False positive newborn hearing screening results and autism spectrum disorder

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Abstract Biomarkers have garnered great interest in the study of autism spectrum disorder (ASD) due to their potential to inform etiology as well as diagnostic risk prediction. Despite the diversity of biological processes implicated in ASD (epigenetic, metabolic, immune), final common pathways involve disruptions to prenatal and/or early postnatal brain development. As a result, brain-based biomarkers – particularly those that can be assessed during early infancy -- hold unique potential in advancing our understanding of the disorder. To this end, auditory brainstem responses (ABRs) may be a biomarker worth further consideration. ABRs exhibit strong cross-sectional associations with ASD, can be non-invasively and reliably assessed in young infants, and are a common target of population-based newborn hearing screening programs. However, it remains unclear whether ABR alterations precede the onset of ASD symptoms, are confounded by or interact with known ASD risk factors (e.g., family history, perinatal risk), or generalize to other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder). The objective of this proposal is to evaluate whether false positive, ABR-based newborn hearing screening results (i.e., failure in the absence of hearing loss) are prospectively associated with ASD. To do this, we will combine and analyze Michigan Department of Health and Human Services (MDHHS) datasets from 2004- 2020: newborn hearing screening records, birth certificates, and Medicaid claims. As part of this effort, we will evaluate whether findings differ according to known ASD risk factors (male sex; preterm delivery; sibling ASD diagnosis) and comorbidities (intellectual disability; epilepsy). We will also examine whether false positive newborn hearing screening findings are associated with attention deficit hyperactivity disorder (ADHD) – a neurodevelopmental disorder that, like ASD, is linked to perinatal etiologies as well as ABR alterations. Findings from this rigorous and well-powered population-based analysis have the potential to launch multiple lines of research that may lead to breakthroughs in our understanding of and surveillance for ASD.