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

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. Published by Elsevier Inc.

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…

Two faces of patient advocacy: the current controversy in newborn screening.

PubMed

Arnold, Cosby G

2014-08-01

Newborn screening programmes began in the 1960s, have traditionally been conducted without parental permission and have grown dramatically in the last decade. Whether these programmes serve patients' best interests has recently become a point of controversy. Privacy advocates, concerned that newborn screening infringes upon individual liberties, are demanding fundamental changes to these programmes. These include parental permission and limiting the research on the blood samples obtained, an agenda at odds with the viewpoints of newborn screening advocates. This essay presents the history of newborn screening in the USA, with attention to factors that have contributed to concerns about these programmes. The essay suggests that the rapid increase in the number of disorders screened for and the addition of research without either public knowledge or informed consent were critical to the development of resistance to mandatory newborn screening and research. Future newborn screening initiatives should include public education and comment to ensure continued support. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Factors Accounting for a Missed Diagnosis of Cystic Fibrosis After Newborn Screening

PubMed Central

Rock, Michael J.; Levy, Hara; Zaleski, Christina; Farrell, Philip M.

2015-01-01

Summary Newborn screening is a public health policy program involving the centralized testing laboratory, infant and their family, primary care provider, and subspecialist for confirmatory testing and follow-up of abnormal results. Cystic fibrosis (CF) newborn screening has now been enacted in all 50 states and the District of Columbia and throughout many countries in the world. Although CF neonatal screening will identify the vast majority of infants with CF, there are many factors in the newborn screening system that can lead to a missed diagnosis of CF. To inform clinicians, this article summarizes the CF newborn screening system and highlights 14 factors that can account for a missed diagnosis of CF. Care providers should maintain a high suspicion for CF if there are compatible symptoms, regardless of the results of the newborn screening test. These factors in newborn screening programs leading to a missed diagnosis of CF present opportunities for quality improvement in specimen collection, laboratory analysis of immunoreactive tryspinogen (IRT) and CF mutation testing, communication, and sweat testing. PMID:22081556

Cost-Effectiveness of Routine Screening for Critical Congenital Heart Disease in US Newborns

PubMed Central

Peterson, Cora; Grosse, Scott D.; Oster, Matthew E.; Olney, Richard S.; Cassell, Cynthia H.

2015-01-01

OBJECTIVES Clinical evidence indicates newborn critical congenital heart disease (CCHD) screening through pulse oximetry is lifesaving. In 2011, CCHD was added to the US Recommended Uniform Screening Panel for newborns. Several states have implemented or are considering screening mandates. This study aimed to estimate the cost-effectiveness of routine screening among US newborns unsuspected of having CCHD. METHODS We developed a cohort model with a time horizon of infancy to estimate the inpatient medical costs and health benefits of CCHD screening. Model inputs were derived from new estimates of hospital screening costs and inpatient care for infants with late-detected CCHD, defined as no diagnosis at the birth hospital. We estimated the number of newborns with CCHD detected at birth hospitals and life-years saved with routine screening compared with no screening. RESULTS Screening was estimated to incur an additional cost of $6.28 per newborn, with incremental costs of $20 862 per newborn with CCHD detected at birth hospitals and $40 385 per life-year gained (2011 US dollars). We estimated 1189 more newborns with CCHD would be identified at birth hospitals and 20 infant deaths averted annually with screening. Another 1975 false-positive results not associated with CCHD were estimated to occur, although these results had a minimal impact on total estimated costs. CONCLUSIONS This study provides the first US cost-effectiveness analysis of CCHD screening in the United States could be reasonably cost-effective. We anticipate data from states that have recently approved or initiated CCHD screening will become available over the next few years to refine these projections. PMID:23918890

Fifty years of newborn screening.

PubMed

Wilcken, Bridget; Wiley, Veronica

2015-01-01

Newborn screening has evolved fast following recent advances in diagnosis and treatment of disease, particularly the development of multiplex testing and applications of molecular testing. Formal evidence of benefit from newborn screening has been largely lacking, due to the rarity of individual disorders. There are wide international differences in the choice of disorders screened, and ethical issues in both screening and not screening are apparent. More evidence is needed about benefit and harm of screening for specific disorders and renewed discussion about the basic aims of newborn screening must be undertaken. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Diagnostic guidelines for newborns who screen positive in newborn screening.

PubMed

Kronn, David; Mofidi, Shideh; Braverman, Nancy; Harris, Katharine

2010-12-01

Recent expansion of the newborn screening panels has presented an interesting challenge to specialty care centers, especially the clinical genetics community. Some of the conditions in the core and secondary newborn screening panels have extremely variable clinical presentations; others are so rare that only a handful of newborns have been diagnosed with them to date (Region 4 Collaborative MS/MS project-http://region4genetics.org/msms_data_project/data_project_home.aspx). Definition of some disorders is problematic-does continued abnormality of the screening analyte constitute diagnosis or is further testing necessary? A work group of the New York Mid-Atlantic Consortium for Genetic and Newborn Screening Services (region 2), one of seven regional collaboratives funded by the Federal Health Resources and Services Administration and administered by the Maternal and Child Health Bureau (U22MC03956), has developed guidelines for the confirmation of diagnosis of the conditions in the newborn screening panels for use by the specialty care centers. The diagnostic guidelines are a work in progress and are being reviewed and revised regularly as our understanding of the newborn screened disorders improves. The aim is to make it a relevant guide for specialty care physicians and other healthcare professionals in the diagnostic workup of these patients.

The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study.

PubMed

Karaceper, Maria D; Chakraborty, Pranesh; Coyle, Doug; Wilson, Kumanan; Kronick, Jonathan B; Hawken, Steven; Davies, Christine; Brownell, Marni; Dodds, Linda; Feigenbaum, Annette; Fell, Deshayne B; Grosse, Scott D; Guttmann, Astrid; Laberge, Anne-Marie; Mhanni, Aizeddin; Miller, Fiona A; Mitchell, John J; Nakhla, Meranda; Prasad, Chitra; Rockman-Greenberg, Cheryl; Sparkes, Rebecca; Wilson, Brenda J; Potter, Beth K

2016-02-03

There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use. We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life. The higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.

Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening.

PubMed

Wolf, Barry

2017-04-01

We began screening newborns for biotinidase deficiency disorder in 1984, and now all states in the United States and many countries perform this screening. The purpose of this study was to determine the outcomes of older adolescent and adult individuals with the disorder identified by newborn screening. We located and surveyed, by questionnaire and telephone interviews, 44 individuals with profound biotinidase deficiency identified by newborn screening with a mean age of 23.1 years. All individuals had successfully completed high school, and many were attending or had completed college or graduate school. Compliance in using biotin has been excellent. Several individuals developed a variety of symptoms when they discontinued biotin for days or weeks. These features readily resolved when biotin was resumed. In addition, five treated women had nine uneventful pregnancies and deliveries. Newborn screening for profound biotinidase deficiency and early treatment with biotin result in excellent outcomes for older adolescents and adults with the disorder. In addition, mothers with profound biotinidase deficiency who were treated with biotin had pregnancies with good outcomes. These outcome results indicate that newborn screening for biotinidase deficiency is one of the most successful newborn screening programs.Genet Med 19 4, 396-402.

Newborn screening policy in the United Kingdom & the United States: two different communities of practice.

PubMed

Patch, Christine

2006-01-01

Newborn screening is a rapidly developing area driven by both technological advances and public pressure. If they are not yet, all nurses working with mothers and children will soon be involved with implementing newborn-screening programs, and it is therefore important that they appreciate both the benefits and potential harms of such programs. In the United Kingdom, policy regarding the implementation of newborn-screening programs is developed at national level, and consideration of the introduction of new tests is subject to a formalized evaluation framework. In the United States, by contrast, each state develops its own screening program. Knowledge of developments in newborn screening in different countries that have diverse types of healthcare systems helps to inform nurses about the totality of healthcare for newborns, and assists them in becoming more knowledgeable about how international standards differ from those in the United States.

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. Copyright 2010 Elsevier Inc. All rights reserved.

Consolidating newborn screening efforts in the Asia Pacific region : Networking and shared education.

PubMed

Padilla, Carmencita David; Therrell, Bradford L

2012-01-01

Many of the countries in the Asia Pacific Region, particularly those with depressed and developing economies, are just initiating newborn screening programs for selected metabolic and other congenital disorders. The cultural, geographic, language, and economic differences that exist throughout the region add to the challenges of developing sustainable newborn screening systems. There are currently more developing programs than developed programs within the region. Newborn screening activities in the Asia Pacific Region are particularly important since births there account for approximately half of the world's births. To date, there have been two workshops to facilitate formation of the Asia Pacific Newborn Screening Collaboratives. The 1st Workshop on Consolidating Newborn Screening Efforts in the Asia Pacific Region occurred in Cebu, Philippines, on March 30-April 1, 2008, as a satellite meeting to the 7th Asia Pacific Conference on Human Genetics. The second workshop was held on June 4-5, 2010, in Manila, Philippines. Workshop participants included key policy-makers, service providers, researchers, and consumer advocates from 11 countries with 50% or less newborn screening coverage. Expert lectures included experiences in the United States and the Netherlands, international quality assurance activities and ongoing and potential research activities. Additional meeting support was provided by the U.S. National Institutes of Health, the Centers for Disease Control and Prevention, the U.S. National Newborn Screening and Genetics Resource Center, the International Society for Neonatal Screening, and the March of Dimes. As part of both meeting activities, participants shared individual experiences in program implementation with formal updates of screening information for each country. This report reviews the activities and country reports from two Workshops on Consolidating Newborn Screening Efforts in the Asia Pacific Region with emphasis on the second workshop. It also updates the literature on screening activities and implementation/expansion challenges in the participating countries.

Important considerations for the newborn: access to postdischarge newborn care, pulse oximetry screening for congenital heart disease, and circumcision.

PubMed

Pattishall, Amy E; Spector, Nancy D; McPeak, Katie E

2014-12-01

This article addresses three areas in which new policies and research demonstrate the opportunity to impact the health of neonates: access to postdischarge newborn care, pulse oximetry screening for congenital heart disease, and circumcision. Recent research has identified that child healthcare providers are not typically adhering to the recommended first newborn visit within 48 h of hospital discharge. Despite its benefits, cost-effectiveness, and the recommendation that routine screening for cyanotic congenital heart disease be added to the panel of universal newborn screening, adoption of this practice is variable. Evidence suggests a significant reduction in the transmission of HIV linked to circumcision, leading professional organizations to generate new policy statements on neonatal male circumcision. Pediatric healthcare providers should pay careful attention to the timing of the first newborn outpatient follow-up visit. Pulse oximetry screening for cyanotic congenital heart disease is specific, sensitive and meets criteria for universal screening, and providers should utilize well designed screening protocols. In addition, healthcare providers for newborns, especially those who perform circumcisions, should provide nonbiased, up-to-date information on the medical, financial, and ethical aspects of the procedure.

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.

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 tandem...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 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 tandem...

Pediatric Provider Insight Into Newborn Screening for Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Bernardo, Janine; Nock, Mary

2015-06-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a major contributor to neonatal hyperbilirubinemia, yet newborn screening for this disorder in the United States is not standard practice. We surveyed pediatric providers regarding a novel newborn G6PD screening program successfully implemented in 2007 at a US urban women's hospital newborn nursery. An electronic survey was distributed to 472 pediatric providers addressing extent to which they were influenced by the screening program. Ninety-two (20%) providers responded, of whom 74 (80%) had taken care of G6PD-deficient patients diagnosed by the screening program. A majority found the diagnosis helpful for patient management and influential in their management. Most common changes in management included more counseling on jaundice and follow-up and avoidance of hemolytic crisis triggers. General pediatric providers support newborn G6PD screening and appreciate the current program. Knowing the G6PD deficiency status of newborns informed and influenced pediatric providers' care. © The Author(s) 2014.

Newborn screening for remethylation disorders and vitamin B12 deficiency-evaluation of new strategies in cohorts from Qatar and Germany.

PubMed

Gramer, Gwendolyn; Abdoh, Ghassan; Ben-Omran, Tawfeg; Shahbeck, Noora; Ali, Rehab; Mahmoud, Laila; Fang-Hoffmann, Junmin; Hoffmann, Georg F; Al Rifai, Hilal; Okun, Jürgen G

2017-04-01

Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-ß-synthase deficiency). Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar. A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine, methionine-phenylalanine-ratio and propionylcarnitine as second-tiers. Proposed cut-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B 12 deficiency from Qatar and Germany. Over a 12 months period, the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%, while allowing for additional systematic inclusion of remethylation disorders and vitamin B 12 deficiency into the screening panel for Qatar. In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B 12 deficiency and one patient with an isolated remethylation disorder. Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B 12 deficiency showed that all of these patients would have been detected by the cut-offs used in the proposed new strategy. In addition, an adapted strategy for Germany using methionine, methionine-phenylalanine-ratio and propionylcarnitine as first-tier, and homocysteine as a second-tier test was also positively evaluated retrospectively. The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B 12 deficiency in the screening panel, while lowering the recall rate. An adapted second-tier strategy is presented for screening in Germany and will be prospectively evaluated over the next years in a pilot project named "Newborn Screening 2020".

Newborn Screening Information Supports Public Health More than Informed Choice

ERIC Educational Resources Information Center

Hargreaves, Katrina; Stewart, Ruth; Oliver, Sandy

2005-01-01

Objective: To appraise information resources on newborn blood spot screening currently available for parents and health professionals internationally. Method: Health information on newborn blood spot screening was sourced internationally through the internet and, in the United Kingdom, through health service providers and support organisations. An…

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 ...

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

Public Attitudes Toward Expanded Newborn Screening.

PubMed

DeLuca, Jane M

There is limited research available on public knowledge and understanding of expanded newborn screening (NBS). The aims of this study were to assess current public knowledge and understanding of newborn screening disorders and procedures, perceived education needs, and preferences for the delivery of NBS information and education. An additional aim was to develop a beginning understanding of public attitudes toward screening for complex, severe, and in some cases untreatable disorders. In this preliminary descriptive study, eighty-eight participants completed surveys querying their general knowledge of NBS, preferred means of receiving NBS information and education, and their opinions about screening for severe disorders such as lysosomal storage diseases (LSD). Most study participants lacked general knowledge about current NBS practices, however, they supported expanding screening for severe and in some cases untreatable conditions. Most participants were enthusiastic about expanding NBS; however, those with more years of education were cautious regarding extensive costs of diagnosing and treating rare disorders. Newborn screening continues to evolve through new technological developments and the addition of more disorders to screening panels. More research of into public acceptance of newborn screening is needed. Addressing the educational needs of the public is important for improving their understanding of NBS and promoting patient-centered care in the era of genomic screening. Enhanced educational efforts are necessary for improving public understanding of newborn screening. Copyright © 2017 Elsevier Inc. All rights reserved.

Recommendations for newborn screening for galactokinase deficiency: A systematic review and evaluation of Dutch newborn screening data.

PubMed

Stroek, Kevin; Bouva, Marelle J; Schielen, Peter C J I; Vaz, Frédéric M; Heijboer, Annemieke C; de Jonge, Robert; Boelen, Anita; Bosch, Annet M

2018-03-21

Galactokinase (GALK) deficiency causes cataract leading to severe developmental consequences unless treated early. Because of the easy prevention and rapid reversibility of cataract with treatment, the Dutch Health Council advised to include GALK deficiency in the Dutch newborn screening program. The aim of this study is to establish the optimal screening method and cut-off value (COV) for GALK deficiency screening by performing a systematic review of the literature of screening strategies and total galactose (TGAL) values and by evaluating TGAL values in the first week of life in a cohort of screened newborns in the Netherlands. Systematic literature search strategies in OVID MEDLINE and OVID EMBASE were developed and study selection, data collection and analyses were performed by two independent investigators. A range of TGAL values measured by the Quantase Neonatal Total Galactose screening assay in a cohort of Dutch newborns in 2007 was evaluated. Eight publications were included in the systematic review. All four studies describing screening strategies used TGAL as the primary screening marker combined with galactose-1-phosphate uridyltransferase (GALT) measurement that is used for classical galactosemia screening. TGAL COVs of 2200 μmol/L, 1665 μmol/L and 1110 μmol/L blood resulted in positive predictive values (PPV) of 100%, 82% and 10% respectively. TGAL values measured in the newborn period were reported for 39 GALK deficiency patients with individual values ranging from 3963 to 8159 μmol/L blood and 2 group values with mean 8892 μmol/L blood (SD ± 5243) and 4856 μmol/L blood (SD ± 461). Dutch newborn screening data of 72,786 newborns from 2007 provided a median TGAL value of 110 μmol/L blood with a range of 30-2431 μmol/L blood. Based on TGAL values measured in GALK deficiency patients reported in the literature and TGAL measurements in the Dutch cohort by newborn screening we suggest to perform the GALK screening with TGAL as a primary marker with a COV of 2500 μmol/L blood, combined with GALT enzyme activity measurement as used in the classical galactosemia screening, to ensure detection of GALK deficiency patients and minimize false positive referrals. Copyright © 2018. Published by Elsevier Inc.

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…

Case Definitions for Conditions Identified by Newborn Screening Public Health Surveillance.

PubMed

Sontag, Marci K; Sarkar, Deboshree; Comeau, Anne M; Hassell, Kathryn; Botto, Lorenzo D; Parad, Richard; Rose, Susan R; Wintergerst, Kupper A; Smith-Whitley, Kim; Singh, Sikha; Yusuf, Careema; Ojodu, Jelili; Copeland, Sara; Hinton, Cynthia F

2018-01-01

Newborn screening (NBS) identifies infants with rare conditions to prevent death or the onset of irreversible morbidities. Conditions on the Health and Human Services Secretary's Recommended Uniform Screening Panel have been adopted by most state NBS programs, providing a consistent approach for identification of affected newborns across the United States. Screen-positive newborns are identified and referred for confirmatory diagnosis and follow-up. The designation of a clinically significant phenotype precursor to a clinical diagnosis may vary between clinical specialists, resulting in diagnostic variation. Determination of disease burden and birth prevalence of the screened conditions by public health tracking is made challenging by these variations. This report describes the development of a core group of new case definitions, along with implications, plans for their use, and links to the definitions that were developed by panels of clinical experts. These definitions have been developed through an iterative process and are piloted in NBS programs. Consensus public health surveillance case definitions for newborn screened disorders will allow for consistent categorization and tracking of short- and long-term follow-up of identified newborns at the local, regional, and national levels.

Case Definitions for Conditions Identified by Newborn Screening Public Health Surveillance

PubMed Central

Sontag, Marci K.; Sarkar, Deboshree; Comeau, Anne M.; Hassell, Kathryn; Botto, Lorenzo D.; Parad, Richard; Rose, Susan R.; Wintergerst, Kupper A.; Smith-Whitley, Kim; Singh, Sikha; Yusuf, Careema; Ojodu, Jelili; Copeland, Sara; Hinton, Cynthia F.

2018-01-01

Newborn screening (NBS) identifies infants with rare conditions to prevent death or the onset of irreversible morbidities. Conditions on the Health and Human Services Secretary’s Recommended Uniform Screening Panel have been adopted by most state NBS programs, providing a consistent approach for identification of affected newborns across the United States. Screen-positive newborns are identified and referred for confirmatory diagnosis and follow-up. The designation of a clinically significant phenotype precursor to a clinical diagnosis may vary between clinical specialists, resulting in diagnostic variation. Determination of disease burden and birth prevalence of the screened conditions by public health tracking is made challenging by these variations. This report describes the development of a core group of new case definitions, along with implications, plans for their use, and links to the definitions that were developed by panels of clinical experts. These definitions have been developed through an iterative process and are piloted in NBS programs. Consensus public health surveillance case definitions for newborn screened disorders will allow for consistent categorization and tracking of short- and long-term follow-up of identified newborns at the local, regional, and national levels.

An Evaluation of the Addition of Critical Congenital Heart Defect Screening in Georgia Newborn Screening Procedures.

PubMed

Rentmeester, Shelby T; Pringle, Johanna; Hogue, Carol R

2017-11-01

Objectives Each year in the U.S., approximately 7200 infants are born with a critical congenital heart defect (CCHD). The Georgia Department of Public Health (DPH) mandated routine screening for CCHD starting January 2015. The current study evaluated hospital performance of the mandated CCHD screenings in Georgia. Methods Utilizing the DPH newborn screening surveillance system, data from 6 months before and after the mandate were analyzed for reports submitted and positive CCHD screening results. Chi square tests of independence were performed to examine the association between reporting of results for CCHD screening after the mandate and hospital nursery level [level I (well-baby/newborn); level II (special care); level III (neonatal intensive care unit-NICU)] and NICU submissions. Results In the 6 months following implementation, reports of the screening increased, but the DPH had not received information for approximately 40% of newborns. Hospitals with level III nurseries had poorer reporting rates compared to hospitals with level I or II nurseries. Newborn screening (NBS) cards submitted by NICUs were less likely to contain the CCHD screening results compared to cards submitted by regular Labor and Delivery units. Conclusions for Practice Further attention should focus on improving both CCHD screening and reporting of screening results within hospitals with level III nurseries and from NICUs at all hospital levels. Identifying and addressing the root of the issue, whether it be hospital compliance with CCHD screening or reporting of the results, will help to improve screening rates for all newborns, especially those most vulnerable.

Expanded newborn metabolic screening programme in Hong Kong: a three-year journey.

PubMed

Chong, S C; Law, L K; Hui, J; Lai, C Y; Leung, T Y; Yuen, Y P

2017-10-01

No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme. We retrieved the demographics of the screened newborns and the screening results from July 2013 to July 2016. These data were used to calculate quality metrics such as call-back rate and false-positive rate. Clinical details of true-positive and false-negative cases and their outcomes were described. Finally, the call-back logistics for newborns with positive screening results were reviewed. During the study period, 30 448 newborns referred from 13 private and public units were screened. Of the samples, 98.3% were collected within 7 days of life. The overall call-back rate was 0.128% (39/30 448) and the false-positive rate was 0.105% (32/30 448). Six neonates were confirmed to have inborn errors of metabolism, including two cases of medium-chain acyl-coenzyme A dehydrogenase deficiency, one case of carnitine-acylcarnitine translocase deficiency, and three milder conditions. One case of maternal carnitine uptake defect was diagnosed. All patients remained asymptomatic at their last follow-up. The Centre of Inborn Errors of Metabolism has established a comprehensive expanded newborn screening programme for selected inborn errors of metabolism. It sets a standard against which the performance of other private newborn screening tests can be compared. Our experience can also serve as a reference for policymakers when they contemplate establishing a government-funded universal expanded newborn screening programme in the future.

Challenges and Opportunities in Establishing and Maintaining Newborn Screening in a Rural Area of Andhra Pradesh - Task Force Study by Indian Council of Medical Research.

PubMed

Radha Rama Devi, A; Ananthalakshmi, Y; Srimannarayana Rao, K

2018-02-19

The primary objective was to evaluate the feasibility of setting up newborn screening in rural areas in India. Secondary objective was to enhance the knowledge and awareness towards early detection of diseases by newborn screening, management of the affected baby and to impart genetic counseling. Awareness programs were conducted at different mandals in the district for the medical practioners during the preparatory phase of the Task Force Project. Educative lectures and clinical meetings regarding the importance and relevance of newborn screening were held every 3 months initially and half yearly later. Families were counselled during antenatal check-ups. Good co-operation was obtained from medical doctors and their willingness to participate in sample collection from the hospitals. Families accepted screening after an initial period of resistance. The fact that screening of this kind will help their babies made a positive impact. Many families started promoting newborn screening to their friends and relations. Confirmation of diagnosis, treatment, and follow-up were satisfactory with almost negligible number of cases lost to follow-up. With proper planning and commitment on the part of health authorities, it is possible to implement newborn screening in rural areas in India as well.

Carrier screening for single gene disorders.

PubMed

Rose, Nancy C; Wick, Myra

2018-04-01

Screening for genetic disorders began in 1963 with the initiation of newborn screening for phenylketonuria. Advances in molecular technology have made both newborn screening for newborns affected with serious disorders, and carrier screening of individuals at risk for offspring with genetic disorders, more complex and more widely available. Carrier screening today can be performed secondary to family history-based screening, ethnic-based screening, and expanded carrier screening (ECS). ECS is panel-based screening, which analyzes carrier status for hundreds of genetic disorders irrespective of patient race or ethnicity. In this article, we review the historical and current aspects of carrier screening for single gene disorders, including future research directions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Critical role of the March of Dimes in the expansion of newborn screening.

PubMed

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 state NBS programs. From the historic vantage point of four decades of March of Dimes involvement with newborn screening, this report reviews the unique origin of the first newborn screening test, and identifies from this point of origin several of the elements which still define the evolution of advocacy for NBS today. It also documents activities at the federal level and in seven states that have lead to expanded screening for newborns. Advances in NBS technology and medical treatment have informed policy development. Mobilization of volunteers and focused advocacy activities have brought about expansion of screening opportunities for newborns across the United States. But more work is needed. Continued application of the effective strategies identified in this report will help assure that all families have the best possible chance of assuring that their newborns do not have to suffer the complications of conditions that we know can be treated effectively. Copyright (c) 2006 Wiley-Liss, Inc.

Legal and Ethical Considerations in Allowing Parental Exemptions From Newborn Critical Congenital Heart Disease (CCHD) Screening.

PubMed

Hom, Lisa A; Silber, Tomas J; Ennis-Durstine, Kathleen; Hilliard, Mary Anne; Martin, Gerard R

2016-01-01

Critical congenital heart disease (CCHD) screening is rapidly becoming the standard of care in the United States after being added to the Recommended Uniform Screening Panel (RUSP) in 2011. Newborn screens typically do not require affirmative parental consent. In fact, most states allow parents to exempt their baby from receiving the required screen on the basis of religious or personally held beliefs. There are many ethical considerations implicated with allowing parents to exempt their child from newborn screening for CCHD. Considerations include the treatment of religious exemptions in our current legal system, as well as medical and ethical principles in relation to the rights of infants. Although there are significant benefits to screening newborns for CCHD, when a parent refuses for religious or personal beliefs, in the case of CCHD screening, the parental decision should stand.

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 definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined. PMID:25138334

Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada.

PubMed

Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G; Lillquist, Yolanda P; Waters, Paula J; Olpin, S; Andresen, B S; Palaty, Jan; Nelson, Judie; Vallance, Hilary

2008-01-01

Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency is an autosomal recessive disorder of fatty acid oxidation, with potential fatal outcome. MCAD deficiency is diagnosed by acylcarnitine analysis on newborn screening blood spot cards by tandem mass spectrometry. Early diagnosis of MCAD and presymptomatic treatment can potentially reduce morbidity and mortality. To evaluate incidence, clinical outcome, biochemical and molecular phenotype of MCAD cases detected in the first three years of newborn screening in British Columbia (BC). Medium chain length acylcarnitines, octanoylcarnitine (C8) and decanoylcarnitine (C10), were measured on newborn screening blood spot cards. Out of 121,000 live births, 17 newborns had C8 values above the screening cut-off of 0.38 umol/L. Ten newborns had elevated C8 on repeat cards and were investigated further. Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A > G MCAD mutation and three others were compound heterozygous for the c.985A > G and a second mutation. Two novel mutations were identified (c.260T > C and c.382T > A). The estimated incidence of MCAD was approximately 1:12,000 live births. Upon frequent feeding and carnitine supplementation, none of the patients had metabolic crises or adverse outcomes. Frequency of MCAD in BC is comparable to reports from other newborn screening programs. Persistence of elevated C8 levels and C8/C10 ratios in confirmed MCAD cases suggest that these are sensitive markers for newborn screening. Early detection and treatment have successfully prevented adverse health outcomes in patients with MCAD.

Impact of expanded newborn screening--United States, 2006.

PubMed

2008-09-19

Universal newborn screening for selected metabolic, endocrine, hematologic, and functional disorders is a well-established practice of state public health programs. Recent developments in tandem mass spectrometry (MS/MS), which is now capable of multi-analyte analysis in a high throughput capacity, has enabled newborn screening to include many more disorders detectable from a newborn blood spot. In 2006, to address the substantial variation that existed from state to state in the number of disorders included in newborn screening panels, the American College of Medical Genetics (ACMG), under guidance from the Health Resources and Services Administration, recommended a uniform panel of 29 disorders, which was subsequently endorsed by the federal Advisory Committee on Heritable Disorders in Newborns and Children. After 2006, most states began to expand their panels to include all 29 disorders; currently, 21 states and the District of Columbia have fully implemented the ACMG panel. To estimate the burden to state newborn screening programs resulting from this expansion, CDC used 2001-2006 data from those states with well-established MS/MS screening programs to estimate the number of children in the United States who would have been identified with disorders in 2006 if all 50 states and the District of Columbia had been using the ACMG panel. This report describes the results of that analysis, which indicated that, although such an expansion would have increased the number of children identified by only 32% (from 4,370 to 6,439), these children would have had many rare disorders that require local or regional capacity to deliver expertise in screening, diagnosis, and management. The findings underscore the need for public health and health-care delivery systems to build or expand the programs required to manage the rare disorders detected through expanded newborn screening, while also continuing programs to address more common disorders.

Parents are interested in newborn genomic testing during the early postpartum period.

PubMed

Waisbren, Susan E; Bäck, Danielle K; Liu, Christina; Kalia, Sarah S; Ringer, Steven A; Holm, Ingrid A; Green, Robert C

2015-06-01

We surveyed parents to ascertain interest in newborn genomic testing and determine whether these queries would provoke refusal of conventional state-mandated newborn screening. After a brief genetics orientation, parents rated their interest in receiving genomic testing for their healthy newborn on a 5-point Likert scale and answered questions about demographics and health history. We used logistic regression to explore factors associated with interest in genomic testing and tracked any subsequent rejection of newborn screening. We queried 514 parents within 48 hours after birth while still in hospital (mean age (SD) 32.7 (6.4) years, 65.2% female, 61.2% white, 79.3% married). Parents reported being not at all (6.4%), a little (10.9%), somewhat (36.6%), very (28.0%), or extremely (18.1%) interested in genomic testing for their newborns. None refused state-mandated newborn screening. Married participants and those with health concerns about their infant were less interested in newborn genomic testing (P = 0.012 and P = 0.030, respectively). Degree of interest for mothers and fathers was discordant (at least two categories different) for 24.4% of couples. Interest in newborn genomic testing was high among parents of healthy newborns, and the majority of couples had similar levels of interest. Surveying parents about genomic sequencing did not prompt rejection of newborn screening.Genet Med 17 6, 501-504.

Genomic newborn screening: public health policy considerations and recommendations.

PubMed

Friedman, Jan M; Cornel, Martina C; Goldenberg, Aaron J; Lister, Karla J; Sénécal, Karine; Vears, Danya F

2017-02-21

The use of genome-wide (whole genome or exome) sequencing for population-based newborn screening presents an opportunity to detect and treat or prevent many more serious early-onset health conditions than is possible today. The Paediatric Task Team of the Global Alliance for Genomics and Health's Regulatory and Ethics Working Group reviewed current understanding and concerns regarding the use of genomic technologies for population-based newborn screening and developed, by consensus, eight recommendations for clinicians, clinical laboratory scientists, and policy makers. Before genome-wide sequencing can be implemented in newborn screening programs, its clinical utility and cost-effectiveness must be demonstrated, and the ability to distinguish disease-causing and benign variants of all genes screened must be established. In addition, each jurisdiction needs to resolve ethical and policy issues regarding the disclosure of incidental or secondary findings to families and ownership, appropriate storage and sharing of genomic data. The best interests of children should be the basis for all decisions regarding the implementation of genomic newborn screening.

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

PubMed

Wang, Li-Yun; Chen, Nien-I; Chen, Pin-Wen; Chiang, Shu-Chuan; Hwu, Wuh-Liang; Lee, Ni-Chung; Chien, Yin-Hsiu

2013-02-10

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. 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). 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. Utilizing a molecular second-tier test for citrin deficiency and carnitine transporter deficiency is feasible.

Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis.

PubMed

Pfeil, Johannes; Listl, Stefan; Hoffmann, Georg F; Kölker, Stefan; Lindner, Martin; Burgard, Peter

2013-10-17

Glutaric aciduria type I (GA-I) is a rare metabolic disorder caused by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for GA-I. So far only limited data is available enabling health care decision makers to evaluate whether investing into GA-I screening represents value for money. The aim of our study was therefore to assess the cost-effectiveness of newborn screening for GA-I by tandem mass spectrometry (MS/MS) compared to a scenario where GA-I is not included in the MS/MS screening panel. We assessed the cost-effectiveness of newborn screening for GA-I against the alternative of not including GA-I in MS/MS screening. A Markov model was developed simulating the clinical course of screened and unscreened newborns within different time horizons of 20 and 70 years. Monte Carlo simulation based probabilistic sensitivity analysis was used to determine the probability of GA-I screening representing a cost-effective therapeutic strategy. Within a 20 year time horizon, GA-I screening averts approximately 3.7 DALYs (95% CI 2.9 - 4.5) and about one life year is gained (95% CI 0.7 - 1.4) per 100,000 neonates screened initially . Moreover, the screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176 Euro) per 100,000 screened neonates over a 20 year time horizon. Within the limitations of the present study, extending pre-existing MS/MS newborn screening programmes by GA-I represents a highly cost-effective diagnostic strategy when assessed under conditions comparable to the German health care system.

[Maternal and neonatal vitamin B12 deficiency detected by expanded newborn screening].

PubMed

Papp, Ferenc; Rácz, Gábor; Lénárt, István; Kóbor, Jenő; Bereczki, Csaba; Karg, Eszter; Baráth, Ákos

2017-12-01

Infant vitamin B 12 deficiency can manifest as a severe neurodegenerative disorder and is usually caused by maternal deficiency due to vegetarian diet or pernicious anaemia. Its early recognition and treatment can prevent potentially serious and irreversible neurologic damage. Biochemically, vitamin B 12 deficiency leads to an accumulation of methylmalonic acid, homocysteine, and propionylcarnitine. Expanded newborn screening using tandem mass spectrometry may identify neonatal and maternal vitamin B 12 deficiency by measurement of propionylcarnitine and other metabolites in the dried blood spot sample of newborns. To summarize our experiences gained by screening for vitamin B 12 deficiency. Clinical and laboratory data of vitamin B 12 -deficient infants diagnosed in Szeged Screening Centre were retrospectively analysed. In Hungary, expanded newborn screening was introduced in 2007. Since then approximately 395 000 newborns were screened in our centre and among them, we identified four newborns with vitamin B 12 deficiency based on their screening results. In three cases an elevated propionylcarnitine level and in the fourth one a low methionine level were indicative of vitamin B 12 deficiency. We also detected an additional vitamin B 12 -deficient infant with neurological symptoms at 4 months of age, after a normal newborn screening, because of elevated urinary methylmalonic acid concentration. Vitamin B 12 deficiency was secondary to maternal autoimmune pernicious anaemia in all the five infants. As a result of the recognized cases the incidence of infant vitamin B 12 deficiency in the East-Hungarian region was 1.26/100 000 births, but the real frequency may be higher. Conslusions: Optimizing the cut off values of current screening parameters and measuring of methylmalonic acid and/or homocysteine in the dried blood spot, as a second tier test, can improve recognition rate of vitamin B 12 deficiency. Orv Hetil. 2017; 158(48): 1909-1918.

The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience.

PubMed

Grosse, Scott D; Thompson, John D; Ding, Yao; Glass, Michael

2016-06-01

Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families. Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late-diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis. Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence-based economic evaluations of disorders proposed for addition to the state-mandated newborn screening panel. Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost-benefit models in Washington State as part of the rule-making process that resulted in the implementation of screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer-reviewed literature. The MCAD model projected a benefit-cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit-cost ratio of 4.0-5.4 to 1 for a discount rate of 3%-4% and a plausible range of 1-2 percentage point reductions in deaths up to age 10 years. The Washington State cost-benefit models of newborn screening were broadly consistent with peer-reviewed literature, and their findings of net benefit appear to be robust to uncertainty in parameters. Public health newborn screening programs can develop their own capacity to project expected costs and benefits of expansion of newborn screening panels, although it would be most efficient if this capacity were shared among programs. © 2016 Milbank Memorial Fund.

The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience

PubMed Central

THOMPSON, JOHN D.; DING, YAO; GLASS, MICHAEL

2016-01-01

Policy Points: Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families.Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late‐diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis.Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence‐based economic evaluations of disorders proposed for addition to the state‐mandated newborn screening panel. Context Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost‐benefit models in Washington State as part of the rule‐making process that resulted in the implementation of screening for medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. Methods We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer‐reviewed literature. Findings The MCAD model projected a benefit‐cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit‐cost ratio of 4.0‐5.4 to 1 for a discount rate of 3%‐4% and a plausible range of 1‐2 percentage point reductions in deaths up to age 10 years. Conclusions The Washington State cost‐benefit models of newborn screening were broadly consistent with peer‐reviewed literature, and their findings of net benefit appear to be robust to uncertainty in parameters. Public health newborn screening programs can develop their own capacity to project expected costs and benefits of expansion of newborn screening panels, although it would be most efficient if this capacity were shared among programs. PMID:27265561

Willingness to Pay for a Newborn Screening Test for Spinal Muscular Atrophy.

PubMed

Lin, Pei-Jung; Yeh, Wei-Shi; Neumann, Peter J

2017-01-01

The current US mandatory newborn screening panel does not include spinal muscular atrophy, the most common fatal genetic disease among children. We assessed population preferences for newborn screening for spinal muscular atrophy, and how test preferences varied depending on immediate treatment implications. We conducted an online willingness-to-pay survey of US adults (n = 982). Respondents were asked to imagine being parents of a newborn. Each respondent was presented with two hypothetical scenarios following the spinal muscular atrophy screening test: current standard of care (no treatment available) and one of three randomly assigned scenarios (new treatment available to improve functioning, survival, or both). We used a bidding game to elicit willingness to pay for the spinal muscular atrophy test, and performed a two-part model to estimate median and mean willingness-to-pay values. Most respondents (79% to 87%) would prefer screening their newborns for spinal muscular atrophy. People expressed a willingness to pay for spinal muscular atrophy screening even without an available therapy (median: $142; mean: $253). Willingness to pay increased with treatment availability (median: $161 to $182; mean: $270 to $297) and respondent income. Most respondents considered test accuracy, treatment availability, and treatment effectiveness very important or important factors in deciding willingness to pay. Most people would prefer and would be willing to pay for testing their newborn for spinal muscular atrophy, even in the absence of direct treatment. People perceive the spinal muscular atrophy test more valuable if treatment were available to improve the newborn's functioning and survival. Despite preferences for the test information, adding spinal muscular atrophy to newborn screening programs remains controversial. Future studies are needed to determine how early detection may impact long-term patient outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis of glutathione synthetase deficiency in newborn screening.

PubMed

Simon, E; Vogel, M; Fingerhut, R; Ristoff, E; Mayatepek, E; Spiekerkötter, U

2009-12-01

Glutathione synthetase (GSS) deficiency is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with haemolytic anaemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low GSS activity in erythrocytes or cultured skin fibroblasts. Diagnosis can be confirmed by mutational analysis. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. The most important determinants for outcome and survival in patients with GSS deficiency are early diagnosis and early initiation of treatment. The case of a newborn with GSS deficiency diagnosed by tandem mass spectrometry (MS/MS)-based newborn screening is described. After onset of clinical symptoms on the 2nd day of life, expanded newborn screening revealed normal results for all disorders included in the German screening programme; however, selective MS/MS screening revealed a >10-fold elevation of 5-oxoproline in dried blood, leading to the presumptive diagnosis of GSS deficiency by the 5th day of life. Diagnosis was later confirmed by detection of markedly reduced glutathione concentration in erythrocytes and mutational analysis of the GSS gene. Presently, GSS deficiency is not included in newborn screening programmes in Europe. As outcome depends significantly on early start of treatment, routine inclusion of this disorder in newborn screening panels should be considered.

Newborn screening 50 years later: access issues faced by adults with PKU

PubMed Central

Berry, Susan A.; Brown, Christine; Grant, Mitzie; Greene, Carol L.; Jurecki, Elaina; Koch, Jean; Moseley, Kathryn; Suter, Ruth; van Calcar, Sandra C.; Wiles, Judy; Cederbaum, Stephen

2013-01-01

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease. Genet Med 2013:15(8):591–599 PMID:23470838

Newborn screening 50 years later: access issues faced by adults with PKU.

PubMed

Berry, Susan A; Brown, Christine; Grant, Mitzie; Greene, Carol L; Jurecki, Elaina; Koch, Jean; Moseley, Kathryn; Suter, Ruth; van Calcar, Sandra C; Wiles, Judy; Cederbaum, Stephen

2013-08-01

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease.

Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening.

PubMed

Chien, Yin-Hsiu; Chiang, Shu-Chuan; Weng, Wen-Chin; Lee, Ni-Chung; Lin, Ching-Jie; Hsieh, Wu-Shiun; Lee, Wang-Tso; Jong, Yuh-Jyh; Ko, Tsang-Ming; Hwu, Wuh-Liang

2017-11-01

To demonstrate the feasibility of presymptomatic diagnosis of spinal muscular atrophy (SMA) through newborn screening (NBS). We performed a screening trial to assess all newborns who underwent routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center between November 2014 and September 2016. A real-time polymerase chain reaction (RT-PCR) genotyping assay for the SMN1/SMN2 intron 7 c.888+100A/G polymorphism was performed to detect homozygous SMN1 deletion using dried blood spot (DBS) samples. Then the exon 7 c.840C>T mutation and SMN2 copy number were determined by both droplet digital PCR (ddPCR) using the original screening DBS and multiplex ligation-dependent probe amplification (MLPA) using a whole blood sample. Of the 120 267 newborns, 15 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded 8 false-positives, and the other 7 patients were confirmed by the MLPA assay. Inclusion of the second-tier DBS ddPCR screening assay resulted in a positive prediction value of 100%. The incidence of SMA was 1 in 17 181 (95% CI, 1 in 8323 to 1 in 35 468). Two of the 3 patients with 2 copies of SMN2 and all 4 patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Five of the 8 false-positives were caused by intragenic recombination between SMN1 and SMN2. Newborn screening can detect patients affected by SMA before symptom onset and enable early therapeutic intervention. A combination of a RT-PCR and a second-tier ddPCR can accurately diagnose SMA from DBS samples with no false-positives. ClinicalTrials.gov NCT02123186. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of newborn screening parent education materials.

PubMed

Arnold, Connie L; Davis, Terry C; Frempong, Janet Ohene; Humiston, Sharon G; Bocchini, Anna; Kennen, Estela M; Lloyd-Puryear, Michele

2006-05-01

The purpose of this study was to measure the readability and user-friendliness (clarity, complexity, organization, appearance, and cultural appropriateness of materials) of parent education brochures on newborn screening. We studied English-language versions of the brochures that state newborn screening programs prepare and distribute. We obtained brochures from 48 states and Puerto Rico. We evaluated each brochure for readability with the Flesch reading ease formula. User-friendliness of the brochures was assessed with an instrument we created that contained 22 specific criteria grouped into 5 categories, ie, layout, illustrations, message, manageable information, and cultural appropriateness. Most current newborn screening brochures should be revised to make them more readable and user-friendly for parents. Ninety-two percent of brochures were written at a reading level that is higher than the average reading level of US adults (eighth-grade level). In most brochures, the essential information for parents was buried. Although all brochures were brief and focused on the newborn screening tests being performed, 81% needed improvement in getting to the point quickly and making it easy for parents to identify what they needed to know or to do. None of the brochures scored high in all 22 criteria on the user-friendliness checklist. Parent education materials about newborn screening should be revised to be easier to read and more user-friendly, by lowering the reading difficulty to eighth-grade level and focusing on issues such as layout, illustrations, message, information, and cultural appropriateness. It is important that state newborn screening programs and organizations work with parents to develop and to evaluate materials to ensure that they are user-friendly.

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…

75 FR 21645 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... with pre- and post-natal care about newborn screening and the potential use of residual dried blood... further access after newborn screening tests are completed. Multidisciplinary input, including from... quality check) or process improvement (e.g., non-commercial, internal program new test development or...

Parental Decision-Making and Acceptance of Newborn Bloodspot Screening: An Exploratory Study

PubMed Central

Nicholls, Stuart G.; Southern, Kevin W.

2013-01-01

Objective Newborn bloodspot screening is an internationally established public health measure. Despite this, there is a paucity of information relating to the decision-making process that parents go through when accepting newborn screening. This is important as screening panels are expanding; potentially leading to an increasing amount of complex information. This study sought to understand the factors that influence parental decisions and roles they play in the decision-making process. Patients and Methods Qualitative thematic evaluation of semi structured interviews with parents whose children had recently undergone newborn screening in the Merseyside and Cheshire region of England, UK. Results Eighteen interviews with first time parents (n = 12) and those with previous children (n = 6). Seven factors were identified as being either explicitly or implicitly related to parental decision-making: Experience, Attitudes to medicine, Information-seeking behaviour, Perceived knowledge, Attitudes to screening, and Perceived choice, all of which ultimately impact on Perceived decisional quality. Conclusions These results indicate that while content is important, other contextual factors such as personal experience, perceived choice, and general attitudes toward medicine, are also highly influential. In particular, relationships with key healthcare professionals are central to information collection, attitudes toward screening, and the level of deliberation that is invested in decisions to accept newborn bloodspot screening. PMID:24265771

Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis

PubMed Central

2013-01-01

Background Glutaric aciduria type I (GA-I) is a rare metabolic disorder caused by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for GA-I. So far only limited data is available enabling health care decision makers to evaluate whether investing into GA-I screening represents value for money. The aim of our study was therefore to assess the cost-effectiveness of newborn screening for GA-I by tandem mass spectrometry (MS/MS) compared to a scenario where GA-I is not included in the MS/MS screening panel. Methods We assessed the cost-effectiveness of newborn screening for GA-I against the alternative of not including GA-I in MS/MS screening. A Markov model was developed simulating the clinical course of screened and unscreened newborns within different time horizons of 20 and 70 years. Monte Carlo simulation based probabilistic sensitivity analysis was used to determine the probability of GA-I screening representing a cost-effective therapeutic strategy. Results Within a 20 year time horizon, GA-I screening averts approximately 3.7 DALYs (95% CI 2.9 – 4.5) and about one life year is gained (95% CI 0.7 – 1.4) per 100,000 neonates screened initially . Moreover, the screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176 Euro) per 100,000 screened neonates over a 20 year time horizon. Conclusion Within the limitations of the present study, extending pre-existing MS/MS newborn screening programmes by GA-I represents a highly cost-effective diagnostic strategy when assessed under conditions comparable to the German health care system. PMID:24135440

Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France

PubMed Central

2012-01-01

Background Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. Methods We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. Results We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Conclusions Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme to MCADD would appear to be cost-effective. The results of this analysis have been used to produce recommendations for the introduction of universal newborn screening for MCADD in France. PMID:22681855

Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France.

PubMed

Hamers, Françoise F; Rumeau-Pichon, Catherine

2012-06-08

Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme to MCADD would appear to be cost-effective. The results of this analysis have been used to produce recommendations for the introduction of universal newborn screening for MCADD in France.

Improving the Sensitivity and Positive Predictive Value in a Cystic Fibrosis Newborn Screening Program Using a Repeat Immunoreactive Trypsinogen and Genetic Analysis.

PubMed

Sontag, Marci K; Lee, Rachel; Wright, Daniel; Freedenberg, Debra; Sagel, Scott D

2016-08-01

To evaluate the performance of a new cystic fibrosis (CF) newborn screening algorithm, comprised of immunoreactive trypsinogen (IRT) in first (24-48 hours of life) and second (7-14 days of life) dried blood spot plus DNA on second dried blood spot, over existing algorithms. A retrospective review of the IRT/IRT/DNA algorithm implemented in Colorado, Wyoming, and Texas. A total of 1 520 079 newborns were screened, 32 557 (2.1%) had abnormal first IRT; 8794 (0.54%) on second. Furthermore, 14 653 mutation analyses were performed; 1391 newborns were referred for diagnostic testing; 274 newborns were diagnosed; and 201/274 (73%) of newborns had 2 mutations on the newborn screening CFTR panel. Sensitivity was 96.2%, compared with sensitivity of 76.1% observed with IRT/IRT (105 ng/mL cut-offs, P < .0001). The ratio of newborns with CF to heterozygote carriers was 1:2.5, and newborns with CF to newborns with CFTR-related metabolic syndrome was 10.8:1. The overall positive predictive value was 20%. The median age of diagnosis was 28, 30, and 39.5 days in the 3 states. IRT/IRT/DNA is more sensitive than IRT/IRT because of lower cut-offs (∼97 percentile or 60 ng/mL); higher cut-offs in IRT/IRT programs (>99 percentile, 105 ng/mL) would not achieve sufficient sensitivity. Carrier identification and identification of newborns with CFTR-related metabolic syndrome is less common in IRT/IRT/DNA compared with IRT/DNA. The time to diagnosis is nominally longer, but diagnosis can be achieved in the neonatal period and opportunities to further improve timeliness have been enacted. IRT/IRT/DNA algorithm should be considered by programs with 2 routine screens. Copyright © 2016 Elsevier Inc. All rights reserved.

Newborn screening: new developments, new dilemmas.

PubMed

Kerruish, N J; Robertson, S P

2005-07-01

Scientific and technological advances are lending pressure to expand the scope of newborn screening. Whereas this has great potential for improving child health, it also challenges our current perception of such programmes. Standard newborn screening programmes are clearly justified by the fact that early detection and treatment of affected individuals avoids significant morbidity and mortality. However, proposals to expand the scope and complexity of such testing are not all supported by a similar level of evidence for unequivocal benefit. We argue that screening for genetic susceptibility to complex disorders is inherently different from standard screening and, while of potential value, must be considered separately from conventional testing.

A Decision-Tree Approach to Cost Comparison of Newborn Screening Strategies for Cystic Fibrosis

PubMed Central

Wells, Janelle; Rosenberg, Marjorie; Hoffman, Gary; Anstead, Michael

2012-01-01

OBJECTIVE: Because cystic fibrosis can be difficult to diagnose and treat early, newborn screening programs have rapidly developed nationwide but methods vary widely. We therefore investigated the costs and consequences or specific outcomes of the 2 most commonly used methods. METHODS: With available data on screening and follow-up, we used a simulation approach with decision trees to compare immunoreactive trypsinogen (IRT) screening followed by a second IRT test against an IRT/DNA analysis. By using a Monte Carlo simulation program, variation in the model parameters for counts at various nodes of the decision trees, as well as for costs, are included and applied to fictional cohorts of 100 000 newborns. The outcome measures included the numbers of newborns given a diagnosis of cystic fibrosis and costs of screening strategy at each branch and cost per newborn. RESULTS: Simulations revealed a substantial number of potential missed diagnoses for the IRT/IRT system versus IRT/DNA. Although the IRT/IRT strategy with commonly used cutoff values offers an average overall cost savings of $2.30 per newborn, a breakdown of costs by societal segments demonstrated higher out-of-pocket costs for families. Two potential system failures causing delayed diagnoses were identified relating to the screening protocols and the follow-up system. CONCLUSIONS: The IRT/IRT screening algorithm reduces the costs to laboratories and insurance companies but has more system failures. IRT/DNA offers other advantages, including fewer delayed diagnoses and lower out-of-pocket costs to families. PMID:22291119

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

PubMed Central

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.

2016-01-01

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

Newborn Screening for Glutaric Aciduria-II: The New England Experience.

PubMed

Sahai, I; Garganta, C L; Bailey, J; James, P; Levy, H L; Martin, M; Neilan, E; Phornphutkul, C; Sweetser, D A; Zytkovicz, T H; Eaton, R B

2014-01-01

Newborn screening (NBS) using tandem mass spectrometry (MS/MS) permits detection of neonates with Glutaric Aciduria-Type II (GA-II). We report follow-up of positive GA-II screens by the New England Newborn Screening Program. 1.5 million infants were screened for GA-II (Feb 1999-Dec 2012). Specialist consult was suggested for infants with two or more acylcarnitine elevations suggestive of GA-II. 82 neonates screened positive for GA-II, 21 weighing > 1.5 kg and 61 weighing ≤ 1.5 kg. Seven (one weighing < 1.5 kg), were confirmed with GA-II. Four of these had the severe form (died < 1 week). The other three have a milder form and were identified because of newborn screening. Two (ages > 5 years) have a G-Tube in place, had multiple hospitalizations and are slightly hypotonic. The third infant remains asymptomatic (9 months old). Two GA-II carriers were also identified. The remaining positive screens were classified as false positives (FP). Six infants (> 1.5 kg) classified as FP had limited diagnostic work-up. Characteristics and outcomes of all specimens and neonates with a positive screen were reviewed, and marker profiles of the cases and FP were compared to identify characteristic profiles. In addition to the severe form of GA-II, milder forms of GA-II and some GA-II carriers are identified by newborn screening. Some positive screens classified as FP may be affected with a milder form of the disorder. Characteristic GA-II profiles, quantified as GA-II indexes, may be utilized to predict probability of disorder and direct urgency of intervention for positive screens.

[Results from ten years newborn hearing screening in a secondary hospital].

PubMed

Sequi Canet, José Miguel; Sala Langa, Maria José; Collar Del Castillo, José Ignacio

2016-10-01

A critical analysis is performed on the results of a newborn hearing screening program in a regional hospital. Screening results from 14,247 newborns in our maternity ward from 2002 to 2013. Two step recordings of bilateral otoacoustic emissions (initial and repeat, if failed, at about one month of life). Assessment by clinical brainstem responses. The first step was performed on 14,015 newborns (98.3% of the total) reaching the screening objective. The first step pass figures were 93.7%, which implies a good pass rate with a few patients to repeat. The second step is also good because it has a pass rate of 88.9% of newborns examined (only 0.63% of initial group needed brainstem responses assessment), but 10.6% were lost to follow up, and that is a major problem. In newborns, scheduled for brainstem responses, the loss to follow-up is worse, with a figure of 29.5%, despite the high accuracy of this test given that 69.4% of those assessed showed hearing loss. This figure represents a 0.31% of the initial group, and is a similar to that published for congenital hearing loss. Including patients that were lost to follow up this figure could be greater. Newborn hearing screening is useful but needs stronger control to avoid the follow up loss. In order to achieve this, it is crucial to have a good database and a screening coordinator. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Newborn screening: a review of history, recent advancements, and future perspectives in the era of next generation sequencing.

PubMed

Almannai, Mohammed; Marom, Ronit; Sutton, V Reid

2016-12-01

The purpose of this review is to summarize the development and recent advancements of newborn screening. Early initiation of medical care has modified the outcome for many disorders that were previously associated with high morbidity (such as cystic fibrosis, primary immune deficiencies, and inborn errors of metabolism) or with significant neurodevelopmental disabilities (such as phenylketonuria and congenital hypothyroidism). The new era of mass spectrometry and next generation sequencing enables the expansion of the newborn screen panel, and will help to address technical issues such as turnaround time, and decreasing false-positive and false-negative rates for the testing. The newborn screening program is a successful public health initiative that facilitates early diagnosis of treatable disorders to reduce long-term morbidity and mortality.

Newborn hearing screening update for midwifery practice.

PubMed

Narrigan, D

2000-01-01

Neonatal identification of congenital hearing impairment allows interventions during the first 3 years, the critical period for language and speech development. Two recently developed biophysical testing methods offer simple, accurate, and relatively inexpensive means to identify the one to three in 1,000 healthy newborns with hearing loss. Universal screening for auditory system integrity is advocated, because almost half of all newborns with hearing impairment have no risk factors associated with this impairment. Critics of universal screening cite the high rate of false positive tests (up to 7%), which increases program costs from follow-up and re-testing large numbers of infants to ensure identifying the few affected infants. As of early 2000, 24 states had introduced some type of auditory screening program, and the U.S. Congress had passed legislation with appropriations mandating state-based auditory screening for all newborns. Midwives practicing in states already mandating biophysical screening need to comply with their local requirements; those in other states may voluntarily incorporate new auditory test methods into practice.

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

Newborn Screening and Cascade Testing for FMR1 Mutations

PubMed Central

Sorensen, Page L.; Gane, Louise W.; Yarborough, Mark; Hagerman, Randi; Tassone, Flora

2014-01-01

We describe an ongoing pilot project in which newborn screening (NBS) for FMR1 mutations and subsequent cascade testing are performed by the MIND Institute at the University of California, Davis Medical Center (UCDMC). To date, out of 3042 newborns initially screened, 44 extended family members have been screened by cascade testing of extended family members once a newborn is identified. 14 newborns (7 males and 7 females) and 27 extended family members (5 males and 22 females) have been identified with FMR1 mutations. Three family histories are discussed in detail, each demonstrating some benefits and risks of NBS and cascade testing for FMR1 mutations in extended family members. While we acknowledge inherent risks, we propose that with genetic counseling, clinical follow-up of identified individuals and cascade testing, newborn screening (NBS) has significant benefits. Treatment for individuals in the extended family who would otherwise not have received treatment can be beneficial. In addition, knowledge of carrier status can lead to lifestyle changes and prophylactic interventions that are likely to reduce the risk of late onset neurological or psychiatric problems in carriers. Also with identification of carrier family members through NBS, reproductive choices become available to those who would not have known that they were at risk to have offspring with fragile X syndrome. PMID:23239591

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study

PubMed Central

Yamaguchi, Akira; Oh-ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nodoka; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, Tadashi; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

2017-01-01

Objective Approximately 8–10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. Study design The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. Results The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×106 copies/mL (95% CI 7.97×105 to 4.02×106). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). Conclusions We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders. PMID:28110288

Dangerous and Expensive Screening and Treatment for Rare Childhood Diseases: The Case of Krabbe Disease

ERIC Educational Resources Information Center

Lantos, John D.

2011-01-01

Public policy surrounding newborn screening is in flux. New technology allows more screening for more diseases at lower cost. Traditional criteria for target diseases have been criticized by leading health policymakers. The example of newborn screening for Krabbe disease highlights many of the dilemmas associated with population-based screening…

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

Transient evoked oto-acoustic emission screening in newborns in Bogotá, Colombia: a retrospective study.

PubMed

Rojas, Jorge A; Bernal, Jaime E; García, Mary A; Zarante, Ignacio; Ramírez, Natalia; Bernal, Constanza; Gelvez, Nancy; Tamayo, Marta L

2014-10-01

The aim of this study was to investigate the characteristics and performance of transient evoked oto-acoustic emission (TEOAE) hearing screening in newborns in Colombia, and analyze all possible variables and factors affecting the results. An observational, descriptive and retrospective study with bivariate analysis was performed. The study population consisted of 56,822 newborns evaluated at the private institution, PREGEN. TEOAE testing was carried out as a pediatric hearing screening test from December 2003 to March 2012. The database from PREGEN was revised, and the protocol for evaluation included the same screening test performed twice. Demographic characteristics were recorded and the newborn's background was evaluated. Basic statistics of the qualitative and quantitative variables, and statistical analysis were obtained using the chi-square test. Of the 56,822 records examined, 0.28% were classed as abnormal, which corresponded to a prevalence of 1 in 350. In the screened newborns, 0.08% had a major abnormality or other clinical condition diagnosed, and 0.29% reported a family history of hearing loss. A prevalence of 6.7 in 10,000 was obtained for microtia, which is similar to the 6.4 in 10,000 previously reported in Colombia (database of the Latin-American Collaborative Study of Congenital Malformations - ECLAMC). Statistical analysis demonstrated an association between presenting with a major anomaly and a higher frequency of abnormal results on both TEOAE tests. Newborns in Colombia do not currently undergo screening for the early detection of hearing impairment. The results from this study suggest TEOAE screening tests, when performed twice, are able to detect hearing abnormalities in newborns. This highlights the need to improve the long-term evaluation and monitoring of patients in Colombia through diagnostic tests, and to provide tests that are both sensitive and specific. Furthermore, the use of TEOAE screening is justified by the favorable cost: benefit ratio demonstrated in many countries worldwide. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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)

78 FR 4411 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-22

... potential study population is unique in that their children experienced newborn CMV screening as part of a previous research study. Universal CMV screening has not been recommended by medical associations or state.... Newborn CMV screening offers some clear potential benefits, but few studies have assessed the potential...

High incidence of congenital hypothyroidism in one region of the republic of macedonia.

PubMed

Anastasovska, V; Koviloska, R; Kocova, M

2014-06-01

Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation in children. Diagnosis is difficult at birth without neonatal screening. Neonatal thyroid screening was established in Prilep, Republic of Macedonia as an integral part of the nationwide screening program. To estimate the prevalence of CH in this region, neonatal thyroid screening was performed on 9757 newborns, during the period 2002-2011. The DELFIA method was applied to measure the thyroid-stimulating hormone (TSH) concentration in dried blood spot samples on standard filter paper taken 48 hours after birth by heel-stick. The TSH cut-off level was 10 mU/L. The neonatal thyroid screening coverage was 93.4%. Eight newborns with CH were detected, with an incidence of 1:1220 live births, significantly higher compared to the nationwide results 1:2602. The TSH level was not significantly dependent on the gender of the newborn. There was a statistically significant difference between the TSH level and the timing of newborn screening sampling (p <0.05) and between the TSH level and the newborn birth weight (p = 0.01). One point ninety-two percent of newborns with TSH levels above 5 mU/L indicated an iodine sufficiency in Prilep. The incidence of CH in Prilep, which is higher when compared with that reported in surrounding countries, might be a consequence of the higher percentage of the Romany population in this region. Further analysis of this population in other regions is warranted.

Implementing recommended screening for critical congenital heart disease.

PubMed

Martin, Gerard R; Beekman, Robert H; Mikula, Elizabeth Bradshaw; Fasules, James; Garg, Lorraine F; Kemper, Alex R; Morrow, W Robert; Pearson, Gail D; Mahle, William T

2013-07-01

Critical congenital heart disease (CCHD) is endorsed by the US Secretary of Health and Human Services as part of the recommended uniform screening panel for newborns. Although initial recommendations for implementation exist, as states and hospitals have moved forward with implementation of screening, new challenges and areas for additional focus have been identified. The objective of this study was to develop recommendations to address current challenges and areas of focus surrounding CCHD newborn screening. A workgroup of experts and stakeholders was convened in Washington, District of Columbia, for a 1-day meeting in February 2012. At the beginning of the meeting, the stakeholders held a brainstorming session to identify areas of main priority based on their experience. After this, stakeholders broke into small groups to refine recommendations, which were then finalized by consensus. Recommendations to address selection of screening equipment, standards for reporting of screening outcomes to stakeholders, training of health care providers and educating families, future research priorities, payment for screening, follow-up diagnostic testing, and public health oversight, and advocacy to facilitate effective and comprehensive screening were proposed. Suggestions for future work were developed. Screening for CCHD presents novel challenges and opportunities; however, addressing these will strengthen newborn screening and newborn care networks, and ultimately improve health outcomes.

Hearing Screening of High-Risk Newborns with Brainstem Auditory Evoked Potentials: A Follow-Up Study.

ERIC Educational Resources Information Center

Shannon, Dorothy A.; And Others

1984-01-01

The brainstem auditory evoked potential (BAEP) was evaluated as a hearing screening test in 168 high-risk newborns. The BAEP was found to be a sensitive procedure for the early identification of hearing-impaired newborns. However, the yield of significant hearing abnormalities was less than predicted in other studies using BAEP. (Author/CL)

Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy.

PubMed

Burlina, Alberto B; Polo, Giulia; Salviati, Leonardo; Duro, Giovanni; Zizzo, Carmela; Dardis, Andrea; Bembi, Bruno; Cazzorla, Chiara; Rubert, Laura; Zordan, Roberta; Desnick, Robert J; Burlina, Alessandro P

2018-03-01

Lysosomal storage diseases (LSDs) are inborn errors of metabolism resulting from 50 different inherited disorders. The increasing availability of treatments and the importance of early intervention have stimulated newborn screening (NBS) to diagnose LSDs and permit early intervention to prevent irreversible impairment or severe disability. We present our experience screening newborns in North East Italy to identify neonates with Mucopolysaccharidosis type I (MPS I) and Pompe, Fabry, and Gaucher diseases. Activities of acid β-glucocerebrosidase (ABG; Gaucher), acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), and acid α-L-iduronidase (IDUA; MPS-I) in dried blood spots (DBS) from all newborns during a 17-month period were determined by multiplexed tandem mass spectrometry (MS/MS) using the NeoLSD ® assay system. Enzymatic activity cutoff values were determined from 3500 anonymous newborn DBS. In the screening study, samples were retested if the value was below cutoff and a second spot was requested, with referral for confirmatory testing and medical evaluation if a low value was obtained. From September 2015 to January 2017, 44,411 newborns were screened for the four LSDs. We recalled 40 neonates (0.09%) for collection of a second DBS. Low activity was confirmed in 20, who had confirmatory testing. Ten of 20 had pathogenic mutations: two Pompe, two Gaucher, five Fabry, and one MPS-I. The incidences of Pompe and Gaucher diseases were similar (1/22,205), with Fabry disease the most frequent (1/8882) and MPS-I the rarest (1/44411). The combined incidence of the four disorders was 1/4411 births. Simultaneously determining multiple enzyme activities by MS/MS, with a focus on specific biochemical markers, successfully detected newborns with LSDs. The high incidence of these disorders supports this screening program.

Primary care role in expanded newborn screening

PubMed Central

Hayeems, Robin Z.; Miller, Fiona A.; Carroll, June C.; Little, Julian; Allanson, Judith; Bytautas, Jessica P.; Chakraborty, Pranesh; Wilson, Brenda J.

2013-01-01

Abstract Objective To examine the role of primary care providers in informing and supporting families who receive positive screening results. Design Cross-sectional survey. Setting Ontario. Participants Family physicians, pediatricians, and midwives involved in newborn care. Main outcome measures Beliefs, practices, and barriers related to providing information to families who receive positive screening results for their newborns. Results A total of 819 providers participated (adjusted response rate of 60.9%). Of the respondents, 67.4% to 81.0% agreed that it was their responsibility to provide care to families of newborns who received positive screening results, and 64.2% to 84.8% agreed they should provide brochures or engage in general discussions about the identified conditions. Of the pediatricians, 67.3% endorsed having detailed discussions with families, but only 24.1% of family physicians and 27.6% of midwives endorsed this practice. All provider groups reported less involvement in information provision than they believed they should have. This discrepancy was most evident for family physicians: most stated that they should provide brochures (64.2%) or engage in general discussions (73.5%), but only a minority did so (15.3% and 27.7%, respectively). Family physicians reported insufficient time (42.2%), compensation (52.2%), and training (72.3%) to play this role, and only a minority agreed they were up to date (18.5%) or confident (16.5%) regarding newborn screening. Conclusion Providers of primary newborn care see an information-provision role for themselves in caring for families who receive positive newborn screening results. Efforts to further define the scope of this role combined with efforts to mitigate existing barriers are warranted. PMID:23946032

Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon.

PubMed

Khneisser, I; Adib, S; Assaad, S; Megarbane, A; Karam, P

2015-12-01

Few countries in the Middle East-North Africa region have adopted national newborn screening for inborn errors of metabolism by tandem mass spectrometry (MS/MS). We aimed to evaluate the cost-benefit of newborn screening for such disorders in Lebanon, as a model for other developing countries in the region. Average costs of expected care for inborn errors of metabolism cases as a group, between ages 0 and 18, early and late diagnosed, were calculated from 2007 to 2013. The monetary value of early detection using MS/MS was compared with that of clinical "late detection", including cost of diagnosis and hospitalizations. During this period, 126000 newborns were screened. Incidence of detected cases was 1/1482, which can be explained by high consanguinity rates in Lebanon. A reduction by half of direct cost of care, reaching on average 31,631 USD per detected case was shown. This difference more than covers the expense of starting a newborn screening programme. Although this model does not take into consideration the indirect benefits of the better quality of life of those screened early, it can be argued that direct and indirect costs saved through early detection of these disorders are important enough to justify universal publicly-funded screening, especially in developing countries with high consanguinity rates, as shown through this data from Lebanon. © The Author(s) 2015.

Thyroid function and perchlorate in drinking water: an evaluation among California newborns, 1998.

PubMed

Buffler, Patricia A; Kelsh, Michael A; Lau, Edmund C; Edinboro, Charlotte H; Barnard, Julie C; Rutherford, George W; Daaboul, Jorge J; Palmer, Lynn; Lorey, Fred W

2006-05-01

Perchlorate (ClO4-) has been detected in groundwater sources in numerous communities in California and other parts of the United States, raising concerns about potential impacts on health. For California communities where ClO4- was tested in 1997 and 1998, we evaluated the prevalence of primary congenital hypothyroidism (PCH) and high thyroid-stimulating hormone (TSH) levels among the 342,257 California newborns screened in 1998. We compared thyroid function results among newborns from 24 communities with average ClO4- concentrations in drinking water>5 microg/L (n=50,326) to newborns from 287 communities with average concentrations5 microg/L were observed, with 20.4 expected [adjusted prevalence odds ratio (POR)=0.71; 95% confidence interval (CI), 0.40-1.19]. Although only 36% of all California newborns were screened before 24 hr of age in 1998, nearly 80% of newborns with high TSH were screened before 24 hr of age. Because of the physiologic postnatal surge of TSH, the results for newborns screened before 24 hr were uninformative for assessing an environmental impact. For newborns screened>or=24 hr, the adjusted POR for high TSH was 0.73 (95% CI, 0.40-1.23). All adjusted odds ratios (ORs) were controlled for sex, ethnicity, birth weight, and multiple birth status. Using an assessment of ClO4- in drinking water based on available data, we did not observe an association between estimated average ClO4- concentrations>5 microg/L in drinking water supplies and the prevalence of clinically diagnosed PCH or high TSH concentrations.

Utility of a precursor-to-product ratio in the evaluation of presumptive positives in newborn screening of congenital adrenal hyperplasia.

PubMed

Tieh, P Y; Yee, J K; Hicks, R A; Mao, C S; Lee, W-Np

2017-03-01

Screening for congenital adrenal hyperplasia (CAH) caused by 21-α-hydroxylase deficiency is challenging because factors such as prematurity and stress increase intermediate steroid metabolite levels in newborn infants. The objective of this study was to explore the use of the 17-α-hydroxyprogesterone (17-OHP)/11-deoxycortisol ratio as an adjunct measure in the follow-up evaluation of infants with presumptive positive newborn screens for CAH to distinguish between infants with no disorder and those with CAH. This was a retrospective cohort study of infants with presumptive positive newborn screens for CAH. The precursor-to-product ratio of 17-OHP/11-deoxycortisol was compared between infants with no disorder (n=47) and infants with CAH (n=5). The CAH infants had higher 17-OHP/11-deoxycortisol ratios than infants with no disorder: 26 (18 to 58) and 1.05 (0.69 to 1.46), respectively (P<0.05). Among infants with no disorder, higher levels of serum 17-OHP did not reflect higher ratios, indicating sufficient enzyme activity. The results suggest that a low 17-OHP/11-deoxycortisol ratio represents 21-α-hydroxylase sufficiency among presumptive positives in newborn screening of CAH.

Screening Newborns | NIH MedlinePlus the Magazine

MedlinePlus

... signed the Newborn and Infant Hearing Screening and Intervention Act, authorizing the coordination and funding of statewide ... hearing loss before they leave the hospital. → Early interventions and treatments (hearing aids, cochlear implants, sign language, ...

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…

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…

Minimizing risks: the ethics of predictive diabetes mellitus screening research in newborns.

PubMed

Ross, Lainie Friedman

2003-01-01

Type 1 diabetes mellitus is the most common metabolic disease of childhood. Two states offer newborn screening to identify children with a genetic predisposition to it. It is a voluntary test offered in conjunction with the mandatory newborn metabolic screening. There are no preventive treatments, but children discovered to be at increased risk may participate in follow-up studies to determine whether and when the child develops autoantibodies (preclinical disease) or overt diabetes. This study examined the ethics of predictive genetic research in newborns for type 1 diabetes. Prediction research has serious psychosocial implications, and research designs must account for them. The study concluded that, to minimize harm to infants and their families, (1) if the research does not incorporate a prevention strategy, studies should avoid disclosure of results; and (2) if disclosure is necessary, then the research should be restricted to newborns with an affected first-degree relative.

Main Report

PubMed Central

2006-01-01

Background: States vary widely in their use of newborn screening tests, with some mandating screening for as few as three conditions and others mandating as many as 43 conditions, including varying numbers of the 40+ conditions that can be detected by tandem mass spectrometry (MS/MS). There has been no national guidance on the best candidate conditions for newborn screening since the National Academy of Sciences report of 19751 and the United States Congress Office of Technology Assessment report of 1988,2 despite rapid developments since then in genetics, in screening technologies, and in some treatments. Objectives: In 2002, the Maternal and Child Health Bureau (MCHB) of the Health Resources and Services Administration (HRSA) of the United States Department of Health and Human Services (DHHS) commissioned the American College of Medical Genetics (ACMG) to: Conduct an analysis of the scientific literature on the effectiveness of newborn screening.Gather expert opinion to delineate the best evidence for screening for specified conditions and develop recommendations focused on newborn screening, including but not limited to the development of a uniform condition panel.Consider other components of the newborn screening system that are critical to achieving the expected outcomes in those screened. Methods: A group of experts in various areas of subspecialty medicine and primary care, health policy, law, public health, and consumers worked with a steering committee and several expert work groups, using a two-tiered approach to assess and rank conditions. A first step was developing a set of principles to guide the analysis. This was followed by developing criteria by which conditions could be evaluated, and then identifying the conditions to be evaluated. A large and broadly representative group of experts was asked to provide their opinions on the extent to which particular conditions met the selected criteria, relying on supporting evidence and references from the scientific literature. The criteria were distributed among three main categories for each condition: The availability and characteristics of the screening test;The availability and complexity of diagnostic services; andThe availability and efficacy of treatments related to the conditions. A survey process utilizing a data collection instrument was used to gather expert opinion on the conditions in the first tier of the assessment. The data collection format and survey provided the opportunity to quantify expert opinion and to obtain the views of a diverse set of interest groups (necessary due to the subjective nature of some of the criteria). Statistical analysis of data produced a score for each condition, which determined its ranking and initial placement in one of three categories (high scoring, moderately scoring, or low scoring/absence of a newborn screening test). In the second tier of these analyses, the evidence base related to each condition was assessed in depth (e.g., via systematic reviews of reference lists including MedLine, PubMed and others; books; Internet searches; professional guidelines; clinical evidence; and cost/economic evidence and modeling). The fact sheets reflecting these analyses were evaluated by at least two acknowledged experts for each condition. These experts assessed the data and the associated references related to each criterion and provided corrections where appropriate, assigned a value to the level of evidence and the quality of the studies that established the evidence base, and determined whether there were significant variances from the survey data. Survey results were subsequently realigned with the evidence obtained from the scientific literature during the second-tier analysis for all objective criteria, based on input from at least three acknowledged experts in each condition. The information from these two tiers of assessment was then considered with regard to the overriding principles and other technology or condition-specific recommendations. On the basis of this information, conditions were assigned to one of three categories as described above:Core Panel;Secondary Targets (conditions that are part of the differential diagnosis of a core panel condition.); andNot Appropriate for Newborn Screening (either no newborn screening test is available or there is poor performance with regard to multiple other evaluation criteria). ACMG also considered features of optimal newborn screening programs beyond the tests themselves by assessing the degree to which programs met certain goals (e.g., availability of educational programs, proportions of newborns screened and followed up). Assessments were based on the input of experts serving in various capacities in newborn screening programs and on 2002 data provided by the programs of the National Newborn Screening and Genetics Resource Center (NNSGRC). In addition, a brief cost-effectiveness assessment of newborn screening was conducted. Results: Uniform panel A total of 292 individuals determined to be generally representative of the regional distribution of the United States population and of areas of expertise or involvement in newborn screening provided a total of 3,949 evaluations of 84 conditions. For each condition, the responses of at least three experts in that condition were compared with those of all respondents for that condition and found to be consistent. A score of 1,200 on the data collection instrument provided a logical separation point between high scoring conditions (1,200–1,799 of a possible 2,100) and low scoring (<1,000) conditions. A group of conditions with intermediate scores (1,000–1,199) was identified, all of which were part of the differential diagnosis of a high scoring condition or apparent in the result of the multiplex assay. Some are identified by screening laboratories and others by diagnostic laboratories. This group was designated as a “secondary target” category for which the program must report the diagnostic result. Using the validated evidence base and expert opinion, each condition that had previously been assigned to a category based on scores gathered through the data collection instrument was reconsidered. Again, the factors taken into consideration were: 1) available scientific evidence; 2) availability of a screening test; 3) presence of an efficacious treatment; 4) adequate understanding of the natural history of the condition; and 5) whether the condition was either part of the differential diagnosis of another condition or whether the screening test results related to a clinically significant condition. The conditions were then assigned to one of three categories as previously described (core panel, secondary targets, or not appropriate for Newborn Screening). Among the 29 conditions assigned to the core panel are three hemoglobinopathies associated with a Hb/S allele, six amino acidurias, five disorders of fatty oxidation, nine organic acidurias, and six unrelated conditions (congenital hypothyroidism (CH), biotinidase deficiency (BIOT), congenital adrenal hyperplasia (CAH), classical galactosemia (GALT), hearing loss (HEAR) and cystic fibrosis (CF)). Twenty-three of the 29 conditions in the core panel are identified with multiplex technologies such as tandem mass spectrometry (MS/MS) or high pressure liquid chromatography (HPLC). On the basis of the evidence, six of the 35 conditions initially placed in the core panel were moved into the secondary target category, which expanded to 25 conditions. Test results not associated with potential disease in the infant (e.g., carriers) were also placed in the secondary target category. When newborn screening laboratory results definitively establish carrier status, the result should be made available to the health care professional community and families. Twenty-seven conditions were determined to be inappropriate for newborn screening at this time. Conditions with limited evidence reported in the scientific literature were more difficult to evaluate, quantify and place in one of the three categories. In addition, many conditions were found to occur in multiple forms distinguished by age-of-onset, severity, or other features. Further, unless a condition was already included in newborn screening programs, there was a potential for bias in the information related to some criteria. In such circumstances, the quality of the studies underlying the data such as expert opinion that considered case reports and reasoning from first principles determined the placement of the conditions into particular categories. Newborn screening program optimization – Assessment of the activities of newborn screening programs, based on program reports, was done for the six program components: education; screening; follow-up; diagnostic confirmation; management; and program evaluation. Considerable variation was found between programs with regard to whether particular aspects (e.g., prenatal education program availability, tracking of specimen collection and delivery) were included and the degree to which they are provided. Newborn screening program evaluation systems also were assessed in order to determine their adequacy and uniformity with the goal being to improve interprogram evaluation and comparison to ensure that the expected outcomes from having been identified in screening are realized. Conclusions: The state of the published evidence in the fast-moving worlds of newborn screening and medical genetics has not kept up with the implementation of new technologies, thus requiring the considerable use of expert opinion to develop recommendations about a core panel of conditions for newborn screening. Twenty-nine conditions were identified as primary targets for screening from which all components of the newborn screening system should be maximized. An additional 25 conditions were listed that could be identified in the course of screening for core panel conditions. Programs are obligated to establish a diagnosis and communicate the result to the health care provider and family. It is recognized that screening may not have been maximized for the detection of these secondary conditions but that some proportion of such cases may be found among those screened for core panel conditions. With additional screening, greater training of primary care health care professionals and subspecialists will be needed, as will the development of an infrastructure for appropriate follow-up and management throughout the lives of children who have been identified as having one of these rare conditions. Recommended actions to overcome barriers to an optimal newborn screening system include: The establishment of a national role in the scientific evaluation of conditions and the technologies by which they are screened;Standardization of case definitions and reporting procedures;Enhanced oversight of hospital-based screening activities;Long-term data collection and surveillance; andConsideration of the financial needs of programs to allow them to deliver the appropriate services to the screened population.

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study.

PubMed

Yamaguchi, Akira; Oh-Ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nodoka; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, Tadashi; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

2017-01-20

Approximately 8-10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×10 6 copies/mL (95% CI 7.97×10 5 to 4.02×10 6 ). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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.

A three-year follow-up of congenital adrenal hyperplasia newborn screening.

PubMed

Pezzuti, Isabela L; Barra, Cristina B; Mantovani, Rafael M; Januário, José N; Silva, Ivani N

2014-01-01

congenital adrenal hyperplasia (CAH) newborn screening can prevent neonatal mortality in children with the salt-wasting form of the disease and prevent incorrect gender assignments, which can occur in females. However, the occurrence of false-positive results in preterm or low-birth-weight newborns creates some diagnostic difficulties, with consequent therapeutic implications. This study aimed to report the results of a pilot project for neonatal CAH screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008 with a three-year follow-up. dried blood specimens were collected on filter paper cards three to seven days after birth of all newborns in the period. Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked immunosorbent assay (ELISA). a total of 159,415 children were screened. The apparent incidence of the classic variant of the disease was 1:9,963, based on initial diagnoses following newborn screening. During the follow-up period, eight of 16 children initially diagnosed with CAH were reclassified as unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate was 0.31%, and the positive predictive value was 2.1%. Sensitivity and specificity were 100% and 99.7%, respectively. newborn screening is an important public health policy in developing countries such as Brazil, where CAH remains underdiagnosed. It has great potential to identify children with the disease who otherwise cannot be diagnosed earlier. Long-term follow-up and monitoring of all children with positive screening results are crucial to ensure a correct diagnosis and to calculate a reliable incidence ratio of the disease. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.

PubMed

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

2013-05-23

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. 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. 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 collected in year 2011 were used as predicting cases. The feature selection strategies were implemented and the optimal markers for PKU, hypermethioninemia, and 3-MCC deficiency were obtained. The results of the machine learning approach were compared with the cutoff scheme. The number of the false positive cases were reduced from 21 to 2 for PKU, from 30 to 10 for hypermethioninemia, and 209 to 46 for 3-MCC deficiency. This SOA Web service-based newborn screening system can accelerate screening procedures effectively and efficiently. An SVM learning methodology for PKU, hypermethioninemia, and 3-MCC deficiency metabolic diseases classification, including optimal feature selection strategies, is presented. By adopting the results of this study, the number of suspected cases could be reduced dramatically.

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 collected in year 2011 were used as predicting cases. Results The feature selection strategies were implemented and the optimal markers for PKU, hypermethioninemia, and 3-MCC deficiency were obtained. The results of the machine learning approach were compared with the cutoff scheme. The number of the false positive cases were reduced from 21 to 2 for PKU, from 30 to 10 for hypermethioninemia, and 209 to 46 for 3-MCC deficiency. Conclusions This SOA Web service–based newborn screening system can accelerate screening procedures effectively and efficiently. An SVM learning methodology for PKU, hypermethioninemia, and 3-MCC deficiency metabolic diseases classification, including optimal feature selection strategies, is presented. By adopting the results of this study, the number of suspected cases could be reduced dramatically. PMID:23702487

Population newborn screening for inherited metabolic disease: current UK perspectives.

PubMed

Green, A; Pollitt, R J

1999-06-01

Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

Parents' interest in whole-genome sequencing of newborns.

PubMed

Goldenberg, Aaron J; Dodson, Daniel S; Davis, Matthew M; Tarini, Beth A

2014-01-01

The aim of this study was to assess parents' interest in whole-genome sequencing for newborns. We conducted a survey of a nationally representative sample of 1,539 parents about their interest in whole-genome sequencing of newborns. Participants were randomly presented with one of two scenarios that differed in the venue of testing: one offered whole-genome sequencing through a state newborn screening program, whereas the other offered whole-genome sequencing in a pediatrician's office. Overall interest in having future newborns undergo whole-genome sequencing was generally high among parents. If whole-genome sequencing were offered through a state's newborn-screening program, 74% of parents were either definitely or somewhat interested in utilizing this technology. If offered in a pediatrician's office, 70% of parents were either definitely or somewhat interested. Parents in both groups most frequently identified test accuracy and the ability to prevent a child from developing a disease as "very important" in making a decision to have a newborn's whole genome sequenced. These data may help health departments and children's health-care providers anticipate parents' level of interest in genomic screening for newborns. As whole-genome sequencing is integrated into clinical and public health services, these findings may inform the development of educational strategies and outreach messages for parents.

Financing state newborn screening programs: sources and uses of funds.

PubMed

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

2006-05-01

Financing for newborn screening is different from virtually all other public health programs. All except 5 screening programs collect fees as the primary source of program funding. A fee-based approach to financing newborn screening has been adopted by most states, to ensure consistent funding for this critical public health activity. Two types of data are reported here, ie, primary data from a survey of 37 state public health agencies and findings from exploratory case studies from 7 states. Most of the programs that participated in this survey (73%) reported that their newborn screening funding increased between 2002 and 2005, typically through increased fees and to a lesser extent through Medicaid, Title V Maternal and Child Health Services Block Grant, and state general revenue funding. All of the responding states that collect fees (n = 31) use such funds to support laboratory expenses, and most (70%) finance short-term follow-up services and program management. Nearly one half (47%) finance longer-term follow-up services, case management, or family support beyond diagnosis. Other states (43%) finance genetic or nutritional counseling and formula foods or treatment. Regardless of the source of funds, the available evidence indicates that states are committed to maintaining their programs and securing the necessary financing for the initial screening through diagnosis. Use of federal funding is currently limited; however, pressure to provide dedicated federal funding would likely increase if national recommendations for a uniform newborn screening panel were issued.

Two-Way Radio Modem Data Transfer for Newborn Hearing Screening Devices.

PubMed

Matulat, Peter; Lepper, Ingo; Böttcher, Peter; Parfitt, Ross; Oswald, Hans; Am Zehnhoff-Dinnesen, Antoinette; Deuster, Dirk

2017-01-01

The success of a newborn hearing screening program depends on successful tracking and follow-up to ensure that children who have had positive screening results in the first few days of life receive appropriate and timely diagnostic and intervention services. The easy availability, through a suitable infrastructure, of the data necessary for the tracking, diagnosis, and care of children concerned is a major key to enhancing the quality and efficiency of newborn hearing screening programs. Two systems for the automated two-way transmission of newborn hearing screening and configuration data, based on mobile communication technology, for the screening devices MADSEN AccuScreen ® and Natus Echo-Screen ® were developed and tested in a field study. Radio modem connections were compared with conventional analogue modem transmissions from Natus Echo-Screen devices for duration, transmission rate, number of lost connections, and frequency of use. The average session duration was significantly lower with the MADSEN AccuScreen (12 s) and Natus Echo-Screen both with radio modem (15 s) than the Natus Echo-Screen with analogue modem (108 s). The transmission rate was significantly higher (898 and 1,758 vs. 181 bytes/s) for the devices with radio modems. Both radio modem devices had significantly lower rates of broken connections after initial connection (2.1 and 0.9 vs. 5.5%). An increase in the frequency of data transmission from the clinics with mobile radio devices was found. The use of mobile communication technology in newborn hearing screening devices offers improvements in the average session duration, transmission rate, and reliability of the connection over analogue solutions. We observed a behavioral change in clinical staff using the new technology: the data exchange with the tracking center is more often used. The requirements for on-site support were reduced. These savings outweigh the small increase in costs for the Internet service provider.

Estimated number of infants detected and missed by critical congenital heart defect screening.

PubMed

Ailes, Elizabeth C; Gilboa, Suzanne M; Honein, Margaret A; Oster, Matthew E

2015-06-01

In 2011, the US Secretary of Health and Human Services recommended universal screening of newborns for critical congenital heart defects (CCHDs), yet few estimates of the number of infants with CCHDs likely to be detected through universal screening exist. Our objective was to estimate the number of infants with nonsyndromic CCHDs in the United States likely to be detected (true positives) and missed (false negatives) through universal newborn CCHD screening. We developed a simulation model based on estimates of birth prevalence, prenatal diagnosis, late detection, and sensitivity of newborn CCHD screening through pulse oximetry to estimate the number of true-positive and false-negative nonsyndromic cases of the 7 primary and 5 secondary CCHD screening targets identified through screening. We estimated that 875 (95% uncertainty interval [UI]: 705-1060) US infants with nonsyndromic CCHDs, including 470 (95% UI: 360-585) infants with primary CCHD screening targets, will be detected annually through newborn CCHD screening. An additional 880 (UI: 700-1080) false-negative screenings, including 280 (95% UI: 195-385) among primary screening targets, are expected. We estimated that similar numbers of CCHDs would be detected under scenarios comparing "lower" (∼19%) and "higher" (∼41%) than current prenatal detection prevalences. A substantial number of nonsyndromic CCHD cases are likely to be detected through universal CCHD screening; however, an equal number of false-negative screenings, primarily among secondary targets of screening, are likely to occur. Future efforts should document the true impact of CCHD screening in practice. Copyright © 2015 by the American Academy of Pediatrics.

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)

Expanded Newborn Screening Program in Saudi Arabia: Incidence of screened disorders.

PubMed

Alfadhel, Majid; Al Othaim, Ali; Al Saif, Saif; Al Mutairi, Fuad; Alsayed, Moeenaldeen; Rahbeeni, Zuhair; Alzaidan, Hamad; Alowain, Mohammed; Al-Hassnan, Zuhair; Saeedi, Mohamad; Aljohery, Saeed; Alasmari, Ali; Faqeih, Eissa; Alwakeel, Mansour; AlMashary, Maher; Almohameed, Sulaiman; Alzahrani, Mohammed; Migdad, Abeer; Al-Dirbashi, Osama Y; Rashed, Mohamed; Alamoudi, Mohamed; Jacob, Minnie; Alahaidib, Lujane; El-Badaoui, Fahd; Saadallah, Amal; Alsulaiman, Ayman; Eyaid, Wafaa; Al-Odaib, Ali

2017-06-01

To address the implementation of the National Newborn Screening Program (NBS) in Saudi Arabia and stratify the incidence of the screened disorders. A retrospective study conducted between 1 August 2005 and 31 December 2012, total of 775 000 newborns were screened from 139 hospitals distributed among all regions of Saudi Arabia. The NBS Program screens for 16 disorders from a selective list of inborn errors of metabolism (IEM) and endocrine disorders. Heel prick dry blood spot samples were obtained from all newborns for biochemical and immunoassay testing. Recall screening testing was performed for Initial positive results and confirmed by specific biochemical assays. A total of 743 cases were identified giving an overall incidence of 1:1043. Frequently detected disorders nationwide were congenital hypothyroidism and congenital adrenal hyperplasia with an incidence of 1:7175 and 1:7908 correspondingly. The highest incidence among the IEM was propionic acidaemia with an incidence rate of 1:14 000. The article highlights the experience of the NBS Program in Saudi Arabia and providing data on specific regional incidences of all the screened disorders included in the programme; and showed that the incidence of these disorders is one of the highest reported so far world-wide. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Recent developments and new applications of tandem mass spectrometry in newborn screening.

PubMed

Rinaldo, Piero; Tortorelli, Silvia; Matern, Dietrich

2004-08-01

To summarize recent developments in the field of newborn screening related to the use of tandem mass spectrometry as an analytic platform. Novel inborn errors of metabolism with informative amino acid and/or acylcarnitine profiles have been characterized, increasing the complexity of the differential diagnosis of abnormal results. In addition, methods have been developed for the analysis in dried blood spots of steroids and lysosomal enzymes. Previously unrecognized genotype/phenotype correlations have been found among cohorts of patients whose conditions were diagnosed by screening rather than clinically. Several government entities and professional organizations have issued position statements on newborn screening, and worldwide outcome studies continue to underscore the clinical and financial benefits of expanded newborn screening. Although it is done inconsistently, newborn screening in the United States is undergoing a rapid expansion driven by the introduction of tandem mass spectrometry in at least 34 state programs. This technology is also used to detect disease markers beyond acylcarnitines and amino acids, as both primary and second-tier tests. In addition to analytic improvements, there is a trend toward the development of joint programs not limited to contiguous geographic areas, often based upon public-private partnerships. This review will summarize several new developments in the field that have occurred since early 2003 and will mention others likely to occur in the near future.

Texas Pulse Oximetry Project: A Multicenter Educational and Quality Improvement Project for Implementation of Critical Congenital Heart Disease Screening Using Pulse Oximetry.

PubMed

Guillory, Charleta; Gong, Alice; Livingston, Judith; Creel, Liza; Ocampo, Elena; McKee-Garrett, Tiffany

2017-07-01

Objective  Critical congenital heart disease (CCHD) is a leading cause of death in infants. Newborn screening (NBS) by pulse oximetry allows early identification of CCHD in asymptomatic newborns. To improve readiness of hospital neonatal birthing facilities for mandatory screening in Texas, an educational and quality improvement (QI) project was piloted to identify an implementation strategy for CCHD NBS in a range of birthing hospitals. Study Design  Thirteen Texas hospitals implemented standardized CCHD screening by pulse oximetry. An educational program was devised and a tool kit was created to facilitate education and implementation. Newborn nursery nurses' knowledge was assessed using a pre- and posttest instrument. Results  The nurses' knowledge assessment improved from 71 to 92.5% ( p  < 0.0001). Of 11,322 asymptomatic newborns screened after 24 hours of age, 11 had a positive screen, with 1 confirmed case of CCHD. Pulse oximetry CCHD NBS had sensitivity of 100%, specificity of 99.91%, false-positive rate of 0.088%, positive predictive value of 9.09%, and negative predictive value of 100%. Conclusion  Our educational program, including a tool kit, QI processes, and standardized pulse oximetry CCHD NBS, is applicable for a range of hospital birthing facilities and may facilitate wide-scale implementation, thereby improving newborn health. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Healthy Start, Grow Smart: Your Newborn.

ERIC Educational Resources Information Center

Department of Education, Washington, DC.

This booklet offers guidance to parents in caring for their newborn babies. Advice is given on the following topics: (1) newborn health screening; (2) what a healthy newborn looks like; (3) newborn reflexes; (4) baby checkups; (5) fathers' role; (6) the baby blues; (7) sleeping position; (8) breast milk; (9) breast feeding; (10) bottle feeding;…

Screening of lysosomal storage disorders: application of the online trapping-and-cleanup liquid chromatography/mass spectrometry method for mucopolysaccharidosis I.

PubMed

Ombrone, Daniela; Malvagia, Sabrina; Funghini, Silvia; Giocaliere, Elisa; Della Bona, Maria Luisa; Forni, Giulia; De Luca, Alessio; Villanelli, Fabio; Casetta, Bruno; Guerrini, Renzo; la Marca, Giancarlo

2013-01-01

In recent years, new treatments have become available to treat some lysosomal storage disorders (LSDs) and many studies suggest that there is a benefit with starting therapy early. Newborn screening should detect diseases early enough for prompt treatment. Some countries include additional conditions, such as some LSDs, into their newborn screening panels. Mucopolysaccharidosis Type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase (IDUA) activity. Currently, enzyme replacement therapy (ERT) or bone marrow transplantation is available and this has raised a growing interest for the development of a newborn screening test. In 2009, we reported a new fast and simplified tandem mass spectrometry-based method for quantifying five enzyme activities on dried blood spots. Here, we describe the inclusion of IDUA activity determination for the simultaneous detection of six lysosomal storage diseases. We have defined reference normal ranges by testing 680 healthy newborns and 240 adults. The assay was checked through three confirmed MPS I patients whose IDUA activity was below the normal range. Reproducibility of the assays has been established by assessing the intra-day and inter-day assay imprecisions. This quick assay has been devised to be implemented in newborn screening by liquid chromatography tandem mass spectrometry.

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…

Newborn Screening for Biliary Atresia.

PubMed

Wang, Kasper S

2015-12-01

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. Copyright © 2015 by the American Academy of Pediatrics.

Experiences during newborn screening for glutaric aciduria type 1: Diagnosis, treatment, genotype, phenotype, and outcomes.

PubMed

Tsai, Fang-Chih; Lee, Han-Jui; Wang, An-Guor; Hsieh, Shu-Chen; Lu, Yung-Hsiu; Lee, Ming-Che; Pai, Ju-Shan; Chu, Tzu-Hung; Yang, Chia-Feng; Hsu, Ting-Rong; Lai, Chih-Jou; Tsai, Ming-Tzu; Ho, Ping-Hsun; Lin, Min-Chieh; Cheng, Ling-Yee; Chuang, Ya-Chin; Niu, Dau-Ming

2017-04-01

Glutaric aciduria type 1 (GA-1) is an organic acidemia with potentially severe neurological sequelae. In Taiwan, newborn screening (NBS) for GA-1 began in 2001, but large-scale reporting is lacking. This study describes Taiwan's largest newborn screening population to date. Between 2001 and 2015, 1,490,636 newborns were screened for GA-1. Confirmatory examinations included the carnitine loading test. Confirmed patients were treated with a low lysine diet, carnitine, and high-energy intake during illness. Clinical, laboratory, and neuroimaging data were analyzed. Fourteen newborns were diagnosed with GA-1 (incidence: 1/106,474). C5DC concentration was clearly increased after carnitine loading in the affected newborns, but not in false-positive newborns (p = 0.004), indicating that this test is useful as an adjuvant diagnostic method. Eleven patients followed in our hospital were enrolled, namely nine NBS patients and two patients diagnosed clinically. IVS10-2A>C was the most common mutation. Two novel mutations (T36fs and N291K) were identified. Pendular nystagmus was found in two pediatric GA-1 patients. The corresponding pathology was optic atrophy in one patient, but remained undetermined in the other patient. The frequency of encephalopathic crisis decreased substantially following NBS. Among patients diagnosed by NBS, cognitive functioning was better among patients with good compliance than patients with poor compliance (p = 0.03). Abnormalities were detected by brain MRI including diffusion-weighted imaging and apparent diffusion coefficient maps; these affected various brain regions at different stages of the disease. Basal ganglion injuries occurred after an encephalopathic crisis. White matter disease was prevalent among older patients, either with or without an encephalopathic crisis. Early diagnosis by newborn screening followed by full compliance with treatment guidelines is important to a good outcome. Copyright © 2017. Published by Elsevier Taiwan LLC.

Risk factors and prevalence of newborn hearing loss in a private health care system of Porto Velho, Northern Brazil

PubMed Central

de Oliveira, Juliana Santos; Rodrigues, Liliane Barbosa; Aurélio, Fernanda Soares; da Silva, Virgínia Braz

2013-01-01

OBJECTIVE: To determine the prevalence of hearing loss and to analyze the results of newborn hearing screening and audiological diagnosis in private health care systems. METHODS Cross-sectional and retrospective study in a database of newborn hearing screening performed by a private clinic in neonates born in private hospitals of Porto Velho, Rondônia, Northern Brazil. The screening results, the risk for hearing loss, the risk indicators for hearing loss and the diagnosis were descriptively analyzed. Newborns cared in rooming in with their mothers were compared to those admitted to the Intensive Care Unit regarding risk factors for hearing loss. RESULTS: Among 1,146 (100%) enrolled newborns, 1,064 (92.8%) passed and 82 (7.2%) failed the hearing screening. Among all screened neonates, 1,063 (92.8%) were cared in rooming and 83 (7.2%) needed intensive care; 986 (86.0%) were considered at low risk and 160 (14.0%) at high risk for hearing problems. Of the 160 patients identified as having high risk for hearing loss, 83 (37.7%) were admitted to an hospitalized in the Intensive Care Unit, 76 (34.5%) used ototoxic drugs and 38 (17.2%) had a family history of hearing loss in childhood. Hearing loss was diagnosed in two patients (0.2% of the screened sample). CONCLUSIONS: The prevalence of hearing loss in newborns from private hospitals was two cases per 1,000 evaluated patients. The use of ototoxic drugs, admission to Intensive Care Unit and family history of hearing loss were the most common risk factors for hearing loss in the studied population. PMID:24142311

Utility of Decision Rules for Transcutaneous Bilirubin Measurements

PubMed Central

Burgos, Anthony E.; Flaherman, Valerie; Chung, Esther K.; Simpson, Elizabeth A.; Goyal, Neera K.; Von Kohorn, Isabelle; Dhepyasuwan, Niramol

2016-01-01

BACKGROUND: Transcutaneous bilirubin (TcB) meters are widely used for screening newborns for jaundice, with a total serum bilirubin (TSB) measurement indicated when the TcB value is classified as “positive” by using a decision rule. The goal of our study was to assess the clinical utility of 3 recommended TcB screening decision rules. METHODS: Paired TcB/TSB measurements were collected at 34 newborn nursery sites. At 27 sites (sample 1), newborns were routinely screened with a TcB measurement. For sample 2, sites that typically screen with TSB levels also obtained a TcB measurement for the study. Three decision rules to define a positive TcB measurement were evaluated: ≥75th percentile on the Bhutani nomogram, 70% of the phototherapy level, and within 3 mg/dL of the phototherapy threshold. The primary outcome was a TSB level at/above the phototherapy threshold. The rate of false-negative TcB screens and percentage of blood draws avoided were calculated for each decision rule. RESULTS: For sample 1, data were analyzed on 911 paired TcB-TSB measurements from a total of 8316 TcB measurements. False-negative rates were <10% with all decision rules; none identified all 31 newborns with a TSB level at/above the phototherapy threshold. The percentage of blood draws avoided ranged from 79.4% to 90.7%. In sample 2, each rule correctly identified all 8 newborns with TSB levels at/above the phototherapy threshold. CONCLUSIONS: Although all of the decision rules can be used effectively to screen newborns for jaundice, each will “miss” some infants with a TSB level at/above the phototherapy threshold. PMID:27244792

Parental views on informed consent for expanded newborn screening.

PubMed

Moody, Louise; Choudhry, Kubra

2013-09-01

An increasing array of rare inherited conditions can be detected as part of the universal newborn screening programme. The introduction and evaluation of these service developments require consideration of the ethical issues involved and appropriate mechanisms for informing parents and gaining consent if required. Exploration of parental views is needed to inform the debate and specifically consider whether more flexible protocols are needed to fit with the public perception of new developments in this context. This study has been undertaken to explore perceptions and attitudes of parents and future parents to an expanded newborn screening programme in the United Kingdom and the necessary information provision and consent processes. A mixed methods study involving focus groups (n = 29) and a web-survey (n = 142) undertaken with parents and future parents. Parents want guaranteed information provision with clear decision-making powers and an awareness of the choices available to them. The difference between existing screening provision and expanded screening was not considered to be significant enough by participants to warrant formal written, informed consent for expanded screening. It is argued that the ethical review processes need to be more flexible towards the provision of information and consent processes for service developments in newborn screening. © 2011 John Wiley & Sons Ltd.

A retrospective review of newborn screening for congenital hypothyroidism and newborn thyroid disease at a major medical center.

PubMed

Cameo, Tamara; Gumer, Lindsey Barst; Williams, Kristen M; Gomez, Jackie; McMahon, Donald J; Oberfield, Sharon E

2013-11-01

Objective. To study the frequency of congenital hypothyroidism (CH)/thyroid disorders at a major, urban medical center. Methods. We conducted a retrospective review of a preexisting database for 2007 to 2011. Infants were classified as having CH, secondary/tertiary hypothyroidism, thyroid-binding globulin deficiency, and other types of newborn thyroid dysfunctions. Results. A total of 353 (50%) abnormal newborn screens were found to be normal and 42% were abnormal on repeat. Of the latter, 14% had true CH, 1% had thyroid-binding globulin deficiency, and 27% had other causes of thyroid dysfunction. The 5-year incidence of CH at NYP Morgan Stanley Children's Hospital was significantly greater than in New York City, New York State, and Upstate New York. Conclusion. The incidence of CH and other thyroid dysfunctions were greater in our population for 2007 to 2010, after which there was an unexplained decline. The study underlines the importance of continued newborn screening for thyroid dysfunction.

How Do Health Care Providers Diagnose Klinefelter Syndrome?

MedlinePlus

... and when a diagnosis occurs: Few newborns and boys are tested for or diagnosed with KS. Although newborns in the United States are screened for some conditions, they are not screened for XXY or other sex-chromosome differences. In childhood, symptoms can be subtle ...

The Influence of Education on Public Trust and Consent Preferences With Residual Newborn Screening Dried Blood spots.

PubMed

Rothwell, Erin; Wong, Bob; Anderson, Rebecca A; Botkin, Jeffrey R

2016-07-01

The objectives of this study were to evaluate the impact of educational interventions during prenatal care on public trust for newborn screening and consent preferences for the retention and use of leftover newborn screening dried blood spots. Women who were 30 to 36 weeks pregnant were recruited, and outcomes were measured by telephone survey 2 to 4 weeks postpartum (n = 901). Approximately 40% of the sample chose the opt-out approach but those who watched educational interventions delivered during prenatal care were significantly associated with higher levels of trust and support for an opt-out consent approach. Providing education during prenatal care about newborn screening and the storage and use of leftover dried blood spots along with brochure-based education provided in the hospital when the baby is born is associated with improved trust for the program and support for research with the leftover blood spots. © The Author(s) 2016.

Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency.

PubMed

Ho, Sirikit; Lukacs, Zoltan; Hoffmann, Georg F; Lindner, Martin; Wetter, Thomas

2007-07-01

In newborn screening with tandem mass spectrometry, multiple intermediary metabolites are quantified in a single analytical run for the diagnosis of fatty-acid oxidation disorders, organic acidurias, and aminoacidurias. Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the markers have been chosen to reflect metabolic pathway deviations. We applied a procedure to extract new markers and diagnostic criteria for newborn screening to the data of newborns with confirmed medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and a control group from the newborn screening program, Heidelberg, Germany. We validated the results with external data of the screening center in Hamburg, Germany. We extracted new markers by performing a systematic search for analyte combinations (features) with high discriminatory performance for MCADD. To select feature thresholds, we applied automated procedures to separate controls and cases on the basis of the feature values. Finally, we built classifiers from these new markers to serve as diagnostic criteria in screening for MCADD. On the basis of chi(2) scores, we identified approximately 800 of >628,000 new analyte combinations with superior discriminatory performance compared with the best published combinations. Classifiers built with the new features achieved diagnostic sensitivities and specificities approaching 100%. Feature construction methods provide ways to disclose information hidden in the set of measured analytes. Other diagnostic tasks based on high-dimensional metabolic data might also profit from this approach.

New tools and approaches to newborn screening: ready to open Pandora's box?

PubMed

Ficicioglu, Can

2017-05-01

The landscape of newborn screening (NBS) is changing as new tools are developed. We must acknowledge that NBS is a very important and extraordinarily positive initiative especially for rare and serious inherited disorders; however, lessons learned from current NBS should guide the future of NBS as we enter the era of "omics" that will expand NBS for many other genetic disorders. In this article, I will first discuss new tools such as genomics and metabolomics for NBS. I will then turn to assessing how best to take advantage of new technical developments while considering the best interests of patients and the success of newborn screening.

Newborn screening for galactosaemia.

PubMed

Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

2017-12-23

Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the review. We were unable to identify any eligible studies for inclusion in this review and hence it is not possible to draw any conclusions based on randomised controlled studies. However, we are aware of uncontrolled studies which support the efficacy of newborn screening for galactosaemia. There are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate.

Buen Comienzo, Buen Futuro: Su Recien Nacido. (Healthy Start, Grow Smart: Your Newborn).

ERIC Educational Resources Information Center

Department of Education, Washington, DC.

This booklet offers guidance to parents in caring for their newborn babies. Advice is given on the following topics: (1) newborn health screening; (2) what a healthy newborn looks like; (3) newborn reflexes; (4) baby checkups; (5) fathers' role; (6) the baby blues; (7) sleeping position; (8) breast milk; (9) breast feeding; (10) bottle feeding;…

[A pilot study of ocular diseases screening for neonates in China].

PubMed

Nie, Wen-ying; Wu, Han-rong; Qi, Yi-sheng; Zhang, Min; Hou, Qian; Yang, Hai-xia; Gong, Lu-xia; Dong, Yan-ru; Guo, Yu-luan; Shi, Jin-na; Yin, Su-ying; Li, Ping-yu

2008-06-01

To explore the clinical strategies for the screening of newborn eye diseases and obtain information concerning the incidence of newborn ocular diseases. Newborns in a baby-friendly nursery were evaluated for mass screening of eye diseases 2 to 7 days after birth (including reaction to light stimulation, external ocular examination and test for pupil red reflex) and those with abnormalities were subjected to diagnostic examination (external ocular examination with a hand-held slit-lamp, pupil red reflex and mydriatic examination). Newborns in neonatal intensive care unit (NICU) were subjected to screening 5 to 14 days after birth and then, together with those with high risk factors, received a comprehensive examination for screening and diagnostic purposes. The suspected cases were referred to department of ophthalmology for definite diagnosis. Among the 15,398 (91.65%) newborns who were enrolled the screening program, 12 different eye diseases (involving 1266 cases) were detected, with a prevalence of 8.22%. Of these eye diseases, 7 were congenital ocular diseases, involving 809 cases (5. 254%) and including congenital ptosis in 2 cases (0.013%), congenital corneal opacity in 6 cases (0.039%), persistent pupillary membrane in 724 cases (4.702%), congenital cataract in 15 cases (0.097%), persistent hyaloid artery in 54 cases (0.351%), obstruction of nasolacrimal duct in 7 cases (0.046%) and lacrimal gland prolapse in 1 cases (0.007%). Five different diseases (457 cases, 2. 968%) detected were acquired in nature, including neonatal conjunctivitis in 391 case (2.539%), vitreous hemorrhage in 6 cases (0.039%), retinal hemorrhage in 34 cases (0.221%), and neonatal dacryocystitis in 23 cases (0.149%). Of 27 premature babies with body weight lower than 1500 g, 3 had retinopathy of prematurity (ROP, 6 eyes involved). Early intervention is of great importance for the prevention and treatment of neonatal ocular diseases. The screening of newborn ocular diseases is not only feasible but also effective in the monitoring and control of the eye diseases in neonates.

Cost-benefit analysis of hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency: for consideration of expanded newborn screening in Hong Kong.

PubMed

Lee, Hencher Han-Chih; Mak, Chloe Miu; Poon, Grace Wing-Kit; Wong, Kar-Yin; Lam, Ching-Wan

2014-06-01

To evaluate the cost-benefit of implementing an expanded newborn screening programme for hyperphenylalaninemias due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency in Hong Kong. Regional public hospitals in Hong Kong providing care for cases of inborn errors of metabolism. Implementational and operational costs of a new expanded mass spectrometry-based newborn screening programme were estimated. Data on various medical expenditures for the mild and severe phenotypic subtypes were gathered from a case cohort diagnosed with PTPS deficiency from 2001 to 2009. Local incidence from a previously published study was used. Implementation and operational costs of an expanded newborn screening programme in Hong Kong were estimated at HKD 10,473,848 (USD 1,342,801) annually. Assuming a birthrate of 50,000 per year and an incidence of 1 in 29,542 live births, the medical costs and adjusted loss of workforce per year would be HKD 20,773,207 (USD 2,663,232). Overall the annual savings from implementing the programme would be HKD 9,632,750 (USD 1,234,968). Our estimates show that implementation of an expanded newborn screening programme in Hong Kong is cost-effective, with a significant annual saving for public expenditure. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

First case of Hb Fontainebleau with sickle haemoglobin and other non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders.

PubMed

Upadhye, Dipti S; Jain, Dipty; Nair, Sona B; Nadkarni, Anita H; Ghosh, Kanjaksha; Colah, Roshan B

2012-07-01

To evaluate the significance of non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders. 1534 newborn babies were screened in the last 2 years for sickle cell disease using a targeted screening approach. Investigations included a complete blood count, high performance liquid chromatography analysis, cellulose acetate electrophoresis (pH 8.9), heat stability test, restriction digestion and Amplified Refractory Mutation System for confirmation of sickle haemoglobin (Hb S), α genotyping by multiplex PCR and DNA sequencing. Three non-deletional α gene variants, Hb Fontainebleau, Hb O Indonesia and Hb Koya Dora, were identified in heterozygous condition in newborns. This is the first report of Hb Fontainebleau in association with Hb S. The baby had anaemia at birth (Hb 11.4 g/dl) with no cyanosis, icterus or need for transfusion. She had occipital encephalocoele and was operated on day 24 to remove the mass. The baby diagnosed with Hb O Indonesia in combination with Hb S also had a low haemoglobin level of 12.7 g/dl. Newborn screening for sickle cell disorders also enabled us to identify three α globin chain variants. Two babies who inherited Hb Fontainebleau and Hb O Indonesia along with Hb S had reduced Hb levels at birth and need to be followed up.

Implications of Maple Syrup Urine Disease in Newborns.

PubMed

Harris-Haman, Pamela; Brown, Lenora; Massey, Susan; Ramamoorthy, Sivaranjani

Maple syrup urine disease (MSUD) is an inherited metabolic disorder that affects the body's ability to metabolize amino acids. If left untreated, it places newborns at risk for life-threatening health problems, including episodes of illness called metabolic crisis. Newborn screening for MSUD should ideally be done within the first 24 to 48 hours after birth. With proper screening, along with genetic counseling, nutritional counseling, primary care follow-up, and ongoing monitoring, newborns with MSUD can typically go on to live healthful lives. Nurses play a key role in supporting families with a diagnosis of MSUD. © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

Newborn screening for proximal urea cycle disorders: Current evidence supporting recommendations for newborn screening.

PubMed

Merritt, J Lawrence; Brody, Linnea L; Pino, Gisele; Rinaldo, Piero

2018-04-20

Current newborn screening (NBS) for urea cycle disorders (UCD) is incomplete as only distal UCDs are included in most NBS programs by measuring elevated amino acid concentrations. NBS for the proximal UCDs involves the detection in NBS spots of low citrulline values, a finding which is often overlooked because it is considered to be inadequate. We retrospectively analyzed NBS blood spots from known UCD patients comparing the utility of the Region 4 Stork (R4S) interpretive tools to conventional cutoff based interpretation. This study shows the utility of R4S tools in detecting all UCDs, and provides evidence to support the nomination to add proximal UCDs to the recommended uniform screening panel. Copyright © 2018 Elsevier Inc. All rights reserved.

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…

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…

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…

[Prevalence of diseases diagnosed by the Program of Neonatal Screening in Maringá, Paraná, Brazil: 2001-2006].

PubMed

Luz, Geisa dos Santos; Carvalho, Maria Dalva de Barros; Pelloso, Sandra Marisa; Higarashi, Ieda Harumi

2008-09-01

Irreversible sequels of some genetic diseases can be prevented by neonatal screening. The aim of this paper was to verify the prevalence of diseases diagnosed by the National Program of Neonatal Screening (PNTN) in Maringá, Paraná, Brazil, between 2001 and 2006. This cross-sectional descriptive study included 20,529 newborn infants screened by that program. Out of those, 859 were re-examined, and 21 had the disease confirmed. Considering all screened newborn infants and the number of diagnostics per disease, the following disease prevalence was determine: phenylketonuria--1:20,529; congenital hypothyrodism--1:2,281; hemoglobinopahies--1:3,421; cystic fibrosis--1:10,264; and biotinidase deficiency--1:6,843. Understanding disease status and prevalence of newborns in a population allows the establishment and the improvement of public policies aimed at the children.

A framework for assessing outcomes from newborn screening: on the road to measuring its promise

PubMed Central

Hinton, Cynthia F.; Homer, Charles J.; Thompson, Alexis A.; Williams, Andrea; Hassell, Kathryn L.; Feuchtbaum, Lisa; Berry, Susan A.; Comeau, Anne Marie; Therrell, Bradford L.; Brower, Amy; Harris, Katharine B.; Brown, Christine; Monaco, Jana; Ostrander, Robert J.; Zuckerman, Alan E.; Kaye, Celia; Dougherty, Denise; Greene, Carol; Green, Nancy S.

2016-01-01

Newborn screening (NBS) is intended to identify congenital conditions prior to the onset of symptoms in order to provide early intervention that leads to improved outcomes. NBS is a public health success, providing reduction in mortality and improved developmental outcomes for screened conditions.. However, it is less clear to what extent newborn screening achieves the long-term goals relating to improved health, growth, development and function. We propose a framework for assessing outcomes for the health and well-being of children identified through NBS programs. The framework proposed here, and this manuscript, were approved for publication by the Secretary of Health and Human Services’ Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC). This framework can be applied to each screened condition within the Recommended Uniform Screening Panel (RUSP), recognizing that the data elements and measures will vary by condition. As an example, we applied the framework to sickle cell disease and phenylketonuria (PKU), two diverse conditions with different outcome measures and potential sources of data. Widespread and consistent application of this framework across state NBS and child health systems is envisioned as useful to standardize approaches to assessment of outcomes and for continuous improvement of the NBS and child health systems. PMID:27268406

Ethical, legal, and social issues in health technology assessment for prenatal/preconceptional and newborn screening: a workshop report.

PubMed

Potter, B K; Avard, D; Entwistle, V; Kennedy, C; Chakraborty, P; McGuire, M; Wilson, B J

2009-01-01

Prenatal/preconceptional and newborn screening programs have been a focus of recent policy debates that have included attention to ethical, legal, and social issues (ELSIs). In parallel, there has been an ongoing discussion about whether and how ELSIs may be addressed in health technology assessment (HTA). We conducted a knowledge synthesis study to explore both guidance and current practice regarding the consideration of ELSIs in HTA for prenatal/preconceptional and newborn screening. As the concluding activity for this project, we held a Canadian workshop to discuss the issues with a diverse group of stakeholders. Based on key workshop themes integrated with our study results, we suggest that population-based genetic screening programs may present particular types of ELSIs and that a public health ethics perspective is potentially highly relevant when considering them. We also suggest that approaches to addressing ELSIs in HTA for prenatal/preconceptional and newborn screening may need to be flexible enough to respond to diversity in HTA organizations, cultural values, stakeholder communities, and contextual factors. Finally, we highlight a need for transparency in the way that HTA producers move from evidence to conclusions and the ways in which screening policy decisions are made. Copyright © 2008 S. Karger AG, Basel.

Ethical, Legal, and Social Issues in Health Technology Assessment for Prenatal/Preconceptional and Newborn Screening: A Workshop Report

PubMed Central

Potter, B.K.; Avard, D.; Entwistle, V.; Kennedy, C.; Chakraborty, P.; McGuire, M.; Wilson, B.J.

2008-01-01

Prenatal/preconceptional and newborn screening programs have been a focus of recent policy debates that have included attention to ethical, legal, and social issues (ELSIs). In parallel, there has been an ongoing discussion about whether and how ELSIs may be addressed in health technology assessment (HTA). We conducted a knowledge synthesis study to explore both guidance and current practice regarding the consideration of ELSIs in HTA for prenatal/preconceptional and newborn screening. As the concluding activity for this project, we held a Canadian workshop to discuss the issues with a diverse group of stakeholders. Based on key workshop themes integrated with our study results, we suggest that population-based genetic screening programs may present particular types of ELSIs and that a public health ethics perspective is potentially highly relevant when considering them. We also suggest that approaches to addressing ELSIs in HTA for prenatal/preconceptional and newborn screening may need to be flexible enough to respond to diversity in HTA organizations, cultural values, stakeholder communities, and contextual factors. Finally, we highlight a need for transparency in the way that HTA producers move from evidence to conclusions and the ways in which screening policy decisions are made. PMID:19023190

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

The importance of retesting the hearing screening as an indicator of the real early hearing disorder.

PubMed

Silva, Daniela Polo Camargo da; Lopez, Priscila Suman; Ribeiro, Georgea Espíndola; Luna, Marcos Otávio de Mesquita; Lyra, João César; Montovani, Jair Cortez

2015-01-01

Early diagnosis of hearing loss minimizes its impact on child development. We studied factors that influence the effectiveness of screening programs. To investigate the relationship between gender, weight at birth, gestational age, risk factors for hearing loss, venue for newborn hearing screening and "pass" and "fail" results in the retest. Prospective cohort study was carried out in a tertiary referral hospital. The screening was performed in 565 newborns through transient evoked otoacoustic emissions in three admission units before hospital discharge and retest in the outpatient clinic. Gender, weight at birth, gestational age, presence of risk indicators for hearing loss and venue for newborn hearing screening were considered. Full-term infants comprised 86% of the cases, preterm 14%, and risk factors for hearing loss were identified in 11%. Considering the 165 newborns retested, only the venue for screening, Intermediate Care Unit, was related to "fail" result in the retest. Gender, weight at birth, gestational age and presence of risk factors for hearing loss were not related to "pass" and/or "fail" results in the retest. The screening performed in intermediate care units increases the chance of continued "fail" result in the Transient Otoacoustic Evoked Emissions test. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Predicting gestational age using neonatal metabolic markers

PubMed Central

Ryckman, Kelli K.; Berberich, Stanton L.; Dagle, John M.

2016-01-01

Background Accurate gestational age estimation is extremely important for clinical care decisions of the newborn as well as for perinatal health research. Although prenatal ultrasound dating is one of the most accurate methods for estimating gestational age, it is not feasible in all settings. Identifying novel and accurate methods for gestational age estimation at birth is important, particularly for surveillance of preterm birth rates in areas without routine ultrasound dating. Objective We hypothesized that metabolic and endocrine markers captured by routine newborn screening could improve gestational age estimation in the absence of prenatal ultrasound technology. Study Design This is a retrospective analysis of 230,013 newborn metabolic screening records collected by the Iowa Newborn Screening Program between 2004 and 2009. The data were randomly split into a model-building dataset (n = 153,342) and a model-testing dataset (n = 76,671). We performed multiple linear regression modeling with gestational age, in weeks, as the outcome measure. We examined 44 metabolites, including biomarkers of amino acid and fatty acid metabolism, thyroid-stimulating hormone, and 17-hydroxyprogesterone. The coefficient of determination (R2) and the root-mean-square error were used to evaluate models in the model-building dataset that were then tested in the model-testing dataset. Results The newborn metabolic regression model consisted of 88 parameters, including the intercept, 37 metabolite measures, 29 squared metabolite measures, and 21 cubed metabolite measures. This model explained 52.8% of the variation in gestational age in the model-testing dataset. Gestational age was predicted within 1 week for 78% of the individuals and within 2 weeks of gestation for 95% of the individuals. This model yielded an area under the curve of 0.899 (95% confidence interval 0.895−0.903) in differentiating those born preterm (<37 weeks) from those born term (≥37 weeks). In the subset of infants born small-for-gestational age, the average difference between gestational ages predicted by the newborn metabolic model and the recorded gestational age was 1.5 weeks. In contrast, the average difference between gestational ages predicted by the model including only newborn weight and the recorded gestational age was 1.9 weeks. The estimated prevalence of preterm birth <37 weeks’ gestation in the subset of infants that were small for gestational age was 18.79% when the model including only newborn weight was used, over twice that of the actual prevalence of 9.20%. The newborn metabolic model underestimated the preterm birth prevalence at 6.94% but was closer to the prevalence based on the recorded gestational age than the model including only newborn weight. Conclusions The newborn metabolic profile, as derived from routine newborn screening markers, is an accurate method for estimating gestational age. In small-for-gestational age neonates, the newborn metabolic model predicts gestational age to a better degree than newborn weight alone. Newborn metabolic screening is a potentially effective method for population surveillance of preterm birth in the absence of prenatal ultrasound measurements or newborn weight. PMID:26645954

Predicting gestational age using neonatal metabolic markers.

PubMed

Ryckman, Kelli K; Berberich, Stanton L; Dagle, John M

2016-04-01

Accurate gestational age estimation is extremely important for clinical care decisions of the newborn as well as for perinatal health research. Although prenatal ultrasound dating is one of the most accurate methods for estimating gestational age, it is not feasible in all settings. Identifying novel and accurate methods for gestational age estimation at birth is important, particularly for surveillance of preterm birth rates in areas without routine ultrasound dating. We hypothesized that metabolic and endocrine markers captured by routine newborn screening could improve gestational age estimation in the absence of prenatal ultrasound technology. This is a retrospective analysis of 230,013 newborn metabolic screening records collected by the Iowa Newborn Screening Program between 2004 and 2009. The data were randomly split into a model-building dataset (n = 153,342) and a model-testing dataset (n = 76,671). We performed multiple linear regression modeling with gestational age, in weeks, as the outcome measure. We examined 44 metabolites, including biomarkers of amino acid and fatty acid metabolism, thyroid-stimulating hormone, and 17-hydroxyprogesterone. The coefficient of determination (R(2)) and the root-mean-square error were used to evaluate models in the model-building dataset that were then tested in the model-testing dataset. The newborn metabolic regression model consisted of 88 parameters, including the intercept, 37 metabolite measures, 29 squared metabolite measures, and 21 cubed metabolite measures. This model explained 52.8% of the variation in gestational age in the model-testing dataset. Gestational age was predicted within 1 week for 78% of the individuals and within 2 weeks of gestation for 95% of the individuals. This model yielded an area under the curve of 0.899 (95% confidence interval 0.895-0.903) in differentiating those born preterm (<37 weeks) from those born term (≥37 weeks). In the subset of infants born small-for-gestational age, the average difference between gestational ages predicted by the newborn metabolic model and the recorded gestational age was 1.5 weeks. In contrast, the average difference between gestational ages predicted by the model including only newborn weight and the recorded gestational age was 1.9 weeks. The estimated prevalence of preterm birth <37 weeks' gestation in the subset of infants that were small for gestational age was 18.79% when the model including only newborn weight was used, over twice that of the actual prevalence of 9.20%. The newborn metabolic model underestimated the preterm birth prevalence at 6.94% but was closer to the prevalence based on the recorded gestational age than the model including only newborn weight. The newborn metabolic profile, as derived from routine newborn screening markers, is an accurate method for estimating gestational age. In small-for-gestational age neonates, the newborn metabolic model predicts gestational age to a better degree than newborn weight alone. Newborn metabolic screening is a potentially effective method for population surveillance of preterm birth in the absence of prenatal ultrasound measurements or newborn weight. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Newborn Screening for Vitamin B6 Non-responsive Classical Homocystinuria: Systematical Evaluation of a Two-Tier Strategy.

PubMed

Okun, Jürgen G; Gan-Schreier, Hongying; Ben-Omran, Tawfeq; Schmidt, Kathrin V; Fang-Hoffmann, Junmin; Gramer, Gwendolyn; Abdoh, Ghassan; Shahbeck, Noora; Al Rifai, Hilal; Al Khal, Abdul Latif; Haege, Gisela; Chiang, Chuan-Chi; Kasper, David C; Wilcken, Bridget; Burgard, Peter; Hoffmann, Georg F

2017-01-01

In classical homocystinuria (HCU, MIM# 236200) due to the deficiency of cystathionine β-synthase (EC 4.2.1.22) there is a clear evidence for the success of early treatment. The aim of this study was to develop and evaluate a two-tier strategy for HCU newborn screening. We reevaluated data from our newborn screening programme for Qatar in a total number of 125,047 neonates including 30 confirmed HCU patients. Our hitherto existing screening strategy includes homocysteine (Hcy) measurements in every child, resulting in a unique dataset for evaluation of two-tier strategies. Reevaluation included methionine (Met) levels, Met to phenylalanine (Phe) ratio, and Hcy. Four HCU cases identified after database closure were also included in the evaluation. In addition, dried blood spot samples selected by Met values >P97 in the newborn screening programs in Austria, Australia, the Netherlands, and Taiwan were analyzed for Hcy. Met to Phe ratio was found to be more effective for first sieve than Met, sorting out nearly 90% of normal samples. Only 10% of the samples would have to be processed by second-tier measurement of Hcy in dried blood spots. As no patient with HCU was found neither in the samples investigated for HCU, nor by clinical diagnosis in the other countries, the generalization of our two-tier strategy could only be tested indirectly. The finally derived two-tier algorithm using Met to Phe ratio as first- and Hcy as second-tier requires 10% first-tier positives to be transferred to Hcy measurement, resulting in 100% sensitivity and specificity in HCU newborn screening.

A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening

PubMed Central

McCollister, Faye P.; Sabo, Diane L.; Shoup, Angela G.; Owen, Kris E.; Woodruff, Julie L.; Cox, Edith; Mohamed, Lisa S.; Choo, Daniel I.; Boppana, Suresh B.

2017-01-01

BACKGROUND AND OBJECTIVE: Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). METHODS: Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. RESULTS: Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P < .0001). Among the cCMV infants who failed NHS, diagnostic testing confirmed that 65% had SNHL. In addition, 3.6% of CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. CONCLUSIONS: A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS. PMID:28049114

Critical congenital heart disease screening practices among licensed midwives in washington state.

PubMed

Evers, Patrick D; Vernon, Margaret M; Schultz, Amy H

2015-01-01

Since 2011, pulse oximetry screening for critical congenital heart disease (CCHD) has been recommended for newborns. Initial implementation guidelines focused on in-hospital births. Recent publications affirm the importance of universal screening, including for out-of-hospital births. No published data describe CCHD screening rates for out-of-hospital births. Licensed midwives in Washington state were surveyed regarding their current CCHD screening practices, volume of births attended annually, and typical newborn follow-up practices. For those who indicated they were screening, additional information was obtained about equipment used, timing of screening, and rationale for voluntarily initiating screening. For those who indicated that they were not screening, information regarding barriers to implementation was solicited. Of the 61 midwives in our sample, 98% indicated they were aware of published guidelines recommending universal newborn screening for CCHD utilizing pulse oximetry. Furthermore, 52% indicated that they were screening for CCHD currently. Ten percent stated they do not intend to screen, whereas the remaining respondents indicated that they plan to screen in the future. The primary barriers to screening were the cost of pulse oximetry equipment and inadequate training in screening technique and interpretation. Although voluntary implementation of CCHD screening by licensed midwives in Washington is increasing, it lags behind the implementation rates reported for in-hospital births. © 2015 by the American College of Nurse-Midwives.

Is the Neonatal Tongue Screening Test a valid and reliable tool for detecting ankyloglossia in newborns?

PubMed

Brandão, Clarissa de Almeida; de Marsillac, Mirian de Waele Souchois; Barja-Fidalgo, Fernanda; Oliveira, Branca Heloisa

2018-05-16

Although there is a lack of strong evidence for the association between ankyloglossia in newborns and impaired breastfeeding, screening for ankyloglossia using the Neonatal Tongue Screening Test (NTST) is mandated by law in Brazilian maternities. To assess the reliability and validity of the NTST. cohort study; baseline sample comprised 268 mother-newborn dyads. At follow-up, 169 mothers were contacted by telephone. Interviews with the mothers for data collection were performed up to 48 h and at 1-3 months after childbirth. Trained and calibrated personnel performed the oral examinations of the newborns. Thirty newborns were examined for inter-reproducibility assessment. Of the 268 newborns included, 212 had a lingual frenulum that could be visually inspected and their NTST scores ranged from zero to nine (mean = 2.0, ±2.0). Interexaminer reproducibility was acceptable (Intraclass correlation coefficient = 0.77). Internal consistency of the NTST was poor (Cronbach's alpha = 0.28). Construct validity was investigated through the association between NTST scores and difficulties in breastfeeding at baseline and follow-up, and infants' weight gain at follow-up (mean age 32 ± 6.7 days). No statistically significant associations were found. NTST is neither reliable nor valid for detecting ankyloglossia that may interfere with breastfeeding in newborns. © 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Changing Perspectives on the Benefits of Newborn Screening

ERIC Educational Resources Information Center

Bailey, Donald B., Jr.; Beskow, Laura M.; Davis, Arlene M.; Skinner, Debra

2006-01-01

The likelihood of benefit is fundamental to decision making about newborn screening. But benefit is construed in different ways by different stakeholders. This article begins with a review of benefit as considered historically by various expert panels and organizations. We then show how 78 conditions fared when experts recently rated them on…

Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen.

PubMed

Woodruff, Samantha A; Sontag, Marci K; Accurso, Frank J; Sokol, Ronald J; Narkewicz, Michael R

2017-01-01

Prevalence and risks for elevated liver enzymes have not been studied systematically in children with CF identified by newborn screen. 298 CF children identified by newborn screen since 1982. AST, ALT and GGT tested at annual visits. Percent of children with 1 or ≥2 values of elevated AST, ALT and GGT determined. Relationship of liver enzymes to clinical factors or subsequent liver disease was analyzed RESULTS: At least one abnormal value for AST (63%), ALT (93%) and ALT ≥1.5× ULN (52%) occurred by 21years of age. Liver enzyme elevations were not correlated with CFTR mutation, meconium ileus or ethnicity. AST and GGT ≥1.5× ULN were associated with later advanced liver disease HR (CI) 6.53 (2.02-21.1) and 4.03 (1.15-13.45), respectively. Elevated liver enzymes are common during childhood in CF patients identified by newborn screen. Elevated AST and GGT may be markers for risk of advanced liver disease. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Screening of a healthy newborn identifies three adult family members with symptomatic glutaric aciduria type I.

PubMed

McH, Janssen; Laj, Kluijtmans; S B, Wortmann

2014-06-01

We report three adult sibs (one female, two males) with symptomatic glutaric acidura type I, who were diagnosed after a low carnitine level was found by newborn screening in a healthy newborn of the women. All three adults had low plasma carnitine, elevated glutaric acid levels and pronounced 3-hydroxyglutaric aciduria. The diagnosis was confirmed by undetectable glutaryl-CoA dehydrogenase activity in lymphocytes and two pathogenic heterozygous mutations in the GCDH gene (c.1060A > G, c.1154C > T). These results reinforce the notion that abnormal metabolite levels in newborns may lead to the diagnosis of adult metabolic disease in the mother and potentially other family members.

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

PubMed

la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

2014-01-01

Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine <0.09μmol/L, adenosine <1.61μmol/L). We also developed a second tier test to distinguish true positives from false positives and improve the positive predictive value of an initial abnormal result. In the first 18 months, the pilot project has identified a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Evaluation of identifier field agreement in linked neonatal records.

PubMed

Hall, E S; Marsolo, K; Greenberg, J M

2017-08-01

To better address barriers arising from missing and unreliable identifiers in neonatal medical records, we evaluated agreement and discordance among traditional and non-traditional linkage fields within a linked neonatal data set. The retrospective, descriptive analysis represents infants born from 2013 to 2015. We linked children's hospital neonatal physician billing records to newborn medical records originating from an academic delivery hospital and evaluated rates of agreement, discordance and missingness for a set of 12 identifier field pairs used in the linkage algorithm. We linked 7293 of 7404 physician billing records (98.5%), all of which were deemed valid upon manual review. Linked records contained a mean of 9.1 matching and 1.6 non-matching identifier pairs. Only 4.8% had complete agreement among all 12 identifier pairs. Our approach to selection of linkage variables and data formatting preparatory to linkage have generalizability, which may inform future neonatal and perinatal record linkage efforts.

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

PubMed

2012-04-06

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 screening laboratories. The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. These recommendations are intended for laboratories that perform biochemical genetic testing to improve the quality of laboratory services and for newborn screening laboratories to ensure the quality of laboratory practices for inherited metabolic disorders. These recommendations also are intended as a resource for medical and public health professionals who evaluate laboratory practices, for users of laboratory services to facilitate their collaboration with newborn screening systems and use of biochemical genetic tests, and for standard-setting organizations and professional societies in developing future laboratory quality standards and practice recommendations. This report complements Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6]) to provide guidance for ensuring and improving the quality of genetic laboratory services and public health outcomes. Future recommendations for additional areas of genetic testing will be considered on the basis of continued monitoring and evaluation of laboratory practices, technology advancements, and the development of laboratory standards and guidelines.

The hearing system in newborns from the Upper Silesia. Assessment of TEOAE depending on selected parameters of delivery disorders.

PubMed

Namyslowski, G; Morawski, K; Urbaniec, N; Lisowska, G; Trybalska, G; Bazowska, G; Oslislo, A

2001-01-01

Transient evoked otoacoustic emission (TEOAE) is an accepted test for screening of the cochlea function in newborns. In this study 300 newborns was tested using TEOAE, as well as analysing such parameters as birth weight, Apgar scale, bilirubinaemia. The study indicated the tendency of TEOAE to decrease in newborns with low birth weight and low Apgar scores. Hyperbilirubinaemia seems to have an influence on cochlea function monitored by TEOAE, especially if there were simultaneously low Apgar scores. A similar tendency, although slightly stronger, was observed in the preterm newborn group. TEOAE seems to be a good method of recording the negative influence on the cochlea activity such factors as low birth weight and asphyxia. Hyperbilirubinaemia with asphyxia acts upon the cochlea similarly. All these tendencies were observed more strongly in the preterm newborn group. It is concluded that TEOAE analysis demonstrated its utility as a screening test assessing the hearing state in newborns, additionally the associations of cochlea activity was found with a few parameters of delivery disorders.

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…

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,…

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…

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

Putting newborn hearing screening on the political agenda in Belgium: local initiatives toward a community programme – a qualitative study

PubMed Central

2014-01-01

Background The Kingdon model, based on the convergence of three streams (problem, policy, and politics) and the opening of a policy window, analyses the process by which a health issue is placed on the political agenda. We used this model to document the political agenda-setting process of the newborn hearing screening programme in Belgium. Methods A qualitative study based on a document review and on semi-directed interviews was carried out. The interviews were conducted with nine people who had played a role in putting the issue in question on the political agenda, and the documents reviewed included scientific literature and internal reports and publications from the newborn hearing screening programme. The thematic analysis of the data collected was carried out on the basis of the Kingdon model’s three streams. Results The political agenda-setting of this screening programme was based on many factors. The problem stream included factors external to the context under study, such as the technological developments and the contribution of the scientific literature which led to the recommendation to provide newborn hearing screening. The two other streams (policy and politics) covered factors internal to the Belgian context. The fact that it was locally feasible with financial support, the network of doctors convinced of the need for newborn hearing screening, the drafting of various proposals, and the search for financing were all part of the policy stream. The Belgian political context and the policy opportunities concerning preventive medicine were identified as significant factors in the third stream. When these three streams converged, a policy window opened, allowing newborn hearing screening onto the political agenda and enabling the policy decision for its introduction. Conclusions The advantage of applying the Kingdon model in our approach was the ability to demonstrate the political agenda-setting process, using the three streams. This made it possible to identify the many factors involved in the process. However, the roles of the stakeholders and of the context were somewhat inexplicit in this model. PMID:24986647

Putting newborn hearing screening on the political agenda in Belgium: local initiatives toward a community programme - a qualitative study.

PubMed

Vos, Bénédicte; Lagasse, Raphaël; Levêque, Alain

2014-07-01

The Kingdon model, based on the convergence of three streams (problem, policy, and politics) and the opening of a policy window, analyses the process by which a health issue is placed on the political agenda. We used this model to document the political agenda-setting process of the newborn hearing screening programme in Belgium. A qualitative study based on a document review and on semi-directed interviews was carried out. The interviews were conducted with nine people who had played a role in putting the issue in question on the political agenda, and the documents reviewed included scientific literature and internal reports and publications from the newborn hearing screening programme. The thematic analysis of the data collected was carried out on the basis of the Kingdon model's three streams. The political agenda-setting of this screening programme was based on many factors. The problem stream included factors external to the context under study, such as the technological developments and the contribution of the scientific literature which led to the recommendation to provide newborn hearing screening. The two other streams (policy and politics) covered factors internal to the Belgian context. The fact that it was locally feasible with financial support, the network of doctors convinced of the need for newborn hearing screening, the drafting of various proposals, and the search for financing were all part of the policy stream. The Belgian political context and the policy opportunities concerning preventive medicine were identified as significant factors in the third stream. When these three streams converged, a policy window opened, allowing newborn hearing screening onto the political agenda and enabling the policy decision for its introduction. The advantage of applying the Kingdon model in our approach was the ability to demonstrate the political agenda-setting process, using the three streams. This made it possible to identify the many factors involved in the process. However, the roles of the stakeholders and of the context were somewhat inexplicit in this model.

Systematic review of knowledge of, attitudes towards, and practices for newborn hearing screening among healthcare professionals.

PubMed

Ravi, Rohit; Gunjawate, Dhanshree R; Yerraguntla, Krishna; Rajashekhar, Bellur

2018-01-01

The success of newborn hearing screening programs lies in the timely identification, diagnosis, and management of children with hearing loss accomplished via a multidisciplinary newborn hearing screening (NHS) team. The team is typically comprised of various healthcare professionals who act as decision makers as well as facilitators for different stages in the screening process. Team members' knowledge of, attitudes towards, and practices for early hearing detection and intervention programs are critical for success and prevention of loss to follow up. In this context, it becomes crucial to understand their knowledge of, attitudes towards, and practices for towards newborn hearing screening. A systematic review was conducted on the following databases; PubMed/Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, Science Direct and Cochrane Library. This search was carried out using various keywords such as practitioners, newborn hearing screening, knowledge, attitudes, and practices in different combinations. The review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. A total of 271 hits were obtained of which 20 articles were found suitable for inclusion in the final review. Overall, similar results were found regarding team members' knowledge of NHS programs, regardless of country of origin. Similarly, attitudes toward NHS programs were positive. Team members' experiences with NHS programs varied from country-to-country and across healthcare professionals. Results consistently showed gaps in team members' knowledge suggesting the need for outreach and professional education programs on NHS. NHS teams members from different countries, healthcare systems, and early hearing detection and intervention programs show gaps in critical knowledge warranting outreach and educational programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Promising outcomes in glutaric aciduria type I patients detected by newborn screening.

PubMed

Lee, Chee-Seng; Chien, Yin-Hsiu; Peng, Shinn-Forng; Cheng, Pin-Wen; Chang, Lih-Maan; Huang, Ai-Chu; Hwu, Wuh-Liang; Lee, Ni-Chung

2013-03-01

Glutaric aciduria type I (GA-I) is an inborn error of lysine and tryptophan metabolism. Clinical manifestations of GA-I include dystonic or dyskinetic cerebral palsy, but when the symptoms occur, treatment is not effective. In Taiwan, newborn screening for GA-I started in 2001; we wish to evaluate the outcomes of patients detected through newborn screening. Newborns diagnosed with GA-I by abnormal dried blood spot glutarylcarnitine (C5DC) levels followed in our hospital were included in this study. They were treated with special diets, carnitine supplements, and immediate stress avoidance. Six patients were included in this study. All patients were treated prior to reaching 1 month of age. They were followed up with for 4 to 9 years. One patient had encephalopathic crisis episodes prior to turning 1 year old that caused pallidal lesions. Another patient had a chronic progressive disease during infancy that caused bilateral putamen lesions. These two patients had delayed development, but their brain lesions were resolved. The other four patients ran uneventful courses. They had normal intelligenece, ranged between average to low average level and their brain magnetic resonance imaging showed only high intensity over deep white matter. Patients with GA-I diagnosed by newborn screening have promising outcomes, though the risks of disease progression prior to 1 year of age remain significant.

Newborn screening for congenital adrenal hyperplasia in Cuba: six years of experience.

PubMed

González, Ernesto Carlos; Carvajal, Frank; Frómeta, Amarilys; Arteaga, Ana Luisa; Castells, Elisa María; Espinosa, Tania; Coto, Remigio; Pérez, Pedro Lucio; Tejeda, Yileidis; Del Río, Lesley; Segura, Mary Triny; Almenares, Pedro; Robaina, René; Fernández, José Luis

2013-06-05

Since 2005, a newborn screening program for congenital adrenal hyperplasia (CAH) by measuring 17-alpha-hydroxyprogesterone (17OHP) in dried blood spots was introduced in Cuba. The hormone was measured by the 17OHP Neonatal UMELISA method, in samples collected on the 5th day as average. Confirmatory test was performed to those neonates with 17OHP values above 55 nmol/l. Some perinatal factors that can influence on 17OHP levels were studied. From January 2005 to December 2010, 621,303 newborns were screened and 39 CAH cases were detected. Coverage of the program reached 98%. The incidence of CAH in Cuba was 1:15,931, similar to that reported by other programs. A recall for suspected CAH was performed in 10,799 cases (1.74%). Therapy in classical CAH patients was started at the mean age of 22 days. 17OHP levels were significantly higher in newborns with lower birth-weight (BW) and/or gestational age (GA). In addition, 17OHP values were affected by the gender, twin status or mode of delivery. In Cuba, the nationwide newborn screening program has allowed the early detection of CAH. The use of an optimized cut-off level for BW or GA could lead to a reduction in the percentage of recalled babies. Copyright © 2013 Elsevier B.V. All rights reserved.

Economic evaluation of long-term impacts of universal newborn hearing screening.

PubMed

Chiou, Shu-Ti; Lung, Hou-Ling; Chen, Li-Sheng; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Chiu, Sherry Yueh-Hsia; Chen, Hsiu-Hsi

2017-01-01

Little is known about the long-term efficacious and economic impacts of universal newborn hearing screening (UNHS). An analytical Markov decision model was framed with two screening strategies: UNHS with transient evoked otoacoustic emission (TEOAE) test and automatic acoustic brainstem response (aABR) test against no screening. By estimating intervention and long-term costs on treatment and productivity losses and the utility of life years determined by the status of hearing loss, we computed base-case estimates of the incremental cost-utility ratios (ICURs). The scattered plot of ICUR and acceptability curve was used to assess the economic results of aABR versus TEOAE or both versus no screening. A hypothetical cohort of 200,000 Taiwanese newborns. TEOAE and aABR dominated over no screening strategy (ICUR = $-4800.89 and $-4111.23, indicating less cost and more utility). Given $20,000 of willingness to pay (WTP), the probability of being cost-effective of aABR against TEOAE was up to 90%. UNHS for hearing loss with aABR is the most economic option and supported by economically evidence-based evaluation from societal perspective.

Implementation of newborn screening for cystic fibrosis in Norway. Results from the first three years.

PubMed

Lundman, Emma; Gaup, H Junita; Bakkeheim, Egil; Olafsdottir, Edda J; Rootwelt, Terje; Storrøsten, Olav Trond; Pettersen, Rolf D

2016-05-01

Norway introduced newborn screening for cystic fibrosis (CF) March 1, 2012. We present results from the first three years of the national newborn CF screening program. Positive primary screening of immunoreactive trypsinogen (IRT) was followed by DNA testing of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. Infants with two CFTR mutations were reported for diagnostic follow-up. Of 181,859 infants tested, 1454 samples (0.80%) were assessed for CFTR mutations. Forty children (1:4546) had two CFTR mutations, of which only 21 (1:8660) were confirmed to have a CF diagnosis. The CFTR mutations differed from previously clinically diagnosed CF patients, and p.R117H outnumbered p.F508del as the most frequent mutation. One child with a negative IRT screening test was later clinically diagnosed with CF. The CF screening program identified fewer children with a conclusive CF diagnosis than expected. Our data suggest a revision of the IRT/DNA protocol. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Two-year pilot study of newborn screening for congenital adrenal hyperplasia in New South Wales compared with nationwide case surveillance in Australia.

PubMed

Gleeson, Helena K; Wiley, Veronica; Wilcken, Bridget; Elliott, Elizabeth; Cowell, Christopher; Thonsett, Michael; Byrne, Geoffrey; Ambler, Geoffrey

2008-10-01

To assess the benefits and practicalities of setting up a newborn screening (NBS) program in Australia for congenital adrenal hyperplasia (CAH) through a 2 year pilot screening in ACT/NSW and comparing with case surveillance in other states. The pilot newborn screening occurred between 1/10/95 and 30/9/97 in NSW/ACT. Concurrently, case reporting for all new CAH cases occurred through the Australian Paediatric Surveillance Unit (APSU) across Australia. Details of clinical presentation, re-sampling and laboratory performance were assessed. 185,854 newborn infants were screened for CAH in NSW/ACT. Concurrently, 30 cases of CAH were reported to APSU, twelve of which were from NSW/ACT. CAH incidence was 1 in 15 488 (screened population) vs 1 in 18,034 births (unscreened) (difference not significant). Median age of initial notification was day 8 with confirmed diagnosis at 13(5-23) days in the screened population vs 16(7-37) days in the unscreened population (not significant). Of the 5 clinically unsuspected males in the screened population, one had mild salt-wasting by the time of notification, compared with salt-wasting crisis in all 6 males from the unscreened population. 96% of results were reported by day 10. Resampling was requested in 637 (0.4%) and median re-sampling delay was 11(0-28) days with higher resample rates in males (p < 0.0001). The within-laboratory cost per case of clinically unsuspected cases was A$42 717. There seems good justification for NBS for CAH based on clear prevention of salt-wasting crises and their potential long-term consequences. Also, prospects exist for enhancing screening performance.

Effects of background noise on recording of portable transient-evoked otoacoustic emission in newborn hearing screening.

PubMed

Salina, Husain; Abdullah, Asma; Mukari, Siti Zamratol Mai-sarah; Azmi, Mohd Tamil

2010-04-01

Transient-evoked otoacoustic emission (TEOAE) is a well-established screening tool for universal newborn hearing screening. The aims of this study are to measure the effects of background noise on recording of TEOAE and the duration required to complete the test at various noise levels. This study is a prospective study from June 2006 until May 2007. The study population were newborns from postnatal wards who were delivered at term pregnancy. Newborns who were more than 8-h old and passed a hearing screening testing using screening auditory brainstem response (SABRe) were further tested with TEOAE in four different test environments [isolation room in the ward during non-peak hour (E1), isolation room in the ward during peak hour (E2), maternal bedside in the ward during non-peak hour (E3) and maternal bedside in the ward during peak hour (E4)]. This study showed that test environment significantly influenced the time required to complete testing in both ears with F [534.23] = 0.945; P < 0.001 on the right ear and F [636.54] = 0.954; P < 0.001 on the left. Our study revealed that TEOAE testing was efficient in defining the presence of normal hearing in our postnatal wards at maternal bedside during non-peak hour with a specificity of 96.8%. Our study concludes that background noise levels for acceptable and accurate TEOAE recording in newborns should not exceed 65 dB A. In addition, when using TEOAE assessment in noisy environments, the time taken to obtain accurate results will greatly increase.

Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012-2014.

PubMed

Linde, Ann C; Sweet, Kristin A; Nelson, Kailey; Mamo, Blain; Chute, Sara M

2016-01-01

The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (p<0.001). In the context of a strong screening and surveillance infrastructure, a simple intervention improved the linkage-to-care rate for HBsAg-positive refugees.

Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012–2014

PubMed Central

Sweet, Kristin A.; Nelson, Kailey; Mamo, Blain; Chute, Sara M.

2016-01-01

Objective The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. Methods MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. Results In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (p<0.001). Conclusion In the context of a strong screening and surveillance infrastructure, a simple intervention improved the linkage-to-care rate for HBsAg-positive refugees. PMID:27168670

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…

Storage and use of residual dried blood spots from state newborn screening programs.

PubMed

Olney, Richard S; Moore, Cynthia A; Ojodu, Jelili A; Lindegren, Mary Lou; Hannon, W Harry

2006-05-01

To provide current data for policy discussions and to assess future needs among newborn screening programs regarding the storage and use of residual dried blood spots (DBS) in the United States. An electronic questionnaire was administered to U.S. state health department laboratory directors in 2003. Responses were received from 49 of the 50 states. Approximately half of them stored residual DBS for more than 6 months, 57% did not have a written policy that determines how residual DBS can or cannot be used, and 16% informed parents that DBS might be retained. Residual DBS were used by 74% of respondents for evaluation of newborn screening tests, by 52% for clinical or forensic testing, and by 28% for epidemiologic studies. Use of DBS was reported more frequently by states with extended storage. When asked if they might participate in an anonymous multistate epidemiologic study by contributing unlinked DBS, 41% responded affirmatively. More states have used residual DBS for evaluating newborn screening tests than for epidemiologic studies. There is potential interest among states in using unlinked DBS for multistate studies and a need for written policies addressing all uses of residual DBS.

Pulse oximetry screening in Wisconsin.

PubMed

Beissel, Daniel J; Goetz, Elizabeth M; Hokanson, John S

2012-01-01

Pulse oximetry can be used as a screening tool to detect critical congenital heart disease (CCHD) in neonates prior to hospital discharge and the development of symptoms. Newborns suspected of having CCHD based on pulse oximetry screening should have the diagnosis excluded or confirmed with echocardiography. However, echocardiography is not immediately available in all settings in which newborns are delivered and the best course of action in these settings remains to be determined. The purpose of this study was to evaluate the resources available to diagnose and treat newborns with CCHD born in the state of Wisconsin. We surveyed the nurse managers or administrators of the 99 Wisconsin hospitals in which babies are routinely delivered in the state of Wisconsin. A telephone survey was performed in February and March 2011. The number of births per facility was estimated from the most recent available data (2010). There were 66 179 total births occurring in 106 hospitals in the state of Wisconsin in 2010, with 99 hospitals routinely delivering newborns. Surveys were completed in 88/99 (88.9%), representing 95% of the state's in-hospital births. All responding hospitals had pulse oximetry available in the nursery. Twenty-five of 88 (28.4%) of responding hospitals routinely use pulse oximetry to screen for CCHD, representing 35.2% of surveyed hospital births. Same-day neonatal echocardiography was available at 33/88 (37.5%) of the responding hospitals, representing 74.4% of surveyed hospital births. The average distance to the higher-level care facility of choice from the hospitals without neonatal echocardiography is 53.1 miles. Pulse oximetry is universally available in Wisconsin newborn nurseries, and pulse oximetry screening for CCHD is currently being performed for many of Wisconsin's newborns. The majority of births in Wisconsin occur in hospitals where same-day neonatal echocardiography is available for confirmatory diagnosis of CCHD when necessary. © 2012 Wiley Periodicals, Inc.

Association between use of systematic reviews and national policy recommendations on screening newborn babies for rare diseases: systematic review and meta-analysis.

PubMed

Taylor-Phillips, Sian; Stinton, Chris; Ferrante di Ruffano, Lavinia; Seedat, Farah; Clarke, Aileen; Deeks, Jonathan J

2018-05-09

To understand whether international differences in recommendations of whether to screen for rare diseases using the newborn blood spot test might in part be explained by use of systematic review methods. Systematic review and meta-analysis. Website searches of 26 national screening organisations. Journal articles, papers, legal documents, presentations, conference abstracts, or reports relating to a national recommendation on whether to screen for any condition using the newborn blood spot test, with no restrictions on date or language. Two reviewers independently assessed whether the recommendation for or against screening included systematic reviews, and data on test accuracy, benefits of early detection, and potential harms of overdiagnosis. The odds of recommending screening according to the use of systematic review methods was estimated across conditions using meta-analysis. 93 reports were included that assessed 104 conditions across 14 countries, totalling 276 recommendations (units of analysis). Screening was favoured in 159 (58%) recommendations, not favoured in 98 (36%), and not recommended either way in 19 (7%). Only 60 (22%) of the recommendations included a systematic review. Use of a systematic review was associated with a reduced probability of screening being recommended (23/60 (38%) v 136/216 (63%), odds ratio 0.17, 95% confidence interval 0.07 to 0.43). Of the recommendations, evidence for test accuracy, benefits of early detection, and overdiagnosis was not considered in 115 (42%), 83 (30%), and 211 (76%), respectively. Using systematic review methods is associated with a reduced probability of screening being recommended. Many national policy reviews of screening for rare conditions using the newborn blood spot test do not assess the evidence on the key benefits and harms of screening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Screening newborn blood spots for 22q11.2 deletion syndrome using multiplex droplet digital PCR.

PubMed

Pretto, Dalyir; Maar, Dianna; Yrigollen, Carolyn M; Regan, Jack; Tassone, Flora

2015-01-01

The diagnosis of 22q11 deletion syndrome (22q11DS) is often delayed or missed due to the wide spectrum of clinical involvement ranging from mild to severe, often life-threatening conditions. A delayed diagnosis can lead to life-long health issues that could be ameliorated with early intervention and treatment. Owing to the high impact of 22q11DS on public health, propositions have been made to include 22q11DS in newborn screening panels; however, the method of choice for detecting 22q11DS, fluorescent in situ hybridization, requires specialized equipment and is cumbersome for most laboratories to implement as part of their routine screening. We sought to develop a new genetic screen for 22q11DS that is rapid, cost-effective, and easily used by laboratories currently performing newborn screening. We evaluated the accuracy of multiplex droplet digital PCR (ddPCR) in the detection of copy number of 22q11DS by screening samples from 26 patients with 22q11DS blindly intermixed with 1096 blood spot cards from the general population (total n = 1122). Multiplex ddPCR correctly identified all 22q11DS samples and distinguished between 1.5- and 3-Mb deletions, suggesting the approach is sensitive and specific for the detection of 22q11DS. These data demonstrate the utility of multiplex ddPCR for large-scale population-based studies that screen for 22q11DS. The use of samples from blood spot cards suggests that this approach has promise for newborn screening of 22q11DS, and potentially for other microdeletion syndromes, for which early detection can positively impact clinical outcome for those affected. © 2014 American Association for Clinical Chemistry.

Impact of Neonatal Screening and Surveillance for the TP53 R337H Mutation on Early Detection of Childhood Adrenocortical Tumors

PubMed Central

Custódio, Gislaine; Parise, Guilherme A.; Kiesel Filho, Nilton; Komechen, Heloisa; Sabbaga, Cesar C.; Rosati, Roberto; Grisa, Leila; Parise, Ivy Z.S.; Pianovski, Mara A.D.; Fiori, Carmem M.C.M.; Ledesma, Jorge A.; Barbosa, José Renato S.; Figueiredo, Francisco R.O.; Sade, Elis R.; Ibañez, Humberto; Arram, Sohaila B.I.; Stinghen, Sérvio T.; Mengarelli, Luciano R.; Figueiredo, Mirna M.O.; Carvalho, Danilo C.; Avilla, Sylvio G.A.; Woiski, Thiago D.; Poncio, Lisiane C.; Lima, Geneci F.R.; Pontarolo, Roberto; Lalli, Enzo; Zhou, Yinmei; Zambetti, Gerard P.; Ribeiro, Raul C.; Figueiredo, Bonald C.

2013-01-01

Purpose The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers. Patients and Methods Free newborn screening was offered at all hospitals in the state of Paraná. Parents of positive newborns were tested, and relatives in the carrier line were offered screening. Positive newborns and their relatives age < 15 years were offered surveillance (periodic clinical, laboratory, and ultrasound evaluations). ACTs detected by imaging were surgically resected. Results Of 180,000 newborns offered screening, 171,649 were screened, and 461 (0.27%) were carriers. As of April 2012, ACTs had been diagnosed in 11 of these carriers but in only two neonatally screened noncarriers (P < .001); six patient cases were identified among 228 carrier relatives age < 15 years (total, 19 ACTs). Surveillance participants included 347 (49.6%) of 699 carriers. Tumors were smaller in surveillance participants (P < .001) and more advanced in nonparticipants (four with stage III disease; two deaths). Neonatally screened carriers also had neuroblastoma (n = 1), glioblastoma multiforme (n = 1), choroid plexus carcinoma (n = 2), and Burkitt lymphoma (n = 1). Cancer histories and pedigrees were obtained for 353 families that included 1,704 identified carriers. ACTs were the most frequent cancer among carrier children (n = 48). Conclusion These findings establish the prevalence of the TP53 R337H mutation in Paraná state and the penetrance of ACTs among carriers. Importantly, screening and surveillance of heterozygous carriers are effective in detecting ACTs when readily curable. PMID:23733769

Newborn screening for six lysosomal storage disorders in a cohort of Mexican patients: Three-year findings from a screening program in a closed Mexican health system.

PubMed

Navarrete-Martínez, Juana Inés; Limón-Rojas, Ana Elena; Gaytán-García, Maria de Jesús; Reyna-Figueroa, Jesús; Wakida-Kusunoki, Guillermo; Delgado-Calvillo, Ma Del Rocío; Cantú-Reyna, Consuelo; Cruz-Camino, Héctor; Cervantes-Barragán, David Eduardo

2017-05-01

To evaluate the results of a lysosomal newborn screening (NBS) program in a cohort of 20,018 Mexican patients over the course of 3years in a closed Mexican Health System (Petróleos Mexicanos [PEMEX] Health Services). Using dried blood spots (DBS), we performed a multiplex tandem mass spectrometry enzymatic assay for six lysosomal storage disorders (LSDs) including Pompe disease, Fabry disease, Gaucher disease, mucopolysaccharidosis type I (MPS-I), Niemann-Pick type A/B, and Krabbe disease. Screen-positive cases were confirmed using leukocyte enzymatic activity and DNA molecular analysis. From July 2012 to April 2016, 20,018 patients were screened; 20 patients were confirmed to have an LSD phenotype (99.9 in 100,000 newborns). Final distributions include 11 Pompe disease, five Fabry disease, two MPS-I, and two Niemann-Pick type A/B patients. We did not find any Gaucher or Krabbe patients. A final frequency of 1 in 1001 LSD newborn phenotypes was established. NBS is a major public health achievement that has decreased the morbidity and mortality of inborn errors of metabolism. The introduction of NBS for LSD presents new challenges. This is the first multiplex Latin-American study of six LSDs detected through NBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Pilot study of newborn screening of inborn error of metabolism using tandem mass spectrometry in Malaysia: outcome and challenges.

PubMed

Yunus, Zabedah Md; Rahman, Salina Abdul; Choy, Yew Sing; Keng, Wee Teik; Ngu, Lock Hock

2016-09-01

The aim of this study was to determine the feasibility of performing newborn screening (NBS) of inborn errors of metabolism (IEMs) using tandem mass spectrometry (TMS) and the impact on its detection rate in Malaysia. During the study period between June 2006 and December 2008, 30,247 newborns from 11 major public hospitals in Malaysia were screened for 27 inborn errors of amino acid, organic acid and fatty acid metabolism by TMS. Dried blood spot (DBS) samples were collected between 24 h and 7 days with parental consent. Samples with abnormal results were repeated and the babies were recalled to confirm the diagnosis with follow-up testing. Cut-off values for amino acids and acylcarnitines were established. Eight newborns were confirmed to have IEM: two newborns with Maple syrup urine disease (MSUD), two with methylmalonic aciduria (MMA) one with ethylmalonic aciduria, two with argininosuccinic aciduria and one with isovaleric aciduria. Diagnosis was missed in two newborns. The detection rate of IEMs in this study was one in 2916 newborns. The sensitivity and specificity of TMS were 80% and 99%, respectively. IEMs are common in Malaysia. NBS of IEMs by TMS is a valuable preventive strategy by enabling the diagnosis and early treatment of IEM before the onset of symptoms aiming at prevention of mental retardation and physical handicap. A number of shortcomings warrant further solution so that in near future NBS for IEMs will become a standard of care for all babies in Malaysia in tandem with the developed world.

Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa

PubMed Central

Govindasamy, Darshini; Kranzer, Katharina; van Schaik, Nienke; Noubary, Farzad; Wood, Robin; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.; Bekker, Linda-Gail

2013-01-01

Background HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care. PMID:24236170

Trends in Use of Referral Hospital Services for Care of Sick Newborns in a Community-based Intervention in Tangail District, Bangladesh

PubMed Central

Bari, Sanwarul; Mannan, Ishtiaq; Rahman, Mohammed Anisur; Darmstadt, Gary L.; Seraji, M. Habibur R.; Baqui, Abdullah H.; Arifeen, Shams El; Rahman, Syed Moshfiqur; Saha, Samir K.; Ahmed, A.S.M. Nawshad Uddin; Ahmed, Saifuddin; Santosham, Mathuram; Black, Robert E.

2006-01-01

The Projahnmo-II Project in Mirzapur upazila (sub-district), Tangail district, Bangladesh, is promoting care-seeking for sick newborns through health education of families, identification and referral of sick newborns in the community by community health workers (CHWs), and strengthening of neonatal care in Kumudini Hospital, Mirzapur. Data were drawn from records maintained by the CHWs, referral hospital registers, a baseline household survey of recently-delivered women conducted from March to June 2003, and two interim household surveys in January and September 2005. Increases were observed in self-referral of sick newborns for care, compliance after referral by the CHWs, and care-seeking from qualified providers and from the Kumudini Hospital, and decreases were observed in care-seeking from unqualified providers in the intervention arm. An active surveillance for illness by the CHWs in the home, education of families by them on recognition of danger signs and counselling to seek immediate care for serious illness, and improved linkages between the community and the hospital can produce substantial increases in care-seeking for sick newborns. PMID:17591349

A prospective newborn screening and treatment program for sickle cell anemia in Luanda, Angola.

PubMed

McGann, Patrick T; Ferris, Margaret G; Ramamurthy, Uma; Santos, Brigida; de Oliveira, Vysolela; Bernardino, Luis; Ware, Russell E

2013-12-01

Over 300,000 infants are born annually with sickle cell anemia (SCA) in sub-Saharan Africa, and >50% die young from infection or anemia, usually without diagnosis of SCA. Early identification by newborn screening (NBS), followed by simple interventions dramatically reduced the mortality of SCA in the United States, but this strategy is not yet established in Africa. We designed and implemented a proof-of-principle NBS and treatment program for SCA in Angola, with focus on capacity building and local ownership. Dried bloodspots from newborns were collected from five birthing centers. Hemoglobin identification was performed using isoelectric focusing; samples with abnormal hemoglobin patterns were analyzed by capillary electrophoresis. Infants with abnormal FS or FSC patterns were enrolled in a newborn clinic to initiate penicillin prophylaxis and receive education, pneumococcal immunization, and insecticide-treated bed nets. A total of 36,453 infants were screened with 77.31% FA, 21.03% FAS, 1.51% FS, and 0.019% FSC. A majority (54.3%) of affected infants were successfully contacted and brought to clinical care. Compliance in the newborn clinic was excellent (96.6%). Calculated first-year mortality rate for babies with SCA compares favorably to the national infant mortality rate (6.8 vs. 9.8%). The SCA burden is extremely high in Angola, but NBS is feasible. Capacity building and training provide local healthcare workers with skills needed for a functional screening program and clinic. Contact and retrieval of all affected SCA infants remains a challenge, but families are compliant with clinic appointments and treatment. Early mortality data suggest screening and early preventive care saves lives. Copyright © 2013 Wiley Periodicals, Inc.

The Role of Genetic Counseling in Pompe Disease After Patients Are Identified Through Newborn Screening.

PubMed

Atherton, Andrea M; Day-Salvatore, Debra

2017-07-01

An important part of the coordinated care by experienced health care teams for all Pompe disease patients, whether diagnosed through newborn screening (NBS), clinical diagnosis, or prenatal diagnosis, is genetic counseling. Genetic counseling helps families better understand medical recommendations and options presented by the patient's health care team so they can make informed decisions. In addition to providing important information about the inheritance and genetic risks, genetic counseling also provides information about Pompe disease and available treatments and resources and should be offered to families with an affected child and all adults diagnosed with Pompe disease. Although the need for genetic counseling after a positive newborn screen for Pompe disease is recognized, the role that genetic counseling plays for both families of affected patients and health care teams is not fully understood. Consistent best genetic counseling practices also are lacking. The guidance in this article in the "Newborn Screening, Diagnosis, and Treatment for Pompe Disease" supplement is derived from expert consensus from the Pompe Disease Newborn Screening Working Group. It is intended to help guide genetic counseling efforts and provide a clear understanding of the role for families or carriers of Pompe disease identified through NBS; explain special considerations (eg, diagnosis of late-onset Pompe disease before the appearance of symptoms) and the impact and implications associated with a diagnosis (eg, determination of genetic risk and carrier status and preconception counseling); and provide health care teams caring for patients with a framework for a standardized approach to genetic counseling for patients and at-risk family members. Copyright © 2017 by the American Academy of Pediatrics.

Hearing loss screening tool (COBRA score) for newborns in primary care setting

PubMed Central

Poonual, Watcharapol; Navacharoen, Niramon; Kangsanarak, Jaran; Namwongprom, Sirianong

2017-01-01

Purpose To develop and evaluate a simple screening tool to assess hearing loss in newborns. A derived score was compared with the standard clinical practice tool. Methods This cohort study was designed to screen the hearing of newborns using transiently evoked otoacoustic emission and auditory brain stem response, and to determine the risk factors associated with hearing loss of newborns in 3 tertiary hospitals in Northern Thailand. Data were prospectively collected from November 1, 2010 to May 31, 2012. To develop the risk score, clinical-risk indicators were measured by Poisson risk regression. The regression coefficients were transformed into item scores dividing each regression-coefficient with the smallest coefficient in the model, rounding the number to its nearest integer, and adding up to a total score. Results Five clinical risk factors (Craniofacial anomaly, Ototoxicity, Birth weight, family history [Relative] of congenital sensorineural hearing loss, and Apgar score) were included in our COBRA score. The screening tool detected, by area under the receiver operating characteristic curve, more than 80% of existing hearing loss. The positive-likelihood ratio of hearing loss in patients with scores of 4, 6, and 8 were 25.21 (95% confidence interval [CI], 14.69–43.26), 58.52 (95% CI, 36.26–94.44), and 51.56 (95% CI, 33.74–78.82), respectively. This result was similar to the standard tool (The Joint Committee on Infant Hearing) of 26.72 (95% CI, 20.59–34.66). Conclusion A simple screening tool of five predictors provides good prediction indices for newborn hearing loss, which may motivate parents to bring children for further appropriate testing and investigations. PMID:29234358

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

PubMed

Hannon, W Harry

2003-01-01

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

Consensus Statement of the Indian Academy of Pediatrics on Newborn Hearing Screening.

PubMed

Paul, Abraham; Prasad, Chhaya; Kamath, S S; Dalwai, Samir; C Nair, M K; Pagarkar, Waheeda

2017-08-15

Hearing impairment is one of the most critical sensory impairments with significant social and psychological consequences. Evidence-based, standardized national guidelines are needed for professionals to screen for hearing impairment during the neonatal period. The meeting on formulation of national consensus guidelines on developmental disorders was organized by Indian Academy of Pediatrics in Mumbai, on 18th and 19th December, 2015. The invited experts included Pediatricians, Developmental Pediatricians, Pediatric Neurologists and Clinical Psychologists. The participants framed guidelines after extensive discussions. To provide guidelines on newborn hearing screening in India. The first screening should be conducted before the neonate's discharge from the hospital - if it 'fails', then it should be repeated after four weeks, or at first immunization visit. If it 'fails' again, then Auditory Brainstem Response (ABR) audiometry should be conducted. All babies admitted to intensive care unit should be screened via ABR. All babies with abnormal ABR should undergo detailed evaluation, hearing aid fitting and auditory rehabilitation, before six months of age. The goal is to screen newborn babies before one month of age, diagnose hearing loss before three months of age and start intervention before six months of age.

Elevated phenylalanine on newborn screening: follow-up testing may reveal undiagnosed galactosaemia.

PubMed

Shakespeare, Lynette; Downing, Melanie; Allen, Joyce; Casbolt, Ann-Marie; Ellin, Sheila; Maloney, Martin; Race, Gillian; Bonham, Jim

2010-11-01

Introduction Newborn screening for phenylketonuria (PKU) can reveal other conditions which lead to an increased blood spot phenylalanine (Phe) concentration. We have investigated the proportion of blood spot samples that gave a positive screen due to clinically significant conditions other than PKU, compared the positive predictive value (PPV) of our referral Phe cut-off with that recommended by the UK Newborn Screening Programme Centre (UKNSPC) (>210 and >240 μmol/L, respectively) and evaluated the effectiveness of reflex testing for galactosaemia using a lower blood spot Phe cut-off concentration of 130 μmol/L. All blood spot samples that screened positive, for an increased Phe concentration, between April 2001 and March 2008, were identified from the records of the Sheffield Newborn Screening Laboratory and the diagnoses noted. In addition, all cases of galactosaemia detected in or notified to our screening laboratory within this time were also examined and the screened Phe concentrations compared. Out of 438,674 babies who were screened, 67 had Phe concentration >210 μmol/L (15 per 100,000). Of these, 40 had PKU or persistent hyperphenylalaninaemia with a Phe concentration identified by screening between 270 and 2350 μmol/L. A further 11 were diagnosed with another clinically significant disorder: galactosaemia (n = 8), biopterin defects (n = 2), tyrosinaemia Type 1 (n = 1). In addition, 16 had transient elevations in Phe. In total, nine cases of galactosaemia were identified, of whom, three had Phe concentrations <240 μmol/L with one asymptomatic individual having a concentration <210 μmol/L. Adoption of the UKNSPC recommended cut-off (>240 μmol/L) will not affect the detection rate of classical PKU, but will improve the PPV from 76% to 80%. The use of a lower cut-off (130 μmol/L) for reflex galactosaemia testing enables the timely identification of asymptomatic cases that benefit particularly from early treatment, without prompting any unnecessary clinical referrals or delaying any referrals. This intervention may reduce mortality in this vulnerable group.

[Pulse oximetry screening of critical congenital heart defects in the neonatal period. The Spanish National Neonatal Society recommendation].

PubMed

Sánchez Luna, Manuel; Pérez Muñuzuri, Alejandro; Sanz López, Ester; Leante Castellanos, José Luis; Benavente Fernández, Isabel; Ruiz Campillo, César W; Sánchez Redondo, M Dolores; Vento Torres, Máximo; Rite Gracia, Segundo

2018-02-01

Due to its severity, as well as the consequences of a late diagnosis, critical congenital heart defects (CCHD) represent a challenging situation, making an early diagnosis necessary and ideally before symptoms appear when circulatory collapse or death of the newborn can occur. Due to this, a prenatal and very early postnatal diagnosis is very important. Prenatal ultrasound screening and physical examination of the newborn can miss a considerable number of CCHD cases. Pulse oximetry screening has been demonstrated to be an effective, non-invasive, inexpensive, and well accepted tool in the early diagnosis of CCHD. The Spanish National Society of Neonatology, through its Standards Committee, and based on the current evidence, recommend the implementation of pulse oximetry screening of CCHD in Spain, and then to offer the best therapy possible to these newborn infants. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Newborn screening for cystic fibrosis: Polish 4 years' experience with CFTR sequencing strategy.

PubMed

Sobczyńska-Tomaszewska, Agnieszka; Ołtarzewski, Mariusz; Czerska, Kamila; Wertheim-Tysarowska, Katarzyna; Sands, Dorota; Walkowiak, Jarosław; Bal, Jerzy; Mazurczak, Tadeusz

2013-04-01

Newborn screening for cystic fibrosis (NBS CF) in Poland was started in September 2006. Summary from 4 years' experience is presented in this study. The immunoreactive trypsin/DNA sequencing strategy was implemented. The group of 1,212,487 newborns were screened for cystic fibrosis during the programme. We identified a total of 221 CF cases during this period, including, 4 CF cases were reported to be omitted by NBS CF. Disease incidence in Poland based on the programme results was estimated as 1/4394 and carrier frequency as 1/33. The frequency of the F508del was similar (62%) to population data previously reported. This strategy allowed us to identify 29 affected infants with rare genotypes. The frequency of some mutations (eg, 2184insA, K710X) was assessed in Poland for the first time. Thus, sequencing assay seems to be accurate method for screening programme using blood spots in the Polish population.

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.

Variability in State-Based Recommendations for Management of Alpha Thalassemia Trait and Silent Carrier Detected on the Newborn Screen.

PubMed

Fogel, Benjamin N; Nguyen, Hong Loan T; Smink, Gayle; Sekhar, Deepa L

2018-04-01

We conducted an inventory of state-based recommendations for follow-up of alpha thalassemia silent carrier and trait identified on newborn screen. We found wide variability in the nature and timing of these recommendations. We recommend a standardized recommendation to guide pediatricians in evidenced-based care for this population. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

Targeting regional pediatric congenital hearing loss using a spatial scan statistic.

PubMed

Bush, Matthew L; Christian, Warren Jay; Bianchi, Kristin; Lester, Cathy; Schoenberg, Nancy

2015-01-01

Congenital hearing loss is a common problem, and timely identification and intervention are paramount for language development. Patients from rural regions may have many barriers to timely diagnosis and intervention. The purpose of this study was to examine the spatial and hospital-based distribution of failed infant hearing screening testing and pediatric congenital hearing loss throughout Kentucky. Data on live births and audiological reporting of infant hearing loss results in Kentucky from 2009 to 2011 were analyzed. The authors used spatial scan statistics to identify high-rate clusters of failed newborn screening tests and permanent congenital hearing loss (PCHL), based on the total number of live births per county. The authors conducted further analyses on PCHL and failed newborn hearing screening tests, based on birth hospital data and method of screening. The authors observed four statistically significant (p < 0.05) high-rate clusters with failed newborn hearing screenings in Kentucky, including two in the Appalachian region. Hospitals using two-stage otoacoustic emission testing demonstrated higher rates of failed screening (p = 0.009) than those using two-stage automated auditory brainstem response testing. A significant cluster of high rate of PCHL was observed in Western Kentucky. Five of the 54 birthing hospitals were found to have higher relative risk of PCHL, and two of those hospitals are located in a very rural region of Western Kentucky within the cluster. This spatial analysis in children in Kentucky has identified specific regions throughout the state with high rates of congenital hearing loss and failed newborn hearing screening tests. Further investigation regarding causative factors is warranted. This method of analysis can be useful in the setting of hearing health disparities to focus efforts on regions facing high incidence of congenital hearing loss.

Gender disparities in screening for congenital hypothyroidism using thyroxine as a primary screen.

PubMed

DeMartino, Lenore; McMahon, Rebecca; Caggana, Michele; Tavakoli, Norma Parvin

2018-06-26

Newborn screening for congenital hypothyroidism (CH) is based on testing for the markers thyroxine (T4) and/or thyroid stimulating hormone (TSH). Diagnosis of CH is complicated because many factors affect the levels of these hormones including infant birth weight, prematurity, and age at specimen collection. We investigated whether the sex of the newborn affected the levels of T4 and TSH and consequently the outcome of newborn screening. In New York State, the Newborn Screening program initially tests all infants for T4 and any baby with a result in the lowest 10% is triaged for TSH screening. We analyzed data from 2008 to 2016 to determine mean and median T4 and TSH values and how these results correlate with the sex of infants who are reported as borderline, referred and confirmed with CH. T4 and TSH concentrations in dried blood spots were measured using commercially available fluoroimmunoassays. From 2008 to 2016, of the 2.4 million specimens tested for thyroxine, 51.5% were from male and 48.5% were from female infants. Male infants constituted 60% of specimens triaged for TSH testing, 64.9% of repeat requests and 59.6% of referrals, but only 49% of confirmed CH cases. The mean and median T4 values were lower (a difference of approximately 0.8-1.1 μg/dL each year), and the median TSH values were higher in male compared to female infants. Natural differences in thyroid hormone levels in male and female infants leads to male infants being disproportionately represented in the false positive category.

Multiplex tandem mass spectrometry assay for newborn screening of X-linked adrenoleukodystrophy, biotinidase deficiency, and galactosemia with flexibility to assay other enzyme assays and biomarkers.

PubMed

Hong, Xinying; Kumar, Arun Babu; Ronald Scott, C; Gelb, Michael H

2018-03-29

All States screen for biotinidase deficiency and galactosemia, and X-linked adrenoleukodystrophy (X-ALD) has recently been added to the Recommended Uniform Screening Panel (RUSP).We sought to consolidate these tests by combining them into a single multiplex tandem mass spectrometry assay as well as to improve the current protocol for newborn screening of galactosemia.A 3 mm punch of a dried blood spot (DBS) was extracted with organic solvent for analysis of the C26:0-lysophosphatidylcholine biomarker for X-ALD.An additional punch was used to assay galactose-1-phosphate uridyltransferase (GALT) and biotinidase.All assays were combined for a single injection for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (2.3 min per sample).The GALT LC-MS/MS assay does not give a false positive for galactosemia if glucose-6-phosphate dehydrogenase is deficient.The multiplex assay shows acceptable reproducibility and provides for rapid analysis of X-ALD, biotinidase deficiency, and galactosemia.The throughput and ease of sample preparation are acceptable for newborn screening laboratories.We also show that the LC-MS/MS assay is expandable to include several other diseases including Pompe and Hurler diseases (enzymatic activities and biomarkers).Because of consolidation of assays, less manpower is needed compared to running individual assays on separate platforms.The flexibility of the LC-MS/MS platform allows each newborn screening laboratory to analyze the set of diseases offered in their panel. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessment of knowledge, attitudes and practices towards newborn screening for congenital hypothyroidism before and after a health education intervention in pregnant women in a hospital setting in Pakistan.

PubMed

Tariq, Batha; Ahmed, Ayesha; Habib, Atif; Turab, Ali; Ali, Noshad; Soofi, Sajid Bashir; Nooruddin, Shanila; Kumar, Rekha J; Tariq, Amin; Shaheen, Fariha; Ariff, Shabina

2018-03-01

Most congenital hypothyroidism (CH) is not avertable; however, the adverse effects of CH are preventable with early detection and treatment. It is a common congenital endocrine disorder that affects 1 in 2000-4000 newborns globally. The true incidence in Pakistan is unknown. Data from hospital studies quote an incidence of 1 in 1600-2000. The aim of this study was to uncover existing knowledge of CH and screening for the condition and to assess the impact of health education on mothers' knowledge and attitudes towards having their newborns screened. The study was conducted from January 2012 to August 2013 at a local hospital in Karachi, Pakistan. This was a prospective, interventional cohort study implemented through a pre- and post-cross-sectional knowledge, attitudes and practices (KAP) survey. Interviews were conducted using structured questionnaires on CH. At baseline (pre-intervention survey), 400 participants consented and 355 (88.9%) completed the study. There was a significant increase in awareness among participating women following the intervention (20% to approximately 98%). Similarly, 78.9% agreed to opt for a screening test for their newborns following delivery as compared with 57.7% in the pre-intervention KAP survey (relative risk 1.38, p-value <0.0001). Unfortunately, the majority of mothers were unaware of CH and its implications, leading to less screening and fewer diagnoses. This study underlines the importance of education in screening programmes to create awareness and maximize uptake.

Postnatal gestational age estimation using newborn screening blood spots: a proposed validation protocol

PubMed Central

Murphy, Malia S Q; Hawken, Steven; Atkinson, Katherine M; Milburn, Jennifer; Pervin, Jesmin; Gravett, Courtney; Stringer, Jeffrey S A; Rahman, Anisur; Lackritz, Eve; Chakraborty, Pranesh; Wilson, Kumanan

2017-01-01

Background Knowledge of gestational age (GA) is critical for guiding neonatal care and quantifying regional burdens of preterm birth. In settings where access to ultrasound dating is limited, postnatal estimates are frequently used despite the issues of accuracy associated with postnatal approaches. Newborn metabolic profiles are known to vary by severity of preterm birth. Recent work by our group and others has highlighted the accuracy of postnatal GA estimation algorithms derived from routinely collected newborn screening profiles. This protocol outlines the validation of a GA model originally developed in a North American cohort among international newborn cohorts. Methods Our primary objective is to use blood spot samples collected from infants born in Zambia and Bangladesh to evaluate our algorithm’s capacity to correctly classify GA within 1, 2, 3 and 4 weeks. Secondary objectives are to 1) determine the algorithm's accuracy in small-for-gestational-age and large-for-gestational-age infants, 2) determine its ability to correctly discriminate GA of newborns across dichotomous thresholds of preterm birth (≤34 weeks, <37 weeks GA) and 3) compare the relative performance of algorithms derived from newborn screening panels including all available analytes and those restricted to analyte subsets. The study population will consist of infants born to mothers already enrolled in one of two preterm birth cohorts in Lusaka, Zambia, and Matlab, Bangladesh. Dried blood spot samples will be collected and sent for analysis in Ontario, Canada, for model validation. Discussion This study will determine the validity of a GA estimation algorithm across ethnically diverse infant populations and assess population specific variations in newborn metabolic profiles. PMID:29104765

Comparison of Newborn Hearing Screening in Well-Baby Nursery and NICU: A Study Applied to Reduce Referral Rate in NICU

PubMed Central

Li, Pei-Chun; Chen, Wei-I; Huang, Chih-Ming; Liu, Ching-Ju; Chang, Hsiu-wen; Lin, Hung-Ching

2016-01-01

Objectives To determine whether newborn hearing screening in a well-baby nursery (WBN) and neonatal intensive care unit (NICU) nursery: 1) meet three targeted, screening, referral, and diagnostic follow-up rates; 2) compare the average age of diagnosis for infants admitted to the WIN and NICU; and 3) determine prevalence of hearing loss in neonatal population; and 4) try to find a practical newborn hearing screening time algorithm to reduce refer rate in NICU Materials and Methods It examined 15,624 newborns in the WBN (13,676) and NICU (1948) screened for congenital HL using AABR. The variables analyzed in it were the screening rate, referral rate, follow-up rate, diagnostic rate and diagnostic age, prevalence rate, degrees of congenital bilateral HL. The study was approved by the hospital’s institutional review board (13MMHISO23). Results The screening rates were 99.8% and 99.6% in the WBN and NICU groups, respectively, without significant difference. The referral rates were 0.7% and 2.8% in the WBN and NICU groups, with significant difference. Furthermore, the diagnostic follow-up rates were 76.7% and 89.1% in the WBN and NICU groups, without significant difference. The average initial diagnostic ages were 1.9 months and 3.8 months in the WBN and NICU groups, with significant difference. The prevalence of congenital bilateral hearing loss were 0.27% and 1.6% in the WBN and NICU groups, with significant difference. Conclusion The screening, referral and follow-up rate in the WBN and NICU groups were equivalent to the quality indicators. For NICU group, screening and diagnostic follow up were performed later than those in WBN group; however the lower referral rate in our NICU group was successfully achieved in this study and can be applied clinically. The prevalence of congenital bilateral hearing loss was higher in the NICU group than in the WBN group. PMID:27023324

Comparison of Newborn Hearing Screening in Well-Baby Nursery and NICU: A Study Applied to Reduce Referral Rate in NICU.

PubMed

Li, Pei-Chun; Chen, Wei-I; Huang, Chih-Ming; Liu, Ching-Ju; Chang, Hsiu-wen; Lin, Hung-Ching

2016-01-01

To determine whether newborn hearing screening in a well-baby nursery (WBN) and neonatal intensive care unit (NICU) nursery: 1) meet three targeted, screening, referral, and diagnostic follow-up rates; 2) compare the average age of diagnosis for infants admitted to the WIN and NICU; and 3) determine prevalence of hearing loss in neonatal population; and 4) try to find a practical newborn hearing screening time algorithm to reduce refer rate in NICU. It examined 15,624 newborns in the WBN (13,676) and NICU (1948) screened for congenital HL using AABR. The variables analyzed in it were the screening rate, referral rate, follow-up rate, diagnostic rate and diagnostic age, prevalence rate, degrees of congenital bilateral HL. The study was approved by the hospital's institutional review board (13MMHISO23). The screening rates were 99.8% and 99.6% in the WBN and NICU groups, respectively, without significant difference. The referral rates were 0.7% and 2.8% in the WBN and NICU groups, with significant difference. Furthermore, the diagnostic follow-up rates were 76.7% and 89.1% in the WBN and NICU groups, without significant difference. The average initial diagnostic ages were 1.9 months and 3.8 months in the WBN and NICU groups, with significant difference. The prevalence of congenital bilateral hearing loss were 0.27% and 1.6% in the WBN and NICU groups, with significant difference. The screening, referral and follow-up rate in the WBN and NICU groups were equivalent to the quality indicators. For NICU group, screening and diagnostic follow up were performed later than those in WBN group; however the lower referral rate in our NICU group was successfully achieved in this study and can be applied clinically. The prevalence of congenital bilateral hearing loss was higher in the NICU group than in the WBN group.

Newborn hearing screening in Queensland 2009-2011: Comparison of hearing screening and diagnostic audiological assessment between term and preterm infants.

PubMed

Calcutt, Trent L; Dornan, Dimity; Beswick, Rachael; Tudehope, David I

2016-08-13

This study compares rates and timing of newborn hearing screening outcomes, audiological assessment and hearing loss diagnosis between infants of different gestational age groups. Early identification and management of sensorineural hearing loss (SNHL), ideally by 3-6 months of age, facilitates speech and language optimisation. Literature stratifying hearing screening and diagnostic audiology assessment by gestational age groups is lacking. Subjects were infants with recorded gestational ages receiving newborn hearing screening in Queensland between 2009 and 2011. Data were provided through the Queensland Healthy Hearing database. Infants were analysed in <34 weeks, 34-36 +6 weeks, 37-38 +6 weeks and ≥39 weeks gestational age groups. Infants (175 911) were eligible for analysis, 7.9% being preterm. Per 1000 infants analysed, bilateral SNHL of >40 dB occurred in 2.4 for <34, 1.4 for 34-36 +6 , 0.7 for 37-38 +6 and 0.7 for ≥39 weeks gestation. Diagnoses attributable to newborn hearing screening direct referral were 93.1% for bilateral >40 dB SNHL and 88.2% for other hearing loss. Relative to term, preterm infants had a higher incidence of direct and targeted surveillance referrals, audiology assessment and hearing loss diagnosis. Preterm infants were screened later after birth. Specific hearing screening and diagnosis characteristics differed between preterm infants <34 and 34-36 +6 weeks gestation, and term infants. Consideration of unique gestational age strata characteristics supports care individualisation. Preterm infants represent a diagnostic challenge, with higher rates of bilateral >40 dB SNHL than term but correspondingly higher false positive results on screening, justifying vigilant monitoring. Focused research into specific risk factors in preterm infants is warranted. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Newborn Screening (NBS): Answers to Frequently Asked Questions

MedlinePlus

... states consider the NBS recommendations made by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children, a federal panel that reports to the Secretary of Health and Human Services. Some states may ...

Incidence and molecular characterization of Glucose-6-Phosphate Dehydrogenase deficiency among neonates for newborn screening in Chaozhou, China.

PubMed

Yang, H; Wang, Q; Zheng, L; Zhan, X-F; Lin, M; Lin, F; Tong, X; Luo, Z-Y; Huang, Y; Yang, L-Y

2015-06-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in southern China. The aim of this study is to assess the extent of this disease in Chinese neonates and determine its molecular characteristics using a novel molecular screening method. A total of 2500 neonates were routinely screened for G6PD deficiency using a modified fluorescent spot test (FST). PCR-high-resolution melting (HRM) analysis was then used for the molecular assay. The overall incidence of G6PD deficiency was 2.68% in our study cohort. Frequency in male population was 3.22% (44 neonates of 1365 male neonates), and in female population was 2.03% (23 neonates of 1135 female neonates). Of the 67 newborns suspected to be G6PD deficient based on FST (44 males, 23 females), 58 of 67 (87%) were detected with gene alterations. Seven kinds of mutations [c.95A>G, c.392G>T, c.493A>G, c.871G>A, c.1360C>T, c.1376G>T, and c.1388G>A] were identified by HRM analysis. Routine newborn screening in Chaozhou, China with a relatively high prevalence of G6PD deficiency is justified and meets the World Health Organization recommendation. The usage of molecular diagnosis can favor the detection of heterozygotes which can be a supplement to regular newborn screening and useful for premarital and prenatal diagnosis for G6PD deficiency. © 2014 John Wiley & Sons Ltd.

Fifty years of phenylketonuria newborn screening - A great success for many, but what about the rest?

PubMed

Groselj, Urh; Tansek, Mojca Zerjav; Battelino, Tadej

2014-01-01

Guthrie's landmark discovery and the subsequent implementation of the first newborn screening programs for phenylketonuria (PKU) and other inherited errors of metabolism (IEM) could be - in a 50 year retrospective - easily considered among the greatest advances in medicine. They have not just improved the quality of hundreds of thousands of lives, but also transformed our understanding and approach to PKU and IEM in general. However, according to the available albeit very scarce data, many countries and regions seem not to share the benefits of the last 50 years of development. Many of them have not yet introduced the newborn screening for PKU or face significant problems in its implementation. In addition, the issue seems to be underrated by the relevant professional forums. Action to improve the current situation should urgently be taken. Copyright © 2014 Elsevier Inc. All rights reserved.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Newborn bloodspot screening in the UK--past, present and future.

PubMed

Downing, Melanie; Pollitt, Rodney

2008-01-01

Screening newborn babies for inherited metabolic disease began in the UK in the late 1950s with the 'nappy test' for phenylketonuria. In 1969 the Department of Health recommended changing to bloodspot screening using the techniques developed in the USA by Robert Guthrie and his associates. Bloodspot screening for various other disorders (galactosaemia, maple syrup urine disease, homocystinuria, cystic fibrosis and others) was introduced on a patchy local basis but, until 2000, the only additional disorder officially recommended was congenital hypothyroidism. Screening for haemoglobinopathies received official support in 2000 and for cystic fibrosis in 2001 though implementation was slow, particularly for the latter. Both these screens have raised difficult issues relating to genetic privacy and the detection of carrier status in children. During the last decade screening has become increasingly subject to central control. Though a more consistent and systematic approach was clearly needed, this has undoubtedly slowed the rate of innovation. In particular the UK has lagged behind many other European countries in the application of tandem mass spectrometry (MS-MS) though, following a major pilot study, screening for medium-chain acyl-CoA dehydrogenase deficiency is now in the process of introduction. Attempts to codify clinical and laboratory procedures have also proved controversial, highlighting marked differences in practice in various parts of the country and the difficulty of rationalizing these within a practicable and scientifically justified framework. Notwithstanding this, there are many positive developments and newborn screening remains a stimulating and rewarding field in which to work.

Reverse cascade screening of newborns for hereditary haemochromatosis: a model for other late onset diseases?

PubMed

Cadet, E; Capron, D; Gallet, M; Omanga-Léké, M-L; Boutignon, H; Julier, C; Robson, K J H; Rochette, J

2005-05-01

Genetic testing can determine those at risk for hereditary haemochromatosis (HH) caused by HFE mutations before the onset of symptoms. However, there is no optimum screening strategy, mainly owing to the variable penetrance in those who are homozygous for the HFE Cys282Tyr (C282Y) mutation. The objective of this study was to identify the majority of individuals at serious risk of developing HFE haemochromatosis before they developed life threatening complications. We first estimated the therapeutic penetrance of the C282Y mutation in people living in la Somme, France, using genetic, demographic, biochemical, and follow up data. We examined the benefits of neonatal screening on the basis of increased risk to relatives of newborns carrying one or two copies of the C282Y mutation. Between 1999 and 2002, we screened 7038 newborns from two maternity hospitals in the north of France for the C282Y and His63Asp (H63D) mutations in the HFE gene, using bloodspots collected on Guthrie cards. Family studies and genetic counselling were undertaken, based on the results of the baby's genotype. In la Somme, we found that 24% of the adults homozygous for the C282Y mutation required at least 5 g iron to be removed to restore normal iron parameters (that is, the therapeutic penetrance). In the reverse cascade screening study, we identified 19 C282Y homozygotes (1/370), 491 heterozygotes (1/14) and 166 compound heterozygotes (1/42) in 7038 newborns tested. The reverse cascade screening strategy resulted in 80 adults being screened for both mutations. We identified 10 previously unknown C282Y homozygotes of whom six (four men and two women) required venesection. Acceptance of neonatal screening was high; parents understood the risks of having HH and the benefits of early detection, but a number of parents were reluctant to take the test themselves. Neonatal screening for HH is straightforward. Reverse cascade screening increased the efficiency of detecting affected adults with undiagnosed haemochromatosis. This strategy allows almost complete coverage for HH and could be a model for efficient screening for other late onset genetic diseases.

Fragile X-related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study.

PubMed

Inaba, Yoshimi; Herlihy, Amy S; Schwartz, Charles E; Skinner, Cindy; Bui, Quang M; Cobb, Joanna; Shi, Elva Z; Francis, David; Arvaj, Alison; Amor, David J; Pope, Kate; Wotton, Tiffany; Cohen, Jonathan; Hewitt, Jacqueline K; Hagerman, Randi J; Metcalfe, Sylvia A; Hopper, John L; Loesch, Danuta Z; Slater, Howard R; Godler, David E

2013-04-01

We show that a novel fragile X-related epigenetic element 2 FMR1 methylation test can be used along with a test for sex-determining region Y (SRY) to provide the option of combined fragile X syndrome and sex chromosome aneuploidy newborn screening. Fragile X-related epigenetic element 2, SRY, and FMR1 CGG repeat analyses were performed on blood and saliva DNA, and in adult and newborn blood spots. The cohort consisted of 159 controls (CGG <40), 187 premutation (CGG 56-170), and 242 full-mutation (CGG ~200-2,000) males and females, 106 sex chromosome aneuploidy individuals, and 151 cytogenetically normal controls. At the 0.435 threshold, fragile X-related epigenetic element 2 analysis in males was robust on both blood DNA and newborn blood spots, with specificity and sensitivity of ~100% for full-mutation genotype. In females, the specificity was 99%, whereas half of full-mutation females were above the 0.435 threshold in both blood DNA and newborn blood spots. Furthermore, at this threshold, the test could not differentiate individuals with Klinefelter syndrome from female controls without using the SRY marker. When combined with SRY analysis, the test was consistent with most results for sex chromosome aneuploidies from karyotyping. Setting specific thresholds for fragile X-related epigenetic element 2 analysis and including the SRY marker provides the option to either include or exclude detection of sex chromosome aneuploidies as part of fragile X syndrome newborn screening.

A cluster of lysinuric protein intolerance (LPI) patients in a northern part of Iwate, Japan due to a founder effect. The Mass Screening Group.

PubMed

Koizumi, A; Shoji, Y; Nozaki, J; Noguchi, A; E, X; Dakeishi, M; Ohura, T; Tsuyoshi, K; Yasuhiko, W; Manabe, M; Takasago, Y; Takada, G

2000-09-01

Lysinuric protein intolerance is an autosomal recessive disease characterized by defective transport of the dibasic aminoacids. Mutational analysis of LPI patients in the northern part of Japan revealed that six were homozygous for the R410X mutation and two others were compound heterozygotes of R410X and other unknown mutations. In the population epidemiology study in a local cluster in the northern part of Iwate, ten heterozygotes were found in 1190 newborn babies leading to an estimated LPI incidence of 1/57,000. Polymorphism analysis revealed two major alleles, A and B, in intron 8. While the population frequency of allele A was 0.9 and that of allele B was 0.1 in the northern part of Japan the R410X mutations were exclusively on allele B in 31 chromosomes suggesting a founder effect. Genetic analysis in patients revealed strong linkage disequilibrium with D14S283 and TCRA indicating that the R410X mutation occurred before at least 130 generations ago (about 2600 years). The R410X mutation was shown to be useful as a molecular marker for screening LPI patients in the northern part of Japan. Copyright 2000 Wiley-Liss, Inc.

How Are My Newborn's Screening Results Used?

MedlinePlus

... Pinterest Email Print How are my newborn’s screening results used? In most cases, parents don't hear ... for a particular condition(s). 1 Out of Range Results If the screening detects one or more conditions, ...

The Impact of the Affordable Care Act on Funding for Newborn Screening Services.

PubMed

Costich, Julia F; Durst, Andrea L

2016-01-01

The Affordable Care Act requires most health plans to cover the federal Recommended Uniform Screening Panel of newborn screening (NBS) tests with no cost sharing. However, state NBS programs vary widely in both the number of mandated tests and their funding mechanisms, including a combination of state laboratory fees, third-party billing, and other federal and state funding. We assessed the potential impact of the Affordable Care Act coverage mandate on states' NBS funding. We performed an extensive review of the refereed literature, federal and state agency reports, relevant organizations' websites, and applicable state laws and regulations; interviewed 28 state and federal officials from August to December 2014; and then assessed the interview findings manually. Although a majority of states had well-established systems for including laboratory-based NBS tests in bundled charges for newborn care, billing practices for critical congenital heart disease and newborn hearing tests were less uniform. Most commonly, birthing facilities either prepaid the costs of laboratory-based tests when acquiring the filter paper kits, or the facilities paid for the tests when the kits were submitted. Some states had separate arrangements for billing Medicaid, and smaller facilities sometimes contracted with hearing test vendors that billed families separately. Although the Affordable Care Act coverage mandate may offset some state NBS funding for the screenings themselves, federal support is still required to assure access to the full range of NBS program services. Limiting reimbursement to the costs of screening tests alone would undermine the common practice of using screening charges to fund follow-up services counseling, and medical food or formula, particularly for low-income families.

Neonatal screening for biotinidase deficiency: A 30-year single center experience.

PubMed

Porta, Francesco; Pagliardini, Veronica; Celestino, Isabella; Pavanello, Enza; Pagliardini, Severo; Guardamagna, Ornella; Ponzone, Alberto; Spada, Marco

2017-12-01

We reviewed the outcome of newborn screening for biotinidase deficiency performed at our department since 1987. Among 1,097,894 newborns screened, 461 were recalled, and 18 were identified as affected by complete or partial biotinidase deficiency (incidence 1:61,000, false positive rate 0.04%). The common missense mutation Q456H was found in 80% of patients with profound biotinidase deficiency. Of them, one patient harbored the novel mutation M399I in compound heterozygosity (M399I/Q456H). The complex allele A171T/D444H in cis was found in two patients with profound biotinidase deficiency (in homozygosity and in compound heterozygosity with the R211H mutation, respectively) and in one patient with partial biotinidase deficiency (in compound heterozygosity with the protective allele D444H in trans ). All detected patients were treated and followed up at our Center until present. Biotin therapy (10-20 mg/day) allowed the full prevention of clinical symptoms in all patients with no adverse effects. These excellent outcomes confirm that newborn screening for biotinidase deficiency is a very effective secondary prevention program.

Human Newborns Match Tongue Protrusion of Disembodied Human and Robotic Mouths

ERIC Educational Resources Information Center

Soussignan, Robert; Courtial, Alexis; Canet, Pierre; Danon-Apter, Gisele; Nadel, Jacqueline

2011-01-01

No evidence had been provided so far of newborns' capacity to give a matching response to 2D stimuli. We report evidence from 18 newborns who were presented with three types of stimuli on a 2D screen. The stimuli were video-recorded displays of tongue protrusion shown by: (a) a human face, (b) a human tongue from a disembodied mouth, and (c) an…

Effectiveness of sucrose analgesia in newborns undergoing painful medical procedures

PubMed Central

Taddio, Anna; Shah, Vibhuti; Hancock, Rebecca; Smith, Ryan W.; Stephens, Derek; Atenafu, Eshetu; Beyene, Joseph; Koren, Gideon; Stevens, Bonnie; Katz, Joel

2008-01-01

Background Sucrose is widely used to manage procedural pain in term newborns despite a lack of evidence of its effectiveness for different procedures and infant populations. Our objectives were to evaluate the effectiveness and safety of sucrose in newborns undergoing various medical procedures within 2 days of birth. Methods We performed a double-blind, randomized controlled trial. We included newborns (≥ 36 weeks gestation) of diabetic mothers and nondiabetic mothers. Each newborn received 2 mL of a 24%-sucrose or placebo solution before all procedures. We used the Premature Infant Pain Profile to assess pain during intramuscular injection of vitamin K, venipuncture for the newborn screening test and the first 3 heel lances for glucose monitoring (newborns of diabetic mothers only). Scores ranged from from 0 (no pain) to 18 (maximum pain). Results We included 240 newborns (120 from diabetic mothers, 120 from nondiabetic mothers). The overall mean pain score was lower among newborns who received sucrose than among those who received a placebo (mean difference –1.3, 95% confidence interval [CI] –2.0 to –0.6). We found that pain scores during intramuscular injection did not differ significantly between the sucrose and placebo groups for newborns of diabetic or nondiabetic mothers (newborns of nondiabetic mothers: mean difference –1.1, 95% CI –2.4 to 0.2; newborns of diabetic mothers: mean difference –1.0, 95% CI –2.4 to 0.4). During venipuncture, newborns who received sucrose had lower pain scores compared with those who received a placebo (newborns of nondiabetic mothers: mean difference –3.2, 95% CI –4.6 to –1.8; newborns of diabetic mothers: mean difference –2.4, 95% CI –3.8 to –1.0). Among newborns of diabetic mothers, there was no difference in pain during the first 3 heel lances or mean glucose levels between the sucrose and placebo groups (p = 0.94 and p = 0.29 respectively). Interpretation We found a modest reduction of pain in newborns of both diabetic and nondiabetic mothers when sucrose was used for all medical procedures performed in the first 2 days after birth. However, when each procedure was analyzed separately, we found that the effectiveness of sucrose was limited to venipuncture for the newborn screening test. (http://Clinicaltrials.gov trial register no. NCT00213213.) PMID:18591525

Communication of carrier status information following universal newborn screening for sickle cell disorders and cystic fibrosis: qualitative study of experience and practice.

PubMed

Kai, J; Ulph, F; Cullinan, T; Qureshi, N

2009-11-01

To describe and explore current practice, methods and experience of communicating carrier status information following newborn screening for cystic fibrosis (CF) and sickle cell (SC) disorders, to inform practice and further research. Three linked qualitative studies. All nine health regions in England. Child health screening coordinators in all English health regions, health professionals communicating results to parents and parents of newborn carriers. A preliminary phase of semi-structured telephone interviews with child health screening coordinators in all nine English health regions, and thematic analysis of data; semi-structured face-to-face interviews with purposeful samples of 67 family members of 51 infants identified by universal newborn screening as carriers of CF or SC with data analysis by constant comparison; and semi-structured telephone interviews, and focus groups, with a key informant sample of 16 differing health professionals currently tasked with communicating results to parents in a range of ways, with thematic analysis of data. Methods for and respondents' experiences of communication of carrier results varied considerably within and between regions, and within and between SC and CF contexts. Approaches ranged from letter or telephone call alone, to in-person communication in the clinic or at home, with health professionals from haemoglobinopathy, CF, screening and genetics backgrounds, or from community and primary care, such as health visitors with SC carrier results. Health professionals identified pros and cons of different methods, preferring opportunity for face-to-face communication with parents where possible, particularly for CF carrier results. They were concerned by regional variations in protocols, the lack of availability of translated information on SC carrier results, and the feasibility of sustaining more 'specialist' involvement at current levels, particularly for SC carriers. Parents were often poorly prepared for the possibility of a newborn carrier result. Some had felt overloaded by screening information received during pregnancy or prior to newborn screening, or found this information failed to meet their needs. Opportunity for face-to-face communication of results was valued by parents of SC carriers and appeared particularly necessary for those without prior knowledge of SC carrier status or where English was not their first language. Indirect communication of results by letter appeared effective and feasible for parents more aware of SC carrier status from antenatal or earlier experience, and where this communication contained an unambiguous opening statement emphasising 'your child is not ill'. Face-to-face communication of CF carrier results by professionals with screening, CF or genetics backgrounds worked well for parents, but communication and information was crucially lacking at the earlier stage of repeat blood spot testing, creating considerable distress among half of respondents. Respondents had no particular preference for the type of health professional who communicated results to them, as long as they were well informed and could answer their queries. Parents regarded carrier results as valuable information gained fortuitously. Methods of communication of newborn carrier results vary considerably across England. Parents' needs for timely and appropriate information may not be met consistently or adequately. Respondents' experiences suggest a need for greater recognition of communication with individuals occurring across a screening pathway, rather than as a discrete event.

Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

PubMed

Mak, Chloe Miu; Lam, Ching-Wan; Chim, Stella; Siu, Tak-Shing; Ng, King-Fai; Tam, Sidney

2013-01-01

Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report. A two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described. The patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment. Because of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden-a 2-Year Pilot TREC and KREC Screening Study.

PubMed

Barbaro, Michela; Ohlsson, Annika; Borte, Stephan; Jonsson, Susanne; Zetterström, Rolf H; King, Jovanka; Winiarski, Jacek; von Döbeln, Ulrika; Hammarström, Lennart

2017-01-01

Newborn screening for severe primary immunodeficiencies (PID), characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm County, Sweden, over a 2-year period, encompassing 58,834 children. T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) were measured simultaneously using a quantitative PCR-based method on DNA extracted from dried blood spots (DBS), with beta-actin serving as a quality control for DNA quantity. Diagnostic cutoff levels enabling identification of newborns with milder and reversible T and/or B cell lymphopenia were also evaluated. Sixty-four children were recalled for follow-up due to low TREC and/or KREC levels, and three patients with immunodeficiency (Artemis-SCID, ATM, and an as yet unclassified T cell lymphopenia/hypogammaglobulinemia) were identified. Of the positive samples, 24 were associated with prematurity. Thirteen children born to mothers treated with immunosuppressive agents during pregnancy (azathioprine (n = 9), mercaptopurine (n = 1), azathioprine and tacrolimus (n = 3)) showed low KREC levels at birth, which spontaneously normalized. Twenty-nine newborns had no apparent cause identified for their abnormal results, but normalized with time. Children with trisomy 21 (n = 43) showed a lower median number of both TREC (104 vs. 174 copies/μL blood) and KREC (45 vs. 100 copies/3.2 mm blood spot), but only one, born prematurely, fell below the cutoff level. Two children diagnosed with DiGeorge syndrome were found to have low TREC levels, but these were still above the cutoff level. This is the first large-scale screening study with a simultaneous detection of both TREC and KREC, allowing identification of newborns with both T and B cell defects.

The Initial Evaluation of Patients After Positive Newborn Screening: Recommended Algorithms Leading to a Confirmed Diagnosis of Pompe Disease.

PubMed

Burton, Barbara K; Kronn, David F; Hwu, Wuh-Liang; Kishnani, Priya S

2017-07-01

Newborn screening (NBS) for Pompe disease is done through analysis of acid α-glucosidase (GAA) activity in dried blood spots. When GAA levels are below established cutoff values, then second-tier testing is required to confirm or refute a diagnosis of Pompe disease. This article in the "Newborn Screening, Diagnosis, and Treatment for Pompe Disease" guidance supplement provides recommendations for confirmatory testing after a positive NBS result indicative of Pompe disease is obtained. Two algorithms were developed by the Pompe Disease Newborn Screening Working Group, a group of international experts on both NBS and Pompe disease, based on whether DNA sequencing is performed as part of the screening method. Using the recommendations in either algorithm will lead to 1 of 3 diagnoses: classic infantile-onset Pompe disease, late-onset Pompe disease, or no disease/not affected/carrier. Mutation analysis of the GAA gene is essential for confirming the biochemical diagnosis of Pompe disease. For NBS laboratories that do not have DNA sequencing capabilities, the responsibility of obtaining sequencing of the GAA gene will fall on the referral center. The recommendations for confirmatory testing and the initial evaluation are intended for a broad global audience. However, the Working Group recognizes that clinical practices, standards of care, and resource capabilities vary not only regionally, but also by testing centers. Individual patient needs and health status as well as local/regional insurance reimbursement programs and regulations also must be considered. Copyright © 2017 by the American Academy of Pediatrics.

Digital microfluidic platform for multiplexing enzyme assays: implications for lysosomal storage disease screening in newborns.

PubMed

Sista, Ramakrishna S; Eckhardt, Allen E; Wang, Tong; Graham, Carrie; Rouse, Jeremy L; Norton, Scott M; Srinivasan, Vijay; Pollack, Michael G; Tolun, Adviye A; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2011-10-01

Newborn screening for lysosomal storage diseases (LSDs) has been gaining considerable interest owing to the availability of enzyme replacement therapies. We present a digital microfluidic platform to perform rapid, multiplexed enzymatic analysis of acid α-glucosidase (GAA) and acid α-galactosidase to screen for Pompe and Fabry disorders. The results were compared with those obtained using standard fluorometric methods. We performed bench-based, fluorometric enzymatic analysis on 60 deidentified newborn dried blood spots (DBSs), plus 10 Pompe-affected and 11 Fabry-affected samples, at Duke Biochemical Genetics Laboratory using a 3-mm punch for each assay and an incubation time of 20 h. We used a digital microfluidic platform to automate fluorometric enzymatic assays at Advanced Liquid Logic Inc. using extract from a single punch for both assays, with an incubation time of 6 h. Assays were also performed with an incubation time of 1 h. Assay results were generally comparable, although mean enzymatic activity for GAA using microfluidics was approximately 3 times higher than that obtained using bench-based methods, which could be attributed to higher substrate concentration. Clear separation was observed between the normal and affected samples at both 6- and 1-h incubation times using digital microfluidics. A digital microfluidic platform compared favorably with a clinical reference laboratory to perform enzymatic analysis in DBSs for Pompe and Fabry disorders. This platform presents a new technology for a newborn screening laboratory to screen LSDs by fully automating all the liquid-handling operations in an inexpensive system, providing rapid results.

Changing Trends within the Population of Children Who Are Deaf or Hard of Hearing in Flanders (Belgium): Effects of 12 Years of Universal Newborn Hearing Screening, Early Intervention, and Early Cochlear Implantation

ERIC Educational Resources Information Center

De Raeve, Leo; Lichtert, Guido

2012-01-01

The purpose of this study is to show the changing trends within the population of children who are deaf and hard of hearing in Belgium over the last 12 years. The combination of Universal Newborn Hearing Screening programs, early intervention, and cochlear implants have tremendously influenced the education and support of children who are deaf or…

Giving them a good start: informatics support of newborn screening and clinical care.

PubMed

Wetter, T; Haschler, I; Ho, S; Hoffmann, G F; Linderkamp, O; Philipp, F; Skonetzki, S

2005-01-01

Newborns are a vulnerable population: Exposed to dramatically changing environmental conditions, potentially suffering from impairments that cannot realistically be diagnosed during pregnancy, with the risk that unfavorable conditions escalate fast. We have investigated informatics methods and tools to make screening for congenital diseases and containment of critical processes that start in the first days safer and more efficient. This poster present a set of three different methodological approaches that all aim at comprehensive improvement of neonatal care.

The incidence of urea cycle disorders.

PubMed

Summar, Marshall L; Koelker, Stefan; Freedenberg, Debra; Le Mons, Cynthia; Haberle, Johannes; Lee, Hye-Seung; Kirmse, Brian

2013-01-01

A key question for urea cycle disorders is their incidence. In the United States two UCDs, argininosuccinic synthetase and lyase deficiency, are currently detected by newborn screening. We used newborn screening data on over 6million births and data from the large US and European longitudinal registries to determine how common these conditions are. The incidence for the United States is predicted to be 1 urea cycle disorder patient for every 35,000 births presenting about 113 new patients per year across all age groups. © 2013.

Postdeployment Behavioral Health Screens and Linkage to the Veterans Health Administration for Army Reserve Component Members.

PubMed

Vanneman, Megan E; Harris, Alex H S; Chen, Cheng; Adams, Rachel Sayko; Williams, Thomas V; Larson, Mary Jo

2017-08-01

Approximately three to six months after returning from deployment, military service members complete the Post-Deployment Health Reassessment (PDHRA), which includes screens for alcohol misuse, depression, and posttraumatic stress disorder (PTSD). To determine whether Army Reserve Component (RC) members (Army National Guard and Army Reserve) with positive screening scores on the PDHRA receive needed care, the investigators examined the association between positive scores and enrollment and utilization of care ("linkage") in the Veterans Health Administration (VHA), as well as rescreening scores, diagnosis, and behavioral treatment in VHA. Mixed-effects regression models were used to predict linkage to VHA within six months after RC members (N=73,164) completed the PDHRA, with alcohol misuse, depression, and PTSD screen scores as key independent variables. Regression models were stratified by gender and National Guard versus Reserve status. Among those who linked to VHA (N=25,168), screening scores and subsequent diagnosis and treatment in VHA were also examined. Army RC members with positive PTSD and depression screening scores were more likely than those with negative screens to link to VHA, and most (54%-84%) received VHA treatment once diagnosed. Positive screens for alcohol misuse were associated with linkage to VHA for men but not for women, and treatment rates for alcohol use disorders were relatively low (0%-25%) for both men and women diagnosed as having an alcohol use disorder. The finding that Army RC members with greater indications of behavioral health problems linked to VHA is encouraging. However, more outreach and treatment engagement strategies could be directed to those with alcohol use disorder, particularly women.

Healthcare professionals' and parents' experiences of the confirmatory testing period: a qualitative study of the UK expanded newborn screening pilot.

PubMed

Moody, Louise; Atkinson, Lou; Kehal, Isher; Bonham, James R

2017-05-08

With further expansion of the number of conditions for which newborn screening can be undertaken, it is timely to consider the impact of positive screening results and the confirmatory testing period on the families involved. This study was undertaken as part of a larger programme of work to evaluate the Expanded Newborn Screening (ENBS) programme in the United Kingdom (UK). It was aimed to determine the views and experiences of healthcare professionals (HCPs) and parents on communication and interaction during the period of confirmatory testing following a positive screening result. Semi-structured interviews were undertaken with parents of children who had received a positive ENBS result and HCPs who had been involved with the diagnosis and support of parents. Ten parents and 11 healthcare professionals took part in the in-depth interviews. Questions considered the journey from the positive screening result through confirmatory testing to a confirmed diagnosis and the communication and interaction between the parents and HCPs that they had been experienced. Key themes were identified through thematic analysis. The results point to a number of elements within the path through confirmatory testing that are difficult for parents and could be further developed to improve the experience. These include the way in which the results are communicated to parents, rapid turnaround of results, offering a consistent approach, exploring interventions to support family relationships and reviewing the workload and scheduling implications for healthcare professionals. As technology enables newborn screening of a larger number of conditions, there is an increasing need to consider and mediate the potentially negative effects on families. The findings from this study point to a number of elements within the path through confirmatory testing that are difficult for parents and could be further developed to benefit the family experience.

Screening for Multiple Genes Influencing Dyslexia.

ERIC Educational Resources Information Center

Smith, Shelley D.; And Others

1991-01-01

Examines the "sib pair" method of linkage analysis designed to locate genes influencing dyslexia, which has several advantages over the "LOD" score method. Notes that the sib pair analysis was able to detect the same linkages as the LOD method, plus a possible third region. Confirms that the sib pair method is an effective means of screening. (RS)

Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective

PubMed Central

2011-01-01

Background A screening programme for pregnant women has been in place since the 1950s in the Netherlands. In 2004 universal HIV screening according to opting out was implemented. Here, we describe the evaluation of the effectiveness of antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus (HBV) and syphilis in preventing mother-to-child transmission, by using various data sources. Methods The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. Results Each year, around 185,000 pregnant women were screened for HIV, HBV and syphilis. Refusal rates for the screening tests were low, and were highest (0.2%) for HIV. The estimated annual prevalence of HIV among pregnant women was 0.05%. Prior to the introduction of screening, 5-10 children were born with HIV annually After the introduction of screening in 2004, only 4 children were born with HIV (an average of 1 per year). Two of these mothers had become pregnant prior to 2004; the third mother was HIV negative at screening and probably became infected after screening; the fourth mother's background was unknown. Congenital syphilis was diagnosed in fewer than 5 newborns annually and 5 children were infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually as a result of screening. Conclusions The screening programme was effective in detecting HIV, HBV and syphilis in pregnant women and in preventing transmission to the child. Since the introduction of the HIV screening the number of children born with HIV has fallen dramatically. Previous publication [Translation from: 'Prenatale screening op hiv, hepatitis B en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine ' (NTVG, in Dutch)] PMID:21718466

The HI HOPES data set of deaf children under the age of 6 in South Africa: maternal suspicion, age of identification and newborn hearing screening.

PubMed

Störbeck, Claudine; Young, Alys

2016-03-22

Identification of deafness before 3 months of age substantially improves the socio-linguistic and cognitive development of deaf children. Existing studies demonstrating the feasibility of newborn hearing screening in South Africa have used small samples unrepresentative of general population characteristics. This study establishes the characteristics of the largest data set of deaf infants and their families in South Africa on which there is baseline and longitudinal data (n = 532); explores its representativeness in terms of socio-demographic features and reports on access to and quality of newborn hearing screening within the sample. It examines specifically the relationship between age of maternal suspicion of childhood deafness and age of identification of deafness by cohort characteristics. Secondary analysis, using descriptive and inferential statistics, of a pre-existing longitudinal data set (n = 532) of deaf infants under 6 years of age, and their families, collected as routine monitoring of the HI HOPES (HH) early intervention programme. The HH cohort is representative in terms of racial profile and private/public health care use but displays slightly higher level of maternal education and slightly lower socio-economic status than national comparators. 102 out of 532 infants had undergone newborn hearing screening, resulting in 29 true positives, 15 of whom would have met the criteria for targeted screening. Later onset deafness does not account for the 73 false negatives. The median age of maternal suspicion (n = 247) of infant deafness was 18 months; the median age of identification of 28 months. Age of identification was unrelated to private/public health care status. The median delay between age of suspicion and age of identification was significantly longer in the public sector (7 m; IQR 0-15 m) compared to the private sector (2 m; IQR 0-8.5 m) (p = 0.035). Age of suspicion was unrelated to level of maternal education. Earlier age of suspicion did not predict earlier identification. Targeted screening as timely response to maternal suspicion offers a viable means to reduce substantially the age of identification of deafness in South Africa until implementation of newborn hearing screening on a population-wide basis can be justified.

A simple method for the analysis by MS/MS of underivatized amino acids on dry blood spots from newborn screening.

PubMed

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

2012-05-01

The analysis by electrospray-ionization tandem mass spectrometry of amino acids with butyl esterification and isotopically labeled internal standard is routine in newborn screening laboratories worldwide. In the present study, we established a direct analysis method of higher accuracy that uses a non-deuterated internal standard. The automatic sampler and the pump of an LC apparatus were used to inject sample and mobile phase to MS, but no LC column was needed. The dry blood spot (DBS) material was prepared at levels of low, medium and high concentration; the running time was 1 min. In parallel to the new procedure, we applied the established method to analyze nine amino acids on DBS of healthy newborns and phenylketonuria newborns. The newly proposed method of product ion confirmation scan along with multiple reaction monitoring resulted in a very accurate identification of each amino acid. Our innovative protocol had high sensitivity and specificity in the analysis of cases of suspected metabolic diseases.

Facebook Advertising Across an Engagement Spectrum: A Case Example for Public Health Communication.

PubMed

Platt, Tevah; Platt, Jodyn; Thiel, Daniel B; Kardia, Sharon L R

2016-05-30

The interpersonal, dialogic features of social networking sites have untapped potential for public health communication. We ran a Facebook advertising campaign to raise statewide awareness of Michigan's newborn screening and biobanking programs. We ran a Facebook advertising campaign to stimulate public engagement on the complex and sensitive issue of Michigan's newborn screening and biobank programs. We ran an 11-week, US $15,000 Facebook advertising campaign engaging Michigan Facebook users aged 18-64 years about the state's newborn screening and population biobank programs, and we used a novel "engagement spectrum" framework to contextualize and evaluate engagement outcomes ranging from observation to multi-way conversation. The campaign reached 1.88 million Facebook users, yielding a range of engagement outcomes across ad sets that varied by objective, content, budget, duration, and bid type. Ad sets yielded 9009 page likes (US $4125), 15,958 website clicks (US $5578), and 12,909 complete video views to 100% (US $3750). "Boosted posts" yielded 528 comments and 35,966 page post engagements (US $1500). Overall, the campaign led to 452 shares and 642 comments, including 176 discussing newborn screening and biobanking. Facebook advertising campaigns can efficiently reach large populations and achieve a range of engagement outcomes by diversifying ad types, bid types, and content. This campaign provided a population-based approach to communication that also increased transparency on a sensitive and complex topic by creating a forum for multi-way interaction.

Facebook Advertising Across an Engagement Spectrum: A Case Example for Public Health Communication

PubMed Central

Platt, Jodyn; Thiel, Daniel B; Kardia, Sharon L. R

2016-01-01

Background The interpersonal, dialogic features of social networking sites have untapped potential for public health communication. We ran a Facebook advertising campaign to raise statewide awareness of Michigan’s newborn screening and biobanking programs. Objective We ran a Facebook advertising campaign to stimulate public engagement on the complex and sensitive issue of Michigan’s newborn screening and biobank programs. Methods We ran an 11-week, US $15,000 Facebook advertising campaign engaging Michigan Facebook users aged 18-64 years about the state’s newborn screening and population biobank programs, and we used a novel “engagement spectrum” framework to contextualize and evaluate engagement outcomes ranging from observation to multi-way conversation. Results The campaign reached 1.88 million Facebook users, yielding a range of engagement outcomes across ad sets that varied by objective, content, budget, duration, and bid type. Ad sets yielded 9009 page likes (US $4125), 15,958 website clicks (US $5578), and 12,909 complete video views to 100% (US $3750). “Boosted posts” yielded 528 comments and 35,966 page post engagements (US $1500). Overall, the campaign led to 452 shares and 642 comments, including 176 discussing newborn screening and biobanking. Conclusions Facebook advertising campaigns can efficiently reach large populations and achieve a range of engagement outcomes by diversifying ad types, bid types, and content. This campaign provided a population-based approach to communication that also increased transparency on a sensitive and complex topic by creating a forum for multi-way interaction. PMID:27244774

Comprehensive CFTR gene analysis of the French cystic fibrosis screened newborn cohort: implications for diagnosis, genetic counseling, and mutation-specific therapy.

PubMed

Audrézet, Marie Pierre; Munck, Anne; Scotet, Virginie; Claustres, Mireille; Roussey, Michel; Delmas, Dominique; Férec, Claude; Desgeorges, Marie

2015-02-01

Newborn screening (NBS) for cystic fibrosis (CF) was implemented throughout France in 2002. It involves a four-tiered procedure: immunoreactive trypsin (IRT)/DNA/IRT/sweat test [corrected] was implemented throughout France in 2002. The aim of this study was to assess the performance of molecular CFTR gene analysis from the French NBS cohort, to evaluate CF incidence, mutation detection rate, and allelic heterogeneity. During the 8-year period, 5,947,148 newborns were screened for cystic fibrosis. The data were collected by the Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant. The mutations identified were classified into four groups based on their potential for causing disease, and a diagnostic algorithm was proposed. Combining the genetic and sweat test results, 1,160 neonates were diagnosed as having cystic fibrosis. The corresponding incidence, including both the meconium ileus (MI) and false-negative cases, was calculated at 1 in 4,726 live births. The CF30 kit, completed with a comprehensive CFTR gene analysis, provides an excellent detection rate of 99.77% for the mutated alleles, enabling the identification of a complete genotype in 99.55% of affected neonates. With more than 200 different mutations characterized, we confirmed the French allelic heterogeneity. The very good sensitivity, specificity, and positive predictive value obtained suggest that the four-tiered IRT/DNA/IRT/sweat test procedure may provide an effective strategy for newborn screening for cystic fibrosis.

Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis.

PubMed

Lefterova, Martina I; Shen, Peidong; Odegaard, Justin I; Fung, Eula; Chiang, Tsoyu; Peng, Gang; Davis, Ronald W; Wang, Wenyi; Kharrazi, Martin; Schrijver, Iris; Scharfe, Curt

2016-03-01

Newborn screening for cystic fibrosis enables early detection and management of this debilitating genetic disease. Implementing comprehensive CFTR analysis using Sanger sequencing as a component of confirmatory testing of all screen-positive newborns has remained impractical due to relatively lengthy turnaround times and high cost. Here, we describe CFseq, a highly sensitive, specific, rapid (<3 days), and cost-effective assay for comprehensive CFTR gene analysis from dried blood spots, the common newborn screening specimen. The unique design of CFseq integrates optimized dried blood spot sample processing, a novel multiplex amplification method from as little as 1 ng of genomic DNA, and multiplex next-generation sequencing of 96 samples in a single run to detect all relevant CFTR mutation types. Sequence data analysis utilizes publicly available software supplemented by an expert-curated compendium of >2000 CFTR variants. Validation studies across 190 dried blood spots demonstrated 100% sensitivity and a positive predictive value of 100% for single-nucleotide variants and insertions and deletions and complete concordance across the polymorphic poly-TG and consecutive poly-T tracts. Additionally, we accurately detected both a known exon 2,3 deletion and a previously undetected exon 22,23 deletion. CFseq is thus able to replace all existing CFTR molecular assays with a single robust, definitive assay at significant cost and time savings and could be adapted to high-throughput screening of other inherited conditions. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Critical Congenital Heart Disease Screening by Pulse Oximetry in a Neonatal Intensive Care Unit

PubMed Central

Manja, Veena; Mathew, Bobby; Carrion, Vivien; Lakshminrusimha, Satyan

2014-01-01

Critical congenital heart disease (CCHD) screening is effective in asymptomatic late preterm and term newborn infants with a low false positive rate (0.035%). Objective (1) To compare 2817 NICU discharges before and after implementation of CCHD screening; and (2) to evaluate CCHD screening at < 35 weeks gestation. Methods collection of results of CCHD screening including preductal and postductal SpO2 values. Results During the pre-CCHD screen period, 1247 infants were discharged from the NICU and one case of CCHD was missed. After 3/1/12, 1508 CCHD screens were performed among 1570 discharges and no CCHDs were missed. The preductal and postductal SpO2 values were 98.8±1.4% and 99±1.3% respectively in preterm and 98.9±1.3% and 98.9±1.4% in term infants. Ten infants had false positive screens (10/1508=0.66%). Conclusions Performing universal screening in the NICU is feasible but is associated with a higher false positive rate compared to asymptomatic newborn infants. PMID:25058746

The use of high resolution melting analysis to detect Fabry mutations in heterozygous females via dry bloodspots.

PubMed

Tai, Chang-Long; Liu, Mei-Ying; Yu, Hsiao-Chi; Chiang, Chiang-Chuan; Chiang, Hung; Suen, Jeng-Hung; Kao, Shu-Min; Huang, Yu-Hsiu; Wu, Tina Jui-Ting; Yang, Chia-Feng; Tsai, Fang-Chih; Lin, Ching-Yuang; Chang, Jan-Gowth; Chen, Hong-Duo; Niu, Dau-Ming

2012-02-18

As an X-linked genetic disorder, Fabry disease was first thought to affect males only, and females were generally considered to be asymptomatic carriers. However, recent research suggests that female carriers of Fabry disease may still develop vital organ damage causing severe morbidity and mortality. In the previous newborn screening, from 299,007 newborns, we identified a total of 20 different Fabry mutations and 121 newborns with Fabry mutations. However, we found that most female carriers are not detected by enzyme assays. A streamlined method for high resolution melting (HRM) analysis was designed to screen for GLA gene mutations using a same PCR and melting program. Primer sets were designed to cover the 7 exons and the Chinese common intronic mutation, IVS4+919G>A of GLA gene. The HRM analysis was successful in identifying heterozygous and hemizygous patients with the 20 surveyed mutations. We were also successful in using this method to test dry blood spots of newborns afflicted with Fabry mutations without having to determine DNA concentration before PCR amplification. The results of this study show that HRM could be a reliable and sensitive method for use in the rapid screening of females for GLA mutations. Copyright © 2011 Elsevier B.V. All rights reserved.

Critical congenital heart disease screening with a pulse oximetry in neonates.

PubMed

Hamilçıkan, Şahin; Can, Emrah

2018-02-23

To compare the results of pulse oximetry screening for critical congenital heart disease (CCHD) in newborn infants performed at <24 h and >24 h following. Measurements were taken for each group at <24 h and >24 h following birth. Echocardiography was performed if the SpO2 readings remained abnormal results. A total of 4518 newborns were included in this prospective descriptive study. Of these, 2484 (60.3%) were delivered vaginally and 1685 (39.7%) by cesarean section. Median time points of the screening were 25.4 (25.3-25.5) vs. 17.3 (12.2-22.4) hours after birth. In 4109 infants screened 24 h after birth, the mean pre- and postductal oxygen saturations (SpO2) were 96.5±1.99 and 97.7±1.98, while 127 infants screened within 24 h of mean preductal and postductal SpO2 were 91.33±2.64 and 94.0±4.44. No CCHD was detected during the study period. Pulse oximetry screening was false positive for CCHD in 9 of 4109 infants (0.02%); of these, six infants were referred to pediatric cardiology and three cases were diagnosed as other significant, non-cardiac pathology. There were two cases with AVSD (atrioventricular septal defect, three cases with ventricular septal defect (VSD), and one case with patent ductus arteriosus (PDA). Saturation values are different between <24-h and >24-h neonates in pulse oximetry screening. The screening in this study identified infants with other important pathologies, this forms an added value as an assessment tool for newborn infants.

Molecular diagnostics and newborns at risk for genital herpes simplex virus.

PubMed

Chua, Caroline; Arnolds, Marin; Niklas, Victoria

2015-05-01

Herpes simplex virus (HSV) infection in the newborn carries a high mortality rate and can result in lifelong neurologic impairment. The severity of HSV infection in the newborn has always dictated conservative management when prodromal symptoms or active genital lesions (or those suggestive of genital herpes) are present during labor and delivery. The risk of intrapartum infection, however, is related to the presence or absence of maternal immunity (neutralizing antibody) to HSV. The most significant risk of transmission is in first-episode primary infections with active lesions at delivery. Recent recommendations from the American Academy of Pediatrics Committees on Infectious Diseases and the Fetus and Newborn use rapid serologic and virologic screening in the management of asymptomatic infants born to mothers with active genital herpes. The revised guidelines highlight infants at greatest risk for HSV disease but do not apply to asymptomatic infants born to mothers with a history of HSV but no genital lesions at delivery. The current guidelines also stipulate that maternal serologic screening and molecular assays for HSV in newborn blood and cerebrospinal fluid must be available and reported in a timely fashion. Copyright 2015, SLACK Incorporated.

Newborn screening for congenital hypothyroidism in Henan province, China.

PubMed

Zhao, De-Hua; Shen, Yong; Gong, Jiao-Mei; Meng, Yun; Su, Li; Zhang, Xia

2016-01-15

Congenital hypothyroidism is the most common congenital endocrine disorder. The study aimed to determine the congenital hypothyroidism incidence by newborn screening programs in Henan Province, China. The screening programs for congenital hypothyroidism are based on the measurement of TSH in dried blood spots. The TSH concentration was measured in the dry blood spot specimen using a DELFIA fluoroimmunoassay. The TSH cutoff concentration was 8mU/l. The total coverage and the incidence of congenital hypothyroidism were 24.85% (5,142,148/20,694,441) and 0.37‰ (1992/5,142,148), respectively. The coverage and the incidence of CH were only 0.58% (4526/784,580) and 0.22‰ (1/4526) in 1997, respectively. However, the coverage and the incidence of CH were increased to 74.67% (1,203,278/1,611,582) and 0.32‰ (389/1,203,278). There were no significant differences in the number of congenital hypothyroidism between males and females (P>0.05). The number of congenital hypothyroidism was increased year after year. The newborn screening program for CH is successful and quite effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry☆

PubMed Central

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

2017-01-01

Background There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life. Objective To evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic activity assay of 6 lysosomal enzymes in a NBS laboratory for the identification of newborns at risk for developing Pompe, Mucopolysaccharidosis-I (MPS-I), Fabry, Gaucher, Niemann Pick-A/B, and Krabbe diseases. Methods and Results Enzyme activities (acid α-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), α-galactosidase A (GLA), α-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk. The 6-plex assay was efficiently performed in the Washington state NBS laboratory by a single laboratory technician at the bench using a single MS/MS instrument. The number of screen positive samples per 100,000 newborns were as follows: GAA (4.5), IDUA (13.6), GLA (18.2), SMPD1 (11.4), GBA (6.8), and GALC (25.0). Discussion A 6-plex MS/MS assay for 6 lysosomal enzymes can be successfully performed in a NBS laboratory. The analytical ranges (enzyme-dependent assay response for the quality control HIGH sample divided by that for all enzyme-independent processes) for the 6-enzymes with the MS/MS is 5- to 15-fold higher than comparable fluorimetric assays using 4-methylumbelliferyl substrates. The rate of screen positive detection is consistently lower for the MS/MS assay compared to the fluorimetric assay using a digital microfluidics platform. PMID:27238910

Fabry disease: Review and experience during newborn screening.

PubMed

Hsu, Ting-Rong; Niu, Dau-Ming

2018-05-01

Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD. Copyright © 2017 Elsevier Inc. All rights reserved.

Save Babies through Screening Foundation

MedlinePlus

... birth. The Foundation pursues its mission through the education of parents, pediatric healthcare workers, lawmakers, and institutional policymakers. Our educational programs emphasize the importance of newborn screening through comprehensive testing to identify ...

Detection of other inborn errors of metabolism in hyperphenylalaninemic babies picked up on narrow-spectrum screening programs.

PubMed

Unal, Ozlem; Oztürk-Hişmi, Burcu; Coşkun, Turgay; Tokatlı, Ayşegül; Dursun, Ali; Sivri, Hatice Serap

2012-01-01

In many countries, neonatal screening programs have been unable to expand and have been limited to a few diseases. We highlight herein the opportunity available for the early detection of some inborn errors of metabolism (IEMs) in those countries in which newborn screening programs are limited. All the newborns that are referred to us for hyperphenylalaninemia are examined physically and their blood samples are checked by both high-performance liquid chromatography (HPLC) for blood phenylalanine levels and by amino acid analyzer for the measurement of blood amino acid concentrations. Seven patients who had been referred to our unit for hyperphenylalaninemia were eventually diagnosed with another IEM. A careful physical examination of the babies sent for positive screening test result combined with the utilization of low expense screening techniques at the experienced referring centers might facilitate otherwise missed opportunities for the early detection of some IEMs.

Newborn Screening for CF

MedlinePlus

... Testing for Cystic Fibrosis CFTR-Related Metabolic Syndrome (CRMS) How Babies Are Screened in IRT-Only vs. ... Guidelines Infant Care Clinical Care Guidelines Management of CRMS in First 2 Years and Beyond Clinical Care ...

Pulse Oximetry and Auscultation for Congenital Heart Disease Detection.

PubMed

Hu, Xiao-Jing; Ma, Xiao-Jing; Zhao, Qu-Ming; Yan, Wei-Li; Ge, Xiao-Ling; Jia, Bing; Liu, Fang; Wu, Lin; Ye, Ming; Liang, Xue-Cun; Zhang, Jing; Gao, Yan; Zhai, Xiao-Wen; Huang, Guo-Ying

2017-10-01

Pulse oximetry (POX) has been confirmed as a specific screening modality for critical congenital heart disease (CCHD), with moderate sensitivity. However, POX is not able to detect most serious and critical cardiac lesions (major congenital heart disease [CHD]) without hypoxemia. In this study, we investigated the accuracy and feasibility of the addition of cardiac auscultation to POX as a screening method for asymptomatic major CHD. A multicenter prospective observational screening study was conducted at 15 hospitals in Shanghai between July 1, 2012, and December 31, 2014. Newborns with either an abnormal POX or cardiac auscultation were defined as screen positive. All screen-positive newborns underwent further echocardiography. False-negative results were identified by clinical follow-up, parents' feedback, and telephone review. We assessed the accuracy of POX plus cardiac auscultation for the detection of major CHD. CHD screening was completed in all 15 hospitals, with a screening rate of 94.0% to 99.8%. In total, 167 190 consecutive asymptomatic newborn infants were screened, of which 203 had major CHD (44 critical and 159 serious). The sensitivity of POX plus cardiac auscultation was 95.5% (95% confidence interval 84.9%-98.7%) for CCHD and 92.1% (95% confidence interval 87.7%-95.1%) for major CHD. The false-positive rate was 1.2% for detecting CCHD and 1.1% for detecting major CHD. In our current study, we show that using POX plus cardiac auscultation significantly improved the detection rate of major CHD in the early neonatal stage, with high sensitivity and a reasonable false-positive rate. It provides strong evidence and a reliable method for neonatal CHD screening. Copyright © 2017 by the American Academy of Pediatrics.

Steroid profiling for congenital adrenal hyperplasia by tandem mass spectrometry as a second-tier test reduces follow-up burdens in a tertiary care hospital: a retrospective and prospective evaluation.

PubMed

Seo, Ja Young; Park, Hyung-Doo; Kim, Jong Won; Oh, Hyeon Ju; Yang, Jeong Soo; Chang, Yun Sil; Park, Won Soon; Lee, Soo-Youn

2014-01-01

Newborn screening for congenital adrenal hyperplasia (CAH) based on measuring 17-hydroxyprogesterone (17-OHP) by immunoassay generates a number of false-positive results, especially in preterm neonates. We applied steroid profiling by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a second-tier test in newborns with positive CAH screening and evaluated its clinical utility in a tertiary care hospital setting. By performing a 4-year retrospective data review, we were able to test 121 dried blood spots from newborns with positive CAH screening for 17-OHP, androstenedione and cortisol levels by LC-MS/MS. We prospectively evaluated the clinical utility of steroid profiling after the implementation of steroid profiling as a second-tier test in our routine clinical practice. During the 2-year prospective study period, 104 cases with positive initial screening by FIA were tested by LC-MS/MS. Clinical and laboratory follow-up were performed for at least 6 months. The preterm neonates accounted for 50.7% (76/150) and 70.4% (88/125) of screening-positive cases in retrospective and prospective cohorts, respectively. By applying steroid profiling as a second-tier test for positive CAH screening, we eliminated all false-positive results and decreased the median follow-up time from 75 to 8 days. Our data showed that steroid profiling reduced the burden of follow-up exams by improving the positive predictive value of the CAH screening program. The use of steroid profiling as a second-tier test for positive CAH screening will improve clinical practice particularly in a tertiary care hospital setting where positive CAH screening from preterm neonates is frequently encountered.

Identifying Candidate Chemical-Disease Linkages ...

EPA Pesticide Factsheets

Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment. Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment.

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. © 2013 Wiley Periodicals, Inc.

Improved Newborn Hearing Screening Follow-up Results in More Infants Identified

PubMed Central

Alam, Suhana; Gaffney, Marcus; Eichwald, John

2015-01-01

Longitudinal research suggests that efforts at the national, state, and local levels are leading to improved follow-up and data reporting. Data now support the assumption that the number of deaf or hard-of-hearing infants identified through newborn hearing screening increases with a reduction in the number of infants lost to follow-up. Documenting the receipt of services has made a noticeable impact on reducing lost to follow-up rates and early identification of infants with hearing loss; however, continued improvement and monitoring of services are still needed. PMID:23803975

Improved newborn hearing screening follow-up results in more infants identified.

PubMed

Alam, Suhana; Gaffney, Marcus; Eichwald, John

2014-01-01

Longitudinal research suggests that efforts at the national, state, and local levels are leading to improved follow-up and data reporting. Data now support the assumption that the number of deaf or hard-of-hearing infants identified through newborn hearing screening increases with a reduction in the number of infants lost to follow-up. Documenting the receipt of services has made a noticeable impact on reducing lost to follow-up rates and early identification of infants with hearing loss; however, continued improvement and monitoring of services are still needed.

78 FR 23770 - Establishment of the Discretionary Advisory Committee on Heritable Disorders in Newborns and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

... child screening, counseling and health care services for newborns and children having, or at risk for... heritable disorders who have worked and published material in the area of public health and genetic... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Establishment...

78 FR 51195 - Discretionary Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Discretionary... the webinar through in-person attendance at the Health Resources and Services Administration (HRSA... Department of Health and Human Services about the development of newborn screening activities, technologies...

Newborn Screening in the Era of Precision Medicine.

PubMed

Yang, Lan; Chen, Jiajia; Shen, Bairong

2017-01-01

As newborn screening success stories gained general confirmation during the past 50 years, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. Outstanding progress in sequencing technologies over the last two decades has made it possible to comprehensively profile newborn screening (NBS) and identify clinically relevant genomic alterations. With the rapid developments in whole-genome sequencing (WGS) and whole-exome sequencing (WES) recently, we can detect newborns at the genomic level and be able to direct the appropriate diagnosis to the different individuals at the appropriate time, which is also encompassed in the concept of precision medicine. Besides, we can develop novel interventions directed at the molecular characteristics of genetic diseases in newborns. The implementation of genomics in NBS programs would provide an effective premise for the identification of the majority of genetic aberrations and primarily help in accurate guidance in treatment and better prediction. However, there are some debate correlated with the widespread application of genome sequencing in NBS due to some major concerns such as clinical analysis, result interpretation, storage of sequencing data, and communication of clinically relevant mutations to pediatricians and parents, along with the ethical, legal, and social implications (so-called ELSI). This review is focused on these critical issues and concerns about the expanding role of genomics in NBS for precision medicine. If WGS or WES is to be incorporated into NBS practice, considerations about these challenges should be carefully regarded and tackled properly to adapt the requirement of genome sequencing in the era of precision medicine.

Applying Public Health Screening Criteria: How Does Universal Newborn Screening Compare to Universal Tumor Screening for Lynch Syndrome in Adults with Colorectal Cancer?

PubMed Central

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

2014-01-01

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 compares and contrasts 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

Screening, testing, and reporting for drug and alcohol use on labor and delivery: a survey of Maryland birthing hospitals.

PubMed

Miller, Catherine; Lanham, Amy; Welsh, Christopher; Ramanadhan, Shaalini; Terplan, Mishka

2014-01-01

Recent amendments to the Child Abuse Prevention and Treatment Act tie the receipt of federal block grants to mandatory reporting of substance-exposed newborns. To determine rates of screening, testing, and reporting of drug and alcohol use at the time of delivery, we administered a telephone survey of nursing managers and perinatal social workers at Maryland birthing hospitals. Of the 34 hospitals, 31 responded (response rate 91%). Although 97% of hospitals reported universal screening, only 6% used a validated instrument. Testing was reported by 94% with 45% reporting universal maternal testing and 7% universal newborn testing. Only 32% reported obtaining maternal consent prior to testing. There is significant heterogeneity in screening and testing for substance use in birthing hospitals. Given federal reporting mandates, state-level practices need to be standardized.

Higher Incidence Rates of Hypothyroidism and Late TSH Rise in Preterm Very-Low-Birth-Weight Infants at a Tertiary Care Center.

PubMed

Tfayli, Hala; Charafeddine, Lama; Tamim, Hani; Saade, Joanne; Daher, Rose T; Yunis, Khalid

2018-04-11

Preterm newborns with a very low birth weight (VLBW) of < 1,500 g have an atypical form of hypothyroidism with a delayed rise in TSH, necessitating a second newborn screening specimen collection. The aims of this study were to survey the compliance with second newborn screening to detect delayed TSH rise in VLBW preterm infants at a tertiary care center, and to determine the rate of atypical hypothyroidism. Retrospective review of the records of 104 preterm VLBW infants. Late TSH rise was defined as an increase in TSH concentration after 14 days of age in the presence of a normal initial screen. The compliance rate was 92% for the second screening. High rates of hypothyroidism (16.3%) and of late TSH rise (4.8%) were detected. Patients with hypothyroidism had a significantly lower birth weight (p = 0.01) and longer hospital stay (p = 0.004). Patients with late versus those with early TSH rise had a significantly lower mean birth weight (851 ± 302 vs. 1,191 ± 121 g, p = 0.004). The rates of early and late TSH rise in this VLBW population were higher than those in the literature and could be due to the use of povidone-iodine disinfectants. The yield of a second TSH screening in this study was high indicating the need for vigilance in screening VLBW preterm infants. © 2018 S. Karger AG, Basel.

First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency-Clinical Achievements and Insights.

PubMed

Rechavi, Erez; Lev, Atar; Simon, Amos J; Stauber, Tali; Daas, Suha; Saraf-Levy, Talia; Broides, Arnon; Nahum, Amit; Marcus, Nufar; Hanna, Suhair; Stepensky, Polina; Toker, Ori; Dalal, Ilan; Etzioni, Amos; Almashanu, Shlomo; Somech, Raz

2017-01-01

Severe combined immunodeficiency (SCID), the most severe form of T cell immunodeficiency, is detectable through quantification of T cell receptor excision circles (TRECs) in dried blood spots obtained at birth. Herein, we describe the results of the first year of the Israeli SCID newborn screening (NBS) program. This important, life-saving screening test is available at no cost for every newborn in Israel. Eight SCID patients were diagnosed through the NBS program in its first year, revealing an incidence of 1:22,500 births in the Israeli population. Consanguine marriages and Muslim ethnic origin were found to be a risk factor in affected newborns, and a founder effect was detected for both IL7Rα and DCLRE1C deficiency SCID. Lymphocyte subset analysis and TREC quantification in the peripheral blood appear to be sufficient for confirmation of typical and leaky SCID and ruling out false positive (FP) results. Detection of secondary targets (infants with non-SCID lymphopenia) did not significantly affect the management or outcomes of these infants in our cohort. In the general, non-immunodeficient population, TREC rises along with gestational age and birth weight, and is significantly higher in females and the firstborn of twin pairs. Low TREC correlates with both gestational age and birth weight in extremely premature newborns. Additionally, the rate of TREC increase per week consistently accelerates with gestational age. Together, these findings mandate a lower cutoff or a more lenient screening algorithm for extremely premature infants, in order to reduce the high rate of FPs within this group. A significant surge in TREC values was observed between 28 and 30 weeks of gestation, where median TREC copy numbers rise by 50% over 2 weeks. These findings suggest a maturational step in T cell development around week 29 gestation, and imply moderate to late preterms should be screened with the same cutoff as term infants. The SCID NBS program is still in its infancy, but is already bearing fruit in the early detection and improved outcomes of children with SCID in Israel and other countries.

What follows newborn screening? An evaluation of a residential education program for parents of infants with newly diagnosed cystic fibrosis.

PubMed

Sawyer, Susan M; Glazner, Judith A

2004-08-01

The diagnosis of a severe life-limiting condition, such as cystic fibrosis (CF), is generally followed by assessment and treatment of the child and education and counseling for parents. The introduction of newborn screening for CF provides an opportunity for standardized assessment and education. The aim of this study was to evaluate a 5-day residential assessment and education program for parents of infants who receive a diagnosis of CF after newborn screening. Eligible parents had a 6- to 30-month-old infant with CF diagnosed by newborn screening. Parents were interviewed by telephone using a structured questionnaire that addressed 3 main themes: 1) initial communication of the diagnosis of CF, 2) the perceived value of the 5-day assessment and education program, and 3) the perceived advantages and disadvantages of the residential component (Care-By-Parent unit) of the program. Fifteen of 17 eligible families took part in the 5-day assessment and education program, 12 of whom used the residential Care-By-Parent unit. At the end of the program, parents believed that they had the knowledge and skills required to manage their child's CF at home. One hundred percent endorsed the timing of the assessment and education program immediately after the child's diagnosis and would recommend it to other families in the same situation. Perceived advantages of the residential program were not having to travel (89%), being able to concentrate on CF (50%), and the benefit of a "home base" at the hospital (39%). Twenty-two percent reported that financial costs related to participation (paternal time off work) were a disadvantage, 17% reported additional strain on family members caring for siblings, and 17% mentioned lack of comfort within the unit. This time-intensive residential program was evaluated positively by parents of children with newly diagnosed CF. It provides a model for education programs after the diagnosis of CF by newborn screening, as well as for other pediatric conditions that require intensive parent education.

Evidence for a Right-Ear Advantage in Newborn Hearing Screening Results.

PubMed

Ari-Even Roth, Daphne; Hildesheimer, Minka; Roziner, Ilan; Henkin, Yael

2016-12-06

The aim of the present study was to investigate the effect of ear asymmetry, order of testing, and gender on transient-evoked otoacoustic emission (TEOAE) pass rates and response levels in newborn hearing screening. The screening results of 879 newborns, of whom 387 (study group) passed screening successfully in only one ear in the first TEOAE screening, but passed screening successfully in both ears thereafter, and 492 (control group) who passed screening successfully in both ears in the first TEOAE, were retrospectively examined for pass rates and TEOAE characteristics. Results indicated a right-ear advantage, as manifested by significantly higher pass rates in the right ear (61% and 39% for right and left ears, respectively) in the study group, and in 1.75 dB greater TEOAE response amplitudes in the control group. The right-ear advantage was enhanced when the first tested ear was the right ear (76%). When the left ear was tested first, pass rates were comparable in both ears. The right-ear advantage in pass rates was similar in females versus males, but manifested in 1.5 dB higher response amplitudes in females compared with males, regardless of the tested ear and order of testing in both study and control groups. The study provides further evidence for the functional lateralization of the auditory system at the cochlear level already apparent soon after birth in both males and females. While order of testing plays a significant role in the asymmetry in pass rates, the innate right-ear advantage seems to be a more dominant contributor. © The Author(s) 2016.

Evidence for a Right-Ear Advantage in Newborn Hearing Screening Results

PubMed Central

Hildesheimer, Minka; Roziner, Ilan; Henkin, Yael

2016-01-01

The aim of the present study was to investigate the effect of ear asymmetry, order of testing, and gender on transient-evoked otoacoustic emission (TEOAE) pass rates and response levels in newborn hearing screening. The screening results of 879 newborns, of whom 387 (study group) passed screening successfully in only one ear in the first TEOAE screening, but passed screening successfully in both ears thereafter, and 492 (control group) who passed screening successfully in both ears in the first TEOAE, were retrospectively examined for pass rates and TEOAE characteristics. Results indicated a right-ear advantage, as manifested by significantly higher pass rates in the right ear (61% and 39% for right and left ears, respectively) in the study group, and in 1.75 dB greater TEOAE response amplitudes in the control group. The right-ear advantage was enhanced when the first tested ear was the right ear (76%). When the left ear was tested first, pass rates were comparable in both ears. The right-ear advantage in pass rates was similar in females versus males, but manifested in 1.5 dB higher response amplitudes in females compared with males, regardless of the tested ear and order of testing in both study and control groups. The study provides further evidence for the functional lateralization of the auditory system at the cochlear level already apparent soon after birth in both males and females. While order of testing plays a significant role in the asymmetry in pass rates, the innate right-ear advantage seems to be a more dominant contributor. PMID:27927982

Evaluating the diagnostic gap: statewide incidence of undiagnosed critical congenital heart disease before newborn screening with pulse oximetry.

PubMed

Mouledoux, Jessica H; Walsh, William F

2013-10-01

Screening for critical congenital heart disease (CCHD) using pulse oximetry has been endorsed by the American Academy of Pediatrics and the American Heart Association. We sought to determine the incidence of undetected CCHD in Tennessee and the diagnostic gap of CCHD in Middle Tennessee prior to screening implementation. The Tennessee Initiative for Perinatal Quality Care (TIPQC) Undetected CCHD Registry is a quality improvement initiative established to identify neonates discharged from the nursery with undetected CCHD. The TIPQC database was queried and a simultaneous review of all neonates with CCHD in the Middle Tennessee region was performed to define the incidence and identify the pre-screen diagnostic gap of undetected CCHD at the time of hospital discharge. In 2011, of 79,462 live births in Tennessee, 12 newborns had undiagnosed CCHD (incidence 15 per 100,000; 95 % CI 9-26 per 100,000). Nine of 12 (75 %) had coarctation of the aorta (CoA). There were no deaths due to undiagnosed CCHD. In the Middle Tennessee region, 6 of 45 neonates with CCHD were missed, for a diagnostic gap of 13 % (95 % CI 6-26 %). Prior to implementation of CCHD screening using pulse oximetry, 12 Tennessee neonates with CCHD were missed by prenatal ultrasound and newborn examination. CoA was the most common lesion missed and is also the CCHD most likely to be missed despite addition of screening using pulse oximetry. Continued evaluation of the diagnostic gap with particular attention to missed diagnoses of CoA should accompany institution of CCHD screening programs.

Population screening for genetic disorders in the 21st century: evidence, economics, and ethics.

PubMed

Grosse, S D; Rogowski, W H; Ross, L F; Cornel, M C; Dondorp, W J; Khoury, M J

2010-01-01

Proposals for population screening for genetic diseases require careful scrutiny by decision makers because of the potential for harms and the need to demonstrate benefits commensurate with the opportunity cost of resources expended. We review current evidence-based processes used in the United States, the United Kingdom, and the Netherlands to assess genetic screening programs, including newborn screening programs, carrier screening, and organized cascade testing of relatives of patients with genetic syndromes. In particular, we address critical evidentiary, economic, and ethical issues that arise in the appraisal of screening tests offered to the population. Specific case studies include newborn screening for congenital adrenal hyperplasia and cystic fibrosis and adult screening for hereditary hemochromatosis. Organizations and countries often reach different conclusions about the suitability of screening tests for implementation on a population basis. Deciding when and how to introduce pilot screening programs is challenging. In certain cases, e.g., hereditary hemochromatosis, a consensus does not support general screening although cascade screening may be cost-effective. Genetic screening policies have often been determined by technological capability, advocacy, and medical opinion rather than through a rigorous evidence-based review process. Decision making should take into account principles of ethics and opportunity costs. Copyright 2009 S. Karger AG, Basel.

Incidence of congenital hypothyroidism in China: data from the national newborn screening program, 2013-2015.

PubMed

Deng, Kui; He, Chunhua; Zhu, Jun; Liang, Juan; Li, Xiaohong; Xie, Xiaoyan; Yu, Ping; Li, Nana; Li, Qi; Wang, Yanping

2018-06-27

Congenital hypothyroidism (CH) is one of the most frequent, preventable causes of mental retardation. Little has been reported on the epidemiological characteristics of CH in China. We aimed to estimate the incidence of CH in China and investigate its geographical variation. We analyzed data from the nationwide newborn screening program for CH between 2013 and 2015. Poisson regression was used to generate the odds ratios (ORs) and 95% confidence intervals (CIs) between the rates of CH and selected demographic characteristics and assess the potential association between CH incidence and geographical locations. A total of 18,666 patients with CH were identified from 45.2 million newborns, yielding an overall incidence rate of 4.13 per 10,000 live births. Compared with those in the remote area, regardless of infant sex, a higher incidence risk for CH was present in newborns in coastal areas and inland areas (females: OR=2.00, 95% CI: 1.86-2.16 and OR=1.74, 95% CI: 1.61-1.87, respectively; males: OR=1.70, 95% CI: 1.59-1.83 and OR=1.52, 95% CI: 1.42-1.63, respectively). Additionally, the highest risk of CH for thyroid-stimulating hormone (TSH) screening values <40 mU/L was observed among neonates in the coastal areas, while TSH screening values of 70-100 mU/L were observed among those in the inland areas. The overall incidence of CH is high in China. The significant geographical variations of CH incidence are presented in this study.

Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?†

PubMed Central

Cannon, Michael J.; Griffiths, Paul D.; Aston, Van; Rawlinson, William D.

2015-01-01

SUMMARY Congenital CMV infection is a leading cause of childhood disability. Many children born with congenital CMV infection are asymptomatic or have nonspecific symptoms and therefore are typically not diagnosed. A strategy of newborn CMV screening could allow for early detection and intervention to improve clinical outcomes. Interventions might include antiviral drugs or nonpharmaceutical therapies such as speech-language therapy or cochlear implants. Using published data from developed countries, we analyzed existing evidence of potential benefit that could result from newborn CMV screening. We first estimated the numbers of children with the most important CMV-related disabilities (i.e. hearing loss, cognitive deficit, and vision impairment), including the age at which the disabilities occur. Then, for each of the disabilities, we examined the existing evidence for the effectiveness of various interventions. We concluded that there is good evidence of potential benefit from nonpharmaceutical interventions for children with delayed hearing loss that occurs by 9 months of age. Similarly, we concluded that there is fair evidence of potential benefit from antiviral therapy for children with hearing loss at birth and from nonpharmaceutical interventions for children with delayed hearing loss occurring between 9 and 24 months of age and for children with CMV-related cognitive deficits. We found poor evidence of potential benefit for children with delayed hearing loss occurring after 24 months of age and for children with vision impairment. Overall, we estimated that in the United States, several thousand children with congenital CMV could benefit each year from newborn CMV screening, early detection, and interventions. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24760655

The Role of Information Provision in Economic Evaluations of Newborn Bloodspot Screening: A Systematic Review.

PubMed

Wright, Stuart J; Jones, Cheryl; Payne, Katherine; Dharni, Nimarta; Ulph, Fiona

2015-12-01

The extent to which economic evaluations have included the healthcare resource and outcome-related implications of information provision in national newborn bloodspot screening programmes (NBSPs) is not currently known. To identify if, and how, information provision has been incorporated into published economic evaluations of NBSPs. A systematic review of economic evaluations of NBSPs (up to November 2014) was conducted. Three electronic databases were searched (Ovid: Medline, Embase, CINAHL) using an electronic search strategy combining a published economic search filter with terms related to national NBSPs and screening-related technologies. These electronic searches were supplemented by searching the NHS Economic Evaluations Database (NHS EED) and hand-searching identified study reference lists. The results were tabulated and summarised as part of a narrative synthesis. A total of 27 economic evaluations [screening-related technologies (n = 11) and NBSPs (n = 16)] were identified. The majority of economic evaluations did not quantify the impact of information provision in terms of healthcare costs or outcomes. Five studies did include an estimate of the time cost associated with information provision. Four studies included a value to reflect the disutility associated with parental anxiety caused by false-positive results, which was used as a proxy for the impact of imperfect information. A limited evidence base currently quantifies the impact of information provision on the healthcare costs and impact on the users of NBSPs; the parents of newborns. We suggest that economic evaluations of expanded NBSPs need to take account of information provision otherwise the impact on healthcare costs and the outcomes for newborns and their parents may be underestimated.

Living with an inborn error of metabolism detected by newborn screening-parents' perspectives on child development and impact on family life.

PubMed

Gramer, Gwendolyn; Haege, Gisela; Glahn, Esther M; Hoffmann, Georg F; Lindner, Martin; Burgard, Peter

2014-03-01

Newborn screening for inborn errors of metabolism is regarded as highly successful by health professionals. Little is known about parents' perspectives on child development and social impact on families. Parents of 187 patients with metabolic disorders detected by newborn screening rated child development, perceived burdens on child and family, and future expectations on a questionnaire with standardized answers. Parental ratings were compared with standardized psychometric test results. Regression analysis was performed to identify factors associated with extent of perceived burden. In 26.2% of patients, parents perceived delays in global development and/or specific developmental domains (physical, social, intellectual, language). Parents expected normal future development in 95.7%, and an independent adult life for their child in 94.6%. Comparison with psychometric test results showed that parents of children with cognitive impairments tended to overrate their child's abilities. Mild/medium burden posed on the family (child) by the metabolic disorder was stated by 56.1% (48.9%) of parents, severe/very severe burden by 19.3% (8.6%). One third of families reported financial burden due to the metabolic disorder. Dietary treatment and diagnoses with risk for metabolic decompensation despite treatment were associated with higher perceived burden for the family. Disorders rated as potentially very burdensome by experts were not rated accordingly by parents, demonstrating different perspectives of professionals and parents. Although newborn screening leads to favourable physical and cognitive outcome, living with a metabolic disorder may cause considerable stress on patients and families, emphasizing the need for comprehensive multidisciplinary care including psychological and social support.

Assessment of parental understanding by pediatric residents during counseling after newborn genetic screening.

PubMed

Farrell, Michael H; Kuruvilla, Pramita

2008-03-01

To investigate pediatric residents' efforts to assess understanding in discussions about positive newborn screening test results. Newborn screening saves lives, but confusion about false-positive and carrier results often leads to psychosocial problems. Explicit-criteria abstraction of transcripts of encounters with standardized parents of a fictitious infant found to carry cystic fibrosis or sickle cell hemoglobinopathy. Simulated doctor-patient encounter. Pediatric residents participating in an educational workshop on how to inform parents about positive newborn screening test results. Abstraction used an explicit-criteria data dictionary with definitions for 5 different ways to assess understanding. A "partial" designation was used for leading syntax or no pause for response. Interabstractor reliability over 59 transcripts (2 per resident) was kappa = 0.93. Only 26 of 59 transcripts (44.1%) met definite criteria for at least 1 assessment of understanding. Most assessments were the less effective close-ended (37.3% of transcripts) and "OK?" question types (32.2% of transcripts). Only 3 transcripts met definite criteria for an open-ended assessment and no transcripts included a request for a teach-back, the type thought to be most effective. Four transcripts (6.8%) included an advance request for questions. With partial-criteria assessments included, an additional 31 transcripts (52%) were identified. The small number of assessments of understanding and the high fraction of less effective assessments do not bode well for parental understanding, especially for parents with limited health literacy. Training programs should address assessments of understanding, but quality improvement activities using these types of assessment methods may also be needed.

High-throughput multiplexed T-cell-receptor excision circle quantitative PCR assay with internal controls for detection of severe combined immunodeficiency in population-based newborn screening.

PubMed

Gerstel-Thompson, Jacalyn L; Wilkey, Jonathan F; Baptiste, Jennifer C; Navas, Jennifer S; Pai, Sung-Yun; Pass, Kenneth A; Eaton, Roger B; Comeau, Anne Marie

2010-09-01

Real-time quantitative PCR (qPCR) targeting a specific marker of functional T cells, the T-cell-receptor excision circle (TREC), detects the absence of functional T cells and has a demonstrated clinical validity for detecting severe combined immunodeficiency (SCID) in infants. There is need for a qPCR TREC assay with an internal control to monitor DNA quality and the relative cellular content of the particular dried blood spot punch sampled in each reaction. The utility of the qPCR TREC assay would also be far improved if more tests could be performed on the same newborn screening sample. We approached the multiplexing of qPCR for TREC by attenuating the reaction for the reference gene, with focus on maintaining tight quality assurance for reproducible slopes and for prevention of sample-to-sample cross contamination. Statewide newborn screening for SCID using the multiplexed assay was implemented, and quality-assurance data were recorded. The multiplex qPCR TREC assay showed nearly 100% amplification efficiency for each of the TREC and reference sequences, clinical validity for multiple forms of SCID, and an analytic limit of detection consistent with prevention of contamination. The eluate and residual ghost from a 3.2-mm dried blood spot could be used as source material for multiplexed immunoassays and multiplexed DNA tests (Multiplex Plus), with no disruption to the multiplex TREC qPCR. Population-based SCID newborn screening programs should consider multiplexing for quality assurance purposes. Potential benefits of using Multiplex Plus include the ability to perform multianalyte profiling.

[Perinatal factors affecting the detection of otoacoustic emissions in vaginally delivered, healthy newborns, during the first 48 hours of life].

PubMed

Sequi-Canet, José M; Sala-Langa, María J; Collar Del Castillo, José I

2014-01-01

Most hospitals perform neonatal hearing screening because it is a very useful procedure. Otoacoustic emissions are an ideal technique for this screening. We analyse the possible influence on screening results of some perinatal factors. We collected retrospective data from 8,239 healthy newborns delivered vaginally at the maternity ward of our hospital. We compared multiple perinatal factors vs the results of otoacoustic emissions performed within the first 48 h of life, before discharge. A total of 6.4% of newborns had an abnormal response and failed the screening. Univariate and multivariate analysis showed a significant (P<.0001) positive relationship between breastfeeding and normal otoacoustic emissions (OR: 0.65). Another, less significant factor was female gender. The remaining variables, including origin, education or employment status of the mother, maternal smoking, dystocic delivery, presentation, need for resuscitation, preterm labour (34-36 weeks), weight, length and frequent maternal pathology, such as streptococcus detection, hypothyroidism, hypertension or diabetes, were not significant. Breastfeeding was the most important factor related to a normal response in otoacoustic emissions. It may improve final results and reduce the number of neonates who need to be rescheduled for a repeated test, as well as the associated anxiety and the possibility of losing patients during follow-up. These are major problems in neonatal hearing screening. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Screening for cystic fibrosis in New York State: considerations for algorithm improvements.

PubMed

Kay, Denise M; Maloney, Breanne; Hamel, Rhonda; Pearce, Melissa; DeMartino, Lenore; McMahon, Rebecca; McGrath, Emily; Krein, Lea; Vogel, Beth; Saavedra-Matiz, Carlos A; Caggana, Michele; Tavakoli, Norma P

2016-02-01

Newborn screening for cystic fibrosis (CF), a chronic progressive disease affecting mucus viscosity, has been beneficial in both improving life expectancy and the quality of life for individuals with CF. In New York State from 2007 to 2012 screening for CF involved measuring immunoreactive trypsinogen (IRT) levels in dried blood spots from newborns using the IMMUCHEM(™) Blood Spot Trypsin-MW ELISA kit. Any specimen in the top 5% IRT level underwent DNA analysis using the InPlex(®) CF Molecular Test. Of the 1.48 million newborns screened during the 6-year time period, 7631 babies were referred for follow-up. CF was confirmed in 251 cases, and 94 cases were diagnosed with CF transmembrane conductance regulated-related metabolic syndrome or possible CF. Nine reports of false negatives were made to the program. Variation in daily average IRT was observed depending on the season (4-6 ng/ml) and kit lot (<3 ng/ml), supporting the use of a floating cutoff. The screening method had a sensitivity of 96.5%, specificity of 99.6%, positive predictive value of 4.5%, and negative predictive value of 99.5%. Considerations for CF screening algorithms should include IRT variations resulting from age at specimen collection, sex, race/ethnicity, season, and manufacturer kit lots. Measuring IRT level in dried blood spots is the first-tier screen for CF. Current algorithms for CF screening lead to substantial false-positive referral rates. IRT values were affected by age of infant when specimen is collected, race/ethnicity and sex of infant, and changes in seasons and manufacturer kit lots The prevalence of CF in NYS is 1 in 4200 with the highest prevalence in White infants (1 in 2600) and the lowest in Black infants (1 in 15,400).

Development of a Bile Acid-Based Newborn Screen for Niemann-Pick C Disease

PubMed Central

Jiang, Xuntian; Sidhu, Rohini; Mydock, 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.

2017-01-01

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, both of 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

A patient with an inborn error of vitamin B12 metabolism (cblF) detected by newborn screening.

PubMed

Armour, Christine M; Brebner, Alison; Watkins, David; Geraghty, Michael T; Chan, Alicia; Rosenblatt, David S

2013-07-01

A neonate, who was found to have an elevated C3/C2 ratio and minimally elevated propionylcarnitine on newborn screening, was subsequently identified as having the rare cblF inborn error of vitamin B12 (cobalamin) metabolism. This disorder is characterized by the retention of unmetabolized cobalamin in lysosomes such that it is not readily available for cellular metabolism. Although cultured fibroblasts from the patient did not show the expected functional abnormalities of the cobalamin-dependent enzymes, methylmalonyl-CoA mutase and methionine synthase, they did show reduced synthesis of the active cobalamin cofactors adenosylcobalamin and methylcobalamin. Mutation analysis of LMBRD1 established that the patient had the cblF disorder. Treatment was initiated promptly, and the patient showed a robust response to regular injections of cyanocobalamin, and she was later switched to hydroxocobalamin. Currently, at 3 years of age, the child is clinically well, with appropriate development. Adjusted newborn screening cutoffs in Ontario allowed detection of a deficiency that might not have otherwise been identified, allowing early treatment and perhaps preventing the adverse sequelae seen in some untreated patients.

Economic evaluation of Chagas disease screening in Spain.

PubMed

Imaz-Iglesia, Iñaki; Miguel, Lucía García-San; Ayala-Morillas, L Eduardo; García-Pérez, Lidia; González-Enríquez, Jesús; Blasco-Hernández, Teresa; Martín-Águeda, María Belén; Sarría-Santamera, Antonio

2015-08-01

Although Spain is the European country with the highest Chagas disease burden, the country does not have a national control program of the disease. The purpose of this study is to evaluate the efficiency of several strategies for Chagas disease screening among Latin American residents living in Spain. The following screening strategies were evaluated: (1) non-screening; (2) screening of the Latin American pregnant women and their newborns; (3) screening also the relatives of the positive pregnant women; (4) screening also the relatives of the negative pregnant women. A cost-utility analysis was carried out to compare the four strategies from two perspectives, the societal and the Spanish National Health System (SNHS). A decision tree representing the clinical evolution of Chagas disease throughout patient's life was built. The strategies were compared through the incremental cost-utility ratio, using euros as cost measurement and quality-adjusted life years as utility measurement. A sensitivity analysis was performed to test the model parameters and their influence on the results. We found the "Non-screening" as the most expensive and less effective of the evaluated strategies, from both the societal and the SNHS perspectives. Among the screening evaluated strategies the most efficient was, from both perspectives, to extent the antenatal screening of the Latin American pregnant women and their newborns up to the relatives of the positive women. Several parameters influenced significantly on the sensitivity analyses, particularly the chronic treatment efficacy or the prevalence of Chagas disease. In conclusion, for the general Latin American immigrants living in Spain the most efficient would be to screen the Latin American mothers, their newborns and the close relatives of the mothers with a positive serology. However for higher prevalence immigrant population the most efficient intervention would be to extend the program to the close relatives of the negative mothers. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening for Hypoglycemia in Exclusively Breastfed High-risk Neonates.

PubMed

Singh, Princy; Upadhyay, Amit; Sreenivas, Vishnubhatla; Jaiswal, Vijay; Saxena, Pranjali

2017-06-15

To determine incidence of hypoglycemia in exclusively breastfed, high-risk but healthy newborns, and risk factors for its development. This observational study enrolled 407 exclusively breastfed high-risk (low birth weight newborns (1800-2499 g), late preterms, small-for-gestation, large-for-gestation and infant of diabetic mother), who did not require admission to neonatal intensive care unit and were kept in postnatal wards with mother. Hypoglycemia was defined as blood glucose £46 mg/dL (2.6 mmol/L). Blood glucose was monitored till 48 hours of life. 27% of the screened newborns developed hypoglycemia in first 48 hours. 31 (7.6%) developed recurrent (>2) episodes, 28 (6.8%) had moderate (<37mg/dL) while 8 (1.9%) developed symptomatic hypoglycemia. With increase in birthweight, risk of hypoglycemia reduced significantly (P=0.003). Hypoglycemia was observed more frequently in first 2 hours as compared to next 48 hours (P=0.0001). Low birth- weight, preterm gestation and male gender was significantly associated with increased risk of hypoglycemia. Healthy, high-risk exclusively breastfed newborns in postnatal wards need close monitoring for hypoglycemia in first 24 hrs of life.

Diagnostic problems in cystic fibrosis - specific characteristics of a group of infants and young children diagnosed positive through neonatal screening, in whom cystic fibrosis had not been diagnosed.

PubMed

Woś, Halina; Sankiewicz-Szkółka, Magda; Więcek, Sabina; Kordys-Darmolińska, Bożena; Grzybowska-Chlebowczyk, Urszula; Kniażewska, Maria

2015-01-01

Neonatal cystic fibrosis screening contributes to an early diagnosis of cystic fibrosis and to implementing appropriate therapeutic management. Long-standing screening tests have made it possible to identify a group of newborns in whom the diagnosis was ambiguous and required further specialised tests. The aim is to present cases of patients with a positive result of newborn screening for cystic fibrosis who were found to be carriers of the mutation in both alleles, however the lack of clinical symptoms and correct sweat testing values did not lead doctors to diagnosing cystic fibrosis and by the same token implementing the treatment. The analysis encompassed a group of 22 infants and children 3 months to 3 years of age, in whom, in spite of a positive result of newborn screening for cystic fibrosis and the presence of 2 mutations in the CFTR gene, the diagnosis of cystic fibrosis was not made, and appropriate treatment was not administered because of diagnostic doubts (due to correct concentration of chlorides in sweat, correct IRT level and lack of clinical signs of cystic fibrosis). The control group consisted of 55 children treated in our centre, in whom neonatal screening for cystic fibrosis was positive and the diagnosis was confirmed by genetic testing, sweat chloride testing and IRT concentration. There were no differences in birth body weight between the groups. The differences in chlorideion levels in sweat secretion tests and mean IRT values were statistically significant and were: 97.5 for the control group and 26.4 for the test group. At the present time there are no clinical symptoms to give a diagnosis of cystic fibrosis and start treatment in the test group. Newborn screening contributes not only to an early diagnosis of cystic fibrosis but also to CFTR-related metabolic syndromes (CRMS), which is a phenomenon requiring further observation. This fact constitutes a definite psychological problem for the parents of these patients. .

Cystic fibrosis newborn screening programs: implications of the CFTR variant spectrum in nonwhite patients.

PubMed

Pique, Lynn; Graham, Steve; Pearl, Michelle; Kharrazi, Martin; Schrijver, Iris

2017-01-01

Cystic fibrosis newborn screening (CFNBS) has been offered across the United States since 2010. However, as compared with white patients with CF, CFTR variant identification in nonwhite populations remains inequitable. Utilizing the recent characterization of the nonwhite CF variant spectrum, we examined the effectiveness of current CFNBS molecular panels in identifying affected nonwhite newborns. Based on a cross-sectional evaluation of genotyping data from the CF Foundation Patient Registry that compared 3,496 nonwhite with 22,206 white CF patients, the current CFNBS algorithms used in the 50 states and the District of Columbia were analyzed. We assessed the percentage of CF patients of Hispanic, African, Asian, and Native American heritage who would not be identified by the molecular panels most commonly used. Compared with whites, variant detection was significantly lower in Hispanic, black, and Asian newborns (P ≤ 0.0001 each), as well as in Native American newborns (P values ranged from 0.001 to 0.0003), for the most common CFNBS panels. This study provides a perspective on the applicability of current panels to a diverse population and enables CFNBS programs to consider more inclusive test approaches to facilitate diagnosis, timely clinical intervention, and enhanced prognosis for CF patients of nonwhite and mixed ethnicities.Genet Med 19 1, 36-44.

Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platform.

PubMed

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

2013-09-23

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. 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). 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. 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 3h. Copyright © 2013 Elsevier B.V. All rights reserved.

Utility of genetic testing for the detection of late-onset hearing loss in neonates.

PubMed

Lim, B Gail; Clark, Reese H; Kelleher, Amy S; Lin, Zhili; Spitzer, Alan R

2013-12-01

The purpose of this study was to demonstrate the utility of molecular testing in the detection of potentially important causes of delayed hearing loss missed by current audiometric screening at birth. We enrolled infants who had received a newborn audiometric hearing screen and a filter paper blood collection for state newborn screening. A central laboratory ran the SoundGene® panel. Of 3,681 infants studied, 35 (0.95%) had a positive SoundGene panel, 16 had mitochondrial mutations, 9 had Pendred mutations, 5 were cytomegalovirus (CMV) DNA positive, 2 had connexin mutations, and 3 had a combination of different mutations. Infants with an abnormal SoundGene panel were at increased risk for hearing loss compared to neonates without mutations. Three (8.6%) of the 35 subjects had persistent hearing loss compared to 5 (0.21%) of 2,398 subjects with no report of mutation (p < .01). Of 3,681 infants studied, 8 (0.22%) had persistent hearing loss: 5 (62.5%) had abnormal newborn audiometric screens, 2 (25%) had an abnormal SoundGene panel (1 was CMV positive, 1 had a mitochondrial mutation), and 1 (12.5%) had no identifiable risk factors. A positive SoundGene panel identifies infants who are not identified by audiometric testing and may be at risk for hearing loss.

Implementation of the first worldwide quality assurance program for cystic fibrosis multiple mutation detection in population-based screening.

PubMed

Earley, Marie C; Laxova, Anita; Farrell, Philip M; Driscoll-Dunn, Rena; Cordovado, Suzanne; Mogayzel, Peter J; Konstan, Michael W; Hannon, W Harry

2011-07-15

CDC's Newborn Screening Quality Assurance Program collaborated with several U.S. Cystic Fibrosis Care Centers to collect specimens for development of a molecular CFTR proficiency testing program using dried-blood spots for newborn screening laboratories. Adult and adolescent patients or carriers donated whole blood that was aliquoted onto filter paper cards. Five blind-coded specimens were sent to participating newborn screening laboratories quarterly. Proficiency testing results were evaluated based on presumptive clinical assessment. Individual evaluations and summary reports were sent to each participating laboratory and technical consultations were offered if incorrect assessments were reported. The current CDC repository contains specimens with 39 different CFTR mutations. Up to 45 laboratories have participated in the program. Three years of data showed that correct assessments were reported 97.7% of the time overall when both mutations could be determined. Incorrect assessments that could have lead to a missed case occurred 0.9% of the time, and no information was reported 1.1% of the time due to sample failure. Results show that laboratories using molecular assays to detect CFTR mutations are performing satisfactorily. The programmatic results presented demonstrate the importance and complexity of providing proficiency testing for DNA-based assays. Published by Elsevier B.V.

Pilot proficiency testing study for second tier congenital adrenal hyperplasia newborn screening.

PubMed

De Jesús, Víctor R; Simms, David A; Schiffer, Jarad; Kennedy, Meredith; Mei, Joanne V; Hannon, W Harry

2010-11-11

Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroid biosynthesis. The Newborn Screening Quality Assurance Program (NSQAP) initiated a pilot, dried-blood spot (DBS)-based proficiency testing program designed to investigate materials and laboratory performance for second tier CAH screening by tandem mass spectrometry (MS/MS). The ratio of 17-α-hydroxyprogesterone (17-OHP), androstenedione (4-AD) and cortisol is used as an indicator of CAH in laboratory protocols for second tier analysis of DBS specimens. DBS prepared by NSQAP contained a range of steroid concentrations resulting in different clinical ratios. Laboratories received blind-coded DBS specimens and reported results to NSQAP for evaluation. Quantitative values reported by participants for 17-OHP, 4-AD, and cortisol, reflected small differences in their analytical methods. Average quantitative values for 17-OHP increased from 81% to 107% recovery over the 3.5-year period; cortisol recoveries increased from 61.9% to 89.5%; and 4-AD recoveries decreased from 184% to 68%. Laboratory participation in the CAH second tier proficiency testing program has resulted in improved analyte recoveries and enhanced sample preparation methodologies. NSQAP services for the second tier CAH analysis in DBS demonstrate the need for surveillance to ensure harmonization and continuous improvements, and to achieve sustained high-performance of newborn screening laboratories worldwide. Published by Elsevier B.V.

Can formalizing links among community health workers, accredited drug dispensing outlet dispensers, and health facility staff increase their collaboration to improve prompt access to maternal and child care? A qualitative study in Tanzania.

PubMed

Dillip, Angel; Kimatta, Suleiman; Embrey, Martha; Chalker, John C; Valimba, Richard; Malliwah, Mariam; Meena, John; Lieber, Rachel; Johnson, Keith

2017-06-19

In Tanzania, progress toward achieving the 2015 Millennium Development Goals for maternal and newborn health was slow. An intervention brought together community health workers, health facility staff, and accredited drug dispensing outlet (ADDO) dispensers to improve maternal and newborn health through a mechanism of collaboration and referral. This study explored barriers, successes, and promising approaches to increasing timely access to care by linking the three levels of health care provision. The study was conducted in the Kibaha district, where we applied qualitative approaches with in-depth interviews and focus group discussions. In-depth interview participants included retail drug shop dispensers (36), community health workers (45), and health facility staff members (15). We conducted one focus group discussion with district officials and four with mothers of newborns and children under 5 years old. Relationships among the three levels of care improved after the linkage intervention, especially for ADDO dispensers and health facility staff who previously had no formal communication pathway. The study participants perceptions of success included improved knowledge of case management and relationships among the three levels of care, more timely access to care, increased numbers of patients/customers, more meetings between community health workers and health facility staff, and a decrease in child and maternal mortality. Reported challenges included stock-outs of medicines at the health facility, participating ADDO dispensers who left to work in other regions, documentation of referrals, and lack of treatment available at health facilities on the weekend. The primary issue that threatens the sustainability of the intervention is that local council health management team members, who are responsible for facilitating the linkage, had not made any supervision visits and were therefore unaware of how the program was running. The study highlights the benefits of approaches that link different levels of care providers to improve access to maternal and child health care. To strengthen this collaboration further, health campaign platforms should include retail drug dispensers as a type of community health care provider. To increase linkage sustainability, the council health management team needs to develop feasible supervision plans.

Infants and Toddlers (Ages 0-3) - Raising Healthy Children

MedlinePlus

... Washing Hearing Screening Infant & Toddler Health Infant & Toddler Nutrition Maternal and Infant Health Newborn Screening Parenting Tips Perchlorate in Baby Formula Special Needs Families Test Your Knowledge about Kids’ Health Tips for Calming a Crying ...

Newborn screening for metabolic disorders: parental perceptions of the initial communication of results.

PubMed

Buchbinder, Mara; Timmermans, Stefan

2012-08-01

Positive newborn screening (NBS) results cause significant parental distress, but little is known about how parents find out about children's screening results and what they are told. This qualitative, exploratory study reports on parents' perceptions of the initial communication of NBS results. Participants included the parents of 75 infants referred to a metabolic clinic in California over a 3-year period (2007-2010). Parents provided information about the initial communication of NBS results during audiotaped clinical encounters and open-ended interviews. Transcripts were analyzed inductively using thematic coding. Responses fell into 3 primary themes: sources of news delivery, providing information, and mitigation strategies. The findings suggest that health care providers have access to a range of communicative resources to buffer the impact of positive screening results that may be mobilized in future interventions. Recommendations for improving the communication process and future research directions are discussed.

Newborn Screening Guidelines for Congenital Hypothyroidism in India: Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) - Part I: Screening and Confirmation of Diagnosis.

PubMed

Desai, M P; Sharma, R; Riaz, I; Sudhanshu, S; Parikh, R; Bhatia, V

2018-06-01

The Indian Society for Pediatric and Adolescent Endocrinology has formulated locally relevant Clinical Practice Guidelines for newborn screening, diagnosis and management of primary congenital hypothyroidism (CH). Screening should be done for every newborn using cord blood, or postnatal blood, ideally at 48 to 72 h of age. On this screen sample, neonates with TSH > 20 mIU/L serum units (or >34 mIU/L for samples taken between 24 to 48 h of age) should be recalled for confirmation. For screen TSH > 40 mIU/L, immediate confirmatory venous T4/FT4 and TSH, and for milder elevation of screen TSH, a second screening TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight infants should undergo screening at 48-72 h postnatal age. Sick babies should be screened at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10 mIU/L after age 2 wk, with low T4 (<10 μg/dL) or FT4 (<1.17 ng/dL) indicate primary CH and treatment initiation. Imaging is recommended by radionuclide scintigraphy and ultrasonography after CH is biochemically confirmed but treatment should not be delayed till scans are performed. Levothyroxine is commenced at 10 to 15 μg/kg in the neonatal period. Serum T4/FT4 is measured at 2 wk and TSH and T4/FT4 at 1 mo, then 2 monthly till 6 mo, 3 monthly from 6 mo-3 y and every 3-6 mo thereafter. Babies with the possibility of transient congenital hypothyroidism should be re-evaluated at age 3 y, to assess the need for lifelong therapy.

CLINICAL FOLLOW-UP FOR DUCHENNE MUSCULAR DYSTROPHY NEWBORN SCREENING: A PROPOSAL

PubMed Central

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.

2017-01-01

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. PMID:27170260

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. © 2016 Wiley Periodicals, Inc.

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. © The Author(s) 2015.

Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran.

PubMed

Nourizadeh, Maryam; Shakerian, Leila; Borte, Stephan; Fazlollahi, Mohammadreza; Badalzadeh, Mohsen; Houshmand, Massoud; Alizadeh, Zahra; Dalili, Hossein; Rashidi-Nezhad, Ali; Kazemnejad, Anoshirvan; Moin, Mostafa; Hammarström, Lennart; Pourpak, Zahra

2018-06-26

T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs) are recently used for detection of T or B cell lymphopenia in neonates based on region-specific cutoff levels. Here, we report cutoffs for TREC and KREC copies useful for newborn screening and/or diagnosis of primary immunodeficiency diseases (PID) in Iran. DNA was extracted from a single 3.2 mm punch of dried blood spots collected from 2160 anonymized newborns referred to two major referral health centers between 2014 and 2016. For refinement of the cutoffs, 51 patients with a definite diagnosis of severe combined immunodeficiency, X-linked agammaglobulinaemia and combined immunodeficiency, including ataxia telangiectasia, human phosphoglucomutase 3 and Janus kinase-3 deficiency, as well as 47 healthy controls were included. Samples from patients with an X-linked hyper-IgM-syndrome, Wiskott-Aldrich syndrome and DNA ligase 4 deficiency were considered as disease controls. Triplex-quantitative real-time PCR was used. Cutoffs were calculated as TRECs < 11 and KRECs < 6 copies with an ACTB > 700 copies with sensitivity of 100% for TREC and 97% for KREC. Among thirty anonymized newborn samples (1.5%) with abnormal results for TREC and/or KREC, only twenty one available cases were retested and shown to be in the normal range except for three samples (0.15%). All of the patients with a definitive diagnosis were correctly identified based on our established TREC/KREC copy numbers. Determining cutoffs for TREC/KREC is essential for correctly identifying children with PID in newborn screening. Early diagnosis of PID patients enables appropriate measures and therapies like stem cell transplantation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

77 FR 22791 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... connection with the development of newborn screening activities, technologies, policies, guidelines and... this as part of the online registration process by 5 p.m. EDT, Tuesday, May 15, 2012 at http://altarum... will be limited to five to ten minutes depending on the number of presenters. Oral comments will be...

PHENYLKETONURIA, DETECTION IN THE NEWBORN INFANT AS A ROUTINE HOSPITAL PROCEDURE.

ERIC Educational Resources Information Center

GUTHRIE, ROBERT; WHITNEY, STEWART

A FIELD TRIAL OF AN INHIBITION ASSAY METHOD FOR SCREENING FOR PHENYLKETONURIA (PKU) TESTED MORE THAN 400,000 NEWBORN INFANTS PRIOR TO DISCHARGE FROM THE HOSPTIAL. IN ALL, 39 CASES WERE FOUND, A HIGHER INCIDENCE THAN HAD PREVIOUSLY BEEN EXPECTED. THE PRACTICALITY OF THE INHIBITION ASSAY METHOD WAS ALSO DEMONSTRATED. THE REPORT DETAILS THE TRIAL'S…

[Incidence of hypoacusia secondary to hyperbilirubinaemia in a universal neonatal auditory screening programme based on otoacoustic emissions and evoked auditory potentials].

PubMed

Núñez-Batalla, Faustino; Carro-Fernández, Pilar; Antuña-León, María Eva; González-Trelles, Teresa

2008-03-01

Hyperbilirubinaemia is a neonatal risk factor that has been proved to be associated with sensorineural hearing loss. A high concentration of unconjugated bilirubin place newborn children at risk of suffering toxic effects, including hypoacusia. Review of the newborn screening results with a diagnosis of pathological hyperbilirubinaemia as part of a hearing-loss early detection protocol in the general population based on otoemissions and evoked potentials. Retrospective study of 21 590 newborn children screened between 2002 and 2006. The selection criteria for defining pathological hyperbilirubinaemia were bilirubin concentrations in excess of 14 mg/dL in pre-term infants and 20 mg/dL in full-term babies. The Universal Neonatal Hearing Screening Programme is a two-phase protocol in which all children are initially subjected to a transient otoacoustic emissions test (TOAE). Children presenting risk factors associated with auditory neuropathy were always given brainstem auditory evoked potentials (BAEP). The patients identified as having severe hyperbilirubinaemia in the neonatal period numbered 109 (0.5 %) and 96 of these (88.07 %) passed the otoacoustic emissions test at the first attempt and 13 (11.93 %) did not; 11 of the 13 children in whom the otoacoustic emissions test was repeated passed it successfully. The 2 children who failed to pass the otoacoustic emissions test has normal BAEP results; 3 (2.75 %) of the newborn infants who passed the TOAE test did not pass the BAEP. Hyperbilirubinaemia values previously considered safe may harm the hearing system and give rise to isolated problems in auditory processing without being associated with other signs of classical kernicterus. Our results show that hyperbilirubinaemia-related auditory neuropathy reveals changes over time in the audiometric outcomes.

Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

PubMed

Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

2017-01-01

Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

Newborn screening for isovaleric acidemia using tandem mass spectrometry: data from 1.6 million newborns.

PubMed

Ensenauer, Regina; Fingerhut, Ralph; Maier, Esther M; Polanetz, Roman; Olgemöller, Bernhard; Röschinger, Wulf; Muntau, Ania C

2011-04-01

Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) has been used in the Bavarian newborn screening (NBS) program since 1999. The use of ESI-MS/MS has led to the inclusion of isovaleric acidemia (IVA) into NBS. We retrospectively evaluated data on more than 1.6 million newborns screened during 9.5 years. Acylcarnitines from whole blood spotted on filter paper were converted to their corresponding butyl esters, and the samples were analyzed by use of ESI-MS/MS with stable isotope labeled internal standards. A total of 24 individuals with IVA were detected by use of a multiparametric threshold criteria panel including isovalerylcarnitine (C5) and the ratios of C5 to octanoyl-, butyryl-, and propionylcarnitine. A cutoff set at the 99.99th percentile for isolated C5 or at the 99th percentile for C5 plus at least 2 ratios resulted in a positive predictive value for IVA screening of 7.0% and an overall recall rate of 0.024%. Adjusted reference ranges for age and birth weight were applied, and the incidence of IVA in the study population was calculated to be 1 in 67,000. Missed cases were not brought to our attention. IVA was also detectable in cord blood and early postnatal blood samples. IVA can be reliably detected in NBS through acylcarnitine analysis in dried blood spots by using multiparametric threshold criteria. Further improvement (positive predictive value 13.0%, recall rate 0.01%) can be achieved by using more stringent recall criteria. In view of the potentially life-threatening natural course of IVA in early life, presymptomatic diagnosis may thus prevent mortality and morbidity.

Efficacy of Distortion Product Oto-Acoustic Emission (OAE)/Auditory Brainstem Evoked Response (ABR) Protocols in Universal Neonatal Hearing Screening and Detecting Hearing Loss in Children <2 Years of Age.

PubMed

Mishra, Girish; Sharma, Yojana; Mehta, Kanishk; Patel, Gunjan

2013-04-01

Deafness is commonest curable childhood handicap. Most remedies and programmes don't address this issue at childhood level leading to detrimental impact on development of newborns. Aims and objectives are (A) screen all newborns for deafness and detect prevalence of deafness in children less than 2 years of age. and (B) assess efficacy of multi-staged OAE/ABR protocol for hearing screening. Non-randomized, prospective study from August 2008 to August 2011. All infants underwent a series of oto-acoustic emission (OAE) and final confirmatory auditory brainstem evoked response (ABR) audiometry. Finally, out of 1,101 children, 1,069 children passed the test while 12 children had impaired hearing after final testing, confirmed by ABR. Positive predictive value of OAE after multiple test increased to 100 %. OAE-ABR test series is effective in screening neonates and multiple tests reduce economic burden. High risk screening will miss nearly 50 % deaf children, thus universal screening is indispensable in picking early deafness.

An analysis of hearing screening test results in 2291 premature infants of Chinese population.

PubMed

Huang, Lili; Xiong, Fei; Li, Jinrong; Yang, Fan

2017-04-01

The aim of this study was to analyze the hearing screening program among preterm infants as well as to identify risk factors associated with failing primary newborn hearing screening. The retrospectively selected population included all preterm infants who had primary hearing screening in a neonatal ward from January 1st, 2013 to December 31st, 2015 at West China Second University Hospital, Sichuan University. The newborn hearing screening (NHS) procedure was performed in all preterm infants by automated auditory brainstem response (AABR). Infants who failed the primary hearing screening received a second screening at 42 days after birth. Infants who failed both tests were referred to a tertiary audiology center for diagnostic confirmation and management before 6 months of age. The final diagnosis for referred infants was obtained by telephone follow-up. The risk factors associated with failure to pass the primary hearing screen were evaluated and analyzed for preterm infants. Among 2291 preterm infants recruited, 155 infants (6.8%) failed the primary hearing screening with an abnormal AABR. Of these 155 infants, 113 (72.9%) passed the secondary screening. At the end of the follow-up, 1 infant (0.04%) was diagnosed with hearing loss, 3 infants had delayed language development, and 40 infants were lost to follow up. Multivariate regression analysis revealed that gestational age ≤32 weeks (Odds ratio [OR] = 2.093, 95% confidence interval [CI] 1.370-3.196), super hyperbilirubinemia (≥25 mg/dl) (OR = 3.560, 95% CI 1.009-12.560), and respiratory failure (OR = 1.971, 95% CI 1.188-3.265) were associated with failure to pass newborn hearing screening. The prevalence of failure to pass primary hearing screening among preterm infants was 6.8% in our study, and we found a relatively low prevalence of hearing loss (0.04%). Super hyperbilirubinemia, gestational age ≤32weeks, and respiratory failure were risk factors associated with failure of preterm infants to pass the primary hearing screening. Our results suggest that preterm infants with hyperbilirubinemia, gestational age ≤32 weeks, and respiratory failure should be closely followed. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Sichuan, China.

PubMed

Zhang, Jing; Cui, Yali; Wang, Xia; Li, Yingying; Jiang, Dongmei; Dai, Wei; Jiang, Yongmei

2018-03-01

Our goals were to screen newborns and characterize the occurrence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southwestern China. Meanwhile, we would like to analyze the factors that might affect the results of neonatal dried blood spots for glucose-6-phosphate dehydrogenase screening test, to improve the clinical quality control level, effectively reduce the external factors in the process of detection. This study involved an evaluation of G6PD data for 20,644 newborns from a universal newborn screening program. Heel prick blood specimens were collected around 72 hours after birth and were dried on filter papers. For G6PD deficiency the fluorescent spot test was employed. We studied the association between incidence of G6PD deficiency and influence factors. This study involved an evaluation of G6PD data for 20,644 neonatal heel prick blood samples from 10,984 males and 9,660 females. There were 503 positive results for G6PD deficiency (299 males and 204 females), and the G6PD deficiency-positive rate was estimated to be around 2.4%. The gender-specific prevalence for males was 2.7%, and for females 2.1%. Multiple factors may influence the result of the G6PD test, such as season, temperature, and specimen of indwelling time. This study analyzed the prevalence of G6PD deficiency in Sichuan, China. Accelerating the speed of sample delivery and ensuring availability of screening results can aid the screening and diagnosis.

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 population served. PMID:25066104

Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-Year Results of the Newborn Eye Screen Test Study.

PubMed

Callaway, Natalia F; Ludwig, Cassie A; Blumenkranz, Mark S; Jones, Jennifer Michelle; Fredrick, Douglas R; Moshfeghi, Darius M

2016-05-01

To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth. Prospective cohort study at Stanford University School of Medicine. All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded. Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist. Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events. The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant. Fundus hemorrhages are common among newborns. They often involve multiple areas and layers of the retina. Vaginal delivery was associated with a significantly increased risk of FH, whereas self-identified Hispanic or Latino ethnicity was protective against FH in this study. The long-term consequences of FH on visual development remain unknown. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Newborn Screening Guidelines for Congenital Hypothyroidism in India: Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) - Part II: Imaging, Treatment and Follow-up.

PubMed

Sudhanshu, S; Riaz, I; Sharma, R; Desai, M P; Parikh, R; Bhatia, V

2018-06-01

The Indian Society for Pediatric and Adolescent Endocrinology has formulated Clinical Practice Guidelines for newborn screening, diagnosis and management of congenital hypothyroidism (CH). This manuscript, part II addresses management and follow-up. Screening should be done for every newborn using cord blood, or postnatal blood ideally at 48 to 72 h of age. Neonates with screen TSH > 20 mIU/L serum units (or >34 mIU/L for samples taken between 24 and 48 h of age) should be recalled for confirmation. For screen TSH > 40 mIU/L, immediate confirmatory venous T4/FT4 and TSH, and for mildly elevated screen TSH, a second screening TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight infants should undergo screening at 48-72 h age. Sick babies should be screened at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10 mIU/L after age 2 wk, with low T4 (<10 μg/dL) or FT4 (<1.17 ng/dL) indicate primary CH and treatment initiation. Imaging is recommended by radionuclide scintigraphy and ultrasonography after CH is biochemically confirmed but treatment should not be delayed till scans are performed. Levothyroxine is commenced at 10-15 μg/kg in the neonatal period. Serum T4/FT4 is measured at 2 wk and TSH and T4/FT4 at 1 mo, then 2 monthly till 6 mo, 3 monthly from 6 mo-3 y and every 3-6 mo thereafter. Babies with the possibility of transient CH should be re-evaluated at age 3 y, to assess the need for lifelong therapy.

[Evaluations of newborn screening program performance and enzymatic diagnosis of glucose-6-phosphate dehydrogenase deficiency in Guangzhou].

PubMed

Tang, F; Huang, Y L; Jiang, X; Jia, X F; Li, B; Feng, Y; Chen, Q Y; Tang, C F

2018-05-02

Objective: To reveal the molecular epidemiologic characteristics of glucose-6-phosphate dehydrogenase (G6PD) gene and to evaluate based on the genetic analysis the newborn screening program performance and enzymatic diagnosis of G6PD deficiency in Guangzhou. Methods: G6PD enzyme activities were measured by quantitative fluorescence assay in dry blood spots of 16 319 newborns(8 725 males, 7 594 females) 3-7 days after birth in Guangzhou Newborn Center. They were born in Guangzhou form Oct. 1 to 20, 2016. The cutoff value of G6PD was less than 2.6 U/g Hb in dry blood spots. G6PD deficiency was diagnosed when G6PD<1 700 U/L or G6PD/6PGD<1 in red blood cells. Genetic analysis of G6PD gene was performed on the dry blood spot samples of 823 newborns (including positive 346, negative 477)with various levels of G6PD enzyme activities through fluorescence PCR melting curve analysis(FMCA) to detect 15 kinds of mutations reported to be common among Chinese.G6PD gene Sanger sequency was performed in seven highly suspicious patients with negative results by FMCA. Results: (1) Using the cutoff value of G6PD< 2.6 U/g Hb , a total of 687(4.2%) newborns showed positive screening results, including 560 (6.4%) males and 127(1.7%) females. (2) Among the newborns with positive screening results, 214 males and 122 females were randomly chosen for G6PD gene analysis. The results showed that 197 (92.1%) males were hemizygote and 108(88.6%) females were mutation carriers with one to four alleles. Among the newborns with negative screening results, 41 males with G6PD 2.6-2.8 U/g Hb and 436 females with G6PD 2.6-4.5 U/g Hb were chosen for genetic analysis.Mutations were detected in 5(12.2%)boys, and 226(51.8%) girls were carriers.G6PD gene Sanger sequency of seven highly suspicious patients showed that c.406C>T, c.551C>T, c.835A>T hemizygote were found in 3 male's samples, respectively. (3) The estimated prevalence of harboring mutation was 6.0% in males and 13.5% in females according to rates of mutation in samples with various levels of G6PD enzyme activities. Six common mutations were c.1388G>A、c.1376G>T, c.95A> G, c.871G>A, c.1024C>T, c.392G>T, accounting for 95.5% of detected alleles .(4) based on results of G6PD gene analysis, the newborn scereening of G6PD deficiency with cutoff value G6PD<2.6 U/g Hb yielded a positive predict value(PPV) of 93.5%, a false-positive rate of 0.5%, and a sensitivity of 99.0% for males. A PPV of 88.5%, a false-positive rate of 0.2% . The prevalence of severe type G6PD deficiency in females was about 1.5%. Compared with to genetic analysis, the sensitivity and PPV of G6PD activity assay in red blood cells were 95.5%, 97.2%, respectively. Conclusions: The prevalence of G6PD deficiency in males was 6.0% in Guangzhou. Six mutations c.1388G>A, c.1376G>T, c.95A>G, c.871G>A, c.1024C>T, c.392G>T accounted for 95.5%. The cutoff value of G6PD<2.6 U/g Hb innewborn screening program and the criteria of biochemical diagnosis could accurately identify G6PD deficiency . Combined with biochemical and molecular analysis will improve the accuracy of diagnosis of G6PD deficiency and detect more heterozygous females.

Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

PubMed

Bateman, J B; Kojis, T L; Cantor, R M; Heinzmann, C; Ngo, J T; Spence, M A; Inana, G; Kivlin, J D; Curtis, D; Sparkes, R S

1993-01-01

Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns.

Socio-demographic determinants of hearing impairment studied in 103,835 term babies.

PubMed

Van Kerschaver, Erwin; Boudewyns, An N; Declau, Frank; Van de Heyning, Paul H; Wuyts, Floris L

2013-02-01

Serious hearing problems appear in approximately one in 1000 newborns. In 2000, the Joint Committee on Infant Hearing defined a list of risk factors for neonatal hearing impairment relating to health, physical characteristics and family history. The aim of this study is to determine which personal, environmental and social factors are associated with the prevalence of congenital hearing impairment (CHI). The entire population of 103,835 term newborns in Flanders, Belgium, was tested by a universal neonatal hearing screening (UNHS) programme using automated auditory brainstem responses (AABR). In the case of a positive result, a CHI diagnosis was verified in specialized referral centres. Socio-demographic risk factors were investigated across the entire population to study any relationship with CHI. The prevalence of bilateral CHI of 35 dB nHL (normal hearing level) or more was 0.87/1000 newborns. The sensitivity and specificity of the screening test were 94.02 and 99.96%, respectively. The socio-demographic factors of gender, birth order, birth length, feeding type, level of education and origin of the mother were found to be independent predictors of CHI. The socio-demographic factors found to be associated with CHI extend the list of classic risk factors as defined by the American Academy of Pediatrics (AAP). Assessment of these additional factors may alert the treating physician to the increased risk of newborn hearing impairment and urge the need for accurate follow-up. Moreover, this extended assessment may improve decision making in medical practice and screening policy.

Newborn screening for cystic fibrosis - The parent perspective.

PubMed

Rueegg, Corina S; Barben, Jürg; Hafen, Gaudenz M; Moeller, Alexander; Jurca, Maja; Fingerhut, Ralph; Kuehni, Claudia E

2016-07-01

Newborn screening for CF started 01/2011 in Switzerland. We investigated the parents' opinions about the information received, their feelings, and overall approval of the screening. This is a prospective questionnaire survey of all parents of positively screened children. Parents were phoned by CF-centres and invited for diagnostic investigations. They completed a questionnaire after the visit to the CF-centre. From 2011-2013, 246 families received the questionnaire and 138 (56%) replied. Of these 77 (60%) found the information received at birth satisfactory; 124 (91%) found the information provided in the CF-centre satisfactory. Most parents (n=98, 78%) felt troubled or anxious when the CF-centre called, 51 (38%) remained anxious after the visit. Most parents (n=122; 88%) were satisfied with the screening, 4 (3%) were not, and 12 (9%) were unsure. The smooth organisation of the screening process, with personal information by a CF specialist and short delays between this information and the final diagnostic testing, might have contributed to reduce anxiety among parents. Most families were grateful that their child had been screened, and are happy with the process. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Potential Uses and Inherent Challenges of Using Genome-Scale Sequencing to Augment Current Newborn Screening.

PubMed

Berg, Jonathan S; Powell, Cynthia M

2015-10-05

Since newborn screening (NBS) began in the 1960s, technological advances have enabled its expansion to include an increasing number of disorders. Recent developments now make it possible to sequence an infant's genome relatively quickly and economically. Clinical application of whole-exome and whole-genome sequencing is expanding at a rapid pace but presents many challenges. Its utility in NBS has yet to be demonstrated and its application in the pediatric population requires examination, not only for potential clinical benefits, but also for the unique ethical challenges it presents. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Genetics Evaluation Guidelines for the Etiologic Diagnosis of Congenital Hearing Loss

PubMed Central

2002-01-01

The advent of hearing screening in newborns in many states has led to an increase in the use of genetic testing and related genetic services in the follow-up of infants with hearing loss. A significant proportion of those with congenital hearing loss have genetic etiologies underlying their hearing loss. To ensure that those identified with congenital hearing loss receive the genetic services appropriate to their conditions, the Maternal and Child Health Bureau of the Health Resources and Services Administration funded the American College of Medical Genetics to convene an expert panel to develop guidelines for the genetic evaluation of congential hearing loss. After a brief overview of the current knowledge of hearing loss, newborn screening, and newborn hearing screening, we provide an overview of genetic services and a guideline that describes how best to ensure that patients receive appropriate genetic services. The significant contribution of genetic factors to these conditions combined with the rapid evolution of knowledge about the genetics of these conditions overlaid with the inherently multidisciplinary nature of genetic services provides an example of a condition for which a well-integrated multidisciplinary approach to care is clearly needed. PMID:12180152

Newborn screening: an appeal for improved parent education.

PubMed

Tluczek, Audrey; Orland, Kate Murphy; Nick, Sara Wolfgram; Brown, Roger L

2009-01-01

The purpose of this study, which was part of a larger investigation of newborn screening (NBS) for cystic fibrosis (CF), was to learn how parents were informed about NBS and obtain their suggestions for improving the process of educating parents about NBS. Qualitative study using directed and summative content analyses was conducted on 100 interviews with 193 parents of 100 newborns recruited from 4 clinical populations including parents of infants with (1) a CF diagnosis, (2) one CF mutation and therefore CF carriers, (3) congenital hypothyroidism, and (4) normal screening results. Parents described much inconsistency in the timing of and methods used to inform them about NBS. Mothers with higher income were 3.69 times more likely to receive information before their infants' births than mothers with lower income. Parents recommended improving verbal and written communication with parents about NBS at multiple junctures from preconception to the infant's first few days of life. Parents suggested that providers take time to explain the purpose and importance of NBS, which diseases are included in testing, and when parents can expect results. These findings suggest a need to establish evidence-based guidelines for informing parents about NBS.

Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning✰

PubMed Central

Therrell, Bradford L.; Lloyd-Puryear, Michele A.; Camp, Kathryn M.; Mann, Marie Y.

2014-01-01

Inborn errors of metabolism (IEM) are genetic disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. In the U.S., many IEM are detected through state newborn screening (NBS) programs. To inform research on IEM and provide necessary resources for researchers, we are providing: tabulation of ten-year state NBS data for selected IEM detected through NBS; costs of medical foods used in the management of IEM; and an assessment of corporate policies regarding provision of nutritional interventions at no or reduced cost to individuals with IEM. The calculated IEM incidences are based on analyses of ten-year data (2001–2011) from the National Newborn Screening Information System (NNSIS). Costs to feed an average person with an IEM were approximated by determining costs to feed an individual with an IEM, minus the annual expenditure for food for an individual without an IEM. Both the incidence and costs of nutritional intervention data will be useful in future research concerning the impact of IEM disorders on families, individuals and society. PMID:25085281

Quantification of sulfatides in dried blood and urine spots from metachromatic leukodystrophy patients by liquid chromatography/electrospray tandem mass spectrometry.

PubMed

Barcenas, Mariana; Suhr, Teryn R; Scott, C Ronald; Turecek, Frantisek; Gelb, Michael H

2014-06-10

Treatments are being developed for metachromatic leukodystrophy (MLD), suggesting the need for eventual newborn screening. Previous studies have shown that sulfatide molecular species are increased in the urine of MLD patients compared to samples from non-MLD individuals, but there is no data using dried blood spots (DBS), the most common sample available for newborn screening laboratories. We used ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) to quantify sulfatides in DBS and dried urine spots from 14 MLD patients and 50 non-MLD individuals. Several sulfatide molecular species were increased in dried urine samples from all MLD samples compared to non-MLD samples. Sulfatides, especially low molecular species, were increased in DBS from MLD patients, but the sulfatide levels were relatively low. There was good separation in sulfatide levels between MLD and non-MLD samples when dried urine spots were used, but not with DBS, because DBS from non-MLD individuals have measurable levels of sulfatides. Sulfatide accumulation studies in urine, but not in DBS, emerges as the method of choice if newborn screening is to be proposed for MLD. Copyright © 2013 Elsevier B.V. All rights reserved.

Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals.

PubMed

Wang, Raymond Y; Bodamer, Olaf A; Watson, Michael S; Wilcox, William R

2011-05-01

To develop educational guidelines for the diagnostic confirmation and management of individuals identified by newborn screening, family-based testing after proband identification, or carrier testing in at-risk populations, and subsequent prenatal or postnatal testing of those who are presymptomatic for a lysosomal storage disease. Review of English language literature and discussions in a consensus development panel comprised an international group of experts in the clinical and laboratory diagnosis, treatment and management, newborn screening, and genetic aspects of lysosomal storage diseases. Although clinical trial and longitudinal data were used when available, the evidence in the literature is limited and consequently the recommendations must be considered as expert opinion. Guidelines were developed for Fabry, Gaucher, and Niemann-Pick A/B diseases, glycogen storage type II (Pompe disease), globoid cell leukodystrophy (Krabbe disease), metachromatic leukodystrophy, and mucopolysaccharidoses types I, II, and VI. These guidelines serve as an educational resource for confirmatory testing and subsequent clinical management of presymptomatic individuals suspected to have a lysosomal storage disease; they also help to define a research agenda for longitudinal studies such as the American College of Medical Genetics/National Institutes of Health Newborn Screening Translational Research Network.

Newborn hearing screening programme in Belgium: a consensus recommendation on risk factors.

PubMed

Vos, Bénédicte; Senterre, Christelle; Lagasse, Raphaël; Levêque, Alain

2015-10-16

Understanding the risk factors for hearing loss is essential for designing the Belgian newborn hearing screening programme. Accordingly, they needed to be updated in accordance with current scientific knowledge. This study aimed to update the recommendations for the clinical management and follow-up of newborns with neonatal risk factors of hearing loss for the newborn screening programme in Belgium. A literature review was performed, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system assessment method was used to determine the level of evidence quality and strength of the recommendation for each risk factor. The state of scientific knowledge, levels of evidence quality, and graded recommendations were subsequently assessed using a three-round Delphi consensus process (two online questionnaires and one face-to-face meeting). Congenital infections (i.e., cytomegalovirus, toxoplasmosis, and syphilis), a family history of hearing loss, consanguinity in (grand)parents, malformation syndromes, and foetal alcohol syndrome presented a 'high' level of evidence quality as neonatal risk factors for hearing loss. Because of the sensitivity of auditory function to bilirubin toxicity, hyperbilirubinaemia was assessed at a 'moderate' level of evidence quality. In contrast, a very low birth weight, low Apgar score, and hospitalisation in the neonatal intensive care unit ranged from 'very low' to 'low' levels, and ototoxic drugs were evidenced as 'very low'. Possible explanations for these 'very low' and 'low' levels include the improved management of these health conditions or treatments, and methodological weaknesses such as confounding effects, which make it difficult to conclude on individual risk factors. In the recommendation statements, the experts emphasised avoiding unidentified neonatal hearing loss and opted to include risk factors for hearing loss even in cases with weak evidence. The panel also highlighted the cumulative effect of risk factors for hearing loss. We revised the recommendations for the clinical management and follow-up of newborns exhibiting neonatal risk factors for hearing loss on the basis of the aforementioned evidence-based approach and clinical experience from experts. The next step is the implementation of these findings in the Belgian screening programme.

Changes in detection of birth defects and perinatal mortality after introduction of prenatal ultrasound screening in the Kola Peninsula (North-West Russia): combination of two birth registries.

PubMed

Postoev, Vitaly A; Grjibovski, Andrej M; Nieboer, Evert; Odland, Jon Øyvind

2015-11-23

Prenatal diagnostics ultrasound was established in Russia in 2000 as a routine method of screening for birth defects. The aims of the current study were twofold: to assess changes in birth defects prevalence at birth and perinatal mortality after ultrasound screening was implemented and to estimate prenatal detection rates for congenital malformations in the city of Monchegorsk (Murmansk County, North-West Russia). The Murmansk County Birth Registry and the Kola Birth Registry were the primary sources of information, and include 30 448 pregnancy outcomes in Monchegorsk for the period 1973-2011. Data from these registries were supplemented with information derived from hospital records about pregnancy terminations for 2000-2007. The total number of newborns with any kind of birth defects in Monchegorsk during 1973-2011 was 1099, of whom 816 were born in the 1973-2000 period. The prevalence of defects at birth increased from 34.2/1000 (95% CI = 31.9-36.5) to 42.8/1000 newborns (95% CI = 38.0-47.7) after prenatal ultrasound screening was formally implemented. We observed significant decreases (p < 0.05) in the birth prevalence of congenital malformations of the circulatory system, the musculoskeletal system (including deformations), and other (excluding multiple); those of the urinary system increased from 0.9/1000 to 17.1/1000 (p < 0.0001). The perinatal mortality among newborns with any kind of malformation decreased from 106.6 per 1000 newborns with birth defects (95% CI = 84.3-129.1) to 21.2 (95 % CI = 4.3-38.1). Mothers who had undergone at least one ultrasound examination during pregnancy (n = 9883) had a decreased risk of having a newborn die during the perinatal period [adjusted OR = 0.49 (95% CI = 0.27-0.89)]. The overall prenatal detection rate was 34.9% with the highest for malformations of the nervous system. Improved detection of severe malformations with subsequent pregnancy termination was likely the main contributor to the observed decrease in perinatal mortality in Murmansk County, Russia.

Association of US State Implementation of Newborn Screening Policies for Critical Congenital Heart Disease With Early Infant Cardiac Deaths.

PubMed

Abouk, Rahi; Grosse, Scott D; Ailes, Elizabeth C; Oster, Matthew E

2017-12-05

In 2011, critical congenital heart disease was added to the US Recommended Uniform Screening Panel for newborns, but whether state implementation of screening policies has been associated with infant death rates is unknown. To assess whether there was an association between implementation of state newborn screening policies for critical congenital heart disease and infant death rates. Observational study with group-level analyses. A difference-in-differences analysis was conducted using the National Center for Health Statistics' period linked birth/infant death data set files for 2007-2013 for 26 546 503 US births through June 30, 2013, aggregated by month and state of birth. State policies were classified as mandatory or nonmandatory (including voluntary policies and mandates that were not yet implemented). As of June 1, 2013, 8 states had implemented mandatory screening policies, 5 states had voluntary screening policies, and 9 states had adopted but not yet implemented mandates. Numbers of early infant deaths (between 24 hours and 6 months of age) coded for critical congenital heart disease or other/unspecified congenital cardiac causes for each state-month birth cohort. Between 2007 and 2013, there were 2734 deaths due to critical congenital heart disease and 3967 deaths due to other/unspecified causes. Critical congenital heart disease death rates in states with mandatory screening policies were 8.0 (95% CI, 5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100 000 births (n = 13) in 2013 (for births by the end of July); for other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per 100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n = 21) in 2013. Early infant deaths from critical congenital heart disease through December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after states implemented mandatory screening compared with prior periods and states without screening policies. Early infant deaths from other/unspecified cardiac causes declined by 21.4% (95% CI, 6.9%-33.7%), with an absolute decline of 3.5 (95% CI, 3.2-3.8) deaths per 100 000 births. No significant decrease was associated with nonmandatory screening policies. Statewide implementation of mandatory policies for newborn screening for critical congenital heart disease was associated with a significant decrease in infant cardiac deaths between 2007 and 2013 compared with states without these policies.

Newborn Screening for Sickle Cell Disease in Liberia: A Pilot Study.

PubMed

Tubman, Venée N; Marshall, Roseda; Jallah, Wilhemina; Guo, Dongjing; Ma, Clement; Ohene-Frempong, Kwaku; London, Wendy B; Heeney, Matthew M

2016-04-01

In malaria-endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta-thalassemia trait were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in country. This pilot study aimed to determine the feasibility of NBS using a South-South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia. This descriptive epidemiologic feasibility study collected dried blood spots from 2,785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care. SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened [1.19% (95% confidence interval [CI]: 0.79-1.59%)] (FS: 28/33, FSB: 2/33, FSA: 2/33, FSX: 1/33). There were no infants with FSC phenotype observed. Nonsickling hemoglobin phenotypes "FC" and "F" were each present in three infants screened. Seventy-six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach. The incidence of SCD and other hemoglobinopathies remains high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta-thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health. © 2016 Wiley Periodicals, Inc.

Newborn Screening for Sickle Cell Disease in Liberia: A Pilot Study

PubMed Central

Tubman, Venée N; Marshall, Roseda; Jallah, Wilhemina; Guo, Dongjing; Ma, Clement; Ohene-Frempong, Kwaku; London, Wendy B; Heeney, Matthew M

2015-01-01

Background In malaria-endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta-thalassemia trait were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in-country. This pilot study aimed to determine the feasibility of NBS using a South-South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia. Procedure This descriptive epidemiologic feasibility study collected dried blood spots from 2785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care. Results SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened [1.19% (95% CI: 0.79%–1.59%)](FS: 28/33, FSB: 2/33, FSA: 2/33, FSX 1/33). There were no infants with FSC phenotype observed. Non-sickling hemoglobin phenotypes ‘FC’ and ‘F’ were each present in 3 infants screened. Seventy-six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach. Conclusions The incidence of SCD and other hemoglobinopathies remain high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta-thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health. PMID:26739520

Cost-Effectiveness/Cost-Benefit Analysis of Newborn Screening for Severe Combined Immune Deficiency in Washington State.

PubMed

Ding, Yao; Thompson, John D; Kobrynski, Lisa; Ojodu, Jelili; Zarbalian, Guisou; Grosse, Scott D

2016-05-01

To evaluate the expected cost-effectiveness and net benefit of the recent implementation of newborn screening (NBS) for severe combined immunodeficiency (SCID) in Washington State. We constructed a decision analysis model to estimate the costs and benefits of NBS in an annual birth cohort of 86 600 infants based on projections of avoided infant deaths. Point estimates and ranges for input variables, including the birth prevalence of SCID, proportion detected asymptomatically without screening through family history, screening test characteristics, survival rates, and costs of screening, diagnosis, and treatment were derived from published estimates, expert opinion, and the Washington NBS program. We estimated treatment costs stratified by age of identification and SCID type (with or without adenosine deaminase deficiency). Economic benefit was estimated using values of $4.2 and $9.0 million per death averted. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost-effectiveness ratio (ICER) of net direct cost per life-year saved. Our model predicts an additional 1.19 newborn infants with SCID detected preclinically through screening, in addition to those who would have been detected early through family history, and 0.40 deaths averted annually. Our base-case model suggests an ICER of $35 311 per life-year saved, and a benefit-cost ratio of either 5.31 or 2.71. Sensitivity analyses found ICER values <$100 000 and positive net benefit for plausible assumptions on all variables. Our model suggests that NBS for SCID in Washington is likely to be cost-effective and to show positive net economic benefit. Published by Elsevier Inc.

Reliability and Validity of a Smartphone-Paired Pulse Oximeter for Screening of Critical Congenital Heart Defects in Newborns.

PubMed

Huizing, Maurice J; Villamor-Martínez, Eduardo; Chavagne, Ingrid A; Vanagt, Ward Y; Spaanderman, Marc A E; Villamor, Eduardo

2017-01-01

Barriers to widespread implementation of pulse oximetry screening of critical congenital heart defects (CCHD) in newborns include increasing trends of out-of-hospital births and cost of equipment. In recent years, smartphone-compatible pulse oximeters have appeared on the market, but the validity of such devices in the setting of CCHD screening has not been evaluated. To compare the performance in CCHD screening of a smartphone-paired pulse oximeter (Masimo iSpO2-Rx™) and a hospital-grade pulse oximeter (Masimo Radical-7™). Preductal (right hand) and postductal (either foot) saturations were determined in a population of 201 term newborns by 2 independent teams, one using the Radical-7 and the other using the iSpO2-Rx. Bland-Altman analysis was applied to calculate mean bias and 95% limits of agreement between the 2 pulse oximeters. For the preductal oxygen saturation, the mean bias (Radical-7 minus iSpO2-Rx) was -0.08 (SD 1.76) and the lower and upper limits of agreement were -3.52 and 3.36, respectively. For the postductal oxygen saturation, the mean bias was -0.11 (SD 1.68) and the lower and upper limits of agreement were -3.49 and 3.18, respectively. In addition, the iSpO2-Rx provided reliable measurements of saturations below 95% in a group of 12 infants admitted to the neonatal intensive care unit. Our data suggest that CCHD screening with the Masimo iSpO2-Rx is feasible and accurate. The use of reliable smartphone-paired pulse oximeters may contribute to the extension of CCHD screening to home births and low resource settings. © 2017 S. Karger AG, Basel.

Cost and Cost-Effectiveness Assessments of Newborn Screening for Critical Congenital Heart Disease Using Pulse Oximetry: A Review.

PubMed

Grosse, Scott D; Peterson, Cora; Abouk, Rahi; Glidewell, Jill; Oster, Matthew E

2017-01-01

Screening newborns for critical congenital heart disease (CCHD) using pulse oximetry is recommended to allow for the prompt diagnosis and prevention of life-threatening crises. The present review summarizes and critiques six previously published estimates of the costs or cost-effectiveness of CCHD screening from the United Kingdom, United States, and China. Several elements that affect CCHD screening costs were assessed in varying numbers of studies, including screening staff time, instrumentation, and consumables, as well as costs of diagnosis and treatment. A previous US study that used conservative assumptions suggested that CCHD screening is likely to be considered cost-effective from the healthcare sector perspective. Newly available estimates of avoided infant CCHD deaths in several US states that implemented mandatory CCHD screening policies during 2011-2013 suggest a substantially larger reduction in deaths than was projected in the previous US cost-effectiveness analysis. Taking into account these new estimates, we estimate that cost per life-year gained could be as low as USD 12,000. However, that estimate does not take into account future costs of health care and education for surviving children with CCHD nor the costs incurred by health departments to support and monitor CCHD screening policies and programs.

Cost and Cost-Effectiveness Assessments of Newborn Screening for Critical Congenital Heart Disease Using Pulse Oximetry: A Review

PubMed Central

Grosse, Scott D.; Peterson, Cora; Abouk, Rahi; Glidewell, Jill; Oster, Matthew E.

2018-01-01

Screening newborns for critical congenital heart disease (CCHD) using pulse oximetry is recommended to allow for the prompt diagnosis and prevention of life-threatening crises. The present review summarizes and critiques six previously published estimates of the costs or cost-effectiveness of CCHD screening from the United Kingdom, United States, and China. Several elements that affect CCHD screening costs were assessed in varying numbers of studies, including screening staff time, instrumentation, and consumables, as well as costs of diagnosis and treatment. A previous US study that used conservative assumptions suggested that CCHD screening is likely to be considered cost-effective from the healthcare sector perspective. Newly available estimates of avoided infant CCHD deaths in several US states that implemented mandatory CCHD screening policies during 2011–2013 suggest a substantially larger reduction in deaths than was projected in the previous US cost-effectiveness analysis. Taking into account these new estimates, we estimate that cost per life-year gained could be as low as USD 12,000. However, that estimate does not take into account future costs of health care and education for surviving children with CCHD nor the costs incurred by health departments to support and monitor CCHD screening policies and programs. PMID:29376140

Brain Ultrasonography Findings in Neonatal Seizure; a Cross-sectional Study.

PubMed

Nabavi, Seyed Saeed; Partovi, Parinaz

2017-01-01

Screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. The present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. The present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. Neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 - 28 day old newborns. 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). Most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. A correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). Based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. Hemorrhage (12%) and hydrocephaly (7%) were the most common findings. The only factor correlating with increased probability of positive findings was the newborns being pre-term.

Prenatal diagnosis of hypoparathyroidism retardation and dysmorphism (HRD) syndrome.

PubMed

Hershkovitz, E; Hershkovitz, R; Hertzug, L; Gorodischer, R; Mazor, M; Parvari, R

2000-06-01

We used linkage analysis for prenatal diagnosis of the recently reported hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome. Five cases from four families were evaluated. Three fetuses were carriers and were born healthy. Two fetuses were affected but the parents decided not to terminate the pregnancies. The diagnosis of HRD syndrome was confirmed in these newborns. This is the first report about prenatal diagnosis of HRD syndrome. Copyright 2000 John Wiley & Sons, Ltd.

Parent Experience With False-Positive Newborn Screening Results for Cystic Fibrosis.

PubMed

Hayeems, Robin Z; Miller, Fiona A; Barg, Carolyn J; Bombard, Yvonne; Kerr, Elizabeth; Tam, Karen; Carroll, June C; Potter, Beth K; Chakraborty, Pranesh; Davies, Christine; Milburn, Jennifer; Patton, Sarah; Bytautas, Jessica P; Taylor, Louise; Price, April; Gonska, Tanja; Keenan, Katherine; Ratjen, Felix; Guttmann, Astrid

2016-09-01

The risk of psychosocial harm in families of infants with false-positive (FP) newborn bloodspot screening (NBS) results for cystic fibrosis (CF) is a longstanding concern. Whether well designed retrieval and confirmatory testing systems can mitigate risks remains unknown. Using a mixed-methods cohort design, we obtained prospective self-report data from mothers of infants with FP CF NBS results 2 to 3 months after confirmatory testing at Ontario's largest follow-up center, and from a randomly selected control sample of mothers of screen negative infants from the same region. Mothers completed a questionnaire assessing experience and psychosocial response. A sample of mothers of FP infants completed qualitative interviews. One hundred thirty-four mothers of FP infants (response rate, 55%) and 411 controls (response rate, 47%) completed questionnaires; 54 mothers of FP infants were interviewed. Selected psychosocial response measures did not detect psychosocial distress in newborns or 1 year later (P > .05). Mothers recalled distress during notification of the positive result and in the follow-up testing period related to fear of chronic illness, but valued the screening system of care in mitigating concerns. Although immediate distress was reported among mothers of FP infants, selected psychometric tools did not detect these concerns. The NBS center from which mothers were recruited minimizes delay between notification and confirmatory testing and ensures trained professionals are communicating results and facilitating follow-up. These factors may explain the presence of minimal psychosocial burden. The screening system reflected herein may be a model for NBS programs working to minimize FP-related psychosocial harm. Copyright © 2016 by the American Academy of Pediatrics.

Assessing the Fragile X Syndrome Newborn Screening Landscape.

PubMed

Riley, Catharine; Wheeler, Anne

2017-06-01

Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life. Copyright © 2017 by the American Academy of Pediatrics.

Drug Development Pipeline

MedlinePlus

... Care Guidelines Newborn Screening Clinical Care Guidelines Sweat Test Clinical Care Guidelines Infection Prevention and Control Care Guidelines Allergic Bronchopulmonary Aspergillosis Clinical Care Guidelines ...

Cohort study on maternal cytomegalovirus seroprevalence and prevalence and clinical manifestations of congenital infection in China

PubMed Central

Wang, Shiwen; Wang, Tongzhan; Zhang, Wenqiang; Liu, Xiaolin; Wang, Xiaofang; Wang, Haiyan; He, Xiaozhou; Zhang, Shunxian; Xu, Shuhui; Yu, Yang; Jia, Xingbing; Wang, Maolin; Xu, Aiqiang; Ma, Wei; Amin, Minal M.; Bialek, Stephanie R.; Dollard, Sheila C.; Wang, Chengbin

2017-01-01

Abstract Congenital cytomegalovirus (CMV) infection is the leading viral cause of birth defects and developmental disabilities in developed countries. However, CMV seroprevalence and burden of congenital CMV infection are not well defined in China. Cohort of newborns from 5 birthing hospitals in 2 counties of Shandong Province, China, were enrolled from March 2011 to August 2013. Dried blood spots (DBS) and saliva were collected within 4 days after birth for IgG testing for maternal seroprevalence and real-time PCR testing for congenital CMV infection, respectively. Among 5020 newborns tested for CMV IgG, 4827 were seropositive, resulting in CMV maternal seroprevalence of 96.2% (95% confidence interval [CI]:95.6%–96.7%). Of the 10,933 newborns screened for congenital CMV infection, 75 had CMV detected, resulting in an overall prevalence of 0.7% (95% CI: 0.5%–0.9%), with prevalences of 0.4% (14/3995), 0.6% (66/10,857), and 0.7% (52/7761) for DBS, wet saliva, and dried saliva specimens screened, respectively. Prevalence of congenital CMV infection decreased with increasing maternal age (0.9%, 0.6%, and 0.3% among newborns delivered from mothers aged 16–25, 26–35, and >35 years, respectively; P = 0.03), and was higher among preterm infants than full term infants (1.3% vs 0.6%, P = 0.04), infants with intrauterine growth restriction (IUGR) than those without (1.8% vs 0.7%, P = 0.03), and twins or triplets than singleton pregnancies (2.8% vs 0.7%, P = 0.04). None of the 75 newborns exhibited symptomatic congenital CMV infection, and there was no difference in clinical characteristics and newborn hearing screening results between infants with and without congenital CMV infection at birth. Congenital CMV infection prevalence was lower and the clinical manifestations were milder in this relatively developed region of China compared to populations from other countries with similarly high maternal seroprevalence. Follow-up on children with congenital CMV infection will clarify the burden of disabilities from congenital CMV infection in China. PMID:28151899

Newborn Screening for Krabbe’s Disease

PubMed Central

Orsini, Joseph J.; Saavedra-Matiz, Carlos A.; Gelb, Michael H.; Caggana, Michele

2017-01-01

Live newborn screening for Krabbe’s disease (KD) was initiated in New York on August 7, 2006, and started in Missouri in August, 2012. As of August 7, 2015, nearly 2.5 million infants had been screened, and 443 (0.018%) infants had been referred for followup clinical evaluation; only five infants had been determined to have KD. As of August, 2015, the combined incidence of infantile KD in New York and Missouri is ~1 per 500,000; however, patients who develop later-onset forms of KD may still emerge. This Review provides an overview of the processes used to develop the screening and followup algorithms. It also includes updated results from screening and discussion of observations, lessons learned, and suggested areas for improvement that will reduce referral rates and the number of infants defined as at risk for later-onset forms of KD. Although current treatment options for infants with early-infantile Krabbe’s disease are not curative, over time treatment options should improve; in the meantime, it is essential to evaluate the lessons learned and to ensure that screening is completed in the best possible manner until these improvements can be realized. PMID:27638592

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis.

PubMed

Hayeems, Robin Z; Miller, Fiona A; Barg, Carolyn J; Bombard, Yvonne; Carroll, June C; Tam, Karen; Kerr, Elizabeth; Chakraborty, Pranesh; Potter, Beth K; Patton, Sarah; Bytautas, Jessica P; Taylor, Louise; Davies, Christine; Milburn, Jennifer; Price, April; Gonska, Tanja; Keenan, Katherine; Ratjen, Felix; Guttmann, Astrid

2017-05-01

To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P < .006) but no differences in anxiety or vulnerability (P > .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome Sequencing Technologies and Nursing: What Are the Roles of Nurses and Nurse Scientists?

PubMed

Taylor, Jacquelyn Y; Wright, Michelle L; Hickey, Kathleen T; Housman, David E

Advances in DNA sequencing technology have resulted in an abundance of personalized data with challenging clinical utility and meaning for clinicians. This wealth of data has potential to dramatically impact the quality of healthcare. Nurses are at the focal point in educating patients regarding relevant healthcare needs; therefore, an understanding of sequencing technology and utilizing these data are critical. The objective of this study was to explicate the role of nurses and nurse scientists as integral members of healthcare teams in improving understanding of DNA sequencing data and translational genomics for patients. A history of the nurse role in newborn screening is used as an exemplar. This study serves as an exemplar on how genome sequencing has been utilized in nursing science and incorporates linkages of other omics approaches used by nurses that are included in this special issue. This special issue showcased nurse scientists conducting multi-omic research from various methods, including targeted candidate genes, pharmacogenomics, proteomics, epigenomics, and the microbiome. From this vantage point, we provide an overview of the roles of nurse scientists in genome sequencing research and provide recommendations for the best utilization of nurses and nurse scientists related to genome sequencing.

Sickle cell in Latin America and the United States [corrected].

PubMed

Huttle, Alexandra; Maestre, Gladys E; Lantigua, Rafael; Green, Nancy S

2015-07-01

Latin Americans are an underappreciated population affected by sickle cell disease (SCD). Sickle trait and SCD exist throughout Latin America and U.S. Latino communities. We describe the epidemiology and genetic heterogeneity of SCD among Latin Americans, and fetal hemoglobin expression. National population-based newborn screening for SCD is limited to Brazil, Costa Rica, and the U.S. Available and extrapolated data suggest that over 6,000 annual births and 100,000-150,000 Latin Americans are affected by SCD. This comprehensive review highlights the substantial numbers and population distribution of SCD and sickle trait in Latin America, and where national newborn screening programs for SCD exist. © 2015 Wiley Periodicals, Inc.

Neonatal carnitine palmitoyltransferase II deficiency associated with Dandy-Walker syndrome and sudden death.

PubMed

Yahyaoui, Raquel; Espinosa, María Gracia; Gómez, Celia; Dayaldasani, Anita; Rueda, Inmaculada; Roldán, Ana; Ugarte, Magdalena; Lastra, Gonzalo; Pérez, Vidal

2011-11-01

Neonatal onset of carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive, often lethal disorder of the mitochondrial beta-oxidation of long-chain fatty acids. It is a rare multiorgan disease which includes hypoketotic hypoglycemia, severe hepatomuscular symptoms, cardiac abnormalities, seizures and lethargy, as well as dysmorphic features. Until now, only 22 affected families have been described in the literature. An increasing number of mutations are being identified in the CPT2 gene, with a distinct genotype-phenotype correlation in most cases. Herein we report a new case of neonatal CPT II deficiency associated with Dandy-Walker syndrome and sudden death at 13 days of life. CPT II deficiency was suggested by acylcarnitine analysis of dried-blood on filter paper in the expanded newborn screening. Genetic analysis of the CPT2 gene identified the presence of a previously described mutation in homozygosity (c.534_558del25bpinsT). All lethal neonatal CPT II deficiency patients previously described presented severe symptoms during the first week of life, although this was not the case in our patient, who remained stable and without apparent vital risk during the first 11 days of life. The introduction of tandem mass spectrometry to newborn screening has substantially improved our ability to detect metabolic diseases in the newborn period. This case illustrates the value of expanded newborn screening in a neonate with an unusual clinical presentation, combining hydrocephalus and sudden death, that might not commonly lead to the suspicion of an inborn error of metabolism. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular diagnosis of cystic fibrosis.

PubMed

Shrimpton, Antony E

2002-05-01

A review of the current molecular diagnosis of cystic fibrosis including an introduction to cystic fibrosis, the gene function, the phenotypic variation, who should be screened for which mutation, newborn and couple screening, quality assurance, phenotype-genotype correlation, methods and method limitations, options, statements, recommendations, useful Websites and treatments.

Expanded newborn screening: social and ethical issues.

PubMed

Dhondt, Jean-Louis

2010-10-01

Newborn screening and genetic testing have expanded rapidly in the last decade with the advent of multiplex (e.g., tandem mass spectrometry) and/or DNA technologies. However, screening panels include a large number of disorders, which may not meet all of the traditional screening criteria, established in late 1960s, and used for years to justify screening programs. After a period of expansion driven by technological advances, many reports have reconsidered the justification of expanded programs. Many factors have contributed to test-panel discrepancies between countries. The test-panel review methodology, the way health benefits are weighed against harms, and the socioeconomic-political environment all play a role. Expansion of screening also requires reconsideration of the infrastructure (ideally, in the context of national plans for rare diseases) to support testing, counselling, education, treatment, and follow-up. Consequently, economic aspects cannot be ignored and can be a limitation for expansion. New ethical questions have emerged: risks of discrimination or stigmatization, respect of the autonomy of persons to make decisions, parental anxiety resulting from a false positive test (especially when reporting to parents screening results for untreatable conditions identified as by-products of screening), etc. For disorders where there is not yet confirmation of benefit, it may be prudent to recommend pilot screening and to have a mechanism that can be used to adapt or even to stop a program.

Positive screening on the Modified Checklist for Autism in Toddlers (M-CHAT) in extremely low gestational age newborns.

PubMed

Kuban, Karl C K; O'Shea, T Michael; Allred, Elizabeth N; Tager-Flusberg, Helen; Goldstein, Donald J; Leviton, Alan

2009-04-01

To test the hypothesis that children born preterm are more likely to screen positive on the M-CHAT for an autism spectrum disorder. We compared the M-CHAT positive rate of those with cerebral palsy, cognitive impairment, and vision and hearing impairments to those without such deficits. Relative to children who could walk, the odds for screening positive on the M-CHAT were increased 23-fold for those unable to sit or stand independently and more than 7-fold for those requiring assistance to walk. Compared with children without a diagnosis of cerebral palsy, those with quadriparesis were 13 times more likely to screen positive, and those with hemiparesis were 4 times more likely to screen positive. Children with major vision or hearing impairments were 8 times more likely to screen positive than those without such impairments. Relative to those with a Mental Development Index (MDI) of >70, the odds for screening positive were increased 13-fold for those with an MDI of <55 and more than 4-fold for those with an MDI of 55 to 69. Major motor, cognitive, visual, and hearing impairments appear to account for more than half of the positive M-CHAT screens in extremely low gestational age newborns. Even after those with such impairments were eliminated, 10% of children--nearly double the expected rate--screened positive.

Hepatitis C virus infection in the 1945-1965 birth cohort (baby boomers) in a large urban ED.

PubMed

Allison, Waridibo E; Chiang, William; Rubin, Ada; O'Donnell, Lauren; Saldivar, Miguel A; Maurantonio, Michael; Dela Cruz, Jeffrey; Duvidovich, Svetlana; Carmody, Ellie

2016-04-01

The US Preventive Services Task Force recommends one-time screening of the 1945-1965 birth cohort (baby boomers) for hepatitis C (HCV) infection. New York State legislation mandates screening of baby boomers for HCV in most patient care settings except the emergency department (ED). This cross-sectional study explores baby boomer knowledge of HCV, prevalence of HCV infection, and linkage to care from a large urban ED. Patients participated in a researcher-administered structured interview and were offered an HCV screening test. If HCV antibody reactive, a follow-up clinic appointment was made within 6 weeks. Reminder telephone calls were made a week before the appointment. Attendance at the follow-up appointment was considered successful linkage to care. A total of 915 eligible patients were approached between October 21, 2014, and July 13, 2015. A total of 427 patients participated in the structured interview; 383 agreed to an HCV rapid test. Prevalence of HCV antibody reactivity was 7.3%. Four patients were successfully linked to care. General knowledge about HCV was fair. Misconceptions about transmission were apparent. Beliefs that "if someone is infected with HCV they will most likely carry the virus all their lives unless treated" and that "someone with hepatitis can look and feel fine" were significantly associated with agreement to testing. Better linkage to care is needed to justify HCV screening in the 1945-1965 birth cohort in this particular ED setting. Linkage to care from the ED is challenging but can potentially be improved with specific measures including simplified screening algorithms and supportive resources. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency in the neonatal period.

PubMed

Keihanian, F; Basirjafari, S; Darbandi, B; Saeidinia, A; Jafroodi, M; Sharafi, R; Shakiba, M

2017-06-01

Considering the high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among newborns, different screening methods have been established in various countries. In this study, we aimed to assess the prevalence of G6PD deficiency among newborns in Rasht, Iran, and compare G6PD activity in cord blood samples, using quantitative and qualitative tests. This cross-sectional, prospective study was performed at five largest hospitals in Rasht, Guilan Province, Iran. The screening tests were performed for all the newborns, referred to these hospitals. Specimens were characterized in terms of G6PD activity under ultraviolet light, using the kinetic method and the qualitative fluorescent spot test (FST). We also determined the sensitivity, specificity, negative predictive value, and positive predictive value of the qualitative assay. Blood samples were collected from 1474 newborns. Overall, 757 (51.4%) subjects were male. As the findings revealed, 1376 (93.4%) newborns showed normal G6PD activity, while 98 (6.6%) had G6PD deficiency. There was a significant difference in the mean G6PD level between males and females (P = 0.0001). Also, a significant relationship was detected between FST results and the mean values obtained in the quantitative test (P < 0.0001). According to the present study, FST showed acceptable sensitivity and specificity for G6PD activity, although it appeared inefficient for diagnostic purposes in some cases. © 2017 John Wiley & Sons Ltd.

Identifying Candidate Chemical-Disease Linkages (Environmental and Epigenetic Determinants of IBD)

EPA Science Inventory

Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This h...

Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?

PubMed Central

Lain, Samantha; Trumpff, Caroline; Grosse, Scott D; Olivieri, Antonella; Van Vliet, Guy

2018-01-01

When newborn screening (NBS) for congenital hypothyroidism (CH) using thyroid-stimulating hormone (TSH) as a primary screening test was introduced, typical TSH screening cutoffs were 20–50 U/L of whole blood. Over the years, lowering of TSH cutoffs has contributed to an increased prevalence of detected CH. However, a consensus on the benefit deriving from lowering TSH cutoffs at screening is lacking. The present paper outlines arguments both for and against the lowering of TSH cutoffs at NBS. It includes a review of recently published evidence from Australia, Belgium and Italy. A section focused on economic implications of lowering TSH cutoffs is also provided. One issue that bears further examination is the extent to which mild iodine deficiency at the population level might affect the association of neonatal TSH values with cognitive and developmental outcomes. A debate on TSH cutoffs provides the opportunity to reflect on how to make NBS for CH more effective and to guarantee optimum neurocognitive development and a good quality of life to babies with mild as well as with severe CH. All authors of this debate article agree on the need to establish optimal TSH cutoffs for screening programs in various settings and to ensure the benefits of screening and access to care for newborns worldwide. PMID:28694389

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

PubMed

Wood, Molly F; Hughes, Sarah C; Hache, Lauren P; Naylor, Edwin W; Abdel-Hamid, Hoda Z; Barmada, M Michael; Dobrowolski, Steven F; Stickler, David E; Clemens, Paula R

2014-06-01

Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Copyright © 2013 Wiley Periodicals, Inc.

Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas.

PubMed

Brennan, Marie-Luise; Schrijver, Iris

2016-01-01

Cystic fibrosis (CF) is an autosomal recessive disease with significant associated morbidity and mortality. It is now appreciated that the broad phenotypic CF spectrum is not explained by obvious genotype-phenotype correlations, suggesting that CF transmembrane conductance regulator (CFTR)-related disease may occur because of multiple additive effects. These contributing effects include complex CFTR alleles, modifier genes, mutations in alternative genes that produce CF-like phenotypes, epigenetic factors, and environmental influences. Most patients in the United States are now diagnosed through newborn screening and use of molecular testing methods. We review the molecular testing approaches and laboratory guidelines for carrier screening, prenatal testing, newborn screening, and clinical diagnostic testing, as well as recent developments in CF treatment, and reasons for the lack of a molecular diagnosis in some patients. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review.

PubMed

El-Metwally, Ashraf; Yousef Al-Ahaidib, Lujane; Ayman Sunqurah, Alaa; Al-Surimi, Khaled; Househ, Mowafa; Alshehri, Ali; Da'ar, Omar B; Abdul Razzak, Hira; AlOdaib, Ali Nasser

2018-01-01

This paper seeks to identify the prevalence of Phenylketonuria (PKU) in Arab countries, Turkey, and Iran. The study reviewed the existence of comprehensive national newborn screening programs and reported consanguinity rates. A computer based literature search was conducted using relevant keywords to retrieve studies conducted on PKU. A total of 34 articles were included. Prevalence was categorized based on the type of screening method used for PKU diagnoses. The prevalence of classical PKU diagnosed through a comprehensive national newborn screening program ranged from 0.005% to 0.0167%. The highest prevalence was reported in Turkey at 0.0167%, whereas the lowest prevalence was reported in the UAE, 0.005%. The findings of this review emphasize the need for the establishment of more efficient reporting systems in these countries that would help measure Disability-Adjusted Life Year (DALY) in order to estimate the overall societal burden of PKU.

Neonatal hypothyroid screening in monitoring of iodine deficiency and iodine supplementation in Poland.

PubMed

Ołtarzewski, M; Szymborski, J

2003-01-01

Neonatal hypothyroid screening in Poland is standardised and all newborns screening data are registered in central data base in the National Institute of Mother and Child. About 400,000 newborns are screened per year for hypothyroidism (TSH) and phenylketonuria (PKU). Unfortunately, obstetric clinics still use antiseptics that contain iodine. According to our data 71% of clinics used iodine in 1998 (58% iodine tincture and 13% povidone iodine) and 58.2% (35.4 iodine tincture and 13% povidone iodine) in the year 2000. Presence of iodine resulted in over 3 times increase of a percentage of TSH levels over cut off, increasing the number of false positives in the hypothyroid screening. Analysis of TSH distribution for iodine containing and iodine free hospitals gave totally different estimation of iodine deficiency according to WHO criteria. In the group of iodine free hospitals 24 regions were classified as not deficient, 9 regions were borderline with a fraction of TSH levels over 5 mlU/l of 3-5%. 10 regions could not be analysed because all hospitals declared use of iodine. In the second group all regions were iodine deficient. TSH distribution since 1994 shows significant decrease of percentage of TSH levels over cut off from 2.23% in 1994 to 0.16 in 1997 and to 0.12 in 2000. These changes are most probably connected with successive introduction of iodine supplementation which became obligatory in 1997 and suggest that iodine supplementation covers iodine requirements during pregnancy. Iodine deficiency and iodine supplementation in Poland can be studied using TSH blood spot newborn screening results in correlation with data on interfering factors and in reference to modified criteria for the analytical test and the population. To reduce false positive rate in neonatal hypothyroid screening iodine containing antiseptics, particularly iodine tincture, should be withdrawn from all obstetrics clinics in Poland.

Cascade carrier testing after a child is diagnosed with cystic fibrosis through newborn screening: investigating why most relatives do not have testing.

PubMed

McClaren, Belinda J; Aitken, Maryanne; Massie, John; Amor, David; Ukoumunne, Obioha C; Metcalfe, Sylvia A

2013-07-01

Newborn screening for cystic fibrosis is increasingly available, but cascade testing following the diagnosis in a child has received little attention. We previously reported low levels of cascade testing over time, and this study investigated motivators as well as barriers to testing. Parents were interviewed about communicating the genetic information and also asked to recruit their relatives to receive a specifically developed questionnaire. Thirty parents were interviewed and addresses of 284 relatives were provided; completed questionnaires were received from 225 (79%). A relative's relationship to the child, as well as knowledge, is associated with having had carrier testing. Relatives' reasons for testing included curiosity and wanting information for other relatives and for reproductive planning. Reasons for not testing were perceived irrelevance, lacking awareness, and viewing it as something to do in the future. Parents communicated the genetic information to relatives in various ways, which contributed to whether relatives accessed carrier testing. Newborn screening programs should provide support to parents to aid communication of genetic information to relatives. (Ir)relevance of testing is often linked to life stage; ongoing support and communication may allow relatives to learn of their risk and then seek testing, if they wish, at a time perceived to be most relevant to them.

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

Health Vulnerability Index and newborn hearing screening: urban inequality.

PubMed

Januário, Gabriela Cintra; Alves, Claudia Regina Lindgren; Lemos, Stela Maris Aguiar; Almeida, Maria Cristina de Mattos; Cruz, Ramon Costa; Friche, Amélia Augusta de Lima

To analyze the intra-urban differentials related to the outcome of the Newborn Hearing Screening (NHS) of children living in Belo Horizonte tested in a reference service using the Health Vulnerability Index (HVI). cross-sectional study with children living in Belo Horizonte evaluated by a Newborn Hearing Screening Reference Service (NHSRS) between 2010 and 2011. The HVI of the census tract of each child was obtained by the georeferencing of their respective addresses. Multivariate analysis was conducted using the decision tree technique, considering a statistical model for each response. A thematic map of points representing the geographic distribution of the children evaluated by the NHS program was also developed. The NHS failure rate for children living in areas with very high HVI, or without HVI data, was 1.5 times higher than that for children living in other census tracts. For children living in areas of low, medium, and high HVI, who underwent NHS after 30 days of life, the NHS failure rate was 2.1 times higher in children that presented Risk Indicator for Hearing Loss (RIHL) (17.2%) than in those who did not (8.1%). Uneven distribution was observed between areas for children that underwent the NHS and those who failed it. Significant intra-urban differentials were found in Belo Horizonte, indicating correlation between health vulnerability and NHS outcomes.

Can a decision aid enable informed decisions in neonatal nursery recruitment for a fragile X newborn screening study?

PubMed

Bailey, Donald B; Bann, Carla; Bishop, Ellen; Guarda, Sonia; Barnum, Leah; Roche, Myra

2013-04-01

To determine whether a brochure based on principles of informed decision making improved attention to study materials or altered decisions made by parents invited to participate in a fragile X syndrome newborn screening study. A total of 1,323 families were invited to participate in a newborn screening study to identify infants with fragile X syndrome as well as premutation carrier infants. Of these families, 716 received the original project brochure and 607 were given a new decision aid brochure. Families were more likely to look at the new decision aid and mothers were more likely to read it completely, but the proportion of mothers who read the entire decision aid was only 14%. Families were more likely to rate the decision aid as very helpful. Consistent with informed decision making theory and research, participants receiving the decision aid brochure were less likely to agree to participate. The decision aid increased attention to and perceived helpfulness of educational information about the study, but most families did not read it completely. The study suggests that even well-designed study materials are not fully reviewed in the context of in-hospital postpartum study recruitment and may need to be accompanied by a research recruiter to obtain informed consent.

Improving the quality of physician communication with rapid-throughput analysis and report cards.

PubMed

Farrell, Michael H; Christopher, Stephanie A; La Pean Kirschner, Alison; Roedl, Sara J; O'Tool, Faith O; Ahmad, Nadia Y; Farrell, Philip M

2014-11-01

Problems with clinician-patient communication negatively impact newborn screening, genetics, and all of healthcare. Training programs teach communication, but educational methods are not feasible for entire populations of clinicians. To address this healthcare quality gap, we developed a Communication Quality Assurance intervention. Child health providers volunteered for a randomized controlled trial of assessment and a report card. Participants provided telephone counseling to a standardized parent regarding a newborn screening result showing heterozygous status for cystic fibrosis or sickle cell disease. Our rapid-throughput timeline allows individualized feedback within a week. Two encounters were recorded (baseline and after a random sample received the report card) and abstracted for four groups of communication quality indicators. 92 participants finished both counseling encounters within our rapid-throughput time limits. Participants randomized to receive the report card improved communication behaviors more than controls, including request for teach-back (p<0.01), opening behaviors (p=0.01), anticipate/validate emotion (p<0.001) and the ratio of explained to unexplained jargon words (p<0.03). The rapid-throughput report card is effective at improving specific communication behaviors. Communication can be taught, but this project shows how healthcare organizations can assure communication quality everywhere. Further implementation could improve newborn screening, genetics, and healthcare in general. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Prevalence and Clinical Study of Galactosemia Disease in a Pilot Screening Program of Neonates, Southern Iran

PubMed Central

Senemar, S; Ganjekarimi, AH; Senemar, S; Tarami, B; Bazrgar, M

2011-01-01

Background The aim of the study was to research concerning the epidemiology of newborns’ galactosemia during 2007–2008 to find out whether screening was necessary for Iranian newborns or not and also what the symptoms of this disease before or after diet were. Methods: The data were collected from 24000 newborn babies from Fars Province, southern Iran. The enzymatic calorimetric test was done on their blood and Red questions from the children’s parents. For treatment, free lactose milk or soya milk have been used for the feeding of the newborns. Results: The prevalence of galactosemia in Fars Province was 5:24000 in neonates, being more than those reported among the white race are and Asians are. The maximum clinical symptoms before diet in 10 days after birth were vomiting and jaundice and those after using diet were sepsis, full fontanels, and hepatic failure. Conclusion: Consanguineous marriage is a major cause of inheritance of the disease in Iran. The number of familial marriage in children’s parents was very high. Screening should be executed for all of the families with a history of Galactosemia in Iran. To the best of our knowledge, this is the first large study report on the prevalence of Galactosemia in Iran. PMID:23113108

Cost-Effectiveness Analysis of a National Newborn Screening Program for Biotinidase Deficiency.

PubMed

Vallejo-Torres, Laura; Castilla, Iván; Couce, María L; Pérez-Cerdá, Celia; Martín-Hernández, Elena; Pineda, Mercé; Campistol, Jaume; Arrospide, Arantzazu; Morris, Stephen; Serrano-Aguilar, Pedro

2015-08-01

There are conflicting views as to whether testing for biotinidase deficiency (BD) ought to be incorporated into universal newborn screening (NBS) programs. The aim of this study was to evaluate the cost-effectiveness of adding BD to the panel of conditions currently screened under the national NBS program in Spain. We used information from the regional NBS program for BD that has been in place in the Spanish region of Galicia since 1987. These data, along with other sources, were used to develop a cost-effectiveness decision model that compared lifetime costs and health outcomes of a national birth cohort of newborns with and without an early detection program. The analysis took the perspective of the Spanish National Health Service. Effectiveness was measured in terms of quality-adjusted life years (QALYs). We undertook extensive sensitivity analyses around the main model assumptions, including a probabilistic sensitivity analysis. In the base case analysis, NBS for BD led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of $24,677. Lower costs per QALY gained were found when conservative assumptions were relaxed, yielding cost savings in some scenarios. The probability that BD screening was cost-effective was estimated to be >70% in the base case at a standard threshold value. This study indicates that NBS for BD is likely to be a cost-effective use of resources. Copyright © 2015 by the American Academy of Pediatrics.

Comparison of ABR response amplitude, test time, and estimation of hearing threshold using frequency specific chirp and tone pip stimuli in newborns.

PubMed

Ferm, Inga; Lightfoot, Guy; Stevens, John

2013-06-01

To evaluate the auditory brainstem response (ABR) amplitudes evoked by tone pip and narrowband chirp (NB CE-Chirp) stimuli when testing post-screening newborns and to determine the difference in estimated hearing level correction values. Tests were performed with tone pips and NB CE-Chirps at 4 kHz or 1 kHz. The response amplitude, response quality (Fmp), and residual noise were compared for both stimuli. Thirty babies (42 ears) who passed our ABR discharge criterion at 4 kHz following referral from their newborn hearing screen. Overall, NB CE-Chirp responses were 64% larger than the tone pip responses, closer to those evoked by clicks. Fmp was significantly higher for NB CE-Chirps. It is anticipated that there could be significant reductions in test time for the same signal to noise ratio by using NB CE-Chirps when testing newborns. This effect may vary in practice and is likely to be most beneficial for babies with low amplitude ABR responses. We propose that the ABR nHL threshold to eHL correction for NB CE-Chirps should be approximately 5 dB less than the corrections for tone pips at 4 and 1 kHz.

Blood Sampling in Newborns: A Systematic Review of YouTube Videos.

PubMed

Bueno, Mariana; Nishi, Érika Tihemi; Costa, Taine; Freire, Laís Machado; Harrison, Denise

Objective of this study was to conduct a systematic review of YouTube videos showing neonatal blood sampling, and to evaluate pain management and comforting interventions used. Selected videos were consumer- or professional-produced videos showing human newborns undergoing heel lancing or venipuncture for blood sampling, videos showing the entire blood sampling procedure (from the first attempt or puncture to the time of application of a cotton ball or bandage), publication date prior to October 2014, Portuguese titles, available audio. Search terms included "neonate," "newborn," "neonatal screening," and "blood collection." Two reviewers independently screened the videos and extracted the following data. A total of 13 140 videos were retrieved, of which 1354 were further evaluated, and 68 were included. Videos were mostly consumer produced (97%). Heel lancing was performed in 62 (91%). Forty-nine infants (72%) were held by an adult during the procedure. Median pain score immediately after puncture was 4 (interquartile range [IQR] = 0-5), and median length of cry throughout the procedure was 61 seconds (IQR = 88). Breastfeeding (3%) and swaddling (1.5%) were rarely implemented. Posted YouTube videos in Portuguese of newborns undergoing blood collection demonstrate minimal use of pain treatment, and maximal distress during procedures. Knowledge translation strategies are needed to implement effective measures for neonatal pain relief and comfort.

[Newborn hearing screening program: association between hearing loss and risk factors].

PubMed

Pereira, Priscila Karla Santana; Martins, Adriana de Souza; Vieira, Márcia Ribeiro; Azevedo, Marisa Frasson de

2007-01-01

Hearing loss in newborns. To verify the prevalence of auditory alterations in newborns of Hospital São Paulo (hospital), observing if there are any correlations with the following variables: birth weight, gestational age, relation weight/gestational age and risk factors for hearing loss. A retrospective analysis of the hospital records of 1696 newborns; 648 records of preterm infants and 1048 records of infants born at term. All of the infants had been submitted to an auditory evaluation consisting of: Transient Otoacoustic Emissions, investigation of the cochleal-palpebral reflexes and acoustic imittance tests, identifying the type and level of hearing loss. Sensorineural hearing loss was identified in .82% of the infants who were born at term and in 3.1% of the preterm infants -- with a statistically significant difference. Conductive hearing loss was the most frequent type of hearing loss in both groups, occurring in 14.6% of the term infants and in 16.3% of the preterm infants. Alteration of the central auditory system was considered as a possible diagnosis for 5.8% of the preterm infants and for 3.3% of the term infants. For the group of infants who were born at term, a significant correlation was observed between failure in the hearing screening test and the presence of risk factors such as family history and presence of a syndrome -- the child who presented a syndrome had 37 times more chances of failing in the hearing screening test and seven times more chances of failing in the right ear when there was a family history for hearing loss. The lower the gestational age (< 30 weeks) and birth weight (< 1500 g), the higher the chances of failing in the hearing screening test (3 times more). Hearing loss had a higher occurrence in preterm infants who remained in the ICU. Gestational age and birth weight were important variables related to the possibility of failure in the hearing screening test. A correlation was observed between the presence of a syndrome and sensorineural hearing loss in infants who were born at term.

A Low-Cost and Simple Genetic Screening for Cystic Fibrosis Provided by the Brazilian Public Health System.

PubMed

Rispoli, Thaiane; Martins de Castro, Simone; Grandi, Tarciana; Prado, Mayara; Filippon, Letícia; Dornelles da Silva, Cláudia Maria; Vargas, José Eduardo; Rossetti, Lucia Maria Rosa

2018-05-03

Cystic fibrosis newborn screening was implemented in Brazil by the Public Health System in 2012. Because of cost, only 1 mutation was tested - p.Phe508del. We developed a robust low-cost genetic test for screening 11 CFTR gene mutations with potential use in developing countries. Copyright © 2018 Elsevier Inc. All rights reserved.

Relationships Among Health-Related Quality of Life, Pulmonary Health, and Newborn Screening for Cystic Fibrosis

PubMed Central

Becker, Tara; Laxova, Anita; Grieve, Adam; Racine Gilles, Caroline N.; Rock, Michael J.; Gershan, William M.; Green, Christopher G.; Farrell, Philip M.

2011-01-01

Background: The objective of this study was to examine relationships between pulmonary health and health-related quality of life (HRQOL) in patients with cystic fibrosis (CF) evaluated longitudinally in the Wisconsin Newborn Screening Project. Methods: Patients aged 8 to 18 years (mean ± SD, 13.5 ± 2.8) in early diagnosis (n = 45) and control (n = 50) groups completed Cystic Fibrosis Questionnaires (CFQs) to measure HRQOL at three data points over a 2-year period. Pulmonary health was evaluated concurrently by the Wisconsin chest x-ray scoring system (WCXR) and pulmonary function tests (PFTs). Results: WCXR showed significant group differences (P ≤ .023), with the early diagnosis group showing more-severe lung disease. When adjusted for group differences in mucoid Pseudomonas aeruginosa status and pancreatic status, however, WCXR differences and PFT data were not significant. Most patients (74%) had FEV1 values ≥ 80% predicted (within normal range). For patients aged < 14 years, as WCXR scores worsened CFQ respiratory and physical domain scores decreased (both P ≤ .007). FEV1/FVC showed a positive relationship with the respiratory and physical domains (both P ≤ .006). WCXR scores for patients aged ≥ 14 years were associated with CFQ weight, respiratory, and health domains (all P ≤ .011). FEV1 was associated with CFQ weight, respiratory, health, and physical domains (all P ≤ .003). Changes in pulmonary health were not associated with changes in CFQ over time. Significant group differences on the CFQ-Child social functioning domain favored the control group. Conclusions: To our knowledge, this study is the first to compare pulmonary outcomes with HRQOL indicators assessed by serial, standardized, patient-reported outcome measures for patients with CF identified either through newborn screening or diagnosed by use of traditional methods. This study found no benefits of newborn screening for pulmonary health or HRQOL after controlling for risk factors. Using WCXR and PFT data collectively helped to identify associations between pulmonary health and HRQOL. PMID:21106659

Trends in Scottish newborn screening programme for congenital hypothyroidism 1980-2014: strategies for reducing age at notification after initial and repeat sampling.

PubMed

Mansour, Chourouk; Ouarezki, Yasmine; Jones, Jeremy; Fitch, Moira; Smith, Sarah; Mason, Avril; Donaldson, Malcolm

2017-10-01

To determine ages at first capillary sampling and notification and age at notification after second sampling in Scottish newborns referred with elevated thyroid-stimulating hormone (TSH). Referrals between 1980 and 2014 inclusive were grouped into seven 5-year blocks and analysed according to agreed standards. Of 2 116 132 newborn infants screened, 919 were referred with capillary TSH elevation ≥8 mU/L of whom 624 had definite (606) or probable (18) congenital hypothyroidism. Median age at first sampling fell from 7 to 5 days between 1980 and 2014 (standard 4-7 days), with 22, 8 and 3 infants sampled >7 days during 2000-2004, 2005-2009 and 2010-2014. Median age at notification was consistently ≤14 days, range falling during 2000-2004, 2005-2009 and 2010-2014 from 6 to 78, 7-52 and 7-32 days with 12 (14.6%), 6 (5.6%) and 5 (4.3%) infants notified >14 days. However 18/123 (14.6%) of infants undergoing second sampling from 2000 onwards breached the ≤26-day standard for notification. By 2010-2014, the 91 infants with confirmed congenital hypothyroidism had shown favourable median age at first sample (5 days) with start of treatment (10.5 days) approaching age at notification. Most standards for newborn thyroid screening are being met by the Scottish programme, but there is a need to reduce age range at notification, particularly following second sampling. Strategies to improve screening performance include carrying out initial capillary sampling as close to 96 hours as possible; introducing 6-day laboratory reporting and use of electronic transmission for communicating repeat requests. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

PubMed Central

Bateman, J B; Kojis, T L; Cantor, R M; Heinzmann, C; Ngo, J T; Spence, M A; Inana, G; Kivlin, J D; Curtis, D; Sparkes, R S

1993-01-01

Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns. PMID:7908152

Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program.

PubMed

Lim, J S; Tan, E S; John, C M; Poh, S; Yeo, S J; Ang, J S M; Adakalaisamy, P; Rozalli, R A; Hart, C; Tan, E T H; Ranieri, E; Rajadurai, V S; Cleary, M A; Goh, D L M

2014-01-01

IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore. Copyright © 2014 Elsevier Inc. All rights reserved.

Newborn Sequencing in Genomic Medicine and Public Health

PubMed Central

Agrawal, Pankaj B.; Bailey, Donald B.; Beggs, Alan H.; Brenner, Steven E.; Brower, Amy M.; Cakici, Julie A.; Ceyhan-Birsoy, Ozge; Chan, Kee; Chen, Flavia; Currier, Robert J.; Dukhovny, Dmitry; Green, Robert C.; Harris-Wai, Julie; Holm, Ingrid A.; Iglesias, Brenda; Joseph, Galen; Kingsmore, Stephen F.; Koenig, Barbara A.; Kwok, Pui-Yan; Lantos, John; Leeder, Steven J.; Lewis, Megan A.; McGuire, Amy L.; Milko, Laura V.; Mooney, Sean D.; Parad, Richard B.; Pereira, Stacey; Petrikin, Joshua; Powell, Bradford C.; Powell, Cynthia M.; Puck, Jennifer M.; Rehm, Heidi L.; Risch, Neil; Roche, Myra; Shieh, Joseph T.; Veeraraghavan, Narayanan; Watson, Michael S.; Willig, Laurel; Yu, Timothy W.; Urv, Tiina; Wise, Anastasia L.

2017-01-01

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening. PMID:28096516

Acoustic reflex on newborns: the influence of the 226 and 1,000 Hz probes.

PubMed

Jacob-Corteletti, Lilian Cássia Bórnia; Duarte, Josilene Luciene; Zucki, Fernanda; Mariotto, Luciane Domingues Figueiredo; Lauris, José Roberto Pereira; Alvarenga, Kátia de Freitas

2015-01-01

To analyze the occurrence of acoustic reflex and its threshold on newborns using the 226 and 1,000 Hz probes. Thirty-six newborns with "PASS" results in newborn hearing screening and tympanogram with one or two peaks for both probe tones were included. Group I comprised 20 full-term newborns without risk indicator for hearing loss, and Group II comprised 16 newborns with at least one risk indicator. The study about ipsilateral acoustic reflex thresholds was conducted in 500, 1,000, 2,000, and 4,000 Hz. The groups presented the acoustic reflex thresholds between 50 and 100 dB for both probe tones. In the comparison between the probes, there were differences in all frequencies evaluated in Group I, with the lowest threshold mean for the 1,000 Hz probe. In Group II, differences were detected at 2,000 Hz. The mean acoustic reflex thresholds were similar in both groups for the 226 Hz probe. There was a difference for the 1,000 Hz probe in all tested frequencies. The percentage of response was higher in both groups for the 1,000 Hz probe. The kappa test showed extremely poor agreement in the comparison of results between both probes. The occurrence of acoustic reflex was higher in newborns and its thresholds were lower with the 1,000 Hz probe both for healthy newborns and for newborns at risk.

Newborn screening tests

MedlinePlus

... adrenal hyperplasia Congenital hypothyroidism Cystic fibrosis Fatty acid metabolism disorders Galactosemia Glucose-6-phosphate dehydrogenase deficiency (G6PD) Human immunodeficiency disease (HIV) Organic acid metabolism disorders Phenylketonuria ( ...

Postdeployment Behavioral Health Screens and Linkage to the Veterans Health Administration for Army Reserve Component Members

PubMed Central

Vanneman, Megan E.; Harris, Alex H. S.; Chen, Cheng; Adams, Rachel Sayko; Williams, Thomas V.; Larson, Mary Jo

2017-01-01

Objective Approximately three to six months after returning from deployment, military service members complete the Post-Deployment Health Reassessment (PDHRA), which includes screens for alcohol misuse, depression, and post-traumatic stress disorder (PTSD). To determine whether Army Reserve Component (RC) members (Army National Guard and Army Reserve) with positive screening scores on the PDHRA receive needed care, the investigators examined the association between positive scores and enrollment and utilization of care (“linkage”) in the Veterans Health Administration (VHA), as well as rescreening scores, diagnosis, and behavioral treatment in VHA. Methods Mixed-effects regression models were used to predict linkage to VHA within six months after RC members (N=73,164) completed the PDHRA, with alcohol misuse, depression, and PTSD screen scores as key independent variables. Regression models were stratified by gender and National Guard versus Reserve status. Among those who linked to VHA (N=25,168), screening scores and subsequent diagnosis and treatment in VHA were also examined. Results Army RC members with positive PTSD and depression screening scores were more likely than those with negative screens to link to VHA, and most (54%–84%) received VHA treatment once diagnosed. Positive screens for alcohol misuse were associated with linkage to VHA for men but not for women, and treatment rates for alcohol use disorders were relatively low (0%–25%) for both men and women diagnosed as having an alcohol use disorder. Conclusions The finding that Army RC members with greater indications of behavioral health problems linked to VHA is encouraging. However, more outreach and treatment engagement strategies could be directed to those with alcohol use disorder, particularly women. PMID:28412888

Measurement of nasal potential difference in young children with an equivocal sweat test following newborn screening for cystic fibrosis.

PubMed

Sermet-Gaudelus, Isabelle; Girodon, Emmanuelle; Roussel, Delphine; Deneuville, Eric; Bui, Stéphanie; Huet, Frédéric; Guillot, Marcel; Aboutaam, Rola; Renouil, Michel; Munck, Anne; des Georges, Marie; Iron, Albert; Thauvin-Robinet, Christel; Fajac, Isabelle; Lenoir, Gerard; Roussey, Michel; Edelman, Aleksander

2010-06-01

A challenging problem arising from cystic fibrosis (CF) newborn screening is the significant number of infants with hypertrypsinaemia (HIRT) with sweat chloride levels in the intermediate range and only one or no identified CF-causing mutations. To investigate the diagnostic value for CF of assessing CF transmembrane conductance regulator (CFTR) protein function by measuring nasal potential difference in children with HIRT. A specially designed protocol was used to assess nasal potential difference (NPD) in 23 young children with HIRT (3 months-4 years) with inconclusive neonatal screening. Results were analysed with a composite score including CFTR-dependent sodium and chloride secretion. Results were correlated with genotype after extensive genetic screening and with clinical phenotype at follow-up 3 years later. NPD was interpretable for 21 children with HIRT: 13 had NPD composite scores in the CF range. All 13 were finally found to carry two CFTR mutations. At follow-up, nine had developed a chronic pulmonary disease consistent with a CF diagnosis. The sweat test could be repeated in nine children, and six had sweat chloride values >or=60 mmol/l. Of the eight children with normal NPD scores, only two had two CFTR mutations, both wide-spectrum mutations. None had developed a CF-like lung disease at follow-up. The sweat test could be reassessed in five of these eight children and all had sweat chloride values <60 mmol/l. CF diagnosis was ruled out in six of these eight children. Evaluation of CFTR function in the nasal epithelium of young children with inconclusive results at CF newborn screening is a useful diagnostic tool for CF.

Glutaric aciduria type I: outcome of patients with early- versus late-diagnosis.

PubMed

Couce, Ma Luz; López-Suárez, Olalla; Bóveda, Ma Dolores; Castiñeiras, Daisy E; Cocho, José A; García-Villoria, Judith; Castro-Gago, Manuel; Fraga, José Ma; Ribes, Antonia

2013-07-01

Patients with Glutaric aciduria type 1 (GA-1) can be identified by newborn screening using tandem mass spectrometry. The clinical evolution of screened patients seems to be more favourable compared with those diagnosed later, although long-term evolution is still doubtful. We have evaluated the outcome in nine GA-1 patients diagnosed in our region during 12 years. Six were detected by newborn screening and 3 clinically. The birth prevalence was 1:35,027. High blood C5DC concentration, in 8/9 patients, was found, whereas all patients exhibited high concentration of this metabolite in urine. Therefore, urine C5DC was a good marker for the detection of this disease. Eight different mutations in the GCDH gene were identified, four of them were novel (p.R88H, p.Y398C, p.R372K, p.D220N); being p.R227P the mostcommon. Macrocephaly with enlarged frontotemporal subarachnoid space was present in 4/6 patients diagnosed by newborn screening, all these patients required high energy intake, and in two cases, enteral feeding during the first year of life was needed. One child had an intercurrent episode of feeding refuse with hypoglycemia at two years of age. The mean follow-up time of screened patients was 56 months, and patients still remain asymptomatic. However, after a mean follow-up of 97 months treatment efficacy was poor in unscreened patients, two of them showing a severe spastic tetraparesis. Plasma levels of lysine, tryptophan and carnitine, were the most useful biomarkers for the follow-up. Our data support that, early diagnosis and treatment strategies are essential measures for the good clinical evolution of GA-1 patients. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

HealthNavigator: a mobile application for chronic disease screening and linkage to services at an urban Primary Health Network.

PubMed

Seneviratne, Martin G; Hersch, Fred; Peiris, David P

2018-03-26

Mobile applications (apps) are promising tools to support chronic disease screening and linkage to health services. They have the potential to increase healthcare access for vulnerable populations. The HealthNavigator app was developed to provide chronic disease risk assessments, linkage to local general practitioners (GPs) and lifestyle programs, and a personalised health report for discussion with a GP. Assessments were either self-administered or facilitated by community health workers through a Primary Health Network (PHN) initiative targeting ethnically diverse communities. In total, 1492 assessments (80.4% self-administered, 19.6% facilitated) were conducted over a 12-month period in Queensland, Australia. Of these, 26% of people screened came from postcodes representing the lowest quartile of socioeconomic disadvantage. When compared against self-administered assessments, subjects screened by the facilitated program were more likely to be born outside Australia (80.5 v. 33.2%, P<0.001), and to fall within a high risk category based on cardiovascular risk scores (19.8 v. 13.7%, P<0.01) and type 2 diabetes mellitus risk scores (58.0 v. 40.1%, P<0.001). Mobile apps embedded into PHN programs may be a useful adjunct for the implementation of community screening programs. Further research is needed to determine their effect on health service access and health outcomes.

The economics of screening infants at risk of hearing impairment: an international analysis.

PubMed

Burke, Martyn J; Shenton, Ruth C; Taylor, Matthew J

2012-02-01

Hearing impairment in children across the world constitutes a particularly serious obstacle to their optimal development and education, including language acquisition. Around 0.5-6 in every 1000 neonates and infants have congenital or early childhood onset sensorineural deafness or severe-to-profound hearing impairment, with significant consequences. Therefore, early detection is a vitally important element in providing appropriate support for deaf and hearing-impaired babies that will help them enjoy equal opportunities in society alongside all other children. This analysis estimates the costs and effectiveness of various interventions to screen infants at risk of hearing impairment. The economic analysis used a decision tree approach to determine the cost-effectiveness of newborn hearing screening strategies. Two unique models were built to capture different strategic screening decisions. Firstly, the cost-effectiveness of universal newborn hearing screening (UNHS) was compared to selective screening of newborns with risk factors. Secondly, the cost-effectiveness of providing a one-stage screening process vs. a two-stage screening process was investigated. Two countries, the United Kingdom and India, were used as case studies to illustrate the likely cost outcomes associated with the various strategies to diagnose hearing loss in infants. In the UK, the universal strategy incurs a further cost of approximately £2.3 million but detected an extra 63 cases. An incremental cost per case detected of £36,181 was estimated. The estimated economic burden was substantially higher in India when adopting a universal strategy due to the higher baseline prevalence of hearing loss. The one-stage screening strategy accumulated an additional 13,480 and 13,432 extra cases of false-positives, in the UK and India respectively when compared to a two-stage screening strategy. This represented increased costs by approximately £1.3 million and INR 34.6 million. The cost-effectiveness of a screening intervention was largely dependent upon two key factors. As would be expected, the cost (per patient) of the intervention drives the model substantially, with higher costs leading to higher cost-effectiveness ratios. Likewise, the baseline prevalence (risk) of hearing impairment also affected the results. In scenarios where the baseline risk was low, the intervention was less likely to be cost-effective compared to when the baseline risk was high. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Newborn screening: need of the hour in India.

PubMed

Verma, Ishwar C; Bijarnia-Mahay, Sunita; Jhingan, Geetu; Verma, Jyotsna

2015-01-01

After a review of the current health scene in India, the authors suggest that the Government of India should consider seriously, the introduction of new born screening. As a first step, a central advisory committee should be constituted to recommend what is required to be done to strengthen the infrastructure and the manpower to carry out new born screening, and the disorders to be screened. In the urban hospitals newborn screening (NBS) for three disorders can be easily introduced (congenital hypothyroidism, congenital adrenal hyperplasia and G-6-PD deficiency), while in the rural areas this should begin with congenital hypothyroidism, especially in the sub Himalayan areas. Concurrently, logistic issues regarding diets and special therapies for inborn errors of metabolism should be sorted out, laboratories to confirm the diagnosis should be set up, and a cadre of metabolic physicians should be build up to treat those identified to have inborn errors of metabolism. Once these are established on a firm footing, tandem mass spectrometry should be introduced as it allows the identification of a number of disorders in an affordable manner. The recent improvements and current trends in health care in India have created the necessary infrastructure for adopting NBS for the benefit of infants in India.

[Using an employee survey as a means of quality assurance in newborn hearing screening].

PubMed

Depenbrock, A; Matulat, P; am Zehnhoff-Dinnesen, A

2013-03-01

Studies drawing information not only from technical data but also from surveying human resources behind the universal newborn hearing screening (UNHS) appear to be a rarity. This study aims at showing how the state of both knowledge and practical skills among the screening staff are essential aspects in future quality management. A self-developed questionnaire was sent to hospital staff addressing a total of 710 nurses who were registered as having undertaken a UNHS training course. Questions were aimed at aspects of organization, personal practical skills, current problems and improvement possibilities. High rates of occupancy, lack of trained personnel, technical issues and background noise disturbances were considered to be factors that increased time pressure and slowed down procedures. Of the participants 16 % considered communicating a "refer" result to parents a difficult step and 8 % felt insecure when explaining the aims and procedures to parents. There was a high interest in further training sessions. This survey served well to reveal aspects of improvement in screening procedures and meeting staff needs. The training sessions should outline practical aspects of conducting screening and also professional, sensitive communication to parents.

Showing Value in Newborn Screening: Challenges in Quantifying the Effectiveness and Cost-Effectiveness of Early Detection of Phenylketonuria and Cystic Fibrosis

PubMed Central

Grosse, Scott D.

2015-01-01

Decision makers sometimes request information on the cost savings, cost-effectiveness, or cost-benefit of public health programs. In practice, quantifying the health and economic benefits of population-level screening programs such as newborn screening (NBS) is challenging. It requires that one specify the frequencies of health outcomes and events, such as hospitalizations, for a cohort of children with a given condition under two different scenarios—with or without NBS. Such analyses also assume that everything else, including treatments, is the same between groups. Lack of comparable data for representative screened and unscreened cohorts that are exposed to the same treatments following diagnosis can result in either under- or over-statement of differences. Accordingly, the benefits of early detection may be understated or overstated. This paper illustrates these common problems through a review of past economic evaluations of screening for two historically significant conditions, phenylketonuria and cystic fibrosis. In both examples qualitative judgments about the value of prompt identification and early treatment to an affected child were more influential than specific numerical estimates of lives or costs saved. PMID:26702401

Cost effectiveness analysis of strategies for maternal and neonatal health in developing countries.

PubMed

Adam, Taghreed; Lim, Stephen S; Mehta, Sumi; Bhutta, Zulfiqar A; Fogstad, Helga; Mathai, Matthews; Zupan, Jelka; Darmstadt, Gary L

2005-11-12

To determine the costs and benefits of interventions for maternal and newborn health to assess the appropriateness of current strategies and guide future plans to attain the millennium development goals. Cost effectiveness analysis. Two regions classified by the World Health Organization according to their epidemiological grouping: Afr-E, those countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, comprising countries in South East Asia with high adult and high child mortality. Effectiveness data from several sources, including trials, observational studies, and expert opinion. For resource inputs, quantities came from WHO guidelines, literature, and expert opinion, and prices from the WHO choosing interventions that are cost effective database. Cost per disability adjusted life year (DALY) averted in year 2000 international dollars. The most cost effective mix of interventions was similar in Afr-E and Sear-D. These were the community based newborn care package, followed by antenatal care (tetanus toxoid, screening for pre-eclampsia, screening and treatment of asymptomatic bacteriuria and syphilis); skilled attendance at birth, offering first level maternal and neonatal care around childbirth; and emergency obstetric and neonatal care around and after birth. Screening and treatment of maternal syphilis, community based management of neonatal pneumonia, and steroids given during the antenatal period were relatively less cost effective in Sear-D. Scaling up all of the included interventions to 95% coverage would halve neonatal and maternal deaths. Preventive interventions at the community level for newborn babies and at the primary care level for mothers and newborn babies are extremely cost effective, but the millennium development goals for maternal and child health will not be achieved without universal access to clinical services as well.

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

PubMed

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

2016-03-01

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. 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. 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. 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.

Blueberry muffin rash, hyperbilirubinemia, and hypoglycemia: a case of hemolytic disease of the fetus and newborn due to anti-Kp(a).

PubMed

Brumbaugh, J E; Morgan, S; Beck, J C; Zantek, N; Kearney, S; Bendel, C M; Roberts, K D

2011-05-01

Hemolytic disease of the fetus and newborn occurs when maternal IgG antibodies cross the placenta and cause hemolysis of fetal red blood cells. Kp(a) is a low frequency red blood cell antigen that has rarely been implicated in hemolytic disease of the fetus and newborn. The few reported cases attributed to anti-Kp(a) have typically had minimal clinical consequences. We report a critically ill neonate who presented with purpura, respiratory failure, severe liver dysfunction, hyperbilirubinemia, hypoglycemia and anemia. This case report broadens the spectrum of neonatal disease associated with anti-Kp(a), addresses the evaluation of hemolysis with liver failure in a neonate, and emphasizes the importance of screening for antibodies to low frequency red blood cell antigens in suspected hemolytic disease of the fetus and newborn.

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

... mass spectrometry is a device that consists of stable isotope internal standards, control materials..., free carnitine, and acylcarnitines using tandem mass spectrometry. 862.1055 Section 862.1055 Food and... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a...

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

... mass spectrometry is a device that consists of stable isotope internal standards, control materials..., free carnitine, and acylcarnitines using tandem mass spectrometry. 862.1055 Section 862.1055 Food and... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a...

[Relevance of the detection of complex congenital heart disease by screening with pulse oximetry in apparently healthy newborns in health establishments].

PubMed

Jiménez-Carbajal, María Guadalupe; López Pérez, Didier; Fernández Luna, Claudia Paola

2018-03-13

A review is presented of data published in medical literature related to the screening used for the early detection of complex congenital heart disease in apparently healthy newborns in several cities of the world, including those reported in Mexico. The screening was performed due to the knowledge of the pathophysiology of indirect hypoxia data, observation of differential cyanosis and the consequent difference in the values of pre- and post-ductal pulse oximetry derived from the ductal and/or atrial septal defect dependence of several severe congenital heart diseases. Multicentre research studies have also been carried out on a massive scale, thus justifying the usefulness of the practice for its daily implementation and at international level. Additionally, legislative topics are cited in our country as part of the efforts to establish the mandatory nature of the screening throughout the Mexican Republic. Copyright © 2018 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening.

PubMed

Stafler, Patrick; Mei-Zahav, Meir; Wilschanski, Michael; Mussaffi, Huda; Efrati, Ori; Lavie, Moran; Shoseyov, David; Cohen-Cymberknoh, Malena; Gur, Michal; Bentur, Lea; Livnat, Galit; Aviram, Micha; Alkrinawi, Soliman; Picard, Elie; Prais, Dario; Steuer, Guy; Inbar, Ori; Kerem, Eitan; Blau, Hannah

2016-07-01

Population carrier screening (PCS) has been available in Israel since 1999 and universally subsidized since 2008. We sought to evaluate its impact. A retrospective review of governmental databanks, the national CF registry and CF centers. CF rate per 100,000 live births has decreased from 14.5 in 1990 to 6 in 2011. From 2004-2011 there were 95 CF births: 22 utilized PCS; 68 (72%) had 2 known CFTR mutations; 37% were pancreatic sufficient. At diagnosis, age was 6 (0-98) months; 53/95 had respiratory symptoms, 41/95 failure to thrive and 19/95 pseudomonas. Thirty-four (36%) were Arabs and 19 (20%) orthodox Jews, compared to 20% and 8% respectively, in the general population. PCS markedly reduced CF birth rates with a shift towards milder mutations, but was often avoided for cultural reasons. As children regularly have significant disease at diagnosis, we suggest a balanced approach, utilizing both PCS and newborn screening. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

[Model project for updating neonatal screening in Bavaria: concept and initial results].

PubMed

Liebl, B; Fingerhut, R; Röschinger, W; Muntau, A; Knerr, I; Olgemöller, B; Zapf, A; Roscher, A A

2000-04-01

The newborn screening programme in Bavaria was confronted with several problems. Number of disorders and process quality no longer complied with screening guidelines. Mixed financing, distributed between the state (PKU, galactosaemia) and health insurances (hypothyroidism) had promoted an increasing dissipation of the system. Notified participation rates had dropped to < 80%. Increasing need for a second screening due to early discharge was an additional challenge. To overcome these problems, and considering the availability of improved screening methodology (tandem mass spectrometry) the programme was reorganised. The project, which started on Jan 1, 1999, is based on a cooperation model between laboratory (logistics, analysis), universities (treatment, scientific evaluation), and public health services (coordination, tracking). Time of blood sampling was predated to the third day of life. Screening was extended to biotinidase deficiency, congenital adrenal hyperplasia (CAH) and by introduction of tandem mass spectrometry for screening of many other disorders (besides PKU). Insurances now finance complete laboratory analysis which was transferred to the private sector. To enable all newborn to participate, the names of screened children are matched against birth lists by public health services on a regional basis. Recalls and conspicuous results are consistently followed up until disorders are either excluded or confirmed. Two clinical hotlines were established in the children's hospitals of the universities in Munich (Southern Bavaria) and in Erlangen (Northern Bavaria). Written consent is required for participation in the programme. Participation in the new programme could be continually increased; coverage is > 95% since April. In several cases screening was made up for not tested children by contacting their parents. Omitted screening was mostly due to misunderstandings regarding testing responsibility or lost samples. Altogether 52 cases of disorder were found in the 87,000 newborn screened until August 1999. Hence, the detection rate of children affected by inborn errors of metabolism was about twice as high than before changes. Among the newly screened diseases CAH was detected most often (11 cases). In 22 cases diagnosis was based on the use of tandem mass spectrometry. Among these (besides PKU, 9 cases) MCAD deficiency (6 cases) was detected most frequently. Whereas recall rates of most disorders were < 0.1%, screening for CAH still revealed a high recall rate, particularly in premature births. Second screening due to early discharge (< 48 h) was required in 1.3%. About 20% of pending recalls required contacting birth hospitals, doctors, midwives or parents. So far all affected children could be brought to treatment in time.

Pharmacist-initiated hepatitis C virus screening in a community pharmacy to increase awareness and link to care at the medical center.

PubMed

Isho, Nadine Y; Kachlic, Marlowe Djuric; Marcelo, Jennifer Chan; Martin, Michelle T

To describe the design and implementation of a pharmacist-led hepatitis C virus (HCV) screening and education program in a community pharmacy with a protocol for linkage to care at the affiliated hepatology clinic for patients born between 1945 and 1965. Outpatient pharmacy affiliated with the University of Illinois Hospital and Health Sciences System. The community pharmacist resident conducted the HCV screening at the health system-based community pharmacy. Community pharmacists provided patients with HCV screening and education while patients waited for their prescriptions to be ready or upon appointment. Patients were given a questionnaire before and after HCV education to assess the impact of pharmacist-provided education on patient knowledge. A protocol was developed to link patients with a positive HCV antibody test result to care with a hepatologist for confirmatory testing at a follow-up appointment at the medical center. Investigators assessed the feasibility of providing the screening and education, recorded the number of patients screened, and recorded the differences in the questionnaire responses before and after education. Pharmacist-led HCV screening services were implemented successfully at the community pharmacy. All patients had a negative antibody result; therefore, linkage to care at the medical center, although available, was not necessary. The self-reported posttest HCV knowledge scores were significantly higher than pretest scores. This article outlines the methodology for providing a multidisciplinary HCV screening, education, and referral program in a community pharmacy affiliated with a medical center. Pharmacist-initiated HCV screening in a community pharmacy can assist with identifying patients at risk for HCV infection and provide patients with linkage to care in the health system. This report may encourage community pharmacists to conduct future prospective trials to evaluate clinical and economic outcomes of community-based HCV screenings. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Assessing infant and maternal readiness for newborn discharge.

PubMed

Jing, Ling; Bethancourt, Casidhe-Nicole; McDonagh, Thomas

2017-10-01

The review highlights the shift from prescribed length of stay (LOS) to mother-infant dyad readiness as the basis for making discharge decisions for healthy term newborns. We describe the components of readiness that should be considered in making the decision, focusing on infant clinical readiness, and maternal and familial readiness. Although the Newborns' and Mothers' Health Protection Act of 1996 aimed to protect infants and mothers by establishing a minimum LOS, the American Academy of Pediatrics 2015 policy on newborn discharge acknowledges the shift from LOS-based to readiness-based discharge decision-making. Healthcare providers must consider a variety of infant and maternal characteristics in determining the appropriate time to discharge a dyad, and mothers should be actively involved in the decision-making process. Criteria for infant clinical readiness include the following: establishment of effective feeding, evaluation of jaundice risk, review and discussion of infant and household vaccination status, obtainment of specimen for metabolic screening, tests of hearing ability, assessment of sepsis risk factors, screening for congenital heart disease, and evaluation of parental knowledge about infant safety measures. Important consideration should also be given to the mother's sociodemographic vulnerabilities, maternal confidence and perception of discharge readiness, and availability of postdischarge care continuity. The timing of newborn discharge should be a joint decision made by the mother and healthcare providers based on readiness. The decision should consider the infant's health status, the mother's health status, the mother's perception of readiness, and the availability of social and familial support for the mother and infant. Accessible and comprehensive support postdischarge is also important for helping infants achieve optimal health outcomes.

Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

PubMed Central

Auchus, Richard J.; Witchel, Selma Feldman; Leight, Kelly R.; Aisenberg, Javier; Azziz, Ricardo; Bachega, Tânia A.; Baker, Linda A.; Baratz, Arlene B.; Baskin, Laurence S.; Berenbaum, Sheri A.; Breault, David T.; Cerame, Barbara I.; Conway, Gerard S.; Eugster, Erica A.; Fracassa, Stephanie; Gearhart, John P.; Geffner, Mitchell E.; Harris, Katharine B.; Hurwitz, Richard S.; Katz, Aviva L.; Kalro, Brinda N.; Lee, Peter A.; Alger Lin, Gretchen; Loechner, Karen J.; Marshall, Ian; Merke, Deborah P.; Migeon, Claude J.; Miller, Walter L.; Nenadovich, Tamara L.; Oberfield, Sharon E.; Pass, Kenneth A.; Poppas, Dix P.; Lloyd-Puryear, Michele A.; Quigley, Charmian A.; Riepe, Felix G.; Rink, Richard C.; Rivkees, Scott A.; Sandberg, David E.; Schaeffer, Traci L.; Schlussel, Richard N.; Schneck, Francis X.; Seely, Ellen W.; Snyder, Diane; Speiser, Phyllis W.; Therrell, Bradford L.; VanRyzin, Carol; Vogiatzi, Maria G.; Wajnrajch, Michael P.; White, Perrin C.; Zuckerman, Alan E.

2010-01-01

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a “roadmap” for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH. PMID:21274448

Experience of the Manitoba Perinatal Screening Program, 1965-85.

PubMed Central

Fox, J G

1987-01-01

The Manitoba Perinatal Screening Program is guided by a committee of medical specialists with skills in the diagnosis and management of disorders of metabolism in the newborn. The program is voluntary and is centralized at Cadham Provincial Laboratory, in Winnipeg. A filter card blood specimen is collected from newborns on discharge from hospital, and a filter card urine sample is collected and mailed to the laboratory by the mother when the infant is about 2 weeks of age. The overall compliance rates for the blood and urine specimens are approximately 100% and 84% respectively. The blood specimen is screened for phenylalanine and other amino acids, thyroxine, galactose, galactose-1-phosphate and biotinidase. The urine specimen is screened for amino acids, including cystine, as well as methylmalonic acid and homocystine. Between 1965 and 1985, 83 cases of metabolic disorders were detected, including 23 cases of primary hypothyroidism, 14 of classic phenylketonuria, 5 of galactosemia variants, 3 of galactosemia, 2 of maple syrup urine disease and 1 of hereditary tyrosinemia. The direct cost per infant screened is $5.50, and the cost:benefit ratio is approximately 7.5:1. Maternal serum alpha-fetoprotein screening is being made available as the necessary supporting clinical facilities become available. On the basis of this experience, the author outlines the components that are important for an effective screening program. PMID:3676929

Newborn Screening: MedlinePlus Health Topic

MedlinePlus

... deficiency (National Library of Medicine) Genetics Home Reference: glutaric acidemia type I (National Library of Medicine) Genetics Home Reference: glutaric acidemia type II (National Library of Medicine) Genetics ...

Psychosocial Distress and Knowledge Deficiencies in Parents of Children in Ireland Who Carry an Altered Cystic Fibrosis Gene.

PubMed

Quigley, S J; Linnane, B; Connellan, S; Ward, A; Ryan, P

2018-06-01

Significant gaps have been identified in parental understanding of CF newborn screening and the consequences of carrying an altered CF gene. Seven potential causes of psychosocial adversity arising from false positive newborn screening for CF have been identified. The current study aimed to increase parents understanding of CF, reduce their levels of stress, and investigate psychosocial adversity arising from false-positive screening. This national study was run over one year in the Republic of Ireland. Parents were recruited for the study following a diagnostic sweat test confirming their child carried a single altered CF gene. Parents were randomly assigned into a control and intervention group, with those in the intervention group receiving a carefully designed information pack. All parents took part in semi-structured interviews. Parents (n = 16) who received an information pack had significantly higher CF knowledge scores than parents (n = 16) in the control group. 66% of parents in the control group misunderstood the health implications of carrying an altered CF gene, no parents in the intervention group had the same misunderstanding. There was no significant difference in stress scores between the groups. Parents of infants who had more than one sweat test due to insufficient sweat quantity had higher overall stress percentiles (50%), than parents of infants who had one sweat test (30%), indicating greater parental stress. The combination of written and audio-visual information contained in the information pack successfully increased parents comprehension of CF. The study also evaluates the potential for psychosocial adversity following false positive newborn screening for CF.

Significant Admixture Linkage Disequilibrium across 30 cM around the FY Locus in African Americans

PubMed Central

Lautenberger, James A.; Stephens, J. Claiborne; O'Brien, Stephen J.; Smith, Michael W.

2000-01-01

Scientists, to understand the importance of allelic polymorphisms on phenotypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chances of discovering functional gene-marker associations. One theoretically valid approach—mapping by admixture linkage disequilibrium (MALD), using recently admixed African Americans—is empirically evaluated here by measurement of marker associations with 15 short tandem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locus in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymorphism (−46T→C) disrupts the GATA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of FY−/− in malaria infections. Analysis of linkage disequilibrium around the FY gene has indicated that there is strong and consistent linkage disequilibrium between FY and three flanking loci (D1S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-disequilibrium signals over a 30-cM region from −4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estimates of centimorgan limits, by MALD assessment in African American population-association analyses, of 5–10 cM. PMID:10712211

Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6.

PubMed

Larson, Austin A; Balasubramaniam, Shanti; Christodoulou, John; Burrage, Lindsay C; Marom, Ronit; Graham, Brett H; Diaz, George A; Glamuzina, Emma; Hauser, Natalie; Heese, Bryce; Horvath, Gabriella; Mattman, Andre; van Karnebeek, Clara; Lane Rutledge, S; Williamson, Amy; Estrella, Lissette; Van Hove, Johan K L; Weisfeld-Adams, James D

2018-01-04

Elevations of specific acylcarnitines in blood reflect carboxylase deficiencies, and have utility in newborn screening for life-threatening organic acidemias and other inherited metabolic diseases. In this report, we describe a newly-identified association of biochemical features of multiple carboxylase deficiency in individuals harboring mitochondrial DNA (mtDNA) mutations in MT-ATP6 and in whom organic acidemias and multiple carboxylase deficiencies were excluded. Using retrospective chart review, we identified eleven individuals with abnormally elevated propionylcarnitine (C3) or hydroxyisovalerylcarnitine (C5OH) with mutations in MT-ATP6, most commonly m.8993T>G in high heteroplasmy or homoplasmy. Most patients were ascertained on newborn screening; most had normal enzymatic or molecular genetic testing to exclude biotinidase and holocarboxylase synthetase deficiencies. MT-ATP6 is associated with some cases of Leigh disease; clinical outcomes in our cohort ranged from death from neurodegenerative disease in early childhood to clinically and developmentally normal after several years of follow-up. These cases expand the biochemical phenotype associated with MT-ATP6 mutations, especially m.8993T>G, to include acylcarnitine abnormalities mimicking carboxylase deficiency states. Clinicians should be aware of this association and its implications for newborn screening, and consider mtDNA sequencing in patients exhibiting similar acylcarnitine abnormalities that are biotin-unresponsive and in whom other enzymatic deficiencies have been excluded. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

A Qualitative Secondary Evaluation of Statewide Follow-Up Interviews for Abnormal Newborn Screening Results for Cystic Fibrosis and Sickle Cell Hemoglobinopathy

PubMed Central

La Pean, Alison; Collins, Jenelle L.; Christopher, Stephanie A.; Eskra, Kerry L.; Roedl, Sara; Tluczek, Audrey; Farrell, Michael H.

2011-01-01

Purpose The purpose of this qualitative analysis was to assess parental acceptability of large-scale, telephone follow-up regarding their infants' newborn screening (NBS) results indicating carrier status for sickle cell hemoglobinopathy (SCH) and cystic fibrosis (CF). Methods Analysis of 195 interview transcripts focused on parents' responses to two open-ended questions “What was your reaction to being called by me?” and “What do you think of the state newborn screening program having follow-up people calling parents like you?” Responses were coded using conventional content analysis procedures and non-parametric tests were performed to analyze quantitative data. Results Most parents reported favorable opinions about the follow-up. Favorable opinions were associated with several emotional reactions to receiving follow-up (p<0.001), and three reasons why parents found the interview beneficial (p<0.05): it provided information, clarified NBS results, and answered questions. Seventeen parents of SCH carriers reportedly had not been told their infant's NBS results and received them for the first time during the follow-up interview. Conclusion Parents of CF and SCH carrier infants had favorable opinions and identified specific benefits to receiving follow-up contact. This analysis demonstrates an information deficit among carrier parents and illustrates the importance of NBS follow-up and need for comprehensive communication and counseling. PMID:22261754

Newborn Sequencing in Genomic Medicine and Public Health.

PubMed

Berg, Jonathan S; Agrawal, Pankaj B; Bailey, Donald B; Beggs, Alan H; Brenner, Steven E; Brower, Amy M; Cakici, Julie A; Ceyhan-Birsoy, Ozge; Chan, Kee; Chen, Flavia; Currier, Robert J; Dukhovny, Dmitry; Green, Robert C; Harris-Wai, Julie; Holm, Ingrid A; Iglesias, Brenda; Joseph, Galen; Kingsmore, Stephen F; Koenig, Barbara A; Kwok, Pui-Yan; Lantos, John; Leeder, Steven J; Lewis, Megan A; McGuire, Amy L; Milko, Laura V; Mooney, Sean D; Parad, Richard B; Pereira, Stacey; Petrikin, Joshua; Powell, Bradford C; Powell, Cynthia M; Puck, Jennifer M; Rehm, Heidi L; Risch, Neil; Roche, Myra; Shieh, Joseph T; Veeraraghavan, Narayanan; Watson, Michael S; Willig, Laurel; Yu, Timothy W; Urv, Tiina; Wise, Anastasia L

2017-02-01

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening. Copyright © 2017 by the American Academy of Pediatrics.

Delays in Diagnosis of Congenital Hearing Loss in Rural Children

PubMed Central

Bush, Matthew L.; Bianchi, Kristin; Lester, Cathy; Shinn, Jennifer B.; Gal, TJ; Fardo, David W.; Schoenberg, Nancy

2013-01-01

Objective To examine the incidence of pediatric congenital hearing loss and the timing of diagnosis in a rural region of hearing healthcare disparity. Study design Data from the Kentucky newborn hearing-screening program was accessed to determine the incidence of congenital hearing loss in Kentucky, both in the extremely rural region of Appalachia and non-Appalachian region of Kentucky. We also performed a retrospective review of records of children with congenital hearing loss at our institution to determine the timing of diagnostic testing. Results In Kentucky, during 2009–2011, there were 6,970 newborns who failed hearing screening; the incidence of newborn hearing loss was 1.71 per 1000 births (1.28/1000 in Appalachia and 1.87/1000 in non-Appalachia). 23.8% of Appalachian newborns compared with 17.3% of non-Appalachian children failed to obtain follow-up diagnostic testing. Children from Appalachia were significantly delayed in obtaining a final diagnosis of hearing loss compared with children from non-Appalachian regions (p=0.04). Conclusion Congenital hearing loss in children from rural regions with hearing healthcare disparities is a common problem and these children are at risk for a delay in the timing of diagnosis, which has the potential to limit language and social development. It is important to further assess the causative factors and develop interventions that can address this hearing healthcare disparity issue. PMID:24183213

Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography-tandem mass spectrometry.

PubMed

Janzen, Nils; Sander, Stefanie; Terhardt, Michael; Steuerwald, Ulrike; Peter, Michael; Das, Anibh M; Sander, Johannes

2011-12-11

Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hydroxyprogesterone using immunoassay. However, this test produces high rates of false positive results caused by cross reacting steroids. Therefore we have developed a selective and specific method with a short run time (1.25 min) for quantification of 17α-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone and cortisol from dried blood spots. The extraction procedure is very simple and steroid separation is ensured on a BEH C18 column and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analysis was done in positive ionization mode (ESI+) and recorded in multiple reaction monitoring mode (MRM). The method gave linear results for all steroids over a range of 5-200 (cortisol: 12.5-500)nmol/L with coefficients of regression >0.992. Absolute recovery was >64.1%. Across the analytical range the inter-assay coefficient of variation (CV) was <3%. Newborn blood samples of patients with confirmed 21-CAH and 11-CAH could clearly be distinguished from samples of unaffected newborns falsely positive on immunoassay. The method is not influenced by cross reactions as found on immunoassay. Analysis of dried blood spots shows that this method is sensitive and fast enough to allow rapid analysis and can therefore improve the newborn screening program. Copyright © 2011 Elsevier Inc. All rights reserved.

Reference values of amino acids, acylcarnitines and succinylacetone by tandem mass spectrometry for use in newborn screening in southwest Colombia.

PubMed

Céspedes, Nora; Valencia, Angela; Echeverry, Carlos Alberto; Arce-Plata, Maria Isabel; Colón, Cristóbal; Castiñeiras, Daisy E; Hurtado, Paula Margarita; Cocho, Jose Angel; Herrera, Sócrates; Arévalo-Herrera, Myriam

2017-09-30

Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality of affected patients, and consequent untimely child death. In contrast to classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation of multiple metabolites associated with IEM offering higher sensitivity, low false positive rates and high throughput. Determine concentration levels for amino acids and acylcarnitines in blood of newborns from Colombia, to establish reference values for further use in diagnosis of IEM. Implementation of a method to determine amino acids, acylcarnitines and succinylacetone in newborn dried blood spots using MS/MS, and its application in a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo cities is described. fifty-seven analytes that allow the diagnosis of more than 40 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 1-18 days of age were included, 523 from Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the concentration levels of amino acids and acylcarnitines were observed whereas no significant differences by gender were found. The study has contributed to reveal the usual concentration levels of amino acids, acylcarnitines and succinylacetone that could be used as reference for the establishment of a newborn metabolic screening program in Colombia.

Community-Clinical Linkages With Community Health Workers in the United States: A Scoping Review.

PubMed

Lohr, Abby M; Ingram, Maia; Nuñez, Annabelle V; Reinschmidt, Kerstin M; Carvajal, Scott C

2018-05-01

Despite the proliferation of community-clinical linkage (CCL) interventions with community health workers (CHWs), little is known about the components of these programs or how linkages are realized. In this scoping review, we synthesize evidence concerning the role of CHWs in creating and sustaining CCLs aimed at improving individual health outcomes. Our inclusion criteria included peer-reviewed articles that described a CHW intervention in the United States that used a CCL model. A total of 2,776 titles and/or abstracts were screened and 47 articles underwent full text review. Two independent reviewers rated the screened articles based on additional criteria including the CHW connection to community and evidence of linkage follow up rather than simple referral. For the 11 peer-reviewed articles included in the final review, we describe the CHW's relationship to the community, training, and role within the intervention, linkage, and outcomes. We used a standardized framework to determine commonalities in CHW roles across the interventions. CCLs with CHWs positively affect the delivery of both clinical care and community resources across a range of disease areas in a variety of contexts. To identify effective CCL models, additional information on CHW training, CCL follow-up methods, and the CHW role in CCLs is recommended.

Diagnosing cystic fibrosis in newborn screening in Poland - 15 years of experience.

PubMed

Sands, Dorota; Zybert, Katarzyna; Mierzejewska, Ewa; Ołtarzewski, Mariusz

2015-01-01

Early diagnosis of cystic fibrosis (CF) made by the introduction of CF NBS (Cystic Fibrosis Newborn Screening) provides the opportunity to undertake preventive measures and provide treatment before the development of irreversible changes in the respiratory tract and other complications. CF NBS was conducted as a pilot programme in four Polish districts in the period 1999-2003. In 2006 CF NBS started again and was gradually extended across the country. The aim of this study was to show the evolution of the Polish CF NBS strategies and assess the diagnostic consequences of this programme. The study involved children diagnosed and treated only in the IMiD Centre. The strategy in Polish CF NBS was modified over time. Firstly, the model IRT/IRT and IRT/IRT/DNA with one mutation was implemented, which was followed by IRT/DNA with a gradually expanding number of CFTR mutations (tab. I). Newborns with positive results of CF NBS were called to the CF IMiD Centre, and sweat tests were performed. The children diagnosed and children with mutations in both alleles of the CFTR gene even if at least one of them had undefined pathogenicity) were taken under IMiD Centre care. Sensitivity, specificity and positive predictive values during subsequent stages of CF NBS were calculated (tab. III). During the 1999-2003 pilot study 444 063 newborns underwent CF NBS and in 74 cases CF was diagnosed. 582 693 newborns were screened from September 2006 to December 2011 in four regions and 100 children were diagnosed with CF. The frequencies of CF in the Polish population in both screening periods were 1:5767 and 1:5712 respectively. Firstly, the IRT/IRT model was implemented, but the number of newborns called to the CF Centre was high - the PPV was 7.6%. In the next step CF NBS DNA analysis was used. Here sensitivity and specificity were high - nearly 100%. In the following years the number of mutations detected was expanded (including 16 most common ones in the Polish population). Due to the panel changes, the number of calls declined and the PPV (predictive positive value) improved (to 26.1%) after the application of expanded genetic analysis. Expanding the panel of mutations resulted in an increased number of carriers and observational subjects. IRT/DNA strategy with expanded DNA analysis provides the opportunity for earlier CF diagnosis even in children with normal sweat test values. However, this model caused frequent carrier detection and inconclusive diagnosis in comparison to IRT/IRT or IRT/IRT/DNA with a limited number of mutations. Further research and changes in Polish CF NBS are needed to increase the PPV, while preserving high sensitivity and specificity..

From Screening to Care: A Qualitative Analysis of the Parental Experiences Related to Screening and (Re)habilitation Care for Children with Congenital Deafness in Flanders, Belgium

ERIC Educational Resources Information Center

Hardonk, Stefan; Desnerck, Greetje; Loots, Gerrit; Matthijs, Liesbeth; Van Hove, Geert; Van Kerschaver, Erwin; Sigurjonsdottir, Hanna Bjorg; Vanroelen, Christophe; Louckx, Fred

2011-01-01

The objective of this study is to analyze parental perspectives concerning the use of (re)habilitation services after Universal Newborn Hearing Screening (UNHS). A qualitative study design was used involving children with moderate-to-profound hearing loss who were born between 1999 and 2001 and who are registered in the UNHS program in Flanders,…

Diagnosis, treatment and outcome of glutaric aciduria type I in Zhejiang Province, China

PubMed Central

Yang, Lili; Yin, Huaiming; Yang, Rongwang; Huang, Xinwen

2011-01-01

Summary Background Glutaric aciduria type I (GA I; MIM 231670) is a rare autosomal recessive disorder resulting from glutaryl-CoA dehydrogenase deficiency. This article reports our experience in the diagnosis, treatment and outcome of GA I patients in Zhejiang Province, China. Material/Methods A total of 129,415 newborns (accounting for approximately one-tenth of the annual births in Zhejiang Province) and 9640 high-risk infants were screened for inborn errors of metabolism in the Neonatal Screening Center of Zhejiang Province during a 3-year period. Tandem mass spectrometry and gas chromatography-mass spectrometry were used for diagnosis of the patients. Dietary modification, carnitine supplementation and aggressive treatment of intercurrent illnesses were adapted for GA I patients. Results Three infants were diagnosed with GA I by high-risk screening (detection rate: 1/3,213) and 2 were diagnosed by newborn screening (incidence: 1/64,708). Four patients (3 by high-risk screening and 1 by neonatal screening) undergoing MRI examination showed remarkable changes on T2-weighted image. Four patients accepted timely treatment, and in the patient diagnosed by neonatal screening, treatment was delayed until hypotonia appeared 3 months later. Neuropsychological assessment showed mental and motor retardation in 3 patients after treatment, including the patient diagnosed by neonatal screening. Conclusions Individualized timely treatment and close monitoring of GA I patients needs to be optimized in China. Appropriate communication with parents may help to achieve successful management of GA I patients. PMID:21709643

[Expand newborn screening using tandem mass spectrometry: two years' experience in Nuevo León, Mexico].

PubMed

Torres-Sepúlveda, María del Rosario; Martínez-de Villarreal, Laura E; Esmer, Carmen; González-Alanís, Rogerio; Ruiz-Herrera, Consuelo; Sánchez-Peña, Alejandra; Mendoza-Cruz, José Alberto; Villarreal-Pérez, Jesús Z

2008-01-01

To initiate a statewide expanded metabolic screening program in neonates with the purpose of identifying the most common inborn errors of metabolism. From March 2002 through February 2004, a blood sample was obtained between 24 and 48 hours after delivery from every consecutive child born in public hospitals in Nuevo León. It was spotted on filter paper and analyzed by tandem mass spectrometry for expanded metabolic screening. A total of 42 264 samples were analyzed. Were obtained seven positive results, one for each disorder: homocystinuria, hyperphenylalaninemia, citrulinemia, transient tyrosinemia, 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl CoA deficiency, and classic galactosemia. The estimated incidence of inborn errors of metabolism is 1:5 000, with a false positive rate of 0.22%. The program permitted the identification of metabolic disorders in the newborn, allowing an early intervention and prevention of life-threatening events and permanent neurological damage.

Multiplicity of experimental approaches to therapy for genetic muscle diseases and necessity for population screening.

PubMed

Laing, Nigel G

2008-01-01

Currently a multiplicity of experimental approaches to therapy for genetic muscle diseases is being investigated. These include replacement of the missing gene, manipulation of the gene message, repair of the mutation, upregulation of an alternative gene and pharmacological interventions targeting a number of systems. A number of these approaches are in current clinical trials. There is considerable anticipation that perhaps more than one of the approaches will finally prove of clinical benefit, but there are many voices of caution. No matter which approaches might ultimately prove effective, there is a consensus that for most benefit to the patients it will be necessary to start treatment as early as possible. A consensus is also developing that the only way to do this is to implement population-based newborn screening to identify affected children shortly after birth. Population-based newborn screening is currently practised in very few places in the world and it brings with it implications for prevention rather than cure of genetic muscle diseases.

The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe.

PubMed

Barben, Jürg; Castellani, Carlo; Dankert-Roelse, Jeannette; Gartner, Silvia; Kashirskaya, Nataliya; Linnane, Barry; Mayell, Sarah; Munck, Anne; Sands, Dorota; Sommerburg, Olaf; Pybus, Simon; Winters, Victoria; Southern, Kevin W

2017-03-01

Newborn screening (NBS) for cystic fibrosis (CF) is a well-established public health strategy with international standards. The aim of this study was to provide an update on NBS for CF in Europe and assess performance against the standards. Questionnaires were sent to key workers in each European country. In 2016, there were 17 national programmes, 4 countries with regional programmes and 25 countries not screening in Europe. All national programmes employed different protocols, with IRT-DNA the most common strategy. Five countries were not using DNA analysis. In addition, the processing and structure of programmes varied considerably. Most programmes were achieving the ECFS standards with respect to timeliness, but were less successful with respect to sensitivity and specificity. There has been a steady increase in national CF NBS programmes across Europe with variable strategies and outcomes that reflect the different approaches. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Screening the High-Risk Newborn for Hearing Loss: The Crib-O-Gram v the Auditory Brainstem Response.

ERIC Educational Resources Information Center

Cox, L. Clarke

1988-01-01

Presented are a rationale for identifying hearing loss in infancy and a history of screening procedures. The Crib-O-Gram and auditory brainstem response (ABR) tests are evaluated for reliability, validity, and cost-effectiveness. The ABR is recommended, and fully automated ABR instrumentation, which lowers expenses for trained personnel and…

Prenatal Sickle Cell Screening Education Effect on the Follow-up Rates of Infants with Sickle Cell Trait.

ERIC Educational Resources Information Center

Yang, Yih-Ming; Andrews, Susan; Peterson, Rose; Shah, Arvind; Cepeda, Manuel

2000-01-01

Assesses the effect of prenatal education about newborn sickle cell screening on parents' compliance with the follow-up for infants with sickle cell trait. Results show that parents whose prenatal education included sickle cell hemoglobinopathy information retained significantly more of the information given during the post-natal education than…

Association Between Transient Newborn Hypoglycemia and Fourth-Grade Achievement Test Proficiency: A Population-Based Study.

PubMed

Kaiser, Jeffrey R; Bai, Shasha; Gibson, Neal; Holland, Greg; Lin, Tsai Mei; Swearingen, Christopher J; Mehl, Jennifer K; ElHassan, Nahed O

2015-10-01

Prolonged neonatal hypoglycemia is associated with poor long-term neurocognitive function. However, little is known about an association between early transient newborn hypoglycemia and academic achievement. To determine if early (within the first 3 hours of life) transient hypoglycemia (a single initial low glucose concentration, followed by a second value above a cutoff) is associated with subsequent poor academic performance. A retrospective population-based cohort study of all infants born between January 1, 1998, and December 31, 1998, at the University of Arkansas for Medical Sciences who had at least 1 recorded glucose concentration (a universal newborn glucose screening policy was in effect) was conducted. Medical record data from newborns with normoglycemia or transient hypoglycemia were matched with their student achievement test scores in 2008 from the Arkansas Department of Education and anonymized. Logistic regression models were developed to evaluate the association between transient hypoglycemia and school-age achievement test proficiency based on perinatal factors. Common hypoglycemia cutoffs of a glucose level less than 35 mg/dL (primary) and less than 40 and 45 mg/dL (secondary) were investigated. All 1943 normoglycemic and transiently hypoglycemic infants (23-42 weeks' gestation) were eligible for inclusion in the study. Infants with prolonged hypoglycemia, congenital anomalies, or chromosomal abnormalities were excluded from the study. Hypoglycemia as a newborn. The primary outcome was proficiency on fourth-grade literacy and mathematics achievement tests at age 10 years. We hypothesized a priori that newborns with early transient hypoglycemia would be less proficient on fourth-grade achievement tests compared with normoglycemic newborns. Perinatal data were matched with fourth-grade achievement test scores in 1395 newborn-student pairs (71.8%). Transient hypoglycemia (glucose level <35, <40, and <45 mg/dL) was observed in 6.4% (89 of 1395), 10.3% (143 of 1395), and 19.3% (269 of 1395) of newborns, respectively. After controlling for gestational age group, race, sex, multifetal gestation, insurance status, maternal educational level and socioeconomic status, and gravidity, transient hypoglycemia was associated with decreased probability of proficiency on literacy and mathematics fourth-grade achievement tests. For the 3 hypoglycemia cutoffs, the adjusted odds ratios (95% CIs) for literacy were 0.49 (0.28-0.83), 0.43 (0.28-0.67), and 0.62 (0.45-0.85), respectively, and the adjusted odds ratios (95% CIs) for mathematics were 0.49 (0.29-0.82), 0.51 (0.34-0.78), and 0.78 (0.57-1.08), respectively. Early transient newborn hypoglycemia was associated with lower achievement test scores at age 10 years. Given that our findings are serious and contrary to expert opinion, the results need to be validated in other populations before universal newborn glucose screening should be adopted.

TORCH Screen

MedlinePlus

... fetus and newborn. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ, eds. Feigin and ... constitute endorsements of those other sites. Copyright 1997-2018, A.D.A.M., Inc. Duplication for commercial ...

Screening Newborns' Hearing Now Standard | NIH MedlinePlus the Magazine

MedlinePlus

... Possible Hearing Problem Your Baby's Hearing and Communicative Development Checklist Communication Considerations —for parents of children with hearing loss Cochlear Implants —surgically implanted hearing ...

Kinetic and molecular orbital analyses of dicarboxylic acylcarnitine methylesterification show that derivatization may affect the screening of newborns by tandem mass spectrometry.

PubMed

Maeda, Yasuhiro; Nakajima, Yoko; Gotoh, Kana; Hotta, Yuji; Kataoka, Tomoya; Sugiyama, Naruji; Shirai, Naohiro; Ito, Tetsuya; Kimura, Kazunori

2016-01-01

Newborns are routinely screened for organic acidemias by acylcarnitine analysis. We previously reported the partial catalytic methylesterification of dicarboxylic acylcarnitines by benzenesulfonic acid moiety in the solid extraction cartridge during extraction from serum. Since the diagnosis of organic acidemias by tandem mass spectrometry is affected by the higher molecular weight of these derivatized acylcarnitines, we investigated the methylesterification conditions. The kinetic constants for the methylesterification of carboxyl groups on the acyl and carnitine sides of carnitine were 2.5 and 0.24h(-1), respectively. The physical basis underlying this difference in methylesterification rates was clarified theoretically, illustrating that methylesterification during extraction proceeds easily and must be prevented. Copyright © 2015 Elsevier Ltd. All rights reserved.

Haemolytic disease of the fetus and newborn.

PubMed

de Haas, M; Thurik, F F; Koelewijn, J M; van der Schoot, C E

2015-08-01

Haemolytic Disease of the Fetus and Newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens. In severe cases, HDFN may lead to fetal anaemia with a risk for fetal death and to severe forms of neonatal hyperbilirubinaemia with a risk for kernicterus. Most severe cases are caused by anti-D, despite the introduction of antental and postnatal anti-D immunoglobulin prophylaxis. In general, red blood cell antibody screening programmes are aimed to detect maternal alloimmunization early in pregnancy to facilitate the identification of high-risk cases to timely start antenatal and postnatal treatment. In this review, an overview of the clinical relevance of red cell alloantibodies in relation to occurrence of HDFN and recent views on prevention, screening and treatment options of HDFN are provided. © 2015 International Society of Blood Transfusion.

Conductive hearing loss and middle ear pathology in young infants referred through a newborn universal hearing screening program in Australia.

PubMed

Aithal, Sreedevi; Aithal, Venkatesh; Kei, Joseph; Driscoll, Carlie

2012-10-01

Although newborn hearing screening programs have been introduced in most states in Australia, the prevalence of conductive hearing loss and middle ear pathology in the infants referred through these programs is not known. This study was designed to (1) evaluate the prevalence of conductive hearing loss and middle ear pathology in infants referred by a newborn hearing screening program in north Queensland, (2) compare prevalence rates of conductive hearing loss and middle ear pathology in indigenous and nonindigenous infants, and (3) review the outcomes of those infants diagnosed with conductive hearing loss and middle ear pathology. Retrospective chart review of infants referred to the Audiology Department of The Townsville Hospital was conducted. Chart review of 234 infants referred for one or both ears from a newborn hearing screening program in north Queensland was conducted. A total of 211 infants attended the diagnostic appointment. Review appointments to monitor hearing status were completed for 46 infants with middle ear pathology or conductive hearing loss. Diagnosis of hearing impairment was made using an age-appropriate battery of audiological tests. Results were analyzed for both initial and review appointments. Mean age at initial diagnostic assessment was 47.5 days (SD = 31.3). Of the 69 infants with middle ear pathology during initial diagnostic assessment, 18 had middle ear pathology with normal hearing, 47 had conductive hearing loss, and 4 had mixed hearing loss. Prevalence of conductive hearing loss in the newborns was 2.97 per 1,000 while prevalence of middle ear pathology (with or without conductive hearing loss) was 4.36 per 1,000. Indigenous Australians or Aboriginal and Torres Strait Islander (ATSI) infants had a significantly higher prevalence of conductive hearing loss and middle ear pathology than non-ATSI infants (35.19 and 44.45% vs 17.83 and 28.66%, respectively). ATSI infants also showed poor resolution of conductive hearing loss over time with 66.67% of ATSI infants reviewed showing persistent conductive hearing loss compared to 17.86% of non-ATSI infants. Medical management of 17 infants with persistent conductive hearing loss included monitoring, antibiotic treatment, examination under anesthesia, and grommet insertion. Conductive hearing loss was found to be a common diagnosis among infants referred through screening. ATSI infants had significantly higher rates of middle ear pathology and conductive hearing loss at birth and showed poor resolution of middle ear pathology over time compared to non-ATSI infants. Future research using a direct measure of middle ear function as an adjunct to the automated auditory brainstem response screening tool to distinguish conductive from sensorineural hearing loss may facilitate prioritization of infants for assessment, thus reducing parental anxiety and streamlining the management strategies for the respective types of hearing loss. American Academy of Audiology.

Analysis of otoacoustic emissions in neonates at term and preterm.

PubMed

Cavalcante, Juliana Maria Soares; Isaac, Myriam de Lima

2013-01-01

The transient evoked otoacoustic emissions (TEOAEs) have been widely used in neonatal hearing screening. To compare the TEOAEs in newborns at term and preterm vis-à-vis the following variables: ear side, gender, frequency spectrum and gestational age. By means of a cross-sectional cohort of 66 newborns up to the 28th day of life (41 newborns at term and 25 premature babies), we recorded TEOAEs. All the individuals did not have risk indicators for hearing loss. There was a signal/noise ratio improvement with frequency increase. No differences were observed between genders and between the ears, but there were differences among the children born at term and preterm in the frequency bands at 3 kHz and 4 kHz. The TEOAEs test is important for assessing the peripheral auditory system of newborns at term and preterm, making it possible to have responses regardless of gender and gestational age.

Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention.

PubMed

Abara, Winston E; Qaseem, Amir; Schillie, Sarah; McMahon, Brian J; Harris, Aaron M

2017-12-05

Vaccination, screening, and linkage to care can reduce the burden of chronic hepatitis B virus (HBV) infection. However, recommendations vary among organizations, and their implementation has been suboptimal. The American College of Physicians' High Value Care Task Force and the Centers for Disease Control and Prevention developed this article to present best practice statements for hepatitis B vaccination, screening, and linkage to care. A narrative literature review of clinical guidelines, systematic reviews, randomized trials, and intervention studies on hepatitis B vaccination, screening, and linkage to care published between January 2005 and June 2017 was conducted. Clinicians should vaccinate against hepatitis B virus (HBV) in all unvaccinated adults (including pregnant women) at risk for infection due to sexual, percutaneous, or mucosal exposure; health care and public safety workers at risk for blood exposure; adults with chronic liver disease, end-stage renal disease (including hemodialysis patients), or HIV infection; travelers to HBV-endemic regions; and adults seeking protection from HBV infection. Clinicians should screen (hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen) for HBV in high-risk persons, including persons born in countries with 2% or higher HBV prevalence, men who have sex with men, persons who inject drugs, HIV-positive persons, household and sexual contacts of HBV-infected persons, persons requiring immunosuppressive therapy, persons with end-stage renal disease (including hemodialysis patients), blood and tissue donors, persons infected with hepatitis C virus, persons with elevated alanine aminotransferase levels (≥19 IU/L for women and ≥30 IU/L for men), incarcerated persons, pregnant women, and infants born to HBV-infected mothers. Clinicians should provide or refer all patients identified with HBV (HBsAg-positive) for posttest counseling and hepatitis B-directed care.

A comparison of effectiveness of hepatitis B screening and linkage to care among foreign-born populations in clinical and nonclinical settings.

PubMed

Chandrasekar, Edwin; Kaur, Ravneet; Song, Sharon; Kim, Karen E

2015-01-01

Hepatitis B (HBV) is an urgent, unmet public health issue that affects Asian Americans disproportionately. Of the estimated 1.2 million living with chronic hepatitis B in USA, more than 50% are of Asian ethnicity, despite the fact that Asian Americans constitute less than 6% of the total US population. The Centers for Disease Control and Prevention recommends HBV screening of persons who are at high risk for the disease. Yet, large numbers of Asian Americans have not been diagnosed or tested, in large part because of perceived cultural and linguistic barriers. Primary care physicians are at the front line of the US health care system, and are in a position to identify individuals and families at risk. Clinical settings integrated into Asian American communities, where physicians are on staff and wellness care is emphasized, can provide testing for HBV. In this study, the Asian Health Coalition and its community partners conducted HBV screenings and follow-up linkage to care in both clinical and nonclinical settings. The nonclinic settings included health fair events organized by churches and social services agencies, and were able to reach large numbers of individuals. Twice as many Asian Americans were screened in nonclinical settings than in health clinics. Chi-square and independent samples t-test showed that participants from the two settings did not differ in test positivity, sex, insurance status, years of residence in USA, or education. Additionally, the same proportion of individuals found to be infected in the two groups underwent successful linkage to care. Nonclinical settings were as effective as clinical settings in screening for HBV, as well as in making treatment options available to those who tested positive; demographic factors did not confound the similarities. Further research is needed to evaluate if linkage to care can be accomplished equally efficiently on a larger scale.

Hemoglobinopathy Evaluation

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... Newborn Screening Cooley's Anemia Foundation National Human Genome Research Institute: Sickle Cell Disease National Human Genome Research ...

Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders

PubMed Central

Grether, Judith K.; Ashwood, Paul; Van de Water, Judy; Yolken, Robert H.; Anderson, Meredith C.; Torres, Anthony R.; Westover, Jonna B.; Sweeten, Thayne; Hansen, Robin L.; Kharrazi, Martin; Croen, Lisa A.

2016-01-01

Background: An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls. Methods: We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP) for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD) identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates.Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated. Results: In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were < 1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls. Discussion: These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure to common infectious agents. Conclusion: Patterns seen in these selected immunoglobulins may provide clues to mechanisms of early abnormalities in neurodevelopment contributing to ASD. We recommend further study of immunoglobulin profiles in larger samples of linked mother-baby pairs to evaluate possible etiologic relevance. PMID:27242422

Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders.

PubMed

Grether, Judith K; Ashwood, Paul; Van de Water, Judy; Yolken, Robert H; Anderson, Meredith C; Torres, Anthony R; Westover, Jonna B; Sweeten, Thayne; Hansen, Robin L; Kharrazi, Martin; Croen, Lisa A

2016-01-01

An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls. We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP) for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD) identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates.Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated. In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were < 1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls. These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure to common infectious agents. Patterns seen in these selected immunoglobulins may provide clues to mechanisms of early abnormalities in neurodevelopment contributing to ASD. We recommend further study of immunoglobulin profiles in larger samples of linked mother-baby pairs to evaluate possible etiologic relevance.

Evaluation of urinary S100B protein level and lactate/creatinine ratio for early diagnosis and prognostic prediction of neonatal hypoxic-ischemic encephalopathy.

PubMed

Liu, Li; Zheng, Chong-Xun; Peng, Shu-Feng; Zhou, Hong-Yan; Su, Zu-You; He, Li; Ai, Ting

2010-01-01

Early identification and prevention of hypoxic-ischemic encephalopathy (HIE) in newborns may reduce neonatal mortality and neurological dysfunction. To analyze the diagnostic and prognostic values of urinary S100B level and lactate/creatinine ratio in newborns with HIE. Seventy-eight full-term newborns with HIE and 25 normal newborns were enrolled. The Neonatal Behavioral Neurological Assessment (NBNA) and Developmental Screening Test were scored. The concentration of urinary S100B protein was determined using the S100B enzyme-linked immunosorbent assay and the levels of urinary lactate and creatinine were measured with the enzyme colorimetric method. Urinary S100B level on days 1-3 after birth and lactate/creatinine ratio on day 1 were significantly higher in newborns with HIE than those in the control group. Both indexes were positively correlated with the clinical grading of HIE. A cutoff value for the S100B level of 0.47 microg/l on day 3 after birth had a sensitivity of 90% and specificity of 92% for prediction of HIE. A lactate/creatinine ratio of more than 0.55 on day 1 showed the highest sensitivity (92%) and specificity (90%). A combination of both indexes improved the sensitivity and specificity to 99 and 97%, respectively. A negative correlation of both lactate/creatinine ratio on day 1 and S100B level on days 1-3 after birth with the NBNA score was identified on days 3, 7 and 14 after birth. The Developmental Screening Test score of 36 newborns with HIE within 6 months after birth showed that 65% of infants with moderate and high HIE had an abnormal developmental quotient. These data suggest that early measurement of both S100B level and lactate/creatinine ratio in the urine of newborns with HIE is a practical convenient and sensitive way to improve diagnosis on the third day of life and prognostic prediction of HIE. Copyright 2009 S. Karger AG, Basel.

Comprehensive Identification Of Specific Genes Controlling Complex Traits Through A Genome-Wide Screen for Cis-Acting Regulatory Elements - An Example Using Marek's Disease

USDA-ARS?s Scientific Manuscript database

The comprehensive identification of genes underlying phenotypic variation of complex traits remains a major challenge. Most genome-wide screens lack sufficient resolving power as they typically depend on linkage. An alternate method is to screen for allele-specific expression (ASE), a simple yet pow...

Screening and prevention of neonatal glucose 6-phosphate dehydrogenase deficiency in Guangzhou, China.

PubMed

Jiang, J; Li, B; Cao, W; Jiang, X; Jia, X; Chen, Q; Wu, J

2014-06-09

We aimed to summarize the results of screening protocol and prevention of neonatal glucose 6-phosphate dehydrogenase (G6PD) deficiency during a 22-year-long period to provide a basis of reference for the screening of this disease. About 1,705,569 newborn subjects in Guangzhou City were screened for this deficiency. Specimens were collected according to the conventional method of specimen acquisition for "newborn dried bloodspot screening", preserved, and inspected. The specimens were studied with fluorescent spot test and quantitative fluorescence assay. Diagnosis was performed using the modified NBTG6PD/6PGD ratio method. Bloodspot filter paper specimens were sent to the laboratory within 24 h via EMS Express, and the G6PD test was performed on the same day. The G6PD deficiency-positive rate was 4.2% in the samples screened using the fluorescent spot test, while it was 5% in case of the quantitative fluorescence assay. Neonatal screening for G6PD deficiency for 11,437 cases (6117 boys and 5320 girls) showed positive results in 481 cases. About 420 cases (318 boys and 102 girls) of G6PD deficiency were confirmed with the modified Duchenne NBT ratio method. The total detection rate was 3.7:5.2% for boys and 1.9% for girls. Quantitative fluorescence assay improved the sensitivity and detection rate. Accelerating the speed of sample delivery by using Internet network systems and ensuring online availability of screening results can aid the screening and diagnosis of this deficiency within 1 week of birth.

Research results: preserving newborn blood samples.

PubMed

Lewis, Michelle Huckaby; Scheurer, Michael E; Green, Robert C; McGuire, Amy L

2012-11-07

Retention and use, without explicit parental permission, of residual dried blood samples from newborn screening has generated public controversy over concerns about violations of family privacy rights and loss of parental autonomy. The public debate about this issue has included little discussion about the destruction of a potentially valuable public resource that can be used for research that may yield improvements in public health. The research community must advocate for policies and infrastructure that promote retention of residual dried blood samples and their use in biomedical research.

How to use: the neonatal neurological examination.

PubMed

Wusthoff, Courtney J

2013-08-01

The neurological exam can be a challenging part of a newborn's full evaluation. At the same time, the neonatal neurological exam is a useful tool in identifying babies needing closer evaluation for potential problems. The Dubowitz assessment is a standardised approach to the neonatal neurological exam designed for use by paediatricians in routine practice. Evidence has validated this technique and delineated its utility as a screening exam in various populations. This paper reviews clinical application of the Dubowitz assessment of the newborn.

Newborn screening for mucopolysaccharidoses: A pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

PubMed Central

Kubaski, Francyne; Mason, Robert W.; Nakatomi, Akiko; Shintaku, Haruo; Xie, Li; van Vlies, Naomi N.; Church, Heather; Giugliani, Roberto; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao; Fukao, Toshiyuki; Montaño, Adriana M.; Tomatsu, Shunji

2016-01-01

BACKGROUND Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible in skeletal, visceral and/or brain damage, highlighting a need for early diagnosis. METHODS This pilot study analyzed 2,862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. RESULTS The cutoffs were as follows: HS-0S> 90ng/mL; HS-NS> 23 ng/mL, DS> 88 ng/mL; mono-sulfated KS> 445 ng/mL; di-sulfated KS> 89 ng/mL and ratio di-KS in total KS> 32%. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03% based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9% based upon a combination of HS-0S and HS-NS. CONCLUSIONS Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS. PMID:27718145

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry.

PubMed

Kubaski, Francyne; Mason, Robert W; Nakatomi, Akiko; Shintaku, Haruo; Xie, Li; van Vlies, Naomi N; Church, Heather; Giugliani, Roberto; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao; Fukao, Toshiyuki; Montaño, Adriana M; Tomatsu, Shunji

2017-01-01

Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis. This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. The cutoffs were as follows: HS-0S > 90 ng/mL; HS-NS > 23 ng/mL, DS > 88 ng/mL; mono-sulfated KS > 445 ng/mL; di-sulfated KS > 89 ng/mL and ratio di-KS in total KS > 32 %. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS, and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03 % based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9 % based upon a combination of HS-0S and HS-NS. Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS.

Thyroid function testing in neonates born to women with hypothyroidism.

PubMed

McGovern, Matthew; Reyani, Zahra; O'Connor, Pamela; White, Martin; Miletin, Jan

2016-12-01

Our aim was to assess the utility of serum thyroxine and thyroid stimulating hormone performed at 10-14 days of life in diagnosing congenital hypothyroidism (CH) in babies born to mothers with hypothyroidism. This was a retrospective study of all babies born in a tertiary referral centre for neonatology over a 12-month period. Infants who had thyroid function testing (TFT) checked at 10-14 days of life because of maternal hypothyroidism during the period of study were included. The results of the newborn bloodspot and day 10-14 TFT were recorded along with whether or not patients were subsequently treated. Of the 319 patients included in the study, only two patients were found to have CH and in both cases the newborn blood spot had been abnormal. No extra cases of CH were detected from the thyroid test at 10-14 days and this practice should be discontinued due to the robust nature of existing newborn screening programmes. What is Known: • Congenital hypothyroidism(CH) is the commonest preventable cause of childhood intellectual impairment. • Family history of hypothyroidism has been implicated as a risk factor for CH. • CH has formed part of newborn screening since the 1970s. What is New: • There is no research recommending thyroid function testing at 10-14 days of life to detect CH in neonates born to mothers with hypothyroidism. • Thyroid function testing at 10-14 days of life does not improve diagnostic yield for CH in babies born to mothers with hypothyroidism. • Newborn blood spot remains the mainstay for accurate and timely diagnosis of CH.

Contralateral ear occlusion for improving the reliability of otoacoustic emission screening tests.

PubMed

Papsin, Emily; Harrison, Adrienne L; Carraro, Mattia; Harrison, Robert V

2014-01-01

Newborn hearing screening is an established healthcare standard in many countries and testing is feasible using otoacoustic emission (OAE) recording. It is well documented that OAEs can be suppressed by acoustic stimulation of the ear contralateral to the test ear. In clinical otoacoustic emission testing carried out in a sound attenuating booth, ambient noise levels are low such that the efferent system is not activated. However in newborn hearing screening, OAEs are often recorded in hospital or clinic environments, where ambient noise levels can be 60-70 dB SPL. Thus, results in the test ear can be influenced by ambient noise stimulating the opposite ear. Surprisingly, in hearing screening protocols there are no recommendations for avoiding contralateral suppression, that is, protecting the opposite ear from noise by blocking the ear canal. In the present study we have compared transient evoked and distortion product OAEs measured with and without contralateral ear plugging, in environmental settings with ambient noise levels <25 dB SPL, 45 dB SPL, and 55 dB SPL. We found out that without contralateral ear occlusion, ambient noise levels above 55 dB SPL can significantly attenuate OAE signals. We strongly suggest contralateral ear occlusion in OAE based hearing screening in noisy environments.

Tricuspid Atresia

MedlinePlus

... help the delivery team plan treatment. A screening pulse oximeter test usually is done on all newborns right ... and help plan treatment. The tests may include: pulse oximeter monitoring a chest X-ray electrocardiogram (also called ...

Screening for Critical Congenital Heart Disease in Newborns

MedlinePlus

... Bridging Disciplines Circulation at Major Meetings Special Themed Issues Global Impact of the 2017 ACC/AHA Hypertension Guidelines Circulation Supplements Cardiovascular Case Series ECG Challenge Hospitals of History Brigham and ...

Kayser-Fleischer Rings

MedlinePlus

... Terminology, 3rd edition; Barbara Cassin, Sheila A.B. Solomon) Description and Location Golden to greenish-brown annular ... Calculator WDA Publications Copper Connection Newsletter Stories Programs & Research Clinical Trials Newborn Screening Advocacy Initiatives Ways You ...

Trypsinogen test

MedlinePlus

... is also used to screen newborn babies for cystic fibrosis. Normal Results Normal value ranges may vary slightly ... to: Abnormal production of pancreatic enzymes Acute pancreatitis Cystic fibrosis Pancreatic cancer Low or normal levels may be ...

Genome Sequencing Technologies and Nursing: What Are the Roles of Nurses and Nurse Scientists?

PubMed Central

Taylor, Jacquelyn Y.; Wright, Michelle L.; Hickey, Kathleen T.; Housman, David

2016-01-01

Background Advances in DNA sequencing technology have resulted in an abundance of personalized data with challenging clinical utility and meaning for clinicians. This wealth of data has potential to dramatically impact the quality of healthcare. Nurses are at the focal point in educating patients regarding relevant healthcare needs; therefore, an understanding of sequencing technology and utilizing these data are critical. Aim The objective of this paper is to explicate the role of nurses and nurse scientists as integral members of healthcare teams in improving understanding of DNA sequencing data and translational genomics for patients. Approach A history of the nurse role in newborn screening is used as an exemplar. Discussion This paper serves as an exemplar on how genome sequencing has been utilized in nursing science and incorporates linkages of other omics approaches used by nurses that are included in this special issue. This special issue showcased nurse scientists conducting multi-omic research from various methods, including targeted candidate genes, pharmacogenomics, proteomics, epigenomics and the microbiome. From this vantage point, we provide an overview of the roles of nurse scientists in genome sequencing research and provide recommendations for the best utilization of nurses and nurse scientists related to genome sequencing. PMID:28252579

Novel heparan sulfate assay by using automated high-throughput mass spectrometry: application to monitoring and screening for mucopolysaccharidoses

PubMed Central

Shimada, Tsutomu; Kelly, Joan; LaMarr, William A; van Vlies, Naomi; Yasuda, Eriko; Mason, Robert W.; Mackenzie, William; Kubaski, Francyne; Giugliani, Roberto; Chinen, Yasutsugu; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E.; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

2014-01-01

Mucopolysaccharidoses (MPS) are caused by deficiency of one of a group of specific lysosomal enzymes, resulting in excessive accumulation of glycosaminoglycans (GAGs). We previously developed GAG assay methods using liquid chromatography tandem mass spectrometry (LC-MS/MS); however, it takes 4–5 min per sample for analysis. For the large numbers of samples in a screening program, a more rapid process is desirable. The automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) integrates a solid phase extraction robot to concentrate and desalt samples prior to direction into the MS/MS without chromatographic separation; thereby allowing each sample to be processed within ten seconds (enabling screening of more than one million samples per year). The aim of this study was to develop a higher throughput system to assay heparan sulfate (HS) using HT-MS/MS, and to compare its reproducibility, sensitivity and specificity with conventional LC-MS/MS. HS levels were measured in blood (plasma and serum) from control subjects and patients with MPS II, III, or IV and in dried blood spots (DBS) from newborn controls and patients with MPS I, II, or III. Results obtained from HT-MS/MS showed 1) that there was a strong correlation of levels of disaccharides derived from HS in blood, between those calculated using conventional LC-MS/MS and HT-MS/MS, 2) that levels of HS in blood were significantly elevated in patients with MPS II and III, but not in MPS IVA, 3) that the level of HS in patients with a severe form of MPS II was higher than that in an attenuated form, 4) that reduction of blood HS level was observed in MPS II patients treated with enzyme replacement therapy or hematopoietic stem cell transplantation, and 5) that levels of HS in newborn DBS were elevated in patients with MPS I, II or III, compared to control newborns. In conclusion, HT-MS/MS provides much higher throughput than LC-MS/MS-based methods with similar sensitivity and specificity in an HS assay, indicating that HT-MS/MS may be feasible for diagnosis, monitoring, and newborn screening of MPS. PMID:25092413

[The level of implementation of the prevention program of group B Streptococcal infection during pregnancy and in newborns in accordance to the recommendations of the Polish Gynaecological Society - questionnaire survey].

PubMed

Jaworowski, Andrzej; Huras, Hubert; Zembala-Szczerba, Margorzata; Babczyk, Dorota; Wolak, Agnieszka; Stettner, Dominika; Jach, Robert

Maternal colonization of Streptococcus agalactiae in pregnancy constitute an important clinical problem, that may result in serious consequences, especially for the newborn. Streptococcus agalactiae is a gram-positive beta-hemolytic streptococci belonging to the serological group B (GBS). According to recent data the GBS is found in 10-30% of healthy women, and the carriage of pathogen is usually asymptomatic. In order to minimize the risk of vertical transmission of the infection to the newborn during the labor, the Polish Society of Gynecology (PTG) has introduced the guidelines of GBS colonization screening for all pregnant women. In this paper, the level of implementation of the screening tests in accordance to the recommendations of the PTG was evaluated. We also assessed the level of knowledge and awareness of pregnant women in detection of GBS colonization during the pregnancy and the prevention of infection in newborn. The survey was conducted among the 172 women hospitalized in hospital maternity wards in the first days of postpartum. Despite the introduction of the Polish Society of Gynecology guidelines, there are still cases of improper screening methods and medical interventions in the event of positive test results. Biological material was collected in 86% of patients (swabs from the genital tract, anus or urine culture). A positive result was found in 22% of patients. In 54% of patients swabs were taken at the recommended period of 35-37 weeks. The recommended collection of the material both from vagina and anus was taken only in 39% of patients. The majority of participated women described their knowledge of the risk associated with group B Streptococcal colonization as good, however only half of them found acquired information sufficient. Despite the implementation of guidelines Polish Gynaecological Society the incorrect conduct of the prevention against GBS is still performed in some cases. It is appropriate to perform consciousnessraising campaigns on screening of GBS among patients and doctors.

Differences in clinical condition and genotype at time of diagnosis of cystic fibrosis by newborn screening or by symptoms.

PubMed

Vernooij-van Langen, A M M; Gerzon, F L G R; Loeber, J G; Dompeling, E; Dankert-Roelse, J E

2014-01-01

Early diagnosis through newborn screening (NBS) and early treatment of cystic fibrosis (CF) do lead to better prognosis. In the Netherlands, the median age for a clinical diagnosis is six months, and after newborn screening this is 30 days. It is unknown if being diagnosed at the age of six months or before two months leads to a clinically relevant difference of the clinical condition at the time of diagnosis. The aim of this study is to assess the differences in clinical parameters at diagnosis between children with CF identified by newborn screening (NBS) or by clinical diagnosis (CD) in the Netherlands. From July 1st, 2007 to January 1st, 2012 all newly diagnosed CF patients were reported to the Dutch Paediatric Surveillance Unit (DPSU). All paediatricians received a questionnaire to collect data on mutations and clinical condition at diagnosis. Non-classical CF was excluded from the analysis on clinical condition. 204 new CF diagnoses were reported to the DPSU, 33 were reported twice and three had no CF after further testing. 127 questionnaires were returned (76%); 85 children were diagnosed because of clinical symptoms, 40 after NBS and two because of a positive family history. The median age at diagnosis was 34 weeks for a clinical diagnosis and 3 weeks after NBS. Non-classical CF was more prevalent in the NBS group (6 clinical, 14 NBS), mostly F508del/R117H7T (12). Compared to the NBS group, significantly more patients in the CD group showed failure to thrive, respiratory symptoms, and hospitalizations. 62% of the CD group showed abnormal signs at physical examination compared to 4% of the NBS group. At the time of diagnosis infants detected after NBS are in a significantly better condition than after a clinical diagnosis. Growth retardation is already seen when after NBS the diagnosis is confirmed, but NBS leads to a diagnosis before respiratory symptoms have developed. Copyright © 2014 Elsevier Inc. All rights reserved.

The reliability of a newborn foot length measurement tool used by community volunteers to identify low birth weight or premature babies born at home in southern Tanzania.

PubMed

Marchant, Tanya; Penfold, Suzanne; Mkumbo, Elibariki; Shamba, Donat; Jaribu, Jennie; Manzi, Fatuma; Schellenberg, Joanna

2014-08-20

Low birthweight babies need extra care, and families need to know whether their newborn is low birthweight in settings where many births are at home and weighing scales are largely absent. In the context of a trial to improve newborn health in southern Tanzania, a counselling card was developed that incorporated a newborn foot length measurement tool to screen newborns for low birth weight and prematurity. This was used by community volunteers at home visits and shows a scale picture of a newborn foot with markers for a 'short foot' (<8 cm). The tool built on previous hospital based research that found newborn foot length <8 cm to have sensitivity and specificity to identify low birthweight (<2500 g) of 87% and 60% respectively. Reliability of the tool used by community volunteers to identify newborns with short feet was tested. Between July-December 2010 a researcher accompanied volunteers to the homes of babies younger than seven days and conducted paired measures of newborn foot length using the counselling card tool and using a plastic ruler. Intra-method reliability of foot length measures was assessed using kappa scores, and differences between measurers were analysed using Bland and Altman plots. 142 paired measures were conducted. The kappa statistic for the foot length tool to classify newborns as having small feet indicated that it was moderately reliable when applied by volunteers, with a kappa score of 0.53 (95% confidence interval 0.40 - 0.66) . Examination of differences revealed that community volunteers systematically underestimated the length of newborn feet compared to the researcher (mean difference -0.26 cm (95% confidence interval -0.31-0.22), thus overestimating the number of newborns needing extra care. The newborn foot length tool used by community volunteers to identify small babies born at home was moderately reliable in southern Tanzania where a large number of births occur at home and scales are not available. Newborn foot length is not the best anthropometric proxy for birthweight but was simple to implement at home in the first days of life when the risk of newborn death is highest.

Glucose-6-Phosphate Dehydrogenase Screening in Israel-Arab and Palestinian-Arab Neonates.

PubMed

Abu Omar, Rawan; Algur, Nurit; Megged, Orli; Hammerman, Cathy; Kaplan, Michael

2015-07-01

To evaluate the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, the incidence of clinically significant jaundice (any serum total bilirubin value >75th percentile on the hour-specific bilirubin nomogram), and the need for phototherapy in the pooled male Israeli-Arab and Palestinian-Arab population born at the Shaare Zedek Medical Center in Jerusalem, Israel. Quantitative G-6-PD enzyme testing of umbilical cord blood was performed during birth hospitalization. G-6-PD deficiency was defined as any G-6-PD value <7.0 U/gHb. Transcutaneous bilirubin was performed daily during birth hospitalization, with serum total bilirubin testing in those with a transcutaneous bilirubin value >75th percentile. Ten of 286 (3.5%) consecutively delivered male Arab newborns had G-6-PD deficiency. Clinically significant jaundice was higher in the population with G-6-PD deficiency compared with normal controls (relative risk, 3.45; 95% CI, 1.24-9.58). Thirty percent of the newborns with G-6-PD deficiency met American Academy of Pediatrics indications for phototherapy according to the high-risk (middle) curve on the phototherapy graph. The frequency of G-6-PD deficiency in the Arab neonatal population delivering at this medical center meets World Health Organization criteria for neonatal G-6-PD screening (3%-5%). As in other ethnic groups, clinically significant jaundice is more frequent in newborns of this ethnic group with G-6-PD deficiency compared with G-6-PD-normal controls. Neonatal G-6-PD screening for both males and females of this population subgroup, in conjunction with parental education regarding the dangers of the condition and its prophylaxis, has now been incorporated into our institution's routine G-6-PD screening program. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation.

PubMed

Kopacek, Cristiane; Prado, Mayara J; da Silva, Claudia M D; de Castro, Simone M; Beltrão, Luciana A; Vargas, Paula R; Grandi, Tarciana; Rossetti, Maria L R; Spritzer, Poli Mara

2018-04-30

To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients. Copyright © 2018. Published by Elsevier Editora Ltda.

[Primary care follow-up of newborns with sickle cell disease detected in neonatal screening in the Community of Madrid].

PubMed

Rodríguez-Moldes, B; Carbajo, A J; Sánchez, B; Fernández, M; Garí, M; Fernández, M C; Álvarez, J; García, A; Cela, E

2015-04-01

The main aim of the study was to assess the effects of the recommended preventive program in the population affected with Sickle Cell Disease in Primary Care. The program included, antibiotic prophylaxis, immunizations and health education, following the introduction of universal neonatal screening program for Sickle Cell Disease in the Community of Madrid. A cross-sectional observational study was performed with retrospective data collected from a cohort of newborns with Sickle Cell Disease diagnosed by neonatal screening test in the Community of Madrid. From the data obtained from a sample of 20 patients, it was found that 95% had been diagnosed by the newborn screening test performed between 5 and 13 days of life. The mean age was 39 months when the study was conducted. During follow-up, from Primary Care Paediatric clinic, it was observed that the compliance for antibiotic prophylaxis was 90%, and the coverage for the official vaccination schedule was 85%. Specific vaccine coverage as a risk population was highly variable (85% for pneumococcal 23V, 50% for influenza, and 15% for hepatitis A). Health education only reached one in every four families. Acceptable compliance with antibiotic prophylaxis was observed during the follow-up of patients with sickle cell disease in Primary Care, but a low coverage of routine immunization, as well as specific immunizations. Coverage of health education was very low. Improving these parameters would require greater coordination and involvement of Primary Care Professionals so that these patients were followed up appropriately, and could be translated into a reduction of disease complications and an improvement in the quality of life of these patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency.

PubMed

Diekman, Eugene; de Sain-van der Velden, Monique; Waterham, Hans; Kluijtmans, Leo; Schielen, Peter; van Veen, Evert Ben; Ferdinandusse, Sacha; Wijburg, Frits; Visser, Gepke

2016-01-01

To improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD). Data on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ≥0.8 μmol/L), six newborns with VLCADD had been identified through NBS during this period. The ratio of C14:1 over C2 was calculated. DNA of all blood spots with a C14:1/C2 ratio of ≥0.020 was isolated and sequenced. Children homozygous or compound heterozygous for mutations in the ACADVL gene were traced back and invited for detailed clinical, biochemical, and genetic evaluation. Retrospective analysis based on the C14:1/C2 ratio with a cutoff of ≥0.020 identified an additional five children with known ACADVL mutations and low enzymatic activity. All were still asymptomatic at the time of diagnosis (age 2-5 years). Increasing the cutoff to ≥0.023 resulted in a sensitivity of 93% and a positive predictive value of 37%. The sensitivity of the previously used screening approach (C14:1 ≥0.8) was 50%. This study shows that the ratio C14:1/C2 is a more sensitive marker than C14:1 for identifying VLCADD patients in NBS. However, as these patients were all asymptomatic at the time of diagnosis, this suggests that a more sensitive screening approach may also identify individuals who may never develop clinical disease. Long-term follow-up studies are needed to establish the risk of these VLCADD-deficient individuals for developing clinical signs and symptoms.

Newborn screening by tandem mass spectrometry: ethical and social issues.

PubMed

Avard, Denise; Vallance, Hilary; Greenberg, Cheryl; Potter, Beth

2007-01-01

Emerging technologies like Tandem Mass Spectrometry (TMS) enable multiple tests on a single blood sample and allow the expansion of Newborn Screening (NBS) to include various metabolic diseases. Introducing TMS for NBS raises important social and ethical questions: what are the criteria for adding disorders to screening panels? What evidence justifies expansion of screening? How can equity in NBS access and standards be ensured? How can policy standards be set, given the multiplicity of stakeholders? To address emerging issues, policy-makers, patient advocates, clinicians and researchers had a workshop during the 2005 Garrod Symposium. The participants received a summary of the discussion and understood the workshop's goal was to provide a basis for further discussion. This article contributes to this ongoing discussion. Several proposed recommendations assert the centrality of including social and ethical issues in the assessment of whether or not to introduce TMS. The article outlines five key recommendations for advancing the NBS agenda: national public health leadership; transparency; increased national consistency in NBS strategy, including minimum standards; collaboration between the federal and provincial/territorial governments and diverse stakeholders; and supporting research and/or programs based on effectiveness, which integrate ethical and social issues into assessment.

Biobank participant support of newborn screening for disorders with variable treatment and intervention options.

PubMed

Bunnell, Megan E; Tarini, Beth A; Petros, Michael; Goldenberg, Aaron J; Arjunan, Aishwarya; Wicklund, Catherine

2016-10-01

We aimed to better understand biobank participant opinions of the benefits of newborn screening (NBS) for certain disorder types and how terminology used in NBS discourse might impact stakeholder opinion. We conducted a between-subjects randomized survey of 5840 members of the Northwestern University Biobank. The survey contained 12 scenarios, each describing a disorder and its treatment. For each scenario, we varied the terminology used to describe treatment options. One survey version used the term intervention and the other treatment. The outcome measured for each scenario was perceived benefit (for the infant) and importance of testing (for participants). Comparisons were made between participants and between scenarios. Ratings of benefit and importance were not influenced by the use of the term intervention versus treatment within scenarios. Nuances existed in ratings of benefit to the infant and importance to participants amongst scenarios. Participants were most likely to perceive benefit and importance in screening for a disorder if treatment/intervention offered a high chance of improved outcomes. While participants perceived benefit to the infant and importance to themselves in screening for most disorders, nuances in inter-scenario ratings suggest participants weighed availability and type of treatment/intervention in consideration of the benefits of NBS.

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait.

PubMed

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-12-31

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits.

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait

PubMed Central

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-01-01

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits. PMID:14975142

Results From the New Jersey Statewide Critical Congenital Heart Defects Screening Program

PubMed Central

Garg, Lorraine F.; Van Naarden Braun, Kim; Knapp, Mary M.; Anderson, Terry M.; Koppel, Robert I.; Hirsch, Daniel; Beres, Leslie M.; Hyg, MS; Sweatlock, Joseph; Olney, Richard S.; Glidewell, Jill; Hinton, Cynthia F.; Kemper, Alex R.

2015-01-01

BACKGROUND AND OBJECTIVE New Jersey was the first state to implement legislatively mandated newborn pulse oximetry screening (POxS) in all licensed birthing facilities to detect critical congenital heart defects (CCHDs). The objective of this report was to evaluate implementation of New Jersey’s statewide POxS mandate. METHODS A 2-pronged approach was used to collect data on infants screened in all New Jersey birthing facilities from August 31, 2011, through May 31, 2012. Aggregate screening results were submitted by each birthing facility. Data on failed screens and clinical characteristics of those newborns were reported to the New Jersey Birth Defects Registry (NJBDR). Three indicators were used to distinguish the added value of mandated POxS from standard clinical care: prenatal congenital heart defect diagnosis, cardiology consultation or echocardiogram indicated or performed before PoxS, or clinical findings at the time of POxS warranting a pulse oximetry measurement. RESULTS Of 75 324 live births in licensed New Jersey birthing facilities, 73 320 were eligible for screening, of which 99% were screened. Forty-nine infants with failed POxS were reported to the NJBDR, 30 of whom had diagnostic evaluations solely attributable to the mandated screening. Three of the 30 infants had previously unsuspected CCHDs and 17 had other diagnoses or non-CCHD echocardiogram findings. CONCLUSIONS In the first 9 months after implementation, New Jersey achieved a high statewide screening rate and established surveillance mechanisms to evaluate the unique contribution of POxS. The screening mandate identified 3 infants with previously unsuspected CCHDs that otherwise might have resulted in significant morbidity and mortality and also identified other significant secondary targets such as sepsis and pneumonia. PMID:23858425

Novel application of digital microfluidics for the detection of biotinidase deficiency in newborns.

PubMed

Graham, Carrie; Sista, Ramakrishna S; Kleinert, Jairus; Wu, Ning; Eckhardt, Allen; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2013-12-01

Newborn screening for biotinidase deficiency can be performed using a fluorometric enzyme assay on dried blood spot specimens. As a pre-requisite to the consolidation of different enzymatic assays onto a single platform, we describe here a novel analytical method for detecting biotinidase deficiency using the same digital microfluidic cartridge that has already been demonstrated to screen for five lysosomal storage diseases (Pompe, Fabry, Gaucher, Hurler and Hunter) in a multiplex format. A novel assay to quantify biotinidase concentration in dried blood spots (DBS) was developed and optimized on the digital microfluidic platform using proficiency testing samples from the Centers for Disease Control and Prevention. The enzymatic assay uses 4-methylumbelliferyl biotin as the fluorogenic substrate. Biotinidase deficiency assays were performed on normal (n=200) and deficient (n=7) newborn DBS specimens. Enzymatic activity analysis of biotinidase deficiency revealed distinct separation between normal and affected DBS specimens using digital microfluidics and these results matched the expected activity. This study has demonstrated performance of biotinidase deficiency assays by measurement of 4-methylumbelliferyl product on a digital microfluidic platform. Due to the inherent ease in multiplexing on such a platform, consolidation of other fluorometric assays onto a single cartridge may be realized. © 2013.

Power reflectance testing in newborns and infants.

PubMed

Lima, Ticianna Garambone de Cerqueira; Becker, Helena Maria Gonçalves; Becker, Celso Gonçalves; Ferreira, Daniele Barreto da Cunha; Resende, Camilo Brandão de; Guimarães, Roberto Eustáquio Santos

2015-01-01

Auditory screening in newborns allows for detection of hearing problems early in life. However, middle ear diseases can make the diagnosis more difficult. To evaluate the power reflectance test as an indicator of the middle ear disease and to compare it to tympanometry. Case study evaluating 105 newborns and infants who participated in the audiology screening in 2013. The following exams were performed: transient otoacoustic emissions, power reflectance, and tympanometry. In the optoacoustic emission evaluation, approximately 95% of the subjects passed the test. The specificity of power reflectance in all frequencies studied ranged from 75.3% to 95.9%, and that of tympanometry at 1000Hz ranged from 83% to 87.2%; there was agreement among these exams. The outcome of power reflectance tests at 2000Hz and 3000Hz showed a correlation with tympanometry and otoacoustic emissions, and these were the most appropriate frequencies to determine middle ear disease through power reflectance measurement. It was also observed that values of power reflectance above reference levels suggested the presence of fluid in the middle ear, and thus a conductive hearing loss. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Recent Developments in Toxico-Cheminformatics; Supporting a New Paradigm for Predictive Toxicology

EPA Science Inventory

EPA's National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-content and high-thoughput screening d...

Advances in Toxico-Cheminformatics: Supporting a New Paradigm for Predictive Toxicology

EPA Science Inventory

EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-throughput screening (HTS) data. The D...

A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families.

PubMed

Amundsen, Silja Svanstrøm; Adamovic, Svetlana; Hellqvist, Asa; Nilsson, Staffan; Gudjónsdóttir, Audur H; Ascher, Henry; Ek, Johan; Larsson, Kristina; Wahlström, Jan; Lie, Benedicte A; Sollid, Ludvig M; Naluai, Asa Torinsson

2007-09-01

Celiac disease (CD) is a gluten-induced enteropathy, which results from the interplay between environmental and genetic factors. There is a strong human leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes appear to be crucial for CD development. Chromosomal region 5q31-33 has demonstrated linkage with CD in several genome-wide studies, including in our Swedish/Norwegian cohort. In a European meta-analysis 5q31-33 was the only region that reached a genome-wide level of significance except for the HLA region. To identify the genetic variant(s) responsible for this linkage signal, we performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families who demonstrate linkage to the region. We selected tag SNPs from a 16 Mb region representing the 95% confidence interval of the linkage peak. A total of 1,404 SNPs were used for the association analysis. We identified several regions with SNPs demonstrating moderate single- or multipoint associations. However, the isolated association signals appeared insufficient to account for the linkage signal seen in our cohort. Collective effects of multiple risk genes within the region, incomplete genetic coverage or effects related to copy number variation are possible explanations for our findings.

Presence and duration of anti-Toxoplasma gondii immunoglobulin M in infants with congenital toxoplasmosis.

PubMed

Lago, Eleonor G; Oliveira, Anna Paula; Bender, Ana Lígia

2014-01-01

to investigate the rate of positivity for immunoglobulin M anti-Toxoplasma gondii (Toxo-IgM) in newborns with congenital toxoplasmosis, and the age when these antibodies become negative. patients with congenital toxoplasmosis who started monitoring in a congenital infection clinic between 1998 and 2009 were included. Inclusion criteria were routine maternal or neonatal serological screening; diagnostic confirmation by persistence of immunoglobulin G anti-Toxoplasma gondii at age ≥ 12 months, and Toxo-IgM screening in the neonatal period. To calculate the frequency of positive Toxo-IgM, cases detected by neonatal screening were excluded. For the study of the age when Toxo-IgM results became negative, patients with negative Toxo-IgM since birth and those in whom it was not possible to identify the month when the negative result was achieved were excluded. among the 28 patients identified through maternal screening, 23 newborns had positive Toxo-IgM (82.1%, 95% CI: 64.7-93.1%). When adding the 37 patients identified by neonatal screening, Toxo-IgM was positive in the first month of life in 60 patients, and it was possible to identify when the result became negative in 51 of them. In 19.6% of patients, these antibodies were already negative at 30 days of life; and in 54.9%, at 90 days. Among the 65 patients included in the study, 40 (61.5%) had some clinical alteration. even with high sensitivity methods, newborns with congenital toxoplasmosis can have negative Toxo-IgM at birth. In those who have these antibodies, the positive period may be quite short. It is important not to interrupt the monitoring of infants with suspected congenital toxoplasmosis simply because they present a negative Toxo-IgM result. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Purpose of Newborn Hearing Screening

MedlinePlus

... services, babies will have trouble with speech and language development. For some babies, early intervention services may include ... baby will have the best chance for normal language development if any hearing loss is discovered and treatment ...

Genetics Home Reference: Floating-Harbor syndrome

MedlinePlus

... Patton MA, Hurst J, Donnai D, McKeown CM, Cole T, Goodship J. Floating-Harbor syndrome. J Med ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

How Are Newborn Screening Tests Done?

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... Health Advances NICHD Nobel Prize Winners Leadership & Other Staff Profiles Leadership Biosketches Get to Know NICHD Budget & ... Listservs About NICHD Organization History Accomplishments Leadership & Other Staff Profiles Budget & Appropriations Advisory Groups Jobs at NICHD ...

Genetics Home Reference: histidinemia

MedlinePlus

... condition characterized by elevated blood levels of the amino acid histidine, a building block of most proteins. Histidinemia ... Additional Information & Resources MedlinePlus (2 links) Health Topic: Amino Acid Metabolism Disorders Health Topic: Newborn Screening Genetic and ...

Early hearing detection and intervention: 2010 CODEPEH recommendation.

PubMed

Trinidad-Ramos, Germán; de Aguilar, Valentín Alzina; Jaudenes-Casaubón, Carmen; Núñez-Batalla, Faustino; Sequí-Canet, José Miguel

2010-01-01

Newborn hearing screening is currently performed routinely in many regional health-care systems in Spain. Despite the remarkable expansion in newborn hearing screening since 2000, its feasibility and the benefits of early identification and intervention, many major challenges still remain. In this article, the Committee for the Early Detection of Hearing Loss (Comisión para la Detección Precoz de la Hipoacusia, CODEPEH) updates the recommendations that are considered important for the future development of early hearing detection and intervention (EDHI) systems in the following points: 1. Screening protocols: Separate protocols are recommended for NICU (Neonatal Intensive Care Units) and well-infant nurseries. 2. Diagnostic audiology evaluation. Professionals with skills and expertise in evaluating newborn and young infants should provide diagnosis, selection and fitting of amplification devices. 3. Medical evaluation. Risk factors for congenital and acquired hearing loss have been combined in a single list rather than grouped by time of onset. A stepwise diagnostic paradigm is diagnostically more efficient and cost-effective than a simultaneous testing approach. 4. Early intervention and surveillance. All individuals providing services to infants with hearing loss should have specialized training and expertise in the development of audition, speech and language. Regular surveillance should be performed on developmental milestones, auditory skills, parental concerns, and middle ear status. 5. Quality control. Data management as part of an integrated system is important to monitor and improve the quality of EDHI services. 2009 Elsevier España, S.L. All rights reserved.

Fostering caring relationships: Suggestions to rethink liberal perspectives on the ethics of newborn screening

PubMed Central

Oerlemans, Anke

2018-01-01

Abstract Newborn screening (NBS) involves the collection of blood from the heel of a newborn baby and testing it for a list of rare and inheritable disorders. New biochemical screening technologies led to expansions of NBS programs in the first decade of the 21st century. It is expected that they will in time be replaced by genetic sequencing technologies. These developments have raised a lot of ethical debate. We reviewed the ethical literature on NBS, analyzed the issues and values that emerged, and paid particular interest to the type of impacts authors think NBS should have on the lives of children and their families. Our review shows that most authors keep their ethical reflection confined to policy decisions, about for instance (a) the purpose of the program, and (b) its voluntary or mandatory nature. While some authors show appreciation of how NBS information empowers parents to care for their (diseased) children, most authors consider these aspects to be ‘private’ and leave their evaluation up to parents themselves. While this division of moral labor fits with the liberal conviction to leave individuals free to decide how they want to live their private lives, it also silences the ethical debate about these issues. Given the present and future capacity of NBS to offer an abundance of health‐related information, we argue that there is good reason to develop a more substantive perspective to whether and how NBS can contribute to parents’ good care for children. PMID:29442381

Newborn screening blood spot analysis in the UK: influence of spot size, punch location and haematocrit.

PubMed

Lawson, A J; Bernstone, L; Hall, S K

2016-03-01

In dried blood spot analysis, punch location and variations in applied sample volume and haematocrit can produce different measured concentrations of analytes. We investigated the magnitude of these effects in newborn screening in the UK. Heparinized blood spiked with thyroid stimulating hormone (TSH), phenylalanine, tyrosine, leucine, methionine, octanoyl carnitine (C8), and immunoreactive trypsinogen (IRT) was spotted onto filter paper: (i) at a constant haematocrit of 50% at various volumes, and (ii) at a range of haematocrits using a constant volume. Subpunches (3.2 mm) of the dried blood spots were then analysed. Compared with a central punch from a 50 µL blood spot with 50% haematocrit, 10 µL spots can have significantly lower measured concentrations of all analytes, with decreases of 15% or more observed for leucine, methionine, phenylalanine, and tyrosine. Punching at the edge of a spot can increase measured concentrations up to 35%. Higher haematocrit decreased measured TSH and C8 yet increased amino acids and IRT by 15% compared with 50% haematocrit. Lower haematocrits had the opposite effect, but only with higher concentrations of some analytes. Differences in blood spot size, haematocrit and punch location substantially affect measured concentrations for analytes used in the UK newborn screening programme, and this could affect false positive and negative rates. To minimize analytical bias, these variables should be controlled or adjusted for where possible. © The Author(s) 2015.

Reference values of amino acids, acylcarnitines and succinylacetone by tandem mass spectrometry for use in newborn screening in southwest Colombia

PubMed Central

Céspedes, Nora; Valencia, Angela; Echeverry, Carlos Alberto; Arce-Plata, Maria Isabel; Colón, Cristóbal; Castiñeiras, Daisy E; Hurtado, Paula Margarita; Cocho, Jose Angel; Herrera, Sócrates

2017-01-01

Abstract Introduction: Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality of affected patients, and consequent untimely child death. In contrast to classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation of multiple metabolites associated with IEM offering higher sensitivity, low false positive rates and high throughput. Aims: Determine concentration levels for amino acids and acylcarnitines in blood of newborns from Colombia, to establish reference values for further use in diagnosis of IEM. Methods: Implementation of a method to determine amino acids, acylcarnitines and succinylacetone in newborn dried blood spots using MS/MS, and its application in a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo cities is described. Results: fifty-seven analytes that allow the diagnosis of more than 40 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 1-18 days of age were included, 523 from Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the concentration levels of amino acids and acylcarnitines were observed whereas no significant differences by gender were found. Conclusion: The study has contributed to reveal the usual concentration levels of amino acids, acylcarnitines and succinylacetone that could be used as reference for the establishment of a newborn metabolic screening program in Colombia. PMID:29213153

Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia.

PubMed

Sarafoglou, Kyriakie; Banks, Kathryn; Gaviglio, Amy; Hietala, Amy; McCann, Mark; Thomas, William

2012-11-01

Newborn screening (NBS) for the classic forms of congenital adrenal hyperplasia (CAH) is mandated in all states in the United States. Compared with other NBS disorders, the false-positive rate (FPR) of CAH screening remains high and has not been significantly improved by adjusting 17α-hydroxyprogesterone cutoff values for birth weight and/or gestational age. Minnesota was the first state to initiate, and only 1 of 4 states currently performing, second-tier steroid profiling for CAH. False-negative rates (FNRs) for CAH are not well known. This is a population-based study of all Minnesota infants (769,834) born 1999-2009, grouped by screening protocol (one-tier with repeat screen, January 1999 to May 2004; two-tier with second-tier steroid profiling, June 2004 to December 2009). FPR, FNR, and positive predictive value (PPV) were calculated per infant, rather than per sample, and compared between protocols. Overall, 15 false-negatives (4 salt-wasting, 11 simple-virilizing) and 45 true-positives were identified from 1999 to 2009. With two-tier screening, FNR was 32%, FPR increased to 0.065%, and PPV decreased to 8%, but these changes were not statistically significant. Second-tier steroid profiling obviated repeat screens of borderline results (355 per year average). In comparing the 2 screening protocols, the FPR of CAH NBS remains high, the PPV remains low, and false-negatives occur more frequently than has been reported. Physicians should be cautioned that a negative NBS does not necessarily rule out classic CAH; therefore, any patient for whom there is clinical concern for CAH should receive immediate diagnostic testing.

Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease: Utility and Limitations

PubMed Central

Zhao, Xiao; Paterson, Andrew D.; Zahirieh, Alireza; He, Ning; Wang, Kairong; Pei, York

2008-01-01

Background and objectives: Gene-based mutation screening is now available and has the potential to provide diagnostic confirmation or exclusion of autosomal dominant polycystic kidney disease. This study illustrates its utility and limitations in the clinical setting. Design, setting, participants, & measurements: Using a molecular diagnostic service, genomic DNA of one affected individual from each study family was screened for pathologic PKD1 and PKD2 mutations. Bidirectional sequencing was performed to identify sequence variants in all exons and splice junctions of both genes and to confirm the specific mutations in other family members. In two multiplex families, microsatellite markers were genotyped at both PDK1 and PKD2 loci, and pair-wise and multipoint linkage analysis was performed. Results: Three of five probands studied were referred for assessment of renal cystic disease without a family history of autosomal dominant polycystic kidney disease, and two others were younger at-risk members of families with autosomal dominant polycystic kidney disease being evaluated as living-related kidney donors. Gene-based mutation screening identified pathogenic mutations that provided confirmation or exclusion of disease in three probands, but in the other two, only unclassified variants were identified. In one proband in which mutation screening was indeterminate, DNA linkage studies provided strong evidence for disease exclusion. Conclusions: Gene-based mutation screening or DNA linkage analysis should be considered in individuals in whom the diagnosis of autosomal dominant polycystic kidney disease is uncertain because of a lack of family history or equivocal imaging results and in younger at-risk individuals who are being evaluated as living-related kidney donors. PMID:18077784

A public health approach to cervical cancer control: considerations of screening and vaccination strategies.

PubMed

Goldie, Sue

2006-11-01

Cervical cancer remains a leading cause of cancer death among women living in low-resource settings. In the last 3 decades, cytologic screening has -in theory -been available and yet more than 6 million women have died of this preventable disease. The necessary resources, infrastructure, and technological expertise, together with the need for repeated screenings at regular intervals, make cytologic screening difficult to implement in poor countries. As noncytologic approaches for the detection of HPV, simple visual screening methods for anogenital lesions caused by HPV, and the availability of an HPV-16/18 vaccine will enhance the linkage between screening and treatment, multiple factors will need to be considered when designing new, or modifying existing prevention strategies. Countryspecific decisions regarding the best strategy for cervical cancer control will need to rely on data from many sources and take into account complex epidemiologic, economic, social, political, and cultural factors, and be made despite uncertainty and incomplete information. A rigorous decision analytic approach using computerbased modeling methods enables linkage of the knowledge gained from empirical studies to real-world situations. This chapter provides an introduction to these methods, reviews lessons learned from cost-effectiveness analyses of cervical cancer screening in developed and developing countries, and emphasizes important qualitative themes to consider in designing cervical cancer prevention policies.

Outcome of the Respiratory Syncytial Virus related acute lower respiratory tract infection among hospitalized newborns: a prospective multicenter study.

PubMed

Alan, Serdar; Erdeve, Omer; Cakir, Ufuk; Akduman, Hasan; Zenciroglu, Aysegul; Akcakus, Mustafa; Tunc, Turan; Gokmen, Zeynel; Ates, Can; Atasay, Begum; Arsan, Saadet

2016-01-01

To determine the incidence and outcomes of respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (ALRI) including morbidity, nosocomial infection and mortality among newborn infants who were admitted to the neonatal intensive care units (NICUs). A multicenter, prospective study was conducted in newborns who were hospitalized with community acquired or nosocomial RSV infection in 44 NICUs throughout Turkey. Newborns with ALRI were screened for RSV infection by Respi-Strip®-test. Main outcome measures were the incidence of RSV-associated admissions in the NICUs and morbidity, mortality and epidemics results related to these admissions. The incidence of RSV infection was 1.24% (n: 250) and RSV infection constituted 19.6% of all ALRI hospitalizations, 226 newborns (90.4%) had community-acquired whereas 24 (9.6%) patients had nosocomial RSV infection in the NICUs. Of the 250 newborns, 171 (68.4%) were full-term infants, 183 (73.2%) had a BW >2500 g. RSV-related mortality rate was 1.2%. Four NICUs reported seven outbreaks on different months, which could be eliminated by palivizumab prophylaxis in one NICU. RSV-associated ALRI both in preterm and term infants accounts an important percent of hospitalizations in the season, and may threat other high-risk patients in the NICU.

Maternal knowledge and attitudes to universal newborn hearing screening: Reviewing an established program.

PubMed

Lam, Maggie Yee Yan; Wong, Eddie Chi Ming; Law, Chi Wai; Lee, Helena Hui Ling; McPherson, Bradley

2018-02-01

To facilitate early diagnosis of infants with hearing loss, a universal newborn hearing screening program (UNHS) has been implemented in Hong Kong's public hospitals for over a decade. However, there have been no known studies investigating parent attitudes to, and satisfaction with, UNHS since its launch in Hong Kong. The present study aimed to investigate knowledge of UNHS as well as infant hearing development, and attitudes and satisfaction with UNHS, in Hong Kong mothers with newborns. The study was designed to help evaluate and improve an established UNHS public hospital program, based on the perspectives of service users. A researcher-developed questionnaire was administered to 102 mothers whose newborn had received UNHS in the postnatal wards of a large public hospital in Hong Kong. The questionnaire considered parental knowledge of UNHS and infant hearing development, attitudes and satisfaction toward public hospital UNHS. In the knowledge dimension, parents' preferred time and location for pre-test information delivery, interpretation of screening results, and knowledge of hearing developmental milestones were surveyed. In addition, maternal attitudes to and satisfaction with UNHS screening services, the potential impact of UNHS on parent emotions and parent-baby bonding, attitudes toward informed consent, and willingness to comply with diagnostic assessment referral were also be surveyed. Mean participant scores on knowledge of infant hearing development were relatively low (M = 2.59/6.0, SD = 0.90). Many mothers also underestimated the potential ongoing risks of hearing impairment in babies. Around 80% of mothers thought an infant could not have hearing impairment after passing the screening. In addition, one-third of mothers thought a baby could not later develop hearing impairment in infancy or childhood. In terms of attitudes and satisfaction, participants gave somewhat negative ratings for questions regarding receiving sufficient information about the screening (M = 2.90/5.0, SD = 1.27), screening procedure (M = 2.20/5.0, SD = 1.08), and sufficiency of information about results (M = 2.87/5.0, SD = 1.14). Nonetheless, participants gave positive ratings concerning whether screening could lead to early diagnosis (M = 4.61/5.0, SD = 0.57) and over 95% of mothers supported UNHS despite potential for false positive results. Mothers reported a high willingness to bring their baby to follow-up assessments if required (M = 4.53/5.0, SD = 0.56). Participants gave positive ratings for their level of satisfaction with the time and location of first UNHS information provision (M = 4.34/5.0, SD = 0.80) and the way permission was asked for screening the baby (M = 4.04/5.0, SD = 0.97) but alternative procedures were also recommended. Most recommendations focused on providing more information about the test and a more detailed explanation of screening results. The survey results highlighted the need to provide more information to parents about infant hearing development to support home monitoring for signs of hearing loss after UNHS, as well as more detailed explanation and information regarding hearing screening and the implications of results to parents. Regardless of location, surveys of this type may provide valuable support for UNHS program quality assurance. Copyright © 2017. Published by Elsevier B.V.

Current practice, accuracy, effectiveness and cost-effectiveness of the school entry hearing screen.

PubMed

Bamford, J; Fortnum, H; Bristow, K; Smith, J; Vamvakas, G; Davies, L; Taylor, R; Watkin, P; Fonseca, S; Davis, A; Hind, S

2007-08-01

To describe and analyse in detail current practice of school entry hearing screening (SES) in the UK. Main electronic databases were searched up to May 2005. A national postal questionnaire survey was addressed to all leads for SES in the UK, considering current practice in terms of implementation, protocols, target population and performance data. Primary data from cohort studies in one area of London were examined. A systematic review of alternative SES tests, test performance and impact on outcomes was carried out. Finally, a review of published studies on costs, plus economic modelling of current and alternative programmes was prepared. The survey suggested that SES is used in most of England, Wales and Scotland; just over 10% of respondents have abandoned the screen; others are awaiting national guidance. Coverage of SES is variable, but is often over 90% for children in state schools. Referral rates are variable, with a median of about 8%. The test used for the screen is the pure tone sweep test but with wide variation in implementation, with differing frequencies, pass criteria and retest protocols; written examples of protocols were often poor and ambiguous. There is no national approach to data collection, audit and quality assurance, and there are variable approaches at local level. The screen is performed in less than ideal test conditions and resources are often limited, which has an impact on the quality of the screen. The primary cohort studies show that the prevalence of permanent childhood hearing loss continues to increase through infancy. Of the 3.47 in 1000 children with a permanent hearing loss at school screen age, 1.89 in 1000 required identification after the newborn screen. Newborn hearing screening is likely to reduce significantly the yield of SES for permanent bilateral and unilateral hearing impairments; yield had fallen from about 1.11 in 1000 before newborn screening to about 0.34 in 1000 for cohorts that had had newborn screening, of which only 0.07 in 1000 were unilateral impairments. Just under 20% of permanent moderate or greater bilateral, mild bilateral and unilateral impairments, known to services as 6-year-olds or older, remained to be identified around the time of school entry. No good-quality published comparative trials of alternative screens or tests for SES were identified and studies concerned with the relative accuracy of alternative tests are difficult to compare and often flawed by differing referral criteria and case definitions; with full pure tone audiometry as the reference test, the pure tone sweep test appears to have high sensitivity and high specificity for minimal, mild and greater hearing impairments, better than alternative tests for which evidence was identified. There is insufficient evidence regarding possible harm of the screen. There were no published studies identified that examined the possible effects of SES on longer term outcomes. No good-quality published economic evaluations of SES were identified and a universal SES based on pure tone sweep tests was associated with higher costs and slightly higher quality-adjusted life-years (QALYs) compared with no screen and other screen alternatives; the incremental cost-effectiveness ratio for such a screen is around 2500 pounds per QALY gained; the range of expected costs, QALYs and net benefits was broad, indicating a considerable degree of uncertainty. Targeted screening could be more cost-effective than universal school entry screening; however, the lack of primary data and the wide limits for variables in the modelling mean that any conclusions must be considered indicative and exploratory only. A national screening programme for permanent hearing impairment at school entry meets all but three of the criteria for a screening programme, but at least six criteria are not met for screening for temporary hearing impairment. The lack of good-quality evidence in this area remains a serious problem. Services should improve quality and audit screen performance for identification of previously unknown permanent hearing impairment, pending evidence-based policy decisions based on the research recommendations. Further research is needed into a number of important areas including the evaluation of an agreed national protocol for services delivering SES to make future studies and audits of screen performance more directly comparable.

Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis.

PubMed

Schreiber, Richard A; Masucci, Lisa; Kaczorowski, Janusz; Collet, J P; Lutley, Pamela; Espinosa, Victor; Bryan, Stirling

2014-09-01

Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained). A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre.

PubMed

Dijk, F Nicole; McKay, Karen; Barzi, Federica; Gaskin, Kevin J; Fitzgerald, Dominic A

2011-12-01

Newborn screening (NBS) for cystic fibrosis (CF) is associated with improved early nutritional outcomes and improved spirometry in children. The aim of this study was to determine whether early diagnosis and treatment of CF with NBS in New South Wales in 1981 led to better clinical outcomes and survival into early adulthood. Retrospective observational study comprising two original cohorts born in the 3 years before ('non-screened cohort', n=57) and after ('screened'; n=60) the introduction of NBS. Patient records were assessed at transfer from paediatric to adult care by age 19 years and survival was documented to age 25 years. Non-screened patients (n=38) when compared with screened patients (n=41) had a higher rate and lower age of Pseudomonas aeruginosa acquisition at age 18 years (p ≤ 0.01). Height, weight and body mass index (BMI) z scores (all p<0.01) and forced expiratory volume in 1 s (FEV(1))% were better in the screened group (n=41) (difference: 16.7 ± 6.4%; p=0.01) compared to non-screened (n=38) subjects on transfer to adult care. Each 1% increase in FEV(1)% was associated with a 3% (95% CI 1% to 5%; p=0.001) decrease in risk of death and each 1.0 kg/m(2) increase in BMI contributed to a 44% (95% CI 31% to 55%; p<0.001) decrease in risk of death. This accumulated in a significant survival difference at age 25 years (25 vs 13 deaths or lung transplants; p=0.01). NBS for CF leads to better lung function, nutritional status and improved survival in screened patients in early adulthood.

Genetics Home Reference: autosomal recessive primary microcephaly

MedlinePlus

... microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet. 2005 May;76( ... genome editing and CRISPR-Cas9? What is precision medicine? What is newborn screening? New Pages Alopecia areata ...

Genetics Home Reference: African iron overload

MedlinePlus

... Hemochromatosis and Iron Overload Screening (HEIRS) Study. Blood Cells Mol Dis. 2007 May-Jun;38(3):247-52. Epub 2007 Feb 5. ... are genome editing and CRISPR-Cas9? What is precision medicine? What is newborn ...

Genetics Home Reference: hypomagnesemia with secondary hypocalcemia

MedlinePlus

... Pelken L, Lotan D, Syrrou M, Prebble JJ, Cole DE, Metzger DL, Rahman S, Tajima T, Shu SG, ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

Role of cerebral ultrasound and magnetic resonance imaging in newborns with congenital cytomegalovirus infection.

PubMed

Capretti, Maria Grazia; Lanari, Marcello; Tani, Giovanni; Ancora, Gina; Sciutti, Rita; Marsico, Concetta; Lazzarotto, Tiziana; Gabrielli, Liliana; Guerra, Brunella; Corvaglia, Luigi; Faldella, Giacomo

2014-03-01

To assess the diagnostic and prognostic value of cerebral magnetic resonance imaging (cMRI) in comparison with that of cerebral ultrasound (cUS) in predicting neurodevelopmental outcome in newborns with congenital cytomegalovirus (CMV) infection. Forty CMV-congenitally infected newborns underwent cUS and cMRI within the first month of life. Clinical course, laboratory findings, visual/hearing function and neurodevelopmental outcome were documented. Thirty newborns showed normal cMRI, cUS and hearing/visual function in the first month of life; none showed CMV-related abnormalities at follow-up. Six newborns showed pathological cMRI and cUS findings (pseudocystis, ventriculomegaly, calcifications, cerebellar hypoplasia) but cMRI provided additional information (white matter abnormalities in three cases, lissencephaly/polymicrogyria in one and a cyst of the temporal lobe in another one); cerebral calcifications were detected in 3/6 infants by cUS but only in 2/6 by cMRI. Four of these 6 infants showed severe neurodevelopmental impairment and five showed deafness during follow-up. Three newborns had a normal cUS, but cMRI documented white matter abnormalities and in one case also cerebellar hypoplasia; all showed neurodevelopmental impairment and two were deaf at follow-up. One more newborn showed normal cUS and cMRI, but brainstem auditory evoked responses were abnormal; psychomotor development was normal at follow-up. Compared with cUS, cMRI disclosed additional pathological findings in CMV-congenitally infected newborns. cUS is a readily available screening tool useful in the identification of infected newborns with major cerebral involvement. Further studies with a larger sample size are needed to determine the prognostic role of MRI, particularly regarding isolated white matter lesions. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Ultrasonography of hydronephrosis in the newborn: a practical review

PubMed Central

2016-01-01

Widespread use of fetal ultrasonography is accompanied by more frequent detection of antenatal hydronephrosis. Therefore, sonographic evaluation of neonates with a history of antenatal hydronephrosis is becoming more widespread. As an initial postnatal non-invasive imaging modality, ultrasonography is used to screen for persistence of hydronephrosis, determine the level and severity of obstruction, and contribute to appropriate diagnosis and treatment. This review aims to provide a practical overview of the sonographic evaluation of neonatal hydronephrosis and to describe the sonographic findings of conditions associated with hydronephrosis in the newborn. PMID:27156562

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

Eye disorders in newborn infants (excluding retinopathy of prematurity).

PubMed

Wan, Michael J; VanderVeen, Deborah K

2015-05-01

A screening eye examination is an essential part of the newborn assessment. The detection of many ocular disorders in newborn infants can be achieved through careful observation of the infant's visual behaviour and the use of a direct ophthalmoscope to assess the ocular structures and check the red reflex. Early diagnosis and subspecialty referral can have a critical impact on the prognosis for many ocular conditions, including potentially blinding but treatable conditions such as congenital cataracts, life-threatening malignancies such as retinoblastoma and harbingers of disease elsewhere such as sporadic aniridia and its association with the development of Wilms tumour. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Moderating Effects of Autism on Parent Views of Genetic Screening for Aggression

ERIC Educational Resources Information Center

May, Michael E.; Brandt, Rachel C.; Bohannan, Joseph K.

2012-01-01

Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies…

Recent Developments in Toxico-Cheminformatics and Progress Towards a New Paradigm for Predictive Toxicology (2)

EPA Science Inventory

EPAs National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through harnessing of legacy toxicity data, creation of data linkages, and generation of new in vitro screening data. In association with EPA...

Recent Developments in Toxico-Cheminformatics and Progress Towards a New Paradigm for Predictive Toxicology

EPA Science Inventory

EPA’s Computational Toxicology Center is building capabilities to support a new paradigm for toxicity screening and prediction through harnessing of legacy toxicity data, creation of data linkages, and generation of new in vitro screening data. In association with EPA’s ToxCastTM...

Transient versus Permanent Congenital Hypothyroidism after the Age of 3 Years in Infants Detected on the First versus Second Newborn Screening Test in Oregon, USA.

PubMed

Ford, George A; Denniston, Sara; Sesser, David; Skeels, Michael R; LaFranchi, Stephen H

2016-01-01

The newborn screening (NBS) program in Oregon, USA, collects two routine specimens in all infants. The aim of our study was to determine the incidence of permanent versus transient congenital hypothyroidism (CH) in infants detected on the first versus second screening test. Thyroid function was determined in infants after the age of 3 years diagnosed with CH and born in Oregon between 2005 and 2011. Permanent hypothyroidism was defined as a TSH rise >10 mIU/ml after the first year on treatment or a TSH rise >6 mIU/ml with temporary discontinuation of l-thyroxine after the age of 3 years. Of the cases detected on the first test, 72 of 87 (83%) were permanent and 15 of 87 (17%) were transient, while of the cases detected on the second test, 5 of 22 (23%) were permanent and 17 of 22 (77%) were transient (OR 16.3, p < 0.001). There was a female preponderance detected on the first screen versus a male preponderance on the second screen. Blood spot and serum thyroid function tests at diagnosis, before treatment, were not meaningfully different between the two groups. The mean l-thyroxine dose at the age of 3 years was greater on the first screen: 61.2 versus 36.6 μg/day. Infants detected on the second NBS specimen have a higher incidence of transient CH. © 2016 S. Karger AG, Basel.

Towards Chagas disease elimination: Neonatal screening for congenital transmission in rural communities.

PubMed

Pennington, Pamela Marie; Juárez, José Guillermo; Arrivillaga, Margarita Rivera; De Urioste-Stone, Sandra María; Doktor, Katherine; Bryan, Joe P; Escobar, Clara Yaseli; Cordón-Rosales, Celia

2017-09-01

Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America. After successful vector control programs, congenital transmission remains as a challenge to disease elimination. We used the PRECEDE-PROCEED planning model to develop strategies for neonatal screening of congenital Chagas disease in rural communities of Guatemala. These communities have persistent high triatomine infestations and low access to healthcare. We used mixed methods with multiple stakeholders to identify and address maternal-infant health behaviors through semi-structured interviews, participatory group meetings, archival reviews and a cross-sectional survey in high risk communities. From December 2015 to April 2016, we jointly developed a strategy to illustratively advertise newborn screening at the Health Center. The strategy included socioculturally appropriate promotional and educational material, in collaboration with midwives, nurses and nongovernmental organizations. By March 2016, eight of 228 (3.9%) pregnant women had been diagnosed with T. cruzi at the Health Center. Up to this date, no neonatal screening had been performed. By August 2016, seven of eight newborns born to Chagas seropositive women had been parasitologically screened at the Health Center, according to international standards. Thus, we implemented a successful community-based neonatal screening strategy to promote congenital Chagas disease healthcare in a rural setting. The success of the health promotion strategies developed will depend on local access to maternal-infant services, integration with detection of other congenital diseases and reliance on community participation in problem and solution definition.

Towards Chagas disease elimination: Neonatal screening for congenital transmission in rural communities

PubMed Central

Juárez, José Guillermo; Arrivillaga, Margarita Rivera; De Urioste-Stone, Sandra María; Doktor, Katherine; Bryan, Joe P.; Escobar, Clara Yaseli; Cordón-Rosales, Celia

2017-01-01

Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America. After successful vector control programs, congenital transmission remains as a challenge to disease elimination. We used the PRECEDE-PROCEED planning model to develop strategies for neonatal screening of congenital Chagas disease in rural communities of Guatemala. These communities have persistent high triatomine infestations and low access to healthcare. We used mixed methods with multiple stakeholders to identify and address maternal-infant health behaviors through semi-structured interviews, participatory group meetings, archival reviews and a cross-sectional survey in high risk communities. From December 2015 to April 2016, we jointly developed a strategy to illustratively advertise newborn screening at the Health Center. The strategy included socioculturally appropriate promotional and educational material, in collaboration with midwives, nurses and nongovernmental organizations. By March 2016, eight of 228 (3.9%) pregnant women had been diagnosed with T. cruzi at the Health Center. Up to this date, no neonatal screening had been performed. By August 2016, seven of eight newborns born to Chagas seropositive women had been parasitologically screened at the Health Center, according to international standards. Thus, we implemented a successful community-based neonatal screening strategy to promote congenital Chagas disease healthcare in a rural setting. The success of the health promotion strategies developed will depend on local access to maternal-infant services, integration with detection of other congenital diseases and reliance on community participation in problem and solution definition. PMID:28892479

Polish universal neonatal hearing screening program-4-year experience (2003-2006).

PubMed

Szyfter, Witold; Wróbel, Maciej; Radziszewska-Konopka, Marzanna; Szyfter-Harris, Joanna; Karlik, Michał

2008-12-01

The aim of this paper is to share our experience and observations in running the Universal Neonatal Hearing Screening Program on a national level, present results and indicate some problems that have arisen during these 4 years. Polish Universal Neonatal Hearing Screening Program started back in 2002 in all neonatal units in Poland. Implemented testing methods consisted of test of transient evoked otoacoustic emission (TEOAE) performed in all new born children in their first 2-3 days of life and auditory brainstem response testing (ABR) conducted on children, who did not meet the TEOAE pass criteria. Additional questionnaire registered information on ototoxic drugs and family history of hearing impairment in every newborn. Diagnosed children were further referred for treatment and rehabilitation. After 4 years of running the program (between 2003 and 2006) a total number of 1,392,427 children were screened for hearing impairment, what stands for 96.3% of all delivered babies, registered in Poland. The screening program enabled to identify and refer for further treatment 2485 children with various types of hearing loss, 312 with profound (0.02% of population) and 145 with severe sensorineural hearing loss (0.11% of population). Our results indicate the accuracy of newborn hearing screening which remain an issue. Although improvement is needed in both intervention systems and diagnostic follow-up of hospitals, the Polish Universal Neonatal Hearing Program fully has achieved the main goal, the identification and treatment of hearing impaired children.

Contamination of dried blood spots - an underestimated risk in newborn screening.

PubMed

Winter, Theresa; Lange, Anja; Hannemann, Anke; Nauck, Matthias; Müller, Cornelia

2018-01-26

Newborn screening (NBS) is an established screening procedure in many countries worldwide, aiming at the early detection of inborn errors of metabolism. For decades, dried blood spots have been the standard specimen for NBS. The procedure of blood collection is well described and standardized and includes many critical pre-analytical steps. We examined the impact of contamination of some anticipated common substances on NBS results obtained from dry spot samples. This possible pre-analytical source of uncertainty has been poorly examined in the past. Capillary blood was obtained from 15 adult volunteers and applied to 10 screening filter papers per volunteer. Nine filter papers were contaminated without visible trace. The contaminants were baby diaper rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The differences between control and contaminated samples were evaluated for 45 NBS quantities. We estimated if the contaminations might lead to false-positive NBS results. Eight of nine investigated contaminants significantly altered NBS analyte concentrations and potentially caused false-positive screening outcomes. A contamination with feces was most influential, affecting 24 of 45 tested analytes followed by liquid infant formula (HA) and urine, affecting 19 and 13 of 45 analytes, respectively. A contamination of filter paper samples can have a substantial effect on the NBS results. Our results underline the importance of good pre-analytical training to make the staff aware of the threat and ensure reliable screening results.

Effectiveness of the critical congenital heart disease screening program for early diagnosis of cardiac abnormalities in newborn infants.

PubMed

Almawazini, Abdulmajid M; Hanafi, Hamdi K; Madkhali, Hasan A; Majrashi, Noura B

2017-10-01

To evaluate the effectiveness of critical congenital heart disease (CCHD) screening program for early diagnosis of cardiac anomalies in newborn infants.  Methods: This is a hospital-based prospective cross-sectional study conducted in the Pediatric and Neonatology Department, King Fahad Hospital at  Albaha, Saudi Arabia, between February 2016 and February 2017. Results: We screened 2961 (95.4%) of 3103 patients in a nursery unit; 142 (4.6%) patients were not screened. The test was positive in 114 (3.9%) patients and negative in 2847 (96.1%). There were 94 (3.2%) false positives and 20 (0.7%) true positives. Critical cardiac defects were diagnosed in 7 (0.2%) patients of all screened infants, and severe pulmonary hypertension was diagnosed in 13 (0.4%) patients. True negative results were found in 2841(96%) patients, and no cardiac defect was diagnosed, whereas false negative results were seen in 6 (0.2%) patients diagnosed with ventricular septal defect. The sensitivity was 77%, and the specificity was very high at 97%, with a positive predictive value of 18%, and a negative predictive value of 99.8% (95% confidence interval 13.78-19.18, p=0.0001). Conclusion: Pulse oximetry was found to be easy, safe, sensitive, and highly specific for diagnosis of CCHD.

What Conditions or Disorders are Commonly Associated with Down Syndrome?

MedlinePlus

... Society Hib Vaccine PKU and Newborn Screening Congenital Hypothyroidism Annual NICHD Research Advances Snapshot of Early Development ... do infants without Down syndrome, for example. 2 Hypothyroidism . The thyroid is a gland that makes hormones ...

Treatment of Infants Identified by Newborn Screening for Severe Combined Immunodeficiency

PubMed Central

Dorsey, Morna J.; Dvorak, Christopher C.; Cowan, Morton J.; Puck, Jennifer M.

2017-01-01

Background Severe combined immunodeficiency (SCID) is characterized by severely impaired T cell development and is fatal without treatment. Newborn screening (NBS) for SCID permits identification of affected infants before development of opportunistic infections and other complications. Substantial variation exists between treatment centers with regard to pre-transplant care and transplant protocols for NBS identified SCID infants, as well as for infants with other T lymphopenic disorders detected by NBS. Methods We developed approaches to management based on the study of infants identified by SCID NBS who received care at UCSF. Results From August 2010 through October 2016, 32 NBS SCID and leaky SCID cases from California and other states were treated and 42 NBS identified non-SCID T cell lymphopenia (TCL) cases were followed. Conclusions Our center’s approach supports successful outcomes; systematic review of our practice provides a framework for diagnosis and management, recognizing that more data will continue to shape best practices. PMID:28270365

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. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale.

Anthropometric surrogates for screening of low birth weight newborns: a community-based study.

PubMed

Rustagi, Neeti; Prasuna, J G; Taneja, D K

2012-03-01

In developing countries, where about 75% of births occur at home or in the community, logistic problems prevent the weighing of every newborn child. This study compares various anthropometric surrogates for identification of low birth weight neonates. A longitudinal community based study was done in an urban resettlement colony and 283 singleton neonates within 7 days of birth were examined for the anthropometric measurements such as head, chest, mid upper arm circumference and foot length as a screening tool for low birth weight. Chest circumference measured within 7 days of birth appeared to be the most appropriate surrogate of low birth weight with highest sensitivity (75.4%), specificity (78.4%), and positive predictive value (48.9%) as compared with other anthropometric parameters. Low birth weight neonates in absence of weighing scales can be early identified by using simple anthropometric measurements for enhanced home-based care and timely referral.

Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening.

PubMed

Stick, Stephen M; Brennan, Siobhain; Murray, Conor; Douglas, Tonia; von Ungern-Sternberg, Britta S; Garratt, Luke W; Gangell, Catherine L; De Klerk, Nicholas; Linnane, Barry; Ranganathan, Sarath; Robinson, Phillip; Robertson, Colin; Sly, Peter D

2009-11-01

To determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection. Children were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96). Scans were analyzed for the presence and extent of abnormalities. The prevalence of bronchiectasis was 22% and increased with age (P = .001). Factors associated with bronchiectasis included absolute neutrophil count (P = .03), neutrophil elastase concentration (P = .001), and Pseudomonas aeruginosa infection (P = .03). Pulmonary abnormalities are common in infants and young children with CF and relate to neutrophilic inflammation and infection with P. aeruginosa. Current models of care for infants with CF fail to prevent respiratory sequelae. Bronchiectasis is a clinically relevant endpoint that could be used for intervention trials that commence soon after CF is diagnosed after NBS.

Electronic health record - public health (EHR-PH) system prototype for interoperability in 21st century healthcare systems.

PubMed

Orlova, Anna O; Dunnagan, Mark; Finitzo, Terese; Higgins, Michael; Watkins, Todd; Tien, Allen; Beales, Steven

2005-01-01

Information exchange, enabled by computable interoperability, is the key to many of the initiatives underway including the development of Regional Health Information Exchanges, Regional Health Information Organizations, and the National Health Information Network. These initiatives must include public health as a full partner in the emerging transformation of our nation's healthcare system through the adoption and use of information technology. An electronic health record - public health (EHR-PH)system prototype was developed to demonstrate the feasibility of electronic data transfer from a health care provider, i.e. hospital or ambulatory care settings, to multiple customized public health systems which include a Newborn Metabolic Screening Registry, a Newborn Hearing Screening Registry, an Immunization Registry and a Communicable Disease Registry, using HL7 messaging standards. Our EHR-PH system prototype can be considered a distributed EHR-based RHIE/RHIO model - a principal element for a potential technical architecture for a NHIN.

Parent educational materials regarding the newborn hearing screening process.

PubMed

Krishnan, Lata A; Lawler, Breanne; Van Hyfte, Shannon

2017-04-01

Newborn hearing screening (NHS) procedures and implementation vary from state to state in the US. The purpose of this study was to evaluate the content and nature of information provided to parents about their infant's NHS across states to answer two questions: 1) what information is included in each state's parent information brochure? and 2) do the brochures include educational information requested by parents that may help reduce parental anxiety, improve satisfaction, and decrease the potential for misunderstandings? Each state's parent brochures and educational resources provided to parents were accessed via the National Center for Hearing Assessment and Management (NCHAM) website, categorized, and reviewed for content. Results indicate that the information provided to parents varies considerably across states and many brochures do not contain important information that is desired by parents. NHS procedures may be improved by providing standardized information regarding the process to parents in all states. Copyright © 2017 Elsevier B.V. All rights reserved.

Neonatal screening for congenital cytomegalovirus infection in preterm and small for gestational age infants.

PubMed

Lorenzoni, F; Lunardi, S; Liumbruno, A; Ferri, G; Madrigali, V; Fiorentini, E; Forli, F; Berrettini, S; Boldrini, A; Ghirri, P

2014-10-01

Congenital cytomegalovirus (CMV) infection affects many organs: reticuloendothelial and central nervous system are particularly involved. Congenital CMV infection is the leading cause of non-genetic sensorineural hearing loss. Hearing impairment can be present at birth or it can occur months or even years after birth. It is as well an important risk factor for antenatal stillbirth, preterm birth and small for gestational age (SGA) condition. For these reasons we should early identify congenital CMV infection investigating at least at risk newborns such as preterm or SGA babies given that a simple and standardized method for a large scale screening program is lacking. In our study, we found an association between congenital CMV infection and preterm births (3.03%) and with SGA condition (3.7%). Consequently, routine CMV urine detection should be performed at least in all babies born before 37 weeks of gestational age and in term SGA newborns.

Birth-weight charts and immigrant populations: A critical review.

PubMed

Urquia, Marcelo L; Sørbye, Ingvil K; Wanigaratne, Susitha

2016-04-01

There is an increasing body of literature focusing on differences in newborn size between different population subgroups defined by racial, ethnic, and immigration status. The interpretation of these differences as pathological or as merely reflecting normal variability is not straightforward and may have consequences for the provision of obstetric and neonatal care to minority populations. In this review, we critically assess some methodological issues affecting the assessment of newborn size and their potential implications for minority populations. In particular, we discuss the pros and cons of different types of newborn birth-weight (BW) charts (i.e., single local population-based references, minority-specific references, and a single international standard) to determine abnormal newborn size, with emphasis on immigrant populations. We conclude that size alone is not enough to inform clinical decisions and that all newborn size charts should be used as screening tools, not as diagnostic tools. Parental minority status may be regarded as a marker and used to further inquire about individual risk factors, particularly among immigrants who may not have a complete medical history in the new country. Finally, we outline areas for further research and recommendations for clinical practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Test-retest reliability of auditory brainstem responses to chirp stimuli in newborns.

PubMed

Cobb, Kensi M; Stuart, Andrew

2014-11-01

The purpose of this study was to examine the test-retest reliability of auditory brainstem responses (ABRs) to air- and bone-conducted chirp stimuli in newborns as a function of intensity. A repeated measures quasi-experimental design was employed. Thirty healthy newborns participated. ABRs were evoked using 60, 45, and 30 dB nHL air-conducted CE-Chirps and 45, 30, and 15 dB nHL bone-conducted CE-Chirps at a rate of 57.7/s. Measures were repeated by a second tester. Statistically significant correlations (p <.0001) and predictive linear relations (p <.0001) were found between testers for wave V latencies and amplitudes to air- and bone-conducted CE-Chirps. There were also no statistically significant differences between testers with wave V latencies and amplitudes to air- and bone-conducted CE-Chirps (p >.05). As expected, significant differences in wave V latencies and amplitudes were seen as a function of stimulus intensity for air- and bone-conducted CE-Chirps (p <.0001). These results suggest that ABRs to air- and bone-conducted CE-Chirps can be reliably repeated in newborns with different testers. The CE-Chirp may be valuable for both screening and diagnostic audiologic assessments of newborns.

Challenging gender inequity through male involvement in maternal and newborn health: critical assessment of an emerging evidence base

PubMed Central

Comrie-Thomson, Liz; Tokhi, Mariam; Ampt, Frances; Portela, Anayda; Chersich, Matthew; Khanna, Renu; Luchters, Stanley

2015-01-01

Men's involvement in the health of women and children is considered an important avenue for addressing gender influences on maternal and newborn health. The impact of male involvement around the time of childbirth on maternal and newborn health outcomes was examined as one part of a systematic review of maternal health intervention studies published between 2000 and 2012. Of 33,888 articles screened, 13 eligible studies relating to male involvement were identified. The interventions documented in these studies comprise an emerging evidence base for male involvement in maternal and newborn health. We conducted a secondary qualitative analysis of the 13 studies, reviewing content that had been systematically extracted. A critical assessment of this extracted content finds important gaps in the evidence base, which are likely to limit how ‘male involvement’ is understood and implemented in maternal and newborn health policy, programmes and research. Collectively, the studies point to the need for an evidence base that includes studies that clearly articulate and document the gender-transformative potential of involving men. This broader evidence base could support the use of male involvement as a strategy to improve both health and gender equity outcomes. PMID:26159766

Fetal adrenal gland enlargement - prenatal and postnatal management.

PubMed

Lackova, Eliska; Cunderlik, Anton; Ticha, Lubica; Gabor, Maria

2017-11-01

The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date was 39 gw. 85% from the patients were born on 40 gw, 15% on 39 gw. We didn't confirm the relation between the suprarenal gland enlargement and the preterm birth (≤ 34 weeks' gestation). In the period of 6 years we didn't find a newborn patient with the prenatal diagnosis of suprarenal gland enlargement. The adrenal gland enlargement didn't have a relation with the low gestation birth, weight, length or the preterm birth.

[Linkage analysis of a family with familial hypertriglyceridemia].

PubMed

Tang, Xin; Lin, Ying; Liu, Bing; Ma, Shi; Yang, Yang; Yang, Zheng-lin

2009-10-01

To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

Performance of two hearing screening protocols in NICU in Shanghai.

PubMed

Xu, Zheng-Min; Cheng, Wen-Xia; Yang, Xiao-Lin

2011-10-01

To study the sensitivity and specificity of targeted neonatal hearing screening for the single-session distortion product otoacoustic emissions (DPOAE) technique and the combined DPOAE/automated auditory brain-stem response (AABR) technique. 3000 high-risk newborns were studied at Children's Hospital of Fudan University. They were required to take two different screening procedures separately. The first procedure consisted of DPOAE alone and the second consisted of DPOAE combined with the AABR. Based upon the etiology in high-risk babies, they were divided into four groups. In group I there were 670 very-low-birth-weight (VLBW) newborns (1340 ears), and in group II there were 890 preterm babies (1780 ears). 850 babies (1700 ears) suffered from hyperbilirubinemia in group III, whereas 790 babies (1580 ears) with asphyxia were in group IV. The babies in groups II, III, and IV came from the neonatal intensive-care unit (NICU) of our hospital. The study protocols consisted of the DPOAE alone and DPOAE combined with AABR hearing screening at an age of less than 1 month, and a diagnostic stage at the age of 2 months. With single-session DPOAE screening, the referral rate (8% of the NICU babies), the false-positive rate (4.96%) and the false-negative rate (0.8%) were higher. The different etiologies in NICU babies had significantly different referral rates (F-test, p<0.01). A 4.46% referral rate of hyperbilirubinemi babies was much lower. The combined DPOAE/AABR screening technique revealed a referral rate of 5.03%, a false-positive rate of 2% and a false-negative rate of 0.06%. The false-positive rate was well below the suggested 3% of the American Academy of Pediatric. Comparisons of the referral rate, false-positive rate and false-negative rate of two hearing screening protocols (DPOAE alone and combined DPOAE/AABR) revealed significant differences (t-test, p<0.05, p<0.01, p<0.01). 91 infants (3.03% of the NICU babies) who failed the combined DPOAE/AABR screening were confirmed on hearing impairment. Of 22 babies who passed DPOAE screening but failed the AABR screening had a severe to profound hearing loss based on classic ABR. These patients (24% of the NICU babies with hearing losses) with hyperbilirubinemia and asphyxia problems at newborn stage were diagnosed as auditory neuropathy based on evaluations of DPOAE screening passed, abnormal ABR and absent middle-ear muscle reflexes (MMR). Our study demonstrates the use of a combination of DPOAE and AABR testing ensures high sensitivity and acceptable specificity, and predict the AN profile in NICU babies. Our efforts identified 22 NICU babies with auditory neuropathy who hopefully will benefit from early remediation of their hearing deficit. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

High-throughput tandem mass spectrometry multiplex analysis for newborn urinary screening of creatine synthesis and transport disorders, Triple H syndrome and OTC deficiency.

PubMed

Auray-Blais, Christiane; Maranda, Bruno; Lavoie, Pamela

2014-09-25

Creatine synthesis and transport disorders, Triple H syndrome and ornithine transcarbamylase deficiency are treatable inborn errors of metabolism. Early screening of patients was found to be beneficial. Mass spectrometry analysis of specific urinary biomarkers might lead to early detection and treatment in the neonatal period. We developed a high-throughput mass spectrometry methodology applicable to newborn screening using dried urine on filter paper for these aforementioned diseases. A high-throughput methodology was devised for the simultaneous analysis of creatine, guanidineacetic acid, orotic acid, uracil, creatinine and respective internal standards, using both positive and negative electrospray ionization modes, depending on the compound. The precision and accuracy varied by <15%. Stability during storage at different temperatures was confirmed for three weeks. The limits of detection and quantification for each biomarker varied from 0.3 to 6.3 μmol/l and from 1.0 to 20.9 μmol/l, respectively. Analyses of urine specimens from affected patients revealed abnormal results. Targeted biomarkers in urine were detected in the first weeks of life. This rapid, simple and robust liquid chromatography/tandem mass spectrometry methodology is an efficient tool applicable to urine screening for inherited disorders by biochemical laboratories. Copyright © 2014 Elsevier B.V. All rights reserved.

Parental Intentions to Enroll Children in a Voluntary Expanded Newborn Screening Program

PubMed Central

Paquin, Ryan S.; Peay, Holly L.; Gehtland, Lisa M.; Lewis, Megan A.; Bailey, Donald B.

2016-01-01

Background and Objectives Nearly all babies in the United States are tested at birth for rare, serious, and treatable disorders through mandatory state newborn screening (NBS). Recently, there have been calls for an expanded, voluntary model to facilitate early diagnosis and treatment of a wider range of disorders. We applied the reasoned action framework to examine parental intentions to participate in voluntary expanded screening. Methods We recruited a national cohort of recent and expectant parents living in the U.S. who completed a self-administered online survey (N = 1,001). Using a mixed-level fractional factorial experiment, we studied parental participation intentions and preferences for timing of consent, cost, consent format, and testing options. Results We conducted a hierarchical regression analysis assessing parental intentions to participate in voluntary expanded NBS. Attitudes, perceived normative influence, and perceived behavioral control explained substantial variance in intention, with perceived normative influence emerging as the strongest predictor. We found no evidence that the manipulated program features altered mean levels of intention, but timing of parental permission, cost, and permission format moderated the relative importance of reasoned action constructs on intention. Conclusion Program design features may impact the psychological mechanisms underlying parental decision making for voluntary expanded screening. These results have important implications for parent education, outreach, and informed parental permission procedures. PMID:27526258

Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates.

PubMed

Bodian, Dale L; Klein, Elisabeth; Iyer, Ramaswamy K; Wong, Wendy S W; Kothiyal, Prachi; Stauffer, Daniel; Huddleston, Kathi C; Gaither, Amber D; Remsburg, Irina; Khromykh, Alina; Baker, Robin L; Maxwell, George L; Vockley, Joseph G; Niederhuber, John E; Solomon, Benjamin D

2016-03-01

To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS). Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing. NBS genes are generally well covered by WGS. There is a median of one (range: 0-6) database-annotated pathogenic variant in the NBS genes per infant. Results of WGS and NBS in detecting 28 state-screened disorders and four hemoglobin traits were concordant for 88.6% of true positives (n = 35) and 98.9% of true negatives (n = 45,757). Of the five infants affected with a state-screened disorder, WGS identified two whereas NBS detected four. WGS yielded fewer false positives than NBS (0.037 vs. 0.17%) but more results of uncertain significance (0.90 vs. 0.013%). WGS may help rule in and rule out NBS disorders, pinpoint molecular diagnoses, and detect conditions not amenable to current NBS assays.

An analysis of the costs of implementing the National Newborn Hearing Screening Programme in England.

PubMed

Uus, K; Bamford, J; Taylor, R

2006-01-01

The primary aim of this analysis was to prospectively assess the full economic costs associated with implementing Newborn Hearing Screening Programme (NHSP) based on a two-stage screen, transient evoked otoacoustic emissions followed, if there is no clear response, by automated auditory brainstem response. Economic data were also collected from the Infant Distraction Test Screening (IDTS) service performed by health visitors at around eight months of age, which was being phased out. A comparison of costs and outcomes associated with NHSP and IDTS was conducted. 20 NHSP sites were invited to provide detailed cost data on NHSP implementation and 14 of these sites were selected to provide costs on the IDTS service that was being supplanted. There was marked variability in the costs. Given the higher yield of NHSP sites, the average cost per case detected across NHSP sites (31,410 pounds/case) was approximately half that of IDTS sites (69,919 pounds/case). Including family costs, the average total cost per case of NHSP (34,826 pounds/case) was almost a quarter of IDTS (117,942 pounds/case). Family costs and cost per case associated with NHSP are considerably less than that with IDTS. These findings support the policy of implementation of NHSP and the phasing out of the IDTS.

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

PubMed

Liang, X; Schnetz-Boutaud, N; Kenealy, S J; Jiang, L; Bartlett, J; Lynch, B; Gaskell, P C; Gwirtsman, H; McFarland, L; Bembe, M L; Bronson, P; Gilbert, J R; Martin, E R; Pericak-Vance, M A; Haines, J L

2006-03-01

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan.

PubMed

Sokoro, AbdulRazaq A H; Lepage, Joyce; Antonishyn, Nick; McDonald, Ryan; Rockman-Greenberg, Cheryl; Irvine, James; Lehotay, Denis C

2010-12-01

Mutations in the SLC25A15 gene, encoding the human inner mitochondrial membrane ornithine transporter, are thought to be responsible for hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome, a rare autosomal recessive condition. HHH syndrome has been detected in several small, isolated communities in northern Saskatchewan (SK). To determine the incidence of HHH syndrome in these communities, a PCR method was set up to detect F188Δ, the common French-Canadian mutation. Neonatal blood spots collected from all newborns from the high risk area were genotyped for the F188Δ mutation for seven consecutive years. Using DNA analysis, we estimated that the heterozygote frequency for the mutant allele for HHH syndrome to be about 1 in 19 individuals, predicting one affected child with HHH syndrome for approximately every 1,500 individuals (1 in 1,550 live births; 1 child every 12 years) in this isolated population. The frequency for the mutant allele for HHH syndrome in this isolated community is probably the highest in the world for this rare disorder. We determined that ornithine levels, by tandem mass spectrometry, were not abnormal in newborns with F188Δ mutation, carriers and normals. Ornithine rises to abnormally high levels at some time after birth well past the time that the newborn screening blood spot is collected. The timing or the reasons for the delayed rise of ornithine in affected children with HHH syndrome have not been determined. Newborn screening for HHH Syndrome in this high risk population is only possible by detection of the mutant allele using DNA analysis.

Human Donor Milk or Formula: A Qualitative Study of Maternal Perspectives on Supplementation.

PubMed

Rabinowitz, Molly R; Kair, Laura R; Sipsma, Heather L; Phillipi, Carrie A; Larson, Ilse A

2018-04-01

Breastfeeding is fundamental to maternal and child health and is the most cost-effective intervention to reduce child mortality. Pasteurized human donor milk (HDM) is increasingly provided for term newborns requiring temporary supplementation. Few studies examine maternal perspectives on supplementation of term newborns. We conducted semistructured in-person interviews with mothers of term newborns (n = 24) during postpartum hospitalization. Mothers were asked whether they had chosen or would choose to supplement with HDM versus infant formula, if medically indicated, and why. Data were gathered to saturation and analyzed inductively by consensus. Emerging semantic themes were compared between mothers who chose or would choose HDM and those who chose or would choose infant formula. Most mothers had concerns about HDM, including uncertainty regarding screening and substances passed through HDM. Experiences with prior children influenced decision-making. Mothers who chose or would choose HDM (56%, n = 14) praised it as "natural," and some felt suspicious of infant formula as "synthetic." Mothers who chose or would choose infant formula (44%, n = 10) did not know enough about HDM to choose it, and many viewed infant formula as a short-term solution to supply concerns. Mothers unanimously mistrusted online milk purchasing sources, although the majority felt positively about using a friend or family member's milk. Counseling regarding term newborn supplementation should focus on HDM education, specifically on areas of greatest concern and uncertainty such as donor selection, screening, transmission of substances, and mother's milk supply. Research is needed to assess the long-term impact of attitudes and choices on breastfeeding.

Fostering caring relationships: Suggestions to rethink liberal perspectives on the ethics of newborn screening.

PubMed

van der Burg, Simone; Oerlemans, Anke

2018-03-01

Newborn screening (NBS) involves the collection of blood from the heel of a newborn baby and testing it for a list of rare and inheritable disorders. New biochemical screening technologies led to expansions of NBS programs in the first decade of the 21st century. It is expected that they will in time be replaced by genetic sequencing technologies. These developments have raised a lot of ethical debate. We reviewed the ethical literature on NBS, analyzed the issues and values that emerged, and paid particular interest to the type of impacts authors think NBS should have on the lives of children and their families. Our review shows that most authors keep their ethical reflection confined to policy decisions, about for instance (a) the purpose of the program, and (b) its voluntary or mandatory nature. While some authors show appreciation of how NBS information empowers parents to care for their (diseased) children, most authors consider these aspects to be 'private' and leave their evaluation up to parents themselves. While this division of moral labor fits with the liberal conviction to leave individuals free to decide how they want to live their private lives, it also silences the ethical debate about these issues. Given the present and future capacity of NBS to offer an abundance of health-related information, we argue that there is good reason to develop a more substantive perspective to whether and how NBS can contribute to parents' good care for children. © 2018 The Authors. Bioethics Published by John Wiley & Sons Ltd.

Neurodevelopmental profiles of children with glutaric aciduria type I diagnosed by newborn screening: a follow-up case series.

PubMed

Brown, Amy; Crowe, Louise; Beauchamp, Miriam H; Anderson, Vicki; Boneh, Avihu

2015-01-01

Glutaric aciduria type I (GA-I) is an inherited metabolic disorder that may lead to severe motor disorder and cognitive impairment. GA-I is now included in the newborn screening programme in many countries as early detection allows for prompt treatment and effectively reduces the risk of poor developmental outcome. Information regarding the long-term neurodevelopmental outcome of children with GA-I treated early is sparse.We recruited children with a confirmed diagnosis of GA-I diagnosed via newborn screening, treated in our centre and >3 years of age (n = 6). Children were assessed at two time points using a comprehensive neuropsychological test battery. Four of these had been the subject of a previous report. All participants were male, 3-6 years at the initial assessment and 6-12 years of age at the follow-up assessment.Fine motor skills were below average in all patients. Speech, which was affected in all four patients reported previously, improved following speech therapy. IQ scores remained generally stable within the normal range. Executive functioning was average to high average in four patients. Behaviour, as assessed through parental questionnaires, was problematic in two patients. Compounding factors included child neglect, family history of autism and multiple admissions to hospital (n = 1 in each).GA-I affects fine motor skills and speech, regardless of early treatment, but not IQ scores. Patients with GA-I should be referred for assessment and appropriate early intervention. Further research is needed to correlate specific neuropsychological deficits with neuroimaging.

Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient.

PubMed

Davies, Gwyneth; Stocks, Janet; Thia, Lena P; Hoo, Ah-Fong; Bush, Andrew; Aurora, Paul; Brennan, Lucy; Lee, Simon; Lum, Sooky; Cottam, Philippa; Miles, Joanne; Chudleigh, Jane; Kirkby, Jane; Balfour-Lynn, Ian M; Carr, Siobhán B; Wallis, Colin; Wyatt, Hilary; Wade, Angie

2017-11-01

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV 0.5 ), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV 0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45-1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV 0.5 on all test occasions, precluding the ability to identify "high-risk" infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up. Copyright ©ERS 2017.