Impaired brainstem auditory evoked potentials after in utero exposure to high dose paracetamol exposure

Abstract

Paracetamol is an analgesic and antipyretic medication regarded as the safest over-the-counter pain and fever relief option during pregnancy. Paracetamol and its metabolites are known to reach the developing fetus through direct placental transfer and can cross the blood brain barrier. Several recent, large-scale epidemiologic studies suggest that in utero paracetamol exposure can increase the risk of neurodevelopmental conditions, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and developmental delay (DD). Since auditory processing deficits are a common feature of ASD, we hypothesized that animals exposed to paracetamol in utero will have impaired auditory brainstem function. We investigated this hypothesis by recording and analyzing click-evoked auditory brainstem responses (ABR) at postnatal day 21 and 29 in Sprague-Dawley rats. In utero exposure to high dose paracetamol exposure had no impact on body or brain weight. However, high dose paracetamol exposure did significantly delay ear opening and resulted in elevated ABR thresholds, and longer wave and interwave latencies. These changes in wave latency extended to the highest click intensity tested but were most severe near threshold. This data suggests that development and function of the auditory brainstem may be impacted by high dose paracetamol exposure and that simple, non-invasive tests of auditory function have utility as an early screening tool for neurodevelopmental disorders.