The genetic testing and genetic screening of children are commonplace. Decisions about whether to offer genetic testing and screening should be driven by the best interest of the child. The growing ...literature on the psychosocial and clinical effects of such testing and screening can help inform best practices. This technical report provides ethical justification and empirical data in support of the proposed policy recommendations regarding such practices in a myriad of settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Severe Combined Immunodeficiency (SCID) is the most profound inborn error of immunity affecting cellular and humoral immunity. Hematopoietic stem cell transplantation has been a curative treatment ...since 1968. Huge progress has been made since then in understanding the underlying genetics, improving outcomes from transplant, and introducing gene therapy in particular for adenosine deaminase deficient- and IL2 receptor gamma-deficient SCID. Newborn screening has been widely introduced across the world to enable definitive treatment before infection occurs. This article aims to review the latest evidence on how to achieve curative treatment with minimal short- and long-term toxicity, normal immune reconstitution and good quality of life.
•Newborn screening improves treatment success for severe combined immunodeficiency.•Reduced toxicity myelo-ablative conditioning regimens are well tolerated and lead to better longterm immune reconstitution.•The number of diseases able to be treated with gene therapy is expanding.•The role of gene therapy versus hematopoietic stem cell transplantation has yet to be determined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine whether socioeconomic status (SES) and small birthweight for gestational age (SGA) exhibit independent or joint effects on infant levels of 42 metabolites.
Population-based retrospective ...cohort of metabolic newborn screening information linked to hospital discharge data. SGA infants defined by birthweight <10th percentile for gestational age by sex. SES was determined by a combined metric including education level, participation in the WIC nutritional assistance program, and receiving California MediCal insurance. We performed linear regression to determine the effects of SES independently, SGA independently, and the interaction of SGA and SES on 42 newborn metabolite levels.
736,435 California infants born in 2005-2011 were included in the analysis. SGA was significantly associated with 36 metabolites. SES was significantly associated with 41 of 42 metabolites. Thirty-eight metabolites exhibited a dose-response relationship between SGA and metabolite levels as SES worsened. Fourteen metabolites showed significant interaction between SES and SGA. Eight metabolites showed significant individual and joint effects of SES and SGA: alanine, glycine, free carnitine, C-3DC, C-5DC, C-16:1, C-18:1, and C-18:2.
SES and SGA exhibited independent effects on a majority of metabolites and joint effects on select metabolites. A better understanding of how SES and SGA status are related to infant metabolites may help identify maternal and newborn interventions that can lead to better outcomes for infants born SGA.
In Romania, congenital hypothyroidism screening is performed by measuring thyroid-stimulating-hormone levels from dried blood samples. If the initial value is above the recommended cut-off value (10 ...mUI/L), the newborn is recalled for a second blood collection. The aim of this study was to investigate and report potential improvements on the screening protocol that is currently applied in our country in order to reduce the time between birth and treatment initiation in newborns positive to congenital hypothyroidism screening.
: Blood samples were collected from 41 full-term newborns between February and March 2019 at the maternity ward from Targu Mures Emergency County Hospital. Thyroid-stimulating-hormone values were measured with a chemiluminescent microparticle immunoassay in serum samples from cord blood collected at birth, and with a fluorometric enzyme-linked immunoassay in dried blood spots collected at day 3-5 after birth. To obtain whole blood values, serum values were transformed using a formula supplied by the kit manufacturer. Calculated cord blood values were compared with dried blood spots values using the Wilcoxon test.
: After serum-to-whole-blood conversion, cord blood values ranged from 2.58 to 3.66 mUI/L (95% CI). Dried blood spot values ranged from 6.70 to 7.50 mUI/L (95% CI). The Wilcoxon test p value between cord blood and dried blood spots thyroid-stimulating-hormone levels was statistically significant (p<0.01).
Thyroid-stimulating-hormone levels above the cut-off value were flagged by both techniques. An improvement to the existing protocol is proposed that may reduce time from positive screening results to confirmation of congenital hypothyroidism and treatment initiation.
Abstract Background Newborn screening (NBS) for cystic fibrosis (CF) results in the recognition of a number of infants with a positive NBS result, but an inconclusive diagnosis. Varied practice ...exists with respect to the management of these infants. Methods A Delphi consensus approach was used to determine agreement on statements generated by a core group of specialists. A designation (naming) exercise was required after Round 1 and further expert opinion was sought to guide that process. After Round 2, a sensitivity analysis was undertaken to assess the impact of attrition on subsequent agreement levels. Results Infants were divided into group A (normal sweat chloride and two CFTR mutations, at least one of which has unclear phenotypic consequences) and group B (intermediate sweat chloride and one or no CFTR mutations). 32 statements were produced for Round 1 and 24 achieved consensus. After Round 1, a designation exercise was undertaken and the term “CF Screen Positive, Inconclusive Diagnosis (CFSPID)” was suggested for Round 2. Agreement was achieved for this statement and for all other statements aside from the need for routine respiratory culture, on which there was divided opinion. The core group advocated local practice for this issue. A sensitivity analysis demonstrated that consensus for Round 2 was achieved by change in opinion rather than attrition. Conclusion We have generated a new designation and statements to guide the management of infants with CFSPID through a robust international Delphi process. These statements will be a valuable tool for CF teams and will improve the consistency of management of these infants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Early diagnosis of lysosomal storage diseases (LSDs) through newborn screening (NBS) has been adapted widely. The National Taiwan University Hospital Newborn Screening Center launched the four-plex ...tandem mass spectrometry LSD newborn screening test in 2015. The test determined activities of acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), acid β-glucocerebrosidase (ABG; Gaucher), and acid α-l-iduronidase (IDUA; MPS-I) in dried blood spots (DBS). Through 2017, 64,148 newborns were screened for these four LSDs. The screening algorithm includes enzyme activity/ratio as the cutoffs for the first screening test and a second-tier test for Pompe disease screening. The second-tier Pompe disease screening test measured activity inhibition by acarbose. Twenty-nine newborns required a confirmatory test; six were confirmed to have Pompe disease, and nine were confirmed to have Fabry disease. The screen-positive rate for Pompe disease was 0.031%. Therefore, in Pompe disease newborn screening, a validated 2nd tier test is necessary to decrease false positives.
Abstract
Background
Estimating the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for setting public health policies. We leveraged deidentified ...Massachusetts newborn screening specimens as an accessible, retrospective source of maternal antibodies for estimating statewide seroprevalence in a nontest-seeking population.
Methods
We analyzed 72 117 newborn specimens collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification.
Results
Statewide seroprevalence was estimated to be 0.03% (90% credible interval CI, 0.00–0.11) in November 2019 and rose to 1.47% (90% CI: 1.00–2.13) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onward, reaching 2.15% (90% CI: 1.56–2.98) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black (β = .024; 90% CI: 0.004–0.044); i.e., a 10% increase in community percent non-Hispanic Black was associated with 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter.
Conclusions
Cumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable.
Measurement of maternal antibodies in specimens collected for newborn screening offers a statewide source of seroprevalence data independent of case testing. We analyzed 72 117 Massachusetts specimens collected from November 2019–December 2020 during the COVID-19 pandemic and estimated longitudinal trends.
To evaluate the incidence, disease spectrum, and genetic characteristics of inherited metabolic disorders (IMDs) of newborns in Quanzhou area, China. We analyze the expanded newborn screening results ...of IMDs detected by tandem mass spectrometry (MS/MS) during 5 years. Suspected positive patients were diagnosed through next-generation sequencing and validated by Sanger sequencing. In addition, multiplex ligation-dependent probe amplification technology has also been applied to assist in diagnosis of diseases with deletion or duplication mutations. A total of 364,545 newborns were screened, 130 IMDs were identified yielding an incidence of 1:2804. In addition, 9 cases of maternal disorders were also identified by our MS/MS newborn screening program. There were 42 newborns with amino acid disorders (1:8680), 39 with organic acid disorders (1:9347), and 49 with fatty acid oxidation disorders (1:7440). Unlike other studies, our study indicated that fatty acid oxidation disorder has the highest proportion (37.7%), particularly primary carnitine deficiency (PCD) with incidence up to 1:10,126 was the most common disorder in the region. The recurrent mutations of relatively common diseases like PCD, phenylalanine hydroxylase deficiency, short-chain acyl-CoA dehydrogenase deficiency, citrin deficiency, glutaric acidemia type I, isobutyryl-CoA dehydrogenase deficiency, and multiple acyl-CoA dehydrogenase deficiency in this region were also clearly elucidated. Therefore, our data indicated that IMDs are never uncommon in Quanzhou, the disease spectrum and genetic backgrounds were clearly elucidated, contributing to the treatment and prenatal genetic counseling of these disorders in this region.
•Our experience shows a different story that fatty acid oxidation disorder has the highest proportion.•Primary carnitine deficiency (PCD) with incidence up to 1:10,126 was the most common disorder in the region.•The recurrent mutations of relatively common diseases were clearly elucidated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the effectiveness of newborn screening for sickle cell disease in eastern Jamaica by determining what proportion of screen-positive infants were registered with the Sickle Cell Unit by ...2 months (60 days) of age and identifying parents’ perceptions of facilitators and barriers impacting age at registration.
This cross-sectional study used a mixed method approach. Ages at diagnosis confirmation and first clinic visit were recorded for screen-positive infants born between February 1, 2015, and November 15, 2017. All parents were invited to complete the survey, and early and late attendees were invited to participate in the qualitative aspect of the study. A researcher-designed questionnaire and an interview guide based on the Capability, Opportunity, Motivation, Behavior, and health belief models examined factors that may affect time to registration. Quantitative data were analyzed to yield descriptive statistics using Stata®v14. All interview data were coded. Similar codes were grouped together into themes.
Most (97.7%) of the 133 screen-positive infants had their diagnosis confirmed. Only 40% had their first clinic visit by age 60 days. Denial of the diagnosis, poor communication, and the costs of treatment and transportation were perceived barriers to registration, whereas family support was a facilitator.
Diagnosis confirmation was almost universal, but most infants did not attend clinic by 2 months of age. In-depth interviews have identified several facilitators and barriers that can be targeted to improve early registration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pompe disease is a rare and deadly muscle disorder. As a clinical entity, the disease has been known for over 75 years. While an optimist might be excited about the advances made during this time, a ...pessimist would note that we have yet to find a cure. However, both sides would agree that many findings in basic science—such as the Nobel prize-winning discoveries of glycogen metabolism, the lysosome, and autophagy—have become the foundation of our understanding of Pompe disease. The disease is a glycogen storage disorder, a lysosomal disorder, and an autophagic myopathy. In this review, we will discuss how these past discoveries have guided Pompe research and impacted recent therapeutic developments.
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