The Alberta Newborn Screening Approach for Sickle Cell Disease: The Advantages of Molecular Testing

Abstract

Sickle cell disease (SCD), a group of inherited red blood cell (RBC) disorders caused by pathogenic variants in the beta-globin gene (HBB), can cause lifelong disabilities and/or early mortality. If diagnosed early, preventative measures significantly reduce adverse outcomes related to SCD. In Alberta, Canada, SCD was added to the newborn screening (NBS) panel in April 2019. The primary conditions screened for are sickle cell anemia (HbS/S), HbS/C disease, and HbS/β thalassemia. In this study, we retrospectively analyzed the first 19 months of SCD screening performance, as well as described our approach for screening of infants that have received a red blood cell transfusion prior to collection of NBS specimen. Hemoglobins eluted from dried blood spots were analyzed using the Bio-Rad™ VARIANT nbs analyzer (Bio-Rad Laboratories, Inc., Hercules, CA, USA). Targeted sequencing of HBB was performed concurrently in samples from all transfused infants. During the period of this study, 43 of 80,314 screened infants received a positive NBS result for SCD, and of these, 34 were confirmed by diagnostic testing, suggesting a local SCD incidence of 1:2400 births. There were 608 infants with sickle cell trait, resulting in a carrier frequency of 1:130. Over 98% of non-transfused infants received their NBS results within 10 days of age. Most of the 188 transfused infants and 2 infants who received intrauterine transfusions received their final SCD screen results within 21 ± 10 d of birth. Our SCD screening algorithm enables detection of affected newborns on the initial NBS specimen, independent of the reported blood transfusion status.

Population characterization of mutations for sickle cell anemia and its treatment: One step towards personalized medicine for the disease

“…En la actualidad, procesos como los cambios migratorios y nuevas modificaciones en la matriz étnica han generado la necesidad de establecer políticas públicas de screening neonatal para la ACF en comunidades donde antes no se realizaban 37 . Por ejemplo, se ha descrito en la literatura que algunos haplotipos de la ACF podrían co-segregarse y potencialmente asociarse con diferentes niveles de HF [38][39][40][41][42][43][44][45] .…”

Sickle cell disease in Ontario, Canada: an epidemiologic profile based on health administrative data

“…At the time of publication, newborn screening for sickle cell disease was being performed in all regions of Canada except Manitoba and Newfoundland and Labrador, but the number of years of data available for analysis varies; Alberta, the most recent addition, began newborn screening only in 2019. 21 A more important consideration is the inclusion of data from out-patient visits. In Canada, this information is captured by NACRS, but the degree to which this database includes visits to emergency departments varies by province.…”

In response: The unintended consequences of hemoglobin solubility testing

“…3 Additionally, SICKLEDEX testing can result in false positives from hyperlipidemia and elevated hematologic counts, which could influence blood collection centers to perform more expensive confirmatory testing on blood donors that have a very low likelihood of SCT. 4 These false positives could complicate blood inventory management, as those that tested SICKLEDEX positive would have increased labor costs to maintain dual inventories for neonates for confirmatory testing.…”

“…Comparatively, the frequency of SCT in the United States is 1:67. 4,5 Although the frequency of SCT in the general population may differ from the blood donor population, the positive predictive value is theoretically much greater in the United States given the higher frequency of SCT, as well as the potential for transfusing a donor RBC unit containing HbS (or potentially other variants). This represents an important area for future investigations to elucidate the true prevalence of HbS variants in various blood donor populations.…”