Newborn Screening Diagnosis Research Articles

Defining the Minimal Long-Term Follow-Up Data Elements for Newborn Screening.

Newborn screening (NBS) is hailed as a public health success, but little is known about the long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on the minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

State Coordinator Perceptions of Linkages Between Newborn Screening and Early Intervention

Early Intervention (EI) aims to lessen the effects of developmental delay by providing services to infants and young children. Newborn screening (NBS) is a public health program that identifies infants with treatable conditions, although many conditions put children at risk of developmental delay even after medical intervention. The purpose of this study is to explore the extent to which these programs coordinate to identify, refer, and qualify children for EI services after an NBS diagnosis. A survey of state EI ( n = 30) and NBS ( n = 39) program leaders (i.e., coordinators) demonstrated variability in familiarity and collaboration; however, most coordinators were willing to pursue future collaboration. We discuss the implications of the survey results and propose policy changes that would facilitate future collaboration and, ultimately, benefit children and families.

Changing clinical manifestations of Gaucher disease in Taiwan

BackgroundGaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA1 gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD during different eras in Taiwan.Materials and methodsData from the health records of two tertiary hospitals responsible for two-thirds of the patients with GD in Taiwan were used. The study population included all patients identified as having GD between 1998, and April 2022, in these two hospitals for review. A total of 42 individuals were included, six of whom were diagnosed by NBS.ResultsOur cohort presented a higher proportion of GD3 individuals, both by clinical suspicion and by NBS diagnosis, than that reported worldwide. The major subtypes that were recognized following NBS diagnosis were GD2 and GD3. The majority of GD patients carry at least one p.Leu483Pro variant. The 5-year survival rates were 0% for GD2 patients and 100% for patients with other subtypes. Patients diagnosed during the post-NBS era were free of symptoms on initial presentation, except for those with the GD2 subtype. For those diagnosed earlier, ERT was shown to be effective in terms of improved hemograms and prevented bone crises. However, the neurological symptoms in GD3 patients progressed despite ERT intervention.ConclusionERT is essential in reversing the hematological presentations and preventing the skeletal complications of GD. Timely diagnosis of GD with NBS allows for early intervention with ERT to prevent disease progression and complications. However, the need for effective intervention for neurological dysfunction remains unmet.

Early disease surveillance in young children with cystic fibrosis: A qualitative analysis of parent experiences

Background. Sensitive measures of early lung disease are being integrated into therapeutic trials and clinical practice in cystic fibrosis (CF). The impact of early disease surveillance (EDS) using these novel and often intensive techniques on young children and their families is not well researched.Methods. The Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) has operated a combined clinical and research early disease surveillance program, based around annual chest CT scan, bronchoscopy and lung function from newborn screening diagnosis until age 6 years, for over two-decades. To explore parental experiences of EDS in their child, a qualitative study was conducted using audio-recorded, semi-structured interviews in n=46 mothers and n=21 fathers of children (aged 3-months to six years) attending CF centres in Perth and Melbourne, Australia. Themes were developed iteratively using thematic analysis and assessed for validity and confirmability.Results. Parents’ experiences were positive overall; affording a sense of control over CF, disease knowledge, and belief that EDS was in the best interests of their child. Challenges included poor understanding about EDS measures leading to anxiety and distress, self-blame surrounding adverse findings, and emotional burden of surveillance visits. Tailored information regarding the practical and psychosocial aspects of EDS were endorsed.Conclusion. While experiences were generally positive there is need for information and psychosocial support for parents to mitigate anxiety and develop positive coping strategies surrounding surveillance procedures and results. Managing expectations regarding risks and benefits of disease surveillance in clinical and research settings are important aspects of care.

Practice pattern changes and improvements in hematopoietic cell transplantation for primary immunodeficiencies

Allogeneic HCT practice patterns for PID changed between 1974–2016. Three-year survival improved to >70% for SCID and non-SCID patients after 1999, and further increased to 94% for SCID patients transplanted 2010–2016 following newborn screening diagnosis.

Impact of Immigration and Migration on Thalassemia Surveillance in California, 2004-2008

On-going public health surveillance efforts are critical for understanding of the impact and outcomes of thalassemias. California implemented newborn screening (NBS) for beta thalassemia in 1990 and for alpha thalassemia and hemoglobin H (HbH) in 1999; over 99% of all live births are screened. This program has identified hundreds of newborns with these life-threatening disorders, and has led to improved care and outcomes. However the impact of immigration and state-to-state migration of high-risk populations is unknown, and this limits understanding of the prevalence of thalassemia in California.The National Heart, Lung and Blood Institute (NHLBI)-funded and Centers for Disease Control and Prevention (CDC)-directed Registry and Surveillance System for Hemoglobinopathies (RuSH) cooperative agreement collected and linked population-based surveillance data in seven states from a variety of data sources for years 2004-2008. In California, these data included case reports of patients from large specialty treatment centers – Children’s Hospital Los Angeles and UCSF Benioff Children’s Hospital Oakland. In a subsequent CDC cooperative agreement, Public Health Research, Epidemiology and Surveillance in Hemoglobinopathies (PHRESH), California collected additional case reports from four treatment centers: University of California (UC) Davis Medical Center, UC Irvine Medical Center, UC San Francisco Medical Center and UC San Diego Rady Children’s Hospital. We linked reported cases born 1990-2008 to NBS hemoglobinopathy registry thalassemia cases using date of birth, sex, diagnosis and name.There were 273 treatment center reported cases born during the NBS time frame (i.e., 1990-2008 for beta thalassemia, 1999-2008 for alpha thalassemia), including 113 HbH, 46 beta thalassemia major, 20 HbH/Constant Spring, 17 beta thalassemia intermedia, 26 other beta thalassemia, 3 alpha thalassemia major and 48 cases with unknown or unreported genotype. Of the 225 with known genotype, 62% were definite links to the NBS registry, an additional 16% were likely matches (same date of birth, sex and genotype with no other match for that registry case, but different surname) and 21% had no match in the registry. Treatment center reported cases with known genotype not in the NBS registry were more likely to be older (45% unlinked in the oldest age group vs. 12% unlinked in the youngest group) and for 4% (n = 8) of linked cases the treatment center diagnosis differed significantly from the NBS diagnosis. Among the 48 reported cases with unknown genotype, only nine linked to registry cases. Without confirmatory testing, it is unknown whether these cases have thalassemia trait or benign forms of hemoglobin disorders (e.g., Hemoglobin EE) or any form of blood disorder, so interpretation of the lack of linkage among these cases is difficult. Table 1 shows proportions of cases linked (definite and likely matches) and unlinked with the registry by genotype and year. Linked cases from these six treatment centers represented 23% of all NBS registry thalassemia cases for the relevant time period.While California’s strong NBS program is effectively capturing incidence of thalassemias at birth, these data show a high number of cases born out of state or otherwise undiagnosed that may represent migration to the state of high risk populations. These data also do not capture the number of NBS-identified infants who moved out of state during this time period. On-going population-based surveillance for thalassemia is important to monitor changes in prevalence and outcomes among those affected, and informs development of standards of care, policy and advocacy efforts.This work was supported by the CDC and the NHLBI, cooperative agreement numbers U50DD000568 and U50DD001008.Abstract 4855. Table 1:Proportion of Eligible Thalassemia Cases Reported by Treatment Centers Linked to NBS Registry Cases – California, 1990-2009Unlinked CasesTreatment Center Reported Genotype/DiagnosisYears Screening BegunTotal Eligible Treatment Center CasesLinked to NBS Registry1990-19941995-19992000-20042005-2008Hemoglobin H1999113105--341Hemoglobin H/Constant Spr.19992016--112α thalassemia major199933--000β thalassemia major199046277921β thalassemia intermedia19901772422β thalassemia other199026191213Total Known Genotype2251771019109Genotype unreported--489410178Total Reported Cases27318614292717 DisclosuresNo relevant conflicts of interest to declare.