Search Results (32)

In Brazil, dried blood spots (DBSs) for newborn screening (NBS) should be collected between the 3rd and 5th days of life at local Basic Health Units (BHUs). This study reports the experience of face-to-face training at BHUs in southern Brazil during a pilot study for tandem mass spectrometry (MS/MS) inclusion in the NBS program. The pilot project involved screening for 22 inborn errors of metabolism (IEMs). The professionals at the BHUs were instructed to carry out the following: (a) explain the study to parents or guardians; (b) collect additional DBS samples on a different collection card (research card); and (c) deliver results to families. In-person visits were conducted at all 137 BHUs. These visits included an overview of the pilot project and distribution of educational materials, including a list of the 22 IEMs and informational leaflets on MS/MS-based NBS. Among the 486 healthcare professionals who participated, 91.2% were women. Overall, 97.1% of the BHUs reported being satisfied with the project. Questions regarding IEMs were raised in 40.1% of BHUs, and 13.1% reported complaints about the research card due to its lighter texture and drying difficulty. Training primary healthcare professionals in IEMs remains an urgent priority in Brazil, particularly in the context of expanded NBS using MS/MS, since they are the frontline professionals in the NBS program. Full article

Background: The advent of tandem mass spectrometry (MS/MS) had an essential role in the expansion of newborn screening (NBS) for different inborn errors of metabolism (IEMs). Nowadays, almost 50 IEMs are screened in Italy. The use of second-tier tests (2-TTs) in NBS minimizes the false positive rate; nevertheless, the metabolic profile is influenced not only by the genome but also by environmental factors and clinical variables. We reviewed the MS/MS NBS data from over 37,000 newborns (of which 8% required 2-TTs) screened in the Italian Abruzzo region to evaluate the impact of neonatal and maternal variables on propionate-related primary biomarker levels. Methods: Expanded NBS and 2-TT analyses were performed using MS/MS and liquid chromatography–MS/MS methods. We set up layered cut-offs dividing all 37,000 newborns into categories. Statistical analysis was used to create alarm thresholds for NBS-positive samples. Statistically significant differences were found in both neonatal and maternal conditions based on the 2-TTs carried out. According to the stratified cut-offs, only 1.47% of the newborns would have required a 2-TT while still retaining the ability to recognize the true-positive case of methylmalonic acidemia with homocystinuria, which has been identified by NBS. To further support the clinical applicability, we performed an external evaluation considering nine positive cases from an extra-regional neonatal population, confirming the potential of our model. Interestingly, the setting of alarm thresholds and their application would allow for establishing the degree of priority/urgency for 2-TTs. Conclusions: Tailoring NBS by customized cut-offs may enhance the application of precision medicine, focusing on true-positive cases and also reducing analysis costs and times. Full article

Newborn Bloodspot Screening (NBS) can detect severe treatable health conditions with onset during infancy. The parents of a newborn baby are vulnerable in the days after birth, and the optimal way to deliver the shocking and distressing news of a potential serious diagnosis is yet to be defined. More data are needed to determine whether access to a genetic counsellor (GC) improves families’ experiences with genetic conditions identified by NBS. This study aimed to explore the similarities and differences for parents who received a positive NBS result for Spinal Muscular Atrophy (SMA) and received access to a GC (GC cohort), to a cohort of parents who received a diagnosis for inborn errors of metabolism (IEM) and did not have access to a GC (non-GC cohort). Semi-structured interviews explored the retrospective experiences of receiving the NBS result, including diagnosis implications and subsequent adaptation to respective genetic diagnoses. Inductive thematic analysis was used from group comparison. 7 SMA families and 5 IEM families were included in the study. Four themes were identified: 1. minimal pre-test counselling; 2. perceived lack of local healthcare team knowledge; 3. enabling factors for adaptation; 4. implications for both individuals and their families. Both the GC and non-GC cohorts reported insufficient counselling in the pre-test period and described feeling traumatised at the time of the diagnosis delivery. Families without subsequent GC input described limited understanding of the disease due to the use of medicalized terms, as well as a decreased understanding of reproductive options, familial communication and subsequent cascade screening. GCs can support information needs and adaptation following a NBS diagnosis. Full article

Background: Newborn screening (NBS) is a preventive healthcare program aiming at identifying the inborn errors of metabolism (IEMs) in asymptomatic infants to reduce the risk of severe complications. The aim of this study was to report the first years (2016–2020) of the expanded NBS program in the Lombardy region, Italy. Methods: Dried blood spots were collected from newborns’ heels at 48–72 h after birth. FIA-MS/MS was performed to evaluate specific biochemical markers. Genetic confirmation was achieved via Sanger or NGS on newborns and reported to a clinical reference center (CRC). Results: A total of 343,507 newborns were tested; 1414/343,507 resulted as positive to NBS and were reported to the CRC. A total of 209 newborns were diagnosed with IEMs: 206 infants received a diagnosis of IEM through NBS, confirmed by genetic analysis; three neonates were not positive to NBS but were subsequentially diagnosed with IEMs. A total of 1208/343,507 were false positive cases. Twenty-seven types of IEMs were diagnosed in 209 patients: 111 newborns were affected by aminoacidemias, 11 by urea cycle disorders, 27 by organic acidemias, 34 by fatty acid oxidation disorders, and 26 by secondary conditions. Conclusions: We report here for the first time the IEM incidence and distribution in the Lombardy region in the first five years of NBS. Full article

Expanded newborn screening (NBS) programs are essential for early detection and treatment. This study highlights the implementation of an expanded NBS program for inborn errors of metabolism (IEMs) and congenital hypothyroidism (CH) in rural Thailand, focusing on Health Regions 7 and 8 as a model for resource-limited settings. Using the KKU-IEM web-based platform, the program streamlined workflows, integrating logistics, real-time sample tracking, and electronic data management. Regular training sessions, continuous feedback, and systematic monitoring improved outcomes. Starting from October 2022, the program covered 98.6% of 123,692 live births, identifying 101 CH cases (1 in 1208 live births) and 20 IEM cases (1 in 6100 live births). The CH incidence was slightly higher than Thailand’s national average, while the IEM incidence was double that found in a previous Bangkok pilot study. Six cases highlighted maternal conditions affecting outcomes. Process improvements reduced the average reporting time from 9.13 days in 2023 to 8.4 days in 2024, with a 19% reduction in Bueng Kan Province. Efficiencies were driven by electronic ordering, real-time tracking, and stakeholder collaboration. This program demonstrates a scalable model for rural settings, emphasizing technology integration, collaboration, and quality control. Future efforts should refine diagnostics, expand disease coverage, and enhance long-term outcomes. Full article

The Portuguese Newborn Screening Program currently includes 28 pathologies: congenital hypothyroidism, cystic fibrosis, 24 inborn errors of metabolism, sickle cell disease and spinal muscular atrophy. This pilot study for sickle cell disease newborn screening, including 188,217 samples, was performed between May 2021 and December 2023, with phase I, including 24,130 newborns, in the Lisbon and Setubal districts and phase II, including 164,087 newborns, in the whole country. DBS samples were analyzed through capillary electrophoresis. In phase I, a high birth incidence of sickle cell disease was found (1:928 NBs), resulting from the identification of 24 HbSS and 2 HbSC patients. This birth incidence decreased but remained significant when the pilot study for sickle cell disease newborn screening was expanded to a national level, with the identification of 67 sickle cell disease patients (59 HbSS and 8 HbSC), revealing a birth incidence of 1:2449 NBs. These data suggest that this condition is becoming increasingly relevant in Portugal, thus reflecting a general European trend, where sickle cell disease is already recognized as a public health problem. Therefore, it highlights the importance of its integration into the Portuguese National Newborn Screening Program panel in January 2024, thus allowing the early identification and clinical follow-up of these patients. Full article

Background: Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to impaired amino acid metabolism. Early diagnosis through newborn screening (NBS) enables prompt treatment, preventing neurological complications. This study aims to describe the genetic and phenotypic spectrum of PKU and mild hyperphenylalaninemia (m-HPA) in patients diagnosed at the Department of Inborn Errors of Metabolism and Newborn Screening, Hospital G. Rodolico-S. Marco, Catania, over four decades (1987–2023). Materials and Methods: The retrospective analysis included 102 patients with elevated blood phenylalanine (Phe) levels born in Sicily and followed at the Institute. The phenotype evaluation comprised the Phe levels at birth/diagnosis, dietary tolerance, and sapropterin dihydrochloride responsiveness. The dietary compliance and Phe/Tyr ratios were assessed and compared across phenotypic classes and age groups. Results: Of 102 patients, 34 were classified as having classic PKU, 9 as having moderate PKU, 26 as having mild PKU, and 33 as having m-HPA, with a median age of 21.72 years. Common PAH variants included c.1066-11G>A (26/204 alleles), c.782G>A (18/204 alleles), and c.165delT (13/204 alleles). The phenotypes sometimes diverged from the genotype predictions, emphasizing dietary tolerance over the initial Phe levels for classification: m-HPA was statistically associated with a higher dietary tolerance (p < 0.001) compared to the classic, moderate, or mild forms of PKU. Conclusions: This study highlights the importance of large databases (e.g., BioPKU) for phenotype prediction and treatment optimization. Regular assessment of Phe/Tyr ratios is crucial for monitoring adherence and health. Phenotype determination, dietary management, and emerging therapies (Pegvaliase and gene therapy) are key to improving outcomes for PKU patients. Full article

Inborn errors of metabolism (IEM) and endocrine disorders are common genetic conditions in the Saudi population with the incidence rate often underestimated. Newborn screening (NBS) using various disease panels provides the first line in the early detection and intervention among infants with a high risk of IEM. Here we aim to assess the incidence of screening disorders and provide an overview of the NBS program at the Ministry of Health Tertiary Care King Fahad Medical City. Dried blood spots (DBS) from 40,965 newborn infants collected on the second day after birth were analyzed for 20 disorders. The total number of positive screen (“repeat”) samples over 10 years was about 1% (n = 382/40,965). The true positive result rate was 15.3% (n = 46/301) with the recall rates of individual disorders ranging from 0.26% (95% CI, 0.17–0.69) to 2.6% (95% CI, 2.19–3.05). The false positive result rate was 84.7% (n = 255/301) with biotinidase activity found to be the most common cause of the second sample repeat. The overall incidence of the screened diseases was 1:891 (95% CI, 11.61–12.47). CH and CAH are the most prevalent among endocrine disorders with an incidence of 1:4097 (95% CI, 2.19–3.05), and PA and ASA among the IEM with an incidence of 1:10,241 (95% CI, 0.09–0.95). In summary, we provide updated data and our experience on the incidence of various IEM and endocrine disorders among the Saudi population, highlight the role of false positive results of biotinidase activity that can increase the recall rate and lead to overestimation of the incidence data, and recommend multicenter studies to achieve a successful national NBS program. Full article

In addition to the numerous immunological and nutritional benefits that breast milk offers to infants, its proportion in the diet must be limited or even excluded in the case of inborn errors of amino acid metabolism (IEM). The objective of the study was to expand knowledge about breastfeeding and the degree of contribution of breast milk to the feeding of infants with IEM before and after the introduction of expanded newborn screening. A retrospective single-centre study was conducted on 127 infants born between 1997 and 2020: 66 with phenylketonuria (PKU), 45 with other IEM (non-PKU), all diagnosed through newborn screening (NBS), and 16 non-PKU diagnosed through selective screening (SS). The time of initiation of dietary treatment and the proportion of breast milk in the diet, both expressed and breastfed, with or without intake control, were analysed at 1, 3, and 6 months after birth. For 47% of the newborns in Groups 1 and 2, the dietary treatment was started before the 10th day of life; in Group 3, the dietary treatment was started after the 10th day of life for all children. During the first month of life, the proportion of infants receiving breast milk was higher in the NBS-PKU (74%) and the NBS non-PKU (80%) groups, compared with 38% in the SS non-PKU infants. In the subsequent months of life, the proportion of infants receiving human milk (either from the breast or a bottle) declined in all groups. This decline occurred more in bottle-fed rather than directly breast-fed infants. Our observations indicate that the model of feeding from a bottle with expressed milk may have had an adverse effect on maintaining lactation and may have contributed to a faster transition to formula milk. Maintaining lactation and extending the period of feeding the infant with human milk in the first 6 months of life is possible by breastfeeding on demand, under regular biochemical monitoring: preferably weekly in PKU infants, and at least every 2–4 weeks in infants with other IEM. Full article

Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable. Full article

The aim of this study was to observe the outcomes of newborn screening (NBS) in a certain population by using next-generation sequencing (NGS) as a first-tier screening test combined with tandem mass spectrometry (MS/MS). We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. The three most common IEMs were methylmalonic academia (MMA), primary carnitine deficiency (PCD) and phenylketonuria (PKU). The five genes with the most common carrier frequencies were PAH (1:42), PRODH (1:51), MMACHC (1:52), SLC25A13 (1:55) and SLC22A5 (1:63). Our study showed that NBS combined with NGS and MS/MS improves the performance of screening methods, optimizes the process, and provides accurate diagnoses. Full article

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

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

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

Rapid advances in the screening, diagnosis, and treatment of genetic disorders have increased the number of conditions that can be detected through universal newborn screening (NBS). However, the addition of conditions to the Recommended Uniform Screening Panel (RUSP) and the implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here, we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders worldwide. The NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs, including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases, have utilized NBSTRN’s tools and, in turn, contributed research data to further expand and refine these resources. Additionally, we discuss ongoing tool development to facilitate the expansion of genetic disease screening in increasingly diverse populations. In conclusion, NBSTRN’s tools and resources provide a trusted platform to enable NBS stakeholders to advance NBS research and improve clinical care for patients and their families. Full article