Association between Sensorineural Hearing Loss and Homozygous Sickle Cell Anemia: A Meta-Analysis

Abstract

Introduction Sickle cell anemia (SCA) is caused by the homozygous inheritance of the βS allele (HbSS). SCA's destructive pathogenesis drives a state of continual oxidative stress and vascular inflammation due to accelerated auto-oxidation, iron de-compartmentalization, and inflammatory cell-derived oxidants. Continuous oxidative stress and vascular inflammation bolsters vaso-occlusion and ischemia-reperfusion cycling, impacting the functionality of multiple organ systems. The auditory system is particularly vulnerable to vaso-occlusive events as an end organ system. Repetitive damage secondary to recurrent SCA crises presents phenotypically as sensorineural hearing loss (SNHL), negatively impacting many children and adults living with SCA. A SCA crisis leads to stasis of the labyrinthine artery which supplies the inner ear, leading to hypoxia of the Organ of Corti and the Stria Vascularis within the cochlea and causing death of outer hair cells--important for amplification of sound. This results in permanent inner ear damage and hearing loss. Hearing loss in children has a documented negative effect on academic performance, speech and language development as well as self-image. For adults, hearing loss can have significant impact on career choices and effective communication in the workplace. Previous studies estimating the rate of SNHL in SCA suffer from significant design flaws, making broad application difficult. The major design flaws were: 1) no matched control population, 2) varying definitions of what qualifies as SNHL, and 3) absence of defined demographics within SCA and control groups. To address these flaws, a strict meta-analysis of the literature was performed comparing the prevalence of hearing loss in SCA and the general population. Methods & Results A comprehensive-- SCOPUS, PubMed, Google Scholar, and Medline--literature search was conducted to identify the prevalence of SCA pediatric SNHL, published between January 1970 and December 2018. Data was extracted by two reviewers per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, whereby there was no blinding to authors, journals of publication, or the results of the studies. Conference abstracts, posters, and single patient case reports were not excluded. Inclusion criteria included studies that examined exclusively SCA populations and rate of SNHL with a clearly defined threshold for hearing loss. Additionally, papers needed to include distinctly defined age ranges and a non-SCA control population. The initial search yielded 49 studies, with 21 studies meeting the inclusion criteria. Of the 21 studies identified, only 6 exclusively examined pediatric patients while the remaining were mixed adult/pediatric studies. To perform the analysis, we conducted a random effect (DerSimonian-Laird) meta-analysis. A Haldane-Anscombe correction was used to account for cases of no hearing loss within certain groups with small samples. The log odds ratio (LogOR) for SNHL in the mixed adult/pediatric population was 1.9 (95% CI 1.33 - 2.4) and the LogOR for SNHL in the pediatric only population was 1.4 (95% CI 0.781 - 2.1). These results indicate a strong association between SNHL and SCA in the adult and pediatric population. Conclusions SNHL among children can have deleterious impacts on their development, this meta-analysis showed a significant association between SCA and the development SNHL. The stronger association between SNHL in AN adult population compared to A pediatric population showed that there is worsening of SNHL over time secondary to SCA. At present, the data implies there should be an increase in audiological testing and screening in all patients diagnosed with SCA. (add in all forms of SCD) Clinical care providers should also make themselves aware of this under-reported and severe pathology in their patient population. The research community must also make efforts to standardize their approaches to measuring and observing this phenomenon to make certain that all future studies are clinically applicable and translatable. Figure Disclosures Vercellotti: Mitobridge, an Astellas Company: Consultancy, Research Funding.