Center

    Toiv, Helene F.; Austin, Janina; Gardiner, Emily Gamble; Tynan, Ann; Hill, Ariel; Milne, Kevin; Moon, Cindy; Lawes, Susan

    Each year, state newborn screening programs test 4 million newborns for disorders that require early detection and treatment to prevent serious illness or death. The U.S. General Accounting Office (GAO) was asked to provide Congress with information on variations among state newborn screening programs. Based on surveys of such programs in all 50…

  13. Newborn Hearing Screening in 2010

    PubMed Central

    Choo, Daniel; Meinzen-Derr, Jareen

    2010-01-01

    Purpose of Review The objectives of this review are to provide the reader with a current and concise review of the data and trends in universal newborn hearing screening(UNHS). Within a relatively short period of time, the concept of screening all infants for hearing loss at the time of birth has evolved from a nascent process to a truly universal system in most developed countries. As a result, the focus and challenges of UNHS have shifted to topics of developing ever more efficient and cost-effective approaches and potentially melding physiologic hearing screenings with ancillary screening techniques. Recent Findings Enhancement of the UNHS process is likely to be accomplished by implementation of novel tools such as wideband reflectance technologies and intelligent incorporation of screening for common genetic and viral causes of congenital hearing loss. Summary With such a rapidly evolving process, it will be critical for clinicians to understand the benefits and limitations of various newborn hearing screening methodologies in order to determine the most appropriate management of children referred from their UNHS. This will entail a working knowledge of emerging audiologic tools as well as infectious and genetic etiologies of pediatric hearing loss. PMID:20808221

  14. Newborn Screening for Fragile X Syndrome

    ERIC Educational Resources Information Center

    Bailey, Donald B., Jr.

    2004-01-01

    Newborn screening for fragile X syndrome (FXS) is technically possible, and in the relatively near future accurate and inexpensive screening technologies are likely to be available. When that happens, will America's public health system adopt newborn screening for fragile X syndrome? This article addresses this issue by first placing screening for…

  15. Cystic Fibrosis Diagnosis and Newborn Screening.

    PubMed

    Rosenfeld, Margaret; Sontag, Marci K; Ren, Clement L

    2016-08-01

    The diagnosis of cystic fibrosis (CF) has evolved over the past decade as newborn screening has become universal in the United States and elsewhere. The heterogeneity of phenotypes associated with CF transmembrane conductance regulator (CFTR) dysfunction and mutations in the CFTR gene has become clearer, ranging from classic pancreatic-insufficient CF to manifestations in only 1 organ system to indeterminate diagnoses identified by newborn screening. The tools available for diagnosis have also expanded. This article reviews the newest diagnostic criteria for CF, newborn screening, prenatal screening and diagnosis, and indeterminate diagnoses in newborn-screened infants and symptomatic adults. PMID:27469178

  16. National Newborn Screening and Genetics Resource Center

    MedlinePlus

    ... GENERAL INFORMATION Conditions Screened by US Programs General Resources Genetics Birth Defects Hearing Screening FOR PROFESSIONALS ACT Sheets(ACMG) General Resources Newborn Screening Genetics Birth Defects FOR FAMILIES FAQs ...

  17. Update: newborn screening for endocrinopathies.

    PubMed

    Pass, Kenneth A; Neto, Eurico Carmago

    2009-12-01

    Congenital hypothyroidism and congenital adrenal hyperplasia are included in many newborn screening (NBS) panels worldwide and in all state-sponsored programs in the United States. Both conditions meet the fundamental prerequisites for NBS: high incidence in the population; biomarkers in the dried blood specimen that are easily detected; and, effective therapies to lessen, if not prevent, the sequelae of late or no treatment. In this review, the history of NBS is discussed for these 2 conditions. The technologies and protocols used in their detection, and related subjects such as genetics, and treatment and outcomes, are also discussed. PMID:19944295

  18. Newborn screening for congenital hypothyroidism.

    PubMed

    Büyükgebiz, Atilla

    2006-11-01

    Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets. PMID:17220056

  19. Newborn Screening (NBS): Answers to Frequently Asked Questions

    MedlinePlus

    ... FREE ADDITONAL NEWBORN SCREENING PACKETS What is Newborn Screening (NBS)? NBS is a system that helps tell ... the condition. What are the benefits of Newborn Screening? Early detection of disorders and conditions detectable through ...

  20. Newborn screening for lysosomal storage disorders.

    PubMed

    Matern, Dietrich; Gavrilov, Dimitar; Oglesbee, Devin; Raymond, Kimiyo; Rinaldo, Piero; Tortorelli, Silvia

    2015-04-01

    Every newborn in the U.S. is screened for at least 29 disorders, where evidence suggests that early detection is possible and beneficial. With new or improved treatment options and development of high-throughput screening tests, additional conditions have been proposed for inclusion in newborn screening programs. Among those are several lysosomal storage disorders that have been evaluated in limited pilot studies or that are already included in a few national or international newborn screening programs. These conditions include Pompe disease, Niemann-Pick type A/B disease, Fabry disease, Krabbe disease, Mucopolysaccharidoses types I and II, and Gaucher disease. Here, we review the current state of newborn screening for these lysosomal storage disorders. PMID:25891428

  1. The Clinical Aspects of Newborn Screening: Importance of Newborn Screening Follow-Up

    ERIC Educational Resources Information Center

    James, Philip M.; Levy, Harvey L.

    2006-01-01

    The aim of newborn screening is to identify presymptomatic healthy infants that will develop significant metabolic or endocrine derangements if left undiagnosed and untreated. The goal of ultimately reducing or eliminating irreversible sequelae is reached by maximizing test sensitivity of the primary newborn screening that measures specific…

  2. NICHD research initiative in newborn screening.

    PubMed

    Alexander, Duane; Hanson, James W

    2006-01-01

    Recent changes in genetics research have created new opportunities to improve the scope and quality of newborn screening services. Changes in newborn screening should be supported and directed by an organized program of research. The NICHD Research Initiative in Newborn Screening includes the development of systematic methods to identify additional conditions appropriate for newborn screening; development and testing innovative interventions and treatments to improve outcomes; education of the provider workforce; development and implementation of appropriate information and communication systems for parents and providers; and, sponsoring an ongoing program of research and research training. Future needs will include the development of a national translational research infrastructure, prevention research and research into behavioral and social sciences issues. The NICHD Research Initiative in Newborn Screening is expected to be an ongoing and vital initiative that adapts itself to new scientific findings, technological developments, changes in the public and personal health care system, and our evolving understanding of the needs of affected individuals, families and the community. PMID:17183575

  3. Newborn screening education on the internet: a content analysis of North American newborn screening program websites.

    PubMed

    Araia, Makda H; Potter, Beth K

    2011-09-01

    The Internet is a potentially important medium for communication about public health programs including newborn screening. This study explores whether the information available on official newborn screening program websites is consistent with existing guidelines regarding educational content for parents. We conducted a systematic search of the public websites of newborn screening programs in the US and Canada, identifying web pages and downloadable brochures that contained educational information. Two researchers independently reviewed all documents to determine the extent to which they included 14 key recommended educational messages. We identified 85 documents containing educational information on 46 US and 6 Canadian newborn screening program websites. The documents contained from 1 to 14 of the recommended messages. The majority of identified materials emphasized the importance and benefits of screening. The differences between US and Canadian materials were related to the importance of parental involvement in follow-up and issues of consent and storage of blood spots. Our findings are consistent with studies of non-web-based newborn screening education materials. The results emphasize the need for further evaluation of newborn screening education, including internet-based resources, particularly in terms of the impact of particular messages on parental attitudes and behaviors. PMID:22109819

  4. National Evaluation of US Newborn Screening System Components

    ERIC Educational Resources Information Center

    Therrell, Bradford L.; Hannon, W. Harry

    2006-01-01

    Newborn screening has existed as a state-based public health service since the early 1960s. Every state and most territorial jurisdictions have comprehensive newborn screening programs in place, but in the United States a national newborn screening policy does not exist. This results in different administrative infrastructures, screening…

  5. Newborn screening for lysosomal storage disorders.

    PubMed

    Nakamura, Kimitoshi; Hattori, Kiyoko; Endo, Fumio

    2011-02-15

    Lysosomes are intracellular organelles containing acid hydrolases that degrade biological macromolecules. Lysosomal storage disorders (LSDs) are caused by absent activity of one or more of these enzymes due to mutations of genes encoding lysosomal hydrolases or enzymes that process, target, and transport these enzymes. The specific signs and symptoms of each LSD derive from the type of material accumulated within the lysosome, the site (organ) of accumulation and the response of the body (sometimes in the form of an inflammatory or immune response) to the accumulated material. Interest for inclusion of these disorders in newborn screening programs derives from the availability of effective therapy in the form of enzyme replacement or substrate reduction therapy and bone marrow transplant that may improve long-term outcome especially if started prior to irreversible organ damage. Based on the availability of therapy and suitable screening methods, Gaucher disease, Fabry disease, Pompe disease, mucopolysaccharidosis I and II, Niemann-Pick disease, and Krabbe disease are candidates for newborn screening. Pilot newborn screening projects have been performed for some of these conditions that indicate the feasibility of this approach. This review will provide insight into these screening strategies and discuss their advantages and limitations. © 2011 Wiley-Liss, Inc. PMID:21312327

  6. Newborn Screening for Lysosomal Storage Disorders and Other Neuronopathic Conditions

    ERIC Educational Resources Information Center

    Matern, Dietrich; Oglesbee, Devin; Tortorelli, Silvia

    2013-01-01

    Newborn screening (NBS) is a public health program aimed at identifying treatable conditions in presymptomatic newborns to avoid premature mortality, morbidity, and disabilities. Currently, every newborn in the Unites States is screened for at least 29 conditions where evidence suggests that early detection is possible and beneficial. With new or…

  7. Newborn Screening To Prevent Mental Retardation. The Arc Q & A.

    ERIC Educational Resources Information Center

    Arc, Arlington, TX.

    This information fact sheet on screening newborns to prevent mental retardation defines newborn screening and outlines how screening is performed. It discusses the six most common disorders resulting in mental retardation for which states most commonly screen. These include phenylketonuria, congenital hypothyroidism, galactosemia, maple syrup…

  8. Newborn screening for lysosomal storage disorders.

    PubMed

    Meikle, Peter J; Grasby, Dallas J; Dean, Caroline J; Lang, Debbie L; Bockmann, Michelle; Whittle, Alison M; Fietz, Michael J; Simonsen, Henrik; Fuller, Maria; Brooks, Douglas A; Hopwood, John J

    2006-08-01

    Lysosomal storage disorders (LSD) are chronic progressive diseases that have a devastating impact on the patient and family. Most patients are clinically normal at birth but develop symptoms early in childhood. Despite no curative treatment, a number of therapeutic options are available to improve quality of life. To achieve this, there is a pressing need for newborn screening to identify affected individuals early, before the onset of severe irreversible pathology. We have developed a multiplexed immune-quantification assay of 11 different lysosomal proteins for the identification of individuals with an LSD and evaluated this assay in a retrospective study using blood-spots from; newborns subsequently diagnosed with an LSD (n=19, six different LSD), individuals sampled after diagnosis of an LSD (n=92, 11 different LSD), newborn controls (n=433), and adult controls (n=200). All patients with mucopolysaccharidosis type I (MPS I), MPS II, MPS IIIA, MPS VI, metachromatic leukodystrophy, Niemann-Pick disease type A/B, and multiple sulfatase deficiency could be identified by reduced enzyme levels compared to controls. All mucolipidosis type II/III patients were identified by the elevation of several lysosomal enzymes, above the control range. Most Fabry, Pompe, and Gaucher disease patients were identified from either single protein differences or profiles of multiple protein markers. Newborn screening for multiple LSD is achievable using multiplexed immune-quantification of a panel of lysosomal proteins. With further validation, this method could be readily incorporated into existing screening laboratories and will have a substantial impact on patient management and counseling of families. PMID:16600651

  9. Newborn screening for neuropathic lysosomal storage disorders.

    PubMed

    Hwu, Wuh-Liang; Chien, Yin-Hsiu; Lee, Ni-Chung

    2010-08-01

    Interest in newborn screening (NBS) for lysosomal storage disorders (LSDs) has increased significantly due to newly developed enzyme replacement therapy (ERT), the need for early diagnosis, and advances in technical developments. Since the central nervous system cannot be treated by ERT, neuronopathic LSDs are generally not the primary target of NBS. An exception is Krabbe disease, in which hematopoietic stem cell transplantation before the onset of symptoms has benefits. However, NBS for LSD relies on measuring enzyme activities, so the most severely affected individuals (usually patients with neuronopathic subtypes) will be detected together with patients with less severe disease. In the near future, NBS is likely to be developed for diseases such as Gaucher, Niemann-Pick A/B, and certain mucopolysaccharidoses. The ability to predict phenotypes (neuronopathic or not) by enzyme activity and genotyping will therefore be critical for adequate patient management. This article reviews the status of LSD screening and issues concerning detection of neuronopathic LSDs by screening. PMID:20532820

  10. Cystic fibrosis: newborn screening in America.

    PubMed

    Kleven, Daniel T; McCudden, Christopher R; Willis, Monte S

    2008-07-01

    Cystic fibrosis is the most common lethal genetic disease in Caucasians, manifesting as progressive lung dysfunction, pancreatic insufficiency, and intestinal disease. CF was traditionally diagnosed clinically, either because of a family history or occurrence of meconium ileus, or as a result of intestinal malabsorption and chronic pulmonary disease. In 1979, it was discovered that immunoreactive trypsinogen was increased in neonatal dried-blood specimens on Guthrie cards, making it possible to screen neonates. During the past decades, survival rates of patients with CF have improved significantly (see Figure 5). To continue this progress, universal newborn screening has been implemented in many states as an addition to the arsenal of therapies and strategies to improve survival. National newborn-screening programs to identify CF patients after birth have been adopted for a number of years in Europe, Australia, and Canada. As expected, many benefits have been seen due to the early identification of CF patients, including improved survival, better lung function and growth with less intensive therapy, and reduced cost of therapy. To date, 37 states in the United States have adopted similar programs, in the hopes of improving CF outcomes. This welcome trend should help improve the lives of CF patients living in America. PMID:18717498

  11. Emergency preparedness for newborn screening and genetic services.

    PubMed

    Pass, Kenneth A; Thoene, Jess; Watson, Michael S

    2009-06-01

    Patients identified in newborn screening programs can be among the most vulnerable during a disaster due to their need to have prompt diagnosis and medical management. Recent disasters have challenged the ability of newborn screening programs to maintain the needed continuity during emergency situations. This has significant implications for the newborn screening laboratories, the diagnostic confirmation providers, and the patients who either require diagnosis or maintenance of their therapeutic interventions. In 2007, the National Coordinating Center (NCC) for the Regional Genetics and Newborn Screening Collaboratives (RCs) sponsored a meeting involving representatives of the Regional Genetics and Newborn Screening Collaborative Groups, state newborn screening programs, providers of diagnosis and confirmation services, manufacturers of equipment, medical foods, and other treatments used in patients identified in newborn screening programs, and individuals from agencies involved in disaster response including the National Disaster Medical Service, the Centers for Disease Control and Prevention, the Emergency Management Assistance Compact, the Federal Emergency Management Agency, and others. In addition to developing contingency plans for newborn screening, we have considered other uses of genetics as it is used in DNA-based kinship identification of mass casualties. The meeting resulted in the description of a wide range of issues facing newborn screening programs, provider groups, and patients for which emergency preparedness development is needed in order that appropriate response is enabled. PMID:19444127

  12. Newborn Screening for Lysosomal Storage Diseases

    PubMed Central

    Gelb, Michael H.; Scott, C. Ronald; Turecek, Frantisek

    2015-01-01

    BACKGROUND There is worldwide interest in newborn screening for lysosomal storage diseases because of the development of treatment options that give better results when carried out early in life. Screens with high differentiation between affected and nonaffected individuals are critical because of the large number of potential false positives. CONTENT This review summarizes 3 screening methods: (a) direct assay of enzymatic activities using tandem mass spectrometry or fluorometry, (b) immunocapture-based measurement of lysosomal enzyme abundance, and (c) measurement of biomarkers. Assay performance is compared on the basis of small-scale studies as well as on large-scale pilot studies of mass spectrometric and fluorometric screens. SUMMARY Tandem mass spectrometry and fluorometry techniques for direct assay of lysosomal enzymatic activity in dried blood spots have emerged as the most studied approaches. Comparative mass spectrometry vs fluorometry studies show that the former better differentiates between nonaffected vs affected individuals. This in turn leads to a manageable number of screen positives that can be further evaluated with second-tier methods. PMID:25477536

  13. Screening Newborns | NIH MedlinePlus the Magazine

    MedlinePlus

    ... infant hearing screening programs. In December 2010, President Obama expanded the funding to include diagnostic services. Now, ... 98% of newborns are screened annually. 2010 President Obama signs the Early Hearing Detection and Intervention Act ...

  14. What Disorders Are Newborns Screened for in the United States?

    MedlinePlus

    ... the most appropriate application of universal newborn screening tests, technologies, policies, guidelines, and standards. A complete list of the conditions screened for in each state can be found at Baby's First Test . What are some examples of the benefits of ...

  15. Universal Newborn Screening and Adverse Medical Outcomes: A Historical Note

    ERIC Educational Resources Information Center

    Brosco, Jeffrey P.; Seider, Michael I.; Dunn, Angela C.

    2006-01-01

    Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and…

  16. Newborn screening progress in developing countries--overcoming internal barriers.

    PubMed

    Padilla, Carmencita D; Krotoski, Danuta; Therrell, Bradford L

    2010-04-01

    Newborn screening is an important public health measure aimed at early identification and management of affected newborns thereby lowering infant morbidity and mortality. It is a comprehensive system of education, screening, follow-up, diagnosis, treatment/management, and evaluation that must be institutionalized and sustained within public health systems often challenged by economic, political, and cultural considerations. As a result, developing countries face unique challenges in implementing and expanding newborn screening that can be grouped into the following categories: (1) planning, (2) leadership, (3) medical support, (4) technical support, (5) logistical support, (6) education, (7) protocol and policy development, (8) administration, (9) evaluation, and (10) sustainability. We review some of the experiences in overcoming implementation challenges in developing newborn screening programs, and discuss recent efforts to encourage increased newborn screening through support networking and information exchange activities in 2 regions-the Asia Pacific and the Middle East/North Africa. PMID:20207264

  17. [Newborn screening : the point of view of the paediatrician].

    PubMed

    De Laet, C; Laeremans, H; Ferster, A; Gulbis, B; Mansbach, A-L; Jonniaux, E; Regal, L; Goyens, P

    2015-09-01

    Newborn screening is a public health effort that has changed the prognosis of some congenital diseases. Newborn screening programmes differ between countries in which it is organized. Demographic, epidemiological or economic factors play a role in the choice of the screening panel. In the French Community of Belgium, the programme focuses on 13 metabolic and endocrine diseases, hearing loss and hemoglobinopathies (Brussels and Liege). Newborn screening is a complex process that requires the involvement of all stakeholders : parent information, blood sampling or testing, lab analysis, follow-up of the results, initiate adequate care in case of positive test and genetic counselling. Newborn screening programmes will evolve in the next years. New therapeutic and diagnostic methods will make other genetic diseases candidates for screening. Whole genome sequencing may be the next expansion; it will create new opportunities but will pose new ethical dilemmas. We must all prepare now for future challenges. PMID:26591303

  18. Newborn Screening: What Does the Emergency Physician Need to Know?

    PubMed

    Lavin, Lindsay Roofe; Higby, Nicholas; Abramo, Thomas

    2015-09-01

    Newborn screening programs were established in the United States in the early 1960s. Newborn screening programs were then developed by states and have continued to be the responsibility of the state. All states require a newborn screening, but what is required of these programs and screening panels has differed greatly by state. Historically, the most commonly screened disorders are the following: congenital hypothyroidism, congenital adrenal hyperplasia, sickle cell disease and associated hemoglobinopathies, biotinidase deficiency, galactosemia, cystic fibrosis and phenylketonuria, maple syrup urine disease, and homocystinuria. However, under new guidelines in 2006 and with new advances in technology, the scope of newborn screening programs has expanded to include at a minimum 9 organic acidurias, 5 fatty acid oxidation disorders, 3 hemoglobinopathies, and 6 other conditions. This CME article reviews the logistics of newborn screening and explores the effect of new technology and recent policy on state screens and what that means for providers. This article also highlights several of the disorders most relevant to emergency room physicians and discusses future considerations of newborn screening. PMID:26335232

  19. National evaluation of US newborn screening system components.

    PubMed

    Therrell, Bradford L; Hannon, W Harry

    2006-01-01

    Newborn screening has existed as a state-based public health service since the early 1960s. Every state and most territorial jurisdictions have comprehensive newborn screening programs in place, but in the United States a national newborn screening policy does not exist. This results in different administrative infrastructures, screening requirements, laboratory and follow-up services, medical management approaches, and related activities across the country. Federal initiatives and support have contributed to limited evaluations of various aspects of individual newborn screening programs at the national level, but funding is an issue. The national evaluation strategies have taken various forms, all with the intent of improving the screening system through review of actions taken and suggestions for future improvements. While participation in the national evaluation effort for newborn screening laboratory practices includes all US programs, and this has aided in improving quality and harmonizing protocols, other national evaluation activities have been only moderately successful. National data reporting of quality indicators for various program elements must be comprehensive and timely, and the elements must be universally accepted in order to meet the evaluation and improvement needs of the national newborn screening system. A comprehensive real time national evaluation activity will likely require additional resources and enforcement incentives. Limited federal actions through grant incentives and selected reporting requirements provide a possible means of stimulating programs to participate in national harmonization efforts. PMID:17183567

  20. Conference on Newborn Hearing Screening; Proceedings Summary and Recommendations.

    ERIC Educational Resources Information Center

    Alexander Graham Bell Association for the Deaf, Inc., Washington, DC.

    Presented in the conference proceedings are schedule and list of participants, seven major papers, and the newborn hearing screening recommendations of the interdisciplinary conference on newborn hearing and early identification of hearing impairment. Neonatal auditory testing is reviewed by Sanford E. Gerber, and Sheldon B. Korones gives a…

  1. Newborn screening cards: a legal quagmire.

    PubMed

    Bowman, Diana M; Studdert, David M

    2011-03-21

    Newborn screening (NBS) programs are a well established and cost-effective method for early identification of genetic disorders. However, a raft of legal questions surrounds the collection, storage, ownership and secondary use of NBS cards. The absence of clear legal rules governing NBS programs in Australia means that there are few straightforward answers to these questions. A series of controversial incidents have exposed this uncertainty in Australia, and remarkably similar controversies have occurred in the United States and European Union. We review the situation, using Victoria as a case study. We also make the case for a dedicated regulatory regime for NBS programs, arguing that the lack of such a regime threatens public trust and the robust operation of NBS programs in Australia. New rules would likely introduce stricter requirements for informed consent at the point of blood collection than has been the norm to date. However, the scope for use of cards in research could expand rather than contract, and it may be possible to reduce the risk that vast card archives will need to be destroyed in response to future public outcries. PMID:21426290

  2. Cystic fibrosis newborn screening: a model for neuromuscular disease screening?

    PubMed

    Scully, Michele A; Farrell, Philip M; Ciafaloni, Emma; Griggs, Robert C; Kwon, Jennifer M

    2015-02-01

    Congenital neuromuscular disorders, such as Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), and Pompe disease (acid maltase deficiency [AMD]), are candidates for universal newborn screening (NBS). In this article, we discuss the future path of NBS for these disorders with particular emphasis on DMD NBS, because of the likely approval of new gene-modifying treatments, the possible benefits of earlier treatment with corticosteroids, and the recently demonstrated feasibility of a 2-tiered approach to NBS with screening by creatine kinase (CK) levels in dried blood spots followed by mutation detection in those with elevated CK. The cystic fibrosis (CF) NBS program is a successful model for NBS. CF outcomes have consistently improved into adulthood following introduction of CF NBS because considerable resources have been devoted to practices that include: attention to improving laboratory screening, consistent confirmatory testing and immediate referral of all newly diagnosed infants to designated CF care centers that follow established practice guidelines, and ongoing evaluation of CF care centers via a centralized clinical database. Like CF, DMD, SMA, and infantile AMD are inexorably debilitating and require lifetime multidisciplinary clinical management. NBS would address the delays in diagnosis that prevent patients from receiving timely treatments. Standardized care following early diagnosis would reduce disparities in clinical care and outcomes. NBS in these neuromuscular disorders should be implemented, utilizing lessons learned from the past 20 years of CF NBS: standardized protocols for all patients identified by DMD NBS, longitudinal follow-up in multidisciplinary clinics, and coordinated oversight of these clinics. PMID:25425541

  3. Whole-Genome Screening of Newborns? The Constitutional Boundaries of State Newborn Screening Programs

    PubMed Central

    King, Jaime S.; Smith, Monica E.

    2016-01-01

    State newborn screening (NBS) programs routinely screen nearly all of the 4 million newborns in the United States each year for ~30 primary conditions and a number of secondary conditions. NBS could be on the cusp of an unprecedented expansion as a result of advances in whole-genome sequencing (WGS). As WGS becomes cheaper and easier and as our knowledge and understanding of human genetics expand, the question of whether WGS has a role to play in state NBS programs becomes increasingly relevant and complex. As geneticists and state public health officials begin to contemplate the technical and procedural details of whether WGS could benefit existing NBS programs, this is an opportune time to revisit the legal framework of state NBS programs. In this article, we examine the constitutional underpinnings of state-mandated NBS and explore the range of current state statutes and regulations that govern the programs. We consider the legal refinements that will be needed to keep state NBS programs within constitutional bounds, focusing on 2 areas of concern: consent procedures and the criteria used to select new conditions for NBS panels. We conclude by providing options for states to consider when contemplating the use of WGS for NBS. PMID:26729704

  4. Lessons Learned From Newborn Screening for Critical Congenital Heart Defects.

    PubMed

    Oster, Matthew E; Aucott, Susan W; Glidewell, Jill; Hackell, Jesse; Kochilas, Lazaros; Martin, Gerard R; Phillippi, Julia; Pinto, Nelangi M; Saarinen, Annamarie; Sontag, Marci; Kemper, Alex R

    2016-05-01

    Newborn screening for critical congenital heart defects (CCHD) was added to the US Recommended Uniform Screening Panel in 2011. Within 4 years, 46 states and the District of Columbia had adopted it into their newborn screening program, leading to CCHD screening being nearly universal in the United States. This rapid adoption occurred while there were still questions about the effectiveness of the recommended screening protocol and barriers to follow-up for infants with a positive screen. In response, the Centers for Disease Control and Prevention partnered with the American Academy of Pediatrics to convene an expert panel between January and September 2015 representing a broad array of primary care, neonatology, pediatric cardiology, nursing, midwifery, public health, and advocacy communities. The panel's goal was to review current practices in newborn screening for CCHD and to identify opportunities for improvement. In this article, we describe the experience of CCHD screening in the United States with regard to: (1) identifying the target lesions for CCHD screening; (2) optimizing the algorithm for screening; (3) determining state-level challenges to implementation and surveillance of CCHD; (4) educating all stakeholders; (5) performing screening using the proper equipment and in a cost-effective manner; and (6) implementing screening in special settings such as the NICU, out-of-hospital settings, and areas of high altitude. PMID:27244826

  5. Newborn Screening for Lysosomal Storage Disorders and Other Neuronopathic Conditions

    PubMed Central

    Matern, Dietrich; Oglesbee, Devin; Tortorelli, Silvia

    2014-01-01

    Newborn screening (NBS) is a public health program aimed at identifying treatable conditions in presymptomatic newborns to avoid premature mortality, morbidity, and disabilities. Currently, every newborn in the Unites States is screened for at least 29 conditions where evidence suggests that early detection is possible and beneficial. With new or improved treatment options and development of high-throughput screening tests, additional conditions have been proposed for inclusion into NBS programs. Among those are several conditions with a strong neuronopathic component. Some of these conditions have already been added to a few national and international screening programs, whereas others are undergoing pilot studies to determine the test performance metrics. Here, we review the current state of NBS for 13 lysosomal storage disorders, X-adrenoleukodystrophy, Wilson disease, and Friedreich ataxia. PMID:23798012

  6. Newborn screening for lysosomal storage disorders and other neuronopathic conditions.

    PubMed

    Matern, Dietrich; Oglesbee, Devin; Tortorelli, Silvia

    2013-01-01

    Newborn screening (NBS) is a public health program aimed at identifying treatable conditions in presymptomatic newborns to avoid premature mortality, morbidity, and disabilities. Currently, every newborn in the Unites States is screened for at least 29 conditions where evidence suggests that early detection is possible and beneficial. With new or improved treatment options and development of high-throughput screening tests, additional conditions have been proposed for inclusion into NBS programs. Among those are several conditions with a strong neuronopathic component. Some of these conditions have already been added to a few national and international screening programs, whereas others are undergoing pilot studies to determine the test performance metrics. Here, we review the current state of NBS for 13 lysosomal storage disorders, X-adrenoleukodystrophy, Wilson disease, and Friedreich ataxia. PMID:23798012

  7. Digital Microfluidics: A Future Technology in the Newborn Screening Laboratory?

    PubMed Central

    Millington, David S.; Sista, Ramakrishna; Eckhardt, Allen; Rouse, Jeremy; Bali, Deeksha; Goldberg, Ronald; Cotten, Michael; Buckley, Rebecca; Pamula, Vamsee

    2010-01-01

    Expansion of newborn screening for inherited metabolic disorders using tandem mass spectrometry has generated interest in screening for other treatable conditions, including lysosomal storage diseases. Limitations to expansion include labor and equipment costs. We describe a cost-effective new platform that reduces the time to result reporting and can perform multiplexing assays requiring different platforms. Immunoassays and enzyme activity assays currently used in newborn screening have been translated to a disposable microchip programmed to dispense, transport, mix, wash, and incubate individual microdroplets from specimens, including dried blood spot extracts, and reagents all under software control. The specimen and reagents consumed are approximately 1% of those required by equivalent bench assays. In addition to immunologic and enzymatic assays, DNA amplification, amplicon detection, and sequencing have been demonstrated using the same microchips and control equipment. Recently, the multiplexing of 4 different enzyme activities has also been demonstrated with negligible cross-contamination. We review assays relevant to newborn screening. PMID:20207266

  8. Newborn Sickle Cell Screening: Benefits and Burdens Realized.

    ERIC Educational Resources Information Center

    Rowley, Peter T.; Huntzinger, Donna J.

    1983-01-01

    Follow-up data on a program that screened 17 newborns for sickle cell anemia suggests that in order to derive maximum benefit from such screening physicians need to better understand the differential diagnosis, treatment, and inheritance of sickle cell disease, and individual guidance must be provided to families. (GC)

  9. Phenylalanine and tyrosine levels in newborn screening blood samples.

    PubMed Central

    Morris, A F; Holton, J B; Burman, D; Colley, J R

    1983-01-01

    A previously described difference in newborn blood phenylalanine concentrations between those living in urban and non-urban areas in the south west of England has been confirmed and shown to be independent of the type of feed. Several factors including the place of abode, type of feed, birthweight, and the accuracy of the test have been found to affect the measured, phenylalanine concentration in the newborn screening blood spot, and the importance of these results to screening practice is considered. Blood tyrosine also varied with the above factors, but severe, neonatal tyrosinaemia was shown to be a rare problem. PMID:6847230

  10. Cost Analysis of TEOAE-Based Universal Newborn Hearing Screening.

    ERIC Educational Resources Information Center

    Weirather, Yusnita; Korth, Nancy; White, Karl R.; Woods-Kershner, Nancy; Downs, Diane

    1997-01-01

    After reviewing the extant literature, this article describes a cost analysis of the transient evoked otoaoustic emissions (TEOAE)-based universal newborn hearing screening program. Reasons why the cost per baby ($7.42) is lower than in previous reports are explained and the benefits of having accurate cost analysis data are summarized. (Author/CR)

  11. Newborn Hearing Screening: An Analysis of Current Practices

    ERIC Educational Resources Information Center

    Houston, K. Todd; Bradham, Tamala S.; Munoz, Karen F.; Guignard, Gayla Hutsell

    2011-01-01

    State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that consisted of 12 evaluative areas of EHDI programs. For the newborn hearing screening area, a total of 293 items were listed by 49 EHDI coordinators, and themes were identified within…

  12. Students as Technicians: Screening Newborns for Cystic Fibrosis

    ERIC Educational Resources Information Center

    Gusky, Sharon

    2014-01-01

    In this activity, freshman college students learn biotechnology techniques while playing the role of a laboratory technician. They perform simulations of three diagnostic tests used to screen newborns for cystic fibrosis. By performing an ELISA, a PCR analysis, and a conductivity test, students learn how biotechnology techniques can be used to…

  13. Expanding Newborn Screening for Lysosomal Disorders: Opportunities and Challenges

    ERIC Educational Resources Information Center

    Waggoner, Darrel J.; Tan, Christopher A.

    2011-01-01

    Newborn screening (NBS), since its implementation in the 1960s, has traditionally been successful in reducing mortality and disability in children with a range of different conditions. Lysosomal storage disorders (LSD) are a heterogeneous group of inherited metabolic diseases that result from lysosomal dysfunction. Based on available treatment and…

  14. Appropriateness of Newborn Screening for α1-Antitrypsin Deficiency

    PubMed Central

    Teckman, Jeffrey; Pardee, Erin; Howell, R. Rodney; Mannino, David; Sharp, Richard R.; Brantly, Mark; Wanner, Adam; Lamson, Jamie

    2014-01-01

    ABSTRACT Objective: The Alpha-1 Foundation convened a workshop to consider the appropriateness of newborn screening for α-1-antitrypsin (AAT) deficiency. Methods: A review of natural history and technical data was conducted. Results: Homozygous ZZ AAT deficiency is a common genetic disease occurring in 1 in 2000 to 3500 births; however, it is underrecognized and most patients are undiagnosed. AAT deficiency can cause chronic liver disease, cirrhosis, and liver failure in children and adults, and lung disease in adults. The clinical course is highly variable. Some neonates present with cholestatic hepatitis and some children require liver transplantation, but many patients remain well into adulthood. Some adults develop emphysema. There is no treatment for AAT liver disease, other than supportive care and liver transplant. There are no data on the effect of early diagnosis on liver disease. Avoidance of smoking is of proven benefit to reduce future lung disease, as is protein replacement therapy. Justifying newborn screening with the aim of reducing smoking and reducing adult lung disease-years in the future would be a significant paradigm shift for the screening field. Recent passage of the Genetic Information Nondiscrimination Act (GINA) and the Affordable Care Act may have a major effect on reducing the psychosocial and financial risks of newborn screening because many asymptomatic children would be identified. Data on the risk–benefit ratio of screening in the new legal climate are lacking. Conclusions: Workshop participants recommended a series of pilot studies focused on generating new data on the risks and benefits of newborn screening. PMID:24121147

  15. Holocarboxylase synthetase deficiency pre and post newborn screening

    PubMed Central

    Donti, Taraka R.; Blackburn, Patrick R.; Atwal, Paldeep S.

    2016-01-01

    Holocarboxylase synthetase deficiency is an autosomal recessive disorder of biotin metabolism resulting in multiple carboxylase deficiency. The typical presentation described in the medical literature is of neonatal onset within hours to weeks of birth with emesis, hypotonia, lethargy, seizures, metabolic ketolactic acidosis, hyperammonemia, developmental delay, skin rash and alopecia. The condition is screened for by newborn screening (NBS) tandem mass spectroscopy by elevated hydroxypentanoylcarnitine on dried blood spots. Urine organic acid profile may demonstrate elevated lactic, 3-OH isovaleric, 3-OH propionic, 3-MCC, methylcitric acids, and tiglylglycine consistent with loss of function of the above carboxylases. Here we describe a cohort of patients, 2 diagnosed pre-NBS and 3 post-NBS with broad differences in initial presentation and phenotype. In addition, prior to the advent of NBS, there are isolated reports of late-onset holocarboxylase synthetase deficiency in the medical literature, which describe patients diagnosed between 1 and 8 years of life, however to our knowledge there are no reports of late-onset HCLS being missed by NBS. Also we report two cases, each with novel pathogenic variants HCLS, diagnosed at age 3 years and 21 months respectively. The first patient had a normal newborn screen whilst the second had an abnormal newborn screen but was misdiagnosed as 3-methylcrotonylcarboxylase (3-MCC) deficiency and subsequently lost to follow-up until they presented again with severe metabolic acidosis. PMID:27114915

  16. Holocarboxylase synthetase deficiency pre and post newborn screening.

    PubMed

    Donti, Taraka R; Blackburn, Patrick R; Atwal, Paldeep S

    2016-06-01

    Holocarboxylase synthetase deficiency is an autosomal recessive disorder of biotin metabolism resulting in multiple carboxylase deficiency. The typical presentation described in the medical literature is of neonatal onset within hours to weeks of birth with emesis, hypotonia, lethargy, seizures, metabolic ketolactic acidosis, hyperammonemia, developmental delay, skin rash and alopecia. The condition is screened for by newborn screening (NBS) tandem mass spectroscopy by elevated hydroxypentanoylcarnitine on dried blood spots. Urine organic acid profile may demonstrate elevated lactic, 3-OH isovaleric, 3-OH propionic, 3-MCC, methylcitric acids, and tiglylglycine consistent with loss of function of the above carboxylases. Here we describe a cohort of patients, 2 diagnosed pre-NBS and 3 post-NBS with broad differences in initial presentation and phenotype. In addition, prior to the advent of NBS, there are isolated reports of late-onset holocarboxylase synthetase deficiency in the medical literature, which describe patients diagnosed between 1 and 8 years of life, however to our knowledge there are no reports of late-onset HCLS being missed by NBS. Also we report two cases, each with novel pathogenic variants HCLS, diagnosed at age 3 years and 21 months respectively. The first patient had a normal newborn screen whilst the second had an abnormal newborn screen but was misdiagnosed as 3-methylcrotonylcarboxylase (3-MCC) deficiency and subsequently lost to follow-up until they presented again with severe metabolic acidosis. PMID:27114915

  17. Governing population screening in an age of expansion: The case of newborn screening.

    PubMed

    Miller, Fiona Alice; Cressman, Céline; Hayeems, Robin

    2015-01-01

    Newborn bloodspot screening is one of the most enduring and successful population screening initiatives. Yet technological innovation to permit simultaneous measurement of multiple biomarkers - and potentially, entire genomes - has spurred expansion and debate. Through a cross-jurisdictional comparison, we describe the varied roles and reach of screening-related governance structures in the United States, the United Kingdom, New Zealand and Canada, and highlight the distinct values and resources brought to bear by the genetics, public health and maternal-child health communities in adjudicating the benefits and burdens of expanded newborn screening. We call for the expansion of formal governance structures that are balanced in resources and perspective and mandated to ensure that the organization and delivery of newborn screening achieves optimal quality. PMID:26285197

  18. Newborn screening and diagnosis of mucopolysaccharidoses

    PubMed Central

    Tomatsu, Shunji; Fujii, Tadashi; Fukushi, Masaru; Oguma, Toshihiro; Shimada, Tsutomu; Maeda, Miho; Kida, Kazuhiro; Shibata, Yuniko; Futatsumori, Hideyuki; Montaño, Adriana M.; Mason, Robert W.; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao

    2013-01-01

    Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and hyaluronan. Their catabolism may be blocked singly or in combination depending on the specific enzyme deficiency. There are 11 known enzyme deficiencies, resulting in seven distinct forms of MPS with a collective incidence of higher than 1 in 25,000 live births. Accumulation of undegraded metabolites in lysosomes gives rise to distinct clinical syndromes. Generally, the clinical conditions progress if untreated, leading to developmental delay, systemic skeletal deformities, and early death. MPS disorders are potentially treatable with enzyme replacement therapy or hematopoietic stem cell transplantation. For maximum benefit of available therapies, early detection and intervention are critical. We recently developed a novel high-throughput multiplex method to assay DS, HS, and KS simultaneously in blood samples by using high performance liquid chromatography/tandem mass spectrometry for MPS. The overall performance metrics of HS and DS values on MPS I, II, and VII patients vs. healthy controls at newborns were as follows using a given set of cut-off values: sensitivity, 100%; specificity, 98.5–99.4%; positive predictive value, 54.5–75%; false positive rate, 0.62–1.54%; and false negative rate, 0%. These findings show that the combined measurements of these three GAGs are sensitive and specific for detecting all types of MPS with acceptable false negative/positive rates. In addition, this method will also be used for monitoring therapeutic efficacy. We review the history of GAG assay and application to diagnosis for MPS. PMID:23860310

  19. Newborn screening and diagnosis of mucopolysaccharidoses.

    PubMed

    Tomatsu, Shunji; Fujii, Tadashi; Fukushi, Masaru; Oguma, Toshihiro; Shimada, Tsutomu; Maeda, Miho; Kida, Kazuhiro; Shibata, Yuniko; Futatsumori, Hideyuki; Montaño, Adriana M; Mason, Robert W; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao

    2013-01-01

    Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and hyaluronan. Their catabolism may be blocked singly or in combination depending on the specific enzyme deficiency. There are 11 known enzyme deficiencies, resulting in seven distinct forms of MPS with a collective incidence of higher than 1 in 25,000 live births. Accumulation of undegraded metabolites in lysosomes gives rise to distinct clinical syndromes. Generally, the clinical conditions progress if untreated, leading to developmental delay, systemic skeletal deformities, and early death. MPS disorders are potentially treatable with enzyme replacement therapy or hematopoietic stem cell transplantation. For maximum benefit of available therapies, early detection and intervention are critical. We recently developed a novel high-throughput multiplex method to assay DS, HS, and KS simultaneously in blood samples by using high performance liquid chromatography/tandem mass spectrometry for MPS. The overall performance metrics of HS and DS values on MPS I, II, and VII patients vs. healthy controls at newborns were as follows using a given set of cut-off values: sensitivity, 100%; specificity, 98.5-99.4%; positive predictive value, 54.5-75%; false positive rate, 0.62-1.54%; and false negative rate, 0%. These findings show that the combined measurements of these three GAGs are sensitive and specific for detecting all types of MPS with acceptable false negative/positive rates. In addition, this method will also be used for monitoring therapeutic efficacy. We review the history of GAG assay and application to diagnosis for MPS. PMID:23860310

  20. Newborn screening for spinal muscular atrophy: Anticipating an imminent need.

    PubMed

    Phan, Han C; Taylor, Jennifer L; Hannon, Harry; Howell, Rodney

    2015-04-01

    Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. Children with type I SMA typically die by the age of 2 years. Recent progress in gene modification and other innovative therapies suggest that improved outcomes may soon be forthcoming. In animal models, therapeutic intervention initiated before the loss of motor neurons alters SMA phenotype and increases lifespan. Presently, supportive care including respiratory, nutritional, physiatry, and orthopedic management can ameliorate clinical symptoms and improve survival rates if SMA is diagnosed early in life. Newborn screening could help optimize these potential benefits. A recent report demonstrated that SMA detection can be multiplexed at minimal additional cost with the assay for severe combined immunodeficiency, already implemented by many newborn screening programs. The public health community should remain alert to the rapidly changing developments in early detection and treatment of SMA. PMID:25979781

  1. Current Status of Newborn Screening: Decision-Making about the Conditions to Include in Screening Programs

    ERIC Educational Resources Information Center

    Watson, Michael S.

    2006-01-01

    Newborn screening is considered a highly successful public health program that has resulted in the reduction of mortality, mental retardation, and other serious disabilities in thousands of children since the introduction of screening for phenylketonuria (PKU) in the 1960s. Programs are based in state public health departments such that each state…

  2. Expanding newborn screening for lysosomal disorders: opportunities and challenges.

    PubMed

    Waggoner, Darrel J; Tan, Christopher A

    2011-01-01

    Newborn screening (NBS), since its implementation in the 1960s, has traditionally been successful in reducing mortality and disability in children with a range of different conditions. Lysosomal storage disorders (LSD) are a heterogeneous group of inherited metabolic diseases that result from lysosomal dysfunction. Based on available treatment and suitable screening methods, the LSDs that are considered for NBS generally include Fabry, Gaucher, Krabbe, MPSI, MPSII, MPSV, Metachromatic leukodystrophy, Niemann-Pick, and Pompe. Utilizing traditional and expanded criteria for consideration of NBS leads to a set of fundamental questions that need to be explored when considering the opportunities and challenges of adding LSDs to NBS panels. PMID:22447749

  3. Newborn screening of metabolic disorders: recent progress and future developments.

    PubMed

    Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

    2008-01-01

    Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation. PMID:18626194

  4. Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

    PubMed Central

    Kwan, Antonia; Abraham, Roshini S.; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K.; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E.; Bonagura, Vincent R.; Bonilla, Francisco A.; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A.; Comeau, Anne Marie; Connelly, James A.; Cowan, Morton J.; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T.; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W.; Hale, Jaime E.; Celine Hanson, I.; Hay, Beverly N.; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M.; Kohn, Donald B.; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B.; Naides, Stanley J.; Notarangelo, Luigi D.; Orange, Jordan S.; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A.; Scott, Ginger; Scott, Patricia M.; Secord, Elizabeth; Seroogy, Christine; Shearer, William T.; Siegel, Subhadra; Silvers, Stacy K.; Stiehm, E. Richard; Sugerman, Robert W.; Sullivan, John L.; Tanksley, Susan; Tierce, Millard L.; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E.; Wasserman, Richard L.; Watson, Michael S.; Weinberg, Geoffrey A.; Weiner, Leonard B.; Wood, Heather; Yates, Anne B.; Puck, Jennifer M.

    2015-01-01

    IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in

  5. Maintaining Acceptably Low Referral Rates in TEOAE-Based Newborn Hearing Screening Programs.

    ERIC Educational Resources Information Center

    Maxon, Antonia Brancia; White, Karl R.; Culpepper, Brandt; Vohr, Betty R.

    1997-01-01

    Describes factors that can affect the referral rate for otoacoustic emission-based newborn hearing screening and discusses the screening results of 1,328 newborns screened with transient evoked otoaoustic emissions prior to hospital discharge. The youngest infants were as likely to pass as infants who were 24-27 hours old. (Author/CR)

  6. Neonatal screening for haemoglobinopathy. Results in 7691 Manchester newborns.

    PubMed Central

    Evans, D I; Blair, V M

    1976-01-01

    Over a period of one year the blood samples collected for phenylketonuria testing from 7691 Manchester newborns were screened by haemoglobin electrophoresis. An abnormality was detected in 47 (0-61%) of the babies. No cases of homozygous haemoglobinopathy were found. The overall incidence of sickle-cell trait was 0-38%, but for the Black population it was 10%. Four Black babies and one White baby had alpha-thalassaemia. No other haemoglobinopathies were found in the White babies and no Asian baby had alpha-thalassaemia. Haemoglobin A2 was precociously developed in three babies, two of whom were coloured--probably a further example of the earlier maturity of coloured babies. The screening programme was stopped when it became cleaasily be combined with screening for metabolic disease in places where the incidence of haemoglobinopathies is higher. PMID:1259457

  7. Newborn screening for congenital adrenal hyperplasia in New York State.

    PubMed

    Pearce, Melissa; DeMartino, Lenore; McMahon, Rebecca; Hamel, Rhonda; Maloney, Breanne; Stansfield, Daniele-Marisa; McGrath, Emily C; Occhionero, Amanda; Gearhart, Adam; Caggana, Michele; Tavakoli, Norma P

    2016-06-01

    From 2007 to 2014 the New York State (NYS) Newborn Screening (NBS) program screened 2 million newborns for congenital adrenal hyperplasia (CAH). The data was analyzed to determine factors that affect 17α-hydroxyprogesterone levels and assist in developing algorithm changes that would improve the positive predictive value of the methodology being used. The concentration of 17-OHP in dried blood spots was measured using the AutoDELFIA Neonatal 17-OHP kit (Perkin Elmer, Turku, Finland). During the 8 year period of this study 2476 babies were referred, 105 babies were diagnosed with CAH (90 with the salt-wasting (SW), 8 with simple virilizing (SV), 5 with non-classical CAH, and 2 with another enzyme deficiency) and, 14 with possible CAH. Three false negative cases with SV-CAH were reported to the program. Of the total 108 known cases, 74 (69%) infants were detected by newborn screening in the absence of clinical information, or, known family history. The incidence of CAH in NYS is 1 in 18,170 with a ratio of SW to SV of 8.2:1. The incidence of CAH is lower in Black infants than in White, Hispanic and Asian infants. Despite a lower mean birth weight, female infants have a lower mean 17-OHP value than male infants and are under-represented in the referred category. As per other NBS programs the false positive rate is exacerbated by prematurity/low birth weight and by over-early specimen collection. PMID:27331001

  8. "Collodion baby": A unique challenge for newborn hearing screening.

    PubMed

    Jasper, Kayla M; Gaudreau, Philip; Cartee, Todd V; Reilly, Brian K

    2016-01-01

    We present an infant with collodion membrane who had an obstructed external auditory canal, causing the infant to fail her newborn hearing screen (otoacoustic emissions) bilaterally. An auditory brainstem response (ABR) test was deferred due to the reported increased risk of infections in these babies. Meticulous but gentle debridement of the membranes on the external auditory canal, using a combination of otic drops (ofloxacin), emollients (baby oil/mineral oil), and suctioning, permitted the infant to ultimately pass otoacoustic emissions bilaterally and subsequent serial audiograms. PMID:27178521

  9. Appropriateness of newborn screening for classic galactosaemia: a systematic review.

    PubMed

    Varela-Lema, L; Paz-Valinas, L; Atienza-Merino, G; Zubizarreta-Alberdi, R; Villares, R Vizoso; López-García, M

    2016-09-01

    Currently, there is no universal agreement on galactosaemia screening, fundamentally because of the risk-benefit uncertainties. We conducted two exhaustive systematic searches in the main electronic databases (PubMed, Embase, Cochrane, etc.) to recover relevant information about the disease and screening test/s in order to support decision making in Spain. All of the 45 studies identified that covered disease issues were retrospective case series or cross-sectional analysis (level-4 evidence). Studies consistently found that the majority of patients presented characteristic symptomatology before diagnosis. Long term disabilities were not significantly correlated with age of diagnosis, onset of dietary restriction or strict diet compliance. The five studies that provided accuracy data used different cut-off points and verification tests, and thus differed in their definitions of a positive case (level-3b evidence). The estimated sensitivity was 100 % and the specificity 99.9 %. The false-positive rate ranged from 0.0005 % to 0.25 %, and the PPV from 0 % to 64.3 %. The comparative clinical effectiveness in relation to not screening or implementation of other programs is unknown. In summary, existing evidence remains insufficient to establish the appropriateness of newborn screening for galactosaemia screening, although health benefits could be expected if early diagnosis and treatment is achieved. If screening is implemented in Spain, it would be important that a pilot programme be implemented to assess false positive rate and ensure that early diagnosis is not delayed. PMID:27116003

  10. Newborn screening for lysosomal storage disorders in hungary.

    PubMed

    Wittmann, Judit; Karg, Eszter; Turi, Sàndor; Legnini, Elisa; Wittmann, Gyula; Giese, Anne-Katrin; Lukas, Jan; Gölnitz, Uta; Klingenhäger, Michael; Bodamer, Olaf; Mühl, Adolf; Rolfs, Arndt

    2012-01-01

    Even though lysosomal storage disorders (LSDs) are considered to be orphan diseases, they pose a highly relevant cause for morbidity and mortality as their cumulative prevalence is estimated to be 1:4,000. This is especially important as treatment in form of enzyme replacement therapy, substrate reduction therapy or stem cell transplantation is amenable for some LSDs. It is plausible that an early start of treatment might improve the overall prognosis and, even more important, prevent irreversible damage of key organs. To get a more precise insight into the real frequency of some LSDs in the general population, we screened 40,024 samples from the Hungarian newborn screening (NBS) program in Szeged for Fabry disease (FD), Gaucher disease (GD), Pompe disease (PD), and Niemann-Pick A/B (NPB) disease using tandem mass spectrometry. Altogether, 663 samples (1.66%) were submitted for retesting. Genetic confirmation was carried out for 120 samples with abnormal screening results after retesting, which identified three cases of GD, three cases of FD, nine cases of PD, and two cases with NPB. In some cases, we detected up to now unknown mutations - one in NPB and seven in PD - which raise questions about the clinical consequences of a NBS in the sense of late-onset manifestations. Overall, we conclude that screening for LSDs by tandem MS/MS followed by a genetic workup in identified patients is a robust, easy, valid, and feasible technology in newborn screening programs. Furthermore, early diagnosis of LSDs gives a chance to early treatment, but needs more clinical long-term data especially regarding the consequence of private mutations. PMID:23430949

  11. Combination of hearing screening and genetic screening for deafness-susceptibility genes in newborns

    PubMed Central

    YAO, GEN-DONG; LI, SHOU-XIA; CHEN, DING-LI; FENG, HAI-QIN; ZHAO, SU-BIN; LIU, YONG-JIE; GUO, LI-LI; YANG, ZHI-MING; ZHANG, XIAO-FANG; SUN, CAI-XIA; WANG, ZE-HUI; ZHANG, WEI-YONG

    2014-01-01

    The aim of this study was to determine the clinical significance of the results of screening of newborn hearing and the incidence of deafness-susceptibility genes. One thousand newborn babies in the Handan Center Hospital (Handan, China) underwent screening of hearing and deafness-susceptibility genes. The first screening test was carried out using otoacoustic emissions (OAEs). Babies with hearing loss who failed to pass the initial screening were scheduled for rescreening at 42 days after birth. Cord blood was used for the screening of deafness-susceptibility genes, namely the GJB2, SLC26A4 and mitochondrial 12S rRNA (MTRNR1) genes. Among the 1,000 neonates that underwent the first hearing screening, 25 exhibited left-sided hearing loss, 21 exhibited right-sided hearing loss and 15 cases had binaural hearing loss. After rescreening 42 days later, only one of the initial 61 cases exhibited hearing loss under OAE testing. The neonatal deafness gene tests showed two cases with 1555A>G mutation and two cases with 1494C>T mutation of the MTRNR1 gene. In the SLC26A4 gene screening, four cases exhibited the heterozygous IVS7-2A>G mutation and one case exhibited heterozygous 1226G>A mutation. In the GJB2 gene screening, two cases exhibited the homozygous 427C>T mutation and 10 exhibited the heterozygous 235delC mutation. The genetic screening revealed 21 newborns with mutations in the three deafness-susceptibility genes. The overall carrier rate was 2.1% (21/1,000). The association of hearing and gene screening may be the promising screening strategy for the diagnosis of hearing loss. PMID:24348793

  12. AB017. The extended newborn screening by tandem mass in Taiwan—results from two national newborn screening centers: Taipei Institute of Pathology & Chinese Foundation of Health

    PubMed Central

    Niu, Dau-Ming; Chiang, Chuan-Chi; Ho, Hui-Chen

    2015-01-01

    Since 2001, tandem mass spectrometry was introduced for newborn screening by two Taiwan national newborn screening centers: Taipei Institute of Pathology and Chinese Foundation of Health, in Taiwan, respectively. A total of 24 metabolic disorders, including 6 amino acidopathies, 8 organic acid disorders and 9 fatty acid disorders, etc., were screened and the newborns with positive screening result were referred to Taipei Veterans General Hospital for confirmatory diagnosis. Until Dec 2014, a total of 1,391,583 newborns have been screened by these two newborn screening centers. The overall incidence of inborn errors of metabolism identified by tandem mass was approximately 1/6,000. The most common inborn errors were defects of phenylalanine metabolism (phenylketonuria: 1/60,000; 6-pyruvoyltertrahydropterin synthase (PTPS): 1/110,000). Maple syrup urine disease was the second most common amino acidopathy (1/100,000) and, significantly, most MSUD patients (75%) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected organic acid disorder was 3-methylcrotonyl-CoA carboxylase deficiency (1/35,000). Glutaric aciduria type 1 and methylmalonic academia were the second most common organic acid disorders (1/100,000 for each disease). The incidence of fatty acid disorder is relatively less than most western countries. Out of them, carnitine transport defect was the most common fatty acid disease (1/100,000). In this report we will present this large population study of tandem mass newborn screening in Chinese population.

  13. Retention and research use of residual newborn screening bloodspots.

    PubMed

    Botkin, Jeffrey R; Goldenberg, Aaron J; Rothwell, Erin; Anderson, Rebecca A; Lewis, Michelle Huckaby

    2013-01-01

    The storage and use of residual newborn screening dried blood specimens has generated significant controversy in the past 5 years, primarily because of public concerns over the lack of parental knowledge and consent for these activities. State policies addressing the management of these specimens vary widely, and there is currently little guidance to aid new state policy development to address the concerns of program professionals, investigators, and the general public. This article offers guidance for state policy based on multiple sources of data, including public attitudes, professional statements, state experience, and an analysis of the ethical, social, legal, and biomedical issues from a multidisciplinary group of scholars. This guidance will be useful for state programs that seek to develop policies that are informed by a contemporary analysis of the key ethical, legal, and social aspects of this practice. This article represents the work of the authors and does not represent American Academy of Pediatrics policy. PMID:23209103

  14. Improving regional universal newborn hearing screening programmes in Italy.

    PubMed

    Molini, E; Cristi, M C; Lapenna, R; Calzolaro, L; Muzzi, E; Ciciriello, E; Della Volpe, A; Orzan, E; Ricci, G

    2016-02-01

    The Universal Newborn Hearing Screening (UNHS) programme aims at achieving early detection of hearing impairment. Subsequent diagnosis and intervention should follow promptly. Within the framework of the Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", the limitations and strengths of current UNHS programs in Italy have been analysed by a group of professionals working in tertiary centres involved in regional UNHS programmes, using SWOT analysis and a subsequent TOWS matrix. Coverage and lost-to-follow up rates are issues related to UNHS programmes. Recommendations to improve the effectiveness of the UNHS programme have been identified. The need for homogeneous policies, high-quality information and dissemination of knowledge for operators and families of hearing-impaired children emerged from the discussion. PMID:27054385

  15. Retention and Research Use of Residual Newborn Screening Bloodspots

    PubMed Central

    Goldenberg, Aaron J.; Rothwell, Erin; Anderson, Rebecca A.; Lewis, Michelle Huckaby

    2013-01-01

    The storage and use of residual newborn screening dried blood specimens has generated significant controversy in the past 5 years, primarily because of public concerns over the lack of parental knowledge and consent for these activities. State policies addressing the management of these specimens vary widely, and there is currently little guidance to aid new state policy development to address the concerns of program professionals, investigators, and the general public. This article offers guidance for state policy based on multiple sources of data, including public attitudes, professional statements, state experience, and an analysis of the ethical, social, legal, and biomedical issues from a multidisciplinary group of scholars. This guidance will be useful for state programs that seek to develop policies that are informed by a contemporary analysis of the key ethical, legal, and social aspects of this practice. This article represents the work of the authors and does not represent American Academy of Pediatrics policy. PMID:23209103

  16. Newborn screening strategies for congenital hypothyroidism: an update.

    PubMed

    LaFranchi, Stephen H

    2010-10-01

    It is the purpose of this article to briefly review the initial development and subsequent evolution of newborn screening programs to detect infants with congenital hypothyroidism (CH) and then to provide an update of the advantages and disadvantages of the main test strategies. Pilot programs began screening newborn populations in North America in the mid-1970s using either primary thyroxine (T4)-follow-up thyroid stimulating hormone (TSH) or primary TSH testing. Many programs in the United States and around the world continue to prefer a primary T4-follow-up TSH test strategy. This approach has the advantage of detecting infants with primary CH, as well as cases of hypopituitary hypothyroidism, by follow-up of infants with a T4 below an absolute cutoff or with a persistently low T4 level, necessitating a higher recall rate. With increasing assay sensitivity and specificity, several programs in the United States and worldwide have elected to switch to a primary TSH test strategy. This test strategy has the advantage of detecting primary CH and subclinical hypothyroidism and at a lower recall rate. Programs considering switching to a primary TSH test strategy need to develop age-related TSH cutoffs to maintain an acceptable recall rate. Both test strategies have the potential to detect infants with CH characterized by "delayed TSH rise," but only if they collect a routine or discretionary second specimen, now recommended in low-birth-weight and acutely ill infants. Lastly, a lower TSH cutoff appears to be one of the explanations for the recently described increased incidence of CH. PMID:20195902

  17. Expanded newborn screening in New South Wales: missed cases.

    PubMed

    Estrella, Jane; Wilcken, Bridget; Carpenter, Kevin; Bhattacharya, Kaustuv; Tchan, Michel; Wiley, Veronica

    2014-11-01

    There have been few reports of cases missed by expanded newborn screening. Tandem mass spectrometry was introduced in New South Wales, Australia in 1998 to screen for selected disorders of amino acid, organic acid and fatty acid metabolism. Of 1,500,000 babies screened by 2012, 1:2700 were diagnosed with a target disorder. Fifteen affected babies were missed by testing, and presented clinically or in family studies. In three cases (cobalamin C defect, very-long-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type 1), this led to modification of analyte cut-off values or protocols during the first 3 years. Two patients with intermittent MSUD, two with β-ketothiolase deficiency, two with citrin deficiency, two siblings with arginosuccinic aciduria, two siblings with homocystinuria, and one with cobalamin C defect had analyte values and ratios below the action limits which could not have been detected without unacceptable false-positive rates. A laboratory interpretation error led to missing one case of cobalamin C defect. Reference ranges, regularly reviewed, were not altered. For citrin deficiency, while relevant metabolites are detectable by tandem mass spectrometry, our cut-off values do not specifically screen for that disorder. Most of the missed cases are doing well and with no acute presentations although eight of 15 are likely to have been somewhat adversely affected by a late diagnosis. Analyte ratio and cut-off value optimisations are important, but for some disorders occasional missed cases may have to be tolerated to maintain an acceptable specificity, and avoid harm from screening. PMID:24970580

  18. Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes

    PubMed Central

    Howard, Heidi Carmen; Knoppers, Bartha Maria; Cornel, Martina C; Wright Clayton, Ellen; Sénécal, Karine; Borry, Pascal

    2015-01-01

    The advent and refinement of sequencing technologies has resulted in a decrease in both the cost and time needed to generate data on the entire sequence of the human genome. This has increased the accessibility of using whole-genome sequencing and whole-exome sequencing approaches for analysis in both the research and clinical contexts. The expectation is that more services based on these and other high-throughput technologies will become available to patients and the wider population. Some authors predict that sequencing will be performed once in a lifetime, namely, shortly after birth. The Public and Professional Policy Committee of the European Society of Human Genetics, the Human Genome Organisation Committee on Ethics, Law and Society, the PHG Foundation and the P3G International Paediatric Platform address herein the important issues and challenges surrounding the potential use of sequencing technologies in publicly funded newborn screening (NBS) programmes. This statement presents the relevant issues and culminates in a set of recommendations to help inform and guide scientists and clinicians, as well as policy makers regarding the necessary considerations for the use of genome sequencing technologies and approaches in NBS programmes. The primary objective of NBS should be the targeted analysis and identification of gene variants conferring a high risk of preventable or treatable conditions, for which treatment has to start in the newborn period or in early childhood. PMID:25626707

  19. Genome Screen to Detect Linkage to Intracranial Aneurysm Susceptibility Genes

    PubMed Central

    Foroud, Tatiana; Sauerbeck, Laura; Brown, Robert; Anderson, Craig; Woo, Daniel; Kleindorfer, Dawn; Flaherty, Matthew L.; Deka, Ranjan; Hornung, Richard; Meissner, Irene; Bailey-Wilson, Joan E.; Rouleau, Guy; Sander Connolly, E.; Lai, Dongbing; Koller, Daniel L.; Huston, John; Broderick, Joseph P.

    2008-01-01

    Background and Purpose Evidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA. Methods Multiplex families having at least 2 individuals with “definite” or “probable” IA were ascertained through an international consortium. First-degree relatives of individuals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped individuals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene×smoking (pack-years) interaction. Results The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5; 156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using the broad disease definition. Using the average pack-years for the affected individuals in each family, the genes on chromosomes 4 (LOD=3.5; P=0.03), 7 (LOD=4.1; P=0.01) and 12 (LOD=3.6; P=0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking. Conclusions We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene×smoking interaction with 3 of the loci. PMID:18323491

  20. The Newborn Screening Quality Assurance Program at the Centers for Disease Control and Prevention: Thirty-five Year Experience Assuring Newborn Screening Laboratory Quality

    PubMed Central

    De Jesús, Víctor R.; Mei, Joanne V.; Cordovado, Suzanne K.; Cuthbert, Carla D.

    2015-01-01

    Newborn screening is the largest genetic testing effort in the United States and is considered one of the ten great public health achievements during the first 10 years of the 21st century. For over 35 years, the Newborn Screening Quality Assurance Program (NSQAP) at the US Centers for Disease Control and Prevention has helped NBS laboratories ensure that their testing does not delay diagnosis, minimizes false-positive reports, and sustains high-quality testing performance. It is a multi-component program that provides comprehensive quality assurance services for dried blood spot testing. The NSQAP, the Biochemical Mass Spectrometry Laboratory (BMSL), the Molecular Quality Improvement Program (MQIP) and the Newborn Screening Translation Research Initiative (NSTRI), aid screening laboratories achieve technical proficiency and maintain confidence in their performance while processing large volumes of specimens daily. The accuracy of screening tests could be the difference between life and death for many babies; in other instances, identifying newborns with a disorder means that they can be treated and thus avoid life-long disability or severe cognitive impairment. Thousands of newborns and their families have benefited from reliable and accurate testing that has been accomplished by a network of screening laboratories and the NSQAP, BMSL, MQIP and NSTRI. PMID:26309908

  1. Review of Current International Decision-Making Processes for Newborn Screening: Lessons for Australia

    PubMed Central

    Metternick-Jones, Selina Carolyne; Lister, Karla Jane; Dawkins, Hugh J. S.; White, Craig Anthony; Weeramanthri, Tarun Stephen

    2015-01-01

    Newborn bloodspot screening has been operating successfully in Australia for almost 50 years. Recently, the development of new technologies and treatments has led to calls for the addition of new conditions to the screening programs. Internationally, it is recognized by governments that national policies for newborn screening should support transparent and evidence-based decision making, and promote consistency between states within a country. Australia is lagging behind the international community, and currently has no national policies or decision-making processes, agreed by government, to support its newborn screening programs. In contrast, New Zealand (NZ), the United Kingdom (UK), and the United States of America (US) have robust and transparent processes to assess conditions for screening, which have been developed by, and have pathways to, government. This review provides detail on the current policy environment for newborn screening in Australia, highlighting that there are a number of risks to the programs resulting from the lack of a decision-making process. It also describes the processes used to assess conditions for newborn screening in the US, UK, and NZ. These examples highlight the benefits of developing a national decision-making process, including ensuring that screening is evidence based and effective. These examples also provide models that might be considered for Australia, as well as other countries currently seeking to introduce or expand newborn bloodspot screening. PMID:26442241

  2. Successful newborn screening for SCID in the Navajo Nation.

    PubMed

    Kwan, Antonia; Hu, Diana; Song, Miran; Gomes, Heidi; Brown, Denise R; Bourque, Trudy; Gonzalez-Espinosa, Diana; Lin, Zhili; Cowan, Morton J; Puck, Jennifer M

    2015-05-01

    Newborn screening (NBS) for severe combined immunodeficiency (SCID) identifies affected infants before the onset of life-threatening infections, permitting optimal treatment. Navajo Native Americans have a founder mutation in the DNA repair enzyme Artemis, resulting in frequent Artemis SCID (SCID-A). A pilot study at 2 Navajo hospitals assessed the feasibility of SCID NBS in this population. Dried blood spots from 1800 infants were assayed by PCR for T-cell receptor excision circles (TRECs), a biomarker for naïve T cells. Starting in February 2012, TREC testing transitioned to standard care throughout the Navajo Area Indian Health Service, and a total of 7900 infants were screened through July 2014. One infant had low TRECs and was diagnosed with non-SCID T lymphopenia, while 4 had undetectable TRECs due to SCID-A, all of whom were referred for hematopoietic cell transplantation. This report establishes the incidence of SCID-A and demonstrates effectiveness of TREC NBS in the Navajo. PMID:25762520

  3. Newborn Hearing Screening in Neonates Exposed to Psychoactive Drugs

    PubMed Central

    Rocha, Bruna Salazar Castro da; Machado, Márcia Salgado; Zanini, Cláudia Fernandes Costa; Paniz, Tatiana de Carvalho; Menegotto, Isabela Hoffmeister

    2013-01-01

    Introduction In pregnancy, the mother and fetus share body structures based on the maternal organism. Exposure to psychoactive drugs in this period may have repercussions on the baby's hearing. Therefore, it is necessary to investigate this association. Aim Analyze the results of newborn hearing screening (NHS), the occurrence of associated risk factors, and the incidence of hearing loss in newborn exposed to psychoactive drugs during pregnancy. Methods This is an observational retrospective study done from a database analysis. From this database, records were selected about the use of psychoactive drugs by mothers during pregnancy, then the neonates were divide into two groups: the study group (146 babies exposed to drugs) and the control group (500 babies not exposed to drugs). The NHS failure rate, the presence of risk factors for hearing loss, and need for audiological diagnosis were analyzed in both groups. From these variables, absolute frequency and prevalence rates were calculated and the results compared between groups. Results There was no statistically significant difference in the comparison of NHS failure rates between the groups (p = 0.267). The occurrence of risk factors for hearing loss was greater in babies exposed to drugs (p < 0.0001). There was only one diagnosis of hearing loss, which occurred in the control group (p = 0.667). Conclusion The use of psychoactive drugs by mothers during pregnancy did not affect the NHS failure rate of this sample. However, the occurrence of significant risk factors in the study group showed a possible sensitivity of babies exposed to psychoactive drugs during pregnancy. PMID:25992062

  4. Ethical and policy issues in newborn screening of children for neurologic and developmental disorders.

    PubMed

    Ross, Lainie Friedman

    2015-06-01

    Genetic testing for neurologic and developmental disorders spans the spectrum from universal newborn screening for conditions like phenylketonuria to diagnostic testing for suspected genetic conditions, to predictive genetic testing for childhood-onset conditions. Given that virtually all children in the United States undergo genetic screening in the newborn period, this article focuses on 3 actual case studies of neurologic and developmental disorders that have been included or proposed for inclusion in newborn screening programs: Duchenne muscular dystrophy (a neuromuscular disorder), Krabbe disease (a neurodegenerative disorder), and fragile X syndrome (a neurodevelopmental disorder). PMID:26022175

  5. A newborn screening system based on service-oriented architecture embedded support vector machine.

    PubMed

    Hsu, Kai-Ping; Hsieh, Sung-Huai; Hsieh, Sheau-Ling; Cheng, Po-Hsun; Weng, Yung-Ching; Wu, Jang-Hung; Lai, Feipei

    2010-10-01

    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. PMID:20703618

  6. The Dried Bloodspot: Newborn Screening Research Saving the Lives of Babies

    ERIC Educational Resources Information Center

    Levy-Fisch, Jill; Gartzke, Micki; Leight, Kelly

    2010-01-01

    Newborn screening is a test done on every child born in the US shortly after birth to detect diseases where, if not diagnosed and treated in the newborn period, the child will suffer significant trauma, disability or die. A few drops of blood from each baby's heel is put on a card and sent to the state's public health lab for testing. Most states…

  7. Newborn screening of phenylketonuria using direct analysis in real time (DART) mass spectrometry.

    PubMed

    Wang, Chunyan; Zhu, Hongbin; Cai, Zongwei; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2013-04-01

    Phenylketonuria (PKU) is commonly included in the newborn screening panel of most countries, with various techniques being used for quantification of L-phenylalanine (Phe). To diagnose PKU as early as possible in newborn screening, a rapid and simple method of analysis was developed. Using direct analysis in real time (DART) ionization coupled with triple-quadrupole tandem mass spectrometry (TQ-MS/MS) and with use of a 12 DIP-it tip scanner autosampler in positive ion mode, we analyzed dried blood spot (DBS) samples from PKU newborns. The concentration of Phe was determined using multiple reaction monitoring mode with the nondeuterated internal standard N,N-dimethylphenylalanine. The results of the analysis of DBS samples from newborns indicated that the DART-TQ-MS/MS method is fast, accurate, and reproducible. The results prove that this assay as a newborn screen for PKU can be performed in 18 s per sample for the quantification of Phe in DBS samples. DART-TQ-MS/MS analysis of the Phe concentration in DBS samples allowed us to screen newborns for PKU. This innovative protocol is rapid and can be effectively applied on a routine basis to analyze a large number of samples in PKU newborn screening and PKU patient monitoring. PMID:23397086

  8. History and Current Status of Newborn Screening for Severe Combined Immunodeficiency

    PubMed Central

    Kwan, Antonia; Puck, Jennifer M.

    2015-01-01

    The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots in universal newborn screening has allowed the early detection of T cell lymphopenia in newborns. Diagnosis of severe combined immunodeficiency (SCID) in affected infants in the neonatal period while asymptomatic permits early treatment and restoration of a functional immune system. SCID was the first immunodeficiency disease to be added to the Recommended Uniform Screening Panel of Core Conditions in the United States in 2010, and is now implemented in 26 states in the U.S. This review covers the development of newborn screening for SCID, the biology of the TREC test, its current implementation in the U.S., new findings for SCID in the newborn screening era, and future directions. PMID:25937517

  9. Screening Newborns' Hearing Now Standard | NIH MedlinePlus the Magazine

    MedlinePlus

    ... the hospital. Combined with similar recommendations by the Joint Committee on Infant Hearing, and further research and workshops supported by the NIDCD, universal newborn hearing screening began in 1999, when President ...

  10. Public views on participating in newborn screening using genome sequencing.

    PubMed

    Bombard, Yvonne; Miller, Fiona A; Hayeems, Robin Z; Barg, Carolyn; Cressman, Celine; Carroll, June C; Wilson, Brenda J; Little, Julian; Avard, Denise; Painter-Main, Michael; Allanson, Judith; Giguere, Yves; Chakraborty, Pranesh

    2014-11-01

    Growing discussion on the use of whole-genome or exome sequencing (WG/ES) in newborn screening (NBS) has raised concerns regarding the generation of incidental information on millions of infants annually. It is unknown whether integrating WG/ES would alter public expectations regarding participation in universal NBS. We assessed public willingness to participate in NBS using WG/ES compared with current NBS. Our secondary objective was to assess the public's beliefs regarding a parental responsibility to participate in WG/ES-based NBS compared with current NBS. We examined self-reported attitudes regarding willingness to participate in NBS using a cross-sectional national survey of Canadian residents recruited through an internet panel, reflective of the Canadian population by age, gender and region. Our results showed that fewer respondents would be willing to participate in NBS using WG/ES compared with NBS using current technologies (80 vs 94%, P<0.001), or perceived a parental responsibility to participate in WG/ES-based NBS vs current NBS (30 vs 48%, P<0.001). Our findings suggest that integrating WG/ES into NBS might reduce participation, and challenge the moral authority that NBS programmes rely upon to ensure population benefits. These findings point to the need for caution in the untargeted use of WG/ES in public health contexts. PMID:24549052

  11. Mass spectrometry in clinical chemistry: the case of newborn screening.

    PubMed

    la Marca, Giancarlo

    2014-12-01

    Newborn screening (NBS) program is a complex and organized system consisting of family and personnel education, biochemical tests, confirmatory biochemical and genetic tests, diagnosis, therapy, and patient follow up. The program identifies treatable metabolic disorders possibly when asymptomatic by using dried blood spot (DBS). During the last 20 years tandem mass spectrometry (TMS) has become the leading technology in NBS programs demonstrating to be versatile, sensitive and specific. There is consistent evidence of benefits from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fibrosis, congenital adrenal hyperplasia by immune-enzymatic methods. Real time PCR tests have more recently been proposed for the detection of some severe combined immunodeficiences (SCID) along with the use of TMS for ADA and PNP SCID; a first evaluation of their cost-benefit ratio is still ongoing. Avoiding false negative results by using specific biomarkers and reducing the false positive rate by using second tier tests, is fundamental for a successful NBS program. The fully integration of NBS and diagnostic laboratories with clinical service is crucial to have the best effectiveness in a comprehensive NBS system. PMID:24844843

  12. Opportunities for Quality Improvement in Cystic Fibrosis Newborn Screening

    PubMed Central

    Groose, Molly K.; Reynolds, Richard; Li, Zhanhai; M.Farrell, Philip

    2010-01-01

    Background With the rapid implementation of cystic fibrosis (CF) newborn screening (NBS), quality improvement (QI) has become essential to identify and prevent errors. Using Process Failure Modes and Effects Analysis (PFMEA), we adapted this method to determine if it could be applied to discover and rank high priority QI opportunities. Methods Site visits to three programmes were conducted, and PFMEA exercises were accomplished in Colorado, Massachusetts and Wisconsin with 23 experienced professionals. During each of these comprehensive sessions, participants identified and ranked potential failures based on severity, occurrence and detection to calculate risk priority number (RPN) values. Results A total of 96 failure modes were generated and ranked in a list of the 20 riskiest problems that show no significant discordances by site, although there were differences by profession of the rater, particularly nurses. Conclusions Our results illustrate that the PFMEA method applies well to CF NBS and that steps requiring communication and information transfer are perceived to be the highest risks. The number of identified failure makes and their potential impact demonstrate considerable overall risk and a need for ongoing QI. PMID:20471332

  13. Informing parents about positive newborn screen results: parents' recommendations.

    PubMed

    Salm, Natalie; Yetter, Elena; Tluczek, Audrey

    2012-12-01

    This descriptive study examined parents' reactions to newborn screening (NBS) results and their recommendations for improving communication. Dimensional and content analyses were conducted on interviews with 203 parents of 106 infants having positive NBS results. Diagnostic results confirmed infants as having congenital hypothyroidism (n = 37), cystic fibrosis (n = 26), or being cystic fibrosis (CF)-carriers (n = 43). Parents' reactions ranged from 'very scary' to 'not too concerned'. Most reported feeling shock, panic, and worry; some reported guilt. Parents in the CF and CF-carrier groups preferred face-to-face disclosure as the communication channel; whereas congenital hypothyroidism group parents supported telephone contacts. Parents recommended providers be well informed, honest, and calm; personalize disclosure, avoid jargon, listen carefully, encourage questions, recognize parental distress, offer realistic reassurance, pace amount and rate of information, assess parents' understanding, and refer to specialists. We conclude that provider-patient communication approach and channel can exacerbate or alleviate parents' negative reactions to positive NBS results. PMID:22984167

  14. Financing newborn screening: sources, issues, and future considerations.

    PubMed

    Therrell, Bradford L; Williams, Donna; Johnson, Kay; Lloyd-Puryear, Michele A; Mann, Marie Y; Ramos, Lauren Raskin

    2007-01-01

    Newborn screening (NBS) programs are population-based public health programs and are uniquely financed footline compared with many other public health programs. Since they began more than 45 years ago, the financing issues have become more complex for NBS programs. Today, almost all programs have a portion of their costs paid by fees. The fee amounts vary from program to program, with little standardization in the way they are formulated, collected, or used. We previously surveyed 37 of the 51 dried blood spot screening programs throughout the United States, and confirmed an increasing dependence on NBS fees. In this study, we have collected responses from all 51 programs (100%), including updated responses from the original 37, and updated our fee listings. Comments from those surveyed indicated that the lack of a national standardized procedural coding system for NBS contributes to billing complexities. We suggest one coding possibility for discussion and debate for such a system. Differences in Medicaid interpretations may also contribute to financing inequities across NBS programs and there may be benefit from certain clarifications at the national level. Completed survey responses accounted for few changes in the conclusions of our original survey. We confirmed that 90 percent of all NBS programs have a fee paid by parents or a third party payer. Sixty-one percent reported receiving some funds from the Maternal and Child Health Services Title V block grant, 33 percent reported some funding from state general revenue/general public health appropriations; and 24 percent reported obtaining direct reimbursement from Medicaid (without passing through a third party). A majority of programs (63%) reported budget increases between 2002 and 2005, with increases primarily from fees (72%) and to a lesser extent from Medicaid, the Title V block grant, and state general revenues. PMID:17299328

  15. Newborn screening for cystic fibrosis. The Cystic Fibrosis Neonatal Screening Study Group.

    PubMed

    Farrell, P M; Mischler, E H

    1992-01-01

    Many questions remain regarding the efficacy, risks, and costs of CF neonatal screening. The major gap in knowledge that must be closed before CF neonatal screening can be recommended generally in the United States concerns the potential long-term medical benefits of initiating treatment in early infancy. It would be premature, in our opinion, to implement mass population screening of newborns for CF until the benefits and risks have been fully defined, and an adequate and logistically feasible testing system developed and/or highly effective therapy for CF lung disease becomes available. It is for this reason we designed a randomized, controlled investigation of CF neonatal screening and implemented this project in Wisconsin during 1985. The fact that 5 years of randomized screening and systematic evaluation of outcome measures have not yet revealed any pulmonary benefits underscores the importance of rigorous investigation to resolve the efficacy issue. In addition to the medical uncertainties, we believe that the ethical issues described herein need to be resolved; this concern pertains not only to the CF patient but also the heterozygote carrier. On the other hand, financial factors and uncertainty about the cost effectiveness of CF neonatal screening do not appear to be dominant issues according to our assessment of current data. Despite the reservations related to the benefit/risk relationship, we expect that the discovery of the CF gene should have a favorable impact on neonatal screening for the disease, as well as for management. PMID:1442316

  16. Development of a Newborn Screening Program for Critical Congenital Heart Disease (CCHD) in Taipei

    PubMed Central

    Chiang, Szu-Hui; Ho, Hui-Chen; Liu, Yu-Ling; Chung, Yuan-Fang; Lin, Li-Ju; Chen, Ming-Ren; Chang, Jia-Kan; Soong, Wen-Jue; Lin, Hsiu-Lian; Hwang, Betau; Hsiao, Kwang-Jen

    2016-01-01

    Background Early detection of critical congenital heart disease (CCHD) can significantly reduce morbidity and mortality among newborns. We investigate the feasibility of implementing a community-based newborn CCHD screening program in Taipei. Methods Twelve birthing facilities in Taipei participated in a trial screening program between October 1, 2013, and March 31, 2014. Newborns underwent pulse oximetry at 24–36 h old, with probes attached to the right hand and one lower limb. Any screening saturation ≥95% in either extremity, with an absolute difference of ≤3% between the right hand and foot, was accepted as a screening pass. A screening result was considered as a fail if the oxygen saturation was <95% at either probe site, on 3 separate occasions, each separated by 30 min or the first result was <95% at either probe site, and any subsequent oxygen saturation measurement was <90%. Public health nurses would follow up all missed or refused cases. Results Of the 6,387 live births, 6,296 newborns (coverage rate: 6,296/6,387 = 98.6%) underwent appropriate pulse oximetry screening. Sixteen newborns (0.25%) were reported to have a failed screening result. Five of these screen positive newborns were confirmed with CCHD; two of them were diagnosed solely attributed to the failed screening results. The false-positive rate was 0.18%. Implementing a 6-month screening program for CCHD produced good case detection rate, while using efficient screening and referral systems. Conclusion This program was successful in integrating screening, referral and public health tracking systems. The protocol outlined in this report could provide a community-based model for worldwide implementation. PMID:27073996

  17. Detection of critical congenital heart defects: Review of contributions from prenatal and newborn screening.

    PubMed

    Olney, Richard S; Ailes, Elizabeth C; Sontag, Marci K

    2015-04-01

    In 2011, statewide newborn screening programs for critical congenital heart defects began in the United States, and subsequently screening has been implemented widely. In this review, we focus on data reports and collection efforts related to both prenatal diagnosis and newborn screening. Defect-specific, maternal, and geographic factors are associated with variations in prenatal detection, so newborn screening provides a population-wide safety net for early diagnosis. A new web-based repository is collecting information on newborn screening program policies, quality indicators related to screening programs, and specific case-level data on infants with these defects. Birth defects surveillance programs also collect data about critical congenital heart defects, particularly related to diagnostic timing, mortality, and services. Individuals from state programs, federal agencies, and national organizations will be interested in these data to further refine algorithms for screening in normal newborn nurseries, neonatal intensive care settings, and other special populations; and ultimately to evaluate the impact of screening on outcomes. PMID:25979782

  18. Detection of critical congenital heart defects: Review of contributions from prenatal and newborn screening

    PubMed Central

    Olney, Richard S.; Ailes, Elizabeth C.; Sontag, Marci K.

    2015-01-01

    In 2011, statewide newborn screening programs for critical congenital heart defects began in the United States, and subsequently screening has been implemented widely. In this review, we focus on data reports and collection efforts related to both prenatal diagnosis and newborn screening. Defect-specific, maternal, and geographic factors are associated with variations in prenatal detection, so newborn screening provides a population-wide safety net for early diagnosis. A new web-based repository is collecting information on newborn screening program policies, quality indicators related to screening programs, and specific case-level data on infants with these defects. Birth defects surveillance programs also collect data about critical congenital heart defects, particularly related to diagnostic timing, mortality, and services. Individuals from state programs, federal agencies, and national organizations will be interested in these data to further refine algorithms for screening in normal newborn nurseries, neonatal intensive care settings, and other special populations; and ultimately to evaluate the impact of screening on outcomes. PMID:25979782

  19. Specific guidelines for assessing and improving the methodological quality of economic evaluations of newborn screening

    PubMed Central

    2012-01-01

    Background Economic evaluation of newborn screening poses specific methodological challenges. Amongst others, these challenges refer to the use of quality adjusted life years (QALYs) in newborns, and which costs and outcomes need to be considered in a full evaluation of newborn screening programmes. Because of the increasing scale and scope of such programmes, a better understanding of the methods of high-quality economic evaluations may be crucial for both producers/authors and consumers/reviewers of newborn screening-related economic evaluations. The aim of this study was therefore to develop specific guidelines designed to assess and improve the methodological quality of economic evaluations in newborn screening. Methods To develop the guidelines, existing guidelines for assessing the quality of economic evaluations were identified through a literature search, and were reviewed and consolidated using a deductive iterative approach. In a subsequent test phase, these guidelines were applied to various economic evaluations which acted as case studies. Results The guidelines for assessing and improving the methodological quality of economic evaluations in newborn screening are organized into 11 categories: “bibliographic details”, “study question and design”, “modelling”, “health outcomes”, “costs”, “discounting”, “presentation of results”, “sensitivity analyses”, “discussion”, “conclusions”, and “commentary”. Conclusions The application of the guidelines highlights important issues regarding newborn screening-related economic evaluations, and underscores the need for such issues to be afforded greater consideration in future economic evaluations. The variety in methodological quality detected by this study reveals the need for specific guidelines on the appropriate methods for conducting sound economic evaluations in newborn screening. PMID:22947299

  20. Screening of Newborns for Disorders with High Benefit-Risk Ratios Should Be Mandatory.

    PubMed

    Kelly, Nicole; Makarem, Dalia Chehayeb; Wasserstein, Melissa P

    2016-06-01

    Newborn screening has evolved to include an increasingly complex spectrum of diseases, raising concerns that screening should be optional and require parental consent. Early detection of disorders like PKU and MCAD is essential to prevent serious disability and death in affected children. These are examples of high benefit-risk ratio disorders because of the irrefutable health benefits of early detection, coupled with the low risks of treatment. The dire consequences of not diagnosing an infant with a treatable disorder because of parental refusal to screen are wholly unacceptable. Thus, we believe that newborn screening for disorders with high benefit-risk ratios should continue to be mandatory. PMID:27338599

  1. Supporting Parental Decisions About Genomic Sequencing for Newborn Screening: The NC NEXUS Decision Aid.

    PubMed

    Lewis, Megan A; Paquin, Ryan S; Roche, Myra I; Furberg, Robert D; Rini, Christine; Berg, Jonathan S; Powell, Cynthia M; Bailey, Donald B

    2016-01-01

    Advances in genomic sequencing technology have raised fundamental challenges to the traditional ways genomic information is communicated. These challenges will become increasingly complex and will affect a much larger population in the future if genomics is incorporated into standard newborn screening practice. Clinicians, public health officials, and other stakeholders will need to agree on the types of information that they should seek and communicate to parents. Currently, few evidence-based and validated tools are available to support parental informed decision-making. These tools will be necessary as genomics is integrated into clinical practice and public health systems. In this article we describe how the North Carolina Newborn Exome Sequencing for Universal Screening study is addressing the need to support parents in making informed decisions about the use of genomic testing in newborn screening. We outline the context for newborn screening and justify the need for parental decision support. We also describe the process of decision aid development and the data sources, processes, and best practices being used in development. By the end of the study, we will have an evidenced-based process and validated tools to support parental informed decision-making about the use of genomic sequencing in newborn screening. Data from the study will help answer important questions about which genomic information ought to be sought and communicated when testing newborns. PMID:26729698

  2. Supporting Parental Decisions About Genomic Sequencing for Newborn Screening: The NC NEXUS Decision Aid

    PubMed Central

    Lewis, Megan A.; Paquin, Ryan S.; Roche, Myra I.; Furberg, Robert D.; Rini, Christine; Berg, Jonathan S.; Powell, Cynthia M.; Bailey, Donald B.

    2016-01-01

    Advances in genomic sequencing technology have raised fundamental challenges to the traditional ways genomic information is communicated. These challenges will become increasingly complex and will affect a much larger population in the future if genomics is incorporated into standard newborn screening practice. Clinicians, public health officials, and other stakeholders will need to agree on the types of information that they should seek and communicate to parents. Currently, few evidence-based and validated tools are available to support parental informed decision-making. These tools will be necessary as genomics is integrated into clinical practice and public health systems. In this article we describe how the North Carolina Newborn Exome Sequencing for Universal Screening study is addressing the need to support parents in making informed decisions about the use of genomic testing in newborn screening. We outline the context for newborn screening and justify the need for parental decision support. We also describe the process of decision aid development and the data sources, processes, and best practices being used in development. By the end of the study, we will have an evidenced-based process and validated tools to support parental informed decision-making about the use of genomic sequencing in newborn screening. Data from the study will help answer important questions about which genomic information ought to be sought and communicated when testing newborns. PMID:26729698

  3. Improving newborn screening laboratory test ordering and result reporting using health information exchange.

    PubMed

    Downs, Stephen M; van Dyck, Peter C; Rinaldo, Piero; McDonald, Clement; Howell, R Rodrey; Zuckerman, Alan; Downing, Gregory

    2010-01-01

    Capture, coding and communication of newborn screening (NBS) information represent a challenge for public health laboratories, health departments, hospitals, and ambulatory care practices. An increasing number of conditions targeted for screening and the complexity of interpretation contribute to a growing need for integrated information-management strategies. This makes NBS an important test of tools and architecture for electronic health information exchange (HIE) in this convergence of individual patient care and population health activities. For this reason, the American Health Information Community undertook three tasks described in this paper. First, a newborn screening use case was established to facilitate standards harmonization for common terminology and interoperability specifications guiding HIE. Second, newborn screening coding and terminology were developed for integration into electronic HIE activities. Finally, clarification of privacy, security, and clinical laboratory regulatory requirements governing information exchange was provided, serving as a framework to establish pathways for improving screening program timeliness, effectiveness, and efficiency of quality patient care services. PMID:20064796

  4. Improving newborn screening laboratory test ordering and result reporting using health information exchange

    PubMed Central

    van Dyck, Peter C; Rinaldo, Piero; McDonald, Clement; Howell, R Rodrey; Zuckerman, Alan; Downing, Gregory

    2010-01-01

    Capture, coding and communication of newborn screening (NBS) information represent a challenge for public health laboratories, health departments, hospitals, and ambulatory care practices. An increasing number of conditions targeted for screening and the complexity of interpretation contribute to a growing need for integrated information-management strategies. This makes NBS an important test of tools and architecture for electronic health information exchange (HIE) in this convergence of individual patient care and population health activities. For this reason, the American Health Information Community undertook three tasks described in this paper. First, a newborn screening use case was established to facilitate standards harmonization for common terminology and interoperability specifications guiding HIE. Second, newborn screening coding and terminology were developed for integration into electronic HIE activities. Finally, clarification of privacy, security, and clinical laboratory regulatory requirements governing information exchange was provided, serving as a framework to establish pathways for improving screening program timeliness, effectiveness, and efficiency of quality patient care services. PMID:20064796

  5. Evaluating Harms in the Assessment of Net Benefit: A Framework for Newborn Screening Condition Review.

    PubMed

    Goldenberg, Aaron J; Comeau, Anne Marie; Grosse, Scott D; Tanksley, Susan; Prosser, Lisa A; Ojodu, Jelili; Botkin, Jeffrey R; Kemper, Alex R; Green, Nancy S

    2016-03-01

    Background The Department of Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children ("Advisory Committee") makes recommendations to the HHS Secretary regarding addition of new conditions to the national Recommended Uniform Screening Panel for newborns. The Advisory Committee's decision-making process includes assessing the net benefit of screening for nominated conditions, informed by systematic evidence reviews generated by an independent Condition Review Workgroup. The evidence base regarding harms associated with screening for specific conditions is often more limited than that for benefits. Procedures The process for defining potential harms from newborn screening reviewed the frameworks from other public health evidence-based review processes, adapted to newborn screening by experts in systematic review, newborn screening programs and bioethics, with input from and approval by the Advisory Committee. Main findings To support the Advisory Committee's review of nominated conditions, the Workgroup has developed a standardized approach to evaluation of harms and relevant gaps in the evidence. Types of harms include the physical burden to infants; psychosocial and logistic burdens to families from screening or diagnostic evaluation; increased risk of medical treatment for infants diagnosed earlier than children with clinical presentation; delayed diagnosis from false negative results; psychosocial harm from false positive results; uncertainty of clinical diagnosis, age of onset or clinical spectrum; and disparities in access to diagnosis or therapy. Conclusions Estimating the numbers of children at risk, the magnitude, timing and likelihood of harms will be integrated into Workgroup reports to the Advisory Committee. PMID:26833040

  6. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  7. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  8. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  9. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  10. Newborn screening for metabolic diseases: saving children's lives and improving outcomes.

    PubMed

    Bennett, Michael J

    2014-06-01

    Newborn screening for metabolic diseases was initially introduced in the 1960s with a program for the early diagnosis of phenylketonuria. Guidelines for the introduction of additional conditions to the screen required that the condition was sufficiently common to merit screening, that it was treatable and that the cost of diagnosis was not prohibitive. Additional conditions added to the screen included congenital hypothyroidism and congenital adrenal hyperplasia. The recognition of medium-chain acyl0CoA dehydrogenase deficiency coupled to the advent of tandem mass spectrometry as a diagnostic tool allowed for the inclusion of many more conditions into screening programs, some of which do not fit the original criteria for inclusion. This presentation will discuss the current state of newborn screening for metabolic diseases and report on clinical outcome measures of patients identified by screening. PMID:24886768

  11. Current Sickle Cell Screening Program for Newborns in New York City, 1979-1980.

    ERIC Educational Resources Information Center

    Grover, Ranjeet; And Others

    1983-01-01

    Screening tests indicated that 141 out of 106,565 infants examined in New York City during 1979-80, had various forms of sickle cell anemia. Follow-up of 131 patients confirmed the original diagnoses, suggesting that the New York City Follow-up Program for Sickle Cell Screening of newborns was successful. (Author/MJL)

  12. Parents' Decisions to Screen Their Newborn for Fragile X Syndrome. FPG Snapshot #63

    ERIC Educational Resources Information Center

    FPG Child Development Institute, 2011

    2011-01-01

    State newborn screening (NBS) programs have expanded in recent years, and more tests may be added in the future. The expansion of neonatal screening raises ethical, legal, and social questions. The questions surrounding NBS for fragile X syndrome (FXS) typify these concerns. FXS is an X-linked genetic condition that is the most common inherited…

  13. Newborn Screening for Genetic-Metabolic Diseases: Progress, Principles and Recommendations.

    ERIC Educational Resources Information Center

    Holtzman, Neil A.

    This monograph, designed for persons involved in the organization and regulation of screening of newborns infants for Phenylketonuria (PKU) and other genetic-metabolic diseases reviews new developments in the field, makes recommendations, and provides information about specific conditions other than PKU that are detectable by screening. Discussed…

  14. Newborn screening healthcare information system based on service-oriented architecture.

    PubMed

    Hsieh, Sung-Huai; Hsieh, Sheau-Ling; Chien, Yin-Hsiu; Weng, Yung-Ching; Hsu, Kai-Ping; Chen, Chi-Huang; Tu, Chien-Ming; Wang, Zhenyu; Lai, Feipei

    2010-08-01

    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. PMID:20703906

  15. State Laws Regarding the Retention and Use of Residual Newborn Screening Blood Samples

    PubMed Central

    Goldenberg, Aaron; Anderson, Rebecca; Rothwell, Erin; Botkin, Jeffrey

    2011-01-01

    BACKGROUND: After newborn screening has been completed, many states retain residual newborn screening dried blood samples for various purposes, including program evaluation, quality assurance, and biomedical research. The extent to which states possess legal authority to retain residual dried blood samples (DBS) and use them for purposes unrelated to newborn screening is unclear. OBJECTIVE: The purpose of this study was to evaluate state laws regarding the retention and use of DBS. METHODS: State statutes and regulations related to newborn screening of all 50 states plus the District of Columbia were accessed online between November 2008 and December 2009 and reviewed by 2 independent reviewers to determine the extent to which the retention and use of DBS were addressed. RESULTS: The retention or use of DBS has not been addressed in 18 states. In 4 states, DBS becomes state property. Eight states require that parents be provided information regarding the retention of DBS. Parents in 5 states may request the destruction of their child's residual sample. Parental consent is required under certain circumstances to release DBS for research in 6 states. One state prohibits DBS from being used for research purposes. CONCLUSIONS: States have wide variability in their policies regarding the retention and use of DBS. Many states have not addressed key issues, and some states that retain DBS may be acting outside the scope of their legal authority. The lack of transparency on the part of states in retaining DBS may undermine public trust in state newborn screening programs and the research enterprise. PMID:21444595

  16. The knowledge gap in expanded newborn screening: survey results from paediatricians in Massachusetts.

    PubMed

    Gennaccaro, M; Waisbren, S E; Marsden, D

    2005-01-01

    Massachusetts currently offers an optional expanded newborn screening programme that tests for 20 biochemical genetic disorders in addition to the mandated newborn screening tests, including phenylketonuria (PKU) and nine other biochemical genetic disorders. We conducted a mail survey of 550 paediatricians listed in the 2000 Massachusetts Healthcare Directory to determine paediatricians' preparedness in discussing expanded newborn screening and its results with families, and to determine in what specific format physicians in Massachusetts would prefer to receive educational materials and updates. Of surveys mailed, 35% (190/550) were returned within the allotted 3 weeks: 25 paediatricians (14%) were unaware of expanded newborn screening; 78 respondents (42%) indicated feeling less than prepared talking about test results with families; 100 paediatricians (54%) indicated a lack of information about metabolic disorders; 134 (73%) preferred information sent in postal mailings, 62 (34%) preferred grand rounds, 60 (33%) preferred educational seminars, and 58 (32%) preferred websites. Other formats receiving preferences of less than 30% included e-mail (27%), phone calls (8%), video (6%), and distance learning (1%). Paediatricians are ill-prepared for expanded newborn screening for biochemical genetic disorders. To address this problem, paediatricians in Massachusetts indicated a preference for unsolicited periodic mailings including short reviews and brochures. PMID:16435173

  17. Effects of newborn screening of cystic fibrosis on reported maternal behaviour.

    PubMed

    Boland, C; Thompson, N L

    1990-11-01

    Screening for cystic fibrosis is highly controversial. Concerns have been expressed that newborn screening may cause mothers, who had considered their child to be healthy before diagnosis, to overprotect their child. Some critics of screening also suggest that a period of delay from onset of symptoms to diagnosis may help a mother adjust to the reality of the child's lethal condition. This study compared the strength of overprotective child rearing attitudes of 29 mothers whose children were screened (13 had symptomatic children and 16 asymptomatic children) with the attitudes of 29 mothers whose children were diagnosed after the onset of symptoms. Results indicate that newborn screening had not increased a mother's tendency to overprotect her child with cystic fibrosis and in some cases the tendency had decreased. Further, delay in diagnosis when screening was not conducted usually caused mothers considerable personal distress. PMID:2248536

  18. Newborn screening for citrin deficiency and carnitine uptake defect using second-tier molecular tests

    PubMed Central

    2013-01-01

    Background Tandem mass spectrometry (MS/MS) analysis is a powerful tool for newborn screening, and many rare inborn errors of metabolism are currently screened using MS/MS. However, the sensitivity of MS/MS screening for several inborn errors, including citrin deficiency (screened by citrulline level) and carnitine uptake defect (CUD, screened by free carnitine level), is not satisfactory. This study was conducted to determine whether a second-tier molecular test could improve the sensitivity of citrin deficiency and CUD detection without increasing the false-positive rate. Methods Three mutations in the SLC25A13 gene (for citrin deficiency) and one mutation in the SLC22A5 gene (for CUD) were analyzed in newborns who demonstrated an inconclusive primary screening result (with levels between the screening and diagnostic cutoffs). Results The results revealed that 314 of 46 699 newborns received a second-tier test for citrin deficiency, and two patients were identified; 206 of 30 237 newborns received a second-tier testing for CUD, and one patient was identified. No patients were identified using the diagnostic cutoffs. Although the incidences for citrin deficiency (1:23 350) and CUD (1:30 000) detected by screening are still lower than the incidences calculated from the mutation carrier rates, the second-tier molecular test increases the sensitivity of newborn screening for citrin deficiency and CUD without increasing the false-positive rate. Conclusions Utilizing a molecular second-tier test for citrin deficiency and carnitine transporter deficiency is feasible. PMID:23394329

  19. Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine Level.

    PubMed

    Ahrens-Nicklas, Rebecca C; Serdaroglu, Esra; Muraresku, Colleen; Ficicioglu, Can

    2015-01-01

    Cobalamin C (CblC) disease is the most common inherited disorder of intracellular cobalamin metabolism. It is a multisystemic disorder mainly affecting the eye and brain and characterized biochemically by methylmalonic aciduria, low methionine level, and homocystinuria. We report a patient found to have CblC disease who initially presented with low carnitine and normal propionylcarnitine (C3) levels on newborn screen. Newborn screening likely failed to detect CblC in this patient because of both his low carnitine level and the presence of a mild phenotype. PMID:25772322

  20. High 17-hydroxyprogesterone level in newborn screening test for congenital adrenal hyperplasia.

    PubMed

    Levy-Shraga, Yael; Pinhas-Hamiel, Orit

    2016-01-01

    We report a case of a female infant with an elevated 17-hydroxyprogesterone level detected in the newborn screening for 21-hydroxylase deficiency, the most common cause of congenital adrenal hyperplasia. The physical examination was unremarkable including no dysmorphism and no signs of virilisation. In the absence of clinical evidence of androgen excess, as would be expected in a female infant with 21-hydroxylase deficiency, further evaluation was performed and led to the diagnosis of the extremely rare disorder, 3β-hydroxysteroid dehydrogenase deficiency. This case highlights the differential diagnosis of elevated 17-hydroxyprogesterone levels in newborn screening and the importance of correct diagnosis for improving patient care. PMID:26912766

  1. Enhancing the quality and efficiency of newborn screening programs through the use of health information technology.

    PubMed

    Downing, Gregory J; Zuckerman, Alan E; Coon, Constanze; Lloyd-Puryear, Michele A

    2010-04-01

    A variety of efforts are underway at national, state, regional, and local levels to enhance the performance of programs for early detection of inherited diseases and conditions of newborn infants. Newborn screening programs serve a vital purpose in identifying nonsymptomatic clinical conditions and enabling early intervention strategies that lessen morbidity and mortality. Currently, the programs of most intense focus are early hearing detection and intervention, using physiological techniques for audiology screening and use of newborn dried blood spots for detection of metabolites or proteins representing inherited disorders. One of the primary challenges to effective newborn screening programs to date has been the inability to provide information in a timely and easily accessible way to a variety of users. Other challenging communication issues being faced include the complexity introduced by the diversity of conditions for which testing is conducted and laboratory methods being used by each state's screening programs, lack of an electronic information infrastructure to facilitate information exchange, and variation in policies that enable access to information while protecting patient privacy and confidentiality. In this study, we address steps being taken to understand these challenges, outline progress made to date to overcome them, and provide examples of how electronic health information exchange will enhance the utility of newborn screening. It is likely that future advances in science and technology will bring many more opportunities to prevent and preempt disabilities among children through early detection programs. To take their advantage, effective communication strategies are needed among the public health, primary care practice, referral/specialty service, and consumer advocacy communities to provide continuity of information required for medical decision-making throughout prenatal, newborn, and early childhood periods of patient care. PMID:20207265

  2. [Justification for the study screening newborn hearing screening in terms of regionalization of perinatal care in Ukraine].

    PubMed

    Shcherbyna, A V; Bychkov, V V

    2014-01-01

    Conducting research screening newborn hearing screening in terms of regional perinatal centers in Ukraine and further rehabilitation of children with hearing impairment is a key step in their integration into society. Universal newborn hearing screening should be mandatory, especially in perinatal centers, because it has significant medical, social and economic effects. It is also necessary to reorganize the existing regional offices surdologichesky and create on their bases and methodological Regional Medical Center hearing and speech problems, which will provide high-quality diagnosis, epidemiological data form, will hold the register of children diagnosed with hearing defects, organize them continuously active surveillance, hearing aids and effective rehabilitation, to ensure the quality of screening. Creating a distributed database for these patients, by far. Will achieve success in the integration of children with special needs in society. PMID:25286608

  3. Web-Based Newborn Screening System for Metabolic Diseases: Machine Learning Versus Clinicians

    PubMed Central

    Chen, Wei-Hsin; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

    2013-01-01

    Background A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. Objective The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. Methods The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets

  4. Newborn screening for autism: in search of candidate biomarkers

    PubMed Central

    Mizejewski, Gerald J; Lindau-Shepard, Barbara; Pass, Kenneth A

    2013-01-01

    Background Autism spectrum disorder (ASD) represents a wide range of neurodevelopmental disorders characterized by impairments in social interaction, language, communication and range of interests. Autism is usually diagnosed in children 3–5 years of age using behavioral characteristics; thus, diagnosis shortly after birth would be beneficial for early initiation of treatment. Aim This retrospective study sought to identify newborns at risk for ASD utilizing bloodspot specimens in an immunoassay. Materials & methods The present study utilized stored frozen specimens from ASD children already diagnosed at 15–36 months of age. The newborn specimens and controls were analyzed by immunoassay in a multiplex system that included 90 serum biomarkers and subjected to statisical analysis. Results Three sets of five biomarkers associated with ASD were found that differed from control groups. The 15 candidate biomarkers were then discussed regarding their association with ASD. Conclusion This study determined that a statistically selected panel of 15 biomarkers successfully discriminated presumptive newborns at risk for ASD from those of nonaffected controls. PMID:23547820

  5. Succinylacetone as Primary Marker to Detect Tyrosinemia Type I in Newborns and its Measurement by Newborn Screening Programs

    PubMed Central

    De Jesús, Víctor R.; Adam, Barbara W.; Mandel, Daniel; Cuthbert, Carla D.; Matern, Dietrich

    2015-01-01

    Tyrosinemia type I (TYR I) is caused by autosomal recessive fumarylacetoacetate hydrolase deficiency and is characterized by development of severe liver disease in infancy and neurologic crises. If left untreated, most patients die of liver failure in the first years of life. Intervention with medication is effective when initiated during the first month of life. This improvement in the treatment of TYR I patients influenced the decision to include TYR I in the US Secretary of the Department of Health and Human Services’ (HHS) Recommended Uniform Screening Panel. However, while tyrosine is routinely measured in newborn screening (NBS) by tandem mass spectrometry (MS/MS), elevated tyrosine levels are not specific to TYR I. To improve the specificity of NBS for TYR I, several assays were developed to measure succinylacetone (SUAC) in dried blood spots (DBS). SUAC is a pathognomonic marker of TYR I, and its detection by NBS MS/MS is possible. This review of the current status of NBS for TYR I in the US is the result of discussions at the HHS Secretary’s (Discretionary) Advisory Committee on Heritable Disorders in Newborns and Children about the inconsistent implementation of effective NBS for TYR I in the US. We sought to understand the different TYR I screening practices in US NBS programs. Results indicate that 50 out of 51 NBS programs in the US screen for TYR I, and a successful SUAC performance evaluation scheme is available from the Centers for Disease Control and Prevention. Programmatic and methodological barriers were identified that prevent widespread adoption of SUAC measurements in NBS laboratories. However, since SUAC detection is currently the best approach to NBS for TYR I, a further delay of the addition of SUAC measurement into NBS procedures is discouraged. SUAC measurement should improve both the false positive and false negative rate in NBS for TYR I thereby yielding the desired benefits for affected patients at no expense to the overall

  6. The Regional Genetic and Newborn Screening Service Collaboratives: The First Two Years

    ERIC Educational Resources Information Center

    Puryear, Michele; Weissman, Gloria; Watson, Michael; Mann, Marie; Strickland, Bonnie; van Dyck, Peter C.

    2006-01-01

    Newborn screening and genetic technologies are expanding and changing rapidly, increasing the demand for genetic specialty services. Because of the scarcity and geographic maldistribution of genetic specialty services, access to these services is a critical issue. This article discusses some of the efforts initiated by the Maternal and Child…

  7. Making the Case for Objective Performance Metrics in Newborn Screening by Tandem Mass Spectrometry

    ERIC Educational Resources Information Center

    Rinaldo, Piero; Zafari, Saba; Tortorelli, Silvia; Matern, Dietrich

    2006-01-01

    The expansion of newborn screening programs to include multiplex testing by tandem mass spectrometry requires understanding and close monitoring of performance metrics. This is not done consistently because of lack of defined targets, and interlaboratory comparison is almost nonexistent. Between July 2004 and April 2006 (N = 176,185 cases), the…

  8. The Impact of the National Newborn Hearing Screening Programme on Educational Services in England

    ERIC Educational Resources Information Center

    McCracken, Wendy; Young, Alys; Tattersall, Helen; Uus, Kai; Bamford, John

    2005-01-01

    This article presents results related to the impact on educational support services of the introduction of the first phase of the national Newborn Hearing Screening Programme (NHSP) in England. This study was funded by the Department of Health and undertaken as one element of a national evaluation of NHSP across a range of domains. It presents…

  9. The Role of National Library of Medicine[R] Web Sites in Newborn Screening Education

    ERIC Educational Resources Information Center

    Fomous, Cathy; Miller, Naomi

    2006-01-01

    Expanded newborn screening programs and subsequent detection of rare genetic disorders challenge parents and their medical providers to learn about the treatment and management of these disorders. Many people seek medical information on the Internet but may encounter requests for registration or fees, or find that resources are out of date,…

  10. Critical Role of the March of Dimes in the Expansion of Newborn Screening

    ERIC Educational Resources Information Center

    Howse, Jennifer L.; Weiss, Marina; Green, Nancy S.

    2006-01-01

    Expansion of newborn screening (NBS) has been driven primarily by a combination of advances in technology and medical treatment, and the sustained advocacy efforts of consumers and voluntary health organizations. The longstanding leadership of the March of Dimes has been credited by many as a critical factor in the expansion and improvement of…

  11. A conceptual framework for rationalized and standardized Universal Newborn Hearing Screening (UNHS) programs.

    PubMed

    Leo, Carlo Giacomo; Mincarone, Pierpaolo; Sabina, Saverio; Latini, Giuseppe; Wong, John B

    2016-01-01

    Congenital hearing loss is the most frequent birth defect. The American Academy of Pediatrics and the Joint Committee on Infant Hearing established quality of care process indicators for Universal Newborn Hearing Screening starting from 1999. In a previous systematic review of Universal Newborn Hearing Screening studies we highlighted substantial variability in program design and in reported performance data. In order to overcome these heterogeneous findings we think it is necessary to optimize the implementation of Universal Newborn Hearing Screening programs with an appropriate application of the planning, executing, and monitoring, verifications and reporting phases. For this reason we propose a conceptual framework that logically integrates these three phases and, consequently, a tool (a check-list) for their rationalization and standardization.Our paper intends to stimulate debate on how to ameliorate the routine application of high quality Universal Newborn Hearing Screening programs. The conceptual framework is proposed to optimize, rationalise and standardise their implementation. The checklist is intended to allow an inter-program comparison by removing heterogeneity in processes description and assessment. PMID:26872853

  12. Levels of Evidence: Universal Newborn Hearing Screening (UNHS) and Early Hearing Detection and Intervention Systems (EHDI)

    ERIC Educational Resources Information Center

    Yoshinaga-Itano, Christine

    2004-01-01

    Levels of evidence differ according to the audience addressed. Implementation of universal newborn hearing screening requires responses to a complex myriad of diverse groups: the general public, families with children who are deaf or hard of hearing, the deaf and hard of hearing communities, hospital administrators, physicians (pediatricians,…

  13. Ultrasonography in screening for developmental dysplasia of the hip in newborns: systematic review

    PubMed Central

    Woolacott, Nerys F; Puhan, Milo A; Steurer, Johann; Kleijnen, Jos

    2005-01-01

    Objective To assess the accuracy and effectiveness of the screening of all newborn infants for developmental dysplasia of the hip (DDH) using ultrasound imaging, as is standard practice in some European countries but not in the United Kingdom, the United States, or Scandinavia. Design Systematic review. Data sources Twenty three medical, economic, and grey literature databases (to March 2004), with no limitations of design or language; some references were provided by experts. Selection of studies Only diagnostic accuracy studies and comparative studies conducted in an unselected newborn population were eligible for the review. Two reviewers independently selected the studies and performed the quality assessment. Results The review identified one diagnostic accuracy study, and this was of limited quality. In this study the reference standard was treatment up to age of 8 months or an abnormal ultrasound finding at age 8 months. Ultrasound screening had a sensitivity of 88.5% (95% confidence interval 84.1% to 92.1%), specificity of 96.7% (96.4% to 97.4%), a positive predictive value of 61.6% and a negative predictive value of 99.4%. Ten studies evaluated the impact of ultrasound in screening, but these too had various methodological weaknesses, limiting the reliability of their findings. Compared with clinical screening, general ultrasound screening in newborns may increase overall treatment rates, but ultrasound screening seems to be associated with shorter and less intrusive treatment. Conclusions Clear evidence is lacking either for or against general ultrasound screening of newborn infants for DDH. Studies that investigate the natural course of the disorder, the optimal treatment for DDH, and the best strategy for ultrasound screening are needed. PMID:15930025

  14. The otolaryngologist's role in newborn hearing screening and early intervention.

    PubMed

    Bower, Charles M; St John, Rachel

    2014-10-01

    Infant hearing loss is common. Screening is performed in more than 98% of US infants. Otolaryngologists play an important role in identification and management of infants and children who are deaf and hard of hearing. Otolaryngologists should routinely assess for hearing screening results and intervene for screens not passed. Long-term follow-up and reassessment of patients with hearing loss is an ongoing component of otolaryngology practice. This article reviews the otolaryngologist's role in the management of infants and children who are deaf or hard of hearing from screening to intervention and management. PMID:25213275

  15. Newborn screening in Japan: restructuring for the new era.

    PubMed

    Yamaguchi, Seiji

    2008-12-01

    Nationwide neonatal mass screening for inherited metabolic diseases has started in Japan since 1977. At least 8000 children have probably been spared from handicaps resulting from such diseases over the past 30 years. Recently remarkable changes have been made to the evolving neonatal screening system. Declining birth rate and economic problems in Japan have demanded a more effective neonatal screening system. Development of new innovative screening methods and treatment tools, e.g. tandem mass spectrometry (MS/MS) technology and enzyme replacement therapy for mucopolysaccharidosis (MPS), have facilitated expansion of target diseases in neonatal screening. We have carried out pilot screening using MS/MS in 6 laboratories in Japan. The incidence of inherited metabolic diseases was found to be 1 in 9330 (65 cases out of 606,380 babies screened) during the period between 1997 and 2007. The incidence was lower than those of Europe or USA (about 1 in 4000 to 5000). The disease frequency between unscreened symptomatic cases and asymptomatic cases detected through MS/MS screening were also found to be different. In MS/MS screening, the most common organic acidemia was propionic acidemia, whereas in symptomatic cases, methylmalonic acidemia was the most common. Further study of ethnic diversity in severity of propionic academia is required. The outcomes of patients detected in the MS/MS screening were significantly favourable. The results showed the benefits of MS/ MS screening. The diagnostic support network for gas chromatography-mass spectrometry (GC/ MS) analysis and enzyme determination has also been developed. We have developed an automated system of GC/MS data processing and auto-diagnosis which allowed the GC/MS data processing to be extremely fast and simple. Enzyme evaluation for diagnostic support for screening, including a method using peripheral blood and high performance liquid chromatography (HPLC), and another method of in-vitro probe assay using cultured

  16. Evaluation of a novel, commercially available mass spectrometry kit for newborn screening including succinylacetone without hydrazine.

    PubMed

    Metz, Thomas F; Mechtler, Thomas P; Merk, Michael; Gottschalk, Anne; Lukačin, Richard; Herkner, Kurt R; Kasper, David C

    2012-08-16

    Newborn screening for tyrosinemia type I (Tyr-I) is mandatory to identify infants at risk before life-threatening symptoms occur. The analysis of tyrosine alone is limited, and might lead to false-negative results. Consequently, the analysis of succinylacetone (SUAC) is needed. Current protocols are time-consuming, and above all, include hazardous reagents such hydrazine. We evaluated a novel, commercial kit to analyze amino acids, acylcarnitines and SUAC with a significantly less harmful hydrazine derivative in a newborn screening laboratory. Dried blood spot specimens from 4683 newborns and samples from known patients with inborn errors of metabolism (IEM) were analyzed by a novel protocol and compared to an in-house screening assay. All samples were derivatized with butanol-HCl after extraction from 1/8-inch DBS punches. For the novel protocol, the residual blood spots were extracted separately for SUAC, converted into hydrazone, combined with amino acids and acylcarnitines, and subsequently analyzed by mass spectrometry using internal isotope-labeled standards. All newborns were successfully tested, and 74 patients with IEMs including three with Tyr-I (SUAC 1.50, 4.80 and 6.49; tyrosine levels 93.10, 172.40 and 317.73, respectively) were detected accurately. The mean SUAC level in non-affected newborns was 0.68 μmol/l (cut-off 1.29 μmol/l). The novel assay was demonstrated to be accurate in the detection of newborns with IEM, robust, and above all, without the risk of the exposure to highly toxic reagents and requirement of additional equipment for toxic fume evacuation. PMID:22521492

  17. Performance and characteristics of the Newborn Hearing Screening Programme in England: The first seven years

    PubMed Central

    Wood, Sally A; Sutton, Graham J; Davis, Adrian C

    2015-01-01

    Abstract Objective: To assess the performance of the universal newborn hearing screen in England. Design: Retrospective analysis of population screening records. Study sample: A total of 4 645 823 children born 1 April 2004 to 31 March 2013. Results: 97.5% of the eligible population complete screening by 4/5 weeks of age and 98.9% complete screening by three months of age. The refer rate for the 12/13 birth cohort is 2.6%. The percentage of screen positive (i.e. referred) babies commencing follow up by four weeks of age and six months of age is 82.5% and 95.8% respectively. The yield of bilateral PCHL from the screen is around 1/1000. For bilateral PCHL in the 12/13 birth cohort the median age is nine days at screen completion, 30 days at entry into follow up, 49 days at confirmation, 50 days at referral to early intervention, and 82 days at hearing-aid fitting. Conclusion: The performance of the newborn hearing screening programme has improved continuously. The yield of bilateral PCHL from the screen is about 1/1000 as expected. The age of identification and management is well within the first six months of life, although there remains scope for further improvement with respect to timely entry into follow up. PMID:25766652

  18. Maternal Glutaric Acidemia, Type I Identified by Newborn Screening*

    PubMed Central

    Crombez, Eric A.; Cederbaum, Stephen D.; Spector, Elaine; Chan, Erica; Salazar, Denise; Neidich, Julie; Goodman, Stephen

    2008-01-01

    We report two women with glutaric acidemia type I in whom the diagnosis was unsuspected until a low carnitine level was found in their newborn children. Both mothers had low carnitine in plasma. In the first, organic acid analysis was only done after fibroblast studies revealed normal carnitine uptake. Having learned from the first family, organic acid analysis was done immediately in the mother of family 2. In both, the plasma acylcarnitine profile was normal but both excreted the metabolites typical of their disorder. One of the women was a compound heterozygote for distinct mutations in the glutaric acid dehydrogenase gene, whereas the second was either homozygous or hemizygous for a mutation in Exon 6 of the gene. PMID:18304851

  19. Parental permission for pilot newborn screening research: guidelines from the NBSTRN.

    PubMed

    Botkin, Jeffrey R; Lewis, Michelle Huckaby; Watson, Michael S; Swoboda, Kathryn J; Anderson, Rebecca; Berry, Susan A; Bonhomme, Natasha; Brosco, Jeffrey P; Comeau, Anne M; Goldenberg, Aaron; Goldman, Edward; Therrell, Bradford; Levy-Fisch, Jill; Tarini, Beth; Wilfond, Benjamin

    2014-02-01

    There is broad recognition of the need for population-based research to assess the safety and efficacy of newborn screening (NBS) for conditions that are not on current panels. However, prospective population-based research poses significant ethical, regulatory, and logistical challenges. In the context of NBS, there have been a variety of approaches that address parental decision-making in pilot studies of new screening tests or conditions. This article presents an ethical and legal analysis of the role of parental permission by the Bioethics and Legal Work Group of the Newborn Screening Translational Research Network created under a contract from the National Institute of Child Health and Human Development to the American College of Medical Genetics and Genomics. Circumstances are outlined in which a waiver of documentation of permission or a waiver of permission may be ethically and legally appropriate in the NBS context. These guidelines do not constitute American Academy of Pediatrics policy. PMID:24394680

  20. Parental Permission for Pilot Newborn Screening Research: Guidelines From the NBSTRN

    PubMed Central

    Lewis, Michelle Huckaby; Watson, Michael S.; Swoboda, Kathryn J.; Anderson, Rebecca; Berry, Susan A.; Bonhomme, Natasha; Brosco, Jeffrey P.; Comeau, Anne M.; Goldenberg, Aaron; Goldman, Edward; Therrell, Bradford; Levy-Fisch, Jill; Tarini, Beth; Wilfond, Benjamin

    2014-01-01

    There is broad recognition of the need for population-based research to assess the safety and efficacy of newborn screening (NBS) for conditions that are not on current panels. However, prospective population-based research poses significant ethical, regulatory, and logistical challenges. In the context of NBS, there have been a variety of approaches that address parental decision-making in pilot studies of new screening tests or conditions. This article presents an ethical and legal analysis of the role of parental permission by the Bioethics and Legal Work Group of the Newborn Screening Translational Research Network created under a contract from the National Institute of Child Health and Human Development to the American College of Medical Genetics and Genomics. Circumstances are outlined in which a waiver of documentation of permission or a waiver of permission may be ethically and legally appropriate in the NBS context. These guidelines do not constitute American Academy of Pediatrics policy. PMID:24394680

  1. Identifying the Optimal Age to Perform Newborn Screening for Hearing Loss in Uganda

    PubMed Central

    Walsh, M; Redshaw, E; Crossley, E; Phillips, C

    2015-01-01

    Background: Permanent congenital hearing loss affects up to 6/1000 births in developing countries. Currently, in Uganda there is no newborn screening for hearing loss (NSHL) program and no published work on this topic. Within the existing healthcare system there are two opportunities to deliver screening, at birth or 6 weeks of age when infants receive their immunizations. Aim: This study explored the outcomes of otoacoustic emission (OAE) testing in infants at birth and 6 weeks of age, to identify the optimal age for screening. Subjects and Methods: This cross-sectional pilot study recruited 60 consecutive infants from two health centres in Kampala, Uganda. Thirty infants were newborns recruited from the postnatal ward and 30 were aged 4–8 weeks from the immunization clinic, we performed OAE testing on all infants. Results: The results showed 56.7% (17/30) of newborn infants passed OAE testing compared with 90.0% (27/30) of the immunization infants, P < 0.01. Furthermore, of the 11 newborn infants aged ≥24 h of age 90.9% (10/11) passed, compared with the 19 infants <24 h of age where 37% (7/19) passed, P < 0.01. Conclusions: This study demonstrates a higher pass rate for OAE testing for infants ≥24 h of age compared to those <24 h of age. The overall lower pass rate of the newborn infants could be due to external ear debris and middle ear fluid compromising the OAE testing. These findings would support a NSHL programme in Uganda that offers screening to infants ≥24 h of age, to maximize the cost-effectiveness of the program. PMID:27057378

  2. FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States

    PubMed Central

    2012-01-01

    Background Population screening for FMR1 mutations has been a topic of considerable discussion since the FMR1 gene was identified in 1991. Advances in understanding the molecular basis of fragile X syndrome (FXS) and in genetic testing methods have led to new, less expensive methodology to use for large screening endeavors. A core criterion for newborn screening is an accurate understanding of the public health burden of a disease, considering both disease severity and prevalence rate. This article addresses this need by reporting prevalence rates observed in a pilot newborn screening study for FXS in the US. Methods Blood spot screening of 14,207 newborns (7,312 males and 6,895 females) was conducted in three birthing hospitals across the United States beginning in November 2008, using a PCR-based approach. Results The prevalence of gray zone alleles was 1:66 females and 1:112 males, while the prevalence of a premutation was 1:209 females and 1:430 males. Differences in prevalence rates were observed among the various ethnic groups; specifically higher frequency for gray zone alleles in males was observed in the White group compared to the Hispanic and African-American groups. One full mutation male was identified (>200 CGG repeats). Conclusions The presented pilot study shows that newborn screening in fragile X is technically feasible and provides overall prevalence of the premutation and gray zone alleles in the USA, suggesting that the prevalence of the premutation, particularly in males, is higher than has been previously reported. PMID:23259642

  3. Maternal Consequences of the Detection of Fragile X Carriers in Newborn Screening

    PubMed Central

    Wheeler, Anne; Berry-Kravis, Elizabeth; Hagerman, Randi; Tassone, Flora; Powell, Cynthia M.; Roche, Myra; Gane, Louise W.; Sideris, John

    2015-01-01

    OBJECTIVES: The possibility of newborn screening for fragile X syndrome is complicated by the potential for identifying premutation carriers. Although knowing the child’s carrier status has potential benefits, the possibility of late-onset disorders in carrier children and their parents raises concerns about whether such information would be distressing to parents and potentially more harmful than helpful. This study sought to answer this question by offering voluntary fragile X screening to new parents and returning results for both the full mutation and premutation FMR1 gene expansions. We tested the assumption that such information could lead to adverse mental health outcomes or decision regret. We also wanted to know if child age and spousal support were associated with the outcomes of interest. METHODS: Eighteen mothers of screen-positive infants with the premutation and 15 comparison mothers completed a battery of assessments of maternal anxiety, postpartum depression, stress, family quality of life, decision regret, and spousal support. The study was longitudinal, with an average of 3 assessments per mother. RESULTS: The premutation group was not statistically different from the comparison group on measures of anxiety, depression, stress, or quality of life. A subset of mothers experienced clinically significant anxiety and decision regret, but factors associated with these outcomes could not be identified. Greater spousal support was generally associated with more positive outcomes. CONCLUSIONS: Although we did not find evidence of significant adverse events, disclosure of newborn carrier status remains an important consideration in newborn screening policy. PMID:26169437

  4. Impact of Co-Occurring Birth Defects on the Timing of Newborn Hearing Screening and Diagnosis

    PubMed Central

    Chapman, Derek A.; Stampfel, Caroline C.; Bodurtha, Joann N.; Dodson, Kelley M.; Pandya, Arti; Lynch, Kathleen B.; Kirby, Russell S.

    2016-01-01

    Purpose Early detection of hearing loss in all newborns and timely intervention are critical to children's cognitive, verbal, behavioral, and social development. The initiation of appropriate early intervention services before 6 months of age can prevent or reduce negative developmental consequences. The purpose of this study was to assess, using large, population-based registries, the effect of co-occurring birth defects (CBDs) on the timing and overall rate of hearing screening and diagnosis. Method The authors linked statewide data from newborn hearing screenings, a birth defects registry, and birth certificates to assess the timeliness of newborn hearing screening and diagnosis of hearing loss (HL) for infants with and without CBDs in 485 children with confirmed HL. Results Nearly one third (31.5%) of children with HL had 1 or more CBDs. The presence of CBDs prolonged the time of the initial infant hearing screening, which contributed to further delays in the subsequent diagnosis of HL. Conclusions Better coordination of HL assessment into treatment plans for children with CBDs may enable earlier diagnosis of HL and provide opportunities for intervention that will affect long-term developmental outcomes for these children. PMID:21940980

  5. Newborn screening for galactosemia in the United States: looking back, looking around, and looking ahead.

    PubMed

    Pyhtila, Brook M; Shaw, Kelly A; Neumann, Samantha E; Fridovich-Keil, Judith L

    2015-01-01

    It has been 50 years since the first newborn screening (NBS) test for galactosemia was conducted in Oregon, and almost 10 years since the last US state added galactosemia to their NBS panel. During that time an estimated >2,500 babies with classic galactosemia have been identified by NBS. Most of these infants were spared the trauma of acute disease by early diagnosis and intervention, and many are alive today because of NBS. Newborn screening for galactosemia is a success story, but not yet a story with a completely happy ending. NBS, follow-up testing, and intervention for galactosemia continue to present challenges that highlight gaps in our knowledge. Here we compare galactosemia screening and follow-up data from 39 NBS programs gathered from the states directly or from public sources. On some matters the programs agreed: for example, those providing relevant data all identify classic galactosemia in close to 1/50,000 newborns and recommend immediate and lifelong dietary restriction of galactose for those infants. On other matters the programs disagree. For example, Duarte galactosemia (DG) detection rates vary dramatically among states, largely reflecting differences in screening approach. For infants diagnosed with DG, >80% of the programs surveyed recommend complete or partial dietary galactose restriction for the first year of life, or give mixed recommendations; <20% recommend no intervention. This disparity presents an ongoing dilemma for families and healthcare providers that could and should be resolved. PMID:24718839

  6. First Colombian Multicentric Newborn Screening for Congenital Toxoplasmosis

    PubMed Central

    Gómez-Marin, Jorge Enrique; de-la-Torre, Alejandra; Angel-Muller, Edith; Rubio, Jorge; Arenas, Jaime; Osorio, Elkin; Nuñez, Lilian; Pinzon, Lyda; Mendez-Cordoba, Luis Carlos; Bustos, Agustin; de-la-Hoz, Isabel; Silva, Pedro; Beltran, Monica; Chacon, Leonor; Marrugo, Martha; Manjarres, Cristina; Baquero, Hernando; Lora, Fabiana; Torres, Elizabeth; Zuluaga, Oscar Elias; Estrada, Monica; Moscote, Lacides; Silva, Myriam Teresa; Rivera, Raul; Molina, Angie; Najera, Shirley; Sanabria, Antonio; Ramirez, Maria Luisa; Alarcon, Claudia; Restrepo, Natalia; Falla, Alejandra; Rodriguez, Tailandia; Castaño, Giovanny

    2011-01-01

    Aims To determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern). Materials and Methods We collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain) to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life. Results 61 positive samples for specific IgM (0.39%) and 9 positives for IgA (0.5%) were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality). A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city. Conclusions Incidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis. PMID:21655304

  7. Infrastructure and Educational Needs of Newborn Screening Short-Term Follow-Up Programs within the Southeast Regional Newborn Screening & Genetics Collaborative: A Pilot Survey

    PubMed Central

    Bellcross, Cecelia A.; Harmond, Lokie; Floyd-Browning, Phaidra; Singh, Rani

    2015-01-01

    Newborn screening (NBS) follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC). Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP) knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families. PMID:27417806

  8. Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

    PubMed

    2012-04-01

    Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn

  9. Questioning the consensus: managing carrier status results generated by newborn screening.

    PubMed

    Miller, Fiona Alice; Robert, Jason Scott; Hayeems, Robin Z

    2009-02-01

    An apparent consensus governs the management of carrier status information generated incidentally through newborn screening: results cannot be withheld from parents. This normative stance encodes the focus on autonomy and distaste for paternalism that characterize the principles of clinical bioethics. However, newborn screening is a classic public health intervention in which paternalism may trump autonomy and through which parents are-in effect-required to receive carrier information. In truth, the disposition of carrier results generates competing moral infringements: to withhold information or require its possession. Resolving this dilemma demands consideration of a distinctive body of public health ethics to highlight the moral imperatives associated with the exercise of collective authority in the pursuit of public health benefits. PMID:19059852

  10. Questioning the Consensus: Managing Carrier Status Results Generated by Newborn Screening

    PubMed Central

    Robert, Jason Scott; Hayeems, Robin Z.

    2009-01-01

    An apparent consensus governs the management of carrier status information generated incidentally through newborn screening: results cannot be withheld from parents. This normative stance encodes the focus on autonomy and distaste for paternalism that characterize the principles of clinical bioethics. However, newborn screening is a classic public health intervention in which paternalism may trump autonomy and through which parents are—in effect—required to receive carrier information. In truth, the disposition of carrier results generates competing moral infringements: to withhold information or require its possession. Resolving this dilemma demands consideration of a distinctive body of public health ethics to highlight the moral imperatives associated with the exercise of collective authority in the pursuit of public health benefits. PMID:19059852

  11. Defining the Newborn Blood Spot Screening Reference Interval for TSH: Impact of Ethnicity

    PubMed Central

    Brooke, Ivan; Heales, Simon; Ifederu, Adeboye; Langham, Shirley; Hindmarsh, Peter; Cole, Tim J.

    2016-01-01

    Context: There is variability in the congenital hypothyroidism (CH) newborn screening TSH cutoff across the United Kingdom. Objective: To determine the influences of year, gender, and ethnicity on screening variability and examine whether there is an optimal operational TSH cutoff. Design and Setting: Single center, retrospective population study using blood spot TSH cards received by the Great Ormond Street Hospital Screening Laboratory between 2006 and 2012. Patients: A total of 824 588 newborn screening blood spot TSH cards. Intervention: Blood spot TSH results were recorded with demographic data including the Ethnic Category Code. Main Outcome Measures: The proportions of samples exceeding different TSH cutoffs, ranked by ethnicity. Results: The proportion of samples exceeding the TSH cutoff increased over time, with the cutoff at 4 mU/L, but not at 6 mU/L. There was a consistent trend with ethnicity, irrespective of cutoff, with the odds ratio of exceeding the TSH cutoff lowest (∼1.0) in White babies, higher in Pakistani and Bangladeshi (>2.0), and highest in Chinese (>3.5). Conclusions: The blood spot TSH screening data demonstrate a clear ranking according to ethnicity for differences in mean TSH. This suggests that there may be ethnic differences in thyroid physiology. Ethnic diversity within populations needs to be considered when establishing and interpreting screening TSH cutoffs. PMID:27399348

  12. Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry

    PubMed Central

    2015-01-01

    The main purpose of newborn screening is to diagnose genetic, metabolic, and other inherited disorders, at their earliest to start treatment before the clinical manifestations become evident. Understanding and tracing the biochemical data obtained from tandem mass spectrometry is vital for early diagnosis of metabolic diseases associated with such disorders. Accordingly, it is important to focus on the entire diagnostic process, including differential and confirmatory diagnostic options, and the major factors that influence the results of biochemical analysis. Compared to regular biochemical testing, this is a complex process carried out by a medical physician specialist. It is comprised of an integrated program requiring multidisciplinary approach such as, pediatric specialist, expert scientist, clinical laboratory technician, and nutritionist. Tandem mass spectrometry is a powerful tool to improve screening of newborns for diverse metabolic diseases. It is likely to be used to analyze other treatable disorders or significantly improve existing newborn tests to allow broad scale and precise testing. This new era of various screening programs, new treatments, and the availability of detection technology will prove to be beneficial for the future generations. PMID:26512346

  13. Improved Reagents for Newborn Screening of Mucopolysaccharidosis Types I, II, and VI by Tandem Mass Spectrometry

    PubMed Central

    2015-01-01

    Tandem mass spectrometry for the multiplex and quantitative analysis of enzyme activities in dried blood spots on newborn screening cards has emerged as a powerful technique for early assessment of lysosomal storage diseases. Here we report the design and process-scale synthesis of substrates for the enzymes α-l-iduronidase, iduronate-2-sulfatase, and N-acetylgalactosamine-4-sulfatase that are used for newborn screening of mucopolysaccharidosis types I, II, and VI. The products contain a bisamide unit that is hypothesized to readily protonate in the gas phase, which improves detection sensitivity by tandem mass spectrometry. The products contain a benzoyl group, which provides a useful site for inexpensive deuteration, thus facilitating the preparation of internal standards for the accurate quantification of enzymatic products. Finally, the reagents are designed with ease of synthesis in mind, thus permitting scale-up preparation to support worldwide newborn screening of lysosomal storage diseases. The new reagents provide the most sensitive assay for the three lysosomal enzymes reported to date as shown by their performance in reactions using dried blood spots as the enzyme source. Also, the ratio of assay signal to that measured in the absence of blood (background) is superior to all previously reported mucopolysaccharidosis types I, II, and VI assays. PMID:24694010

  14. Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry.

    PubMed

    Yoon, Hye-Ran

    2015-09-01

    The main purpose of newborn screening is to diagnose genetic, metabolic, and other inherited disorders, at their earliest to start treatment before the clinical manifestations become evident. Understanding and tracing the biochemical data obtained from tandem mass spectrometry is vital for early diagnosis of metabolic diseases associated with such disorders. Accordingly, it is important to focus on the entire diagnostic process, including differential and confirmatory diagnostic options, and the major factors that influence the results of biochemical analysis. Compared to regular biochemical testing, this is a complex process carried out by a medical physician specialist. It is comprised of an integrated program requiring multidisciplinary approach such as, pediatric specialist, expert scientist, clinical laboratory technician, and nutritionist. Tandem mass spectrometry is a powerful tool to improve screening of newborns for diverse metabolic diseases. It is likely to be used to analyze other treatable disorders or significantly improve existing newborn tests to allow broad scale and precise testing. This new era of various screening programs, new treatments, and the availability of detection technology will prove to be beneficial for the future generations. PMID:26512346

  15. Targeted metabolomics in the expanded newborn screening for inborn errors of metabolism.

    PubMed

    Scolamiero, Emanuela; Cozzolino, Carla; Albano, Lucia; Ansalone, Antonella; Caterino, Marianna; Corbo, Graziella; di Girolamo, Maria Grazia; Di Stefano, Cristina; Durante, Adriano; Franzese, Giovanni; Franzese, Ignazio; Gallo, Giovanna; Giliberti, Paolo; Ingenito, Laura; Ippolito, Giovanni; Malamisura, Basilio; Mazzeo, Pietro; Norma, Antonella; Ombrone, Daniela; Parenti, Giancarlo; Pellecchia, Silvana; Pecce, Rita; Pierucci, Ippolito; Romanelli, Roberta; Rossi, Anna; Siano, Massimo; Stoduto, Teodoro; Villani, Guglielmo R D; Andria, Generoso; Salvatore, Francesco; Frisso, Giulia; Ruoppolo, Margherita

    2015-06-01

    Inborn errors of metabolism are genetic disorders due to impaired activity of enzymes, transporters, or cofactors resulting in accumulation of abnormal metabolites proximal to the metabolic block, lack of essential products or accumulation of by-products. Many of these disorders have serious clinical consequences for affected neonates, and an early diagnosis allows presymptomatic treatment which can prevent severe permanent sequelae and in some cases death. Expanded newborn screening for these diseases is a promising field of targeted metabolomics. Here we report the application, between 2007 and 2014, of this approach to the identification of newborns in southern Italy at risk of developing a potentially fatal disease. The analysis of amino acids and acylcarnitines in dried blood spots by tandem mass spectrometry revealed 24 affected newborns among 45,466 infants evaluated between 48 and 72 hours of life (overall incidence: 1 : 1894). Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Five infants were diagnosed with medium-chain acyl CoA dehydrogenase deficiency, 1 with methylmalonic acidemia with homocystinuria type CblC, 2 with isolated methylmalonic acidemia, 1 with propionic acidemia, 1 with isovaleric academia, 1 with isobutyryl-CoA dehydrogenase deficiency, 1 with beta ketothiolase deficiency, 1 with short branched chain amino acid deficiency, 1 with 3-methlycrotonyl-CoA carboxylase deficiency, 1 with formimino-transferase cyclodeaminase deficiency, and 1 with cystathionine-beta-synthase deficiency. Seven cases of maternal vitamin B12 deficiency and 1 case of maternal carnitine uptake deficiency were detected. This study supports the widespread application of metabolomic-based newborn screening for these genetic diseases. PMID:25689098

  16. Saliva Polymerase-Chain-Reaction Assay for Cytomegalovirus Screening in Newborns

    PubMed Central

    Boppana, Suresh B.; Ross, Shannon A.; Shimamura, Masako; Palmer, April L.; Ahmed, Amina; Michaels, Marian G.; Sánchez, Pablo J.; Bernstein, David I.; Tolan, Robert W.; Novak, Zdenek; Chowdhury, Nazma; Britt, William J.; Fowler, Karen B.

    2011-01-01

    BACKGROUND Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives — real-time polymerase-chain-reaction (PCR)–based testing of a liquid-saliva or dried-saliva specimen obtained at birth — have been developed. METHODS In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. RESULTS A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively. CONCLUSIONS Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be

  17. Ultrasound as a primary screening tool for detecting low birthweight newborns

    PubMed Central

    Goto, Eita

    2016-01-01

    Abstract Background: As low birthweight (i.e., birthweight < 2500 g) is a major determinant of neonatal mortality and morbidity, the pre-delivery detection of low birthweight is clinically advantageous. This study was performed to determine whether ultrasound is suitable for use in primary screening to detect low birthweight newborns. Methods: The primary outcomes included sensitivity, specificity, and positive and negative likelihood ratios of ultrasound detection of low birthweight newborns. Ten databases, including PubMed, were searched. All English language studies that provided true- and false-positive and true- and false-negative results regarding the pre-delivery ultrasound detection of low birthweight newborns were eligible for inclusion in the analysis. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies. Bivariate diagnostic meta-analysis was performed and hierarchical summary receiver operating characteristic curves were constructed. Results: Studies of relatively good quality were included in the analysis to evaluate crown–rump length (n = 12); femur length (n = 5); formulas of Campbell, Hadlock, and Shepard (n = 9); and uterine artery blood flow (n = 7). All showed low sensitivity (=0.24–0.58) regardless of specificity (=0.60–0.96). The formulas of Campbell, Hadlock, and Shepard were usable for a confirmation strategy only (positive and negative likelihood ratios = 14.8 and 0.44, respectively), but crown–rump or femur length, and uterine artery blood flow were not usable for an exclusion or confirmation strategy (positive and negative likelihood ratios = 1.4–2.8 and 0.71–0.85, respectively). Conclusions: Primary screening does not have to confirm low birthweight, but should almost always categorize low birthweight as a positive result and exclude normal birthweight. Therefore, ultrasound is not suitable as a primary screening tool to detect low birthweight newborns. PMID

  18. Parent perception of newborn hearing screening: results of a national survey

    PubMed Central

    Pynnonen, Melissa A.; Handelsman, Jaynee A.; King, Ericka F.; Singer, Dianne C.; Davis, Matthew M.; Lesperance, Marci M.

    2016-01-01

    Importance An unacceptably high number of children who do not pass universal newborn hearing screening (UNHS) are lost to follow-up. Objectives Our objective was to gain insight into parent recall of UNHS. We compared responses of parents whose children were born before versus after UNHS. Design Survey Setting Nationally representative cross-sectional survey Participants 1,539 parent households surveyed in May 2012 Main Outcome(s) and Measures Outcome measures included recall of hearing screen at birth, hearing screen results, and recommendations for follow-up. All outcome measures were based on parent recall and report. We used descriptive statistics and multiple logistic regression analysis. Results Only 62.9% of parents recall a newborn hearing screen, and among those children with risk indicators for hearing loss, only 68.6% recall a hearing screen. Higher parent education (p=0.034), younger age of the child (OR 1.16, 95% CI 1.11 – 1.23, p<0.001), and the presence of any risk indicator for hearing loss (OR 1.5, 95% CI 1.13 – 2.13, p=0.007) were associated with parent recall of hearing screen. Reported pass rates were higher than expected. Parents’ recall of follow-up recommendations was not always consistent with guidelines. Conclusions and Relevance While this study is inherently limited by recall bias, our findings demonstrate a lack of parent awareness of UNHS. We believe changes in the system of reporting UNHS results are necessary to improve parents’ recall of screen results and improve follow up for children who do not pass the screen. PMID:26967534

  19. Molecular newborn screening of four genetic diseases in Guizhou Province of South China.

    PubMed

    Huang, Shengwen; Xu, Yin; Liu, Xingmei; Zhou, Man; Wu, Xian; Jia, Yankai

    2016-10-10

    Genetic disorders have been a major concern for public health in China, especially in the rural regions. However, there is little information available about prevalence of many common single-gene disorders in Guizhou Province in the south western part of China. In the present study, we performed a molecular newborn screening for four genetic disorders, including beta-thalassemia (β-thal), glucose-6-phosphate dehydrogenase (G6PD) deficiency, phenylketonuria (PKU), and non-syndromic hearing loss and deafness (NSHL) in this region. A total of 515 newborns were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) developed for screening the mutations causing these four disorders, and then confirmed by Sanger sequencing. The results showed that 48 out of 515 newborns were carriers of mutations related to these four diseases, with a frequency of 1 in 11 (9.32%). The carrier frequencies for each disease are: β-thal 2.72%; G6PD deficiency 1.94%; PKU 0.78% and NSHL 4.47%. The genotyping results by MALDI-TOF MS were concordant with Sanger sequencing results within 30 randomly selected samples. This is the first study that reveals carrier frequencies of these four diseases in Guizhou Province. These data provide valuable information for the genetic counseling and disease prevention in Guizhou and southwest China. PMID:27395428

  20. Supporting Family Adaptation to Presymptomatic and “Untreatable” Conditions in an Era of Expanded Newborn Screening

    PubMed Central

    Armstrong, F. Daniel; Kemper, Alex R.; Skinner, Debra; Warren, Steven F.

    2009-01-01

    Objective As technology advances, newborn screening will be possible for conditions not screened today. With an expansion of screening, strategies will be needed to support family adaptation to unexpected and possibly uncertain genetic information provided shortly after birth. Method Although candidate conditions for expanded newborn screening will typically be associated with increased morbidity or mortality, for most there is no proven medical treatment that must be implemented quickly. Many will have clinical features that gradually emerge and for which the severity of impact is not predictable. Parents will seek guidance on information, support, and treatment possibilities. This article summarizes issues evoked by expanded newborn screening and suggests strategies for supporting families of identified children. Results We propose four components necessary to support family adaptation to pre-symptomatic and “untreatable” conditions in an era of expanded newborn screening: (1) accurate and understandable information; (2) formal and informal support; (3) active surveillance; and (4) general and targeted interventions. We argue that no condition is “untreatable” and that a well-designed program of prevention and support has the potential to maximize benefit and minimize harm. Conclusions Pediatric psychologists can play important roles in an era of expanded newborn screening by helping families understand genetic information, make informed decisions about genetic testing, and cope with the potential psychosocial consequences of genetic information. PMID:18378512

  1. Newborn screening conditions: What we know, what we do not know, and how we will know it.

    PubMed

    Levy, Harvey L

    2010-12-01

    Expanding newborn screening beyond that for phenylketonuria was always the goal of Guthrie once phenylketonuria screening was on solid ground. He succeeded in this effort to an extent, adding screening for galactosemia, maple syrup urine disease, and homocystinuria. Screening for congenital hypothyroidism, congenital adrenal hyperplasia, biotinidase deficiency, and a few additional disorders was added by others over the years. However, a very large expansion of covered metabolic disorders eluded Guthrie despite his best efforts. This required a new screening technology, tandem mass spectrometry, which was not available until recently. Now, almost all developed newborn screening program use tandem mass spectrometry to cover the 29 metabolic disorders recommended for coverage by the American College of Medical Genetics and additional secondary disorders. The results have in some cases been spectacular in preventing or greatly reducing the burden of disease imposed by many of the screened disorders. However, expanded newborn screening has also brought problems that need to be addressed. These include lack of knowledge about the natural history of some of the disorders, absence of effective preventive therapy for others, identification of seemingly benign disorders or benign variants of severe disorders, and the resulting parental anxiety. To address these and other issues brought by expanded newborn screening, a national effort led by the American College of Medical Genetics has been developed. This effort known as the Newborn Screening Translational Research Network seeks to stimulate research, advocate pilot screening programs for proposed new additions to screening, and develop a protocol-based systematic long-term follow-up of infants identified in expanded screening programs. Upon the outcome, this critical effort will depend on the health and well-being of children throughout the United States. PMID:21150366

  2. Newborn screening strategy for cystic fibrosis: a field study in an area with high allelic heterogeneity.

    PubMed

    Castellani, C; Bonizzato, A; Cabrini, G; Mastella, G

    1997-05-01

    To verify to what extent mutation analysis on blood spot could improve cystic fibrosis neonatal screening in an area with high allelic heterogeneity, we designed a special protocol. Spot trypsin estimation at birth, trypsin re-testing after 1 month, meconium lactase testing and mutation analysis of delta F508, R1162X and N1303K, were retrospectively clustered according to different patterns (trypsin/lactase/mutation; trypsin/lactase/re-testing; trypsin/mutation) and compared. The programme, which lasted 2 years (1993-94) and covered most of North-eastern Italy, included 95,553 screened newborns. Thirty-four affected babies were detected by screening and one by meconium ileus (incidence 1/2730). The combined use of trypsin, lactase and mutation analysis in cystic fibrosis neonatal screening permits a better sensitivity compared to the two other combinations (34 diagnoses vs 32 in both cases). Moreover, the higher specificity of the former method (false positives 42 vs 148) allows a reduction of recalls, which cause considerable anxiety. We confirm in trypsin-positive newborns an increased frequency of cystic fibrosis heterozygotes (1/17). PMID:9183489

  3. Finding Motivation: Online Information Seeking Following Newborn Screening for Cystic Fibrosis.

    PubMed

    Strekalova, Yulia A

    2016-07-01

    Cystic fibrosis (CF) is a genetic disease that has no manifestations for carriers but is terminal for those diagnosed with it. CF is identified through newborn screening (NBS) tests, and most families have no knowledge about CF before their contact with a NBS program. Acknowledging the Internet as a popular health information source, this study examined information exchange about CF in online community forums. This article, guided by self-determination theory, aimed at providing understanding of psychological needs and motivation for health information seeking and active communication about CF. Through online communication with other families who share similar experience, caregivers of newborns diagnosed with CF sought and received support for their competence, autonomy, and relatedness needs during the initial CF testing and diagnosis reconciliation process. Online communities play an important role in the information seeking related to CF diagnosis and could become active partners in strategic knowledge dissemination efforts. PMID:26612888

  4. Clinical Follow-Up for Duchenne Muscular Dystrophy Newborn Screening: A Proposal.

    PubMed

    Kwon, Jennifer M; Abdel-Hamid, Hoda Z; Al-Zaidy, Samiah A; Mendell, Jerry R; Kennedy, Annie; Kinnett, Kathi; Cwik, Valerie A; Street, Natalie; Bolen, Julie; Day, John W; Connolly, Anne M

    2016-08-01

    New developments in the rapid diagnosis and treatment of boys with Duchenne muscular dystrophy (DMD) have led to growing enthusiasm for instituting DMD newborn screening (NBS) in the United States. Our group has been interested in developing clinical guidance to be implemented consistently in specialty care clinics charged with the care of presymptomatically identified newborns referred after DMD-NBS. We reviewed the existing literature covering patient-centered clinical follow-up after NBS, educational material from public health and advocacy sites, and federal recommendations on effective NBS follow-up. We discussed the review as a group and added our own experience to develop materials suitable for initial parent and primary care provider education. These materials and a series of templates for subspecialist encounters could be used to provide consistent care across centers and serve as the basis for ongoing quality improvement. Muscle Nerve 54: 186-191, 2016. PMID:27170260

  5. Newborn screening in Latin America at the beginning of the 21st century.

    PubMed

    Borrajo, G J C

    2007-08-01

    Newborn screening (NBS) in Latin America took its first steps in the mid-1970s. Nevertheless, many years elapsed before it achieved its integration within the public health care system and its systematic and continuous implementation under a programme structure. Latin American countries can be characterized not only by their great geographic, demographic, ethnic, economic and health system diversity, but also by their heterogeneity in NBS activities, which gives rise to variation in degree of organization: countries with optimal fulfilment (Cuba, Costa Rica, Chile, Uruguay); others rapidly expanding their coverage (Brazil, Mexico, Argentina); some others in a recent implementation phase (Colombia, Paraguay, Venezuela, Nicaragua, Peru); others with minimal, isolated and non-organized activities (Guatemala, Dominican Republic, Bolivia, Panama, Ecuador); and finally others without any NBS activities at all (El Salvador, Honduras, Haiti). Despite this disparity, a sustained and significant growth in NBS activities has become evident during the last decade, highlighted by implementation of new programmes, increase in coverage, expansion of NBS panels, increasing involvement of governmental and public health authorities, and integration of NBS teams through scientific societies and External Quality Assurance Schemes. Currently, congenital hypothyroidism (CH) is the most widely screened disease, followed by phenylketonuria, with organized NBS programmes for CH in 14 countries. Other diseases usually included in NBS programmes are screened in a lower rate. Every year, around 11.2 million infants are born in Latin America. During 2005, 49.3% of newborns were screened for CH, indicating that around 5.7 million newborns still did not have access to the benefits of NBS. PMID:17701285

  6. Newborn Screening for Spinal Muscular Atrophy by Calibrated Short-Amplicon Melt Profiling

    PubMed Central

    Dobrowolski, Steven F.; Pham, Ha T.; Pouch-Downes, Frances; Prior, Thomas W.; Naylor, Edwin W.; Swoboda, Kathy J.

    2014-01-01

    BACKGROUND The management options for the autosomal recessive neurodegenerative disorder spinal muscular atrophy (SMA) are evolving; however, their efficacy may require presymptom diagnosis and continuous treatment. To identify presymptomatic SMA patients, we created a DNA-based newborn-screening assay to identify the homozygous deletions of the SMN1 (survival of motor neuron 1, telomeric) gene observed in 95%–98% of affected patients. METHODS We developed primers that amplify a 52-bp PCR product from homologous regions in the SMN1 and SMN2 (survival of motor neuron 2, centromeric) genes that flank a divergent site at site c.840. Post-PCR high-resolution melt profiling assessed the amplification product, and we used a unique means of melt calibration to normalize profiles. Samples that we had previously characterized for the numbers of SMN1 and SMN2 copies established genotypes associated with particular profiles. The system was evaluated with approximately 1000 purified DNA samples, 100 self-created dried blood spots, and >1200 dried blood spots from newborn-screening tests. RESULTS Homozygous deletion of SMN1 exon 7 produced a distinctive melt profile that identified SMA patients. Samples with different numbers of SMN1 and SMN2 copies were resolved by their profiles. All samples with homozygous deletions were unambiguously recognized, and no normal sample was misidentified as a positive. CONCLUSIONS This assay has characteristics suitable for population-based screening. A reliable screening test will facilitate the identification of an SMA-affected cohort to receive early intervention to maximize the benefit from treatment. A prospective screening trial will allow the efficacy of treatment options to be assessed, which may justify the inclusion of SMA as a target for population screening. PMID:22490618

  7. Developing a public health-tracking system for follow-up of newborn screening metabolic conditions: a four-state pilot project structure and initial findings

    PubMed Central

    Hinton, Cynthia F.; Mai, Cara T.; Nabukera, Sarah K.; Botto, Lorenzo D.; Feuchtbaum, Lisa; Romitti, Paul A.; Wang, Ying; Piper, Kimberly Noble; Olney, Richard S.

    2016-01-01

    Purpose The aim of this study was to describe the methods, cases, and initial results of a pilot project using existing public health data collection programs (birth defect surveillance or newborn screening) to conduct long-term follow-up of children with metabolic disorders. Methods California, Iowa, New York, and Utah expanded birth defect surveillance or newborn screening programs to collect long-term follow-up data on 19 metabolic disorders. Data elements to monitor health status and services delivered were identified, and record abstraction and data linkages were conducted. Children were followed up through to the age of 3 years. Results A total of 261 metabolic cases were diagnosed in 1,343,696 live births (19.4 cases/100,000; 95% confidence interval = 17.1–21.8). Four deaths were identified. Children with fatty acid oxidation disorders had a higher percentage of health service encounters compared with children with other disorders of at least one health service encounter (hospitalization, emergency room, metabolic clinic, genetic service provider, or social worker) except for hospitalizations; children with organic acid disorders had a higher percentage of at least one hospitalization during their third year of life than children with other disorders. Conclusion Existing public health data programs can be leveraged to conduct population-based newborn screening long-term follow-up. This approach is flexible according to state needs and resources. These data will enable the states in assessing health burden, assuring access to services, and supporting policy development. PMID:24310309

  8. Newborn Screening: National Library of Medicine Literature Search, January 1980 through March 1987. No. 87-2.

    ERIC Educational Resources Information Center

    Patrias, Karen

    This bibliography, prepared by the National Library of Medicine through a literature search of its online databases, covers all aspects of newborn screening. It includes references to screening for: inborn errors of metabolism, such as phenylketonuria and galactosemia; hemoglobinopathies, particularly sickle cell disease; congenital hypothyroidism…

  9. The tandem mass spectrometry newborn screening experience in North Carolina: 1997-2005.

    PubMed

    Frazier, D M; Millington, D S; McCandless, S E; Koeberl, D D; Weavil, S D; Chaing, S H; Muenzer, J

    2006-02-01

    North Carolina (NC) was the first US state to initiate universal tandem mass spectrometry (MS/MS) newborn screening. This began as a statewide pilot project in 1997 to determine the incidence and feasibility of screening for fatty acid oxidation, organic acid and selected amino acid disorders. The MS/MS analyses were done by a commercial laboratory and all follow-up and confirmatory testing was performed through the NC Newborn Screening (NBS) Program. In April 1999, the NC NBS Laboratory began the MS/MS analyses in-house. Between 28 July 1997 and 28 July 2005, 944,078 infants were screened and 219 diagnoses were confirmed on newborns with elevated screening results, for an overall incidence of 1:4,300. Ninety-nine infants were identified with fatty acid oxidation disorders, 58 with organic acidaemias and 62 with aminoacidopathies. Medium-chain acyl-CoA dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency and disorders of phenylalanine metabolism were the most common disorders detected. Identification of affected infants has allowed retrospective testing of other family members, resulting in an additional 16 diagnoses. Seven neonates died from complications of their metabolic disorders/prematurity despite timely MS/MS screening. In addition, there were six infants who were not identified by elevated NBS results but who presented with symptoms later in infancy. The NC MS/MS NBS Program uses a two-tier system, categorizing results as either 'borderline' or 'diagnostic' elevated, for both the cutoffs and follow-up protocol. Infants with an initial borderline result had only a repeat screen. Infants with a diagnostic or two borderline results were referred for confirmatory testing. The positive predictive value of the NC MS/MS NBS for those infants requiring confirmatory testing was 53% for 2003 and 2004. The success of the NC MS/MS NBS Program in identifying infants with metabolic disorders was dependent on a comprehensive follow-up protocol

  10. The Prevalence of Sickle Cell Disease and Its Implication for Newborn Screening in Germany (Hamburg Metropolitan Area).

    PubMed

    Grosse, Regine; Lukacs, Zoltan; Cobos, Paulina Nieves; Oyen, Florian; Ehmen, Christa; Muntau, Birgit; Timmann, Christian; Noack, Bernd

    2016-01-01

    Sickle cell disease is among hereditary diseases with evidence that early diagnoses and treatment improves the clinical outcome. So far sickle cell disease has not been included in the German newborn screening program despite immigration from countries with populations at risk. To determine the birth prevalence we tested 17,018 newborns. High pressure liquid chromatography and subsequent molecular-genetic testing were used for the detection and confirmation of hemoglobin variants. The frequency of sickle cell disease-consistent genotypes was one in 2,385 newborns. Duffy-blood group typing showed evidence that affected children were likely of Sub-Saharan ancestry. An inclusion of sickle cell disease into the German newborn screening seems reasonable. PMID:26275168

  11. Ethics, genetics and public policies in Uruguay: newborn and infant screening as a paradigm.

    PubMed

    Larrandaburu, Mariela; Matte, Ursula; Noble, Ana; Olivera, Zully; Sanseverino, Maria Teresa V; Nacul, Luis; Schuler-Faccini, Lavinia

    2015-07-01

    Uruguay is a middle-income country and the smallest in South America. Its population is under 3.3 million. The demographic and epidemiological characteristics are similar to those of developed countries, with a high burden associated with congenital anomalies. Infant mortality rate (IMR) decreased from 37/1000 live births, in 1980, to 8.8/1000, in 2013. This is largely explained by medical and social policies. IMR related to congenital anomalies, however, remained unchanged for the last 30 years. Therefore, programmes for prevention of congenital disorders were developed, such as the National Newborn Screening Programme. Mandatory, universal, free infant screening was implemented two decades ago. The Ministry of Public Health created the Comprehensive Plan on Birth Defects and Rare Diseases (PIDCER), to develop a strategic public policy tool enabling comprehensive, universal, quality care during their entire lifetime. Recent national legislation created provisions for newborn and infant screening, including for congenital hypothyroidism, phenylketonuria, congenital adrenal hyperplasia, cystic fibrosis and medium-chain acyl-CoA dehydrogenase, via blood spot test, otoacoustic emissions, systematic physical examination and hip ultrasound. We discuss how this programme was implemented, the current situation of rare diseases, the institution managing disability in Uruguay and the development of new laws based on the MPH's PIDCER. It illustrates how Uruguay is developing public policies in the genomic era, based both on science and bioethics. PMID:26021874

  12. Multiplex Newborn Screening for Pompe, Fabry, Hunter, Gaucher, and Hurler Diseases Using a Digital Microfluidic Platform

    PubMed Central

    Sista, Ramakrishna S.; Wang, Tong; Wu, Ning; Graham, Carrie; Eckhardt, Allen; Winger, Theodore; Srinivasan, Vijay; Bali, Deeksha; Millington, David S.; Pamula, Vamsee K.

    2013-01-01

    Purpose New therapies for lysosomal storage diseases (LSDs) have generated interest in screening newborns for these conditions. We present performance validation data on a digital microfluidic platform that performs multiplex enzymatic assays for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases. Methods We developed an investigational disposable digital microfluidic cartridge that uses a single dried blood spot (DBS) punch for performing a 5-plex fluorometric enzymatic assay on up to 44 DBS samples. Precision and linearity of the assays were determined by analyzing quality control DBS samples; clinical performance was determined by analyzing 600 presumed normal and known affected samples (12 for Pompe, 7 for Fabry and 10 each for Hunter, Gaucher and Hurler). Results Overall coefficient of variation (CV) values between cartridges, days, instruments, and operators ranged from 2 to 21%; linearity correlation coefficients were ≥ 0.98 for all assays. The multiplex enzymatic assay performed from a single DBS punch was able to discriminate presumed normal from known affected samples for 5 LSDs. Conclusions Digital microfluidic technology shows potential for rapid, high-throughput screening for 5 LSDs in a newborn screening laboratory environment. Sample preparation to enzymatic activity on each cartridge is less than 3 hours. PMID:23660237

  13. Cochlear microphonics in sensorineural hearing loss: lesson from newborn hearing screening.

    PubMed

    Ahmmed, Ansar; Brockbank, Christopher; Adshead, June

    2008-08-01

    The diagnostic dilemma surrounding the presence of cochlear microphonics (CM) coupled with significantly elevated auditory brainstem response (ABR) thresholds in babies failing the newborn hearing screening is highlighted. A case report is presented where initial electo-diagnostic assessment could not help in differentiating between Auditory Neuropathy/Auditory Dys-synchrony (AN/AD) and sensorineural hearing loss (SNHL). In line with the protocol and guidelines provided by the national Newborn Hearing Screening Programme in the UK (NHSP) AN/AD was suspected in a baby due to the presence of CM at 85 dBnHL along with click evoked ABR thresholds of 95 dBnHL in one ear and 100 dBnHL in the other ear. Significantly elevated thresholds for 0.5 and 1kHz tone pip ABR fulfilled the audiological diagnostic criteria for AN/AD. However, the possibility of a SNHL could not be ruled out as the 85 dBnHL stimuli presented through inserts for the CM would have been significantly enhanced in the ear canals of the young baby to exceed the threshold level of the ABR that was carried out using headphones. SNHL was eventually diagnosed through clinical and family history, physical examination and imaging that showed enlarged vestibular aqueducts. Presence of CM in the presence of very high click ABR thresholds only suggests a pattern of test results and in such cases measuring thresholds for 0.5 and 1 kHz tone pip ABR may not be adequate to differentiate between SNHL and other conditions associated with AN/AD. There is a need for reviewing the existing AN/AD protocol from NHSP in the UK and new research to establish parameters for CM to assist in the differential diagnosis. A holistic audiological and medical approach is essential to manage babies who fail the newborn hearing screening. PMID:18571245

  14. Sickle cell disease in childhood: from newborn screening through transition to adult medical care.

    PubMed

    Quinn, Charles T

    2013-12-01

    Sickle cell disease (SCD) is the name for a group of related blood disorders caused by an abnormal hemoglobin molecule that polymerizes on deoxygenation. SCD affects the entire body, and the multisystem pathophysiology begins in infancy. Thanks to prognostic and therapeutic advancements, some forms of SCD-related morbidity are decreasing, such as overt stroke. Almost all children born with SCD in developed nations now live to adulthood, and lifelong multidisciplinary care is necessary. This article provides a broad overview of SCD in childhood, from newborn screening through transition to adult medical care. PMID:24237976

  15. Newborn bloodspot screening for Duchenne Muscular Dystrophy: 21 years experience in Wales (UK)

    PubMed Central

    Moat, Stuart J; Bradley, Donald M; Salmon, Rachel; Clarke, Angus; Hartley, Louise

    2013-01-01

    Duchenne muscular dystrophy (DMD), a progressive X-linked neuromuscular disorder, has an estimated worldwide incidence of 1:3500 male births. Currently, there are no curative treatments and the mean age of diagnosis is 5 years. In addition, subsequent pregnancies frequently occur before a diagnosis is made in an index case. An ‘opt in' screening programme was introduced in Wales in 1990 with the aim to: reduce the diagnostic delay, permit reproductive choice and allow planning of the care of the affected boy. Newborn bloodspots were collected routinely as part of the Wales newborn screening programme. Specific consent was obtained for this test separately from the other tests. During the 21-year period, 369 780 bloodspot cards were received from male infants, of these 343 170 (92.8%) were screened using a bloodspot creatine kinase (CK) assay following parental consent. A total of 145 cases had a raised CK activity (≥250 U/l) and at follow-up, at 6–8 weeks of age, 79 cases had a normal serum CK (false-positive rate 0.023%) and 66 cases had an elevated serum CK. DMD was confirmed in 56 cases by genotyping/muscle biopsy studies, Becker muscular dystrophy in 5 cases and other rarer forms of muscular dystrophy in 5 cases. This long-term study has so far identified 13 false-negative cases. The incidence of DMD in Wales of 1:5136 during this period is lower than that of 1:4046 before commencement of screening in Wales. Screening has reduced the diagnostic delay enabling reproductive choice for parents of affected boys and earlier administration of current therapies. PMID:23340516

  16. Public participation in medical policy-making and the status of consumer autonomy: the example of newborn-screening programs in the United States.

    PubMed Central

    Hiller, E H; Landenburger, G; Natowicz, M R

    1997-01-01

    OBJECTIVES: State newborn-screening programs collectively administer the largest genetic-testing initiative in the United States. We sought to assess public involvement in formulating and implementing medical policy in this important area of genetic medicine. METHODS: We surveyed all state newborn-screening programs to ascertain the screening tests performed, the mechanisms and extent of public participation, parental access to information, and policies addressing parental consent or refusal of newborn screening. We also reviewed the laws and regulations of each state pertaining to newborn screening. RESULTS: Only 26 of the 51 state newborn-screening programs reported having advisory committees that include consumer representation. Fifteen states reported having used institutional review boards, another venue for public input. The rights and roles of parents vary markedly among newborn-screening programs in terms of the type and availability of screening information as well as consent-refusal and follow-up policies. CONCLUSIONS: There is clear potential for greater public participation in newborn-screening policy-making. Greater public participation would result in more representative policy-making and could enhance the quality of services provided by newborn-screening programs. PMID:9279262

  17. Useful second-tier tests in expanded newborn screening of isovaleric acidemia and methylmalonic aciduria.

    PubMed

    Shigematsu, Yosuke; Hata, Ikue; Tajima, Go

    2010-10-01

    Common use of pivalate-generating antibiotics in newborns in Japan and low cutoff value of C5-acylcarnitine (C5) to detect mild forms of isovaleric acidemia (IVA) led to 1,065 positive results from IVA screening among 146,000 newborns tested by tandem mass spectrometry over the last 3 years. Using our method to determine isovalerylglycine (IVG) levels in dried blood spots (DBS) as a second-tier test with IVG cutoff value of 0.5 nmol/ml in DBS, one patient with severe IVA was identified, and no recall of the second DBS was needed. Retrospective analysis revealed that most patients with moderate to severe forms of IVA have decreased free-carnitine levels shortly after birth and higher levels of IVG than those of C5, which suggests that this method is useful in evaluating the severity of IVA. Another second-tier test, to measure methylmalonic acid (MMA) levels in DBS by gas chromatography/mass spectrometry (GC/MS), has been developed to overcome difficulties in screening methylmalonic aciduria (MMAU) and propionic acidemia. Methanol extract from DBS was dried and derivatized using N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide. GC/MS was performed using splitless injection, electron-impact ionization, and selected ion monitoring for data recording. MMAU patients had much higher DBS concentrations of MMA (24.2-321.9 nmol/ml) than control newborns (0.34 ± 0.11 nmol/ml). MMA measurement in DBS was thought to provide useful information about the severity of MMAU, as MMAU patients with high levels of MMA had decreased levels of free carnitine and mildly increased levels of propionylcarnitine. PMID:20440648

  18. Incidence of Fragile X Syndrome by Newborn Screening for Methylated FMR1 DNA

    PubMed Central

    Coffee, Bradford; Keith, Krayton; Albizua, Igor; Malone, Tamika; Mowrey, Julie; Sherman, Stephanie L.; Warren, Stephen T.

    2009-01-01

    Fragile X syndrome (FXS) results from a CGG-repeat expansion that triggers hypermethylation and silencing of the FMR1 gene. FXS is referred to as the most common form of inherited intellectual disability, yet its true incidence has never been measured directly by large population screening. Here, we developed an inexpensive and high-throughput assay to quantitatively assess FMR1 methylation in DNA isolated from the dried blood spots of 36,124 deidentified newborn males. This assay displays 100% specificity and 100% sensitivity for detecting FMR1 methylation, successfully distinguishing normal males from males with full-mutation FXS. Furthermore, the assay can detect excess FMR1 methylation in 82% of females with full mutations, although the methylation did not correlate with intellectual disability. With amelogenin PCR used for detecting the presence of a Y chromosome, this assay can also detect males with Klinefelter syndrome (KS) (47, XXY). We identified 64 males with FMR1 methylation and, after confirmatory testing, found seven to have full-mutation FXS and 57 to have KS. Because the precise incidence of KS is known, we used our observed KS incidence as a sentinel to assess ascertainment quality and showed that our KS incidence of 1 in 633 newborn males was not significantly different from the literature incidence of 1 in 576 (p = 0.79). The seven FXS males revealed an FXS incidence in males of 1 in 5161 (95% confidence interval of 1 in 10,653–1 in 2500), consistent with some earlier indirect estimates. Given the trials now underway for possible FXS treatments, this method could be used in newborn or infant screening as a way of ensuring early interventions for FXS. PMID:19804849

  19. Assessment of the Knowledge and Attitudes of Saudi Mothers towards Newborn Screening

    PubMed Central

    Al-Sulaiman, Ayman; Kondkar, Altaf A.; Saeedi, Mohammad Y.; Saadallah, Amal; Al-Odaib, Ali; Abu-Amero, Khaled K.

    2015-01-01

    Objective. To assess the attitude and knowledge of the Saudi mothers toward newborn screening (NBS) program. Methods. A total of 425 Saudi women (only mothers who have at least one pregnancy) participated in the study from different regions in Saudi Arabia and completed the structured questionnaire which sought their views on the NBS services. Results. A majority of the participating women (91.1%) supported the NBS program and felt it was very important and useful. However, knowledge of NBS was found to be very limited and only 34.6% knew that NBS was a test to detect genetic disorders. A lack of communication and counseling to NBS clients by health authorities offering screening is implied. Conclusion. In general, there is a positive attitude towards the NBS program among Saudi women. However, they have several concerns to improve the availability of medication and formulas, genetic counseling, medical interventions, communication, education materials, and awareness. PMID:26543864

  20. Using Formative Research to Develop a Counselor Training Program for Newborn Screening in Ghana

    PubMed Central

    Anie, Kofi A.; Grant, Althea M.; Ofori-Acquah, Solomon F.; Ohene-Frempong, Kwaku

    2015-01-01

    Sickle cell disease (SCD), sickle cell trait (SCT) and related conditions are highly prevalent in sub-Saharan Africa. Despite the public health implications, there is limited understanding of the unique needs regarding establishing and implementing extensive screening for newborns and appropriate family counseling. We sought to gain understanding of community attitudes and beliefs about SCD/SCT from counselors and potential counselors in Ghana; obtain their input about goals for counseling following newborn screening; and obtain guidance about developing effective counselor education. Five focus groups with 32 health care providers and health educators from 9 of 10 regions in Ghana were conducted by trained facilitators according to a structured protocol. Qualitative data were coded and categorized to reflect common themes. Saturation was achieved in themes related to genetics/inheritance; common complications of SCD; potential for stigmatization; marital strain; and emotional stress. Misconceptions about SCT as a form of SCD were prevalent as were cultural and spiritual beliefs about the causes of SCD/SCT. Potential positive aspects included affected children's academic achievement as compensation for physical limitations, and family cohesion. This data informed recommendations for content and structure of a counselor training program that was provided to the Ministry of Health in Ghana. PMID:25193810

  1. VLCAD deficiency: Follow-up and outcome of patients diagnosed through newborn screening in Victoria.

    PubMed

    Evans, Maureen; Andresen, Brage S; Nation, Judy; Boneh, Avihu

    2016-08-01

    Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited metabolic disorder of fatty acid oxidation. Treatment practices of the disorder have changed over the past 10-15years since this disorder was included in newborn screening programs and patients were diagnosed pre-symptomatically. A genotype-phenotype correlation has been suggested but the discovery of novel mutations make this knowledge limited. Herein, we describe our experience in treating patients (n=22) diagnosed through newborn screening and mutational confirmation and followed up over a median period of 104months. We report five novel mutations. In 2013 we formalised our treatment protocol, which essentially follows a European consensus paper from 2009 and our own experience. The prescribed low natural fat diet is relaxed for patients who are asymptomatic when reaching age 5years but medium-chain triglyceride oil is recommended before and after physical activity regardless of age. Metabolic stability, growth, development and cardiac function are satisfactory in all patients. There were no episodes of encephalopathy or hypoglycaemia but three patients had episodes of muscle pain with our without rhabdomyolysis. Body composition studies showed a negative association between dietary protein intake and percent body fat. Larger patient cohort and longer follow up time are required for further elucidation of genotype-phenotype correlations and for establishing the role of dietary protein in metabolic stability and long-term healthier body composition in patients with VLCAD deficiency. PMID:27246109

  2. The role of National Library of Medicine web sites in newborn screening education.

    PubMed

    Fomous, Cathy; Miller, Naomi

    2006-01-01

    Expanded newborn screening programs and subsequent detection of rare genetic disorders challenge parents and their medical providers to learn about the treatment and management of these disorders. Many people seek medical information on the Internet but may encounter requests for registration or fees, or find that resources are out of date, difficult to understand, or buried in advertisements. The U.S. National Library of Medicine (NLM), a component of the National Institutes of Health, provides web-based resources that address the challenges of newborn screening education. These resources include MedlinePlus, Genetics Home Reference, ClinicalTrials.gov, and PubMed. NLM websites are not commercial, do not require registration or fees, and provide varied levels of information for a continuum of audiences from low-literacy consumers to health professionals. Using phenylketonuria as an example, this study describes the information that parents and their medical providers can find through NLM resources. NLM has embraced the digital age and provides the public with reliable, accurate, and up-to-date educational materials. PMID:17183579

  3. m.8993T>G-Associated Leigh Syndrome with Hypocitrullinemia on Newborn Screening.

    PubMed

    Mori, Mari; Mytinger, John R; Martin, Lisa C; Bartholomew, Dennis; Hickey, Scott

    2014-01-01

    Citrulline is among the metabolites measured by expanded newborn screening (NBS). While hypocitrullinemia can be a marker for deficiency of proximal urea cycle enzymes such as ornithine transcarbamylase (OTC), only a handful of state newborn screening programs in the United States officially report a low citrulline value for further work-up due to low positive predictive value. We report a case of a male infant who was found to have hypocitrullinemia on NBS. After excluding proximal urea cycle disorders by DNA sequencing, his NBS result was felt to be a false positive. At 4 months of age, he developed poor feeding, failure to thrive, apnea and infantile spasms with a progression to intractable seizures, as well as persistent hypocitrullinemia. He was diagnosed with Leigh syndrome due to a maternally inherited homoplasmic m.8993T>G mutation in the ATPase 6 gene. His mother, who had previously been diagnosed with cerebral palsy, was concurrently diagnosed with neuropathy, ataxia, and retinitis pigmentosa (NARP) due to heteroplasmy of the same mutation. She had progressive muscle weakness, ataxia, and speech dyspraxia. The m.8993T>G mutation causes mitochondrial ATP synthase deficiency and it is hypothesized to undermine the synthesis of citrulline by CPS1. In addition to proximal urea cycle disorders, the evaluation of an infant with persistent hypocitrullinemia should include testing for the m.8993T>G mutation and other disorders that cause mitochondrial dysfunction. PMID:25240982

  4. Development of a bile acid-based newborn screen for Niemann-Pick disease type C.

    PubMed

    Jiang, Xuntian; Sidhu, Rohini; Mydock-McGrane, Laurel; Hsu, Fong-Fu; Covey, Douglas F; Scherrer, David E; Earley, Brian; Gale, Sarah E; Farhat, Nicole Y; Porter, Forbes D; Dietzen, Dennis J; Orsini, Joseph J; Berry-Kravis, Elizabeth; Zhang, Xiaokui; Reunert, Janice; Marquardt, Thorsten; Runz, Heiko; Giugliani, Roberto; Schaffer, Jean E; Ory, Daniel S

    2016-05-01

    Niemann-Pick disease type C (NPC) is a fatal, neurodegenerative, cholesterol storage disorder. With new therapeutics in clinical trials, it is imperative to improve diagnostics and facilitate early intervention. We used metabolomic profiling to identify potential markers and discovered three unknown bile acids that were increased in plasma from NPC but not control subjects. The bile acids most elevated in the NPC subjects were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β,5α,6β-triol, an oxysterol elevated in NPC. A high-throughput mass spectrometry-based method was developed and validated to measure the glycine-conjugated bile acid in dried blood spots. Analysis of dried blood spots from 4992 controls, 134 NPC carriers, and 44 NPC subjects provided 100% sensitivity and specificity in the study samples. Quantification of the bile acid in dried blood spots, therefore, provides the basis for a newborn screen for NPC that is ready for piloting in newborn screening programs. PMID:27147587

  5. Stakeholder attitudes towards the role and application of informed consent for newborn bloodspot screening: a study protocol

    PubMed Central

    Nicholls, S G; Tessier, L; Etchegary, H; Brehaut, J C; Potter, B K; Hayeems, R Z; Chakraborty, P; Marcadier, J; Milburn, J; Pullman, D; Turner, L; Wilson, B J

    2014-01-01

    Introduction  Newborn bloodspot screening (NBS) involves testing a small sample of blood taken from the heel of the newborn for a number of serious and life-limiting conditions. In Canada, newborn screening programmes fall under provincial and territorial jurisdiction with no federal coordination. To date, we know very little about the underlying beliefs around different consent practices or how terminology is interpreted by different individuals. Differences in attitudes may have important healthcare consequences. This study will provide empirical data comparing stakeholder opinions on their understanding of consent-related terminology, the perceived applicability of different consent approaches to newborn screening, and the requirements of these different approaches. Methods and analysis Parents, healthcare professionals and policymakers will be recruited in the provinces of Ontario and Newfoundland and Labrador. Parents will be identified through records held by each provincial screening programme. Healthcare professionals will be purposively sampled on the basis of engagement with newborn screening. Within each province we will identify policymakers who have policy analysis or advisory responsibilities relating to NBS. Data collection will be by qualitative interviews. We will conduct 20 interviews with parents of young children, 10 interviews with key healthcare professionals across the range of appropriate specialties and 10 with policymakers at each site (40 per site, total, N=80). The examination of the transcripts will follow a thematic analysis approach. Recruitment started in June 2014 and is expected to be complete by June 2015. Ethics and dissemination This study received ethics approval from the Ottawa Health Science Network Research Ethics Board, the Children's Hospital of Eastern Ontario Research Ethics Board (both Ontario), and the Health Research Ethics Authority (Newfoundland and Labrador). Results These will be reported in peer

  6. A review of the psychosocial effects of false-positive results on parents and current communication practices in newborn screening.

    PubMed

    Hewlett, J; Waisbren, S E

    2006-10-01

    As more states adopt expanded newborn screening for metabolic disorders, the overall number of false positives increases. False-positive screening results have been associated with increased anxiety and stress in parents of infants who require follow-up testing, even after the infant's good health is confirmed. This article reviews the literature on the negative impact of false-positive newborn screening results on parents, along with a review of current communication practices for follow-up screening. The results of this review suggest that parental stress and anxiety can be reduced with improved education and communication to parents, specifically at the time of follow-up screening. Communication strategies with sample materials are proposed. PMID:16917730

  7. Ethical, legal, and social concerns about expanded newborn screening: fragile X syndrome as a prototype for emerging issues.

    PubMed

    Bailey, Donald B; Skinner, Debra; Davis, Arlene M; Whitmarsh, Ian; Powell, Cynthia

    2008-03-01

    Technology will make it possible to screen for fragile X syndrome and other conditions that do not meet current guidelines for routine newborn screening. This possibility evokes at least 8 broad ethical, legal, and social concerns: (1) early identification of fragile X syndrome, an "untreatable" condition, could lead to heightened anxiety about parenting, oversensitivity to development, alterations in parenting, or disrupted bonding; (2) because fragile X syndrome screening should be voluntary, informed consent could overwhelm parents with information, significantly burden hospitals, and reduce participation in the core screening program; (3) screening will identify some children who are or appear to be phenotypically normal; (4) screening might identify children with other conditions not originally targeted for screening; (5) screening could overwhelm an already limited capacity for genetic counseling and comprehensive care; (6) screening for fragile X syndrome, especially if carrier status is disclosed, increases the likelihood of negative self-concept, societal stigmatization, and insurance or employment discrimination; (7) screening will suggest risk in extended family members, raising ethical and legal issues (because they never consented to screening) and creating a communication burden for parents or expanding the scope of physician responsibility; and (8) screening for fragile X syndrome could heighten discrepancies in how men and women experience genetic risk or decide about testing. To address these concerns we recommend a national newborn screening research network; the development of models for informed decision-making; materials and approaches for helping families understand genetic information and communicating it to others; a national forum to address carrier testing and the disclosure of secondary or incidental findings; and public engagement of scientists, policy makers, ethicists, practitioners, and other citizens to discuss the desired aims of

  8. Evaluation of universal newborn hearing screening in South African primary care

    PubMed Central

    Harbinson, Shannon

    2015-01-01

    Background: Universal Newborn Hearing Screening (UNHC) is the gold standard toward early hearing detection and intervention, hence the importance of its deliberation within the South African context. Aim: To determine the feasibility of screening in low-risk neonates, using Otoacoustic Emissions (OAEs), within the Midwife Obstetric Unit (MOU) three-day assessment clinic at a Community Health Centre (CHC), at various test times following birth. Method: Within a quantitative, prospective design, 272 neonates were included. Case history interviews, otoscopic examinations and Distortion Product OAEs (DPOAEs) screening were conducted at two sessions (within six hours and approximately three days after birth). Data were analysed via descriptive statistics. Results: Based on current staffing profile and practice, efficient and comprehensive screening is not successful within hours of birth, but is more so at the MOU three-day assessment clinic. Significantly higher numbers of infants were screened at session 2, with significantly less false-positive results. At session 1, only 38.1% of the neonates were screened, as opposed to more than 100% at session 2. Session 1 yielded an 82.1% rate of false positive findings, a rate that not only has important implications for the emotional well-being of the parents; but also for resource-stricken environments where expenditure has to be accounted for carefully. Conclusion: Current findings highlight the importance of studying methodologies to ensure effective reach for hearing screening within the South African context. These findings argue for UNHS initiatives to include the MOU three-day assessment to ensure that a higher number of neonates are reached and confounding variables such as vernix have been eliminated. PMID:26245605

  9. Establishment and Development of a National Newborn Screening Programme for Congenital Hypothyroidism in Turkey

    PubMed Central

    Dilli, Dilek; Özbaş, Sema; Acıcan, Deniz; Yamak, Nergiz; Ertek, Mustafa; Dilmen, Uğur

    2013-01-01

    Objective: To assess the Turkish National Newborn Screening Programme (NNSP) for congenital hypothyroidism (CH). Retrospective study based on the data from NNSP. Methods: Since December 2006, a nationwide screening programme for CH has been conducted in Turkey by the Turkish Directorate of Public Health (TDPH) in cooperation with several institutions. We evaluated the database between January 2008 and July 2010 of this programme. According to the methodology of the NNSP, between three and five days of age (or at discharge from the hospital, if this occurs earlier) blood specimens were routinely collected from neonates on filter paper, by puncturing the heel. The accepted thyroid-stimulating hormone cut-off level for recall was 20 mU/L initially and 15 mU/L subsequently. The incidence of possible CH by years was reported. Results: During the evaluation period, 3223765 newborns were tested. The mean annual incidence of possible CH showed a gradual increase over the years (1:888 in 2008, 1:592 in 2009, and 1:469 in 2010). Regional differences were noted. Although the mean age of blood sampling did not change by years, the mean age at notification for suspected CH decreased from 19.2 to 15.7 days from 2008 to 2010. Conclusions: We reported the first assessment of NNSP in Turkey. An improvement in performance measures for the CH screening programme has been noted. Knowledge on incidence of confirmed CH is not yet available in the database. Conflict of interest:None declared. PMID:23748057

  10. Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study

    PubMed Central

    Baker, Mei W.; Atkins, Anne E.; Cordovado, Suzanne K.; Hendrix, Miyono; Earley, Marie C.; Farrell, Philip M.

    2016-01-01

    Purpose Many regions have implemented newborn screening (NBS) for cystic fibrosis (CF) using a limited panel of cystic fibrosis transmembrane regulator (CFTR) mutations after immunoreactive trypsinogen (IRT) analysis. We sought to assess the feasibility of further improving the screening using next-generation sequencing (NGS) technology. Methods An NGS assay was used to detect 162 CFTR mutations/variants characterized by the CFTR2 project. We used 67 dried blood spots (DBSs) containing 48 distinct CFTR mutations to validate the assay. NGS assay was retrospectively performed on 165 CF screen–positive samples with one CFTR mutation. Results The NGS assay was successfully performed using DNA isolated from DBSs, and it correctly detected all CFTR mutations in the validation. Among 165 screen-positive infants with one CFTR mutation, no additional disease-causing mutation was identified in 151 samples consistent with normal sweat tests. Five infants had a CF-causing mutation that was not included in this panel, and nine with two CF-causing mutations were identified. Conclusion The NGS assay was 100% concordant with traditional methods. Retrospective analysis results indicate an IRT/NGS screening algorithm would enable high sensitivity, better specificity and positive predictive value (PPV). This study lays the foundation for prospective studies and for introducing NGS in NBS laboratories. PMID:25674778

  11. [Performance of record linkage for cancer registry data linked with mammography screening data].

    PubMed

    Giersiepen, K; Bachteler, T; Gramlich, T; Reiher, J; Schubert, B; Novopashenny, I; Schnell, R

    2010-07-01

    The evaluation of the German Mammography Screening Program requires record linkage with data from cancer registries in order to measure the number of false-negative mammograms and interval cancers. This study aims at evaluating the performance of the established linkage method based on identifiers encrypted by the standard procedure of the German cancer registries. In addition, the results are compared with an alternative method based on plain text identifiers. A total of 16,572 records from the Bremen Mammography Screening Pilot Study were linked with data from the Bremen Cancer Registry. Based on a gold standard set of matching record pairs, homonym and synonym errors were determined. Given the customary threshold value in cancer registries, the plain text method showed a lower rate of synonym errors (2.1-5.1%) and a lower rate of homonym errors (0.01-0.15%). As 10.4 million women are invited to take part biennially in screening, the corresponding figures would be 3,237 homonym errors for the standard procedure and 294 using the plain text method provided equivalent conditions. The 11-fold increase in the homonym error rate documents the trade-off for better data protection using encrypted data. PMID:20652484

  12. Applying public health screening criteria: how does universal newborn screening compare to universal tumor screening for Lynch syndrome in adults with colorectal cancer?

    PubMed

    Cragun, Deborah; DeBate, Rita D; Pal, Tuya

    2015-06-01

    Institutions have increasingly begun to adopt universal tumor screening (UTS) programs whereby tumors from all newly diagnosed patients with colorectal cancer (CRC) are screened to identify who should be offered germline testing for Lynch syndrome (the most common cause of hereditary CRC). Given limited information about the impact of universal screening programs to detect hereditary disease in adults, we apply criteria used to evaluate public health screening programs and compare and contrast UTS with universal newborn screening (NBS) for the purpose of examining ethical implications and anticipating potential outcomes of UTS. Both UTS and a core set of NBS conditions clearly meet most of the Wilson and Jungner screening criteria. However, many state NBS panels include additional conditions that do not meet several of these criteria, and there is currently insufficient data to confirm that UTS meets some of these criteria. Comparing UTS and NBS with regard to newer screening criteria raises additional issues that require attention for both UTS and NBS. Comparisons also highlight the importance of evaluating the implementation of genomic tests to ensure or improve their effectiveness at reducing morbidity and mortality while minimizing potential harms. PMID:25323653

  13. Clinical and Environmental Influences on Metabolic Biomarkers Collected for Newborn Screening

    PubMed Central

    Ryckman, Kelli K.; Berberich, Stanton L.; Shchelochkov, Oleg A.; Cook, Daniel E; Murray, Jeffrey C.

    2012-01-01

    Objectives Identifying common clinical and environmental factors that influence newborn metabolic biomarkers will improve the utilization of metabolite panels for clinical diagnostic medicine. Design and Methods Environmental effects including gender, season of birth, gestational age, birth weight, feeding method and age at time of collection were evaluated for over 50 metabolites collected by the Iowa Neonatal Metabolic Screening Program on 221,788 newborns over a six year period. Results We replicated well known observations that low birth weight and preterm infants have higher essential amino acids and lower medium and long chain acylcarnitine levels than their term counterparts. Smaller, but still significant, differences were observed for gender and timing of sample collection, specifically the season in which the infant was born. Most intriguing were our findings of higher thyroid stimulating hormone in the winter months (P<1×10−40) which correlated with an increased false positive rate of congenital hypothyroidism in the winter (0.9%) compared to summer (0.6%). Previous studies, conducted globally, have identified an increased prevalence of suspected and confirmed cases of congenital hypothyroidism in the winter months. We found that the percentage of unresolved suspected cases were slightly higher in the winter (0.3% vs 0.2%). Conclusions We identified differences in metabolites by gestational age, birth weight, gender and season. Some are widely reported such as gestational age and birth weight, while others such as the effect of seasonality are not as well studied. PMID:23010448

  14. Informed Consent Should Be a Required Element for Newborn Screening, Even for Disorders with High Benefit-Risk Ratios.

    PubMed

    Fost, Norman

    2016-06-01

    Over-enthusiastic newborn screening has often caused substantial harm and has been imposed on the public without adequate information on benefits and risks and without parental consent. This problem will become worse when genomic screening is implemented. For the past 40 years, there has been broad agreement about the criteria for ethically responsible screening, but the criteria have been systematically ignored by policy makers and practitioners. Claims of high benefit and low risk are common, but they require precise definition and documentation, which has often not occurred, undermining claims that involuntary testing is justified. Even when the benefits and risks are well established, it does not automatically follow that involuntary testing is justified, a position supported by the widespread tolerance for parental refusal of immunizations and newborn screening. PMID:27338600

  15. Screening of Menkes Disease in Newborns that are likely to Benefit from Copper Treatment | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development's (NICHD) Molecular Medicine Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, or evaluate on a large-scale, population-based newborn screening for Menkes disease (also known as kinky hair disease).

  16. Present Status and Future Concerns of Expanded Newborn Screening in Malaysia: Sustainability, Challenges and Perspectives

    PubMed Central

    LEONG, Yin Hui; GAN, Chee Yuen; TAN, Mohd Adi Firdaus; MAJID, Mohamed Isa Abdul

    2014-01-01

    Newborn screening (NBS) program is an important tool for the early diagnosis and preventive treatment of life-long impairments. NBS is one of the strategies recommended by the World Health Organization to promote the primary prevention of congenital anomalies and the health of children with these conditions. However, NBS initiation and implementation in developing countries, especially South-East Asian and North African regions, are slow and challenging. Expanded NBS is not mandatory and has not yet been incorporated into the public healthcare system in our country. Limited funding, manpower shortages, inadequate support services, low public awareness, and uncertain commitment from healthcare practitioners are the main challenges in establishing this program at the national level. Involvement and support from policy makers are very important to the success of the program and the benefit of the entire population. PMID:24876809

  17. Present status and future concerns of expanded newborn screening in malaysia: sustainability, challenges and perspectives.

    PubMed

    Leong, Yin Hui; Gan, Chee Yuen; Tan, Mohd Adi Firdaus; Majid, Mohamed Isa Abdul

    2014-03-01

    Newborn screening (NBS) program is an important tool for the early diagnosis and preventive treatment of life-long impairments. NBS is one of the strategies recommended by the World Health Organization to promote the primary prevention of congenital anomalies and the health of children with these conditions. However, NBS initiation and implementation in developing countries, especially South-East Asian and North African regions, are slow and challenging. Expanded NBS is not mandatory and has not yet been incorporated into the public healthcare system in our country. Limited funding, manpower shortages, inadequate support services, low public awareness, and uncertain commitment from healthcare practitioners are the main challenges in establishing this program at the national level. Involvement and support from policy makers are very important to the success of the program and the benefit of the entire population. PMID:24876809

  18. Aetiologic diagnosis of hearing loss in children identified through newborn hearing screening testing.

    PubMed

    Forli, F; Giuntini, G; Bruschini, L; Berrettini, S

    2016-02-01

    With the implementation of universal newborn hearing screening (UNHS) programmes and early diagnosis and treatment of hearing problems, the need has clearly emerged to implement and carry out a systematic and coordinated protocol for the aetiological diagnosis of permanent hearing impairment (PHI). Within the framework of the Italian Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", it has been decided to consider the problems relative to aetiological diagnosis of child PHI within UNHS programmes. The specific objective was to apply a shared diagnostic protocol that can identify the cause in at least 70% of cases of PHI. For this part of the project, four main recommendations were identified that can be useful for an efficient aetiological diagnosis in children affected by PHI and that can offer valid suggestions to optimise resources and produce positive changes for third-level audiologic centres. PMID:27054388

  19. Primary care providers' experiences notifying parents of cystic fibrosis newborn screening results.

    PubMed

    Finan, Caitlin; Nasr, Samya Z; Rothwell, Erin; Tarini, Beth A

    2015-01-01

    This study examines primary care provider (PCP) experiences with the initial parental disclosure of cystic fibrosis (CF) newborn screening (NBS) results in order to identify methods to improve parent-provider communication during the CF NBS process. PCPs of infants who received positive CF NBS results participated in semistructured phone interviews. Interviews were analyzed using a qualitative content analysis. PCPs acknowledged the difficulty of "breaking bad news" to parents, and emphasized minimizing parental anxiety and maximizing parental understanding. PCPs used a variety of methods to notify parents, and shared varying information about the significance of the results. Variation in the method of parental notification, information discussed, and attention to parents' emotional needs may limit successful follow-up of children with positive CF NBS results. A multifaceted intervention to improve PCP knowledge, management, and communication could improve provider confidence, optimize information transfer, and minimize parental distress during the initial disclosure of CF NBS results. PMID:25104730

  20. Cordblood-Based High-Throughput Screening for Deafness Gene of 646 Newborns in Jinan Area of China

    PubMed Central

    Li, Shou-Xia; Chen, Ding-Li; Zhao, Su-Bin; Guo, Li-Li; Feng, Hai-Qin; Zhang, Xiao-Fang; Ping, Li-Li; Yang, Zhi-Ming; Sun, Cai-Xia

    2015-01-01

    Objectives Infants with slight/mild or late-onset hearing impairment might be missed in universal newborn hearing screening (UNHS). We identified the mutation hot spot of common deaf gene in the newborns in Jinan area population by screening the mutation spot with neonate cord blood, in order to make clear whether the neonate cord blood for screening is feasible. Methods Six hundred and forty-six newborns were subjected to both UNHS and genetic screening for deafness by using neonate cord blood. The newborn genetic screening targeted four deafness-associated genes, which were commonly found in the Chinese population including gap junction beta-2 protein (GJB2), gap junction beta-3 protein (GJB3), solute carrier family 26 member 4 (SLC26A4), and mtDNA 12S rRNA. The most common 20 spot mutations in 4 deaf genes were detected by MassARRAY iPLEX platform and mitochondrial 12S rRNA A1555G and C1494T mutations were sequenced using Sanger sequencing. Results Among the 646 newborns, 635 cases passed the UNHS and the other 11 cases (1.7%) did not. Of the 11 failures, two cases were found to carry homozygous GJB2 p.R143W pathogenic mutation, one case was found to have heterozygous GJB2 235delC mutation, and another one case carried heterozygous GJB3 p.R180X pathogenic mutation. Six hundred and thirty-five babies passed the newborn hearing screening, in which 25 babies were identified to carry pathogenic mutations, including 12 heterozygotes (1.9%) for GJB2 235delC, eight heterozygotes (1.3%) for SLC26A4 IVS7-2A>G, one heterozygote (0.2%) for p.R409H, two homozygotes (0.3%) for m.1494C>T, and two homozygotes (0.3%) for m.1555A>G. Conclusion Newborn genetic screening through the umbilical cord blood for common deafness-associated mutations may identify carriers sensitive to aminoglycoside antibiotic, and can effectively prevent or delay hearing loss occurs. PMID:26330914

  1. Neonatal newborn hearing screening: four years’ experience at Ferrara University Hospital (CHEAP Project): Part 1

    PubMed Central

    Ciorba, A; Hatzopoulos, S; Camurri, L; Negossi, L; Rossi, M; Cosso, D; Petruccelli, J; Martini, A

    2007-01-01

    Summary The Child Hearing Early Assessment Programme (CHEAP) regional project, was a combined departmental approach (Audiology, Neonatology) of the University Hospital of Ferrara, aimed at identifying neonatal hearing impairment and defining early intervention strategies. Aims of this project have been: i. construction of a neonatal screening programme using evoked otoacoustic emission and auditory brainstem responses; ii. the calculation of a precise estimate of cost-benefits for every child tested; iii. the development of an information flow instrument (database) for the storage of data and the statistical analysis of the results. The present report refers only to the results of the project related to the otoacoustic emission data from well-babies and intensive care unit residents. In the period January 2000-December 2004, 4269 full-term newborns and 654 Neonatal Intensive Care Unit babies were tested at the Neonatology Department. The cost of the Universal Neonatal Hearing Screening was estimated at € 9,20 per child, considering the use of the ILO-292 apparatus, and € 8,28 per child in the case of an automatic screener. In this screening model, the initial hardware costs can be re-iterated into budget in a period of two years, if 1000 children per year are tested. PMID:17601205

  2. Committee report: Method for evaluating conditions nominated for population-based screening of newborns and children.

    PubMed

    Calonge, Ned; Green, Nancy S; Rinaldo, Piero; Lloyd-Puryear, Michele; Dougherty, Denise; Boyle, Coleen; Watson, Michael; Trotter, Tracy; Terry, Sharon F; Howell, R Rodney

    2010-03-01

    The Secretary's Advisory Committee on Heritable Disorders in Newborns and Children is charged with evaluating conditions nominated for addition to the uniform screening panel and consequently making recommendations to the secretary of the US Department of Health and Human Services. This report describes the framework by which the committee approaches its task. Key decision nodes include initial review of every nomination to determine whether conditions are amenable for systematic evidence review, review of systematic evidence reviews conducted by the committee's external review group, and deliberation and formal recommendation for addition or exclusion to the uniform panel. Data analyzed include the accuracy and specificity of screening and diagnostic tests for nominated disorders, the extent of predicted health benefits, harms impact on disease course, and cost from early diagnosis and treatment. The committee process is guided by approaches used by similar entities, but more flexible criteria are sometimes needed to accommodate data limitations stemming from the rarity of many of these conditions. Possible outcomes of committee review range from recommendation to add a nominated condition to the uniform panel; provide feedback on specific gaps in evidence that must be addressed before making a decision; or rejection of a nomination (e.g., because of identified harms). The committee's structured evidence-based assessment of nominated conditions supports a consistently rigorous, iterative and transparent approach to its making recommendations regarding broad population-based screening programs for rare conditions in infants and children. PMID:20154628

  3. Current situation and prospects of newborn screening and treatment for Phenylketonuria in China — compared with the current situation in the United States, UK and Japan

    PubMed Central

    Mei, Lin; Song, Peipei; Kokudo, Norihiro; Xu, Lingzhong; Tang, Wei

    2013-01-01

    Summary Phenylketonuria (PKU) is a treat-able and prevent-able inborn error of metabolism which leads to severe mental retardation and neurobehavioral abnormalities. A screening program, especially for early detection, combined with a Phe-restricted therapeutic diet can help to control the process of PKU of most patients. The China government has put more emphasis on newborn screening and treatment against PKU, yet by comparing the situation of newborn screening and treatment against PKU in China and the relatively developed countries — United States, United Kingdom and Japan, the newborn screening and treatment against PKU in China is relatively weak and many deficiencies are found. More studies concerning multi-stage target blood Phe concentration criteria, a policy that requires newborn screening has to be taken, better financial support for newborn screening, publicity for newborn screening, and national guidelines for treatment of PKU may be prospects in China and may provide some support for better development of newborn screening and treatment against PKU in China. PMID:25343113

  4. Young adults' pre-existing knowledge of cystic fibrosis and sickle cell diseases: implications for newborn screening.

    PubMed

    Noke, Melissa; Ulph, Fiona

    2014-02-01

    Parental distress following newborn screening is thought to result from inadequate preparation for screening results which can result in maladjustment to screening results after birth. Although prior awareness of relevant genetic disorders such as cystic fibrosis and sickle cell diseases, and preparedness for screening is suggested to enhance information uptake and reduce parental distress, little is known about how young adults' prior knowledge prepares them for screening or affects the assimilation and retention of screening information. Thirty-four young adults, without familial genetic disease or screening experience took part in one of seven focus groups which examined knowledge of cystic fibrosis and sickle cell diseases and ability to assimilate new disease information. Thematic analysis revealed that adults had limited understanding of how cystic fibrosis and sickle cell diseases were inherited or how symptoms manifest, leaving them inadequately prepared for screening results if they do not engage with information interventions. Further, they selectively assimilated new disease information and had difficulty understanding new information in the absence of prior disease knowledge. Young adults' prior disease knowledge should be considered within a newborn screening context and written materials should consider the inclusion of carrier statistics to improve information relevance. PMID:23813300

  5. Beyond Critical Congenital Heart Disease: Newborn Screening Using Pulse Oximetry for Neonatal Sepsis and Respiratory Diseases in a Middle-Income Country

    PubMed Central

    Ang, Hak-Lee; Omar, Asma

    2015-01-01

    Background Studies on pulse oximetry screening for neonatal sepsis and respiratory disease in a middle-income country are lacking. Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is an effective and life-saving strategy in developed countries. While most studies have reported false-positive results during CCHD screening, they have not elaborated on the detected disease types. We studied the effectiveness and outcomes of pulse oximetry newborn screening for non-cardiac hypoxemic diseases such as neonatal sepsis, respiratory diseases, and CCHD in a middle-income country. Methods and Findings In a pilot study performed at the University Malaya Medical Centre (UMMC), Malaysia, all apparently healthy term newborns, delivered at UMMC were screened pre-discharge using pulse oximetry. Echocardiography was performed for newborns that had positive screening results on two separate occasions, 1-h apart. Newborns with normal echocardiograms were evaluated and treated for other non-cardiac diseases. Fifteen of 5247 term newborns had positive screening results. The median age at screening was 20 h. Thirteen newborns (0.24%) had significant non-cardiac diseases: sepsis (n = 2) and respiratory diseases (n = 11) that required hospitalization and treatment. The remaining two newborns with normal antenatal ultrasonograms had positive screening test and confirmed to have CCHD. Another 18 newborns with negative screening test were later admitted for treatment of sepsis (n = 16) and penumonia (n = 2). All newborns were treated and alive at the end of the study. The sensitivity and specificity of pulse oximetry screening for non-cardiac diseases were 42% and 99.9% respectively, and 100% and 99.7% for CCHD, respectively. Conclusions Routine pulse oximetry screening test was effective in identifying newborns with CCHD and other hypoxemia illnesses, which may led to potential life-threatening condition. This study showed that the expanded use of pulse

  6. Dataset and standard operating procedure for newborn screening of six lysosomal storage diseases: By tandem mass spectrometry.

    PubMed

    Elliott, Susan; Buroker, Norman; Cournoyer, Jason J; Potier, Anna M; Trometer, Joseph D; Elbin, Carole; Schermer, Mack J; Kantola, Jaana; Boyce, Aaron; Turecek, Frantisek; Gelb, Michael H; Scott, C Ronald

    2016-09-01

    In this data article we provide a detailed standard operating procedure for performing a tandem mass spectrometry, multiplex assay of 6 lysosomal enzymes for newborn screening of the lysosomal storage diseases Mucopolysaccharidosis-I, Pompe, Fabry, Niemann-Pick-A/B, Gaucher, and Krabbe, (Elliott, et al., 2016) [1]. We also provide the mass spectrometry peak areas for the product and internal standard ions typically observed with a dried blood spot punch from a random newborn, and we provide the daily variation of the daily mean activities for all 6 enzymes. PMID:27508243

  7. Newborn screening for severe T and B cell lymphopenia identifies a fraction of patients with Wiskott-Aldrich syndrome.

    PubMed

    Borte, Stephan; Fasth, Anders; von Döbeln, Ulrika; Winiarski, Jacek; Hammarström, Lennart

    2014-11-01

    The lack or marked reduction of recently formed T and B cells provides a basis for neonatal screening for severe combined immunodeficiencies (SCID) and X-linked agammaglobulinemia (XLA). Newborns with other conditions are also identified if a severe T or B cell lymphopenia is present at birth. We retrospectively analyzed Guthrie card samples from 11 children with Wiskott-Aldrich syndrome (WAS), a rare disease that requires early diagnosis and treatment, to determine whether combined T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) screening could identify these patients. 4 of 11 patients showed markedly reduced TREC or KREC copy numbers in their DBS as compared to storage-time matched controls and prospectively screened Swedish and German newborns. No correlation was observed between the WAS gene mutations, the clinical severity/course and the result of the screening assay. A diagnosis of WAS should thus be considered in newborns with positive TREC or KREC screening results. PMID:25217881

  8. Newborn screening for CF in a regional paediatric centre: the psychosocial effects of false-positive IRT results on parents.

    PubMed

    Moran, Janette; Quirk, Kirsten; Duff, Alistair J A; Brownlee, Keith G

    2007-05-01

    Neonatal screening for cystic fibrosis (CF) has been established in Leeds since 1975. The current method is measuring IRT and genotyping. Newborn screening for CF results in a small but significant number of false positives. This study explored the psychosocial reactions to such results in a group of parents (N=21) using semi-structured interviews. Responses were analysed using descriptive statistics and well-validated content analysis. Mothers described a range of emotions during the screening process including anxiety, distress and upset. Waiting for the repeat IRT test results was identified as the most emotionally difficult stage. Discussion focuses on good practice and implications for CF services. PMID:17056302

  9. Committee report: Considerations and recommendations for national guidance regarding the retention and use of residual dried blood spot specimens after newborn screening.

    PubMed

    Therrell, Bradford L; Hannon, W Harry; Bailey, Donald B; Goldman, Edward B; Monaco, Jana; Norgaard-Pedersen, Bent; Terry, Sharon F; Johnson, Alissa; Howell, R Rodney

    2011-07-01

    Newborn screening programs are state based with variable policies. Guidance regarding the retention, storage, and use of portions of newborn screening dried blood spots that remain after screening (residual specimens) was first published in 1996. Since then, newborn screening programs have paid increased attention to specimen storage and usage issues. Standard residual specimen uses include quality assurance and program evaluation, treatment efficacy, test refinement, and result verification. In all cases, privacy and security are primary concerns. In general, two distinct state practices regarding the storage and use of residual newborn screening specimens exist: (1) short-term storage (<3 years), primarily for standard program uses and (2) long-term storage (>18 years), for standard program uses and possible important public health research uses. Recently, there have been concerns in some consumer communities regarding both the potential uses of residual specimens and patient (newborn and family) privacy. To assist in policy improvements that can protect the individual's privacy and allow for important public health uses of residual newborn screening specimens, the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children has developed recommendations (with requested action by the Secretary where applicable). This report presents the Committee's recommendations and reviews the pertinent associated issues. PMID:21602691

  10. Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines.

    PubMed

    Huemer, Martina; Kožich, Viktor; Rinaldo, Piero; Baumgartner, Matthias R; Merinero, Begoña; Pasquini, Elisabetta; Ribes, Antonia; Blom, Henk J

    2015-11-01

    Newborn screening (NBS) is justified if early intervention is effective in a disorder generally not detected early in life on a clinical basis, and if sensitive and specific biochemical markers exist. Experience with NBS for homocystinurias and methylation disorders is limited. However, there is robust evidence for the success of early treatment with diet, betaine and/or pyridoxine for CBS deficiency and good evidence for the success of early betaine treatment in severe MTHFR deficiency. These conditions can be screened in dried blood spots by determining methionine (Met), methionine-to-phenylanine (Met/Phe) ratio, and total homocysteine (tHcy) as a second tier marker. Therefore, we recommend NBS for cystathionine beta-synthase and severe MTHFR deficiency. Weaker evidence is available for the disorders of intracellular cobalamin metabolism. Early treatment is clearly of advantage for patients with the late-onset cblC defect. In the early-onset type, survival and non-neurological symptoms improve but the effect on neurocognitive development is uncertain. The cblC defect can be screened by measuring propionylcarnitine, propionylcarnitine-to-acetylcarnitine ratio combined with the second tier markers methylmalonic acid and tHcy. For the cblE and cblG defects, evidence for the benefit of early treatment is weaker; and data on performance of Met, Met/Phe and tHcy even more limited. Individuals homozygous or compound heterozygous for MAT1A mutations may benefit from detection by NBS using Met, which on the other hand also detects asymptomatic heterozygotes. Clinical and laboratory data is insufficient to develop any recommendation on NBS for the cblD, cblF, cblJ defects, glycineN-methyltransferase-, S-adenosylhomocysteinehydrolase- and adenosine kinase deficiency. PMID:25762406

  11. Improving follow-up to newborn hearing screening: a learning-collaborative experience.

    PubMed

    Russ, Shirley A; Hanna, Doris; DesGeorges, Janet; Forsman, Irene

    2010-08-01

    Although approximately 95% of US newborns are now screened for hearing loss at birth, more than half of those who do not pass the screen lack a documented diagnosis. In an effort to improve the quality of the follow-up process, teams from 8 states participated in a breakthrough-series learning collaborative. Teams were trained in the Model for Improvement, a quality-improvement approach that entails setting clear aims, tracking results, identifying proven or promising change strategies, and the use of small-scale, rapid-cycle plan-do-study-act tests of these changes. Parents acted as equal partners with professionals in guiding system improvement. Teams identified promising change strategies including ensuring the correct identification of the primary care provider before discharge from the birthing hospital; obtaining a second contact number for each family before discharge; "scripting" the message given to families when an infant does not pass the initial screening test; and using a "roadmap for families" as a joint communication tool between parents and professionals to demonstrate each family's location on the "diagnostic journey." A learning-collaborative approach to quality improvement can be applied at a state-system level. Participants reported that the collaborative experience allowed them to move beyond a focus on improving their own service to improving connections between services and viewing themselves as part of a larger system of care. Ongoing quality-improvement efforts will require refinement of measures used to assess improvement, development of valid indicators of system performance, and an active role for families at all levels of system improvement. PMID:20679321

  12. Positive screening and carrier results for the England-wide universal newborn sickle cell screening programme by ethnicity and area for 2005–07

    PubMed Central

    Latinovic, Radoslav; Henthorn, Joan

    2010-01-01

    Aims The overall aim of the new national newborn programme is to identify infants at risk of sickle cell disease to allow early detection and to minimise deaths and complications. Methods Universal screening for sickle cell disease was introduced in England between September 2003 and July 2006. The 13 newborn laboratories each screen between 25 000 and 110 000 babies a year using the existing dried bloodspot cards. The specified conditions to be screened for include sickle cell anaemia (Hb SS), Hb SC disease, Hb S/β thalassaemia, Hb S/DPunjab and Hb S/OArab. Data are reported on screening results by ethnic group and geographical area. Results The prevalence of screen positive results across England is 1:2000. There is a 25-fold variation by geographical area. African babies make up 61% of all screen positive results despite representing only 4% of total births. Combined carrier rates vary widely by ethnicity, from 1.85 per 1000 (1:540) in ‘White British’ to 145 per 1000 (1:7) in ‘African’ babies. Refusal rates for screening show variation by ethnicity. Conclusions These results provide useful information both about the frequency of these conditions and the carrier state and their geographic and ethnic distribution across England. This can be used to refine counselling information and are also useful to target and plan services and public information. PMID:20591912

  13. Abnormal TREC-Based Newborn Screening Test in a Premature Neonate with Massive Perivillous Fibrin Deposition of the Placenta

    PubMed Central

    Kostadinov, Stefan; Robbins, Karen A.; Hayward, Anthony

    2016-01-01

    Severe combined immunodeficiency (SCID), a primary immunodeficiency arising from variable defects in lymphocyte development and survival, is characterized by significant deficiency of thymus derived (T-) lymphocytes and variable defects in the B-lymphocyte population. Newborn screening for SCID is based on detection of low numbers of T-cell receptor excision circles (TRECs) by real time quantitative PCR (RT-qPCR). This screening allows for early identification of individuals with SCID and other disorders characterized by T-lymphopenia. Higher rates of abnormal screens are commonly seen in premature and critically ill neonates, often representing false positives. It is possible that many abnormal screens seen in these populations are result of conditions that are characterized by systemic inflammation or stress, possibly in the context of stress-induced thymic involution. We present a case of a male infant delivered at 27 weeks, 6 days of gestation, with severe intrauterine growth restriction who had an abnormal TREC screen and a massive perivillous fibrin deposition (MPFD) of the placenta. This association has not been reported previously. We are raising the awareness to the fact that conditions, such as MPFD, that can create adverse intrauterine environment are capable of causing severe stress-induced thymic involution of the fetus which can present with abnormal TREC results on newborn screening. PMID:27403355

  14. Abnormal TREC-Based Newborn Screening Test in a Premature Neonate with Massive Perivillous Fibrin Deposition of the Placenta.

    PubMed

    Kostadinov, Stefan; Robbins, Karen A; Hayward, Anthony

    2016-01-01

    Severe combined immunodeficiency (SCID), a primary immunodeficiency arising from variable defects in lymphocyte development and survival, is characterized by significant deficiency of thymus derived (T-) lymphocytes and variable defects in the B-lymphocyte population. Newborn screening for SCID is based on detection of low numbers of T-cell receptor excision circles (TRECs) by real time quantitative PCR (RT-qPCR). This screening allows for early identification of individuals with SCID and other disorders characterized by T-lymphopenia. Higher rates of abnormal screens are commonly seen in premature and critically ill neonates, often representing false positives. It is possible that many abnormal screens seen in these populations are result of conditions that are characterized by systemic inflammation or stress, possibly in the context of stress-induced thymic involution. We present a case of a male infant delivered at 27 weeks, 6 days of gestation, with severe intrauterine growth restriction who had an abnormal TREC screen and a massive perivillous fibrin deposition (MPFD) of the placenta. This association has not been reported previously. We are raising the awareness to the fact that conditions, such as MPFD, that can create adverse intrauterine environment are capable of causing severe stress-induced thymic involution of the fetus which can present with abnormal TREC results on newborn screening. PMID:27403355

  15. Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

    PubMed Central

    Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; la Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A.; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D.; Morrone, Amelia

    2013-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275∗) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. PMID:24294134

  16. Medium-chain acyl-CoA deficiency: outlines from newborn screening, in silico predictions, and molecular studies.

    PubMed

    Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; la Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D; Morrone, Amelia

    2013-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275∗) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the "common" p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. PMID:24294134

  17. Uncertain diagnosis after newborn screening for cystic fibrosis: An ethics-based approach to a clinical dilemma.

    PubMed

    Massie, John; Gillam, Lynn

    2014-01-01

    There is uncertainty about the diagnosis of cystic fibrosis after newborn screening (NBS) for some babies, either because of an intermediate sweat chloride test or inconclusive gene mutation analysis. There is considerable difficulty knowing how best to manage these babies, some of whom will develop cystic fibrosis, but many not. This article offers an ethics-based approach to this clinical dilemma that should be helpful to clinicians managing the baby with an uncertain diagnosis of cystic fibrosis after NBS. PMID:24166986

  18. Postanalytical tools improve performance of newborn screening by tandem mass spectrometry

    PubMed Central

    Hall, Patricia L.; Marquardt, Gregg; McHugh, David M.S.; Currier, Robert J.; Tang, Hao; Stoway, Stephanie D.; Rinaldo, Piero

    2014-01-01

    Purpose: The purpose of this study was to compare performance metrics of postanalytical interpretive tools of the Region 4 Stork collaborative project to the actual outcome based on cutoff values for amino acids and acylcarnitines selected by the California newborn screening program. Methods: This study was a retrospective review of the outcome of 176,186 subjects born in California between 1 January and 30 June 2012. Raw data were uploaded to the Region 4 Stork Web portal as .csv files to calculate tool scores for 48 conditions simultaneously using a previously unpublished functionality, the tool runner. Scores for individual target conditions were deemed informative when equal or greater to the value representing the first percentile rank of known true-positive cases (17,099 cases in total). Results: In the study period, the actual false-positive rate and positive predictive value were 0.26 and 10%, respectively. Utilization of the Region 4 Stork tools, simple interpretation rules, and second-tier tests could have achieved a false-positive rate as low as 0.02% and a positive predictive value >50% by replacing the cutoff system with Region 4 Stork tools as the primary method for postanalytical interpretation. Conclusion: Region 4 Stork interpretive tools, second-tier tests, and other evidence-based interpretation rules could have reduced false-positive cases by up to 90% in California. PMID:24875301

  19. [Ethics and clinical practice guidelines: newborn hearing screening and early deaf childcare].

    PubMed

    André-Vert, J; Laurence, M

    2014-08-01

    A national program for newborn hearing screening is gradually spreading throughout France, coming at a specific historical time: French sign language was recognized as a French language only in 2005, after almost a century of this language being banned in French educational institutions. Therefore, social views on deafness vary considerably depending on hearing status--deaf or hearing--and on the language used: spoken language, sign language, or bilingual. To help professionals take these different perspectives into account, the ethical questions raised during the French Authority for Health clinical practice guidelines development on deaf child care were retrospectively analyzed based on the Childress and Beauchamp principles: autonomy, beneficence, non-maleficence, and justice. This analysis showed that the steps followed during the guideline development were very similar to those devised by J.M. Gomas's model for ethical decision making and were respectful of R. Ogien's minimal ethics principles: equal consideration for everyone, neutrality toward conceptions of what is good for oneself, and interventions limited to cases of obvious harm caused to others. PMID:25001434

  20. Public Health Action in Genomics Is Now Needed beyond Newborn Screening

    PubMed Central

    Bowen, M.S.; Kolor, K.; Dotson, W.D.; Ned, R.M.; Khoury, M.J.

    2016-01-01

    For decades, newborn screening was the only public health program in the US focused on reducing morbidity, mortality and disability in people affected by genetic conditions. The landscape has changed, however, as evidence-based recommendations are now available for several other genomic applications that can save lives now in the US. Many more such applications are expected to emerge in the next decade. An action plan, based on evidence, provides the impetus for a new paradigm for public health practice in genomics across the lifespan using established multilevel processes as a guide. These include policy interventions, education, clinical interventions, and surveillance. Applying what we know today in hereditary breast/ovarian cancer, Lynch syndrome and familial hypercholesterolemia has the potential to affect thousands of people in the US population every year. Enhanced partnerships between genetic and nongenetic providers of clinical medicine and public health are needed to overcome the challenges for implementing genomic medicine applications both now and in the future. PMID:22986915

  1. An update on the use of health information technology in newborn screening.

    PubMed

    Abhyankar, Swapna; Goodwin, Rebecca M; Sontag, Marci; Yusuf, Careema; Ojodu, Jelili; McDonald, Clement J

    2015-04-01

    Newborn screening (NBS) has high-stakes health implications and requires rapid and effective communication between many people and organizations. Multiple NBS stakeholders worked together to create national guidance for reporting NBS results with HL7 (Health Level 7) messages that contain LOINC (Logical Observation Identifiers Names and Codes) and SNOMED-CT (Systematized Nomenclature of Medicine-Clinical Terms) codes, report quantitative test results, and use standardized computer-readable UCUM units of measure. This guidance (a LOINC panel and an example annotated HL7 message) enables standard HL7 v2.5.1 laboratory messages to carry the information required for reporting NBS results. Other efforts include HL7 implementation guides for reporting point-of-care (POC) NBS results as well as standardizing follow-up of patients diagnosed with conditions identified through NBS. If the guidance is used nationally, regional and national registries can aggregate results from state programs to facilitate research and quality assurance and help ensure continuity of operations following a disaster situation. PMID:25935354

  2. Screening of newborn infants for cholestatic hepatobiliary disease with tandem mass spectrometry

    PubMed Central

    Mushtaq, Imran; Logan, Stuart; Morris, Michael; Johnson, Andrew W; Wade, Angie M; Kelly, Deirdre; Clayton, Peter T

    1999-01-01

    Objective To assess the feasibility of screening for cholestatic hepatobiliary disease and extrahepatic biliary atresia by using tandem mass spectrometry to measure conjugated bile acids in dried blood spots obtained from newborn infants at 7-10 days of age for the Guthrie test. Setting Three tertiary referral clinics and regional neonatal screening laboratories. Design Unused blood spots from the Guthrie test were retrieved for infants presenting with cholestatic hepatobiliary disease and from the two cards stored on either side of each card from an index child. Concentrations of conjugated bile acids measured by tandem mass spectrometry in the two groups were compared. Main outcome measures Concentrations of glycodihydroxycholanoates, glycotrihydroxycholanoates, taurodihydroxycholanoates, and taurotrihydroxycholanoates. Receiver operator curves were plotted to determine which parameter (or combination of parameters) would best predict the cases of cholestatic hepatobiliary disease and extrahepatic biliary atresia. The sensitivity and specificity at a selection of cut off values for each bile acid species and for total bile acid concentrations for the detection of the two conditions were calculated. Results 218 children with cholestatic hepatobiliary disease were eligible for inclusion in the study. Two children without a final diagnosis and five who presented at <14 days of age were excluded. Usable blood spots were obtained from 177 index children and 708 comparison children. Mean concentrations of all four bile acid species were significantly raised in children with cholestatic hepatobiliary disease and extrahepatic biliary atresia compared with the unaffected children (P<0.0001). Of 177 children with cholestatic hepatobiliary disease, 104 (59%) had a total bile acid concentration >33 μmol/l (97.5th centile value for comparison group). Of the 61 with extrahepatic biliary atresia, 47 (77%) had total bile acid concentrations >33

  3. Health Disparities in Hepatitis C Screening and Linkage to Care at an Integrated Health System in Southeast Michigan

    PubMed Central

    Brar, Indira; Baker-Genaw, Kimberly

    2016-01-01

    With recommended screening for hepatitis C among the 1945–1965 birth cohort and advent of novel highly effective therapies, little is known about health disparities in the Hepatitis C care cascade. Our objective was to evaluate hepatitis C screening rates and linkage to care, among patients who test positive, at our large integrated health system. We used electronic medical records to retrospectively identify patients, in the birth cohort, who were seen in 21 Internal Medicine clinics from July 2014 to June 2015. Patients previously screened for hepatitis C and those with established disease were excluded. We studied patients’ sociodemographic and medical conditions along with provider-specific factors associated with likelihood of screening. Patients who tested positive for HCV antibody were reviewed to assess appropriate linkage to care and treatment. Of 40,561 patients who met inclusion criteria, 21.3% (8657) were screened, 1.3% (109) tested positive, and 30% (30/100) completed treatment. Multivariate logistic regression showed that African American race, male gender, electronic health engagement, residency teaching clinic visit, and having more than one clinic visit were associated with higher odds of screening. Patients had a significant decrease in the likelihood of screening with sequential interval increase in their Charlson comorbidity index. When evaluating hepatitis C treatment in patients who screened positive, electronic health engagement was associated with higher odds of treatment whereas Medicaid insurance was associated with significantly lower odds. This study shows that hepatitis C screening rates and linkage to care continue to be suboptimal with a significant impact of multiple sociodemographic and insurance factors. Electronic health engagement emerges as a tool in linking patients to the hepatitis C care cascade. PMID:27525983

  4. [The Russian and international experience with the implementation of the programs of universal audiological screening of the newborn infants].

    PubMed

    Tavartkiladze, G A; Markova, T G; Chibisova, S S; Al'shardzhabi, I; Tsygankova, E R

    2016-01-01

    The problem of diagnostics of congenital hearing impairment has acquired special importance in the light of new possibilities for the early rehabilitation of the patients presenting with this condition. The implementation of the programs of universal audiological screening into the clinical practice of Russia and many other countries made it possible to significantly reducethe time necessary to confirm congenital impairment of hearing and begin the rehabilitative treatment. The present paper was designed to analyze the international experience with the implementation of the programs of universal audiological screening of the newborn infants as exemplified by such countries as Great Britain, USA, Germany, and Poland. The main indicators of the quality and the efficiency of such programs are considered taking into account the results of the epidemiological studies on the prevalence of congenital hearing impairment. A total of 1.8 mln newborn infants were examined in Russia during 2013. The first stage of screening involved 96.7% of the children, and only 2.9% of them remained uncovered by the examination. As many as 5,659 children were found to present with the congenital loss of hearing,with the prevalence of this condition being 3 per 1.000 newborn infants and the prevalence of deafness 0.6 per 1.000. The principal problem to be resolved for the organization of the management of these patients, both in Russia and other countries, remains the enhancement of the availability of comprehensive diagnostic examination and the timelyreferral of the patients to such examination (if appropriate based on the results of the screening). The successful solution of this problem requires personalized recording of the screening data with the use of the commonly accepted medical information systems. PMID:27213647

  5. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening.

    PubMed

    Koeberl, Dwight D; Young, Sarah P; Gregersen, Niels S; Vockley, Jerry; Smith, Wendy E; Benjamin, Daniel Kelly; An, Yan; Weavil, Susan D; Chaing, Shu H; Bali, Deeksha; McDonald, Marie T; Kishnani, Priya S; Chen, Y-T; Millington, David S

    2003-08-01

    Tandem mass spectrometry was adopted for newborn screening by North Carolina in April 1999. Since then, three infants with short-chain acyl-CoA dehydrogenase (SCAD) and one with isobutyryl-CoA dehydrogenase deficiency were detected on the basis of elevated butyrylcarnitine/isobutyrylcarnitine (C4-carnitine) concentrations in newborn blood spots analyzed by tandem mass spectrometry. For three SCAD-deficient infants, biochemical evaluation included a plasma acylcarnitine profile with markedly elevated C4-carnitine, urine organic acid analysis with markedly elevated ethylmalonic and 2-methylsuccinic acids, and markedly elevated [U-13C]butyrylcarnitine concentrations in medium from fibroblasts incubated with [U-13C]palmitic acid and excess l-carnitine, consistent with classic SCAD deficiency. Two of three infants diagnosed with classic SCAD deficiency remained asymptomatic; however, the third infant presented with seizures and a cerebral infarct at 10 wk of age. All three infants had putatively inactivating mutations in both alleles of the SCAD gene. The highly elevated plasma C4-carnitine levels in the three infants detected by newborn screening tandem mass spectrometry differentiated them from infants and children who were homozygous or compound heterozygous for one of two SCAD gene susceptibility variations; for the latter group the C4-carnitine levels were normal. Isobutyryl-CoA dehydrogenase deficiency in a fourth infant was confirmed after isolated elevation of C4-carnitine in the acylcarnitine profile. PMID:12736383

  6. Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis.

    PubMed

    Couce, M L; Ramos, F; Bueno, M A; Díaz, J; Meavilla, S; Bóveda, M D; Fernández-Marmiesse, A; García-Cazorla, A

    2015-11-01

    Maple syrup urine disease (MSUD) is a rare metabolic disorder for which the newborn screening (NBS) is possible but it has not been yet implemented for most Spanish regions. In the present study, we assess the clinical features and outcome of 14 MSUD Spanish patients with similar treatment protocol diagnosed either by NBS or by clinical symptoms. Eight patients were detected by NBS, four classic and four moderate MSUD. The average age at detection was 4.6 days, the mean plasmatic concentration of leucine at diagnosis was 1807 μM; the average number of days with leucine >1000 μM was 0.7 (0-4) and the mean number of total hospitalizations was 1.6 (0-5). Mean follow-up time was 70 months. They had good evolution: all remain asymptomatic, but 2 patients have attention deficit and hyperactivity disorder. Six patients with late diagnosis of classic MSUD were followed during 41 months. All presented with acute encephalopathy during the first month of life, mean leucine levels of 2355 μM, mean number of days with leucine >1000 μM of 6.6 (1-13) and mean number of total hospitalizations of 5.3 (4-7). Only two patients have a psychomotor development index in the lower limit (80 and 83). For all patients a good genotype-phenotype correlation was found and four novel mutations were identified: p.A311H, p.T84S, p.T397L, pL398P. Our study support that NBS improves prognosis of MSUD patients. But early diagnosis and an aggressive treatment together with a close monitoring of leucine levels improve neurological evolution in MSUD patients, even for those not detected by NBS. PMID:26232051

  7. Parental Views on Expanded Newborn Screening Using Whole-Genome Sequencing

    PubMed Central

    Joseph, Galen; Chen, Flavia; Harris-Wai, Julie; Puck, Jennifer M.; Young, Charlotte; Koenig, Barbara A.

    2016-01-01

    BACKGROUND AND OBJECTIVE The potential application of whole-genome sequencing (WGS) to state-mandated standard newborn screening (NBS) challenges the traditional public health approach to NBS and raises ethical, policy, and clinical practice issues. This article examines the perspectives and values of diverse healthy pregnant women and parents of children diagnosed with a primary immunodeficiency disorder about traditional NBS and expanded NBS with the use of WGS. METHODS We conducted 4 focus groups (3 in English and 1 in Spanish) with socioeconomically and ethnically diverse pregnant women (n = 26), and a comparison group with parents of children diagnosed with a primary immunodeficiency disorder (n = 5). RESULTS Pediatric policy–relevant themes that emerged from our analysis of the focus group data are presented within 4 categories: (1) perspectives on traditional NBS, (2) informed consent, (3) return of results, and (4) storage and retrieval of results. Analyses indicate that study participants desired greater inclusion in the NBS process. Despite an optimistic orientation to the potential benefits and limited harms likely to result from genomic applications of NBS, parents voiced concerns about privacy and control over test results. Limited trust in the medical system and the state-run NBS program informed these concerns. CONCLUSIONS Expanded NBS with WGS for pediatricians may require management of more genetic conditions, including mutations that convey risk to both the child and parents for adult-onset disorders, and an informed-consent process to manage the genomic data and storage of blood spots. Attention to how these technologies are understood in diverse populations is needed for effective implementation. PMID:26729702

  8. AB093. A case of exogenous C5-acylcarnitine giving rise to a false positive result in newborn screening (NBS)

    PubMed Central

    Yeo, Shu Jun; Tan, Ee Shien; Saumya, Jamuar; Poh, Sherry; Lim, James

    2015-01-01

    Background and objective NBS Screening by MS/MS is considered an effective screening test. However, the technique cannot distinguish between isobaric compounds, thus contributing to some false positive results. One such compound is C5-acylcarnitine in the in the identification of isovaleric acidemia (IVA) in the MS/MS profile. To report and contrast the findings of two newborns with C5-acylcarnitine elevations in newborn screening (NBS). Methods Blood collected on Guthrie card from newborns between 24-72 hours of life is analyzed by MS/MS. C5-acylcarnitine and its related ratios are measured in DBS sample to identify at risk newborn. Results Newborn A: DBS sample C5: 7.96 µmol/L (normal <0.50), C5/C0: 0.99 (normal <0.025), C5/C3: 16.1 (normal <0.40); Plasma acylcarnitines profile: C5: 9.42 µmol/L (normal 0.06-0.29). Urine organic acid profiles showed marked elevations of isovalerylglycine (IVG), ketone bodies and lactate. This profile is consistent with a patient presenting with a diagnosis of IVA. Newborn B: DBS sample C5: 0.84 µmol/L (normal <0.50), C5/C0: 0.041 (normal <0.025), C5/C3: 0.46 (normal <0.40); Despite the abnormal plasma acylcarnitines profile (C5: 4.38 µmol/L, normal 0.06-0.29), the urine acylglycine profile was normal [IVG: 1.02 mg/g Cr (normal 0.3-14.3 mg/g); 2-MBG: 0.16 mg/g Cr (normal: 0.3-7.5 mg/g)]. A 2nd plasma acylcarnitine showed a lower C5 level (1.49 µmol/L) and a repeat urine organic acid profile was normal; no IVG and 2-MBG detected. Mother’s (Newborn B) plasma acylcarnitines and urine organic acid profiles were normal, ruling out a possible maternal condition. Moreover, it was confirmed that mother and newborn were not on any antibiotics or steroids, which have been previously reported as the causal agents of falsely elevated C5-acylcarnitine. Further investigation revealed mom was using Mustela Nursing Comfort Balm which contained neopentanoate, a compound demonstrated by Boemer et al. [2014] as the causal agent for the false

  9. Linkage approach and direct COL4A5 gene mutation screening in Alport syndrome

    SciTech Connect

    Turco, A.E.; Rossetti, S.; Biasi, O.

    1994-09-01

    Alport Syndrome (AS) is transmitted as an X-linked dominant trait in the majority of families, the defective gene being COL4A5 at Xq22. In the remaining cases AS appears to be autosomally inherited. Recently, mutations in COL4A3 and COL4A4 genes at 2q35-q37 were identified in families with autosomal recessive AS. Mutation detection screening is being performed by non-radioactive single stand conformation polymorphism (SSCP), heteroduplex analysis, and automated DNA sequencing in over 170 AS patients enrolled in the ongoing Italian Multicenter Study on AS. So far twenty-five different mutations have been found, including missense, splicing, and frameshifts. Moreover, by using six tightly linked COL4A5 informative makers, we have also typed two larger AS families, and have shown compatible sex-linked transmission in one other, suggesting autosomal recessive inheritance. In this latter three-generation COL4A5-unlinked family we are now looking for linkage and for mutations in the candidate COL4A3 and COL4A4 genes on chromosome 2q.

  10. Using Benefit-Cost Ratio to Select Universal Newborn Hearing Screening Test Criteria

    PubMed Central

    Porter, Heather L.; Neely, Stephen T.; Gorga, Michael P.

    2009-01-01

    Objectives Current protocols presumably use criteria that are chosen on the basis of the sensitivity and specificity rates they produce. Such an approach emphasizes test performance, but does not include societal implications of the benefit of early identification. The purpose of the present analysis was to evaluate an approach to selecting criteria for use in UNHS programs that utilizes BCR to demonstrate an alternative method to audiologists, administrators, and others involved in UNHS protocol decisions. Design Existing data from over 1200 ears were used to analyze benefit-cost ratio (BCR) as a function of DPOAE level. These data were selected because both audiometric and DPOAE data were available on every ear. Although these data were not obtained in newborns, this compromise was necessary because audiometric outcomes (especially in infants with congenital hearing loss) in neonates are either lacking or limited in number. As such, it is important to note that the characteristics of responses from the group of subjects that formed the bases of the present analyses are different from those for neonates. This limits the extent to which actual criterion levels can be selected but should not affect the general approach of using BCR as a framework for considering UNHS criteria. Estimates of the prevalence of congenital hearing loss identified through UNHS in 37 states and U.S. territories in 2004 were used to calculate BCR. A range of estimates for the lifetime monetary benefits and yearly costs for UNHS were used, based on data available in the literature. Still, exact benefits and costs are difficult to know. Both one-step (DPOAE alone) and two-step (DPOAE followed by AABR) screening paradigms were considered in the calculation of BCR. The influence of middle-ear effusion was simulated by incorporating a range of expected DPOAE level reductions into an additional BCR analyses. Results Our calculations indicate that for a range of proposed benefit and cost estimates

  11. Inborn errors of metabolism and expanded newborn screening: review and update.

    PubMed

    Mak, Chloe Miu; Lee, Han-Chih Hencher; Chan, Albert Yan-Wo; Lam, Ching-Wan

    2013-11-01

    Inborn errors of metabolism (IEM) are a phenotypically and genetically heterogeneous group of disorders caused by a defect in a metabolic pathway, leading to malfunctioning metabolism and/or the accumulation of toxic intermediate metabolites. To date, more than 1000 different IEM have been identified. While individually rare, the cumulative incidence has been shown to be upwards of 1 in 800. Clinical presentations are protean, complicating diagnostic pathways. IEM are present in all ethnic groups and across every age. Some IEM are amenable to treatment, with promising outcomes. However, high clinical suspicion alone is not sufficient to reduce morbidities and mortalities. In the last decade, due to the advent of tandem mass spectrometry, expanded newborn screening (NBS) has become a mandatory public health strategy in most developed and developing countries. The technology allows inexpensive simultaneous detection of more than 30 different metabolic disorders in one single blood spot specimen at a cost of about USD 10 per baby, with commendable analytical accuracy and precision. The sensitivity and specificity of this method can be up to 99% and 99.995%, respectively, for most amino acid disorders, organic acidemias, and fatty acid oxidation defects. Cost-effectiveness studies have confirmed that the savings achieved through the use of expanded NBS programs are significantly greater than the costs of implementation. The adverse effects of false positive results are negligible in view of the economic health benefits generated by expanded NBS and these could be minimized through increased education, better communication, and improved technologies. Local screening agencies should be given the autonomy to develop their screening programs in order to keep pace with international advancements. The development of biochemical genetics is closely linked with expanded NBS. With ongoing advancements in nanotechnology and molecular genomics, the field of biochemical genetics

  12. Preliminary investigation of the use of newborn dried blood spots for screening pyridoxine-dependent epilepsy by LC-MS/MS.

    PubMed

    Jung, Sunhee; Tran, Nguyen-Thao B; Gospe, Sidney M; Hahn, Si Houn

    2013-11-01

    α-AASA and P6C were measured retrospectively in original newborn DBS of five patients with PDE using a LC-MS/MS method we developed previously. Both α-AASA and P6C were elevated markedly in the three newborn DBS stored at -20°C. At room temperature, α-AASA and P6C in DBS appeared stable for 3 days and then decreased by up to 70% after 14 days but remained much higher than control, indicating newborn screening for PDE is feasible. PMID:23953072

  13. First pilot newborn screening for four lysosomal storage diseases in an Italian region: identification and analysis of a putative causative mutation in the GBA gene.

    PubMed

    Paciotti, Silvia; Persichetti, Emanuele; Pagliardini, Severo; Deganuto, Marta; Rosano, Camillo; Balducci, Chiara; Codini, Michela; Filocamo, Mirella; Menghini, Anna Rita; Pagliardini, Veronica; Pasqui, Silvio; Bembi, Bruno; Dardis, Andrea; Beccari, Tommaso

    2012-11-20

    We report the first newborn screening pilot study in an Italian region for four lysosomal disorders including Pompe disease, Gaucher disease, Fabry disease and mucopolysaccharidosis type 1. The screening has been performed using enzymatic assay on Dry Blood Spot on filter paper. A total of 3403 newborns were screened. One newborn showed a reduction of β-glucosidase activity in leucocytes. Molecular analysis revealed a status of compound heterozygous for the panethnic mutation N370S and for the sequence variation E388K, not yet correlated to Gaucher disease onset. The functional consequences of the E388K replacement on β-glucosidase activity were evaluated by in vitro expression, showing that the mutant protein retained 48% of wild type activity. Structural modeling predicted that the E388K replacement, localized to a surface of the enzyme, would change the local charges distribution which, in the native protein, displays an overwhelming presence of negative charges. However, the newborn, and a 4 year old sister showing the same genomic alterations, are currently asymptomatic. This pilot newborn screening for lysosomal diseases appears to be feasible and affordable to be extended to large populations. Moreover other lysosomal diseases for which a therapy is available or will be available, could be included in the screening. PMID:22820396

  14. Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort

    PubMed Central

    Chang, Ruey-Kang R.; Lan, Yueh-Tze; Silka, Michael J.; Morrow, Hallie; Kwong, Alan; Smith-Lang, Janna; Wallerstein, Robert; Lin, Henry J.

    2014-01-01

    Objectives Autosomal recessive long QT syndrome (LQTS), or Jervell and Lange-Nielsen syndrome (JLNS), can be associated with sensorineural hearing loss (SNHL). We aimed to explore newborn hearing screening combined with ECGs for early JLNS detection. Study design We conducted California statewide, prospective ECG screening of children ≤6 years of age with unilateral or bilateral, severe or profound, sensorineural or mixed hearing loss. Families were identified through newborn hearing screening and interviewed about medical and family histories. Twelve-lead ECGs were obtained. Those with positive histories or QTc intervals ≥450 ms had repeat ECGs. DNA sequencing of 12 LQTS genes was performed for repeat QTc intervals ≥450 ms. Results We screened 707 subjects by ECGs (number screened/number of responses = 91%; number of responses/number of families who were mailed invitations = 54%). Of these, 73 had repeat ECGs, and 19 underwent gene testing. No subject had homozygous or compound heterozygous LQTS mutations, as in JLNS. However, 3 individuals (with QTc intervals of 472, 457, and 456 ms, respectively) were heterozygous for variants that cause truncation or missplicing: 2 in KCNQ1 (c.1343dupC or p.Glu449Argfs*14; c.1590+1G>A or p.Glu530sp) and 1 in SCN5A (c.5872C>T or p.Arg1958*). Conclusions In contrast to reports of JLNS in up to 4% of children with SNHL, we found no examples of JLNS. Because the 3 variants identified were unrelated to hearing, they likely represent the prevalence of potential LQTS mutations in the general population. Further studies are needed to define consequences of such mutations and assess the overall prevalence. PMID:24388587

  15. Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening.

    PubMed

    Pedersen, Christina B; Bischoff, Claus; Christensen, Ernst; Simonsen, Henrik; Lund, Allan M; Young, Sarah P; Koeberl, Dwight D; Millington, David S; Roe, Charles R; Roe, Diane S; Wanders, Ronald J A; Ruiter, Jos P N; Keppen, Laura D; Stein, Quinn; Knudsen, Inga; Gregersen, Niels; Andresen, Brage S

    2006-09-01

    The isobutyryl-CoA dehydrogenase (IBD) enzyme is involved in the degradation of valine. IBD deficiency was first reported in 1998 and subsequent genetic investigations identified acyl-CoA dehydrogenase (ACAD) 8, now IBD, as the gene responsible for IBD deficiency. Only three individuals homozygous or compound heterozygous for variations in the IBD gene have been reported. We present IBD deficiency in an additional four newborns with elevated C(4)-carnitine identified by tandem mass spectrometry (MS/MS) screening in Denmark and the United States. Three showed urinary excretions of isobutyryl-glycine, and in vitro probe analysis of fibroblasts from two newborns indicated enzymatic IBD defect. Molecular genetic analysis revealed seven new rare variations in the IBD gene (c.348C>A, c.400G>T, c.409G>A, c.455T>C, c.958G>A, c.1000C>T and c.1154G>A). Furthermore, sequence analysis of the short-chain acyl-CoA dehydrogenase (SCAD) gene revealed heterozygosity for the prevalent c.625G>A susceptibility variation in all newborns and in the first reported IBD patient. Functional studies in isolated mitochondria demonstrated that the IBD variations present in the Danish newborn (c.409G>A and c.958G>A) together with a previously published IBD variation (c.905G>A) disturbed protein folding and reduced the levels of correctly folded IBD tetramers. Accordingly, low/no IBD residual enzyme activity was detectable when the variant IBD proteins were overexpressed in Chang cells. PMID:16857760

  16. Surface-enhanced Raman scattering (SERS) for detection of phenylketonuria for newborn screening

    NASA Astrophysics Data System (ADS)

    Javanmard, M.; Davis, R. W.

    2014-02-01

    Diagnosis of Phenylketonuria (PKU) in newborns is important because it can potentially help prevent mental retardation since it is treatable by dietary means. PKU results in phenylketonurics having phenylalanine levels as high as 2 mM whereas the normal upper limit in healthy newborns is 120 uM. To this end, we are developing a microfluidic platform integrated with a SERS substrate for detection of high levels of phenylalanine. We have successfully demonstrated SERS detection of phenylalanine using various SERS substrates fabricated using nanosphere lithography, which exhibit high levels of field enhancement. We show detection of SERS at clinically relevant levels.

  17. Frequency of high-quality communication behaviors used by primary care providers of heterozygous infants after newborn screening

    PubMed Central

    Farrell, Michael H.; Christopher, Stephanie A.

    2013-01-01

    Objective To examine the quality of communication likely to be experienced by parents when being first informed about how newborn screening identified heterozygous “carrier” status for cystic fibrosis or sickle cell disease. Methods Primary care providers (PCPs) of infants found to have carrier status were telephoned over a 48-month period, and asked to rehearse with a standardized patient how they would inform the infants’ parent(s). 214 rehearsal transcripts were abstracted using explicit criteria methods to measure the frequency of five categories of high-quality communication behaviors. Results Overall, PCPs used large amounts of jargon and failed to use high quality communication behaviors. On average, PCPs used 18.6 total jargon words (8.7 unique words), but explained 2.4 jargon words. The most frequent assessment of understanding was the close-ended version, although it was only seen in 129 of 214 transcripts. The most common organizing behavior was importance emphasis (121/214). Precautionary empathy was rare; the most frequent behavior was “instruction about emotion” (33/214). Conclusions The limited use of high-quality communication behaviors in rehearsals raises concern about parental understanding, decision-making, and psychosocial outcomes after newborn screening. Practice Implications Measurement of specific behaviors may help PCPs to improve communication, and thereby improve the patient experience. PMID:23194821

  18. A Genomewide Screen for Autism: Strong Evidence for Linkage to Chromosomes 2q, 7q, and 16p

    PubMed Central

    2001-01-01

    Autism is characterized by impairments in reciprocal communication and social interaction and by repetitive and stereotyped patterns of activities and interests. Evidence for a strong underlying genetic predisposition comes from twin and family studies, although susceptibility genes have not yet been identified. A whole-genome screen for linkage, using 83 sib pairs with autism, has been completed, and 119 markers have been genotyped in 13 candidate regions in a further 69 sib pairs. The addition of new families and markers provides further support for previous reports of linkages on chromosomes 7q and 16p. Two new regions of linkage have also been identified on chromosomes 2q and 17q. The most significant finding was a multipoint maximum LOD score (MLS) of 3.74 at marker D2S2188 on chromosome 2; this MLS increased to 4.80 when only sib pairs fulfilling strict diagnostic criteria were included. The susceptibility region on chromosome 7 was the next most significant, generating a multipoint MLS of 3.20 at marker D7S477. Chromosome 16 generated a multipoint MLS of 2.93 at D16S3102, whereas chromosome 17 generated a multipoint MLS of 2.34 at HTTINT2. With the addition of new families, there was no increased allele sharing at a number of other loci originally showing some evidence of linkage. These results support the continuing collection of multiplex sib-pair families to identify autism-susceptibility genes. PMID:11481586

  19. AB107. Challenges in the management of patients with maple syrup urine disease diagnosed by newborn screening in a developing country

    PubMed Central

    De Castro-Hamoy, Leniza; Chiong, Mary Anne; Estrada, Sylvia; Cordero, Cynthia

    2015-01-01

    Maple syrup urine disease (MSUD) is a rare inborn error of metabolism resulting from a deficiency in the branched-chain alpha-ketoacid dehydrogenase complex. MSUD has been reported to be the most common inborn error of metabolism in the Philippines. This study describes all patients with MSUD patients diagnosed through newborn screening during its first two years of implementation and the challenges encountered during their medical management. We reviewed the medical records of all patients diagnosed with MSUD by newborn screening in the Philippines from its initiation in July 2012 to June 2014. There were 24 patients diagnosed with MSUD by newborn screening for the two-year period. The mean age at newborn screening is 4 days. All patients needed hospital admission. The most common complication during hospital admission was infection, needing intravenous antibiotics which were given to 21 of the patients. Out of the 24 diagnosed, 16 (66.67%) of patients are alive, while 8 (33.33%) have died. Several neurologic and non-neurologic complications have been observed during the follow-up of the patients. The common challenges of MSUD diagnosis and management in a low-resource setting identified in this study were late diagnosis, lack of access to metabolic specialists and medical supplies, nosocomial septicaemia, and protein deficiency. Aside from early properly-timed collection, improvement in other logistical concerns such as an efficient system of sending and delivery of samples will also help in earlier diagnosis. Mechanisms of transfer of critically ill patients, albeit challenging in our setting due to geographical concerns, must be improved. Hospitals in difficult-to-reach areas must be equipped to handle critical metabolic cases when transfers are not possible. Newborn screening has been proven to improve outcome in patients diagnosed to have MSUD but the success of the newborn screening program in preventing disability is also dependent on improvements in other

  20. [Auditory neuropathy due to the Q829X mutation in the gene encoding otoferlin (OTOF) in an infant screened for newborn hearing impairment].

    PubMed

    Gallo-Terán, J; Morales-Angulo, C; Sánchez, N; Manrique, M; Rodríguez-Ballesteros, M; Moreno-Pelayo, M A; Moreno, E; del Castillo, I

    2006-01-01

    We report an infant with auditory neuropathy secondary to the Q829X mutation in the gene encoding otoferlin (OTOF). Included in a universal newborn hearing screening program, the subject passed the otoacoustic emission (OAEs) test. Given that the infant had a familial history of deafness auditory brainstem response (ABR) testing was performed, revealing a profound hearing impairment. The genetic study confirmed that the subject was homozygous for the Q829X mutation in OTOF. The patient underwent a cochlear implant, obtaining satisfactory results. The moderately high prevalence of this mutation in the Spanish population could produce a significant false negative rate in newborn hearing screening programs using OAEs. PMID:17036997

  1. Short-chain acyl-CoA dehydrogenase (SCAD) deficiency: An examination of the medical and neurodevelopmental characteristics of 14 cases identified through newborn screening or clinical symptoms

    PubMed Central

    Waisbren, S.E.; Levy, H.L.; Noble, M.; Matern, D.; Gregersen, N.; Pasley, K.; Marsden, D.

    2014-01-01

    The medical and neurodevelopmental characteristics of 14 children with short-chain acyl-CoA dehydrogenase deficiency (SCADD) are described. Eight were detected as neonates by newborn screening. Three children diagnosed on the basis of clinical symptoms had normal newborn screening results while 3 were born in states that did not screen for SCADD. Treatment included frequent feedings and a low fat diet. All children identified by newborn screening demonstrated medical and neuropsychological development within the normative range on follow-up, although one child had a relative weakness in the motor area and another child exhibited mild speech delay. Of the 3 clinically identified children with newborn screening results below the cut-off value, 2 were healthy and performed within the normal range on cognitive and motor tests at follow-up. Four clinically identified children with SCADD experienced persistent symptoms and/or developmental delay. However, in each of these cases, there were supplementary or alternative explanations for medical and neuropsychological deficits. Results indicated no genotype-phenotype correlations. These findings suggest that SCADD might be benign and the clinical symptoms ascribed to SCADD reflective of ascertainment bias or that early identification and treatment prevented complications that may have occurred due to interaction between genetic susceptibility and other genetic factors or environmental stressors. PMID:18676165

  2. Newborn screening for X-linked adrenoleukodystrophy (X-ALD): validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method.

    PubMed

    Hubbard, Walter C; Moser, Ann B; Liu, Anita C; Jones, Richard O; Steinberg, Steven J; Lorey, Fred; Panny, Susan R; Vogt, Robert F; Macaya, Daniela; Turgeon, Coleman T; Tortorelli, Silvia; Raymond, Gerald V

    2009-07-01

    Newborn screening for X-linked adrenoleukodystrophy (X-ALD) has until now been limited in implementation because of the lack of an accepted standard methodology. We have previously reported a technique using LC-MS/MS analysis that could provide the basis for screening of newborns for X-ALD. The target analyte diagnostic for X-ALD and other peroxisomal disorders of peroxisomal beta-oxidation is 1-hexacosanoyl-2-lyso-sn-3-glycero-phosphorylcholine (26:0-lyso-PC). We report here the validation of the analytical method using an authentic standard of the target compound. The method possesses sensitivity of <1.0fmole injected on column with a correlation coefficient (R(2)) of 0.9987. A tetradeuterated analog of 26:0-lyso-PC served as the internal standard. The sensitivity of this clinical method was confirmed using 17 newborn samples of individuals with peroxisomal disorders retrieved from state newborn screening programs. These samples were run masked with over 1000 newborn samples. All affected individuals were identified with one exception. One sample which was retrieved as an affected did not have the biochemical or genetic abnormality of X-ALD and thus is considered an error in sample identity. These studies clearly show that the method is highly sensitive and accurate in identifying individuals with a defect in peroxisomal beta-oxidation such as X-ALD. PMID:19423374

  3. Parents' responses to receiving sickle cell or cystic fibrosis carrier results for their child following newborn screening

    PubMed Central

    Ulph, Fiona; Cullinan, Tim; Qureshi, Nadeem; Kai, Joe

    2015-01-01

    Universal newborn screening for sickle cell disorders and cystic fibrosis aims to enable the early identification and treatment of affected babies. Screening can also identify infants who are healthy carriers, with carrier results being the commonest outcome for parents and professionals to discuss in practice. However it is unclear what the effect will be on parents on being informed of their baby's carrier result. Semi-structured face-to-face interviews were conducted with a purposeful sample of 67 family members (49 mothers, 16 fathers, 2 grandparents) of 51 infants identified by universal newborn screening as carriers of cystic fibrosis (n=27) and sickle cell (n=24), across all health regions in England. Data were analysed by thematic analysis with subsequent respondent validation. Untoward anxiety or distress among parents appeared influenced by how results were conveyed, rather than the carrier result per se. Parents who had more prior awareness of carrier status or the possibility of a carrier result assimilated the information more readily. Being left in an information vacuum while awaiting results, or before seeing a professional, led some parents to fear that their child had a serious health condition. Parental distress and anxiety appeared mostly transient, subsiding with understanding of carrier status and communication with a professional. Parents regarded carrier results as valuable information and sought to share this with their families and to inform their children in the future. However parents needed greater support after communication of results in considering and accessing cascade testing, and negotiating further communication within their families. PMID:25005733

  4. Newborn Critical Congenital Heart Disease Screening Using Pulse Oximetry: Nursing Aspects.

    PubMed

    Hom, Lisa A; Martin, Gerard R

    2016-09-01

    Congenital heart disease (CCHD) is the most common birth defect. Screening for the most critical forms (CCHD) using pulse oximetry was added to the Recommended Uniform Screening Panel in the United States in 2011. Since then, CCHD screening has become nearly universal in the United States. Nurses are ideally situated to contribute to the development of best practices for implementation and provide education to families on CCHD screening. Much of the standardization, advocacy, and development of national recommendations occurred with key input from nurses. Nurses often have responsibility for educating parents, performing the screening, interpreting the screening algorithm, and the documentation of results. The nurse role often includes implementing follow-up quality improvement initiatives to ensure that systematic and accurate screening occurs. Smooth implementation can be achieved by identifying champions early, obtaining input from a multidisciplinary team including both physician and nursing leaders, and identifying ways to integrate screening into already existing workflow. By knowing the basics of why screening is important, how to screen, current recommendations on the follow-up for positive screens and the limitations of CCHD screening, nurses can advocate for their patients and positively impact outcomes for infants born with CCHD through early identification before discharge. PMID:27603538

  5. Incidence and Interrelated Factors in Patients With Congenital Hypothyroidism as Detected by Newborn Screening in Guangxi, China

    PubMed Central

    Fan, Xin; Qian, Jiale; Sooranna, Suren; Luo, Jingi; Li, Chuan; Tang, Qin; Lin, Caijuan

    2015-01-01

    Background. A newborn screening program (NSP) for congenital hypothyroidism (CH) was carried out in Guangxi in order to understand the incidence of CH and the factors interrelated to major types of CH in this region of China. Methods. During 2009 to 2013, data from 930 612 newborns attending NSP in Guangxi were collected. Patients were classified with either permanent CH (PCH) or transient CH (TCH) after 2 years of progressive study. Results. A total of 1210 patients were confirmed with CH with an incidence of 1/769, including 68 PCH and 126 TCH cases with incidences of 1/6673 and 1/3385, respectively. The frequency of thyroid stimulating hormone values greater than 5 mIU/L was 7.2%, which, based on WHO guidelines, suggests that the population was mildly iodine deficient. Conclusions. The incidence of CH was high in Guangxi. Approximately two thirds of CH patients were TCH, which may be due to a deficiency in iodine within the population. PMID:27335934

  6. Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening.

    PubMed

    Kunz, Joachim B; Awad, Saida; Happich, Margit; Muckenthaler, Lena; Lindner, Martin; Gramer, Gwendolyn; Okun, Jürgen G; Hoffmann, Georg F; Bruckner, Thomas; Muckenthaler, Martina U; Kulozik, Andreas E

    2016-02-01

    Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany. PMID:26658910

  7. Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening

    PubMed Central

    Green, Nancy S.; Mathur, Sanyukta; Kiguli, Sarah; Makani, Julie; Fashakin, Victoria; LaRussa, Philip; Lyimo, Magdalena; Abrams, Elaine J.; Mulumba, Lukia; Mupere, Ezekiel

    2016-01-01

    Sickle cell disease (SCD) is associated with high mortality for children under 5 years of age in sub-Saharan Africa. Newborn sickle screening program and enhanced capacity for SCD treatment are under development to reduce disease burden in Uganda and elsewhere in the region. Based on an international stakeholder meeting and a family-directed conference on SCD in Kampala in 2015, and interviews with parents, multinational experts, and other key informants, we describe health care, community, and family perspectives in support of these initiatives. Key stakeholder meetings, discussions, and interviews were held to understand perspectives of public health and multinational leadership, patients and families, as well as national progress, resource needs, medical and social barriers to program success, and resources leveraged from HIV/AIDS. Partnering with program leadership, professionals, patients and families, multinational stakeholders, and leveraging resources from existing programs are needed for building successful programs in Uganda and elsewhere in sub-Saharan Africa. PMID:27336011

  8. A Common Mutation Is Associated with a Mild, Potentially Asymptomatic Phenotype in Patients with Isovaleric Acidemia Diagnosed by Newborn Screening

    PubMed Central

    Ensenauer, Regina; Vockley, Jerry; Willard, Jan-Marie; Huey, Joseph C.; Sass, Jörn Oliver; Edland, Steven D.; Burton, Barbara K.; Berry, Susan A.; Santer, René; Grünert, Sarah; Koch, Hans-Georg; Marquardt, Iris; Rinaldo, Piero; Hahn, Sihoun; Matern, Dietrich

    2004-01-01

    Isovaleric acidemia (IVA) is an inborn error of leucine metabolism that can cause significant morbidity and mortality. Since the implementation, in many states and countries, of newborn screening (NBS) by tandem mass spectrometry, IVA can now be diagnosed presymptomatically. Molecular genetic analysis of the IVD gene for 19 subjects whose condition was detected through NBS led to the identification of one recurring mutation, 932C→T (A282V), in 47% of mutant alleles. Surprisingly, family studies identified six healthy older siblings with identical genotype and biochemical evidence of IVA. Our findings indicate the frequent occurrence of a novel mild and potentially asymptomatic phenotype of IVA. This has significant consequences for patient management and counseling. PMID:15486829

  9. Second-tier test for quantification of underivatized amino acids in dry blood spot for metabolic diseases in newborn screening.

    PubMed

    Wang, Chunyan; Zhu, Hongbin; Zhang, Wenyan; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2013-02-01

    The quantitative analysis of amino acids (AAs) in single dry blood spot (DBS) samples is an important issue for metabolic diseases as a second-tier test in newborn screening. An analytical method for quantifying underivatized AAs in DBS was developed by using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The sample preparation in this method is simple and ion-pairing agent is not used in the mobile phase that could avoid ion suppression, which happens in mass spectrometry and avoids damage to the column. Through chromatographic separation, some isomeric compounds could be identified and quantified, which cannot be solved through only appropriate multiple reactions monitoring transitions by MS/MS. The concentrations of the different AAs were determined using non-deuterated internal standard. All calibration curves showed excellent linearity within test ranges. For most of the amino acids the accuracy of extraction recovery was between 85.3 and 115 %, and the precision of relative standard deviation was <7.0 %. The 35 AAs could be identified in DBS specimens by the developed LC-MS/MS method in 17-19 min, and eventually 24 AAs in DBS were quantified. The results of the present study prove that this method as a second-tier test in newborn screening for metabolic diseases could be performed by the quantification of free AAs in DBS using the LC-MS/MS method. The assay has advantages of high sensitive, specific, and inexpensive merits because non-deuterated internal standard and acetic acid instead of ion-pairing agent in mobile phase are used in this protocol. PMID:22932943

  10. Observed and expected frequencies of structural hemoglobin variants in newborn screening surveys in Africa and the Middle East: Deviations from Hardy-Weinberg equilibrium

    PubMed Central

    Piel, Frédéric B.; Adamkiewicz, Thomas V.; Amendah, Djesika; Williams, Thomas N.; Gupta, Sunetra; Grosse, Scott D.

    2015-01-01

    Purpose Our objective was to compare observed and expected genotype proportions from newborn screening surveys of structural hemoglobin variants. Methods We conducted a systematic review of newborn screening surveys of hemoglobins S and C in Africa and the Middle-East. We compared observed frequencies to those expected assuming Hardy-Weinberg equilibrium (HWE). Significant deviations were identified by an exact test. The fixation index FIS was calculated to assess excess homozygosity. We compared newborn estimates corrected and uncorrected for HWE deviations using demographic data. Results Sixty samples reported genotype counts for hemoglobin variants in Africa and the Middle-East. Observed and expected counts matched in 27%. The observed number of sickle-cell anemia (SCA) individuals was higher than expected in 42 samples, reaching significance (p<0.05) in 24. High FIS were common across the study regions. The estimated total number of newborns with SCA, corrected based on FIS, were 33,261 annual births instead of 24,958 for the 38 samples across sub-Saharan Africa and 1,109 annual births instead of 578 for 12 samples from the Middle East. Conclusion Differences between observed and expected genotype frequencies are common in surveys of hemoglobin variants in the study regions. Further research is required to identify and quantify factors responsible for such deviations. Estimates based on HWE might substantially underestimate the annual number of SCA affected newborns (up to one third in sub-Saharan Africa and one half in the Middle East). PMID:26633548