Pediatric Laryngopharyngeal Reflux Disease and Otitis Media With Effusion: A Systematic Review and Meta-Analysis

To explore the relationship between recurrent otitis media (ROM), chronic media otitis with effusion (COM), and laryngopharyngeal reflux disease (LPRD) in pediatric populations.

PubMed, Scopus, and Cochrane databases.

Two investigators independently screened papers with PRISMA guidelines considering the following primary outcomes: LPRD prevalence in pediatric ROM and COM, diagnostic methods used, and detection rates of gastroduodenal markers in middle ear effusions. Two random-effects meta-analyses were performed to estimate the pooled prevalence of pepsin/pepsinogen detection in middle ear effusions and to compare pepsin concentrations between COM/ROM patients and controls using standardized mean differences (Hedges' g).

Twenty-eight studies were included (2070 pediatric patients). The cumulated gastroesophageal reflux disease prevalence in COM children was estimated to 50.7%, while 27.6% of children reported pharyngeal reflux events. Fifteen studies measured pepsin in effusions, reporting a pooled detection prevalence of 72.5% (95% CI: 53.7%-88.0%), rising to 85.6% with ELISA-based methods versus 17.9% with enzymatic assays. The pooled standardized mean difference in pepsin concentration between OME patients and controls was large and significant (Hedges' g = 1.92, 95% CI: 0.58-3.25, P = .005). Alkaline-activated gastroduodenal mediators were assessed in 3 studies, with detection rates ranging from 39.6% to 100% for trypsin and from 32% to 42% for bile salts. Substantial heterogeneity was found for COM/ROM and reflux disease diagnostic criteria, gastroduodenal biomarker measurements, and outcomes.

Gastroduodenal biomarkers are present in middle ear effusions of children with COM and ROM. Future prospective transversal studies exploring alkaline-activated enzymes and bile salts in effusion of children with documented pharyngeal reflux events are needed.