International Journal of Neonatal Screening最新文献

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.

Regular reporting of quality control is important in newborn hearing screening, ensuring early diagnosis and intervention. This study reports on a population-based newborn hearing screening program in North-Rhine, Germany and a hospital-based screening at a University Hospital for 2007-2016. The two-staged 'screening' and 'follow-up' program involving TEOAE and AABR recruited newborns through participating birth facilities. Results were sent to the regional tracking center, and the data were analyzed based on recommended benchmarks. The percentage of newborns from the participating birth facilities in the region increased from 1.4% in 2007 to 57.5% in 2016. The 10-year coverage rate for these newborns was 98.7%, the referral rate after a failed two-step screening was 3.4%, and the lost-to-follow-up rate was 1%. At the hospital, >95% of the screened newborns completed screening within 30 days, the 10-year referral rate was 5%, and 64% were referred within 3 months of age. The median time for screening completion was 6 days after birth, for referral it was 74 days after birth, and for diagnosis it was 55 days after birth. Regional-centralized tracking centers with uniform structure are necessary for proper quality control. Obligatory participation of birthing facilities and quality reports may improve performance, but the recommended quality criteria need considerable financial and infrastructural expenditure.

Newborn screening (NBS) of inborn errors of metabolism (IEMs) is based on the reference ranges established on a healthy newborn population using quantile statistics of molar concentrations of biomarkers and their ratios. The aim of this paper is to investigate whether multivariate independent component analysis (ICA) is a useful tool for the analysis of NBS data, and also to address the structure of the calculated ICA scores. NBS data were obtained from a routine NBS program performed between 2013 and 2022. ICA was tested on 10,213/150 free-diseased controls and 77/20 patients (9/3 different IEMs) in the discovery/validation phases, respectively. The same model computed during the discovery phase was used in the validation phase to confirm its validity. The plots of ICA scores were constructed, and the results were evaluated based on 5sd levels. Patient samples from 7/3 different diseases were clearly identified as 5sd-outlying from control groups in both phases of the study. Two IEMs containing only one patient each were separated at the 3sd level in the discovery phase. Moreover, in one latent variable, the effect of neonatal birth weight was evident. The results strongly suggest that ICA, together with an interpretation derived from values of the "average member of the score structure", is generally applicable and has the potential to be included in the decision process in the NBS program.

Advances in an early diagnosis by expanded newborn screening (NBS) have been achieved mainly in developed countries, while populations of middle- and low-income countries have poor access, leading to disparities. Expanded NBS in Mexico is not mandatory. Herein, we present an overview of the differences and unmet NBS needs of a group of Mexican patients with inborn errors of intermediary metabolism (IEiM), emphasizing the odyssey experienced to reach a diagnosis. We conducted a retrospective observational study of a historical cohort of patients with IEiM from a national reference center. A total of 924 patients with IEiM were included. Although 72.5% of the diseases identified are detectable by expanded NBS, only 35.4% of the patients were screened. The mortality in the unscreened group was almost two-fold higher than that in the screened group. Patients experienced a median diagnostic delay of 4 months, which is unacceptably long considering that to prevent disability and death, these disorders must be treated in the first days of life. Patients had to travel long distances to our reference center, contributing to their unacceptable diagnostic odyssey. This study highlights the urgent need to have an updated, expanded NBS program with adequate follow up in Mexico and promote the creation of regional medical care centers. We also provide compelling evidence that could prove valuable to decision makers overseeing public health initiatives for individuals impacted by IEiM from middle- and low-income countries.

There are mixed reports on the inclusion and use of 21 deoxycortisol (21DF) as the primary decision marker for classical 21-hydroxylase deficiency. We hypothesize that this may be due to insufficient recognition of the presence and chromatographic separation of isomeric steroids. The aim of this study was to determine the comparative utility of 21DF for screening and diagnosis of CAH due to classical 21-hydroxylase deficiency using a second-tier LC-MS/MS method that included the separation of isomeric steroids to 17OHP and 21DF. For each baby sample, one 3.2 mm dried blood spot was eluted in a methanolic solution containing isotopically matched internal standards. Data were interrogated by univariate and receiver operator characteristic analysis. Steroid profile results were generated for 924 non-CAH baby samples (median gestational age 37 weeks, range 22 to 43 weeks) and 17 babies with 21-hydroxylase deficiency. The ROC curves demonstrated 21DF to have the best sensitivity and specificity for the diagnosis of classical 21-hydroxylase deficiency with an AUC = 1.0. The heatmap showed the very strong correlation (r = 0.83) between 17OHP and 21DF. Our data support 21DF as a robust marker for CAH due to 21-hydroxylase deficiency. We recommend that 21DF be incorporated into routine newborn screening panels as part of the second-tier LC-MS/MS method, follow-up plasma steroid panels, and external quality assurance material.

Determining the scope of a newborn screening program is a challenging health policy issue. Our study aimed to explore the attitudes of specialists in pediatrics, neonatology, medical genetics, and biochemistry regarding the prospects for expanding the panel of diseases for universal newborn screening in Bulgaria. We conducted an online survey in March-May 2022. The questionnaire listed 35 disorders that could potentially be included in the Bulgarian panel for universal newborn screening. If endorsing a specific condition, participants had to justify their position by judging its performance against the ten principles of Wilson and Jungner. We found a high degree of knowledge about the current universal newborn screening program in Bulgaria. An overwhelming majority (97.4%) supported the expansion of the panel to include more conditions. Four disorders obtained more than 50% approval for inclusion: cystic fibrosis (87.0%), thalassemia (72.7%), spinal muscular atrophy (65.6%), and classical galactosemia (59.1%). The perception of the condition as an important health problem was the most significant factor in this support. The costs of diagnosis and treatment appeared to be the main source of concern. We recommend country-specific economic evaluations and research on the views of other stakeholders, including the government, payers, and patient organizations, to better understand and manage the complex nature of newborn screening policymaking.