Mortality from Sickle Cell Disease in Brazil

Introduction: Many individuals with sickle cell disease (SCD) die before age 60, despite early detection via neonatal screening and implementation of treatments such as vaccines and antibiotic prophylaxis and the increasing availability of disease modifying therapies.  This study evaluated the causes and independent predictors of mortality in a SCD population in Brazil. Methods: This analysis was performed within the multicenter Recipient Epidemiology and Donor Evaluation (REDS)-III SCD cohort which was established at 6 participating centers in Brazil from 2013-2018.  Participants were randomly selected as eligible and recruited at routine visits. Medical records were reviewed to abstract clinical and laboratory data.  Mortality and cause of death were confirmed by local chart review as well as linkage to the Brazilian death certificate database. Key variables were compared between deceased and alive participants using Chi2 test for categorical variables and Mann-Whitney test for continuous variables. Stepwise logistic regression then a Cox regression multivariable model was performed to identify independent predictors for mortality within the adult participants. Results: There were 2,793 participants in the cohort (1,558, 55.8%, <18 years) and 159 (5.7%) were confirmed to be deceased by the end of follow up: 142 adults (>18 years) and 17 children. The median life expectancy was 65.7. Within adults, infection was the main identifiable cause of death (33.3%), followed by pulmonary causes (25.2%) and neurologic causes (14.5%). Five (3.1%) patients had an unknown cause of death. Independent predictors of mortality were age [Hazard Ratio (HR) 1.03; 95% CI 1.01-1.04; p<.01], iron overload (HR 1.68; 95% CI1.09-2.60; p<.02] and previous hospital admission (HR 1.68; 95% CI 1.10-2.56; p<.02). Discussion: Mortality in Brazilian SCD individuals is shifting from children to adults, with increased rates of death in the third and fourth decades of life. Individuals with SCD are dying 10 years before the general population in Brazil.  The main causes of death in our cohort were infections, acute chest syndrome and stroke, highlighting the need for prompt recognition and treatment of these complications. Screening and treatment for iron overload and closer monitoring and consideration of disease modifying therapies for patients with frequent hospital admissions are important as both were identified as independent predictors of mortality. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding for this study was provided by the REDS-III contract of the NHLBI/NIH under HHSN2682011-00007I. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by all six blood centers’ ethical committees, the Brazilian National Ethical Committee for Research (CAAE: 46981615.0.1001.0065), and the Institutional Review Board at Vitalant Research Institute (VRI) in San Francisco, CA. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Authors are able to make fully available and without restriction all data underlying their findings.