Long-term language outcomes in children with prenatal virus exposure

Abstract Prenatal exposure to viruses and toxins places a developing fetus at risk for neurodevelopmental, motor, and sensory deficits that may directly or indirectly impact language ability. To date, most research on prenatal exposure effects have focused on clearly identifiable sequelae (e.g., microcephaly, hearing loss) that can be detected shortly after birth. This approach omits the much larger group of children with a history of prenatal exposure who appeared asymptomatic at birth or during infancy. We have demonstrated that children exposed to the Zika virus (ZIKV) who were asymptomatic at birth exhibit a slower rate of communicative than cognitive development during infancy that cannot be explained by nonverbal cognitive delays or peripheral hearing loss. Our more recent data from exposed and not exposed children during the preschool age indicate group differences in language and communicative skills. The central hypothesis of the proposed study is that prenatal viral exposure can result in altered language development in the absence of peripheral hearing loss or nonverbal cognitive disabilities, that these characteristics become more apparent later in childhood, and can be predicted by well-selected, sensitive behavioral and physiological measures. Children born during the ZIKV pandemic in Brazil in 2015-2017 present a unique cohort with objectively documented exposure status. We have begun study of this well-characterized cohort to evaluate language characteristics and identify auditory neural markers. This application proposes to characterize the impact of prenatal virus exposure on the development of language by addressing these specific aims: Specific Aim 1: To comprehensively characterize language development in school-age children with prenatal exposure to ZIKV. Studies typically have followed exposed children only through toddlerhood and utilized limited language measures. Emerging data suggest that language difficulties increase as these children get older despite normal peripheral hearing and typical cognitive skills. Specific Aim 2: To characterize auditory neural function in children with prenatal ZIKV exposure. Studies of auditory function to date have focused on peripheral hearing sensitivity, which is rarely abnormal, and have not systematically examined auditory neural processing, particularly for speech stimuli. Specific Aim 3: To construct a model that describes concurrent and predictive relationships between language ability, biological, cognitive, and environmental factors in children with prenatal ZIKV exposure. The proposed research facilitates collaboration among researchers in the USA and in Brazil who follow some of the largest cohorts of ZIKV-exposed children in the world. The opportunity to study this well-defined cohort of children will improve understanding of the impact of prenatal virus exposure on language development and auditory neural function, inform future studies investigating the effects of prenatal and postnatal factors on language outcomes, and provide auditory markers for earlier identification of those at risk for language difficulties.