International Journal of Neonatal Screening
EISSN : 2409515X
Current Publisher: MDPI (10.3390)
Total articles ≅ 217
Latest articles in this journal
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030075
Newborn screening (NBS) laboratories cannot accurately compare mass spectrometry-derived results and cutoff values due to differences in testing methodologies. The objective of this study was to assess harmonization of laboratory proficiency test (PT) results using quality control (QC) data. Newborn Screening Quality Assurance Program (NSQAP) QC and PT data reported from 302 laboratories in 2019 were used to compare results among laboratories. QC materials were provided as dried blood spot cards which included a base pool and the base pool enriched with specific concentrations of metabolites in a linear range. QC data reported by laboratories were regressed on QC data reported by the Centers for Disease Control and Prevention (CDC), and laboratory’s regression parameters were used to harmonize their PT result. In general, harmonization tended to reduce overall variation in PT data across laboratories. The metabolites glutarylcarnitine (C5DC), tyrosine, and phenylalanine were displayed to highlight inter- and intra-method variability in NBS results. Several limitations were identified using retrospective data for harmonization, and future studies will address these limitations to further assess feasibility of using NSQAP QC data to harmonize PT data. Harmonizing NBS data using common QC materials appears promising to aid result comparison between laboratories.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030074
Newborn screening for critical congenital heart disease (CCHD) is recommended for implementation in many developed countries as the standard of care. Efforts to implement this point of care screen in developing regions face unique barriers, and present important opportunities. The First Pan-African Newborn Screening Conference, held in Rabat in June 2019, incorporated a workshop dedicated specifically to identifying and discussing CCHD screening issues in the Middle East Northern Africa (MENA) region. The issues explored may be beneficial as part of the greater discussion of CCHD screening’s growing importance in developing regions around the world. Screening experts presented education and lessons learned from previous CCHD implementations, including a hands-on technical demonstration of CCHD screening. Children’s HeartLink, The Newborn Foundation, and Children’s National Hospital each presented on their experiences working with teams and pilot projects from around the world. Experience in implementation from Children’s Hospital Marrakesh was presented and highlighted some of the unique findings, challenges, and experiences of screening in Morocco. As developing regions investigate the implementation of CCHD screening using pulse oximetry either as part of research studies, pilots, regional studies, or as part of a nationally supported program, data to inform policymakers on the benefits of screening and specific needs for infrastructure development and resources are essential. This special issue contains initial lessons learned on newborn CCHD screening from a select number of developing countries, including Saudi Arabia and Morocco and regions such as Latin America.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030073
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, progressive multisystemic lysosomal storage disorder with significant morbidity and premature mortality. Infants with MPS II develop signs and symptoms of the disorder in the early years of life, yet diagnostic delays are very common. Enzyme replacement therapy is an effective treatment option. It has been shown to prolong survival and improve or stabilize many somatic manifestations of the disorder. Our initial experience with newborn screening in 162,000 infants was previously reported. Here, we update that experience with the findings in 339,269 infants. Measurement of iduronate-2-sulfatase (I2S) activity was performed on dried blood spot samples submitted for other newborn screening disorders. A positive screen was defined as I2S activity less than or equal to 10% of the daily median. In this series, 28 infants had a positive screening test result, and four other infants had a borderline result. Three positive diagnoses of MPS II were established, and 25 were diagnosed as having I2S pseudodeficiency. The natural history and the clinical features of MPS II make it an ideal target for newborn screening. Newborn screening was effective in identifying affected infants in our population with an acceptable rate of false positive results.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030072
Two lysosomal storage disorders (LSDs), Pompe disease and Mucopolysaccharidosis type I (MPSI) were added to the Recommended Uniform Screening Panel (RUSP) for newborn screening (NBS) in 2015 and 2016, respectively. These conditions are being screened with variable practice in terms of primary and reflex analytes (either biochemical or molecular testing) as well as collection of short- and long-term follow-up elements. The goal of this study is to evaluate practices of state health departments in regards to screening methods and follow-up data collected. We conducted online surveys and phone questionnaires to determine each U.S. state’s practices for screening and follow-up of positive newborn screens. We report the first snapshot of practices for NBS for the LSDs included on the RUSP. All 50 U.S. states responded to our survey. The majority of U.S. states are not currently screening for Pompe disease and MPSI as of March 2020, but this number will increase to 38 states in the coming 1–3 years based on survey results. Our survey identifies data elements used by state health departments for short-and long-term follow-up that could serve as the basis of common elements for larger, public health-based analyses of the benefits and efficacy of screening for Pompe disease and MPSI.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030071
Congenital adrenal hyperplasia (CAH) was the fourth disorder added to the national Swedish neonatal screening program in 1986, and approximately 115,000 newborns are screened annually. Dried blood spot (DBS) screening with measurement of 17-hydroxyprogesterone (17OHP) is also offered to older children moving to Sweden from countries lacking a national DBS screening program. Here, we report an update on the CAH screening from January 2011 until December 2019. Results: During the study period, 1,030,409 newborns and 34,713 older children were screened. In total, 87 newborns were verified to have CAH, which gives an overall positive predictive value (PPV) of 11% and 21% for term infants. Including the five missed CAH cases identified during this period, this gives an incidence of 1:11,200 of CAH in Sweden. Among the older children, 12 of 14 recalled cases were found to be true positive for CAH. All patients were genotyped as part of the clinical follow-up and 70% of the newborns had salt wasting (SW) CAH and 92% had classic CAH (i.e., SW and simple virilizing (SV) CAH). In the group of 12 older children, none had SW CAH and two had SV CAH. Conclusion: The incidence of classic CAH is relatively high in Sweden. Early genetic confirmation with CYP21A2 genotyping has been a valuable complement to the analysis of 17OHP to predict disease severity, make treatment decisions and for the follow-up and evaluation of the screening program.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030070
Congenital adrenal hyperplasia (CAH) is a common treatable disorder which is associated with life-threatening adrenal crisis, sexual ambiguity, and/or abnormal growth if undiagnosed. Newborn screening is a cost-effective tool to detect affected babies early after birth to optimize their treatment and follow-up. Newborn screening however is in its nascent stage in India where it is not yet introduced universally for all babies. The following review briefly highlights the challenges (e.g., lack of universal screening, healthcare resources) and opportunities (e.g., reduction in morbidity and early correct gender assignment in females) associated with newborn screening for CAH in a large Indian birth cohort.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030068
Neonatal screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency is now performed in an increasing number of countries all over the world. The main goal of the screening is to achieve early diagnosis and treatment in order to prevent neonatal salt-crisis and death. The screening laboratory can also play an important role in increasing the general awareness of the disease and act as the source of information and education for clinicians to facilitate improved initial care, ensure prompt and correct glucocorticoid dosing to optimize the long-term outcome for the patients. A National CAH Registry and CYP21A2 genotyping provide valuable information both for evaluating the screening program and the clinical outcome. The Swedish experience is described.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030069
All newborn screening (NBS) for mucopolysaccharidosis-I (MPS-I) is carried out by the measurement of α-iduronidase (IDUA) enzymatic activity in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and studies from the Mayo Clinic have shown that the false positive rate can be greatly reduced by including a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, we obtained newborn DBS from 13 patients with severe MPS-I and 2 with attenuated phenotypes. These samples were submitted to four different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide; (2) endogenous disaccharide; (3) Sensi-Pro; (4) Sensi-Pro Lite (a variation of Sensi-Pro with a simplified workflow). Patients with attenuated MPS-I show less GAG elevation than those with severe disease, and all MPS-I patients were separated from the reference range using all four methods. The minimal differential factor (lowest GAG marker level in MPS-I samples divided by highest level in the reference range of 30 random newborns) was about two for internal disaccharide, Sensi-Pro, and Sensi-Pro Lite methods. The endogenous disaccharide was clearly the best method with a minimal differential of 16-fold. This study supports use of second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030067
Newborn screening for 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia, has been performed routinely in the United States and other countries for over 20 years. Screening provides the opportunity for early detection and treatment of patients with 21OHD, preventing salt-wasting crisis during the first weeks of life. However, current first-tier screening methodologies lack specificity, leading to a large number of false positive cases, and adequate sensitivity to detect all cases of classic 21OHD that would benefit from treatment. This review summarizes the pathology of 21OHD and also the key stages of fetal hypothalamic-pituitary-adrenal axis development and adrenal steroidogenesis that contribute to limitations in screening accuracy. Factors leading to both false positive and false negative results are highlighted, along with specimen collection best practices used by laboratories in the United States and worldwide. This comprehensive review provides context and insight into the limitations of newborn screening for 21OHD for laboratorians, primary care physicians, and endocrinologists.
International Journal of Neonatal Screening, Volume 6; doi:10.3390/ijns6030066
Newborn screening (NBS) for Krabbe disease (KD) is currently underway in eight states in the USA, and there is continued discussion of whether to implement KD NBS in additional states. Workgroup members sought to survey a large number of families affected by KD. Families in KD and leukodystrophy family registries were contacted to seek their participation in The Krabbe Newborn Screening—Family Perspective Survey. The 170 respondents are comprised of the following: 138 family members with a KD individual diagnosed after development of symptoms, 20 notified about KD via NBS, and 12 with a KD individual diagnosed through family history of KD. The key results are that all NBS families with an early-infantile KD family member elected to pursue hematopoietic stem cell transplantation therapy. Of the 170 responders, 165 supported the implementation of KD NBS in all states in the USA.