PF738 MORTALITY IN CHILDREN WITH SICKLE CELL DISEASE IN METROPOLITAN FRANCE FROM 2000 TO 2015
Authors: Brousse V. , Desselas E. , Kaguelidou F. , Benkerrou M. , De Montalembert M. , Odievre M.‐H. , Lesprit E. , Rumpler E. , Fontanet A. , Thuret I. , Pondarre C. 
Published: June 2019

Background:

Sickle cell disease (SCD) is the most frequent genetic disease screened at birth in France. In developed countries, there has been a spectacular drop of the mortality rate during childhood. This progress has been achieved with the progressive implementation of preventive, supportive and therapeutic measures.

Aims:

The main objective of this study was to update and analyze SCD pediatric mortality in metropolitan France during a 15‐year period, specifically since 2000 when a national targeted newborn screening program was implemented.

Methods:

Identification of cases of pediatric deaths was based on a survey through the national French sickle cell disease network (Filière Nationale des Maladies Rares du Globules Rouge et de l’Erythropoïèse). Inclusion criteria for the study were patients diagnosed with SCD, followed‐up in metropolitan France, aged under 18 years at the time of death, with a fatal outcome recorded between 01/01/2000 and 31/12/2015.

Results:

A total of 84 fatal cases were reported by all but one center of the network (n = 48).During the same period, the national French death registry (CEPIDC) reported 81 fatal cases in children under 18 with SCD as major or associated cause of death. Cases with missing or unavailable data (n = 4), that occurred following hematopoietic stem cell transplantation (n = 2) and cases regarding children who had been mainly followed abroad (n = 5) were excluded from analysis. The remaining 73 cases were thereafter analyzed.

The pediatric mortality rate for SCD was 0,162/100 person‐year (IC95%: 0,122–0,209) and stable during the study period. Under‐five mortality rate was 0,175/ 100 person‐year (IC95%: 0,124–0,239). Median age at death for all cases was 43,5 (0–215) months (3 years 7 months). SCD was diagnosed following newborn screening in 94.4% of cases (n = 69) and was distributed as follows: SS or Sß°‐thalassemia n = 63 (86.3%), SC (n = 4, 5.5 %) Sß+
−thalassemia (n = 3, 4.1%), SD‐Punjab n = 1, and unknown (n = 2). Regardless of genotypes, the cause of death was related to SCD in the majority of cases (n = 54; 73.9%). Altogether, infection was the leading cause (n = 22; 30.1%), followed by hematological (n = 15; 20.5%), neuro‐vascular (n = 10; 13.7%), or cardio‐thoracic (n = 7; 9.6%) causes. Median age at death was lower for infectious and hematological causes (39 [1–185] and 33 [3–184] months respectively), and older for neuro‐vascular and cardio‐thoracic causes (141 [68–210] and 84 [38–215] months respectively).

Infection‐related deaths concerned 21 (95.5%) children with SS/Sß°‐thalassemia genotypes, with a median age at death of 39 months (1–185). The majority died in a context of septic shock (n = 13; 59%), with no microbiological identification in 9 cases (40.9%). A pneumococcal invasive infection with a clinical presentation of either bacteremia or meningitis was evidenced in 8 children (36.3% of infectious causes, 10.9% of all causes). In 2 of these cases, the strains were included in the 23‐valent pneumococcal polysaccharide vaccine (12F and 15B). Although these children had been duly vaccinated, they were reported to be non‐compliant to penicillin prophylaxis.

Among the SCD‐related causes of deaths, over 1/3 were considered preventable deaths, with a significant lack of compliance specifically reported in 13 medical charts (24.1%).

Summary/Conclusion:

These results highlight the need for curative therapies and continued improvement in the comprehensive careincluding psychosocial support of a particularly vulnerable population.