Newborn Screening for Sickle Cell Disease in Catalonia between 2015 and 2022-Epidemiology and Impact on Clinical Events

Abstract

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia's NBS program has effectively reduced morbidity and improved affected children's quality of life.

Keywords: clinical events; hemoglobinopathies; newborn screening; sickle cell disease; treatment intervention.

Figure 1

Catalonian NBS process. DBS: dried blood spots; SCD: sickle cell disease; CRU: Clinical Reference Unit; HPLC: high-performance liquid chromatography.

Figure 2

Clinical events by year of follow-up. SG: screened group; UG: unscreened group; Total: total clinical events; SCD-related: sickle cell disease-related clinical events; ER: visits to the emergency department; HOS: hospitalizations. The level of statistical significance is indicated by asterisks: ** p < 0.001; **** p < 0.00001.

Figure 3

Mean number of SCD-related clinical events by year of age in the study cohorts. SG: screened group; UG: unscreened group. The level of statistical significance is indicated by asterisks: * for p < 0.05, ** for p < 0.01, and *** for p < 0.001.

Figure 4

Clinical events by genotype in the study cohorts. SG: screening group; UG: unscreened group; Total: total clinical events; SCD-related: sickle cell disease-related clinical events; ER: visits to the emergency department; HOS: hospitalizations. The level of statistical significance is indicated by asterisks: * p < 0.05; ** p < 0.01, ns (not significant). Genotypes: SS (HbSS); SC(HbSC); Sβ⁰(HBSβ⁰).

Figure 5

Impact of hydroxyurea treatment on the events in both the UG and SG. UG-PreHU: unscreened group pre-hydroxyurea; UG-PostHU: unscreened group post-hydroxyurea; SG-PreHU: screened group pre-hydroxyurea; SG-PostHU: screened group post-hydorxyurea; Total: total clinical events; SCD-related: sickle cell disease-related clinical events; ER: visits to the emergency department; HOS: hospitalizations. The level of statistical significance is indicated by asterisks: **** p < 0.0001, ns (not significant).

Figure 6

Kaplan–Meier curves for event-free survival by specific events in the SG and UG cohorts. Each graph represents the six-year survival estimate since birth without the corresponding SCD-related event. SG: screened group; UG: unscreened group. (a) Six-year Kaplan–Meier estimate without vaso-occlusive crisis (VOC) was different in both groups (57.0% vs. 30.3%, p = 0.03). (b) Six-year Kaplan–Meier estimate without acute chest syndrome (ACS) was not different in both groups (73.5% vs. 54.3%, p = 0.06). (c) Six-year Kaplan–Meier estimate without infections of probable bacterial origin (BI) was not different in both groups (71.3% vs. 69.8% p = 1.0). (d) Six-year Kaplan–Meier estimate without infections of probable acute anemia requiring transfusion (TRF) was not different in both groups (64.5% vs. 69.7%, p = 0.9). (e) Six-year Kaplan–Meier estimate without acute splenic sequestration (ASSC) was not different in both groups (93.8% vs. 85.0%, p = 0.12).