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Background: Since 2019, Jiangsu province has implemented newborn screening for congenital heart disease (CHD). As of 2023, 591 hospitals (584 public or private midwifery institutions, 7 specialized hospitals for children) in Jiangsu province conduct CHD screening, including 132 with diagnostic capabilities and 21 with treatment facilities, ensuring comprehensive coverage of 13 prefecture-level cities, 95 counties (19 counties, 21 county-level cities, 55 districts) in Jiangsu Province. This study aims to examine the implementation of the newborn CHD screening program within Jiangsu Province's healthcare systems using real-world clinical data and to assess its effectiveness in patient care systematically. Additionally, we seek to offer data-driven recommendations for advancing the development of patient risk screening tools. Methods: Our study analyzed dataset from live births at midwifery institutions across Jiangsu province from 2019 to 2023. All newborns aged 6–72 h were screened by trained medical staff using the dual-index method. Newborns diagnosed without CHD or screened negative were tracked through the Child Health Management program, a basic public health service for children under 7 years of age in China. Newborns testing positive were referred to a diagnostic institution for echocardiographic assessment, and those with confirmed CHDs were directed to a treatment facility for further evaluation and treatment. Results: During the study period, 2,512,635 out of 2,648,298 infants (94.88%) were screened within 72 h of birth. Of these, 71,041 (2.83%) tested positive for screening, and 23,150 (32.59%) of those positive were diagnosed with CHD. From 2018 to 2023, there was approximately a twofold decrease in the infant mortality rate (IMR) due to CHD, from 0.37‰ to 0.14‰ (APC= -17.33, P < 0.001), and a reduction in the under-five mortality rate (U5MR) due to CHD, from 0.45‰ to 0.17‰ (APC= -16.79, P < 0.001). Conclusions and relevance: The current study provides encouraging evidence that the screening program has effectively advanced the diagnosis of CHD in children and reduced infant mortality, thereby supporting health rights and benefiting children with CHD throughout the province. Furthermore, our analysis demonstrates that the newborn CHD screening program has been effectively implemented across Jiangsu province's healthcare systems. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the knowledge, attitudes, and practices of migrant Syrian mothers regarding the neonatal screening programs (NSP) using in-depth interviews. Methods: Women were selected from the Migrant Health Center (MHC), which is the primary health care institution in Istanbul. A translator who spoke Arabic, the native language of participants, used an open-ended, semi-structed interview form to guide face-to-face interviews with participants. Questions were about sociodemographic information, opinions about NSP's heel prick testing, diseases the test screens for, reasons for agreeing to the heel prick test, and challenges faced accessing health care services. The interviews were audio recorded. The translator then transcribed the audio recordings in Arabic and translated them into Turkish. The framework method for analysis of qualitative data was used to analyze transcripts of the interviews. Results: Forty-one migrant women were interviewed. Four themes were identified from analysis of transcripts of the interviews, regarding (1) knowledge of the NSP, (2) attitudes about the NSP, (3) practices that create barriers to accessing health care services, (4) practices to overcome barriers to accessing health care services. Most participants had no knowledge of the diseases the NSP tests for. A few participants had heard of congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and spinal muscular atrophy (SMA), but they were not aware of the symptoms and effects of these diseases. Some participants thought the heel prick test benefited their child's health as it enables early diagnosis and treatment of diseases. All participants agree to heal prick testing after the birth of their most recent child. Participants noted the information and recommendations health care professionals provided influenced their decision to agree to the heel prick test. Most participants experienced language barriers when accessing health care services. Conclusions: Migrant women expressed a positive attitude toward the NSP. Future health care interventions regarding migrants should aim to reduce the negative experiences they encounter accessing health care, such as language barriers. [ABSTRACT FROM AUTHOR]

Newborn screening (NBS) programs are believed to play an important role in the decrease of infant mortality rates in many countries. This is achieved through offering early detection and treatment of many genetic as well as metabolic disorders prior to the onset of symptoms. Our paper examines NBS across seven diverse nations: Saudi Arabia, the United States, Japan, Singapore, Canada, Australia, and the United Kingdom. This paper discusses the diseases screened for by each country, latest additions, as well as future recommendations, when applicable. Employing a comparative approach, we conducted a comprehensive review of the most recent published literature on NBS programs in each country and subsequently examined their latest implemented NBS guidelines as outlined on their respective official government health sector websites. We then reviewed the economic feasibility of each of these programs and factors that affect implementation and overall benefit. While all six countries employ well-developed programs, variations are observed. Those variations are mainly attributed to disparities in access, resource scarcity, financial availability, as well as ethical and cultural considerations. From a local perspective, we recommend conducting further population-based studies to assess the epidemiological data in relation to the disease burden on the country's economy. Moreover, we recommend updating national and international guidelines to contain a more comprehensive approach on policies, operation, and sustainability to deliver a service through the lens of value-based healthcare. [ABSTRACT FROM AUTHOR]

Abstract Newborn screening (NBS) programs are believed to play an important role in the decrease of infant mortality rates in many countries. This is achieved through offering early detection and treatment of many genetic as well as metabolic disorders prior to the onset of symptoms. Our paper examines NBS across seven diverse nations: Saudi Arabia, the United States, Japan, Singapore, Canada, Australia, and the United Kingdom. This paper discusses the diseases screened for by each country, latest additions, as well as future recommendations, when applicable. Employing a comparative approach, we conducted a comprehensive review of the most recent published literature on NBS programs in each country and subsequently examined their latest implemented NBS guidelines as outlined on their respective official government health sector websites. We then reviewed the economic feasibility of each of these programs and factors that affect implementation and overall benefit. While all six countries employ well-developed programs, variations are observed. Those variations are mainly attributed to disparities in access, resource scarcity, financial availability, as well as ethical and cultural considerations. From a local perspective, we recommend conducting further population-based studies to assess the epidemiological data in relation to the disease burden on the country’s economy. Moreover, we recommend updating national and international guidelines to contain a more comprehensive approach on policies, operation, and sustainability to deliver a service through the lens of value-based healthcare.

Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder which results from the inability of biotin-dependent carboxylase enzymes to function due to the release and absorption of biotin, leading to neurological and cutaneous findings. In the present study, evaluation of demographic characteristics, clinical findings, laboratory results, molecular genetic characteristics, and genotype–phenotype correlations of cases with BD. Two hundred forty-seven cases were included in the study who were admitted to the Department of Pediatric Metabolism of Ankara Bilkent City Hospital after being identified with potential BD through the Newborn Screening Program (NBS), during family screening or based on suspicious clinical findings, or following the detection of a pathogenic variant in a BTD genetic analysis during the period of October 2020 and February 2022. The medical files of the cases were reviewed retrospectively. An analysis of the admission routes of all cases to our clinic revealed 89.5% NBS, 5.7% family screening, and 4.9% suspicious clinical findings suggestive of BD. Complete enzyme deficiency was identified in 19.8%, partial enzyme deficiency in 55.1%, and heterogenous enzyme deficiency in 9.7%. The most common pathogenic variants were c.1270G > C (p.Asp424His), c.410G > A (p.Arg137His), and c.38_44delGCGCTGinsTCC (p.Cys13Phefs*36) in BTD gene. The c.1270G > C variant was most common in patients with cutaneous symptoms. The c.410G > A and c.38_44delGCGCTGinsTCC variants were more common in the patients with neurological symptoms. The mean activity level in patients with the c.1270G > C homozygous variant was statistically significantly higher than the mean activity level in the c.1270G > C compound heterozygous patients and the activity level of patients without the c.1270G > C variant. The mean activity level in c.410G > A homozygous patients was statistically significantly lower than the mean activity level of the c.410G > A compound heterozygous patients and the activity level of patients without the c.410G > A variant. In the course of our study, four new pathogenic variants were detected, namely: c.190G > A (p.Glu64Lys), c.249 + 5G > T, c.228delA (p.Val77*), and c.682A > G (p.Ile228Val). Conclusions: The present study has determined the clinical and genetic spectrum of a large group of patients with BD in a single center. The frequent mutations in our study were similar to those reported in literature, and four novel variants were also described. What is Known: • Biotinidase deficiency is an autosomal recessive, treatable inborn error of metabolism. Two hundred ninety-four pathogenic variants in the BTD gene have been identified and the c.1270G > C variant is the most frequent BTD gene mutation in both Turkey and around the world. What is New: • Four new pathogenic variants (c.190G > A, p.Glu64Lys; c.249 + 5G > T; c.228delA, p.Val77*; and c.682A > G, p.Ile228Val) have been identified. It is believed that the c.38_44delGCGGCTGinsTCC variant is more commonly seen in individuals with ocular issues; however, further genotype–phenotype correlations are needed. [ABSTRACT FROM AUTHOR]

Background: Newborn screening is a public health prevention system that intends to detect, early in life, a group of serious diseases that require early intervention. Institutionalizing and sustaining this system presents a remarkable challenge in developing public health systems. Duhok project for expanded newborn screening started in June 2018 with a panel of seven diseases including phenylketonuria (PKU), Galactosemia (GAL), congenital hypothyroidism (CHT), Cystic fibrosifcardiacs (CF), Congenital adrenal hyperplasia (CAH), G6PD deficiency and biotinidase deficiency. In the next few years, the panel expanded to include, finally, 72 tests, to detect various disorders of amino acids, fatty acid oxidation, organic acid, lysosomal storage disease, immunodeficiency, spinal muscular dystrophy, and others. Objectives: To evaluate the Duhok project of expanded newborn screening. Methods: In a retrospective cross-sectional study conducted between June 2018 and 31 November 2021, a total of 3872 newborns were screened from 8 governorates of Iraq and the Kurdistan region. Heel prick dry blood spot samples were obtained from all newborns for biochemical and immunoassay testing. Results: A total of 527 cases were detected, frequently detected disorders were Glucose 6 phosphate dehydrogenase deficiency, cystic fibrosis, congenital adrenal hyperplasia and phenyl ketone urea. Most of the positive cases (66%) were older than 7 days at screening. Conclusion: The article highlights the overview of the expanded newborn screening project in Duhok/Iraq. NBS has not yet become prevalent in Iraq, thus the screening for metabolic disorders is not normally requested until a patient is already experiencing symptoms. [ABSTRACT FROM AUTHOR]

Integrating health interventions in a growing economy like India, with a birth cohort of 27 million/year, one-fifth of all childbirths, and approximately one-third of neonatal deaths globally, is a challenge. While mortality statistics are vital, intact survival and early preventive healthcare, such as newborn screening (NBS), are paramount. The appalling lack of information about the precise burden of metabolic errors at the state/national level or a mandated program encouraged a feasibility study of NBS in a prospective newborn cohort recruited in Delhi State (November 2014–April 2017) using a public–private partnership mode. The major determinants for effective implementation of universal NBS at the national level and limitations encountered are discussed in this report. Data to generate the ‘core’ panel for screening, sustained training of healthcare personnel, dissemination of the power of NBS to ensure neonatal/societal health to the public, and a ‘national policy’ emerge as priorities in a developing country.

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.

Spinal muscular atrophy (SMA) is a rare genetic disease that results in progressive neuromuscular weakness. Without therapy, the most common form of the disease, type 1, typically results in death or chronic respiratory failure in the first 2 years of life. Thanks to the recent introduction of newborn screening programs and the discovery of three disease-modifying therapies in the last decade, the outcomes of children with SMA have dramatically improved. Patients are able to achieve many, if not all, of the typical neuromotor milestones, such as sitting, standing and walking, as well as safe oral intake. As the natural history of treated patients is continuously evolving, children with SMA continue to require complex and multidisciplinary care, posing implementation and sustainability challenges. Accordingly, there is a significant need for the application and evaluation of implementation science to address the steps involved in the diagnosis and treatment of patients with SMA, ensuring that all pertinent stakeholders and systems are working effectively to deliver timely and appropriate care. In thismanuscript, we discuss the current challenges and gaps in the care for children with SMA, as well as how implementation science can advance this field. In addition, we provide an adapted implementation science framework that includes the main domains and subdomains involved in the care of patients with SMA. [ABSTRACT FROM AUTHOR]

Background: Mucopolysaccharidosis II (MPS II) is an X-linked disorder resulting from a deficiency in lysosomal enzyme iduronate-2-sulfatase (IDS), which causes the accumulation of glycosaminoglycans (GAGs) in the lysosomes of many tissues and organs, leading to progressive cellular dysfunction. An MPS II newborn screening program has been available in Taiwan since 2015. The aim of the current study was to collect and analyze the long-term follow-up data of the screen-positive subjects in this program. Methods: From August 2015 to April 2022, 548,624 newborns were screened for MPS II by dried blood spots using tandem mass spectrometry, of which 202 suspected infants were referred to our hospital for confirmation. The diagnosis of MPS II was confirmed by IDS enzyme activity assay in leukocytes, quantitative determination of urinary GAGs by mass spectrometry, and identification of the IDS gene variant. Results: Among the 202 referred infants, 10 (5%) with seven IDS gene variants were diagnosed with confirmed MPS II (Group 1), 151 (75%) with nine IDS gene variants were classified as having suspected MPS II or pseudodeficiency (Group 2), and 41 (20%) with five IDS gene variants were classified as not having MPS II (Group 3). Long-term follow-up every 6 months was arranged for the infants in Group 1 and Group 2. Intravenous enzyme replacement therapy (ERT) was started in four patients at 1, 0.5, 0.4, and 0.5 years of age, respectively. Three patients also received hematopoietic stem cell transplantation (HSCT) at 1.5, 0.9, and 0.6 years of age, respectively. After ERT and/or HSCT, IDS enzyme activity and the quantity of urinary GAGs significantly improved in all of these patients compared with the baseline data. Conclusions: Because of the progressive nature of MPS II, early diagnosis via a newborn screening program and timely initiation of ERT and/or HSCT before the occurrence of irreversible organ damage may lead to better clinical outcomes. The findings of the current study could serve as baseline data for the analysis of the long-term effects of ERT and HSCT in these patients. [ABSTRACT FROM AUTHOR]

Purpose: Mucopolysaccharidosis IVA (MPS IVA) is a rare lysosomal storage disorder arising from a deficiency in N-acetylgalactosamine-6-sulfatase., Methods: From September 2019 to October 2023, a total of 264,843 Taiwanese newborns underwent screening for MPS IVA using dried blood spots and tandem mass spectrometry., Results: Among the 95 referred infants, 9 (9%) were confirmed to have MPS IVA (group 1), 18 (19%) were highly suspected to have MPS IVA (group 2), 61 (64%) were identified as heterozygotes of MPS IVA (group 3), and 7 (7%) were determined not to have MPS IVA (group 4). A total of 34 different GALNS (HGNC:4122) gene variants were identified through our MPS IVA newborn screening program. The most prevalent variant was c.857C>T p.(Thr286Met), found in 33 cases (29%), followed by c.953T>G p.(Met318Arg) in 22 cases (19%). Intravenous enzyme replacement therapy was initiated in 5 patients at ages ranging from 0.3 to 1.7 years. The estimated incidence of MPS IVA in this screening program was 3.4 per 100,000 live births., Conclusion: Because of the progressive nature of MPS IVA, an early diagnosis facilitated by newborn screening and prompt initiation of enzyme replacement therapy before irreversible organ damage occurs may result in improved clinical outcomes., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Introduction: In recent years, researchers have become increasingly interested in immunoglobulins. The antibodies, also known as immunoglobulins, are serum proteins that bind to specific antigens produced by B cells. The complicated nature of the proteins has been emphasized for over 100 years of research on the structure and function of immunoglobulin. A major B-cell protein, which is utilized by the immune system to identify and neutralize foreign objects such as bacteria and viruses, is the Antibody (Ab), also known as immunoglobulin (Ig). Methods: This research focuses on the molecular mechanisms that allow these numerous and diverse roles. Therefore, it is very important to improve the accuracy of immunoglobulin classification by applying effective methods for disease research. We use the immunoglobulin features which reduced feature dimension were selected to extract immunoglobulin features, based on the BLOSUM vector score matrix. We've developed an ensemble learning method called Extreme Gradient Boosting (XGBoost). Results: We proposed learning method called Extreme Gradient Boosting (XGBoost) to predict immunoglobulins with 0.9727% accuracy with quintuple cross-validation of data used. In addition, the best method for identifying mixed 2D key features was used to BLOSUM62 to distinguish immunoglobulins with an ROC AUC predicted score of 0.9700%. The methods used in this paper are very accurate in predicting immunoglobulin levels and finding the key features. Conclusions: The aim of this study was to calculate appropriate concentrations of immunoglobulin and to identify important traits. In this investigation, the BLOSUM62 matrix was employed, which is a frequently utilized device for calculating the alignment of two distinct protein sequences. The value of the BLOSUM62 Matrix is determined through a large-scale analysis of observed polypeptide alignments. The best feature set created by BLOSUM62 matrix was found to reliably predict 0.9727% accuracy score of immunoglobulins using the learning method called Extreme Gradient Boosting (XGBoost) classification model.

Background Glutaric aciduria type 1(GA-1) is an inherited cerebral organic aciduria. Untreated patients with GA-1 have a risk of acute encephalopathic crises during the first 6 years of life. In so far as GA-1 desperately does not exist in Turkish newborn screening (NBS) program, most patients in our study were late-diagnosed. Method This study included 41 patients diagnosed with acylcarnitine profile, urinary organic acids, mutation analyses in the symptomatic period. We presented with clinical, neuroradiological, and molecular data of our 41 patients. Results The mean age at diagnosis was 14.8 ± 13.9 (15 days to 72 months) and, high blood glutaconic acid, glutarylcarnitine and urinary glutaric acid (GA) levels in 41 patients were revealed. Seventeen different mutations in the glutaryl-CoA dehydrogenase gene were identified, five of which were novel. The patients, most of whom were late-diagnosed, had a poor neurological outcome. Treatment strategies made a little improvement in dystonia and the frequency of encephalopathic attacks. Conclusion All GA-1 patients in our study were severely affected since they were late-diagnosed, while others show that GA-1 is a treatable metabolic disorder if it is diagnosed with NBS. This study provides an essential perspective of the severe impact on GA-1 patients unless it is diagnosed with NBS. We immediately advocate GA-1 to be included in the Turkish NBS. [ABSTRACT FROM AUTHOR]

Biotinidase deficiency is one of the most common hereditary metabolic diseases in our country with autosomal recessive transition and has nervous system and skin findings predominantly. Newborns with suspicious results in the national newborn screening program are referred to pediatric metabolic diseases outpatient clinics. COVID-19, announced as a pandemic on March 11, 2020, has led to disruptions in the functioning of the health system and changes in the health behavior of patients. In this study, the effects of the pandemic on the applications of the outpatient clinic to biotinidase deficiency screening were examined. A total of 264 infants who came to Hacettepe University İhsan Doğramacı Children's Hospital Pediatric Metabolism Clinic within one year before and after March 11, 2020 were included in the study. There was no statistically significant difference before and after the pandemic in terms of the times of taking screening samples and applying to our clinic but applicants from the Central Anatolia Region accounted for 49.7% of the total applications before the pandemic, and 63.6% after the pandemic (p=0.03). The rate of applicants from the Eastern Anatolia Region decreased from 17.8% to 3.7% after the pandemic (p<0.01). It was determined that the pandemic did not affect the operation of the neonatal biotinidase screening program, but was associated with changes in the health behaviors of families. [ABSTRACT FROM AUTHOR]

Abstract Biotinidase deficiency is an autosomal recessive disorder that affects the endogenous recycling and release of biotin from dietary protein. This disease was thought to be rare in East Asia. In this report, we delineate the phenotype of biotinidase deficiency in our cohort. The genotypes and phenotypes of patients diagnosed with biotinidase deficiency from a medical center were reviewed. The clinical manifestations, laboratory findings, and molecular test results were retrospectively analyzed. A total of 6 patients were evaluated. Three patients (50%) were diagnosed because of a clinical illness, and the other three (50%) were identified by newborn screening. In all patients, the molecular results confirmed the BTD mutation. The three patients with clinical manifestations had an onset of seizure at the age of 2 to 3 months. Two patients had respiratory problems (one with apnea under bilevel positive airway pressure (BiPAP) therapy at night, and the other with laryngomalacia). Hearing loss and eye problems were found in one patient. Interestingly, cutaneous manifestations including skin eczema, alopecia, and recurrent fungal infection were less commonly seen compared to cases in the literature. None of the patients identified by the newborn screening program developed symptoms. Our findings highlight differences in the genotype and phenotype compared with those in Western countries. Patients with biotinidase deficiency benefit from newborn screening programs for early detection and management.

Performing thyroid function tests (TFT) at 2 weeks of age in neonates of mothers with hypothyroidism, despite having a newborn screening program, is a debated approach. We examined whether there is an additional clinical benefit in TFT at 2 weeks of age in neonates born to mothers with hypothyroidism, in addition to the neonatal screening program. We performed a retrospective study which included all newborns of mothers with a diagnosis of hypothyroidism and gave birth in a single regional hospital between the years 2010 and 2016. Data were collected from a computerized medical record system of the hospital and the community clinics, and from Israel's national newborn screening program. Main outcome measure was results of serum TFT in comparison to the results of the neonatal screening test. There were 1392 newborns eligible according to the study criteria. Of these, 1033 underwent a newborn screening test, and serum TFT at least 2 weeks after birth. Eight babies with congenital hypothyroidism were detected independently by both the newborn screening program and at the TFT performed at 2 weeks of age. Conclusions: No added clinical benefit was found in retesting newborns of hypothyroid mothers for thyroid function in addition to the newborn screening program. What is Known • Performing thyroid function test 2 weeks after birth is a common practice in newborn to a mother with hypothyroidism. • Neonatal screening program for thyroid function is also done in these newborns. What is New • No newborn was found to have a normal newborn screening test but abnormal serum thyroid function test. • No added clinical benefit was found in retesting newborns of hypothyroid mothers for thyroid function in addition to the newborn screening program. [ABSTRACT FROM AUTHOR]

A fast and reliable method for the determination of hemoglobinopathies and thalassemias by high-resolution accurate mass spectrometry (HRAM/MS) is presented. The established method was verified in a prospective clinical study (HRAM/MS vs. high-pressure liquid chromatography [HPLC]) of 5335 de-identified newborn samples from the Hamburg area. The analytical method is based on a dual strategy using intact protein ratios for thalassemias and tryptic digest fragments for the diagnosis of hemoglobinopathies. Due to the minimal sample preparation and the use of flow injection, the assay can be considered as a high-throughput screening approach for newborn screening programs (2 min/sample). Using a simple dried blood spot (DBS) extraction (tryptic digest buffer), the following results were obtained: (1) a carrier incidence of 1:100 newborns (35 FAS, nine FAC, eight FAD and two FAE), and (2) no homozygous affected patient was detected. Using the HRAM/MS protocol, an unknown Hb mutation was identified and confirmed by genetic testing. In addition to greater specificity toward rare mutations and β-thalassemia, the low price/sample (1–2€) as well as an automated data processing represent the major benefits of the described HRAM/MS method. [ABSTRACT FROM AUTHOR]

Screening newborns is recognized as an important health policy. It is cost-effective and is implemented as a national health program in most developed countries. Though births in developing countries contribute to more than half of the total births globally, newborn screening (NBS) is not yet implemented in most developing countries. If not diagnosed and treated timely, some of these infants will contribute to neonatal mortality. In contrast, others will have long-term sequelae like developmental delay, learning disabilities, behavioral abnormalities, and backward academic performance in the future. In addition, the diagnosis, management, and treatment of these conditions also carry a significant financial as well as emotional burden on the family. An NBS program can be the most rational and effective way to prevent such morbidities and mortalities. NBS in developing countries competes with other health issues such as the control of infectious diseases, vaccinations, and poor nutrition. Also, lack of government support, poor economy, inadequate public health education, lack of awareness among health care workers, early discharge from hospital, and many births out of hospital are the significant obstacles in the countries that lack total coverage. It is high time now to change our attitude; our focus should be not only on the reduction of mortality and infectious morbidity but also on reducing disabilities with the introduction of screening for newborns. Integrating NBS with the national healthcare system is crucial for successful implementation in developing countries. Integration should also include a payment scheme to reduce the economic burden on families. In recent years, many developing countries have started implementing pilot projects as a step toward the national program of screening newborns., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Gaikwad et al.)

Background; Critical congenital heart disease is life-threatening and delayed diagnoses increase morbidity and mortality. Pulse oximetry is a useful screening tool for these diseases. Screening outcomes in Mississippi, an underserved state, were evaluated. Methods: A single-center, retrospective study of all infants treated for critical congenital heart disease before and after screen implementation is described. Measures of interest included age, mortality total interventions, length of stay, and complications. Outcome measures of the pre- and post-screen eras were compared. Results: 75,760 infants were born in the pre-screen era, of whom 121 were treated for critical congenital heart defects; 75,154 were born postscreen, of whom 103 were treated for critical congenital heart defects. 23 deaths occurred pre-screen and 9 post-screen a significant decrease by era (0.3 per 1000 live births vs. 0.12 per 1000 live births, p 0.03). Length of stay and total interventions were also significantly lower post-screen. Discussion. Screening was associated with the improved outcomes above, though the study design limits generalizability. There were trends toward fewer delayed diagnoses and complications. Further work can improve screening reliability and availability in resource-poor regions. [ABSTRACT FROM AUTHOR]

Newborn Screening (NS) program for congenital hypothyroidism (CH) has completely changed the natural history of this devastating disorder for the vast majority of children with CH. However, cases of missed CH do happen, and it is important to keep this possibility in mind during every day clinical practice. The objective of this study was to analyze the recognized cases of undiagnosed CH by the NS program in Central Serbia in order to evaluate the reasons for such omissions. Data regarding the recognized missed cases of CH between the years of 1983 and 2013 were collected and analyzed. During 30 years of the NS program for CH on the territory of Central Serbia, 1,547,122 newborns were screened, and during this period, 14 children with CH were missed by the NS. Five missed cases were children with athyreosis (35.8%), 8 had ectopic thyroid gland (57.1%) and one child had dyshormonogenesis (7.1%). The median age at diagnosis of CH in these missed cases was 1.12 years (range 0.08-13.5 years). In the group of children with missed diagnosis of CH, 71.4% were missed due to errors during sample collection, and 28.6% of patients were missed due to false negative screening results. Continuous education of neonatologists as well as nurses in neonatal units of maternity hospital are necessary to avoid errors in sample collection. It is of high importance to notice in a discharge list if a child is referred to the hospital before the sample is taken in a maternity hospital. On the other hand, the maternity hospital has to inform the screening laboratory about any child who was referred to another hospital if the blood samples for screening are not taken. Parents should be better informed that each child has to be included in the NS which is obligatory in Serbia. In addition, awareness amongst pediatricians in primary care should be raised regarding the possibility of missed cases of CH. [ABSTRACT FROM AUTHOR]

• Nine infants with the same genotype presented different CIT concentrations. The relationship between the CIT level and genotype is uncertain. • Four variations, c.851_854delGTAT, c.615 + 5G > A, c.1638_1660dup and IVS16ins3kb, constitute the high-frequency mutations in Quanzhou. • Patient No. 22 possessed compound heterozygous mutations in the SLC25A13 gene accompanied by compound heterozygous variations in the PTS gene. This is the first reported case of the simultaneous occurrence of tetrahydrobiopterin (BH4) deficiency and NICCD. • Patient No. 26 is the first reported case of the simultaneous occurrence of primary carnitine deficiency (PCD) and NICCD. • Combining genetic analysis with the routine NBS program is emphasized. Neonatal intrahepatic cholestasis due to citrin deficiency (NICCD) is an autosomal recessive disorder caused by SLC25A13 genetic mutations. We retrospectively analyzed 26 Chinese infants with NICCD (years 2014-2022) in Quanzhou City. The plasma citrulline (CIT) concentration analyzed by tandem mass spectrometry (MS/MS), biochemical parameters and molecular analysis results are presented. Twelve genotypes were discovered. The relationship between the CIT concentration and genotype is uncertain. In total, 8 mutations were detected, with 4 variations, c.851_854delGTAT, c.615 + 5G > A, c.1638_1660dup and IVS16ins3kb, constituting the high-frequency mutations. Specifically, we demonstrated 2 patients with NICCD combined with another inborn errors of metabolism (IEM). Patient No. 22 possessed compound heterozygous mutations of c.615 + 5G > A and c.790G > A in the SLC25A13 gene accompanied by compound heterozygous variations of c.C259T and c.A155G in the PTS gene. Additionally, Patient No. 26 carried c.51C > G and c.760C > T in the SLC22A5 gene as well as c.615 + 5G > A and IVS16ins3kb in the SLC25A13 gene. We report a case of the simultaneous occurrence of primary carnitine deficiency (PCD) and NICCD. [ABSTRACT FROM AUTHOR]

Background: Antibiotic prophylaxis is a mainstay in sickle cell disease management. However, adherence is estimated at only 66%. This study aimed to develop and validate a Sickle Cell Antibiotic Adherence Level Evaluation (SCAALE) to promote systematic and detailed adherence evaluation. Methods: A 28-item questionnaire was created, covering seven adherence areas. General Adherence Ratings from the parent and one health care provider and medication possession ratios were obtained as validation measures. Results: Internal consistency was very good to excellent for the total SCAALE (α=0.89) and four of the seven subscales. Correlations between SCAALE scores and validation measures were strong for the total SCAALE and five of the seven subscales. Conclusion: The SCAALE provides a detailed, quantitative, multidimensional, and global measurement of adherence and can promote clinical care and research. [ABSTRACT FROM AUTHOR]

The National Program of Newborn Screening for research of the Phenylketonuria, Congenital Hypothyroidism,Cystic Fibrosis, Sickle Cell Disease and other Hemoglobinopathies, it has as objective precociously todetect and to treat illnesses that, if prevented, prevent sequels as the mental deficiency and others. We intend,through this article, to awake the attention of the health professionals, mainly of the nurses, who act in the attendanceof the just-been newborn, of the gestante, the woman in labor and in puerperium, on the importance of theprecocious diagnosis of the diseases searched in the Program, with primordial purposes to assist the suckle for itsgood physical, neurological, psychological and intellectual development, besides offering to familiar the o geneticadvise. The examination gratuitous and is supported by law, and so that the prevention is effective, all the Maternitiesmust always carry through the collections of sample of blood of the heel of the high baby in the hospital one.

Aims: Neonatal screening programs perform different screening tests on the same blood-spot sample collected on a Guthrie card. We retrospectively investigated the incidence of multiple positive results as well as the outcomes and the physical characteristics of newborns with more than one positive result for phenylketonuria (PKU), congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH). Methods: Neonatal screening was performed on blood-spot for PKU (phenylalanine concentration by fluorescent ninhydrine method), for CH (simultaneous total thyroxin (tT4) and thyroid-stimulating hormone (TSH) levels by fluoroimmunometric assay); and for CAH (17-hydroxyprogesteron level by fluoroimmunometric assay). Results: During three years of screening, 39 newborns (37 preterms) showed multiple positive results at screening tests (incidence 1:6387). The most frequent positive results were the combinations of CH and CAH (25/39) and PKU and CH (12/39). At recall, only two newborns were confirmed positive and each for only one disease: one, premature baby, for PKU from the PKU and CH combination; the other, born at term, for CAH from the CH and CAH combination. Conclusions: Multiple positive results are a rare observation at neonatal screening for PKU, CH and CAH, more frequently observed in preterm babies. However, multiple positive results must not be overlooked because of true positive results at recall. [ABSTRACT FROM AUTHOR]

Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.

Background: Congenital hypothyroidism (CH), as one of the most common endocrine disorders, is a preventable cause of mental retardation., Objective: This study aimed to identify familial-related risk factors for CH in Iranian newborns., Methods: A population-based case-control study was performed on the National Registry System of patients with CH in Iran. In this study, 906 controls and 454 cases were studied for one year. Familial related factors were investigated using logistic regression models. Population attributable fraction (PAF) was also calculated for each significant risk factor., Results: Using multivariate analysis, an increased risk for CH was observed in patients with congenital anomalies (odds ratio (OR): 5.77, 95% confidence interval (CI): 2.37 - 14.01), history of mental retardation in family (OR:2.10, 95% CI: 1.15-3.83), mother's hypothyroidism during pregnancy (OR: 2.01, 95% CI: 1.33 - 3.03), intra-family marriage (OR:1.49, 95% CI: 1.18 - 1.89), gestational diabetes (OR: 1.69, 95% CI: 1.09 - 2.63), having a hypothyroid child in the family (OR: 2.48, 95% CI: 1.39 - 4.42), and twins or more (OR: 2.61, 95% CI: 1.31 - 5.21). The highest PAF among familial-related risk factors for CH is related to the intra-family marriage (14.9%)., Conclusions: This study revealed that familial-related risk factors and consanguine marriages play an essential role in the high incidence of CH in Iran. About 15% of CH in Iran could be attributed to intra-family marriage alone., Competing Interests: Conflict of Interests: No potential conflict of interest was reported by the authors., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Objective: To investigate the profiles of blood amino acid and acylcarnitine in early neonates with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and the sensitivity of newborn screening, and to explore potential biochemical metabolic markers for newborn screening program. Methods: Amino acid and acylcarnitine profiles in dried blood spots of newborn screening program were analyzed by tandem mass spectrometry (MS/MS). A total of 158 651 neonates born in Guangzhou from January 1, 2015 to June 30, 2019 were enrolled in this newborn screening program, and additionally 55 patients with NICCD confirmed by SLC25A13 gene analysis in Guangzhou Women and Children Medical Center were included in this study. NICCD screen-positive was defined as the cutoff value of citrulline (Cit) ≥ 30 μmol/L. The values of blood sampling time of the true positive group and those of the false negative group were compared by t -test. The levels of amino acid and acylcarnitine among different groups, including true positive group (Cit≥30 μmol/L), false negative group (Cit 21- < 30 μmol/L and Cit < 21 μmol/L) and the normal control group, were analyzed by F test, respectively. Results: Among 158 651 neonates, 39 neonates were positive for NICCD screening. Three of them were confirmed NICCD and 4 cases were found to be false negatives. The positive predictive value was 7.7% and the sensitivity was about 43.0%. Among 55 patients with NICCD, 18 cases (18/55, 32.7%) were true positives and 37 cases (37/55, 67.3%) were false negatives based on the cutoff value of citrulline in the dried blood spots for newborn screening. The blood sampling time was significantly different between true positive group and false negative group ((4.28±1.6) vs. (2.98±0.74) d, t= 4.06, P< 0.01). The increased levels of tyrosine((176.0±98.4) μmol/L), methionine ((37.0±26.9) μmol/L) and phenylalanine ((133.0±80.9)μmol/L) in Cit≥30 μmol/L group ( n= 18) were significantly different as compared with those in the other three groups, respectively ( F= 117.0, 58.5, 135.0, P< 0.01). The levels of arginine ( (10.0±9.2) , (11.0±9.3) , (9.0±17.8) μmol/L), valine ( (119.0±29.8) , (107.6±14.1) , (102±68) μmol/L) and leucine ( (167.0±37.1) , (161.0±37.7) , (163.5±180.6) μmol/L) were not statistically significant among groups of Cit≥30 μmol/L( n= 18), Cit21-<30 μmol/L( n= 7) and Cit < 21μmol/L( n= 30, P> 0.05), but they were significantly higher than those of the normal control group ((4±3), (78±21), (114.0±31.5) μmol/L, n= 1 000), respectively( F= 30.1, 23.0, 29.8, P< 0.01). Alanine (Ala) ( (150±50) , (156.0±30.2), (168±105), (152±52) μmol/L) levels showed no significant difference ( F= 0.86, P> 0.05) but the ratios of Ala/Cit (1.52±1.44, 6.82±1.56, 12.06±7.71, 19.42±6.27) decreased significantly among the four groups ( F= 69.0, P< 0.05). The acylcarnitine levels showed no statistically significant results among the different groups ( P> 0.05). With Cit≥30 μmol/L and Ala/Cit < 7.5 as cutoff values, the number of screen-positive cases reduced from 39 to 22 cases with no additional false negative case. With Cit≥21 μmol/L and Ala/Cit < 7.5 as cutoff values the number of screen-positive cases increased to 117 cases with 1 additional true positive. Conclusions: The profiles of blood amino acid in early neonates with NICCD present the increased levels of multiple amino acids including citrulline, tyrosine, methionine and phenylalanine, and decreased ratio of Ala/Cit. Taking citrulline and ratio of Ala/Cit as screening markers can improve the positive predictive value appropriately. The limited sensitivity of NICCD newborn screening may be related to early blood sampling time.

Biotinidase deficiency is an autosomal recessive disorder that affects the endogenous recycling and release of biotin from dietary protein. This disease was thought to be rare in East Asia. In this report, we delineate the phenotype of biotinidase deficiency in our cohort. The genotypes and phenotypes of patients diagnosed with biotinidase deficiency from a medical center were reviewed. The clinical manifestations, laboratory findings, and molecular test results were retrospectively analyzed. A total of 6 patients were evaluated. Three patients (50%) were diagnosed because of a clinical illness, and the other three (50%) were identified by newborn screening. In all patients, the molecular results confirmed the BTD mutation. The three patients with clinical manifestations had an onset of seizure at the age of 2 to 3 months. Two patients had respiratory problems (one with apnea under bilevel positive airway pressure (BiPAP) therapy at night, and the other with laryngomalacia). Hearing loss and eye problems were found in one patient. Interestingly, cutaneous manifestations including skin eczema, alopecia, and recurrent fungal infection were less commonly seen compared to cases in the literature. None of the patients identified by the newborn screening program developed symptoms. Our findings highlight differences in the genotype and phenotype compared with those in Western countries. Patients with biotinidase deficiency benefit from newborn screening programs for early detection and management. [ABSTRACT FROM AUTHOR]

Aim: To address the implementation of the National Newborn Screening Program (NBS) in Saudi Arabia and stratify the incidence of the screened disorders.Methods: A retrospective study conducted between 1 August 2005 and 31 December 2012, total of 775 000 newborns were screened from 139 hospitals distributed among all regions of Saudi Arabia. The NBS Program screens for 16 disorders from a selective list of inborn errors of metabolism (IEM) and endocrine disorders. Heel prick dry blood spot samples were obtained from all newborns for biochemical and immunoassay testing. Recall screening testing was performed for Initial positive results and confirmed by specific biochemical assays.Results: A total of 743 cases were identified giving an overall incidence of 1:1043. Frequently detected disorders nationwide were congenital hypothyroidism and congenital adrenal hyperplasia with an incidence of 1:7175 and 1:7908 correspondingly. The highest incidence among the IEM was propionic acidaemia with an incidence rate of 1:14 000.Conclusion: The article highlights the experience of the NBS Program in Saudi Arabia and providing data on specific regional incidences of all the screened disorders included in the programme; and showed that the incidence of these disorders is one of the highest reported so far world-wide. [ABSTRACT FROM AUTHOR]