dépistage néonatal

Paris, le lundi 16 janvier 2023 - L’amyotrophie spinale infantile* est une maladie génétique (autosomique récessive) rare qui touche les neurones moteurs entraînant une atrophie progressive des muscles. Dans sa forme la plus sévère (SMA type I, 60 % cas), 95 % des enfants atteints meurent avant l’âge [...]

Newborn screening tests (NST) are important public health procedures with potential to improve quality of life, and decrease morbidity/mortality by identifying metabolic, genetic, enzymatic, and endocrinological diseases/conditions. In the United States (U.S.), Hawaii conducts the fewest NST (28) and Connecticut conducts the most (75). The purpose of this research is to determine if difficulty receiving specialty care for children with genetic diseases is associated with NST determination of the genetic condition. The research hypothesis is that parents/guardians of children with determination of genetic disease from NST are more likely to report no/slight difficulty accessing specialty care versus parents/guardians of children with genetic diseases whose determination was other than NST. This study has a cross-sectional design with National Survey of Children’s Health, 2020 data. Data were analyzed for frequency, Rao Scott Chi square, and logistic regression analyses. Of 833 children with genetic diseases, most parents/guardians reported no/slight difficulty in receiving needed specialty care; however, children whose determination of a genetic condition was other than NST were 4.82 times as likely (95%CI: 1.66, 14.02; p = 0.0040) to have difficulty. In analysis adjusted for sex, race, age, premature birth, and birthweight, the adjusted odds ratio was 6.71 (95% CI:1.91, 23.60 p = 0.0031). Parents/guardians of children screened with a positive NST reported less difficulty in receiving needed specialist care as compared with reports of parents/guardians of children with genetic conditions who were diagnosed later. The implication is there would be greater population level benefits realized in the U.S. if NST were expanded in states conducting minimal testing.

Parents increasingly utilise the internet to obtain information on health practices, but the quality of online information about screening for inherited metabolic diseases (IMD) needs to be improved. A content analysis examined how IMD blood and urine tests were described online in local healthcare sectors between May and June 2021. Among the nine resources, four were blood test providers and five were urine test providers. All mentioned the test benefits and procedures. Other information, such as false-positive/negative or risk of pain, was infrequently mentioned. The descriptions of urine tests are advertised as outperforming blood tests and can be purchased from commercial laboratory sites without medical guidance. Two urine test providers claimed no false results were reported. A few commercial advertisements highlighted the simplicity of the urine test and potentially overstated the invasiveness of the blood test. We found that some advertisements described IMD as “silent killers” and emphasised the advantage of getting “reassurance” in controlling the child’s developmental health and well-being. To better protect the parents, or broadly, the public interest, regulatory and oversight measures on the urine tests should be implemented to promote the proper use of genetic tests. Without timely regulation and oversight, the incorrect descriptions might create a public misconception about utilising these commercial laboratory tests to inform health decisions.

Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above (“high”) and below (“low”) the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with “high” CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with “low” CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce “high” IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce “low” IRT CFFNs.

The ability to screen newborns for a larger number of disorders, including many with variable phenotypes, is prompting debate regarding the psychosocial impact of expanded newborn bloodspot screening (NBS) on parents. This study compares psychological outcomes of parents of children with a range of NBS/diagnostic experiences, with a particular focus on lysosomal storage disorders (LSDs) and X-linked adrenoleukodystrophy (X-ALD) as representative disorders with complex presentations. An online cross-sectional survey with six domains was completed in 2019 by a volunteer sample of parents with at least one child born between 2013 and 2018. Parents were classified in the analysis stage into four groups based on their child’s rare disorder and means of diagnosis. Stress and depression were estimated using dichotomous measures of the depression subscale of the Hospital Anxiety and Depression Scale and the Parental Stress Scale. Logistic regression models were estimated for the relationship between the parent group and stress/depression, controlling for demographic variables (region of the US, income, education, major life events, relationship to the child, number of children, parent age, and race/ethnicity). One hundred seventy-four parents were included in this analysis. Parents of children with an LSD or X-ALD diagnosis clinically may have higher odds of depression (OR: 6.06, 95% CI: 1.64–24.96) compared to parents of children with the same disorders identified through NBS, controlling for covariates. Although a similar pattern was observed for parental stress (OR: 2.85, 95% CI: 0.82–10.37), this did not reach statistical significance. Ethically expanding NBS and genome sequencing require an understanding of the impacts of early detection for complex disorders on families. These initial findings are reassuring, and may have implications as NBS expands. Given our small sample size, it is difficult to generalize these findings to all families. These preliminary trends warrant further investigation in larger and more diverse populations.

Newborn screening for SMA, coupled with early access to disease-modifying therapies,
effectively ameliorates the functional burden and associated comorbidities for affected
children. For children diagnosed through newborn screening, motor score, CMAP, and
disease status at diagnosis has clinical utility to determine functional independence.

In this study, we modified a fully automatic immunoassay on ceruloplasmin concentration on dried blood spots (DBS) to increase its analytical sensitivity in order to accurately differentiate newborns from true Wilson disease (WD) patients. Modifications to the assay parameters of the Roche/Hitachi Cobas c systems immunoturbidimetric assay are adjusted to lower the limit of quantitation to 0.60 mg/L from 30 mg/L. This enables sensitive measurement of ceruloplasmin in eluent after DBS extraction. In addition, reference intervals and receiver operating characteristic curve analysis for diagnostic cut-off were established using DBS of neonates and WD adult patients. After DBS whole blood calibration, the 95th percentile of the reference interval for newborns was 86–229 mg/L. The cut-off value of 54 mg/L was found to be the most optimal point for differentiating true adult WD from newborn controls. This test shows a high area under curve of 1.000 with 100% sensitivity and specificity in differentiating normal newborns from WD adult samples. However, the results should be further validated with true newborn WD patient samples together with the consideration of other factors that can also lead to low ceruloplasmin levels. This test shows application potential in newborn screening for WD, which can save lives through early identification and timely treatment.

The mucopolysaccharidoses (MPS), Pompe Disease (PD), and Krabbe disease (KD) are inherited conditions known as lysosomal storage disorders (LSDs) The resulting enzyme deficiencies give rise to progressive symptoms. The United States Department of Health and Human Services’ Recommended Uniform Screening Panel (RUSP) suggests LSDs for inclusion in state universal newborn screening (NBS) programs and has identified screening deficiencies in MPS I, KD, and PD NBS programs. MPS I NBS programs utilize newborn dried blood spots and assay alpha L-iduronidase (IDUA) enzyme to screen for potential cases. Glycosaminoglycans (GAGs) offer potential as a confirmatory test. KD NBS programs utilize galactocerebrosidase (GaLC) as an initial test, with psychosine (PSY) activity increasingly used as a confirmatory test for predicting onset of Krabbe disease, though with an excessive false positive rate. PD is marked by a deficiency in acid α-glucosidase (GAA), causing increased glycogen, creatine (CRE), and other biomarkers. Bivariate normal limit (BVNL) methods have been applied to GaLC and PSY activity to produce a NBS tool for KD, and more recently, to IDUA and GAG activity to develop a NBS tool for MPS I. A BVNL tool based on GAA and CRE is in development for infantile PD diagnosis. Early infantile KD, MPS I, and PD cases were pre-symptomatically identified by BVNL-based NBS tools. This article reviews these developments, discusses how they address screening deficiencies identified by the RUSP and may improve NBS more generally.