Joseph P. Pillion

Prenatal antecedents of newborn neurological maturation

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24 to 38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the first weeks after birth were examined. Prenatal measures included fetal heart rate (FHR) variability, fetal movement, and coupling between fetal motor activity and heart rate patterning; neonatal outcomes include a standard neurologic examination (n = 97) and brainstem auditory evoked potential (BAEP; n = 47). Optimality in newborn motor activity and reflexes was predicted by fetal motor activity, FHR variability, and somatic-cardiac coupling predicted BAEP parameters. Maternal pregnancy-specific psychological stress was associated with accelerated neurologic maturation.

Construct Validity of the Auditory Continuous Performance Test for Preschoolers

Development of diagnostic instruments directed toward neuropsychological assessment of preschoolers lags significantly behind those available for school-age children (DeWolfe, Byrne, & Bawden, 2000). This is particularly true for measures of executive function (EF). The Auditory Continuous Performance Test for Preschoolers (ACPT-–P; Mahone, Pillion, & Hiemenz, 2001) is a computerized, Go-No-go test developed to measure selected EF skills in preschoolers. First, to determine whether performance on the ACPT-–P is associated with hearing impairment, we compared performance of children with mild hearing loss (MHL) to controls on the ACPT-–P, and measures of spatial working memory (SWM) and motor persistence (MP). There were no differences between performance of the MHL group and controls on any of these measures. Second, to examine the construct validity of the ACPT-–P, we compared performance of 40 preschoolers with ADHD to 40 age- and sex-matched controls, using the ACPT-–P to measure response preparation, sustained attention, and inhibitory control. We also compared these groups on measures of SWM and MP. The group with attention deficit hyperactivity disorder (ADHD) performed significantly worse than controls on the ACPT-–P (omissions, mean response time, variability) and MP. The ACPT-–P was correlated with the MP, but not with the SWM measure. Both the ACPT-–P and the MP measures showed low to moderate correlations with parent ratings of behavior associated with ADHD. These findings support the use of performance-based assessment of executive control skills in preschoolers suspected of having ADHD. In this age group, the ACPT-–P may be particularly useful in assessing sustained attention and response preparation and may complement behavior rating scales.

Prevalence of hearing loss in Rett syndrome

This study examined the auditory status of females with Rett syndrome (RS) using auditory brainstem response (ABR) testing and measures of acoustic admittance. Prevalence of hearing impairment in 81 female patients (age range 1 year 3 months to 39 years 8 months; mean age 8 years 7 months, SD 6 years 4 months) was evaluated with ABR measurements. If the ABR latencies at 20dB nHL exceeded those of the normative group, a slight hearing loss was diagnosed. For ABR thresholds in the range 30 to 40dB nHL, a mild hearing loss was determined; moderate hearing loss was diagnosed for ABR thresholds in the range 50 to 60dB nHL. Bilateral hearing loss was found in 16 (19.3%) patients and unilateral hearing loss in 13 (16%) patients. Bilateral hearing loss of moderate degree was found in one patient. No patient was found with severe hearing loss (ABR threshold of 70dB nHL and above) in either ear. Slight hearing loss was found in 10.5% of ears (17 of 162), mild hearing loss in 14.2% of ears(23 of 162), and moderate hearing loss in 3.1% of ears (5 of 162). In 72.2% of ears (117 of 162), findings indicated the presence of normal peripheral auditory sensitivity. Prevalence of sensorineural hearing loss was 17.3% (28 of 162). Evidence of conductive involvement (conductive and mixed hearing loss) was observed in 9.9% of ears (16 of 162). In this cross-sectional study, the prevalence of hearing loss was increased in older RS participants and in those with seizures requiring the use of anticonvulsants. Neither the type of hearing loss nor the presence of preserved speech seemed to be correlated with the type of mutation in methyl-CpG-binding protein 2 (MeCP2) gene that is associated with RS.

Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb

Infectious agents have been implicated as triggers of autoimmunity. Prospective epidemiologic studies of infection with specific pathogens and the subsequent elevation of specific autoantibodies are difficult and costly to conduct. As a result, a solid body of evidence regarding this theoretically intriguing connection remains to be accrued. We studied term sera from 1807 pregnancies in 1591 women for whom IgG status for cytomegalovirus, Epstein—Barr virus, herpes simplex virus type 1, herpes simplex virus type 2, and/or Toxoplasma gondii was available from prior analyses. We tested the sera (masked regarding infectious status) for autoantibodies to thyroid peroxidase (TPOaAb) and then unmasked and linked them. Adjusted for other cofactors, prior infection with T. gondii was associated significantly with the elevation of TPOaAb, whereas seropositivity for other infections was not. Negative and positive findings for suspected triggers of autoimmunity should be reported to build the evidentiary basis needed to advance our understanding of the disease process. The positive association observed between prior infection with T. gondii and the elevation of TPOaAb is supported by an almost simultaneous study. These findings require further investigation. We believe that if T. gondii is in fact confirmed to trigger or enhance a TPOaAb response, the most likely mechanism involved is the bystander effect.

Vitamin A supplementation in preschool children and risk of hearing loss as adolescents and young adults in rural Nepal: randomised trial cohort follow-up study

Objective To determine whether vitamin A supplementation administered in the preschool years can lower the risk of hearing loss in adolescence and adulthood. Design Follow-up study of adolescents and young adults who, as preschool aged children in 1989, were enrolled into a cluster randomised, double blinded, placebo controlled trial of vitamin A supplementation. Setting South central, rural Nepal. Participants 2378 adolescents and young adults aged 14 to 23, representing 51% of those who finished the original trial and 71% of those living in the study area in 2006. Interventions Every four months for 16 months preschool children were visited at home, given an oral 200 000 IU dose of vitamin A (half dose at age 1-11 months, quarter dose at <1 month) or placebo and the parents were queried about any childhood illnesses in the previous week, including purulent discharge from the ears. Main outcome measures Prevalence of mild or worse hearing loss (≥30 dB) in the most affected ear and tympanometric measures of middle ear function (peak height, ear canal volume, and gradient). Results During the original trial, the prevalence of middle ear infection during the preschool years did not differ between the supplement groups. By adolescence and early adulthood, a non-significant 17% reduction in hearing loss occurred among those who had periodically received vitamin A compared with placebo as preschool aged children (odds ratio 0.83, 95% confidence interval 0.62 to 1.12). Among participants with any ear discharge in early childhood, vitamin A supplementation was associated with a reduced risk of hearing loss, by 42% (0.58, 0.37 to 0.92) compared with controls, after adjusting the confidence interval for the design effect of the original trial. Abnormal tympanometric peak height of the middle ear system was less likely among participants supplemented with vitamin A in childhood. Conclusion In undernourished settings, periodic, high dose vitamin A supplementation may reduce the risk of hearing loss associated with purulent ear infections in early childhood.

Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations

Osteogenesis imperfecta (OI) is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed.

Prevalence of hearing loss and ear morbidity among adolescents and young adults in rural southern Nepal

Abstract A cross-sectional survey was conducted among 3646 persons, 15 to 23 years of age, in the southern plains District of Sarlahi, Nepal, to assess the prevalence and severity of hearing loss and middle-ear dysfunction, and adverse effects of hearing loss on social integration. Between 2006 and 2008, subjects were enumerated and underwent otoscopic, tympanometric, and audiometric evaluations at central sites in villages. Hearing loss was diagnosed in subjects who failed a hearing screening and exhibited an average air conduction threshold value greater than or equal to 30 dBHL in the worse ear. Clinically, 32.8% of subjects exhibited a dull or retracted tympanic membrane, and 18% had abnormal tympanometry. Nearly 12% failed the hearing screening test, among whom more than half, or 6.1% overall, had hearing loss. Hearing-impaired subjects were six- to eight-fold (ORs, with 95% CIs excluding 1.0) more likely to report problems in hearing usual sounds or communicating with other people. Among young adults living in southern Nepal, hearing loss is common, and associated with social disability. Sumario Se realizó una investigación transversal en 3646 personas de 15 a 23 años de edad en las llanuras del Distrito de Sarlahi, en el Sur del Nepal, para evaluar la prevalencia y severidad de la hipoacusia y de la disfunción del oído medio y los efectos adversos de la pérdida auditiva en la integración social. Entre 2006 y 2008 se incluyeron los sujetos y se evaluaron otoscópica, timpanométrica y audiométricamente en zonas centrales de los poblados. Se diagnosticó hipoacusia a quienes fallaron el tamiz auditivo y mostraron una vía aérea con promedio de umbrales mayor a 30 dBHL en el oído peor. Clínicamente, el 32.8% tenían membrana timpánica opaca o retraída y 18%, timpanometría anormal. Cerca del 12% fallaron en el tamiz auditivo y de ellos, más de la mitad, globalmente el 6.1%, tenían hipoacusia. Estos sujetos fueron 6 a 8 veces (ORs 95% excluyendo 1.0 CIs) mayor probabilidad de reportar problemas para escuchar sonidos comunes o para comunicarse con otras personas. Entre los adultos jóvenes que viven en el sur de Nepal, la hipoacusia es común y se asocia a discapacidad social.

Auditory brainstem responses in Rett syndrome: Effects of hyperventilation, seizures, and tympanometric variables

This study examined the effects of tympanometric variables, stage of disease, hyperventilation, and seizures on the auditory brainstem response (ABR) in Rett syndrome (RS). Thirty-four female children with RS ranging in age from 2 years, 3 months to 15 years, 7 months participated in the study. ABRs and tympanograms were recorded from all of the subjects. When the ABR peaks were identifiable, interpeak latency intervals (IPLIs) for I-III, III-V, and I-V were computed for each waveform. The peaks (I, III, and V) and IPLIs were characterized as abnormal if either the peaks were absent or the latencies were greater than 2 SD from the normative data (obtained on female children). Analyses revealed significant prolongation of wave 1 latencies in Rett children with abnormal tympanograms. ABR wave III latencies were significantly affected by the presence of seizures and hyperventilation. The Pearson chi-square statistic revealed significant differences in the rate of wave III and V abnormalities due to the presence and degree of hyperventilation and the presence of seizures. Wave I abnormalities were also observed in the presence of normal middle ear function, suggesting the presence of sensorineural hearing impairment in some RS children. Clinical implications of these findings are discussed.

Distortion Product Otoacoustic Emission and Auditory Brain Stem Response Measures of Pediatric Sensorineural Hearing Loss with Islands of Normal Sensitivity

Objective: To assess the accuracy of: 1) distortion product otoacoustic emission (DPOAE) measures for the identification of frequencies at which auditory sensitivity is normal or near normal; and 2) click and nonmasked tone burst‐evoked auditory brain stem response (ABR) thresholds for behavioral threshold estimation for children with sensorineural hearing loss characterized by islands of normal sensitivity. Design: DPOAEs and ABRs were recorded from five hearing‐impaired and eight normal‐hearing pediatric ears. The accuracy with which DPOAEs permitted identification of frequencies at which elevated hearing thresholds were present was examined. ABR and pure‐tone threshold differences for the impaired ears were calculated. Results: For three of the five hearing‐impaired ears, significant impairments would have been missed based on click‐evoked ABR thresholds. One of those hearing‐impaired ears provided an essentially normal 500 Hz tone burst‐evoked ABR threshold as well. Four of the hearing‐impaired ears provided a 500 Hz tone burst‐evoked ABR threshold within 10 dB of the respective pure‐tone threshold. However, click‐evoked ABR and 500 Hz tone burst‐evoked ABR threshold data did not adequately delineate the hearing loss configuration for hearing aid frequency response selection. DPOAEs were present at three out of four frequencies from 1000 to 4000 Hz at which sensitivity was normal or near normal (≤25 dB HL) and absent at 10 out of 11 frequencies at which sensitivity was impaired. The use of DPOAEs to identify frequencies at which sensitivity was normal and the use of tone burst ABR thresholds at frequencies where DPOAEs were absent provided a better estimate of these pure‐tone audiograms than was provided by click‐evoked and 500 Hz tone burst‐evoked ABR thresholds.

Effects of sedation on auditory brainstem response in Rett syndrome

Prolongation of the I-V interpeak latency intervals have been reported in Rett syndrome and other neurodevelopmental disorders. It has been suggested that the use of sedation may account for differences in the interpeak latency intervals when comparisons are made across diagnostic groups if sedated control groups are not used for the basis of comparison. This study examined the effects of sedation on auditory brainstem response interpeak latency intervals (i.e., I-III, III-V, and I-V) in two groups: (1) a group with Rett syndrome who were positive for mutations in the MECP2 gene and (2) a group negative for mutations in the MECP2 gene but who were severely to profoundly delayed with other causes of mental retardation. To further assess the effects of sedation, a third group of sedated and nonsedated female participants, taken from an in-house normative auditory brainstem response database was also included. An analysis of variance indicated (1) longer I-V interpeak latency intervals in the sedated participants with Rett syndrome; (2) longer III-V interpeak latency intervals in the mutation-positive participants as compared to non-Rett syndrome, mutation-negative participants; and (3) no significant effects of sedation on the I-III, III-V, or I-V interpeak latency intervals among the normative group participants, according to t tests. The findings suggest a possible biological basis for the discrepancy in the literature on auditory brain stem responses in Rett syndrome, and warrant cautious interpretation of auditory brainstem responses findings in sedated subjects with Rett syndrome, as well as in those with mental retardation and seizures.