Perinatal exposures and upper respiratory tract microbiome composition are associated with age at first acute otitis media episode

Acute otitis media (AOM) is the most common bacterial infection of childhood and the leading indication for antibiotic prescriptions and healthcare consultations globally. Colonization of the upper respiratory tract (URT) microbiome by bacterial respiratory pathogens precedes AOM episodes; however, the factors that influence colonization susceptibility and subsequent AOM are not well understood. We hypothesized that perinatal exposures, including mode of delivery, intrapartum antibiotic exposure, and infant feeding influence the composition of the URT microbiome at birth, modifying risk of AOM in infancy. We characterized the URT microbiome in nasopharyngeal swabs collected from 163 infants at birth. Swabs were generally collected within two days of delivery (median [IQR] collection time: 25 [17, 45] hours) and microbiome composition was evaluated with 16S rRNA V4 sequencing. Exposures evaluated included birth mode, intrapartum antibiotic exposures, and feeding type at hospital discharge. AOM episodes were identified through electronic health records data. We built Cox proportional hazards models to determine if perinatal exposures and/or microbiome characteristics at birth were associated with the time to first AOM episode in the first two years of life. URT microbiome diversity and composition were associated with feeding type at hospital discharge, wherein exclusive formula feeding was associated with increased diversity and the presence of Staphylococcus and Haemophilus spp. Increased URT microbiome diversity was associated with younger age at first AOM episode. Our findings suggest that perinatal exposures may influence the composition of the birth URT microbiome, and that this early composition may be related to AOM susceptibility in infancy. ImportanceEar infections are the most common bacterial infection of childhood and the leading indication for healthcare consultation and antibiotic receipt. Previous studies have demonstrated that the microbes that inhabit the upper respiratory tract, known as the microbiome, influence risk of ear infection. This study sought to understand how exposures around the time of birth, including delivery type, maternal antibiotic exposures, and infant feeding, influence the development of the infant microbiome, and in turn, how the microbiome is related to ear infections. An analysis of nasal swabs collected from infants shortly after birth demonstrated that increased microbial diversity is associated with earlier age at first ear infection episode. Overall, this study demonstrates that exposures in early life influence respiratory microbiome development, which contributes to infection susceptibility.