International Journal of Neonatal Screening

10 pages, 204 KiB

Open AccessArticle

Postponement of the Newborn Hearing Screening during the COVID-19 Pandemic; Parental Experiences and Worries

by Rosanne B. van der Zee, Sanne L. Peet, Noëlle N. Uilenburg, Hedwig J. A. van Bakel and Evelien Dirks

Int. J. Neonatal Screen. 2024, 10(1), 26; https://doi.org/10.3390/ijns10010026 - 21 Mar 2024

Viewed by 527

Abstract

Early identification of hearing loss through newborn hearing screening followed by an early start of intervention has proven to be effective in promoting speech and language development in children with hearing loss. During the COVID-19 pandemic, newborn hearing screening was postponed for a [...] Read more.

Early identification of hearing loss through newborn hearing screening followed by an early start of intervention has proven to be effective in promoting speech and language development in children with hearing loss. During the COVID-19 pandemic, newborn hearing screening was postponed for a group of newborns in the Netherlands. Therefore, meeting the guidelines for early identification was at risk. In this study, we examine parental attitudes, beliefs, and experiences concerning the hearing screening during the COVID-19 pandemic. Our results indicated that parents (n = 1053) were very positive about newborn hearing screening and their experiences with the screening, even during the COVID-19 pandemic. Parents’ beliefs on the information provision around newborn hearing screening were more inconsistent. The results showed that parents with a postponed hearing screening felt less informed about the hearing screening than parents without a postponed screening. Furthermore, child and family characteristics affected how parents experienced newborn hearing screening. Parents with a premature child were more worried about the hearing abilities of their child before the screening took place. The results also indicate that deafness in the family might lead to parental worries around newborn hearing screening. Full article

14 pages, 1296 KiB

Open AccessArticle

Portuguese Neonatal Screening Program: A Cohort Study of 18 Years Using MS/MS

by Maria Miguel Gonçalves, Ana Marcão, Carmen Sousa, Célia Nogueira, Helena Fonseca, Hugo Rocha and Laura Vilarinho

Int. J. Neonatal Screen. 2024, 10(1), 25; https://doi.org/10.3390/ijns10010025 - 20 Mar 2024

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Abstract

The Portuguese Neonatal Screening Program (PNSP) conducts nationwide screening for rare diseases, covering nearly 100% of neonates and screening for 28 disorders, including 24 inborn errors of metabolism (IEMs). The study’s purpose is to assess the epidemiology of the screened metabolic diseases and [...] Read more.

The Portuguese Neonatal Screening Program (PNSP) conducts nationwide screening for rare diseases, covering nearly 100% of neonates and screening for 28 disorders, including 24 inborn errors of metabolism (IEMs). The study’s purpose is to assess the epidemiology of the screened metabolic diseases and to evaluate the impact of second-tier testing (2TT) within the PNSP. From 2004 to 2022, 1,764,830 neonates underwent screening using tandem mass spectrometry (MS/MS) to analyze amino acids and acylcarnitines in dried blood spot samples. 2TT was applied when necessary. Neonates with profiles indicating an IEM were reported to a reference treatment center, and subsequent biochemical and molecular studies were conducted for diagnostic confirmation. Among the screened neonates, 677 patients of IEM were identified, yielding an estimated birth prevalence of 1:2607 neonates. The introduction of 2TT significantly reduced false positives for various disorders, and 59 maternal cases were also detected. This study underscores the transformative role of MS/MS in neonatal screening, emphasizing the positive impact of 2TT in enhancing sensitivity, specificity, and positive predictive value. Our data highlight the efficiency and robustness of neonatal screening for IEM in Portugal, contributing to early and life-changing diagnoses. Full article

(This article belongs to the Special Issue Neonatal Screening in Europe: On the Brink of a New Era)

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9 pages, 1051 KiB

Open AccessArticle

Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK

by Rachel S. Carling, Katy Hedgethorne, Anupam Chakrapani, Patricia L. Hall, Nick Flynn, Toby Greenfield, Stuart J. Moat, Joshua Ssali, Lynette Shakespeare, Nazia Taj, Teresa H. Y. Wu, Mark Anderson, Arunabha Ghosh, Hugh Lemonde, Germaine Pierre, Mark Sharrard, Sreevidya Sreekantam and James R. Bonham

Int. J. Neonatal Screen. 2024, 10(1), 24; https://doi.org/10.3390/ijns10010024 - 13 Mar 2024

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Abstract

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP [...] Read more.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) µmol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those >2.0 and <5.0 µmol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder. Full article

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14 pages, 912 KiB

Open AccessArticle

Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey

by Kiran Moti Belaramani, Toby Chun Hei Chan, Edgar Wai Lok Hau, Matthew Chun Wing Yeung, Anne Mei Kwun Kwok, Ivan Fai Man Lo, Terry Hiu Fung Law, Helen Wu, Sheila Suet Na Wong, Shirley Wai Lam, Gladys Ha Yin Ha, Toby Pui Yee Lau, Tsz Ki Wong, Venus Wai Ching Or, Rosanna Ming Sum Wong, Wong Lap Ming, Jasmine Chi Kwan Chow, Eric Kin Cheong Yau, Antony Fu, Josephine Shuk Ching Chong, Ho Chung Yau, Grace Wing Kit Poon, Kwok Leung Ng, Kwong Tat Chan, Yuen Yu Lam, Joannie Hui, Chloe Miu Mak and Cheuk Wing Fung Show full author list Hide full author list

Int. J. Neonatal Screen. 2024, 10(1), 23; https://doi.org/10.3390/ijns10010023 - 11 Mar 2024

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Abstract

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, [...] Read more.

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period. Full article

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14 pages, 709 KiB

Open AccessArticle

Current Methods of Newborn Screening Follow-Up for Sickle Cell Disease Are Highly Variable and without Quality Assurance: Results from the ENHANCE Study

by Najibah Galadanci, Shannon Phillips, Alyssa Schlenz, Nataliya Ivankova and Julie Kanter

Int. J. Neonatal Screen. 2024, 10(1), 22; https://doi.org/10.3390/ijns10010022 - 08 Mar 2024

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Abstract

Newborn screening (NBS) for sickle cell disease (SCD) has significantly improved childhood survival but there are still gaps resulting in delayed care for affected infants. As a state-run program, there are no national quality assurance programs to ensure each state achieves consistent, reliable [...] Read more.

Newborn screening (NBS) for sickle cell disease (SCD) has significantly improved childhood survival but there are still gaps resulting in delayed care for affected infants. As a state-run program, there are no national quality assurance programs to ensure each state achieves consistent, reliable outcomes. We performed this qualitative study of NBS follow-up practices to better evaluate and understand the multi-level, state-specific processes of how each state’s public health department delivers the NBS results to families, how/if they ensure affected infants are seen quickly by sickle cell specialists, and to determine the close-out processes used in each state. This project used semi-structured interviews conducted with 29 participants across eight states to explore these NBS follow-up processes in each state. Participants included SCD providers, NBS coordinators, or personnel associated with state health departments and community-based SCD organizations (CBO). Our results show significant state-dependent variations in the NBS processes of information delivery and patient management. Specifically, programs differed in how they communicated results to affected families and which other organizations were informed of the diagnosis. There was also state-based (and intrastate) variation in who should assume responsibility for ensuring that infants receive confirmatory testing and are promptly started on penicillin prophylaxis. Case closure was also highly variable and poorly validated. Our results also yielded identifiable challenges and facilitators to NBS which were highly variable by state but potentially addressable in the future. This information suggests opportunities for systematic improvement in NBS follow-up processes. Full article

(This article belongs to the Special Issue A Lifespan Approach to Health and Well-Being Leveraging Neonatal Screening: Efforts in Advocacy, Academia, Research, and Clinical Care)

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13 pages, 2753 KiB

Open AccessArticle

Iowa Newborn Screening Program Experience with Hemoglobinopathy Screening over the Last Two Decades and Its Increasing Global Relevance

by Ryan Jilek, Jennifer Marcy, Carol Johnson, Georgianne Younger, Amy Calhoun and Moon Ley Tung

Int. J. Neonatal Screen. 2024, 10(1), 21; https://doi.org/10.3390/ijns10010021 - 08 Mar 2024

Viewed by 662

Abstract

Hemoglobinopathies are the commonest monogenic disorder worldwide, with approximately seven percent of the world population being carriers of hemoglobinopathies. The healthcare utilization impact of thalassemia has resulted in global public health initiatives to screen for hemoglobinopathies, especially sickle cell disease (SCD). The Iowa [...] Read more.

Hemoglobinopathies are the commonest monogenic disorder worldwide, with approximately seven percent of the world population being carriers of hemoglobinopathies. The healthcare utilization impact of thalassemia has resulted in global public health initiatives to screen for hemoglobinopathies, especially sickle cell disease (SCD). The Iowa Newborn Screening Program (INSP) has been in place for more than 50 years with a primary focus on detecting SCD. Recent changes in migration patterns have led to a global distribution of hemoglobinopathies in the western world, which has translated to an increase in the diagnosis of SCD and the incidental detection of non-sickling hemoglobinopathies within the INSP. This study documents the birth prevalence of hemoglobinopathies diagnosed in newborns through the INSP and highlights the need for newborn screening programs to evolve to meet the healthcare needs of underserved, minority populations. Full article

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17 pages, 1758 KiB

Open AccessArticle

Future of Dutch NGS-Based Newborn Screening: Exploring the Technical Possibilities and Assessment of a Variant Classification Strategy

by Gea Kiewiet, Dineke Westra, Eddy N. de Boer, Emma van Berkel, Tom G. J. Hofste, Martine van Zweeden, Ronny C. Derks, Nico F. A. Leijsten, Martina H. A. Ruiterkamp-Versteeg, Bart Charbon, Lennart Johansson, Janneke Bos-Kruizinga, Inge J. Veenstra, Monique G. M. de Sain-van der Velden, Els Voorhoeve, M. Rebecca Heiner-Fokkema, Francjan van Spronsen, Birgit Sikkema-Raddatz and Marcel Nelen

Int. J. Neonatal Screen. 2024, 10(1), 20; https://doi.org/10.3390/ijns10010020 - 07 Mar 2024

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Abstract

In this study, we compare next-generation sequencing (NGS) approaches (targeted panel (tNGS), whole exome sequencing (WES), and whole genome sequencing (WGS)) for application in newborn screening (NBS). DNA was extracted from dried blood spots (DBS) from 50 patients with genetically confirmed inherited metabolic [...] Read more.

In this study, we compare next-generation sequencing (NGS) approaches (targeted panel (tNGS), whole exome sequencing (WES), and whole genome sequencing (WGS)) for application in newborn screening (NBS). DNA was extracted from dried blood spots (DBS) from 50 patients with genetically confirmed inherited metabolic disorders (IMDs) and 50 control samples. One hundred IMD-related genes were analyzed. Two data-filtering strategies were applied: one to detect only (likely) pathogenic ((L)P) variants, and one to detect (L)P variants in combination with variants of unknown significance (VUS). The variants were filtered and interpreted, defining true/false positives (TP/FP) and true/false negatives (TN/FN). The variant filtering strategies were assessed in a background cohort (BC) of 4833 individuals. Reliable results were obtained within 5 days. TP results (47 patient samples) for tNGS, WES, and WGS results were 33, 31, and 30, respectively, using the (L)P filtering, and 40, 40, and 38, respectively, when including VUS. FN results were 11, 13, and 14, respectively, excluding VUS, and 4, 4, and 6, when including VUS. The remaining FN were mainly samples with a homozygous VUS. All controls were TN. Three BC individuals showed a homozygous (L)P variant, all related to a variable, mild phenotype. The use of NGS-based workflows in NBS seems promising, although more knowledge of data handling, automated variant interpretation, and costs is needed before implementation. Full article

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10 pages, 380 KiB

Open AccessArticle

Harnessing Next-Generation Sequencing as a Timely and Accurate Second-Tier Screening Test for Newborn Screening of Inborn Errors of Metabolism

by Toby Chun Hei Chan, Chloe Miu Mak, Matthew Chun Wing Yeung, Eric Chun-Yiu Law, Jana Cheung, Tsz Ki Wong, Vincent Wing-Sang Cheng, Jacky Kwan Ho Lee, Jimmy Chi Lap Wong, Cheuk Wing Fung, Kiran Moti Belaramani, Anne Mei Kwun Kwok and Kwok Yeung Tsang

Int. J. Neonatal Screen. 2024, 10(1), 19; https://doi.org/10.3390/ijns10010019 - 05 Mar 2024

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Abstract

In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) of six conditions for [...] Read more.

In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) of six conditions for inborn errors of metabolism: citrullinemia type II (MIM #605814), systemic primary carnitine deficiency (MIM #212140), glutaric acidemia type I (MIM #231670), beta-ketothiolase deficiency (#203750), holocarboxylase synthetase deficiency (MIM #253270) and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (MIM # 246450). The custom-designed NGS panel can detect sequence variants in the relevant genes and also specifically screen for the presence of the hotspot variant IVS16ins3kb of SLC25A13 by the copy number variant calling algorithm. Genetic second-tier tests were performed for 1.8% of a total of 22,883 NBS samples. The false positive rate for these six conditions after the NGS second-tier test was only 0.017%, and two cases of citrullinemia type II would have been missed as false negatives if only biochemical first-tier testing was performed. The confirmed true positive cases were citrullinemia type II (n = 2) and systemic primary carnitine deficiency (n = 1). The false positives were later confirmed to be carrier of citrullinemia type II (n = 2), carrier of glutaric acidemia type I (n = 1) and carrier of systemic primary carnitine deficiency (n = 1). There were no false negatives reported. The incorporation of a second-tier genetic screening test by NGS greatly enhanced our program’s performance with 5-working days turn-around time maintained as before. In addition, early genetic information is available at the time of recall to facilitate better clinical management and genetic counseling. Full article

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14 pages, 1148 KiB

Open AccessArticle

Psychosocial Impact of a True-Positive, False-Positive, or Inconclusive Newborn Bloodspot Screening Result: A Questionnaire Study among Parents

by Lieke M. van den Heuvel, Sylvia M. van der Pal, Rendelien K. Verschoof-Puite, Jasmijn E. Klapwijk, Ellen Elsinghorst, Eugènie Dekkers, Catharina P. B. van der Ploeg and Lidewij Henneman

Int. J. Neonatal Screen. 2024, 10(1), 18; https://doi.org/10.3390/ijns10010018 - 05 Mar 2024

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Abstract

Expansion of newborn bloodspot screening (NBS) can increase health gain for more children but also increases the number of false-positive and uncertain results. The impact of abnormal and inconclusive NBS results on parental well-being and healthcare utilization was investigated. A questionnaire was sent [...] Read more.

Expansion of newborn bloodspot screening (NBS) can increase health gain for more children but also increases the number of false-positive and uncertain results. The impact of abnormal and inconclusive NBS results on parental well-being and healthcare utilization was investigated. A questionnaire was sent to Dutch parents receiving an abnormal or inconclusive NBS result five weeks (T1) and four months (T2) post-NBS and compared to parents with a normal result (controls). In total, 35 true-positive (TP), 20 false-positive (FP), and 57 inconclusive (IC) participants and 268 controls filled out T1; 19 TP, 14 FP, 27 IC, and 116 controls filled out T2. Participants showed positive attitudes towards NBS. FP participants more often considered NBS less reliable. TP and FP participants experienced more negative emotions regarding the test result compared to controls at both T1 and T2, and IC only at T1. Parent-reported child vulnerability and perceptions of the newborn’s health status and of parenthood showed no differences. TP and FP participants reported more healthcare utilization at T1, and mainly TP at T2. TP and IC participants showed more emergency department visits at T1. The findings can be used to improve NBS programs and optimize support for families with various NBS results. Full article

(This article belongs to the Special Issue Psychosocial Burden of Positive Newborn Screening)

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9 pages, 606 KiB

Open AccessArticle

New Cases of Maleylacetoacetate Isomerase Deficiency with Detection by Newborn Screening and Natural History over 32 Years: Experience from a German Newborn Screening Center

by Gwendolyn Gramer, Saskia B. Wortmann, Junmin Fang-Hoffmann, Dirk Kohlmüller, Jürgen G. Okun, Holger Prokisch, Thomas Meitinger and Georg F. Hoffmann

Int. J. Neonatal Screen. 2024, 10(1), 17; https://doi.org/10.3390/ijns10010017 - 27 Feb 2024

Viewed by 660

Abstract

Newborn screening (NBS) for hepatorenal tyrosinemia type I (HT1) based on a determination of succinylacetone is performed in countries worldwide. Recently, biallelic pathogenic variants in GSTZ1 underlying maleylacetoacetate isomerase (MAAI) deficiency have been described as a differential diagnosis in individuals with slightly elevated [...] Read more.

Newborn screening (NBS) for hepatorenal tyrosinemia type I (HT1) based on a determination of succinylacetone is performed in countries worldwide. Recently, biallelic pathogenic variants in GSTZ1 underlying maleylacetoacetate isomerase (MAAI) deficiency have been described as a differential diagnosis in individuals with slightly elevated succinylacetone detected by NBS. We report the experience with NBS for HT1 over 53 months in a large German NBS center and the identification and characterization of additional cases with MAAI deficiency, including one individual with a natural history over 32 years. A total of 516,803 children underwent NBS for HT1 at the NBS center in Heidelberg between August 2016 and December 2020. Of 42 children with elevated succinylacetone, HT1 was confirmed in two cases (1 in 258.401). MAAI deficiency was suspected in two cases and genetically confirmed in one who showed traces of succinylacetone in urine. A previously unreported pathogenic GSTZ1 variant was found in the index in a biallelic state. Segregation analysis revealed monoallelic carriership in the index case‘s mother and homozygosity in his father. The 32-year-old father had no medical concerns up to that point and the laboratory work-up was unremarkable. MAAI has to be considered a rare differential diagnosis in NBS for HT1 in cases with slight elevations of succinylacetone to allow for correct counselling and treatment decisions. Our observation of natural history over 32 years adds evidence for a benign clinical course of MAAI deficiency without specific treatment. Full article

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11 pages, 1124 KiB

Open AccessArticle

History of Neonatal Screening of Congenital Hypothyroidism in Portugal

by Maria José Costeira, Patrício Costa, Susana Roque, Ivone Carvalho, Laura Vilarinho and Joana Almeida Palha

Int. J. Neonatal Screen. 2024, 10(1), 16; https://doi.org/10.3390/ijns10010016 - 20 Feb 2024

Viewed by 843

Abstract

Congenital hypothyroidism (CH) leads to growth and development delays and is preventable with early treatment. Neonatal screening for CH was initiated in Portugal in 1981. This study examines the history of CH screening in the country. Data were obtained from annual reports and [...] Read more.

Congenital hypothyroidism (CH) leads to growth and development delays and is preventable with early treatment. Neonatal screening for CH was initiated in Portugal in 1981. This study examines the history of CH screening in the country. Data were obtained from annual reports and from the national database of neonatal screening laboratory. The CH screening strategy primarily relies on the thyroid-stimulating hormone (TSH), followed by total thyroxine measurement as the second tier for confirmation. The TSH cutoff started at 90 mIU/L, decreasing to the actual 10 mIU/L. The coverage of the screening program has increased rapidly; although voluntary, it reached about 90% in 6 years and became universal in 10 years. Guideline and cutoff updates led to the identification of over 200 additional cases, resulting in specific retesting protocols for preterm and very-low-birth-weight babies. The actual decision tree considers CH when TSH levels are above 40 mIU/L. Data from the CH screening also provide an indication of the iodine status of the population, which is presently indicative of iodine insufficiency. The Portuguese neonatal screening for CH is a history of success. It has rapidly and continuously adapted to changes in knowledge and has become a universal voluntary practice within a few years. Full article

(This article belongs to the Special Issue Neonatal Screening in Europe: On the Brink of a New Era)

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12 pages, 1462 KiB

Open AccessArticle

Using the C14:1/Medium-Chain Acylcarnitine Ratio Instead of C14:1 to Reduce False-Positive Results for Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency in Newborn Screening in Japan

by Go Tajima, Junko Aisaki, Keiichi Hara, Miyuki Tsumura, Reiko Kagawa, Fumiaki Sakura, Hideo Sasai, Miori Yuasa, Yosuke Shigematsu and Satoshi Okada

Int. J. Neonatal Screen. 2024, 10(1), 15; https://doi.org/10.3390/ijns10010015 - 20 Feb 2024

Viewed by 914

Abstract

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a long-chain fatty acid oxidation disorder that manifests as either a severe phenotype associated with cardiomyopathy, a hypoglycemic phenotype, or a myopathic phenotype. As the hypoglycemic phenotype can cause sudden infant death, VLCAD deficiency is included in [...] Read more.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a long-chain fatty acid oxidation disorder that manifests as either a severe phenotype associated with cardiomyopathy, a hypoglycemic phenotype, or a myopathic phenotype. As the hypoglycemic phenotype can cause sudden infant death, VLCAD deficiency is included in newborn screening (NBS) panels in many countries. The tetradecenoylcarnitine (C14:1) level in dried blood specimens is commonly used as a primary marker for VLCAD deficiency in NBS panels. Its ratio to acetylcarnitine (C2) and various other acylcarnitines is used as secondary markers. In Japan, tandem mass spectrometry-based NBS, initially launched as a pilot study in 1997, was introduced to the nationwide NBS program in 2013. In the present study, we evaluated levels of acylcarnitine with various chain lengths (C18 to C2), free carnitine, and their ratios in 175 infants who tested positive for VLCAD deficiency with C14:1 and C14:1/C2 ratios. Our analyses indicated that the ratios of C14:1 to medium-chain acylcarnitines (C10, C8, and C6) were the most effective markers in reducing false-positive rates. Their use with appropriate cutoffs is expected to improve NBS performance for VLCAD deficiency. Full article

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

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17 pages, 1077 KiB

Open AccessArticle

Impact of Cytomegalovirus (CMV) on an Academic Pediatric Infectious Diseases Outpatient Clinic Referral Population, 2005–2020: Will the Advent of Universal Congenital CMV (cCMV) Screening Change Clinical Practice Referral Patterns?

by Katelyn J. Rypka and Mark R. Schleiss

Int. J. Neonatal Screen. 2024, 10(1), 14; https://doi.org/10.3390/ijns10010014 - 15 Feb 2024

Viewed by 1034

Abstract

Cytomegalovirus (CMV) infections exert a substantial impact on the practice of pediatric infectious diseases. Although most infections in children are minimally symptomatic, several populations are at risk for CMV-associated disease, including immunosuppressed children, children with HIV infection, and, most significantly, children with congenital [...] Read more.

Cytomegalovirus (CMV) infections exert a substantial impact on the practice of pediatric infectious diseases. Although most infections in children are minimally symptomatic, several populations are at risk for CMV-associated disease, including immunosuppressed children, children with HIV infection, and, most significantly, children with congenital CMV (cCMV) infection. In spite of the ubiquitous nature of CMV infection, few studies have quantified the impact of CMV-associated care in a pediatric outpatient clinic setting. We evaluated the impact of CMV on clinical care in an outpatient clinic setting over a fifteen-year period at the University of Minnesota (UMN) Masonic Children’s Hospital Pediatric Infectious Diseases (PID) Clinic. A retrospective review of clinic appointments identified 253 unique patients specifically evaluated over this time period for consideration of CMV infection. Of these, 242 were pediatric patients. The majority of the pediatric patients evaluated in the PID clinic were referred for either confirmed or suspected cCMV infection, including children referred for consideration of CMV as a potential reason for a failed newborn hearing screen (NHS) and/or for evaluation of CMV as a possible etiology for documented hearing loss. In total, 116 of the children evaluated during this time period (48%) were unequivocally confirmed as having cCMV infection, with an additional 37 (15%) presenting with presumed, probable, or possible cCMV infection. A total of 16 (7%) of the pediatric CMV cases were confirmed to be post-natally acquired infections. Of the 253 total patients, 11 (4%) of the referrals were for pregnant patients seeking advice about potential therapies in the setting of a known or suspected primary maternal infection during their pregnancies, with an attendant risk of fetal CMV infection. This overview of the demographics and referral patterns for patients evaluated for known or suspected CMV infections in a tertiary care center outpatient PID clinic will serve as a useful baseline assessment, even as future patterns of outpatient care are highly likely to evolve. We predict that PID clinic referrals for newborns identified by universal cCMV screening programs will result in a shift of the CMV outpatient population to healthier infants with clinically inapparent infections, and care will need to be taken by practitioners not to over-medicalize management for these asymptomatic newborns. Full article

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17 pages, 244 KiB

Open AccessArticle

Stakeholder Views of the Proposed Introduction of Next Generation Sequencing into the Cystic Fibrosis Screening Protocol in England

by Pru Holder, Corinna C. Clark, Louise Moody, Felicity K. Boardman, Jacqui Cowlard, Lorna Allen, Claire Walter, James R. Bonham and Jane Chudleigh

Int. J. Neonatal Screen. 2024, 10(1), 13; https://doi.org/10.3390/ijns10010013 - 14 Feb 2024

Cited by 1 | Viewed by 822

Abstract

The project aimed to gather, analyse, and compare the views of stakeholders about the proposed UK cystic fibrosis (CF) screening protocol incorporating next generation sequencing (NGS). The study design was based on principles of Q-methodology with a willingness-to-pay exercise. Participants were recruited from [...] Read more.

The project aimed to gather, analyse, and compare the views of stakeholders about the proposed UK cystic fibrosis (CF) screening protocol incorporating next generation sequencing (NGS). The study design was based on principles of Q-methodology with a willingness-to-pay exercise. Participants were recruited from 12 CF centres in the UK. The study contained twenty-eight adults who have experience with CF (parents of children with CF (n = 21), including parents of children with CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS)/CF screen positive—inconclusive diagnosis (CFSPID), an uncertain outcome (n = 3), and adults with CF (n = 4)), and nine health professionals involved in caring for children with CF. Parents and health professionals expressed a preference for a sensitive approach to NGS. This was influenced by the importance participants placed on not missing any children with CF via screening and the balance of harm between missing a case of CF compared to picking up more children with an uncertain outcome (CRMS/CFSPID). Given the preference for a sensitive approach, the need for adequate explanations about potential outcomes including uncertainty (CFSPID) at the time of screening was emphasized. More research is needed to inform definitive guidelines for managing children with an uncertain outcome following CF screening. Full article

11 pages, 212 KiB

Open AccessOpinion

Past as Prologue: Predicting Potential Psychosocial–Ethical Burdens of Positive Newborn Screens as Conditions Propagate

by Lynn W. Bush and Harvey L. Levy

Int. J. Neonatal Screen. 2024, 10(1), 12; https://doi.org/10.3390/ijns10010012 - 06 Feb 2024

Viewed by 762

Abstract

We look to the past as prologue for guidance in predicting and circumventing potential psychosocial–ethical challenges, including those that may influence the attachment process for some parents. We consider the evolution of bioethics and developmental psychology as they intersect with newborn screening while [...] Read more.

We look to the past as prologue for guidance in predicting and circumventing potential psychosocial–ethical challenges, including those that may influence the attachment process for some parents. We consider the evolution of bioethics and developmental psychology as they intersect with newborn screening while exploring potential implications of positive findings, be they false positives, true positives, or secondary as well as incidental findings. We reflect on navigating the complex landscape that may be significantly impacted by variable phenotypes, the age of onset, and uncertain prognoses, mindful of the diagnostic odyssey continuum. We explore select facets of ethical and psychological challenges encountered with positive newborn screening findings by highlighting enduring debates to improve the policy process in public health and medicine. We believe substantive empirical research is needed, including long-term follow-up, routine prenatal assessment of tolerance for uncertainties, and especially innovative methodologies to better evaluate potential psychological distress that may be present in some at-risk individuals during the perinatal period preceding and following reports of positive findings. Mitigation strategies building on lessons learned from NBS and clinical follow-up should be implemented and studied. We conclude by pondering why we remain far afield from providing these services. Research directed towards understanding the implications of positive NBS findings will further reduce the burdens on families and care providers alike and should lead to improved communication. Full article

(This article belongs to the Special Issue Psychosocial Burden of Positive Newborn Screening)

11 pages, 1382 KiB

Open AccessArticle

Leading Risk Factors for Congenital Deafness in the Context of Universal Neonatal Screening: Our Observations in a Four-Year Retrospective Study

by Antoine Paul, Fanny Bense, Claire Boithias Guerot, Sofia De La Rubia, Cécile Lebeaux and Jean-François Papon

Int. J. Neonatal Screen. 2024, 10(1), 11; https://doi.org/10.3390/ijns10010011 - 30 Jan 2024

Viewed by 704

Abstract

It has been demonstrated that universal hearing neonatal screening (UHNS) is efficient at providing early diagnosis and rehabilitation for deafness. The risk factors of deafness in children have been identified, but less specifically in those diagnosed after UHNS. In this study, we aim [...] Read more.

It has been demonstrated that universal hearing neonatal screening (UHNS) is efficient at providing early diagnosis and rehabilitation for deafness. The risk factors of deafness in children have been identified, but less specifically in those diagnosed after UHNS. In this study, we aim to study these factors in infants who were referred after screening and to compare our experience to recent data. We studied infants referred to our department for diagnosis after screening between January 2018 and December 2021. Their medical history and neonatal hearing risk factors were assessed. Associations between factors were also analyzed. Sixty-six infants were included. A family history of deafness (47%), syndromic deafness (41%), intrauterine growth retardation or prematurity (19.7%), and prolonged NICU admission (18%) were the most observed factors. When analyzing according to these associations, family history of deafness and syndromic cases remained the most prevalent factors (74%), while only five cases (7.8%) presented with other neonatal risk factors only. The majority of congenital hearing loss cases are observed in infants with suspected genetic deafness. Parental counseling, the diagnostic pathway, as well as the healthcare system should be adapted according to these risk factors. Full article

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9 pages, 388 KiB

Open AccessArticle

Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements

by Dietrich Matern, Khaja Basheeruddin, Tracy L. Klug, Gwendolyn McKee, Patricia U. Edge, Patricia L. Hall, Joanne Kurtzberg and Joseph J. Orsini

Int. J. Neonatal Screen. 2024, 10(1), 10; https://doi.org/10.3390/ijns10010010 - 28 Jan 2024

Cited by 1 | Viewed by 1712

Abstract

Krabbe disease (KD) is part of newborn screening (NBS) in 11 states with at least one additional state preparing to screen. In July 2021, KD was re-nominated for addition to the federal Recommended Uniform Screening Panel (RUSP) in the USA with a two-tiered [...] Read more.

Krabbe disease (KD) is part of newborn screening (NBS) in 11 states with at least one additional state preparing to screen. In July 2021, KD was re-nominated for addition to the federal Recommended Uniform Screening Panel (RUSP) in the USA with a two-tiered strategy based on psychosine (PSY) as the determinant if an NBS result is positive or negative after a first-tier test revealed decreased galactocerebrosidase activity. Nine states currently screening for KD include PSY analysis in their screening strategy. However, the nomination was rejected in February 2023 because of perceived concerns about a high false positive rate, potential harm to newborns with an uncertain prognosis, and inadequate data on presymptomatic treatment benefit or harm. To address the concern about false positive NBS results, a survey was conducted of the eight NBS programs that use PSY and have been screening for KD for at least 1 year. Seven of eight states responded. We found that: (1) the use of PSY is variable; (2) when modeling the data based on the recommended screening strategy for KD, and applying different cutoffs for PSY, each state could virtually eliminate false positive results without major impact on sensitivity; (3) the reason for the diverse strategies appears to be primarily the difficulty of state programs to adjust screening algorithms due to the concern of possibly missing even an adult-onset case following a change that focuses on infantile and early infantile KD. Contracts with outside vendors and the effort/cost of making changes to a program’s information systems can be additional obstacles. We recommend that programs review their historical NBS outcomes for KD with their advisory committees and make transparent decisions on whether to accept false positive results for such a devastating condition or to adjust their procedures to ensure an efficient, effective, and manageable NBS program for KD. Full article

11 pages, 788 KiB

Open AccessArticle

Establishment of a Pilot Newborn Screening Program for Spinal Muscular Atrophy in Saint Petersburg

by Anton Kiselev, Marianna Maretina, Sofia Shtykalova, Haya Al-Hilal, Natalia Maslyanyuk, Mariya Plokhih, Elena Serebryakova, Marina Frolova, Natalia Shved, Nadezhda Krylova, Arina Il’ina, Svetlana Freund, Natalia Osinovskaya, Iskender Sultanov, Anna Egorova, Anastasia Lobenskaya, Alexander Koroteev, Irina Sosnina, Yulia Gorelik, Olesya Bespalova, Vladislav Baranov, Igor Kogan and Andrey Glotov Show full author list Hide full author list

Int. J. Neonatal Screen. 2024, 10(1), 9; https://doi.org/10.3390/ijns10010009 - 25 Jan 2024

Viewed by 947

Abstract

Spinal muscular atrophy 5q (SMA) is one of the most common neuromuscular inherited diseases and is the most common genetic cause of infant mortality. SMA is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently developed drugs can improve the [...] Read more.

Spinal muscular atrophy 5q (SMA) is one of the most common neuromuscular inherited diseases and is the most common genetic cause of infant mortality. SMA is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently developed drugs can improve the motor functions of infants with SMA when they are treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using a real-time PCR assay with dried blood spots (DBS) was performed from January 2022 through November 2022 in Saint Petersburg, which is a representative Russian megapolis. Here, 36,140 newborns were screened by the GenomeX real-time PCR-based screening test, and three genotypes were identified: homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns), and wild-type individuals (35,364 newborns). The disease status of all four newborns that screened positive for the homozygous SMN1 deletion was confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined the incidence of spinal muscular atrophy in Saint Petersburg to be 1 in 9035 and the SMA carrier frequency to be 1 in 47. In conclusion, providing timely information regarding SMN1, confirmation of disease status, and SMN2 copy number as part of the SMA newborn-screening algorithm can significantly improve clinical follow-up, testing of family members, and treatment of patients with SMA. Full article

(This article belongs to the Special Issue Newborn Screening for SMA—State of the Art)

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13 pages, 209 KiB

Open AccessArticle

Experiences and Challenges with Congenital Hypothyroidism Newborn Screening in Indonesia: A National Cross-Sectional Survey

by Aman Bhakti Pulungan, Helena Arnetta Puteri, Muhammad Faizi, Paul Leslie Hofman, Agustini Utari and Jean-Pierre Chanoine

Int. J. Neonatal Screen. 2024, 10(1), 8; https://doi.org/10.3390/ijns10010008 - 19 Jan 2024

Viewed by 904

Abstract

The expansion of newborn screening (NBS) for congenital hypothyroidism (CH) is essential to reducing the number of preventable intellectual disabilities in children. Because of logistical issues, including geographic extremes, distinct cultures, and 4.8 million births annually, Indonesia has struggled to achieve universal NBS [...] Read more.

The expansion of newborn screening (NBS) for congenital hypothyroidism (CH) is essential to reducing the number of preventable intellectual disabilities in children. Because of logistical issues, including geographic extremes, distinct cultures, and 4.8 million births annually, Indonesia has struggled to achieve universal NBS coverage. A national cross-sectional electronic survey was conducted to explore challenges in CH NBS. Responses from 423 healthcare professionals and program administrators across 30 provinces in Indonesia were collected. The major challenges reported were refusal from families (39.2%), newborns being discharged <24 h (38.3%), and limited availability of filter paper (35.9%). The respondents considered refusal from families to be due to fear, while others did not understand the necessity of CH NBS. The vast majority of respondents believed that parents do not have sufficient understanding regarding CH NBS (96.5%). Our study found that only 38.5% of respondents had received formal CH NBS training, with pediatric endocrinologists being the only profession in which all respondents had been trained. Concerted efforts are needed to improve the access to and availability of resources, increase the capacity for sample collection and analysis, empower healthcare professionals, and develop educational resources to promote understanding and acceptance of NBS amongst families. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital Hypothyroidism)

6 pages, 447 KiB

Open AccessCase Report

A Case of DNAJC12-Deficient Hyperphenylalaninemia Detected on Newborn Screening: Clinical Outcomes from Early Detection

by Colleen Donnelly, Lissette Estrella, Ilona Ginevic and Jaya Ganesh

Int. J. Neonatal Screen. 2024, 10(1), 7; https://doi.org/10.3390/ijns10010007 - 17 Jan 2024

Viewed by 747

Abstract

DNAJC12-deficient hyperphenylalaninemia is a recently described inborn error of metabolism associated with hyperphenylalaninemia, neurotransmitter deficiency, and developmental delay caused by biallelic pathogenic variants of the DNAJC12 gene. The loss of the DNAJC12-encoded chaperone results in the destabilization of the biopterin-dependent aromatic [...] Read more.

DNAJC12-deficient hyperphenylalaninemia is a recently described inborn error of metabolism associated with hyperphenylalaninemia, neurotransmitter deficiency, and developmental delay caused by biallelic pathogenic variants of the DNAJC12 gene. The loss of the DNAJC12-encoded chaperone results in the destabilization of the biopterin-dependent aromatic amino acid hydroxylases, resulting in deficiencies in dopamine, norepinephrine, and serotonin. We present the case of a patient who screened positive for hyperphenylalaninemia on newborn screening and was discovered to be homozygous for a likely pathogenic variant of DNAJC12. Here, we review the management of DNAJC12-related hyperphenylalaninemia and compare our patient to other reported cases in the literature to investigate how early detection and management may impact clinical outcomes. Full article

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15 pages, 279 KiB

Open AccessArticle

Australian Public Perspectives on Genomic Newborn Screening: Risks, Benefits, and Preferences for Implementation

by Fiona Lynch, Stephanie Best, Clara Gaff, Lilian Downie, Alison D. Archibald, Christopher Gyngell, Ilias Goranitis, Riccarda Peters, Julian Savulescu, Sebastian Lunke, Zornitza Stark and Danya F. Vears

Int. J. Neonatal Screen. 2024, 10(1), 6; https://doi.org/10.3390/ijns10010006 - 17 Jan 2024

Cited by 2 | Viewed by 1460

Abstract

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing [...] Read more.

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing need to address the ethical and social issues that such initiatives raise. This study therefore aimed to explore the Australian public’s perspectives and values regarding key gNBS characteristics and preferences for service delivery. We recruited English-speaking members of the Australian public over 18 years of age via social media; 75 people aged 23–72 participated in 1 of 15 focus groups. Participants were generally supportive of introducing genomic sequencing into newborn screening, with several stating that the adoption of such revolutionary and beneficial technology was a moral obligation. Participants consistently highlighted receiving an early diagnosis as the leading benefit, which was frequently linked to the potential for early treatment and intervention, or access to other forms of assistance, such as peer support. Informing parents about the test during pregnancy was considered important. This study provides insights into the Australian public’s views and preferences to inform the delivery of a gNBS program in the Australian context. Full article

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

19 pages, 2438 KiB

Open AccessArticle

Influence of Season, Storage Temperature and Time of Sample Collection in Pancreatitis-Associated Protein-Based Algorithms for Newborn Screening for Cystic Fibrosis

by Pia Maier, Sumathy Jeyaweerasinkam, Janina Eberhard, Lina Soueidan, Susanne Hämmerling, Dirk Kohlmüller, Patrik Feyh, Gwendolyn Gramer, Sven F. Garbade, Georg F. Hoffmann, Jürgen G. Okun and Olaf Sommerburg

Int. J. Neonatal Screen. 2024, 10(1), 5; https://doi.org/10.3390/ijns10010005 - 12 Jan 2024

Viewed by 712

Abstract

Newborn screening (NBS) for cystic fibrosis (CF) based on pancreatitis-associated protein (PAP) has been performed for several years. While some influencing factors are known, there is currently a lack of information on the influence of seasonal temperature on PAP determination or on the [...] Read more.

Newborn screening (NBS) for cystic fibrosis (CF) based on pancreatitis-associated protein (PAP) has been performed for several years. While some influencing factors are known, there is currently a lack of information on the influence of seasonal temperature on PAP determination or on the course of PAP blood concentration in infants during the first year of life. Using data from two PAP studies at the Heidelberg NBS centre and storage experiments, we compared PAP determinations in summer and winter and determined the direct influence of temperature. In addition, PAP concentrations measured in CF-NBS, between days 21–35 and 36–365, were compared. Over a 7-year period, we found no significant differences between PAP concentrations determined in summer or winter. We also found no differences in PAP determination after 8 days of storage at 4 °C, room temperature or 37 °C. When stored for up to 3 months, PAP samples remained stable at 4 °C, but not at room temperature (p = 0.007). After birth, PAP in neonatal blood showed a significant increasing trend up to the 96th hour of life (p < 0.0001). During the first year of life, blood PAP concentrations continued to increase in both CF- (36–72 h vs. 36–365 d p < 0.0001) and non-CF infants (36–72 h vs. 36–365 d p < 0.0001). Seasonal effects in central Europe appear to have a limited impact on PAP determination. The impact of the increase in blood PAP during the critical period for CF-NBS and beyond on the applicability and performance of PAP-based CF-NBS algorithms needs to be re-discussed. Full article

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9 pages, 220 KiB

Open AccessArticle

Landscape Analysis of Neurodevelopmental Comorbidities in Newborn Screening Conditions: Challenges and Opportunities

by Zohreh Talebizadeh, Valerie Hu, Monir Shababi and Amy Brower

Int. J. Neonatal Screen. 2024, 10(1), 4; https://doi.org/10.3390/ijns10010004 - 04 Jan 2024

Viewed by 1065

Abstract

Newborn screening (NBS) is a large-scale public health program in the US that screens 3.8 million newborns for up to 81 genetic conditions each year. Many of these conditions have comorbidities, including neurodevelopmental disorders (NDDs). These comorbidities can have a significant impact on [...] Read more.

Newborn screening (NBS) is a large-scale public health program in the US that screens 3.8 million newborns for up to 81 genetic conditions each year. Many of these conditions have comorbidities, including neurodevelopmental disorders (NDDs). These comorbidities can have a significant impact on health outcomes across the lifespan. Most screened conditions are inborn errors of metabolism. PKU, the first condition identified by NBS, is an inherited metabolic disorder that can cause developmental delays and intellectual/developmental disabilities if not treated. The Newborn Screening Translational Research Network (NBSTRN) is a program that has been funded by the National Institute of Child Health and Human Development since 2008. NBSTRN is charged with developing, maintaining, and enhancing tools, resources, and expertise supporting NBS research. One of the tasks led by NBSTRN is to provide direction for developing question/answer sets used in the Longitudinal Pediatric Data Resource (LPDR) to create consensus-based and standardized common data elements (CDEs) for NBS conditions. There is growing interest in the NBS community in assessing neurodevelopmental trajectories through long-term follow-up studies. This could be streamlined by employing uniform CDEs. To address this unmet need, we conducted a landscape analysis to (1) explore the co-occurrence of NDD-related comorbidities and NBS conditions using text mining in MedGen, (2) compile a list of NDD-related CDEs from existing repositories as well as LPDR data dictionaries, and (3) identify challenges and knowledge gaps hindering the early identification of risks for NDDs in NBS conditions. Our findings can inform future efforts toward advancing the research infrastructure for this established public health program. The renewed awareness of the risk of NDDs after a positive NBS and diagnosis could lead to improved treatment guidelines for mental health conditions. Full article

14 pages, 297 KiB

Open AccessArticle

Light and Shadows in Newborn Screening for Lysosomal Storage Disorders: Eight Years of Experience in Northeast Italy

by Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Andrea Puma, Christian Loro, Elena Porcù, Maria Stornaiuolo, Paolo Miglioranza, Leonardo Salviati, Alessandro P. Burlina and Alberto B. Burlina

Int. J. Neonatal Screen. 2024, 10(1), 3; https://doi.org/10.3390/ijns10010003 - 25 Dec 2023

Viewed by 1137

Abstract

In the last two decades, the development of high-throughput diagnostic methods and the availability of effective treatments have increased the interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report [...] Read more.

In the last two decades, the development of high-throughput diagnostic methods and the availability of effective treatments have increased the interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow-up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry disease, Gaucher disease), using the enzyme activity assay by tandem mass spectrometry, and biomarker quantification as a second-tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive predictive value 40%), with an overall incidence of 1:4874. Of these, three patients with infantile-onset Pompe disease, two with neonatal-onset Gaucher disease and four with mucopolysaccharidosis type I were immediately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrates the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient outcomes. Challenges such as false-positive rates, the diagnosis of variants of uncertain significance or late-onset forms and the lack of treatment for neuronopathic forms, should be addressed. Full article

(This article belongs to the Special Issue Neonatal Screening in Europe: On the Brink of a New Era)

7 pages, 485 KiB

Open AccessCommunication

Incidental Detection of Classical Galactosemia through Newborn Screening for Phenylketonuria: A 10-Year Retrospective Audit to Determine the Efficacy of This Approach

by Nathan W. P. Cantley, Robert Barski, Helena Kemp, Sarah L. Hogg, Hoi Yee Teresa Wu, Ann Bowron, Catherine Collingwood, Jennifer Cundick, Claire Hart, Lynette Shakespeare, Mary Anne Preece, Helen Aitkenhead, Sarah Smith, Rachel S. Carling and Stuart J. Moat

Int. J. Neonatal Screen. 2024, 10(1), 2; https://doi.org/10.3390/ijns10010002 - 22 Dec 2023

Viewed by 725

Abstract

In the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an “Other disorder suspected” (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via [...] Read more.

In the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an “Other disorder suspected” (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via NBS and estimate the incidence of CG in live births in the UK. A survey was sent to all UK NBS laboratories to collate CG cases diagnosed in the UK from 2010 to 2020. Cases of CG diagnosed were determined if detected clinically, NBS, or by family screening, as well as age at diagnosis. Cases referred via the ODS pathway were also collated, including the final diagnosis made. Responses were obtained from 13/16 laboratories. Between 2010 and 2020, a total of 6,642,787 babies were screened, and 172 cases of CG were identified. It should be noted that 85/172 presented clinically, 52/172 were identified by NBS, and 17/172 came from family screening. A total of 117 referrals were made via the ODS pathway, and 45/117 were subsequently diagnosed with CG. Median (interquartile range) age at diagnosis by NBS and clinically was 8 days (7–11) and 10 days (7–16), respectively (Mann–Whitney U test, U = 836.5, p-value = 0.082). The incidence of CG is 1:38,621 live births. The incidence of CG in the UK is comparable with that of other European/western countries. No statistical difference was seen in the timing of diagnosis between NBS and clinical presentation based on the current practice of sampling on day 5. Bringing forward the day of NBS sampling to day 3 would increase the proportion diagnosed with CG by NBS from 52/172 (30.2%) to 66/172 (38.4%). Full article

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14 pages, 894 KiB

Open AccessArticle

Droplet Digital PCR (ddPCR) Does Not Enhance the Sensitivity of Detection of Cytomegalovirus (CMV) DNA in Newborn Dried Blood Spots Evaluated in the Context of Newborn Congenital CMV (cCMV) Screening

by Nelmary Hernandez-Alvarado, Craig J. Bierle and Mark R. Schleiss

Int. J. Neonatal Screen. 2024, 10(1), 1; https://doi.org/10.3390/ijns10010001 - 20 Dec 2023

Cited by 1 | Viewed by 993

Abstract

Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such [...] Read more.

Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such as PCR testing of newborn dried blood spots (DBS). This study aimed to evaluate the sensitivity of droplet digital PCR (ddPCR) compared to quantitative real-time PCR to detect CMV DNA in newborn DBS. The limit of detection of various ddPCR primer/probe combinations (singleplex UL55-HEX, singleplex UL83-FAM, and multiplex UL55-HEX/UL83-FAM) was evaluated using the National Institute of Standards and Technology’s (NIST) CMV quantitative standard. Singleplex UL55-HEX ddPCR exhibited the lowest limit of detection among the primer/probe combinations tested for ddPCR. UL55 ddPCR was then compared to real-time PCR in 49 infants with confirmed cCMV identified through newborn screening for CMV in saliva swabs and confirmed by a urine test. The results showed that ddPCR was only positive for 59% (29 out of 49) of the cCMV infants, while real-time PCR was positive for 80% (39 out of 49). Due to its lower sensitivity and throughput, ddPCR may not be suitable for cCMV newborn screening. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital CMV)

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Int. J. Neonatal Screen., Volume 10, Issue 1 (March 2024) – 26 articles

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