International Journal of Neonatal Screening

2 pages, 182 KiB

Open AccessEditorial

The Editor’s Choice for Issue 3, Volume 7

by Ralph Fingerhut

Int. J. Neonatal Screen. 2021, 7(4), 84; https://doi.org/10.3390/ijns7040084 - 20 Dec 2021

Cited by 1 | Viewed by 2059

Dear Readers: Choosing one paper from a total of 28 papers published in the third issue of Volume 7 was quite a challenge [...] Full article

5 pages, 192 KiB

Open AccessArticle

Newborn Screening Practices for Beta-Thalassemia in the United States

by Michael A. Bender, Mary Hulihan, Mary Christine Dorley, Maria del Pilar Aguinaga, Jelili Ojodu and Careema Yusuf

Int. J. Neonatal Screen. 2021, 7(4), 83; https://doi.org/10.3390/ijns7040083 - 13 Dec 2021

Cited by 8 | Viewed by 2964

Abstract

Beta-thalassemia, a heritable condition of abnormal hemoglobin production, is not a core condition on the United States Recommended Uniform Screening Panel (RUSP) for state and territorial newborn screening (NBS) programs. However, screening for sickle cell disease (which is on the core RUSP) also [...] Read more.

Beta-thalassemia, a heritable condition of abnormal hemoglobin production, is not a core condition on the United States Recommended Uniform Screening Panel (RUSP) for state and territorial newborn screening (NBS) programs. However, screening for sickle cell disease (which is on the core RUSP) also detects reduced or absent levels of hemoglobin (Hb) A and certain other Hb variants associated with beta-thalassemia and, thus, allows for a timely referral to appropriate healthcare to minimize sequalae of the disease. The Association of Public Health Laboratories’ Hemoglobinopathy Workgroup administered a comprehensive survey of all U.S. NBS programs to assess beta-thalassemia testing methodologies, the cutoffs for defining beta-thalassemia major, and the reporting and follow-up practices. Forty-six (87%) of the programs responded. Thirty-nine of the 46 responding programs (85%) report some form of suspected beta-thalassemia; however, the screening methods, the percentage of Hb A used as a cutoff for an indication of beta-thalassemia major, and the screening follow-up vary widely. The standardization of technical and reporting procedures may improve access to specialty care prior to severe complications, increase genetic counseling, and provide data needed to better understand the public health impact and clinical outcomes of beta-thalassemia in the United States. Full article

5 pages, 558 KiB

Open AccessTechnical Note

Sensitive and Robust LC-MS/MS Assay to Quantify 25-Hydroxyvitamin D in Leftover Protein Extract from Dried Blood Spots

by Sanne Grundvad Boelt, Lars Melgaard, Marta Jadwiga Thorbek, Nadia Sara Jensen MacSween, John J. McGrath and Arieh S. Cohen

Int. J. Neonatal Screen. 2021, 7(4), 82; https://doi.org/10.3390/ijns7040082 - 10 Dec 2021

Cited by 3 | Viewed by 2427

Abstract

Neonatal dried blood spots (DBS) provide a remarkable resource for biobanks. These microsamples can provide information related to the genetic correlates of disease and can be used to quantify a range of analytes, such as proteins and small molecules. However, after routine neonatal [...] Read more.

Neonatal dried blood spots (DBS) provide a remarkable resource for biobanks. These microsamples can provide information related to the genetic correlates of disease and can be used to quantify a range of analytes, such as proteins and small molecules. However, after routine neonatal screening, the amount of DBS sample available is limited. To optimize the use of these samples, there is a need for sensitive assays which are integrated across different analytic platforms. For example, after DNA extraction, protein extracts are available for additional analyses. We describe a sensitive and robust LC-MS/MS method for 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃ optimized for leftover protein extracts from DBS, which has excellent recovery, precision, and accuracy. Full article

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13 pages, 829 KiB

Open AccessArticle

Targeted Secondary Screening for Congenital Hypothyroidism in High-Risk Neonates: A 9 Year Review in a Large California Health Care System

by Alan B. Cortez, Bryan Lin and Joshua A. May

Int. J. Neonatal Screen. 2021, 7(4), 81; https://doi.org/10.3390/ijns7040081 - 01 Dec 2021

Cited by 2 | Viewed by 3358

Abstract

Secondary screening for missed congenital hypothyroidism (CH) has been introduced sporadically, but its necessity and optimal strategy have not been recognized. We hypothesized that a simple clinical protocol (performed by a medical group without a governmental mandate) targeting infants at high risk for [...] Read more.

Secondary screening for missed congenital hypothyroidism (CH) has been introduced sporadically, but its necessity and optimal strategy have not been recognized. We hypothesized that a simple clinical protocol (performed by a medical group without a governmental mandate) targeting infants at high risk for missed CH can identify cases. We performed a 9-year retrospective review of 338,478 neonates within a California health plan following the introduction of thyrotropin (TSH) secondary screening for neonates at high risk for missed CH due to very-low-birthweight (VLBW), hospitalized congenital heart disease (CHD), and same-sex multiples (SSM). Screening performance by day 60 of life was 95% successful for VLBW and >50% for CHD and SSM, leading to an additional 35% CH treated cases despite re-testing only 1.7% of the cohort. Infants with VLBW or CHD were 33 times more likely (190 times more likely for CHD with Down Syndrome) to receive treatment for CH than random infants diagnosed by primary screening (p < 0.001), and 92% of these infants were not found by primary newborn screening. Currently, permanent disease has been documented in 84% of CH by primary screening compared to 27% by secondary screening (p < 0.001). This targeted secondary screening program identifies and treats additional CH cases after TSH-only newborn screening. Full article

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13 pages, 236 KiB

Open AccessArticle

Family Perceptions of Newborn Cytomegalovirus Screening: A Qualitative Study

by Michael J. Cannon, Denise M. Levis, Holly McBride, Danie Watson, Carol Rheaume, Mary Ann Kirkconnell Hall, Tatiana M. Lanzieri and Gail Demmler-Harrison

Int. J. Neonatal Screen. 2021, 7(4), 80; https://doi.org/10.3390/ijns7040080 - 19 Nov 2021

Cited by 7 | Viewed by 2581

Abstract

We sought to understand long-term retrospective parental perceptions of the utility of newborn screening in a context where many affected children never develop sequelae but where intensive support services and ongoing healthcare were provided. We conducted focus groups and interviews among parents (N [...] Read more.

We sought to understand long-term retrospective parental perceptions of the utility of newborn screening in a context where many affected children never develop sequelae but where intensive support services and ongoing healthcare were provided. We conducted focus groups and interviews among parents (N = 41) of children with congenital CMV who had been enrolled in a long-term follow-up study at a large medical college for a mean of 22 years following diagnosis. Groups included parents whose children were: symptomatic at birth; initially asymptomatic but later developed sensorineural hearing loss; and who remained asymptomatic into adulthood. With proper follow-up support, newborn CMV screening was viewed positively by parents, who felt empowered by the knowledge, though parents often felt that they and healthcare providers needed more information on congenital CMV. Parents in all groups valued newborn CMV screening in the long term and believed it should be embedded within a comprehensive follow-up program. Despite initial distress, parents of CMV-positive children felt newborn CMV screening was a net positive. Mandatory or opt-out screening for conditions with variable presentations and treatment outcomes may be valuable in contexts where follow-up and care are readily available. Full article

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Open AccessArticle

DBS Screening for Glycogen Storage Disease Type 1a: Detection of c.648G>T Mutation in G6PC by Combination of Modified Competitive Oligonucleotide Priming-PCR and Melting Curve Analysis

by Emma Tabe Eko Niba, Yogik Onky Silvana Wijaya, Hiroyuki Awano, Naoko Taniguchi, Yasuhiro Takeshima, Hisahide Nishio and Masakazu Shinohara

Int. J. Neonatal Screen. 2021, 7(4), 79; https://doi.org/10.3390/ijns7040079 - 16 Nov 2021

Cited by 2 | Viewed by 2859

Abstract

Glycogen storage disease type Ia (GSDIa) is an autosomal recessive disorder caused by glucose-6-phosphatase (G6PC) deficiency. GSDIa causes not only life-threatening hypoglycemia in infancy, but also hepatocellular adenoma as a long-term complication. Hepatocellular adenoma may undergo malignant transformation to hepatocellular carcinoma. New treatment [...] Read more.

Glycogen storage disease type Ia (GSDIa) is an autosomal recessive disorder caused by glucose-6-phosphatase (G6PC) deficiency. GSDIa causes not only life-threatening hypoglycemia in infancy, but also hepatocellular adenoma as a long-term complication. Hepatocellular adenoma may undergo malignant transformation to hepatocellular carcinoma. New treatment approaches are keenly anticipated for the prevention of hepatic tumors. Gene replacement therapy (GRT) is a promising approach, although early treatment in infancy is essential for its safety and efficiency. Thus, GRT requires screening systems for early disease detection. In this study, we developed a screening system for GSDIa using dried blood spots (DBS) on filter paper, which can detect the most common causative mutation in the East-Asian population, c.648G>T in the G6PC gene. Our system consisted of nested PCR analysis with modified competitive oligonucleotide priming (mCOP)-PCR in the second round and melting curve analysis of the amplified products. Here, we tested 54 DBS samples from 50 c.648G (wild type) controls and four c.648T (mutant) patients. This system, using DBS samples, specifically amplified and clearly detected wild-type and mutant alleles from controls and patients, respectively. In conclusion, our system will be applicable to newborn screening for GSDIa in the real world. Full article

(This article belongs to the Collection Newborn Screening in Japan)

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12 pages, 734 KiB

Open AccessArticle

The Alberta Newborn Screening Approach for Sickle Cell Disease: The Advantages of Molecular Testing

by Janet R. Zhou, Ross Ridsdale, Lauren MacNeil, Margaret Lilley, Stephanie Hoang, Susan Christian, Pamela Blumenschein, Vanessa Wolan, Aisha Bruce, Gurpreet Singh, Nicola Wright, Jillian S. Parboosingh, Ryan E. Lamont and Iveta Sosova

Int. J. Neonatal Screen. 2021, 7(4), 78; https://doi.org/10.3390/ijns7040078 - 16 Nov 2021

Cited by 6 | Viewed by 3440

Abstract

Sickle cell disease (SCD), a group of inherited red blood cell (RBC) disorders caused by pathogenic variants in the beta-globin gene (HBB), can cause lifelong disabilities and/or early mortality. If diagnosed early, preventative measures significantly reduce adverse outcomes related to SCD. [...] Read more.

Sickle cell disease (SCD), a group of inherited red blood cell (RBC) disorders caused by pathogenic variants in the beta-globin gene (HBB), can cause lifelong disabilities and/or early mortality. If diagnosed early, preventative measures significantly reduce adverse outcomes related to SCD. In Alberta, Canada, SCD was added to the newborn screening (NBS) panel in April 2019. The primary conditions screened for are sickle cell anemia (HbS/S), HbS/C disease, and HbS/β thalassemia. In this study, we retrospectively analyzed the first 19 months of SCD screening performance, as well as described our approach for screening of infants that have received a red blood cell transfusion prior to collection of NBS specimen. Hemoglobins eluted from dried blood spots were analyzed using the Bio-Rad™ VARIANT nbs analyzer (Bio-Rad Laboratories, Inc., Hercules, CA, USA). Targeted sequencing of HBB was performed concurrently in samples from all transfused infants. During the period of this study, 43 of 80,314 screened infants received a positive NBS result for SCD, and of these, 34 were confirmed by diagnostic testing, suggesting a local SCD incidence of 1:2400 births. There were 608 infants with sickle cell trait, resulting in a carrier frequency of 1:130. Over 98% of non-transfused infants received their NBS results within 10 days of age. Most of the 188 transfused infants and 2 infants who received intrauterine transfusions received their final SCD screen results within 21 ± 10 d of birth. Our SCD screening algorithm enables detection of affected newborns on the initial NBS specimen, independent of the reported blood transfusion status. Full article

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15 pages, 2537 KiB

Open AccessArticle

Implementation of Hospital-Based Supplemental Duchenne Muscular Dystrophy Newborn Screening (sDMDNBS): A Pathway to Broadening Adoption

by Richard B. Parad, Yvonne Sheldon and Arindam Bhattacharjee

Int. J. Neonatal Screen. 2021, 7(4), 77; https://doi.org/10.3390/ijns7040077 - 15 Nov 2021

Cited by 15 | Viewed by 4072

Abstract

Duchenne muscular dystrophy (DMD) is not currently part of mandatory newborn screening, despite the availability of a test since 1975. In the absence of screening, a DMD diagnosis is often not established in patients until 3–6 years of age. During this time, irreversible [...] Read more.

Duchenne muscular dystrophy (DMD) is not currently part of mandatory newborn screening, despite the availability of a test since 1975. In the absence of screening, a DMD diagnosis is often not established in patients until 3–6 years of age. During this time, irreversible muscle degeneration takes place, and clinicians agree that the earlier therapy is initiated, the better the long-term outcome. With recent availability of FDA-approved DMD therapies, interest has renewed for adoption by state public health programs, but such implementation is a multiyear process. To speed access to approved therapies, we implemented a unique, hospital-based program offering parents of newborns an optional, supplemental DMD newborn screen (NBS) via a two-tiered approach: utilizing a creatine kinase (CK) enzyme assay coupled with rapid targeted next-generation sequencing (tNGS) for the DMD gene (using a Whole-Exome Sequencing (WES) assay). The tNGS/WES assay integrates the ability to detect both point mutations and large deletion/duplication events. This tiered newborn screening approach allows for the opportunity to improve treatment and outcomes, avoid the diagnostic delays, and diminish healthcare disparities. To implement this screening algorithm through hospitals in a way that would ultimately be acceptable to public health laboratories, we chose an FDA-approved CK-MM immunoassay to avoid the risks of false-negative/-positive results. Because newborn CK values can be affected due to non-DMD-related causes such as birth trauma, a confirmatory repeat CK assay on a later dried blood spot (DBS) collection has been proposed. Difficulties associated with non-routine repeat DBS collection, including the tracking and recall of families, and the potential creation of parental anxiety associated with false-positive results, can be avoided with this algorithm. Whereas a DMD diagnosis is essentially ruled out by the absence of detected DMD sequence abnormalities, a subsequent CK would still be warranted to confirm resolution of the initial elevation, and thus the absence of non-DMD muscular dystrophy or other pathologies. To date, we have screened over 1500 newborns (uptake rate of ~80%) by a CK-MM assay, and reflexed DMD tNGS in 29 of those babies. We expect the experience from this screening effort will serve as a model that will allow further expansion to other hospital systems until a universal public health screening is established. Full article

(This article belongs to the Special Issue Next Generation Sequencing (NGS) in Newborn Screening)

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8 pages, 241 KiB

Open AccessReview

Select Ethical Aspects of Next-Generation Sequencing Tests for Newborn Screening and Diagnostic Evaluation of Critically Ill Newborns

by Kuntal Sen, Jennifer Harmon and Andrea L. Gropman

Int. J. Neonatal Screen. 2021, 7(4), 76; https://doi.org/10.3390/ijns7040076 - 08 Nov 2021

Cited by 5 | Viewed by 3001

Abstract

In this review, we analyze medical and select ethical aspects of the increasing use of next-generation sequencing (NGS) based tests in newborn medicine. In the last five years, there have been several studies exploring the role of rapid exome sequencing (ES) and genome [...] Read more.

In this review, we analyze medical and select ethical aspects of the increasing use of next-generation sequencing (NGS) based tests in newborn medicine. In the last five years, there have been several studies exploring the role of rapid exome sequencing (ES) and genome sequencing (GS) in critically ill newborns. While the advantages include a high diagnostic yield with potential changes in interventions, there have been ethical dilemmas surrounding consent, information about adult-onset diseases and resolution of variants of uncertain significance. Another active area of research includes a cohort of studies funded under Newborn Sequencing in Genomic Medicine and Public Health pertaining to the use of ES and GS in newborn screening (NBS). While these techniques may allow for screening for several genetic disorders that do not have a detectable biochemical marker, the high costs and long turnaround times of these tests are barriers in their utilization as public health screening tests. Discordant results between conventional NBS and ES-based NBS, as well as challenges with consent, are other potential pitfalls of this approach. Please see the Bush, Al-Hertani and Bodamer article in this Special Issue for the broader scope and further discussion. Full article

(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)

8 pages, 1200 KiB

Open AccessArticle

Province-Wide Stool Color Card Screening for Biliary Atresia in Lower-Saxony: Experiences with Passive Distribution Strategies and Results

by Omid Madadi-Sanjani, Joachim F. Kuebler, Marie Uecker, Eva-Doreen Pfister, Ulrich Baumann, Berit Kunze-Hullmann, Jochen Blaser, Thomas Buck and Claus Petersen

Int. J. Neonatal Screen. 2021, 7(4), 75; https://doi.org/10.3390/ijns7040075 - 04 Nov 2021

Cited by 1 | Viewed by 5024

Abstract

Background: Stool color card (SCC) screenings for biliary atresia (BA) have shown to improve Kasai timing and outcome significantly. Both obligatory and non-obligatory screenings with passive distribution strategies have proven to be effective. Therefore, we have initiated a voluntary SCC program and aim [...] Read more.

Background: Stool color card (SCC) screenings for biliary atresia (BA) have shown to improve Kasai timing and outcome significantly. Both obligatory and non-obligatory screenings with passive distribution strategies have proven to be effective. Therefore, we have initiated a voluntary SCC program and aim to describe our experience. Methods: Since 2017 we supply all maternity wards in Lower-Saxony with SCC. Attending pediatricians and parents of BA infants were contacted via questionnaires and asked for their evaluation of the SCC screening. Results: 85.2% of attending pediatricians support the SCC screening, but only 78.1% considered the initiative useful. In their clinical routine, only 67% of visiting parents report to have received an SCC at the maternity hospital. In the group of parents of BA infants, only 54% (7/13) had received an SCC. Out of those seven parents, only one had referred their child to a children’s hospital based on pathological SCC results. The lack of SCC education in the maternity hospitals was made responsible by parents. Within three years, only one infant with BA was identified through the SCC. Conclusions: Our voluntary SCC screening shows serious limitations with inacceptable distribution of SCCs and low acceptance of attending pediatricians. SCC programs in decentralized health care systems without educational campaigns, standardized diagnostic and treatment algorithms and the definition of reference centers are additional burdens for local health care providers without the promised benefit. Full article

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13 pages, 792 KiB

Open AccessEditor’s ChoiceReview

Future Perspectives of Newborn Screening for Inborn Errors of Immunity

by Maartje Blom, Robbert G. M. Bredius and Mirjam van der Burg

Int. J. Neonatal Screen. 2021, 7(4), 74; https://doi.org/10.3390/ijns7040074 - 02 Nov 2021

Cited by 8 | Viewed by 3784

Abstract

Newborn screening (NBS) programs continue to expand due to innovations in both test methods and treatment options. Since the introduction of the T-cell receptor excision circle (TREC) assay 15 years ago, many countries have adopted screening for severe combined immunodeficiency (SCID) in their [...] Read more.

Newborn screening (NBS) programs continue to expand due to innovations in both test methods and treatment options. Since the introduction of the T-cell receptor excision circle (TREC) assay 15 years ago, many countries have adopted screening for severe combined immunodeficiency (SCID) in their NBS program. SCID became the first inborn error of immunity (IEI) in population-based screening and at the same time the TREC assay became the first high-throughput DNA-based test in NBS laboratories. In addition to SCID, there are many other IEI that could benefit from early diagnosis and intervention by preventing severe infections, immune dysregulation, and autoimmunity, if a suitable NBS test was available. Advances in technologies such as KREC analysis, epigenetic immune cell counting, protein profiling, and genomic techniques such as next-generation sequencing (NGS) and whole-genome sequencing (WGS) could allow early detection of various IEI shortly after birth. In the next years, the role of these technical advances as well as ethical, social, and legal implications, logistics and cost will have to be carefully examined before different IEI can be considered as suitable candidates for inclusion in NBS programs. Full article

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14 pages, 561 KiB

Open AccessArticle

Validation of a Custom Next-Generation Sequencing Assay for Cystic Fibrosis Newborn Screening

by Robert J. Sicko, Colleen F. Stevens, Erin E. Hughes, Melissa Leisner, Helen Ling, Carlos A. Saavedra-Matiz, Michele Caggana and Denise M. Kay

Int. J. Neonatal Screen. 2021, 7(4), 73; https://doi.org/10.3390/ijns7040073 - 02 Nov 2021

Cited by 10 | Viewed by 4140

Abstract

Newborn screening (NBS) for Cystic Fibrosis (CF) is associated with improved outcomes. All US states screen for CF; however, CF NBS algorithms have high false positive (FP) rates. In New York State (NYS), the positive predictive value of CF NBS improved from 3.7% [...] Read more.

Newborn screening (NBS) for Cystic Fibrosis (CF) is associated with improved outcomes. All US states screen for CF; however, CF NBS algorithms have high false positive (FP) rates. In New York State (NYS), the positive predictive value of CF NBS improved from 3.7% to 25.2% following the implementation of a three-tier IRT-DNA-SEQ approach using commercially available tests. Here we describe a modification of the NYS CF NBS algorithm via transition to a new custom next-generation sequencing (NGS) platform for more comprehensive cystic fibrosis transmembrane conductance regulator (CFTR) gene analysis. After full gene sequencing, a tiered strategy is used to first analyze only a specific panel of 338 clinically relevant CFTR variants (second-tier), followed by unblinding of all sequence variants and bioinformatic assessment of deletions/duplications in a subset of samples requiring third-tier analysis. We demonstrate the analytical and clinical validity of the assay and the feasibility of use in the NBS setting. The custom assay has streamlined our molecular workflow, increased throughput, and allows for bioinformatic customization of second-tier variant panel content. NBS aims to identify those infants with the highest disease risk. Technological molecular improvements can be applied to NBS algorithms to reduce the burden of FP referrals without loss of sensitivity. Full article

(This article belongs to the Special Issue Next Generation Sequencing (NGS) in Newborn Screening)

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10 pages, 6040 KiB

Open AccessReview

Establishing Newborn Screening for SCID in the USA: Experience in California

by Jennifer M. Puck and Andrew R. Gennery

Int. J. Neonatal Screen. 2021, 7(4), 72; https://doi.org/10.3390/ijns7040072 - 31 Oct 2021

Cited by 7 | Viewed by 3342

Abstract

Newborn screening for severe combined immunodeficiency (SCID) has developed from the realization that infants affected with SCID require prompt diagnosis and treatment to avoid fatal infectious complications. Screening DNA from infant dried blood spots for T-cell receptor excision circles (TRECs), byproducts of normal [...] Read more.

Newborn screening for severe combined immunodeficiency (SCID) has developed from the realization that infants affected with SCID require prompt diagnosis and treatment to avoid fatal infectious complications. Screening DNA from infant dried blood spots for T-cell receptor excision circles (TRECs), byproducts of normal antigen-receptor gene rearrangement, has proven to be a reliable method to identify infants with SCID and other serious T lymphocyte defects before the onset of serious infections. The experience of the SCID newborn screening program in California after screening over 3 million infants demonstrates the effectiveness of this measure. Full article

(This article belongs to the Special Issue Newborn Screening for Severe Combined Immune Deficiency—Selected Papers from the ISNS-SCID Meeting)

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53 pages, 402 KiB

Open AccessConference Report

12th ISNS European Regional Meeting Oral and Poster Abstracts

by Kate Hall

Int. J. Neonatal Screen. 2021, 7(4), 71; https://doi.org/10.3390/ijns7040071 - 29 Oct 2021

Cited by 3 | Viewed by 3379

Abstract

Due to the impact worldwide of COVID-19, the 12th European ISNS meeting planned to be live in Luxembourg in November 2020 became Luxembourg Going Virtual in November 2021. The conference theme derived from the geographic location of Luxembourg was retained: Newborn screening—working together [...] Read more.

Due to the impact worldwide of COVID-19, the 12th European ISNS meeting planned to be live in Luxembourg in November 2020 became Luxembourg Going Virtual in November 2021. The conference theme derived from the geographic location of Luxembourg was retained: Newborn screening—working together in the heart of Europe. Abstracts of the newborn screening experience and knowledge shared in both oral presentations and posters at the symposium are gathered here to assist in selecting presenters to attend virtually and posters to view online. Some abstract highlights include findings from pilot studies of new screening disorders, the value of screening older previously unscreened children, and benefits of second tier testing. Full article

7 pages, 380 KiB

Open AccessTechnical Note

Towards a Newborn Screening Common Data Model: The Utah Newborn Screening Data Model

by David Jones, Jianyin Shao, Heidi Wallis, Cody Johansen, Kim Hart, Marzia Pasquali, Ramkiran Gouripeddi and Andreas Rohrwasser

Int. J. Neonatal Screen. 2021, 7(4), 70; https://doi.org/10.3390/ijns7040070 - 27 Oct 2021

Cited by 4 | Viewed by 2812

Abstract

As newborn screening programs transition from paper-based data exchange toward automated, electronic methods, significant data exchange challenges must be overcome. This article outlines a data model that maps newborn screening data elements associated with patient demographic information, birthing facilities, laboratories, result reporting, and [...] Read more.

As newborn screening programs transition from paper-based data exchange toward automated, electronic methods, significant data exchange challenges must be overcome. This article outlines a data model that maps newborn screening data elements associated with patient demographic information, birthing facilities, laboratories, result reporting, and follow-up care to the LOINC, SNOMED CT, ICD-10-CM, and HL7 healthcare standards. The described framework lays the foundation for the implementation of standardized electronic data exchange across newborn screening programs, leading to greater data interoperability. The use of this model can accelerate the implementation of electronic data exchange between healthcare providers and newborn screening programs, which would ultimately improve health outcomes for all newborns and standardize data exchange across programs. Full article

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6 pages, 1018 KiB

Open AccessCommunication

Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay

by Stuart P. Adams, Emma Gravett, Natalie Kent, Susanne Kricke, Adeboye Ifederu, Mariacristina Scoto, Salma Samsuddin and Francesco Muntoni

Int. J. Neonatal Screen. 2021, 7(4), 69; https://doi.org/10.3390/ijns7040069 - 26 Oct 2021

Cited by 1 | Viewed by 3155

Abstract

Spinal muscular atrophy (SMA) is an autosomal inherited neuromuscular genetic disease caused, in 95% of cases, by homozygous deletions involving the SMN1 gene exon 7. It remains the leading cause of death in children under 2 years of age. New treatments have been [...] Read more.

Spinal muscular atrophy (SMA) is an autosomal inherited neuromuscular genetic disease caused, in 95% of cases, by homozygous deletions involving the SMN1 gene exon 7. It remains the leading cause of death in children under 2 years of age. New treatments have been developed and adopted for use in many countries, including the UK. Success of these treatments depends on early diagnosis and intervention in newborn babies, and many countries have implemented a newborn screening (NBS) or pilot NBS program to detect SMN1 exon 7 deletions on dried blood spots. In the UK, there is no current NBS program for SMA, and no pilot studies have commenced. For consideration of adoption of NBS for a new condition, numerous criteria must be satisfied, including critical assessment of a working methodology. This study uses a commercially available real-time PCR assay to simultaneously detect two different DNA segments (SMN1 exon 7 and control gene RPP30) using DNA extracted from a dried blood spot. This study was carried out in a routine clinical laboratory to determine the specificity, sensitivity, and feasibility of SMA screening in a UK NBS lab setting. Just under 5000 normal DBSs were used alongside 43 known SMA positive DBSs. Study results demonstrate that NBS for SMA using real-time PCR is feasible within the current UK NBS Laboratory infrastructure using the proposed algorithm. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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7 pages, 386 KiB

Open AccessReview

The Discovery of GALM Deficiency (Type IV Galactosemia) and Newborn Screening System for Galactosemia in Japan

by Atsuo Kikuchi, Yoichi Wada, Toshihiro Ohura and Shigeo Kure

Int. J. Neonatal Screen. 2021, 7(4), 68; https://doi.org/10.3390/ijns7040068 - 25 Oct 2021

Cited by 6 | Viewed by 3838

Abstract

The Leloir pathway, which consists of highly conserved enzymes, metabolizes galactose. Deficits in three enzymes in this pathway, namely galactose-1-phosphate uridylyltransferase (GALT), galactokinase (GALK1), and UDP-galactose-4′-epimerase (GALE), are associated with genetic galactosemia. We recently identified patients with galactosemia and biallelic variants in GALM [...] Read more.

The Leloir pathway, which consists of highly conserved enzymes, metabolizes galactose. Deficits in three enzymes in this pathway, namely galactose-1-phosphate uridylyltransferase (GALT), galactokinase (GALK1), and UDP-galactose-4′-epimerase (GALE), are associated with genetic galactosemia. We recently identified patients with galactosemia and biallelic variants in GALM, encoding galactose epimerase (GALM), an enzyme that is directly upstream of GALK1. GALM deficiency was subsequently designated as type IV galactosemia. Currently, all the published patients with biallelic GALM variants were found through newborn screening in Japan. Here, we review GALM deficiency and describe how we discovered this relatively mild but not rare disease through the newborn screening system in Japan. Full article

(This article belongs to the Collection Newborn Screening in Japan)

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9 pages, 1515 KiB

Open AccessReview

Early Development of Newborn Screening for HCU and Current Challenges

by Harvey L. Levy

Int. J. Neonatal Screen. 2021, 7(4), 67; https://doi.org/10.3390/ijns7040067 - 25 Oct 2021

Cited by 6 | Viewed by 2840

Abstract

Classic homocystinuria (HCU) was added to newborn screening (NBS) by Robert Guthrie a few years after the disorder was first described. The justification for NBS was similar to that for PKU, that presymptomatic identification and early dietary treatment would prevent the clinical consequences, [...] Read more.

Classic homocystinuria (HCU) was added to newborn screening (NBS) by Robert Guthrie a few years after the disorder was first described. The justification for NBS was similar to that for PKU, that presymptomatic identification and early dietary treatment would prevent the clinical consequences, which, for HCU, are mental deficiency, ectopia lentis, skeletal abnormalities, and thromboembolism. It was assumed that identifying increased methionine in the screening blood specimen would identify all affected neonates. However, it is now clear that many with HCU are missed by NBS, mainly because the methionine level in the first days of life is normal or below the cutoff level in the NBS program. This includes virtually all of those with B₆-responsive HCU. Thus, a more effective method of NBS for HCU should be considered. Included among the possibilities are decreasing the methionine cutoff level, requiring an increase in the Met/Phe ratio if the methionine level is not at or greater than the cutoff level, using methionine as the primary screen with homocysteine as a second-tier test, or replacing methionine with homocysteine as the primary screen. Homocysteine is the primary metabolite that increases in HCU, while the methionine increase is secondary, so homocysteine is usually increased before the increase in methionine, almost always during the first few days of life. Finally, targeted gene screening might be considered. All of these possibilities would impose added expense and labor to NBS, so meeting these challenges would likely require a regional or national effort. Full article

(This article belongs to the Special Issue Newborn Screening for Classical Homocystinuria)

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Open AccessCorrection

Correction: Furnier et al. Translating Molecular Technologies into Routine Newborn Screening Practice. Int. J. Neonatal Screen. 2020, 6, 80

by Sarah M. Furnier, Maureen S. Durkin and Mei W. Baker

Int. J. Neonatal Screen. 2021, 7(4), 66; https://doi.org/10.3390/ijns7040066 - 22 Oct 2021

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Abstract

In the original article [...] Full article

16 pages, 1235 KiB

Open AccessArticle

Long-Term Course of Hypothyroidism Detected through Neonatal TSH Screening in a Population-Based Cohort of Very Preterm Infants Born at Less than 32 Weeks of Gestation

by Birgit Odenwald, Aline Fischer, Wulf Röschinger, Bernhard Liebl, Heinrich Schmidt and Uta Nennstiel

Int. J. Neonatal Screen. 2021, 7(4), 65; https://doi.org/10.3390/ijns7040065 - 13 Oct 2021

Cited by 4 | Viewed by 2526

Abstract

After several decades of successful newborn screening (NBS) for congenital hypothyroidism, the optimal hypothyroidism NBS algorithm for very preterm infants is still controversial. Due to concerns about an elevated risk of a false-negative initial thyroid-stimulation hormone (TSH) screening, repeat NBS has been implemented [...] Read more.

After several decades of successful newborn screening (NBS) for congenital hypothyroidism, the optimal hypothyroidism NBS algorithm for very preterm infants is still controversial. Due to concerns about an elevated risk of a false-negative initial thyroid-stimulation hormone (TSH) screening, repeat NBS has been implemented for this group. While transient hypothyroidism is known to be more frequent among very preterm infants, the prevalence of permanent hypothyroidism is generally assumed to be the same as in more mature newborns. This study analyses screening and long-term follow-up data from the population-based cohort of 51 infants born from 1999–2017 at less than 32 weeks of gestation and diagnosed with hypothyroidism after NBS in the German Federal State of Bavaria (total number of infants screened 2,107,864). Severe permanent hypothyroidism was always detected at initial TSH screening unless there was a known confounding factor. Cases detected by repeat screening after a negative initial screen most frequently proved to be transient, less frequently mild permanent, or a definitive diagnosis was not possible because of inadequate re-evaluation of the thyroid axis. The prevalence of both permanent and transient hypothyroidism was elevated compared to a cohort of children from the same region born at a higher gestational age. The results seem to support the need for the repeated NBS of very preterm infants. However, as the recommendation to treat mild hypothyroidism is not based on high quality evidence, important issues for future research include treatment outcome studies or even a general review of whether this diagnosis meets the screening criteria. Meanwhile, involving a paediatric endocrinologist in treatment decisions is crucial for optimising the benefit of hypothyroidism screening for this particularly vulnerable group. Full article

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16 pages, 315 KiB

Open AccessArticle

Processing of Positive Newborn Screening Results for Congenital Hypothyroidism: A Qualitative Exploration of Current Practice in England

by Pru Holder, Tim Cheetham, Alessandra Cocca, Holly Chinnery and Jane Chudleigh

Int. J. Neonatal Screen. 2021, 7(4), 64; https://doi.org/10.3390/ijns7040064 - 13 Oct 2021

Cited by 1 | Viewed by 3214

Abstract

The objective of this research was to explore current communication practices for positive newborn bloodspot screening results for congenital hypothyroidism from the newborn bloodspot screening laboratory to clinicians and then families, in order to (i) understand how the pathway is implemented in practice, [...] Read more.

The objective of this research was to explore current communication practices for positive newborn bloodspot screening results for congenital hypothyroidism from the newborn bloodspot screening laboratory to clinicians and then families, in order to (i) understand how the pathway is implemented in practice, (ii) highlight regional differences and (iii) identify barriers and facilitators. A qualitative exploratory design was employed using semi-structured interviews across 13 newborn bloodspot screening laboratories in England. Participants included 35 clinicians and 17 NBS laboratory staff across the 13 laboratories and 18 members of relevant clinical teams. Findings illuminated variations in how positive newborn bloodspot screening results for congenital hypothyroidism are communicated in practice. This included regional variations due to historical arrangements and local resources. Contacting the appropriate person could be challenging and obtaining feedback from clinical teams to the laboratory after the child has been seen could be time consuming for those involved. Standardised communication model(s) for positive newborn bloodspot screening results for congenital hypothyroidism, which include named contact individuals, defined pathways of care and processes for feeding back to laboratories, may help to ensure the process is less labour intensive, particularly from a laboratory perspective. Full article

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9 pages, 1024 KiB

Open AccessCommentary

Scalable Newborn Screening Solutions: Bioinformatics and Next-Generation Sequencing

by Nicole Ruiz-Schultz, Bryce Asay and Andreas Rohrwasser

Int. J. Neonatal Screen. 2021, 7(4), 63; https://doi.org/10.3390/ijns7040063 - 30 Sep 2021

Cited by 2 | Viewed by 2573

Abstract

Expansion of the newborn disorder panel requires the incorporation of new testing modalities. This is especially true for disorders lacking robust biomarkers for detection in primary screening methods and for disorders requiring genotyping or sequencing as a second-tier and/or diagnostic test. In this [...] Read more.

Expansion of the newborn disorder panel requires the incorporation of new testing modalities. This is especially true for disorders lacking robust biomarkers for detection in primary screening methods and for disorders requiring genotyping or sequencing as a second-tier and/or diagnostic test. In this commentary, we discuss how next-generation sequencing (NGS) methods can be used as a secondary testing method in NBS. Additionally, we elaborate on the importance of genomic variant repositories for the annotation and interpretation of variants. Barriers to the incorporation of NGS and bioinformatics within NBS are discussed, and ideas for a regional bioinformatics model and shared variant repository are presented as potential solutions. Full article

(This article belongs to the Special Issue Next Generation Sequencing (NGS) in Newborn Screening)

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5 pages, 241 KiB

Open AccessCase Report

Early Diagnosis and Treatment of Purine Nucleoside Phosphorylase (PNP) Deficiency through TREC-Based Newborn Screening

by Andrea Martín-Nalda, Jacques G. Rivière, Mireia Català-Besa, Marina García-Prat, Alba Parra-Martínez, Mónica Martínez-Gallo, Roger Colobran, Ana Argudo-Ramírez, Jose Luis Marín-Soria, Judit García-Villoria, Laura Alonso, Jose Antonio Arranz-Amo, Giancarlo la Marca and Pere Soler-Palacín

Int. J. Neonatal Screen. 2021, 7(4), 62; https://doi.org/10.3390/ijns7040062 - 29 Sep 2021

Cited by 2 | Viewed by 3129

Abstract

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disorder, resulting in severe combined immunodeficiency. To date, PNP deficiency has been detected in newborn screening only through the use of liquid chromatography tandem mass spectrometry. We report the first case in which PNP [...] Read more.

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disorder, resulting in severe combined immunodeficiency. To date, PNP deficiency has been detected in newborn screening only through the use of liquid chromatography tandem mass spectrometry. We report the first case in which PNP deficiency was detected by TREC analysis. Full article

(This article belongs to the Special Issue Newborn Screening for Severe Combined Immune Deficiency—Selected Papers from the ISNS-SCID Meeting)

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Int. J. Neonatal Screen., Volume 7, Issue 4 (December 2021) – 23 articles

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