International Journal of Neonatal Screening

10 pages, 1917 KB

Open AccessArticle

Pathogenic Analysis of Two SLC22A5 Variants That Alter RNA Splicing in Patients with Primary Carnitine Deficiency

by Yiming Lin, Yanru Chen, Weihua Lin and Faming Zheng

Int. J. Neonatal Screen. 2026, 12(1), 17; https://doi.org/10.3390/ijns12010017 - 16 Mar 2026

Functional analysis of SLC22A5 variants can improve diagnostic accuracy in patients with primary carnitine deficiency (PCD). Herein, we performed a genetic analysis of three neonates with PCD. Two of the patients harbored a novel synonymous SLC22A5 variant that has not been previously reported, [...] Read more.

Functional analysis of SLC22A5 variants can improve diagnostic accuracy in patients with primary carnitine deficiency (PCD). Herein, we performed a genetic analysis of three neonates with PCD. Two of the patients harbored a novel synonymous SLC22A5 variant that has not been previously reported, and the other patient harbored a classical splice site variant. The splicing patterns of the two SLC22A5 variants were evaluated using three in silico tools, and in vitro minigene analysis was performed to verify the impact of variants on RNA splicing mechanisms. All three in silico tools predicted that both SLC22A5 variants could alter normal RNA splicing. Functional studies using minigene assays demonstrated that the c.450C>T (p.F150=) leads to partial exon 2 skipping, and c.394-1G>A leads to intron 1 retention and exon 2 skipping. Intron 1 retention of 65 nucleotides and exon 2 skipping were confirmed by sequencing cDNA amplification products. These results, along with functional evidence, led to reclassification of c.450C>T (p.F150=) and c.394-1G>A as likely pathogenic and pathogenic, respectively. This is the first reported synonymous variant in the SLC22A5 gene that has been functionally validated to affect RNA splicing, thus enriching the variant spectrum of SLC22A5 and aiding accurate PCD diagnosis. Full article

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13 pages, 606 KB

Open AccessArticle

Clinical Experience of Timing Treatment in Newborns with Spinal Muscular Atrophy: A Call for Standardized Screening Practices in Italy

by Ilaria Bitetti, Rosa Iannaccone, Giovanna Margiotta and Antonio Varone

Int. J. Neonatal Screen. 2026, 12(1), 16; https://doi.org/10.3390/ijns12010016 - 9 Mar 2026

Abstract

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder causing progressive muscle weakness. Severe SMA forms are typically observed up to six months postnatally. Disease-modifying therapies provide significant benefits, making newborn screening (NBS) essential for timely diagnosis and treatment initiation. The NBS programme [...] Read more.

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder causing progressive muscle weakness. Severe SMA forms are typically observed up to six months postnatally. Disease-modifying therapies provide significant benefits, making newborn screening (NBS) essential for timely diagnosis and treatment initiation. The NBS programme evaluated infants born between April 2023 and October 2024 in the Campania region, Italy. DNA was amplified to detect homozygous deletion of the SMN1 gene by RT-PCR and SMN2 copy number using multiplex ligation-dependent probe amplification. Following treatment, motor functions were assessed using CHOP-INTEND and Bayley III scales. Among 62,801 infants screened for SMA, thirteen (11 females, 2 males) tested positive. The distribution of SMN2 copy numbers was as follows: eight patients had two copies, one patient had three, and four patients had four copies. One year after treatment, motor outcome data were available for four of the eight patients with two SMN2 copies. Among these patients, one achieved the milestones of walking without support, and three were standing with support. At 24 months, three of these patients were walking independently. Pre-symptomatic treatment markedly improves motor function development. This underscores the urgent need for large-scale newborn screening to prevent diagnostic delays and ensure timely, effective therapy. Validated care protocols must be established to facilitate early diagnosis and intervention. Full article

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8 pages, 640 KB

Open AccessArticle

Beyond Detection: Comparing State-Based Newborn Screening Methods for Effective Mucopolysaccharidosis I Diagnosis

by Rithika Thampy, Nishitha R. Pillai, Michael Evans, Chester B. Whitley, Paul J. Orchard, Matthew Ellinwood and Amy Gaviglio

Int. J. Neonatal Screen. 2026, 12(1), 15; https://doi.org/10.3390/ijns12010015 - 3 Mar 2026

Abstract

Mucopolysaccharidosis type I (MPS I) results in the accumulation of glycosaminoglycans (GAG) and, for the purposes of newborn screening, is differentiated into two forms: severe (Hurler syndrome) versus attenuated (encompassing Scheie and Hurler-Scheie syndromes). MPS I was added to the federal Recommended Uniform [...] Read more.

Mucopolysaccharidosis type I (MPS I) results in the accumulation of glycosaminoglycans (GAG) and, for the purposes of newborn screening, is differentiated into two forms: severe (Hurler syndrome) versus attenuated (encompassing Scheie and Hurler-Scheie syndromes). MPS I was added to the federal Recommended Uniform Screening Panel for newborn screening (NBS) in 2016, and as of December 2025, 45 of 54 programs in the United States (US) screen for MPS I. Within the newborn screening program, a second-tier analysis of GAG is thought to reduce false-positive rates, particularly through mitigating the detection of pseudodeficiency. However, there have been some concerns that the use of second-tier GAG analysis might inadvertently result in missed detection of attenuated cases. A survey of all US NBS programs was conducted requesting data on the total number of screen-positive NBS results for MPS I as well as the final diagnostic outcome from these results. Diagnostic outcomes after screening were classified as false-positive, pseudodeficiency, severe MPS I, attenuated MPS I, and MPS I of undetermined phenotype. Additionally, information on testing methodologies and dates of MPS I NBS implementation was collected. Responses were obtained from 32 NBS programs. The cohort of screening programs utilizing second-tier blood spot GAG determinations detected a higher proportion of severe cases than those not using this second-tier test (48% vs. 29%). The proportion of attenuated cases remained consistent between both groups (13% vs. 14%). The proportion of pseudodeficiency detection was only slightly lower in the cohort using second-tier GAG analysis (85% vs. 91%). Second-tier GAG analysis appears to reduce the detection of false-positive cases and improves the resolution of severe MPS I cases, though the proportion of pseudodeficiency was only slightly lower compared to the programs that do not use second-tier GAG analysis. Currently, the proportion of attenuated cases is comparable between the two cohorts, but the higher number of “undetermined phenotype” cases may eventually shift the balance toward states not using GAG analysis once the type is determined. Full article

(This article belongs to the Special Issue Advances in Newborn Screening for Lysosomal Disorders: From Laboratory Screening to Diagnosis)

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23 pages, 535 KB

Open AccessArticle

Current Status of Newborn Screening in Southeastern and Central Europe

by Nika Požun, Daša Perko, Violeta Anastasovska, Ivo Barić, Mihail Baša, Tadej Battelino, Iva Bilandžija, Ian Brincat, Miloš Brkušanin, Maja Djordević, Ivanka Dimova, Ana Drole Torkar, Ksenija Fumić, Sergiu Gladun, Panagiotis Girginoudis, Ildikó Szatmári, Ivana Kavečan, Jasmina Katanić, Vjosa Kotori, Nina Marić, Jelena Martić, Olja Manđarelo, Tatjana Milenković, Matej Mlinarič, Florentina Moldovanu, Michaela Nanu, Péter Monostori, Iskra Modeva, Branka Opančina, Dimitris Platis, Maja Raičević, Žiga Iztok Remec, Barbka Repič Lampret, Alexey Savov, Anastasia Skouma, Aleksandar Sovtić, Iva Stoeva, Alma Toromanović, Domen Trampuž, Natalia Usurelu, Jelena Višekruna, Marios Vogazianos, Maximillian Zeyda, Mojca Žerjav Tanšek and Urh Grošelj Show full author list Hide full author list

Int. J. Neonatal Screen. 2026, 12(1), 14; https://doi.org/10.3390/ijns12010014 - 2 Mar 2026

Abstract

Newborn screening (NBS) is a well-established public health program that enables early detection and treatment of rare disorders in newborns, preventing severe complications or death. Despite its recognized importance, the scope and implementation of NBS programs vary across Southeastern (SE) and Central Europe. [...] Read more.

Newborn screening (NBS) is a well-established public health program that enables early detection and treatment of rare disorders in newborns, preventing severe complications or death. Despite its recognized importance, the scope and implementation of NBS programs vary across Southeastern (SE) and Central Europe. This study aimed to evaluate the current status of NBS in 16 countries of SE and Central Europe and assess progress since the previous survey in 2021. A structured questionnaire was distributed to national experts between April and December 2025, collecting data on program organization, coverage, diseases included, laboratory methods, confirmatory testing, consent practices, and future expansion plans. All countries reported universal screening for congenital hypothyroidism, except Kosovo, where a national NBS is in the process of being established. Expanded NBS using tandem mass spectrometry was available in Austria, Bulgaria, Croatia, Cyprus, Greece, Hungary, North Macedonia, Romania, and Slovenia. Spinal muscular atrophy screening became universal in Austria, Croatia, Hungary, Serbia, and Slovenia. Most countries reported plans for further expansion, with congenital adrenal hyperplasia, severe combined immunodeficiency, spinal muscular atrophy, and cystic fibrosis being the most frequently targeted conditions. Although notable infrastructural progress has been achieved, financial constraints, lack of staff, and organizational barriers remain key challenges. The study’s assessment of program effectiveness was further limited by the absence of region-wide systems for capturing end-to-end performance indicators, such as the age of the infant at treatment initiation or missed cases. Regional collaboration and adoption of best practices are therefore vital to ensure equitable access and continuous advancement of NBS programs. Full article

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17 pages, 917 KB

Open AccessArticle

Two Years of Expanded Newborn Screening in Russia: High-Throughput Detection of Inherited Metabolic Disorders by Tandem Mass Spectrometry with Next-Generation Sequencing Confirmation

by Ekaterina Y. Zakharova, Galina V. Baydakova, Polina V. Baranova, Darya Y. Aleksandrova, Olga A. Shchagina, Yulia S. Itkis, Natalya V. Milovanova, Tatyana S. Nagornova, Olga N. Ivanova, Yana D. Nazarenko, Sergey V. Voronin, Alena L. Chukhrova, Varvara A. Kadnikova, Ekaterina E. Lotnik, Nina V. Ryadninskaya, Aleksander V. Polyakov, Kirill V. Savostyanov, Fanil S. Bilalov, Alexander L. Koroteev, Dmitry Y. Trofimov, Tatyana A. Bairova, Gulnara N. Seitova, Sergei V. Mordanov, Svetlana A. Matulevich, Elena B. Nikolaeva and Sergey I. Kutsev Show full author list Hide full author list

Int. J. Neonatal Screen. 2026, 12(1), 13; https://doi.org/10.3390/ijns12010013 - 2 Mar 2026

Abstract

In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and [...] Read more.

In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and December 2024, dried blood spots from 2,466,615 newborns (98.53% of the birth cohort) were analyzed for IMDs using MS/MS. Screen-positive cases were referred to the national reference center for confirmatory testing, which included biochemical (MS/MS and GC-MS) and genetic analyses (NGS). A total of 41,728 neonates (1.69%) screened positive, of whom 37,733 underwent confirmatory testing. It resulted in 834 confirmed diagnoses of IMDs (1 in 2900 live births). Phenylketonuria was the most prevalent IMD (n = 538; 1 in 4600), followed by MCADD (n = 99; 1 in 25,000). Distinct regional and ethnic variations were observed, including a high prevalence of tyrosinemia type 1 in the Chechen Republic and MCADD in North Ossetia. The integration of NGS was essential for resolving complex cases, such as identifying heterozygous carriers and dual diagnoses. These findings underscore the program’s clinical utility, highlight unique epidemiological patterns, and identify challenges such as false positives and diagnostic complexities, which will guide future refinements. Full article

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11 pages, 226 KB

Open AccessArticle

Pediatric Residents’ Awareness and Practices Toward Critical Congenital Heart Disease Screening in Saudi Arabia: A Multicenter Study

by Hussien Abdo Babiker, Turki Omaish Alotaibi, Hiba Hassan, Sulaiman Almohaimeed, Shadin Alamrah, Asalah Alhazmi and Abdulwahab H. Alharbi

Int. J. Neonatal Screen. 2026, 12(1), 12; https://doi.org/10.3390/ijns12010012 - 27 Feb 2026

Abstract

Critical congenital heart disease (CCHD) is a major cause of neonatal morbidity and mortality. Pulse oximetry screening enables early detection, potentially reducing complications and improving outcomes. This study evaluated pediatric residents’ knowledge, attitudes, and practices (KAP) related to CCHD screening in Saudi Arabia. [...] Read more.

Critical congenital heart disease (CCHD) is a major cause of neonatal morbidity and mortality. Pulse oximetry screening enables early detection, potentially reducing complications and improving outcomes. This study evaluated pediatric residents’ knowledge, attitudes, and practices (KAP) related to CCHD screening in Saudi Arabia. A cross-sectional survey was distributed to pediatric residents across Saudi Arabia. The questionnaire assessed knowledge, attitude, and practice regarding CCHD screening. A total of 123 pediatric residents in training were included in the study. Of these, 57 (46.3%) were male, and 66 (53.7%) were female. A progressive increase in mean scores was observed with advancing training years (p = 0.010). A significant difference was observed in knowledge scores based on completion of a cardiology rotation (p = 0.006). A progressive increase in attitude scores was observed with each successive year of training. Current year in training showed a statistically significant association with attitude scores (p < 0.001). Completion of a newborn nursery or NICU rotation was also significantly associated with higher attitude scores (p = 0.027). Similarly, attitude scores were significantly higher among those who had completed a cardiology rotation (mean = 12.99, SD = 1.52) compared to those who had not (mean = 11.60, SD = 1.84; p < 0.001). While practice scores were not statistically different across most groups, senior residents demonstrated better adherence to screening. Residents exhibit increasing awareness and positive attitudes with experience; however, practical implementation remains inconsistent. Targeted education and standardized protocols are necessary to improve outcomes. A positive correlation was observed between knowledge and attitude scores (r = 0.346, p < 0.001). Full article

(This article belongs to the Special Issue Global Updates on the Advancements in CCHD Screening)

8 pages, 228 KB

Open AccessCase Report

Exposure to CFTR Modulators During Pregnancy in Cystic Fibrosis: Four Cases to Highlight Neonatal Diagnostic Challenges and Outcomes

by Louis Domenach, Adrien Pagin, Camille Cisterne, Marie-Pierre Audrezet, Laure Couderc, Laetitia Monteil, Léa Roditis, Marlène Murris, Julie Macey, Michael Fayon, Stéphanie Bui and Marie-Pierre Reboul

Int. J. Neonatal Screen. 2026, 12(1), 11; https://doi.org/10.3390/ijns12010011 - 26 Feb 2026

Abstract

CFTR modulators have transformed the clinical evolution of patients with CF. The number of pregnancies is increasing in women with CF, most of whom are now treated with CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) or Tezacaftor/Ivacaftor. This raises some questions as we still [...] Read more.

CFTR modulators have transformed the clinical evolution of patients with CF. The number of pregnancies is increasing in women with CF, most of whom are now treated with CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) or Tezacaftor/Ivacaftor. This raises some questions as we still lack data on foetal and maternal safety. The preliminary data seem to support the continuation of modulators. Some of these mothers may also give birth to newborns with CF and this raises more questions. We report here four cases of CF newborns whose mothers were treated with CFTR modulators throughout pregnancy to help refine potential foetal outcomes of in utero administration of CF modulators. No maternal or foetal complications could be attributed to CFTR modulators. Three CF newborns were exposed to ETI and were false negative of the newborn screening. Two of them were pancreatic sufficient at birth. The remaining patient, exposed to Tezacaftor/Ivacaftor (TI) alone, showed elevated immunoreactive trypsin (IRT) and severe pancreatic insufficiency at birth. These cases highlight that in utero administration of ETI could potentially improve neonatal outcomes of CF newborns and cause newborn screening false negative. Full article

(This article belongs to the Special Issue Advances in Cystic Fibrosis Newborn Screening: From Laboratory Testing to Diagnosis)

21 pages, 1995 KB

Open AccessReview

Birth Prevalence of Sickle Cell Disease in India: A Systematic Review and Meta-Analysis

by Emine A. Rahiman, Rajendra Prasad Anne and Rajasekharan P. Warrier

Int. J. Neonatal Screen. 2026, 12(1), 10; https://doi.org/10.3390/ijns12010010 - 25 Feb 2026

Abstract

Newborn screening helps identify sickle cell disorder (SCD) early and to promptly initiate effective measures. It is estimated that India accounts for approximately 16% of global annual births with SCD. Multiple reports of screening for SCD in India have emerged in the last [...] Read more.

Newborn screening helps identify sickle cell disorder (SCD) early and to promptly initiate effective measures. It is estimated that India accounts for approximately 16% of global annual births with SCD. Multiple reports of screening for SCD in India have emerged in the last decade. Our aim was to pool the birth prevalence of SCD and sickle cell trait (SCT). A systematic review of published evidence on nontargeted, universal screening for SCD or SCT in newborns was performed (16 studies). The pooled prevalence of SCD was 1100 per 100,000 (10 studies, 88,276 neonates, 95% CI: 432, 1768), while that of SCT was 9639 per 100,000 (7 studies, 72,702 neonates, 95% CI: 6283, 12,995) in endemic regions. Limited data exist from nonendemic regions. Only three studies had data on follow-up and confirmatory genetic diagnosis. Sparse data exist on cost-effectiveness, long-term follow-up, and the impact of early screening on mortality. Concerted ongoing efforts in the identification of the burden are needed. The needs of the hour are universalization of NBS, integration into existing health systems, and maintenance of birth cohorts with early introduction of penicillin prophylaxis, hydroxyurea, parental education, appropriate immunization, and continued follow-up by an experienced medical team. Full article

(This article belongs to the Special Issue Newborn Screening for Sickle Cell Disease Between Point of Care Testing and Next Generation Sequencing – An Impossible Choice or Not?)

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9 pages, 210 KB

Open AccessArticle

Trends in the Timeliness of Spinal Muscular Atrophy Detection in US Infants, 2016–2023

by Scott D. Grosse, Kai Hong, Golriz K. Yazdanpanah, Ashley Nash, Amy Gaviglio, Marcus Gaffney, Kendra A. K. Lawrence and Jennifer M. Kwon

Int. J. Neonatal Screen. 2026, 12(1), 9; https://doi.org/10.3390/ijns12010009 - 18 Feb 2026

Abstract

Screening for spinal muscular atrophy (SMA) was adopted by all US state newborn screening programs between 2018 and 2024; by the end of 2022, 48 states were screening for SMA. We assessed trends in health insurance records of SMA diagnoses to quantify improvements [...] Read more.

Screening for spinal muscular atrophy (SMA) was adopted by all US state newborn screening programs between 2018 and 2024; by the end of 2022, 48 states were screening for SMA. We assessed trends in health insurance records of SMA diagnoses to quantify improvements in the timeliness of SMA identification following the adoption of screening. We used nationally representative Medicaid claims data for approximately half of US births covered by public insurance and a convenience sample of employer-sponsored health plans. We analyzed records for birth cohorts with at least 1 full year of follow-up (i.e., through the end of the following calendar year). For 2017 births, 1.3 per 100,000 infants had SMA codes first recorded by 1 month of age; this increased to 6.6 per 100,000 among publicly insured newborns born in 2022. The rollout of SMA newborn screening across US states was also followed by improvements in the timely detection of SMA. The proportion of infants with SMA detected by 1 month increased from 18% in 2017 to 61% in 2021 and is projected to reach 75% in 2022. Growth in timely detection was even greater in the employer-insured sample. Timely diagnosis of SMA can enable the initiation of treatment prior to the irreversible loss of motor function. Full article

26 pages, 431 KB

Open AccessReview

Newborn Screening for Hemoglobinopathies and Thalassemias: Brief History, Recent Activities, and Global Status—2026

by Bradford L. Therrell, Jr.

Int. J. Neonatal Screen. 2026, 12(1), 8; https://doi.org/10.3390/ijns12010008 - 17 Feb 2026

Abstract

Newborn bloodspot screening (NBS) began in Guthrie’s laboratory in 1961 for phenylketonuria. A federal study the following year formed the basis for expanding NBS as a public health function. Diseases detectable through NBS gradually expanded, eventually including sickle cell anemia, which was included [...] Read more.

Newborn bloodspot screening (NBS) began in Guthrie’s laboratory in 1961 for phenylketonuria. A federal study the following year formed the basis for expanding NBS as a public health function. Diseases detectable through NBS gradually expanded, eventually including sickle cell anemia, which was included in the screening panel in New York in 1975. Universal inclusion of full population screening for sickle cell anemia was included in all US NBS programs by 2006. Through the years, NBS for sickle cell anemia has expanded to include other clinically significant hemoglobin disorders (both hemoglobinopathies and thalassemias). While NBS programs exist in most high-income countries, their implementation in low- and middle-income settings has been slow, with the inclusion of hemoglobin disorders occurring even more slowly. It is particularly noteworthy that the low-resource settings with the highest incidences of sickle cell diseases (Sub-Saharan Africa, the Caribbean Islands, and India) and therefore the greatest potential for benefitting from NBS, continue to struggle with its implementation. Recent advances in curative treatments further emphasize the importance of NBS in early disease identification. This report reviews some of the history of newborn screening for hemoglobinopathies and thalassemias and provides an update of related activities currently ongoing globally. Full article

(This article belongs to the Special Issue Newborn Screening for Sickle Cell Disease Between Point of Care Testing and Next Generation Sequencing – An Impossible Choice or Not?)

11 pages, 731 KB

Open AccessArticle

Optimal Timing for Neonatal Hearing Screening in Well-Babies

by Lisanne Vonk, Paula van Dommelen, Iris Eekhout, Noëlle N. Uilenburg, Paul H. Verkerk and Catharina (Kitty) P. B. van der Ploeg

Int. J. Neonatal Screen. 2026, 12(1), 7; https://doi.org/10.3390/ijns12010007 - 15 Feb 2026

Abstract

In The Netherlands, preventive child healthcare (PCHC) has been carrying out neonatal hearing screening in well-babies since 2006. The aim of this study was to examine the relationship between the age of newborns and the false positive referral rate of the first hearing [...] Read more.

In The Netherlands, preventive child healthcare (PCHC) has been carrying out neonatal hearing screening in well-babies since 2006. The aim of this study was to examine the relationship between the age of newborns and the false positive referral rate of the first hearing screening using a transient evoked otoacoustic emission (OAE) test, to identify the most efficient timing for OAE screening. Additionally, we investigated the relationship between the type of OAE screening device (Echoscreen (ES)I/II versus ESIII) and the referral rate during the first screening. We used data from the Dutch universal well-baby neonatal hearing screening programme by PCHC between 2013 and 2023. Multilevel logistic regression analyses were performed to estimate the probability of a referral in 2023 for newborns screened in 2022 and 2023. We included a total of 1,650,506 newborns for 2013–2022 and 323,194 newborns for 2022–2023. The lowest false positive referral rates were found between days five and thirteen, ranging from 3.3 to 3.9%. ESIII significantly increased the probability of a referral compared to ESI/II (odds ratio = 1.84, 95% confidence interval = 1.65–2.06). In conclusion, the timing of neonatal hearing screening significantly impacts the false positive referral rate. Furthermore, the likelihood of a referral is significantly higher when using the ESIII compared to the ESI/II. Full article

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15 pages, 1199 KB

Open AccessArticle

Neonatal Genetic Screening Results for Spinal Muscular Atrophy in Romania: Insights from a 3-Years Pilot Program

by Madalina Cristina Leanca, Gelu Onose, Georgiana Nicolae, Elena Neagu, Daniela Vasile, Ecaterina Bercu, Oana Mirabela Balanescu, Andrei Capitanescu, Constantin Munteanu, Cristina Popescu and Andrada Mirea

Int. J. Neonatal Screen. 2026, 12(1), 6; https://doi.org/10.3390/ijns12010006 - 1 Feb 2026

Abstract

Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused by bi-allelic deletions or pathogenic SMN1 variants. Early diagnosis through neonatal screening is essential for timely therapeutic intervention, significantly improving clinical outcomes. In August 2022, a pilot neonatal screening program for SMA [...] Read more.

Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused by bi-allelic deletions or pathogenic SMN1 variants. Early diagnosis through neonatal screening is essential for timely therapeutic intervention, significantly improving clinical outcomes. In August 2022, a pilot neonatal screening program for SMA was launched in Romania, aiming to assess feasibility and impact. Objectives are to present the preliminary results of the ongoing SMA neonatal screening pilot program in Romania, evaluating its effectiveness in early detection and referral for treatment. The program started in August 2022 with four maternity hospitals and has progressively expanded to 28 maternity hospitals nationwide. Dried blood spot samples from newborns were analyzed for SMN1 gene deletions using real-time PCR. Positive results were confirmed through genetic testing, and affected infants, along with their families, were referred for further medical evaluation and early therapeutic intervention. Approximately 60,000 newborns have been screened since the program’s inception, and 12 newborns tested positive for SMN1 deletions, resulting in an estimated incidence rate of 1 in 5125 live births. All confirmed cases were promptly referred for specialized care, with early access to disease-modifying therapies. The program has faced challenges in logistics, parental awareness, and equitable access to treatment, but its expansion from 4 to 28 maternities demonstrates increasing feasibility, suitability, and acceptance. Conclusions: The Romanian pilot neonatal screening program for SMA has successfully identified affected infants early, proving its feasibility and clinical impact. The ongoing expansion suggests a strong foundation for a future national program, which could significantly improve early SMA diagnosis and patient outcomes in Romania. Full article

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9 pages, 201 KB

Open AccessConference Report

Integrated Newborn Screening in Nigeria: The Way Forward, A Workshop Report

by Olumuyiwa S. Folayan, Bose E. Orimadegun, Adejumoke I. Ayede, Baba P. Inusa, Marika K. Kase and John I. Anetor

Int. J. Neonatal Screen. 2026, 12(1), 5; https://doi.org/10.3390/ijns12010005 - 29 Jan 2026

Cited by 1

Abstract

Newborn screening (NBS) is a cost-effective public health strategy for the early detection of congenital disorders that cause neonatal/infant morbidity and mortality. It is standard care in many high-income and emerging economies. Nigeria, despite its high birth number, has no newborn screening (NBS) [...] Read more.

Newborn screening (NBS) is a cost-effective public health strategy for the early detection of congenital disorders that cause neonatal/infant morbidity and mortality. It is standard care in many high-income and emerging economies. Nigeria, despite its high birth number, has no newborn screening (NBS) programme for any disorder, causing missed opportunities for early therapy. This manuscript is a workshop report and expert consensus of a three-day national workshop organised by the Newborn Screening Consortium–Nigeria (NSC-N) in conjunction with The Federal Ministry of Health Nigeria, Revvity, and international partners. The first meeting comprised experts in different fields of newborn screening and newborn care who reviewed priority congenital disorders, implementation barriers, and national NBS needs in Nigeria. Experts presented pilot data, opinions, and global best practice evidence. Contributions were examined and debated and conclusions were reached by guided discussions and consensus agreement for a pragmatic nationwide NBS plan. The key outcomes were the urgency for Nigeria to begin an integrated, comprehensive NBS programme. Based on standard prioritisation criteria, sickle cell disease and congenital hypothyroidism were selected. Key implementation strategies included integration into routine maternal and child health services, establishing a national screening database, and developing a robust legislative and policy framework. The NBS workshop developed a framework to commence and incorporate integrated NBS into the Nigerian healthcare system. Two conditions were selected to kickstart the programme and establish a foundation for future expansion. This would improve neonatal health outcomes and reduce the long-term burden of congenital disorders. Full article

14 pages, 266 KB

Open AccessCommentary

Advances and Gaps in Global Newborn Screening for Sickle Cell Disease

by Lisa Marie Shook and Russell E. Ware

Int. J. Neonatal Screen. 2026, 12(1), 4; https://doi.org/10.3390/ijns12010004 - 21 Jan 2026

Cited by 1

Abstract

Newborn screening (NBS) for sickle cell disease (SCD) has been performed in the United States (US) for decades, significantly reducing infant morbidity and mortality. A landmark clinical trial demonstrated that early identification of SCD enabled timely and life-saving prophylactic penicillin; this led to [...] Read more.

Newborn screening (NBS) for sickle cell disease (SCD) has been performed in the United States (US) for decades, significantly reducing infant morbidity and mortality. A landmark clinical trial demonstrated that early identification of SCD enabled timely and life-saving prophylactic penicillin; this led to recommendations for universal NBS across the US. Early use of hydroxyurea as a safe and effective treatment for SCD further improved clinical outcomes by preventing acute and chronic disease complications. These advances add to the importance of early diagnosis through NBS, providing an opportunity for early treatment intervention. In recent years, high-resource countries—including those in Europe, the UK, and Canada—have adopted NBS for SCD using diverse strategies. Simultaneously, pilot programs in lower-resource settings such as Africa, Brazil, and India have demonstrated local feasibility and impact through implementation efforts. An overarching equity gap for achieving global NBS for SCD is the variable access to simple, accurate, and affordable testing. Other challenges include timing of NBS testing, targeted populations, laboratory methods, and parental education with genetic counseling. Questions remain about the equitable enrollment of affected infants worldwide into comprehensive care to ensure early treatment. These challenges raise concerns about sustainability, underscore the need for long-term funding and a strategic plan, and highlight persistent inequities from the lack of global NBS standards. Full article

(This article belongs to the Special Issue Equity Issues in Newborn Screening)

15 pages, 1207 KB

Open AccessArticle

Newborn Screening for Spinal Muscular Atrophy in the UK: Use of Modelling to Identify Priorities for Ongoing Evaluation

by Praveen Thokala, Alice Bessey, Rachel Knowles, John Marshall, Cristina Visintin, Miranda Lawton and Silvia Lombardo

Int. J. Neonatal Screen. 2026, 12(1), 3; https://doi.org/10.3390/ijns12010003 - 13 Jan 2026

Abstract

Spinal muscular atrophy (SMA) is a genetic condition that causes the degeneration of motor neurons in the spinal cord. Newborn blood spot (NBS) screening can potentially enable diagnosis before symptoms, and presymptomatic treatment is considered to be more effective than symptomatic treatment. In [...] Read more.

Spinal muscular atrophy (SMA) is a genetic condition that causes the degeneration of motor neurons in the spinal cord. Newborn blood spot (NBS) screening can potentially enable diagnosis before symptoms, and presymptomatic treatment is considered to be more effective than symptomatic treatment. In this paper, we present an overview of a cost-effectiveness model of NBS screening for SMA in the UK, informed by key clinical trials and the relevant published literature. Our analyses suggest that implementing screening could result in better outcomes and lower costs compared to the current approach of no screening plus treatment. However, several uncertainties and limitations of the model remain. These include uncertainty in the reimbursement status of nusinersen and risdiplam in the future; the ‘actual’ costs of treatments, as they are under confidential commercial agreements; uncertainty in the long-term effectiveness of presymptomatic and symptomatic treatment; and uncertainty around the incidence of SMA and the costs and the accuracy of NBS screening. An SMA in-service evaluation (ISE) that could capture data specific to the UK is under consideration, and an appropriately designed ISE with ongoing data collection could support periodic updates of clinical and cost-effectiveness estimates of NBS screening for SMA in the UK. Full article

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10 pages, 547 KB

Open AccessArticle

Parent Experience and Attitudes Towards Newborn Bloodspot Screening in Ireland

by Mairéad Bracken-Scally, Anna O’Loughlin and Heather Burns

Int. J. Neonatal Screen. 2026, 12(1), 2; https://doi.org/10.3390/ijns12010002 - 7 Jan 2026

Abstract

The aim of the evaluation was to gather information on parents’ experiences and attitudes towards the Irish National Newborn Bloodspot Screening Programme (NNBSP). An interviewer-administered survey was completed by 151 parents whose babies underwent newborn bloodspot screening (NBS) between 2023 and 2025 and [...] Read more.

The aim of the evaluation was to gather information on parents’ experiences and attitudes towards the Irish National Newborn Bloodspot Screening Programme (NNBSP). An interviewer-administered survey was completed by 151 parents whose babies underwent newborn bloodspot screening (NBS) between 2023 and 2025 and for whom the screening result was normal. Results suggest that NBS is highly acceptable to parents, with 100% glad their baby underwent screening. The majority (95%) felt they were provided the information needed to understand the importance of NBS for their baby, and 93% are in favour of screening for more conditions. Positive aspects of NBS reported by parents included the following: blood sampling being undertaken in the home, the sample-taker being very nice and being advised in advance to keep the baby’s heel warm to ease the sampling process. Negative aspects of NBS reported included the following: having to return to the hospital for sampling, the baby becoming distressed, not receiving adequate information and not receiving the screening results. Parents were more likely to report negative experiences if the sample was not taken at home and if the sample was taken by a healthcare professional other than a public health nurse. Parents offered recommendations for improvements to the programme. This study provides important insights into parents’ experiences and attitudes towards NBS in Ireland. Full article

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18 pages, 985 KB

Open AccessArticle

Too Early to Tell? Balancing Diagnostic Accuracy of Newborn Screening for Propionic Acidemia Versus a Timely Referral

by Nils W. F. Meijer, Hidde H. Huidekoper, Klaas Koop, Sabine A. Fuchs, M. Rebecca Heiner Fokkema, Charlotte M. A. Lubout, Andrea B. Haijer-Schreuder, Wouter F. Visser, Rendelien K. Verschoof-Puite, Eugènie Dekkers, Annet M. Bosch, Rose E. Maase and Monique G. M. de Sain-van der Velden

Int. J. Neonatal Screen. 2026, 12(1), 1; https://doi.org/10.3390/ijns12010001 - 24 Dec 2025

Abstract

In the Netherlands, the newborn screening (NBS) program includes screening for propionic aciduria (PA) and methylmalonic aciduria (MMA). When initial screening reveals elevated C3 concentrations or abnormal ratios (C3/C2, C3/C16), a second-tier test measuring methylcitric acid (MCA) for PA and methylmalonic acid (MMA [...] Read more.

In the Netherlands, the newborn screening (NBS) program includes screening for propionic aciduria (PA) and methylmalonic aciduria (MMA). When initial screening reveals elevated C3 concentrations or abnormal ratios (C3/C2, C3/C16), a second-tier test measuring methylcitric acid (MCA) for PA and methylmalonic acid (MMA^mb) for MMA is performed. While this two-tier approach reduces false positives effectively, it can delay referral from the NBS program and diagnosis of propionic aciduria. We describe four early-onset PA cases in which the current Dutch screening algorithm negatively impacted clinical outcomes, highlighting the need for expedited referral. We investigated different alternative screening strategies to identify the most effective approach for improving timeliness, while maintaining the high specificity of Dutch PA NBS. This revised approach prioritizes the evaluation of the C3/C2 ratio in first-tier screening. Specifically, samples with a C3/C2 ratio ≥ 0.75 should be referred directly for medical consultation and confirmatory testing. For all other samples with less pronounced biochemical abnormalities, the existing two-tier screening algorithm remains an appropriate NBS protocol. To position our approach internationally, a survey of European NBS programs was conducted to compare screening and referral protocols for PA across the region. Full article

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11 pages, 318 KB

Open AccessArticle

Neonatal Screening for Congenital Adrenal Hyperplasia in Guangzhou: 7 Years of Experience

by Xuefang Jia, Ting Xie, Xiang Jiang, Fang Tang, Minyi Tan, Qianyu Chen, Sichi Liu, Yonglan Huang and Li Tao

Int. J. Neonatal Screen. 2025, 11(4), 116; https://doi.org/10.3390/ijns11040116 - 17 Dec 2025

Abstract

This study was designed to assess the effectiveness of neonatal congenital adrenal hyperplasia (CAH) screening in Guangzhou, China. A total of 818,417 newborns were screened for CAH by measuring 17-hydroxyprogesterone (17-OHP) concentrations. Cut-off values were stratified based on gestational age (GA) and the [...] Read more.

This study was designed to assess the effectiveness of neonatal congenital adrenal hyperplasia (CAH) screening in Guangzhou, China. A total of 818,417 newborns were screened for CAH by measuring 17-hydroxyprogesterone (17-OHP) concentrations. Cut-off values were stratified based on gestational age (GA) and the timing of sample collection. Neonates with initial positive results (17-OHP ≥ cut-off value) were recalled for a second dried blood spot sample to reassess 17-OHP levels. Confirmatory testing involved biochemical analyses, Sanger sequencing, and multiplex ligation-dependent probe amplification of the CYP21A2 gene. From 2018 to 2024, a total of 40 patients with classical 21-hydroxylase deficiency were identified, including 28 cases (70%) of the salt-wasting form and 12 cases (30%) of the simple virilizing form. The overall incidence of CAH was 1 in 20,653 (95% confidence interval: 1:34,928, 1:14,661). No statistically significant differences in prevalence were observed between sexes or between preterm and full-term infants (p > 0.05). 17-OHP concentrations are influenced by GA and the timing of sample collection. The screening efficiency for CAH could be improved by adopting a multitiered cut-off value system adjusted for GA and collection time. Full article

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15 pages, 472 KB

Open AccessArticle

Psychological Impact of Newborn Screening for 3-Methylcrotonyl-CoA Carboxylase Deficiency: The Parental Experience

by Vincenza Gragnaniello, Giacomo Gaiga, Chiara Cazzorla, Elena Porcù, Daniela Gueraldi, Andrea Puma, Christian Loro, Mara Doimo, Leonardo Salviati and Alberto B. Burlina

Int. J. Neonatal Screen. 2025, 11(4), 115; https://doi.org/10.3390/ijns11040115 - 14 Dec 2025

Abstract

3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is a metabolic disorder with a wide clinical spectrum ranging from asymptomatic individuals to severe metabolic decompensation. Following the introduction of expanded newborn screening, a high number of asymptomatic individuals with 3-MCCD were identified, prompting debates about its inclusion [...] Read more.

3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is a metabolic disorder with a wide clinical spectrum ranging from asymptomatic individuals to severe metabolic decompensation. Following the introduction of expanded newborn screening, a high number of asymptomatic individuals with 3-MCCD were identified, prompting debates about its inclusion in screening panels. In order to inform policy and healthcare decisions regarding the inclusion of 3-MCCD in newborn screening programs, we evaluated the long-term outcomes for newborns with positive results over a decade of screening experience in North-East Italy, as well as the psychological impact on their parents. Of the 336,668 newborns screened between 2014 and 2025, 9 were confirmed to be affected. These infants underwent annual clinical and biochemical assessments, including dried blood spot acylcarnitine profile, plasma free carnitine, and urinary organic acids assays. An emergency protocol was provided to all affected children to manage intercurrent illnesses. An ad hoc survey was developed to assess the psychological impact of the disease on parents. During follow-up (mean age at last visit: 4.2 years), one patient experienced metabolic decompensation during an intercurrent illness, which was promptly treated. One patient presented with growth retardation and another with transient psychomotor delay. Five patients developed carnitine deficiency, requiring supplementation. Psychological assessments revealed an initial high level of parental psychological impact, which decreased over time. All parents strongly supported the screening program. Newborn screening for 3-MCCD enabled the early identification and management of affected individuals, thereby avoiding severe metabolic decompensation. Although there is an initial psychological burden on parents, it significantly decreases over time. Therefore, the long-term benefits of newborn screening for 3-MCCD seem to outweigh the psychological drawbacks. Full article

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International Journal of Neonatal Screening

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