Auditory physiology in children exposed to the Zika virus

Abstract: Prenatal exposure to the mosquito-borne Zika virus (ZIKV) can cause a wide range of neurologic abnormalities and developmental disabilities. Studies in children with microcephaly due to ZIKV have identified language delays, but there is a gap in knowledge regarding the state of the auditory system because most evaluations of auditory function in these populations have been limited to newborn hearing screening and assessment of peripheral hearing sensitivity. Additionally, a large group of children with prenatal exposure to ZIKV but without microcephaly has been largely understudied despite the emerging evidence of residual ZIKV effects on speech/language development in those otherwise asymptomatic cases. Identifying auditory problems that could impact listening and communication is critical for preparing adequate care plans as the children enter school. The proposed international research collaboration will focus on filling in these knowledge gaps by systematically and comprehensively characterizing auditory function and its relationship to communicative developmental outcomes in children 4-8 years of age with history of prenatal exposure to ZIKV. The following groups will be studied: (1) children with ZIKV-related microcephaly; (2) children prenatally exposed to ZIKV without microcephaly; and (3) control subjects matched on age, sex, and socioeconomic status (SES). The proposed longitudinal study will address three specific aims: Specific Aim 1 will characterize auditory function in children with microcephaly due to the ZIKV. We hypothesize that, despite normal peripheral hearing test results, cortical responses will differ from those of age-, sex-, and SES-matched controls. Specific Aim 2 will characterize auditory function in children exposed to the ZIKV but without microcephaly. We hypothesize that this group will have altered auditory function, indexed by atypical cortical responses. Specific Aim 3 will evaluate concurrent and predictive relationships between auditory neural responses and language outcomes in children with prenatal exposure to ZIKV with and without microcephaly. For all participants, we will acquire auditory physiologic responses from the middle ear through cortex and measures of speech/language ability at three time points over 30 months to identify potential indicators related to risk for delays in development of speech, language, and listening problems. We will also examine how additional risk factors, medical history, and general neurodevelopment relate to auditory response findings. The proposed work will be accomplished through a collaboration between scientists at Vanderbilt University Medical Center and researchers in two states in Brazil who follow some of the largest cohorts of ZIKV-exposed infants in the world. Colleagues in the US and Brazil will have complementary roles in providing expertise in characterizing physiologic function and developing clinical applications in this unique and important population. The results of this work will clarify the impact of ZIKV on auditory function and identify clinically useful measures for detection and management of risk for communication delays that are needed to facilitate adaptive functioning and academic success.