OBJECTIVE: Although recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age.
METHODS: The NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach.
RESULTS: Increasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates.
CONCLUSIONS: The current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates.

BACKGROUND: In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early diagnosis. This study aims to describe phenotypes and genotypes at the time of CF diagnosis in a state in the Northeast Region of Brazil.
METHODS: Retrospective cross-sectional study. Clinical data were extracted from the medical records of CF patients. Clinical, laboratory, and genotypic characteristics were described for patients admitted to a tertiary referral center between 2007 and 2021.
RESULTS: Fifty-eight (58) patients were included in the study, 53.5% of whom were diagnosed through clinical suspicion. The median age at diagnosis was 4.7 months (IQR: 1.5-14.8 months). Five patients had false-negative results in the newborn screening. Faltering growth was the most frequent clinical manifestation. Bronchiectasis and a history of pneumonia predominated in those older than ten, while thinness, underweight, and electrolyte imbalances were more frequent in children under two. Sequencing of the CFTR gene identified 27 genotypes, with at least one class I-III variant in all patients, and nine variants that are rare, previously undescribed, or have uncertain significance (619delA, T12991, K162Q, 3195del6, 1678del > T, 124del123bp, 3121-3113 A > T). The most frequent alleles were p.Phe508del, p.Gly542*, p.Arg334Trp, and p.Ser549Arg.
CONCLUSIONS: Malnutrition and electrolyte imbalances were the most frequent phenotypes for children < 2 years and were associated with genotypes including 2 class I-III variants. Rare and previously undescribed variants were identified. The p.Gly542*, p.Arg334Trp, and p.Ser549Arg alleles were among the most frequent variants in this population.

免疫出生缺陷（IEI）是一类主要由单基因变异导致免疫细胞数量和（或）功能异常的疾病。早期诊断和合理治疗是拯救IEI患儿生命，改善其生活质量，减轻家庭及社会医疗负担的重要举措。IEI的新生儿筛查逐渐开展。为此，中华医学会儿科学分会免疫学组、国家儿童健康与疾病临床医学研究中心以及中华儿科杂志编辑委员会组织相关领域专家，围绕IEI新生儿筛查流程与相关问题达成10条共识，以期规范和指导IEI的新生儿筛查工作。.

Organic acid disorders are rare inherited metabolic disorders of key metabolic pathways. For the identification of specific organic acids, investigation of urinary metabolites and genetic testing are required through newborn screening programmes. Delayed diagnosis leads to complications, such as cardiac attacks, respiratory problems, neuro-developmental disorders, intellectual disability, and even premature death. The burden of such inherited disorders is quite high in developing countries of South Asia due to high rate of consanguinity in the region. Unfortunately, such disorders are left untreated due to the lack of screening facilities in such countries. The current narrative review was planned to highlight the urgent need for closing this gap and implementing effective newborn screening programmes for organic acid disorders in developing countries. The implementation of effective programmes is crucial for reducing morbidity and mortality, and for improving the quality of life for the affected children and of their families, thus promoting global health equity.

BACKGROUND: Many newborn screening programs worldwide have introduced screening for diseases using DNA extracted from dried blood spots (DBS). In Germany, DNA-based assays are currently used to screen for severe combined immunodeficiency (SCID), spinal muscular atrophy (SMA), and sickle cell disease (SCD).
METHODS: This study analysed the impact of pre-analytic DNA carry-over in sample preparation on the outcome of DNA-based newborn screening for SCID and SMA and compared the efficacy of rapid extraction versus automated protocols. Additionally, the distribution of T cell receptor excision circles (TREC) on DBS cards, commonly used for routine newborn screening, was determined.
RESULTS: Contaminations from the punching procedure were detected in the SCID and SMA assays in all experimental setups tested. However, a careful evaluation of a cut-off allowed for a clear separation of true positive polymerase chain reaction (PCR) amplifications. Our rapid in-house extraction protocol produced similar amounts compared to automated commercial systems. Therefore, it can be used for reliable DNA-based screening. Additionally, the amount of extracted DNA significantly differs depending on the location of punching within a DBS.
CONCLUSIONS: Newborn screening for SMA and SCID can be performed reliably. It is crucial to ensure that affected newborns are not overlooked. Therefore a carefully consideration of potential contaminating factors and the definition of appropriate cut-offs to minimise the risk of false results are of special concern. It is also important to note that the location of punching plays a pivotal role, and therefore an exact quantification of TREC numbers per μl may not be reliable and should therefore be avoided.

UNASSIGNED: Health economic assessments are used to determine whether the resources needed to generate net benefit from an antenatal or newborn screening programme, driven by multiple benefits and harms, are justifiable. It is not known what benefits and harms have been adopted by economic evaluations assessing these programmes and whether they omit benefits and harms considered important to relevant stakeholders.
UNASSIGNED: (1) To identify the benefits and harms adopted by health economic assessments in this area, and to assess how they have been measured and valued; (2) to identify attributes or relevance to stakeholders that ought to be considered in future economic assessments; and (3) to make recommendations about the benefits and harms that should be considered by these studies.
UNASSIGNED: Mixed methods combining systematic review and qualitative work.
UNASSIGNED: We searched the published and grey literature from January 2000 to January 2021 using all major electronic databases. Economic evaluations of an antenatal or newborn screening programme in one or more Organisation for Economic Co-operation and Development countries were considered eligible. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. We identified benefits and harms using an integrative descriptive analysis and constructed a thematic framework.
UNASSIGNED: We conducted a meta-ethnography of the existing literature on newborn screening experiences, a secondary analysis of existing individual interviews related to antenatal or newborn screening or living with screened-for conditions, and a thematic analysis of primary data collected with stakeholders about their experiences with screening.
UNASSIGNED: The literature searches identified 52,244 articles and reports, and 336 unique studies were included. Thematic framework resulted in seven themes: (1) diagnosis of screened for condition, (2) life-years and health status adjustments, (3) treatment, (4) long-term costs, (5) overdiagnosis, (6) pregnancy loss and (7) spillover effects on family members. Diagnosis of screened-for condition (115, 47.5%), life-years and health status adjustments (90, 37.2%) and treatment (88, 36.4%) accounted for most of the benefits and harms evaluating antenatal screening. The same themes accounted for most of the benefits and harms included in studies assessing newborn screening. Long-term costs, overdiagnosis and spillover effects tended to be ignored. The wide-reaching family implications of screening were considered important to stakeholders. We observed good overlap between the thematic framework and the qualitative evidence.
UNASSIGNED: Dual data extraction within the systematic literature review was not feasible due to the large number of studies included. It was difficult to recruit healthcare professionals in the stakeholder\'s interviews.
UNASSIGNED: There is no consistency in the selection of benefits and harms used in health economic assessments in this area, suggesting that additional methods guidance is needed. Our proposed thematic framework can be used to guide the development of future health economic assessments evaluating antenatal and newborn screening programmes.
UNASSIGNED: This study is registered as PROSPERO CRD42020165236.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127489) and is published in full in Health Technology Assessment; Vol. 28, No. 25. See the NIHR Funding and Awards website for further award information.
Every year the NHS offers pregnant women screening tests to assess the chances of them or their unborn baby having or developing a health condition. It also offers screening tests for newborn babies to look for a range of health conditions. The implementation of screening programmes and the care for women and babies require many resources and funding for the NHS, so it is important that screening programmes represent good value for money. This means that the amount of money the NHS spends on a programme is justified by the amount of benefit that the programme gives. We wanted to see whether researchers consider all the important benefits and harms associated with screening of pregnant women and newborn babies when calculating value for money. To do this, we searched all studies available in developed countries to identify what benefits and harms they considered. We also considered the views of parents and healthcare professionals on the benefits and harms screening that creates for families and wider society. We found that the identification of benefits and harms of screening is complex because screening results affect a range of people (mother–baby, parents, extended family and wider society). Researchers calculating the value for money of screening programmes have, to date, concentrated on a narrow range of benefits and harms and ignored many factors that are important to people affected by screening results. From our discussions with parents and healthcare professionals, we found that wider impacts on families are an important consideration. Only one study we looked at considered wider impacts on families. Our work also found that parent’s ability to recognise, absorb and apply new information to understand their child’s screening results or condition is important. Healthcare professionals involve in screening should consider this when supporting families of children with a condition. We have created a list for researchers to identify the benefits and harms that are important to include in future studies. We have also identified different ways researchers can value these benefits and harms, so they are incorporated into their studies in a meaningful way.

OBJECTIVE: Hearing impairment affects a small but significant percentage of newborns (0.1-0.4%). Newborn hearing screening (NHS) is recommended for early detection and treatment. The implementation of NHS can vary among countries. In this study, we present the methodology, organization, and technical requirements of NHS. This study analyzed results from a tertiary hospital, identified issues, and proposed solutions.
METHODS: In the studied region, there are five maternity hospitals and a perinatal intensive care center and in 2020, there were 5,864 live births. Screening is performed at three levels. The first screening is conducted on the 2nd-3rd day of a newborn\'s life in a maternity hospital, the first rescreening on the 3rd-6th week at a relevant ENT department, and the second rescreening on the 3rd-6th month of life at the regional screening center where the central database is also held.
RESULTS: In the studied region, 5,793 out of 5,864 (98.79%) newborns received NHS in 2020. Of these, 120 (2.07%) were tested positive on their first screening. Ninety-four patients (78.3%) of those attended the ENT department for a first rescreening. Thirty-four patients (0.59% of total) were tested positive again and referred to the regional screening center. Out of the 27 patients who attended the second rescreening, four (0.07% of the total) were ultimately diagnosed with hearing impairment.
CONCLUSIONS: Our study found that newborn hearing screening (NHS) in our region achieved a high compliance rate of 98.8% for initial screenings in 2020. However, challenges remain in the rescreening process due to data management issues, inter-regional cooperation, and public awareness. The recent implementation of mandatory screenings, updated guidelines, and a centralized database is expected to enhance the effectiveness of NHS. Further research is needed to evaluate these improvements.

OBJECTIVE: This study was conducted to determine the level of knowledge of healthcare professionals involved in newborn heel prick tests.
METHODS: The study was conducted between 10.02.2021-10.03.2021 with 147 healthcare workers working in heel prick screening in health institutions where heel prick blood samples were collected in a province and districts in the Central Anatolia region of Turkey. As a data collection tool, a questionnaire prepared by the researcher in line with the literature was used. The data were evaluated by number, percentage, mean and standard deviation analysis and chi-square analysis was performed in IBM SPSS for Windows 29.0v programme.
RESULTS: The majority of healthcare professionals gave correct answers to the questions regarding the collection, storage and transfer of heel prick. It has been observed that healthcare professionals do not have sufficient information regarding the definition of Congenital Metabolic Diseases, their findings and where to refer patients whose results are suspicious.The most significance was found in the distribution of answers regarding the symptoms of the screened diseases according to occupational groups.
CONCLUSIONS: In diseases that can be controlled with treatment and nutrition if detected early, errors in the collection, storage and transport of the sample can affect the test result and delay the diagnosis. Healthcare professionals have important responsibilities issues from genetic counseling before marriage, taking heel blood, from informing the family to caring for the diagnosed baby.
CONCLUSIONS: This study will provide valuable information to health professionals involved in newborn screening and to future studies in this field.

The delivery of genetic services in developing countries is faced with significant challenges, despite medical and technological advances globally. The Philippines, being an archipelago, faces even more challenges, with significant disparities in access to healthcare, and tertiary medical centers and specialists being concentrated in the major cities. The utilization of different networks for the integration of genetic services in the existing public health delivery system has been valuable. Using the well-established network of the national newborn screening program, genetic services have been successfully integrated into the delivery of healthcare, even at the grassroot level. Equitable access to healthcare, including genetic services, was highlighted and supported by the enactment of the Rare Disease Law in 2016. The support of the academe to assure the sustainability of services was evident in the establishment of a genetic counseling program to augment the work of a handful of clinical geneticists. Professional societies and support groups have been instrumental in identifying genetic conditions to be prioritized and lobbying for increased public awareness, leading to national programs and policies. This paper primarily discusses the value of networks in the delivery of genetic services, specifically newborn screening, programs for rare diseases, birth defects, and genetic counseling.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20-40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.