Teaching Matters, Volume 2: Essays by the faculty and staff at the University of Maine at Farmington

Essays by the faculty and staff at the University of Maine at Farmington.https://scholarworks.umf.maine.edu/publications/1087/thumbnail.jp

Incidental detection of classical galactosemia through newborn screening for phenylketonuria: a 10-year retrospective audit to determine the efficacy of this approach

In the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an “Other disorder suspected” (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via NBS and estimate the incidence of CG in live births in the UK. A survey was sent to all UK NBS laboratories to collate CG cases diagnosed in the UK from 2010 to 2020. Cases of CG diagnosed were determined if detected clinically, NBS, or by family screening, as well as age at diagnosis. Cases referred via the ODS pathway were also collated, including the final diagnosis made. Responses were obtained from 13/16 laboratories. Between 2010 and 2020, a total of 6,642,787 babies were screened, and 172 cases of CG were identified. It should be noted that 85/172 presented clinically, 52/172 were identified by NBS, and 17/172 came from family screening. A total of 117 referrals were made via the ODS pathway, and 45/117 were subsequently diagnosed with CG. Median (interquartile range) age at diagnosis by NBS and clinically was 8 days (7–11) and 10 days (7–16), respectively (Mann–Whitney U test, U = 836.5, p-value = 0.082). The incidence of CG is 1:38,621 live births. The incidence of CG in the UK is comparable with that of other European/western countries. No statistical difference was seen in the timing of diagnosis between NBS and clinical presentation based on the current practice of sampling on day 5. Bringing forward the day of NBS sampling to day 3 would increase the proportion diagnosed with CG by NBS from 52/172 (30.2%) to 66/172 (38.4%)

Consistency in the assessment of dried blood spot specimen size and quality in U.K. newborn screening laboratories

In 2015, U.K. newborn screening (NBS) laboratory guidelines were introduced to standardize dried blood spot (DBS) specimen quality acceptance and specify a minimum acceptable DBS diameter of ≥7 mm. The UK ‘acceptable’ avoidable repeat rate (AVRR) is ≤2%. To assess inter-laboratory variability in specimen acceptance/rejection, two sets of colored scanned images (n = 40/set) of both good and poor-quality DBS specimens were distributed to all 16 U.K. NBS laboratories for evaluation as part of an external quality assurance (EQA) assessment. The mean (range) number of specimens rejected in the first EQA distribution was 7 (1–16) and in the second EQA distribution was 7 (0–16), demonstrating that adherence to the 2015 guidelines was highly variable. A new minimum standard for DBS size of ≥8 mm (to enable a minimum of six sub-punches from two DBS) was discussed. NBS laboratories undertook a prospective audit and demonstrated that using ≥8 mm as the minimum acceptable DBS diameter would increase the AVRR from 2.1% (range 0.55% to 5.5%) to 7.8% (range 0.55% to 22.7%). A significant inverse association between the number of specimens rejected in the DBS EQA distributions and the predicted AVVR (using ≥8 mm minimum standard) was observed (r = −0.734, p = 0.003). Before implementing more stringent standards, the impact of a standard operating procedure (SOP) designed to enable a standardized approach of visual assessment and using the existing ≥7 mm diameter (to enable a minimum of four sub-punches from two DBS) as the minimum standard was assessed in a retrospective audit. Implementation of the SOP and using the ≥7 mm DBS diameter would increase the AVRR from 2.3% (range 0.63% to 5.3%) to 6.5% (range 4.3% to 20.9%). The results demonstrate that there is inconsistency in applying the acceptance/rejection criteria, and that a low AVVR is not an indication of good-quality specimens being received into laboratories. Further work is underway to introduce and maintain standards without increasing the AVRR to unacceptable levels

Incidental Detection of Classical Galactosemia through Newborn Screening for Phenylketonuria: A 10-Year Retrospective Audit to Determine the Efficacy of This Approach

Peer reviewed: TruePublication status: PublishedIn the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an “Other disorder suspected” (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via NBS and estimate the incidence of CG in live births in the UK. A survey was sent to all UK NBS laboratories to collate CG cases diagnosed in the UK from 2010 to 2020. Cases of CG diagnosed were determined if detected clinically, NBS, or by family screening, as well as age at diagnosis. Cases referred via the ODS pathway were also collated, including the final diagnosis made. Responses were obtained from 13/16 laboratories. Between 2010 and 2020, a total of 6,642,787 babies were screened, and 172 cases of CG were identified. It should be noted that 85/172 presented clinically, 52/172 were identified by NBS, and 17/172 came from family screening. A total of 117 referrals were made via the ODS pathway, and 45/117 were subsequently diagnosed with CG. Median (interquartile range) age at diagnosis by NBS and clinically was 8 days (7–11) and 10 days (7–16), respectively (Mann–Whitney U test, U = 836.5, p-value = 0.082). The incidence of CG is 1:38,621 live births. The incidence of CG in the UK is comparable with that of other European/western countries. No statistical difference was seen in the timing of diagnosis between NBS and clinical presentation based on the current practice of sampling on day 5. Bringing forward the day of NBS sampling to day 3 would increase the proportion diagnosed with CG by NBS from 52/172 (30.2%) to 66/172 (38.4%)

Consistency in the Assessment of Dried Blood Spot Specimen Size and Quality in U.K. Newborn Screening Laboratories.

Peer reviewed: TrueAcknowledgements: We acknowledge all staff in U.K. newborn screening laboratories.Publication status: PublishedIn 2015, U.K. newborn screening (NBS) laboratory guidelines were introduced to standardize dried blood spot (DBS) specimen quality acceptance and specify a minimum acceptable DBS diameter of ≥7 mm. The UK 'acceptable' avoidable repeat rate (AVRR) is ≤2%. To assess inter-laboratory variability in specimen acceptance/rejection, two sets of colored scanned images (n = 40/set) of both good and poor-quality DBS specimens were distributed to all 16 U.K. NBS laboratories for evaluation as part of an external quality assurance (EQA) assessment. The mean (range) number of specimens rejected in the first EQA distribution was 7 (1-16) and in the second EQA distribution was 7 (0-16), demonstrating that adherence to the 2015 guidelines was highly variable. A new minimum standard for DBS size of ≥8 mm (to enable a minimum of six sub-punches from two DBS) was discussed. NBS laboratories undertook a prospective audit and demonstrated that using ≥8 mm as the minimum acceptable DBS diameter would increase the AVRR from 2.1% (range 0.55% to 5.5%) to 7.8% (range 0.55% to 22.7%). A significant inverse association between the number of specimens rejected in the DBS EQA distributions and the predicted AVVR (using ≥8 mm minimum standard) was observed (r = -0.734, p = 0.003). Before implementing more stringent standards, the impact of a standard operating procedure (SOP) designed to enable a standardized approach of visual assessment and using the existing ≥7 mm diameter (to enable a minimum of four sub-punches from two DBS) as the minimum standard was assessed in a retrospective audit. Implementation of the SOP and using the ≥7 mm DBS diameter would increase the AVRR from 2.3% (range 0.63% to 5.3%) to 6.5% (range 4.3% to 20.9%). The results demonstrate that there is inconsistency in applying the acceptance/rejection criteria, and that a low AVVR is not an indication of good-quality specimens being received into laboratories. Further work is underway to introduce and maintain standards without increasing the AVRR to unacceptable levels

European survey of newborn bloodspot screening for CF: opportunity to address challenges and improve performance

European CF Society Neonatal Screening Working Group (ECFS NSWG): Sabine Renner , Max Zeyda , Elke de Wachter , Luc Regal , Felix Votava, Andrea Holubova, Marianne Skov , Tessa Morgan, Paul Bregeaut , Loretta O'Grady, Ines Bucci , Stefano Pantano , Simonetta Simonetti, Domenica De Venuto, Donatello Salvatore, Nicola Perrotti, Mimma Caloiero, Giuseppe Castaldo, Antonella Tosco, Francesca Righetti, Giovanna Pisi, Fiorella Battistini, Antonio Angeloni, Giuseppe Cimino, Giovanni Fiocchi, Antonella Angiolillo, Michela Cassanello, Luisella Alberti, Laura E Claut, Raffaele Badolato, Enza Pavanello, Benedetta Fabrizzi, Elisabetta Bignamini, Anna Cardillo, Mariangela Lombardo, Letizia Cocciadiferro, Lisa Termini, Daniela Dolce, Vito Terlizzi, Anna Tamanini, Francesca Pauro, Giancarlo la Marca, Elina Aleksejeva, Dita Gaidule-Logina, Stoika Fustik, Violeta Anastasovska, Marelle Bouva, Alastair Reid, Jennifer Cundick, Emma Lundman, Egil Bakkeheim, Katarzyna Zybert, Mariusz Oltarzewski, Laura Vilarinho, Victoria Sherman, Elena Kondratyeva, Sarah Smith, Gordana Vilotijevic Dautovic, Maria Knapkova, Zuzana Mydlova, Rosa Mª López, Valle Velasco, Felicitas Díaz Flores, Cristóbal Colón Mejeras, Eva Sl Pedersen, Ugur Ozcelik, Bulent Karadag, Halyna Makukh, Moat Stuart.European CF Society Neonatal Screening Working Group (ECFS NSWG): INSA - Laura VilarinhoBackground: The aim of this study was to record the current status of newborn bloodspot screening (NBS) for CF across Europe and assess performance. Methods: Survey of representatives of NBS for CF programmes across Europe. Performance was assessed through a framework developed in a previous exercise. Results: In 2022, we identified 22 national and 34 regional programmes in Europe. Barriers to establishing NBS included cost and political inertia. Performance was assessed from 2019 data reported by 21 national and 21 regional programmes. All programmes employed different protocols, with IRT-DNA the most common strategy. Six national and 11 regional programmes did not use DNA analysis. Conclusions: Integrating DNA analysis into the NBS protocol improves PPV, but at the expense of increased carrier and CFSPID recognition. Some programmes employ strategies to mitigate these outcomes. Programmes should constantly strive to improve performance but large datasets are needed to assess outcomes reliably.Highlights: In 2022, newborn bloodspot screening (NBS) for CF is undertaken in 30 European countries, 26 of them are national programmes; Some programmes are still not achieving ECFS standards. Compared to 2014, there is an improvement in sensitivity but a deterioration in achieving a sufficient PPV; There continues to be a wide variety of approaches, but the majority of national programmes are now using DNA analysis as a 2nd tier; This survey demonstrates areas of good practice, but there is considerable scope for improvement in the quality of NBS for CF across Europe; The framework of the 20 parameters to calculate the 8 key outcomes should be part of any annual report of a CF NBS programme, and thus improve future surveys.The survey was funded by the European CF Societyinfo:eu-repo/semantics/publishedVersio