Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management.

AIM

To describe the severity of sickle cell disease (SCD) in newborns in Belgium and evaluate the impact of neonatal screening (NS) on clinical outcome.

METHODS

Universal NS of umbilical cord blood for hemoglobinopathy was progressively deployed in Brussels and Liège starting in 1994. No particular population was targeted. Samples were analyzed initially using the isoelectric focusing technique and since 2008 the capillary electrophoresis technique. If a hemoglobin variant was suspected, further analysis was carried out using high performance liquid chromatography. Children presenting major hemoglobinopathy, especially SCD, were referred to a specialized centre for comprehensive management. Preventive measures included antipneumococcal prophylaxis immunization/antibiotic therapy, parental training to recognize severe anemia and splenic sequestration, and transcranial ultrasound recording for early detection of intracranial stenosis. A database was set up in Belgium to collect clinical and laboratory data including parental phenotype, diagnostic technique (neonatal screening or not), major clinical events (episodes of dactylitis, acute chest syndrome, severe anemia, infection, etc), number and duration of required hospitalizations, and treatment used.

RESULTS

Screening of 222352 newborns in maternity units in Brussels led to diagnosis of SCD in 145 patients, Adequate data for analysis of clinical outcome was available for 96 of these children born before 2007. Median age in the study group was 4.2 years and the total duration of follow-up was 510 years. Most cases occurred in families from the Democratic Republic of Congo. (64/96 patients; 66.7%) and involved homozygous hemoglobin S disease (80/96 patients; 83.3%). Twenty-seven percent of patients (26/96) presented no severe clinical events during the study (17 SS, median age 2,1 years (0-13.1 years). Conversely 33% presented an episode of dactylitis and 47.9% (46/96) presented recurrent vasoocclusive crises. Severe anemia was observed in 39.6% (38/96) of cases. Six patients (6.3%) developed septicemia despite prophylactic antibiotic therapy and anti-pneumococcal immunization using heptavalent conjugate vaccine and polysaccharide vaccine, No penicillin-resistant strains were observed. The incidence of stroke was 2.1% (3/96). Two patients presenting homozygous hemoglobin S disease died due to septicemia due to non-compliance with antibiotic therapy in one case and severe anemia in one case. All episodes of septicemia and both deaths occurred at the beginning of the NS program. Hydroxyurea therapy was used in 30 patients (31.2%) including 7 in whom transcranial Doppler depicted blood flow abnormalities and 8 in whom allogeneic bone marrow transplantation was performed.

CONCLUSIONS

Sickle cell disease is still associated with high morbidity and mortality but clinical care has improved and no death has occurred in the last 10 years. NS is an effective tool for early detection and management of SCD. Neonates with SCD diagnosed by NS in Belgium presented severe manifestations, but clinical outcomes were improved by comprehensive management.