Search Results (7)

Part of the vision of the ISNS is ‘to enhance the quality of neonatal screening and medical services through dissemination of information, guidelines and best practices.’ Although newborn screening encompasses testing in the newborn period for critical congenital heart disease, hearing impairment, birth defects, and congenital biochemical disorders (usually on bloodspots), this guideline is specifically about bloodspot screening. The ISNS has provided neonatal screening guidelines for many years and here presents the renewed 2025 General Guidelines for Neonatal Bloodspot Screening. They are intended to provide a framework for screening programs to develop specific policies around all aspects of the newborn screening system, offering the basic set of items for consideration. These guidelines provide trusted anchors to build, expand, or maintain robustly organized neonatal or newborn screening (NBS) programs and a checklist to evaluate and improve the essential elements of those programs. For starting or developing programs, it is a set of elements for which provisions need to be in place and a checklist of items that the screening program should at a minimum have provisions for. The publication of these guidelines is meant as a starting point for interactive discussion, to further improve this document and expand where necessary. Full article

A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV. Full article

Repeated European surveys of newborn bloodspot screening (NBS) have shown varied strategies for collecting missed cases, and information on data collection differs among countries/regions, hampering data comparison. The ECFS Neonatal Screening Working Group defined missed cases by NBS as either false negatives, protocol-related, concerning analytical issues, or non-protocol-related, concerning pre- and post-analytical issues. A questionnaire has been designed and sent to all key workers identified in each NBS programme to assess the feasibility of collecting data on missed cases, the stage of the NBS programme when the system failed, and individual patient data on each missed case. Full article

Very long-chain acylcarnitine dehydrogenase deficiency (VLCADD) is a rare inherited metabolic disorder associated with fatty acid β-oxidation and characterized by genetic mutations in the ACADVL gene and accumulations of acylcarnitines. VLCADD, developed in neonates or later adults, can be diagnosed using newborn bloodspot screening (NBS) or genetic sequencing. These techniques have limitations, such as a high false discovery rate and variants of uncertain significance (VUS). As a result, an extra diagnostic tool is needed to deliver improved performance and health outcomes. As VLCADD is linked with metabolic disturbance, we postulated that newborn patients with VLCADD could display a distinct metabolomics pattern compared to healthy newborns and other disorders. Herein, we applied an untargeted metabolomics approach using liquid chromatography–high resolution mass spectrometry (LC-HRMS) to measure the global metabolites in dried blood spot (DBS) cards collected from VLCADD newborns (n = 15) and healthy controls (n = 15). Two hundred and six significantly dysregulated endogenous metabolites were identified in VLCADD, in contrast to healthy newborns. Fifty-eight and one hundred and eight up- and down-regulated endogenous metabolites were involved in several pathways such as tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, amino sugar and nucleotide sugar metabolism, pyrimidine metabolism and pantothenate, and CoA biosynthesis. Furthermore, biomarker analyses identified 3,4-Dihydroxytetradecanoylcarnitine (AUC = 1), PIP (20:1)/PGF1alpha) (AUC = 0.982), and PIP2 (16:0/22:3) (AUC = 0.978) as potential metabolic biomarkers for VLCADD diagnosis. Our findings showed that compared to healthy newborns, VLCAADD newborns exhibit a distinctive metabolic profile, and identified potential biomarkers that can be used for early diagnosis, which improves the identification of the affected patients earlier. This allows for the timely administration of proper treatments, leading to improved health. However, further studies with large independent cohorts of VLCADD patients with different ages and phenotypes need to be studied to validate our potential diagnostic biomarkers and their specificity and accuracy during early life. Full article

A national protocol for structured follow-up and texting of repeat newborn bloodspot screening (NBS) sample requests was introduced. Repeat samples are needed where the initial sample is inadequate or the result borderline-positive. This protocol aimed to improve the timeliness and completeness of receipt of repeat NBS samples. Under the structured protocol, all repeat sample requests were phoned or texted to the lead maternity carer (LMC), in addition to the standard written report issued. Weekly text reminders were sent until 4 weeks or the sample was received. National data were monitored following implementation of the protocol. The proportion of repeat samples received within 10 days of request improved after the introduction of the protocol, from 35.0% in 2013 to 81.4% in 2020 (p < 0.001). The proportion of requests lost to follow-up decreased, from 4.1% in 2013 to 1.3% in 2020 (p < 0.001). A structured NBS follow-up protocol that included SMS text messaging led to an earlier and more complete receipt of repeat samples. This is likely due to practitioners receiving the request more quickly, as well as the laboratory adopting a consistent approach to repeated reminders. SMS text messages are a useful adjunctive method for screening programmes to communicate with health care providers. Full article

Severe combined immunodeficiency is a rare inherited disorder, which, if untreated, invariably proves fatal in late infancy or early childhood. With treatment, the prognosis is much improved. Early treatment of the siblings of cases, before they become symptomatic, has shown considerable improvements in outcomes. Based on this and the development of a test that can be used on the whole population of neonates (measurement of T-cell receptor excision circles—TRECs), many countries have added it to their routine newborn bloodspot screening programmes. The UK National Screening Committee (UKNSC) has considered whether SCID should be added to the UK screening programme and concluded that it was likely to be cost effective, but that there were a number of uncertainties that should be resolved before a national roll-out could be recommended. These include some aspects of the test, such as: cost; the use of different assays and cut-off levels to reduce false positive rates, while maintaining sensitivity; the overall benefits of screening for disease outcome in patients with SCID and other identified disorders; the need for a separate pathway for premature babies; the acceptability of the screening programme to parents of babies who have normal and abnormal (both true and false positive) screening results. To achieve this, screening of two thirds of babies born in England over a two-year period has been planned, beginning in September 2021. The outcomes and costs of care of babies identified by the screening will be compared with those of babies identified with SCID in the rest of the UK. The effect of the screening programme on parents will form part of a separate research project. Full article

Lead (Pb) exposure remains a major concern in the United States (US) and around the world, even following the removal of Pb from gasoline and other products. Environmental Pb exposures from aging infrastructure and housing stock are of particular concern to pregnant women, children, and other vulnerable populations. Exposures during sensitive periods of development are known to influence epigenetic modifications which are thought to be one mechanism of the Developmental Origins of Health and Disease (DOHaD) paradigm. To gain insights into early life Pb exposure-induced health risks, we leveraged neonatal dried bloodspots in a cohort of children from Michigan, US to examine associations between blood Pb levels and concomitant DNA methylation profiles (n = 96). DNA methylation analysis was conducted via the Infinium MethylationEPIC array and Pb levels were assessed via high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). While at-birth Pb exposure levels were relatively low (average 0.78 µg/dL, maximum of 5.27 ug/dL), we identified associations between DNA methylation and Pb at 33 CpG sites, with the majority (82%) exhibiting reduced methylation with increasing Pb exposure (q < 0.2). Biological pathways related to development and neurological function were enriched amongst top differentially methylated genes by p-value. In addition to increases/decreases in methylation, we also demonstrate that Pb exposure is related to increased variability in DNA methylation at 16 CpG sites. More work is needed to assess the accuracy and precision of metals assessment using bloodspots, but this study highlights the utility of this unique resource to enhance environmental epigenetics research around the world. Full article