In utero exposure to ADHD medication and long-term offspring outcomes.

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

Does Location of Intralabyrinthine Vestibular Schwannoma Determine Objective and Subjective Vestibular Function?

BACKGROUND AND OBJECTIVE: The incidence of intralabyrinthine schwannomas is increasing, and a growing attention is given to the detrimental effects on hearing function. On the contrary, the vestibular profile of intralabyrinthine vestibular schwannomas (VSs) is still not well understood. We aimed to investigate and report the observed relationships between the intralabyrinthine location of the schwannomas and objective and subjective vestibular profile of the patients. METHODS: Retrospective cohort study of 20 consecutive individuals with sporadic intralabyrinthine schwannomas and grouped according to the intralabyrinthine location of the schwannomas. Vestibular testing consisted of the video head impulse test of all three semicircular canals, the caloric test, cervical and ocular vestibular evoked myogenic potentials, and the dizziness handicap inventory. A nonparametric unpaired t test was performed to compare groups, and Fisher's exact test was used for categorical data. RESULTS: The median video head impulse test gains (lateral, anterior, posterior) were 0.40, 0.50, and 0.75 for intravestibular schwannomas and 0.93, 1.52, and 0.91 for intracochlear schwannomas ( p = 0.0001, p = 0.009, p = 0.33), respectively. Caloric unilateral weakness had a median of 100% for intravestibular schwannomas and 14% for intracochlear schwannomas ( p = 0.0001). The mean dizziness handicap inventory was 21 for intravestibular schwannomas and 1 for cochlear schwannomas ( p = 0.02). There were no significant differences in vestibular evoked myogenic potentials according to intralabyrinthine location. CONCLUSION: By both objective and subjective measures, intralabyrinthine schwannomas with an intravestibular component has significantly worse vestibular function than schwannomas with purely cochlear involvement.

Hepatocyte nuclear factor-4 alpha in noise-induced cochlear neuropathy.

Noise-induced hearing loss (NIHL) is a problem of profound clinical significance and growing magnitude. Alarmingly, even moderate noise levels, previously assumed to cause only temporary shifts in auditory thresholds ("temporary" NIHL), are now known to cause cochlear synaptopathy and subsequent neuropathy. To uncover molecular mechanisms of this neuropathy, a network analysis of genes reported to have significantly altered expression after temporary threshold shift-inducing noise exposure was performed. The transcription factor Hepatocyte Nuclear Factor-4 alpha (HNF4α), which had not previously been studied in the context of cochlear response to noise, was identified as a hub of a top-ranking network. Hnf4α expression and localization using quantitative RT-PCR and in situ hybridization, respectively, were described in adolescent and adult mice exposed to neuropathic noise levels in adolescence. Isoforms α3 and α12 in the cochlea were also identified. At every age examined, Hnf4α mRNA expression in the cochlear apex was similar to expression in the base. Hnf4α expression was evident in select cochlear cells, including spiral ganglion neurons (SGNs) and hair cells, and was significantly upregulated from 6 to 70 weeks of age, especially in SGNs. This age-related Hnf4α upregulation was inhibited by neuropathic noise exposure in adolescence. Hnf4α silencing with shRNA transfection into auditory neuroblast cells (VOT-33) reduced cell viability, as measured with the MTT assay, suggesting that Hnf4α may be involved in SGN survival. Our results motivate future studies of HNF4α in cochlear pathophysiology, especially because HNF4α mutations and polymorphisms are associated with human diseases that may include hearing loss. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1374-1386, 2016.