International Journal of Neonatal Screening最新文献

This study evaluates the incidence of metabolic disorders detected from January 2005 to December 2024 and their clinical outcomes. Data were retrospectively collected from the Louisiana Newborn Screening database. Clinical outcomes were obtained through review of corresponding medical records. In addition, an electronic questionnaire assessing educational attainment and neurodevelopmental disorders was sent to the patients' families. Of 1,230,356 infants screened, 478 were diagnosed with metabolic disorders, corresponding to an incidence of 1 in 2574 live births. The three most commonly identified conditions were biotinidase deficiency, phenylketonuria (PKU), and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). During the study period, at least 11 patients died. The program demonstrated a false-positive rate of 0.93%. Twelve patients (7%) were symptomatic before or at the time of NBS result notification. Recurrent metabolic decompensations occurred in 3 of 4 maple syrup urine disease (MSUD) cases, 7 of 7 methylmalonic acidemia (MMA) cases, 1 of 4 propionic acidemia (PA) cases and 1 of 7 urea cycle defect cases. Regarding long-term outcomes, 45.7% of survey respondents reported adverse neurodevelopmental outcomes of varying severity. Early detection and timely intervention have contributed to normal or near-normal outcomes in many cases. However, the morbidity and mortality observed in some patients despite early diagnosis highlights the severity and complexity of certain metabolic conditions. Additionally, the relatively high false positive rate underscores the need for ongoing efforts to improve the specificity of screening protocols to reduce unnecessary follow-ups and mitigate potential stress for families.

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This study aims to investigate the genotype characteristics of newborns with biallelic GJB2 mutations and their correlation with hearing phenotypes, providing a basis for clinical genetic counseling and hearing management. A retrospective study was conducted on 652 newborns with biallelic GJB2 mutations detected at the Newborn Diseases Screening Center of Shenzhen Maternal and Child Health Care Hospital from January 2022 to December 2024. The differences in mutation types, hearing screening, and diagnostic results were analyzed and compared between the homozygous and compound heterozygous mutation groups to assess their correlation with hearing phenotypes. Genotype analysis identified 543 cases of homozygous mutations, mainly the c.109G>A/c.109G>A genotype (98.90%). Compound heterozygous mutations were identified in 109 cases, with the majority being c.109G>A/c.235delC (76.15%). Following two-stage hearing screening, 227 (34.82%) of the 652 cases were referred, with bilateral failure accounting for the majority (81.94%) of these cases. The referral rates showed no significant difference between the homozygous (35.54%) and compound heterozygous (31.19%) groups (p > 0.05). The overall hearing loss detection rate was 6.90% (45/652); among these, eight infants who had initially passed the newborn hearing screening were later found to have hearing loss between 2.5 and 6 months of age. Among the 45 confirmed deaf children, hearing loss was mainly mild to moderate (87.50%), and profound deafness was only seen in the homozygous mutation group (10.29%, 7/68 ears). Most newborns with biallelic GJB2 mutations passed the two-stage hearing screening, and associated hearing loss was typically mild to moderate. Long-term auditory monitoring remains essential for all genetically confirmed infants to monitor late-onset progression.

Following Newborn Screening (NBS), parents receiving positive results experience various psychosocial effects upon learning their child's genetic information or unexpected findings. These factors warrant careful consideration. The Japanese Medical Association's Guidelines for Genetic Testing and Diagnosis in Medical Care highlight the importance of genetic counseling (GC) in NBS; however, its current implementation status remains unclear. This study aimed to determine current approaches to GC following positive NBS results in Japan. A questionnaire was conducted with pediatric metabolic specialists responsible for treating individuals who screen positive through NBS results to evaluate GC implementation and their views on its provision. GC was provided at most referral centers for NBS (although not routinely at approximately half of the facilities). In over 70% of cases, GC was performed by a metabolic specialist, regardless of clinical geneticist certification. Furthermore, some metabolic specialists may be reluctant to provide GC due to limited understanding or time constraints. Raising awareness that all parents are eligible for GC, regardless of their child's diagnosis or health status, is essential. In addition, a GC system incorporating multidisciplinary and multidepartmental collaboration is important for the multifaceted support of patients and families.

Universal newborn hearing screening (UNHS) has become widely adopted worldwide as a standard of care for the early detection of congenital hearing loss. The Egyptian UNHS program started as a presidential initiative by the Ministry of Health in November 2019. The program was initiated in 1346 primary health care units (PHCUs) located throughout the 26 governorates. A retrospective study was conducted to assess the performance of the Egyptian Program during the period from November 2019 to July 2023. Quality measures recommended by the Joint Committee on Infant Hearing including coverage rate, rate of referral to a second screening, follow up rate of attendance of second screening, referral for diagnosis rate, and follow up rate of attendance of diagnostic assessment, were analyzed. Over a period of 3 years and 9 months, more than five and half million infants underwent a first screening. The coverage rate was initially 39% and increased to reach 82% in 2023. The rate of referral to a second screen was 7.2% in 2019 and reached 5.2% in 2023. The follow-up rate of attendance of a second screening improved throughout the study period, from 75.5% to 92.1% but did not reach the benchmark of 95%. The rate of referrals for diagnosis was less than 1.7% and rate of attendance of a diagnostic assessment was initially 20% and improved to more than 65% in 2023. The very low rate of attendance of diagnostic assessment in 2020 and 2021 was attributed to the effects of the COVID pandemic.

Hemoglobinopathies represent a major public health concern in Tunisia. Although early diagnosis is essential, systemic neonatal screening has not yet been implemented at the national level. We conducted a screening study in Northern Tunisia (Bizerte region) using cord blood samples. Complete blood counts and hemoglobin analysis by capillary electrophoresis were performed. Samples showing abnormal profiles (HbBart's, HbS, HbC, or HbA < 20%) underwent molecular testing. Correlations between hematological parameters, hemoglobin fractions, and β mutation types were assessed. Among 328 neonatal cord blood samples analyzed, we detected 3 silent α⁺-thalassemia, 6 β⁺-thalassemia traits, 3 β⁰-thalassemia traits, 7 HbS traits, 2 HbC traits, and 1 compound heterozygous for α⁺-thalassemia/HbC. No homozygous cases were identified. The heterozygous frequency was estimated at 1.2%, 2.7%, and 2.1% for α-thalassemia, β-thalassemia, and sickle cell disease, respectively. HbF levels were significantly associated with the β-thalassemia trait. This study represents the first hemoglobinopathy screening in Northern Tunisia using cord blood, highlighting the feasibility and reliability of this approach. While pilot programs have already been initiated in some regions, our findings reinforce the need for broader implementation to ensure early and accurate diagnosis across the country.

Newborn screening (NBS) for congenital hypothyroidism (CH) facilitates early diagnosis and treatment and prevents permanent intellectual disability. Sadly, 50 years after the first introduction of NBS for CH, only 29.6% of newborns worldwide are screened. Africa and Asia, the continents with the highest birth rates, have very limited screening coverage. Most NBS programs measure TSH in a dried-blood spot taken from a heel-prick on a filter paper after 24 to 72 h of life. Implementing national NBS programs is logistically complex and expensive, requiring parental consent, specialized laboratories, and excellent infrastructure. In limited-resource settings, introducing such a complex program is often impossible. We propose universal decentralized cord blood TSH screening, offered as routine delivery care for all newborns in limited-resource settings. TSH measurement may be performed by local laboratories using widely available, inexpensive radioimmunoassay kits, with the report available within a few hours. Since the TSH report would be available before discharge, suitable clinical decision making would be possible, with a minimal need for recall, thus minimizing the parental, medical, and financial burden and improving developmental outcomes. The most important requirement is to change to a grassroots approach, with the education of obstetricians and pediatricians worldwide to perform routine cord blood TSH and make sure the TSH result is available before the baby is discharged.

Severe combined immunodeficiency (SCID) and spinal muscular atrophy (SMA) are being added to the Newborn Bloodspot Screening (NBS) programme in the Republic of Ireland. To support this expansion, we conducted a scoping review to identify reported timeframes for implementing national, regional or state-wide expanded NBS programmes. We performed a scoping review of the literature published between 2015 and 2025. Eligible articles described the timeframes for implementation of expanded NBS programmes for SCID, SMA or additional metabolic conditions. Sources included PubMed, Embase, citation searching, the International Journal of Neonatal Screening and grey literature. A narrative synthesis was undertaken. Fourteen articles met the inclusion criteria, describing the addition of new conditions-SCID (N = 7), SMA (N = 4), or multiple conditions (N = 3) to expanded NBS programmes in the United States (US), Europe (Belgium, Catalonia, the Czech Republic, Estonia, Germany, Norway, Poland, Portugal, Slovakia, Slovenia, Sweden, and Tuscany), Hong Kong and New Zealand. In most jurisdictions, the implementation of NBS programmes for new conditions took two to six years. The implementation of NBS for new conditions requires considerable time and coordinated efforts. Further research providing greater detail on the specific implementation steps, along with associated timelines, would provide valuable guidance for jurisdictions aiming to expand NBS programmes globally.

Newborn screening (NBS) is evolving as novel technologies offer the opportunities to include a broader range of treatable disorders in its programs. Multiplexable, high-throughput DNA-based technologies such as next-generation sequencing (NGS) are being explored to improve and expand disease detection, although several issues have been raised with its use. This scoping review aimed to identify multiplexable, high-throughput, DNA-based technologies that were used for screening or confirmatory testing of newborn disorders in published studies. Available evidence on the appropriateness of technologies in the NBS context was extracted. A literature search (Medline, Embase, and Web of Science) was performed from inception up to April 2024 in collaboration with a medical information specialist. After selection, 26 journal articles were included that used these technologies for either screening (n = 12) or confirmatory testing (n = 14). Five technologies were identified: whole-genome sequencing, whole-exome sequencing, targeted gene sequencing (TGS), quantitative polymerase chain reaction, and MassARRAY. The majority used TGS (n = 19, 73.08%). The data extracted concern mainly technical aspects, and these suggest that a combined approach, i.e., testing via NGS plus a biochemical test, in parallel or reflex, emerges as the optimal option. Ethical and economic evidence is limited and rarely reported in the reviewed articles.

A systematic literature review was conducted to evaluate the emerging evidence on newborn screening (NBS) for metachromatic leukodystrophy (MLD; MIM #250100). The review focuses on (1) screening assay performance, (2) diagnostic confirmation methods and care pathways, (3) feasibility of population-based identification, and (4) the impact of early diagnosis and treatment on health outcomes. Electronic databases were searched in February 2025, and supplementary searches were performed up to 17 June 2025, for articles referencing NBS for MLD and treatments for MLD; 52 publications were eligible for inclusion. Nationwide NBS for MLD is currently carried out in Norway and large prospective pilots are running in Germany, Austria, Italy and the US. MLD meets established Wilson and Jungner criteria, with a reliable screening algorithm, established confirmatory diagnostics, and actionable care pathways. There is ongoing work to develop tools to predict disease severity and subtype. Early intervention-via gene therapy for early-onset MLD and hematopoietic stem cell transplantation (HSCT) for late-onset forms-significantly improves outcomes when initiated before symptom onset. This review provides the first comprehensive synthesis of the evidence supporting MLD for inclusion in NBS programs, underscoring the public health value of early identification and intervention.