Hearing function in patients living with HIV/AIDS.

OBJECTIVES: During the earlier years of the HIV/AIDS epidemic, initial reports described sensorineural hearing loss in up to 49% of individuals with HIV/AIDS. During those years, patients commonly progressed to advanced stages of HIV disease and frequently had neurological complications. However, the abnormalities on pure-tone audiometry and brainstem-evoked responses outlined in small studies were not always consistently correlated with advanced stages of HIV/AIDS. Moreover, these studies could not exclude the confounding effect of concurrent opportunistic infections and syphilis. Additional reports also have indicated that some antiretroviral medications may be ototoxic; thus, it has been difficult to make conclusions regarding the cause of changes in hearing function in HIV-infected patients. More recently, accelerated aging has been suggested as a potential explanation for the disproportionate increase in complications of aging described in many HIV-infected patients; hence, accelerated aging-associated hearing loss may also be playing a role in these patients. DESIGN: We conducted a large cross-sectional analysis of hearing function in over 300 patients with HIV-1 infection and in 137 HIV-uninfected controls. HIV-infected participants and HIV-uninfected controls underwent a 2-hr battery of hearing tests including the Hearing Handicap Inventory, standard audiometric pure-tone air and bone conduction testing, tympanometric testing, and speech reception and discrimination testing. RESULTS: Three-way analysis of variance (ANOVA) and logistic regression analysis of 278 eligible HIV-infected subjects stratified by disease stage in early HIV disease (n = 127) and late HIV disease (n = 148) and 120 eligible HIV-uninfected controls revealed no statistically significant differences among the three study groups in either overall 4-frequency pure-tone average (4-PTA) or hearing loss prevalence in either ear. Three-way ANOVA showed significant differences in word recognition scores in the right ear among groups, a significant group effect on tympanogram static admittance in both ears and a significant group effect on tympanic gradient in the right ear. There was significantly larger admittance and gradient in controls as compared to the HIV-infected group at late stage of disease. Hearing loss in the HIV-infected groups was associated with increased age and was similar to that described in the literature for the general population. Three-way ANOVA analysis also indicated significantly greater pure-tone thresholds (worse hearing) at low frequencies in HIV patients in the late stage of disease compared with HIV-uninfected controls. This difference was also found by semi-parametric mixed effects models. CONCLUSIONS: Despite reports of "premature" or "accelerated" aging in HIV-infected subjects, we found no evidence of hearing loss occurring at an earlier age in HIV-infected patients compared to HIV-uninfected controls. Similar to what is described in the general population, the probability of hearing loss increased with age in the HIV-infected subjects and was more common in patients over 60 years of age. Interestingly, HIV-infected subjects had worse hearing at lower frequencies and have significant differences in tympanometry compared to HIV-uninfected controls; these findings deserve further study.

The association of auditory function measures with low-level methylmercury from oceanic fish consumption and mercury vapor from amalgam: The Seychelles Child Development Study Nutrition 1 Cohort.

BACKGROUND: Some authors have reported that low-level exposure to methylmercury (MeHg) adversely impacts measures of auditory function. These reports, however, are not consistent in their findings. Consequently, we examined auditory function in a population exposed to low-level methylmercury (MeHg) exposure from fish consumption and to mercury vapor (Hg0) from dental amalgams. We analyzed their associations with the participants hearing acuity, absolute and interwave ABR latencies, and otoacoustic emissions (distortion product/DPOAE and click evoked/CEOAE). DESIGN: We administered an audiometry test battery to 246 participants from the Seychelles Child Development Study (SCDS) Nutrition Cohort 1 (NC1) at 9 years of age. The test battery included standard pure-tone audiometry, tympanometry, Auditory Brainstem Responses (ABR) and Distortion Product and Click Evoked Otoacoustic Emissions (DPOAE and CEOAE) testing. We measured prenatal MeHg exposure in maternal hair and postnatal MeHg in children's hair. We approximated prenatal Hg0 exposure using maternal amalgam surface area and postnatal Hg0 using children amalgam surface area. Complete exposure records and audiometric data were available on 210 participants and in them we analyzed the association of MeHg and Hg0 exposures with auditory outcomes using covariate-adjusted linear regression models adjusted for sex and tympanometric pressure. RESULTS: Hg exposures were similar for both sexes. Seven of the 210 evaluable participants examined had either a mild (5) or moderate (2) hearing loss. Four had a mild monaural hearing loss and 3 had either a mild (1) or moderate (2) bilateral hearing loss. No participant had greater than a moderate hearing loss in either ear. Hg exposures were higher in participants with either a mild or moderate hearing loss, but these differences were not statistically significant. Among the 210 with complete data, neither prenatal nor postnatal MeHg nor Hg0 exposure was statistically significantly associated with any of the ABR endpoints (p > 0.05 for all 72 associations). Neither prenatal nor postnatal Hg0 exposure was associated with any of the OAE endpoints (p > 0.05). MeHg exposure was statistically associated with 6 of the 56 DPOAE endpoints (p-values between 0.0001 and 0.023), but none of the 40 CEOAE endpoints. Two of the associations occurred with prenatal MeHg exposures and 1 of those would suggest a beneficial effect. Four of the other associations occurred with postnatal MeHg exposures with only 2 found in left ears of both males and females and the other 2 in the left and right ear of females at only one frequency. CONCLUSION: Overall, these data do not present a clear and consistent pattern to suggest that the auditory system is negatively affected by low-level methylmercury exposure due to dietary consumption of oceanic fish or mercury vapor exposure from dental amalgams.

The effects of aggressive vs. conservative phototherapy on the brainstem auditory evoked responses of extremely-low-birth-weight infants.

INTRODUCTION: This study was a two-center, stratified, parallel-group randomized trial comparing the effects of aggressive vs. conservative phototherapy on brainstem auditory evoked response (BAER) latencies in infants with extremely low birth weight (ELBW, ≤ 1,000 g). RESULTS: BAER latencies of 751-1,000 g birth-weight infants were shorter by 0.37 ms (95% confidence interval (CI) = 0.02, 0.73) for wave V, 0.39 ms (0.08, 0.70) for wave III, and 0.33 ms (0.01, 0.65) for wave I after aggressive phototherapy at one center. Interwave intervals did not differ significantly. Similar nonsignificant trends were recorded for 501-750 g birth-weight infants. At the other participating center, no significant differences were recorded, cautioning against overgeneralizing these results. DISCUSSION: The effects of bilirubin on the auditory pathway in ELBW infants depend on a complex interaction of bilirubin exposure, newborn characteristics, and clinical management. METHODS: Aggressive phototherapy was initiated sooner and continued at lower bilirubin levels than conservative phototherapy. A total of 174 ELBW infants were enrolled in the study; 111 infants were successfully tested at 35 weeks postmenstrual age (PMA); 57 died; and 6 were not successfully tested.

Placental expression of the heme transporter, feline leukemia virus subgroup C receptor, is related to maternal iron status in pregnant adolescents.

Little is known about the expression of heme transporters in human placenta and possible associations between these transporters and maternal or neonatal iron status. To address this area of research, relative protein expression of 2 heme transporters, Feline Leukemia Virus, Subgroup C, Receptor 1 (FLVCR1) and Breast Cancer Resistance Protein (BCRP), was assessed using Western-blot analysis in human placental tissue in relation to maternal/neonatal iron status and placental iron concentration. Placental FLVCR1 (n = 71) and BCRP (n = 83) expression were assessed at term (36.6-41.7 wk gestation) in a cohort of pregnant adolescents (13-18 y of age) at high-risk of iron deficiency. Both FLVCR1 and BCRP were detected in all placental samples assayed. Placental FLVCR1 expression was positively related to placental BCRP expression (n = 69; R(2) = 0.104; P < 0.05). Adolescents that were anemic at delivery had lower placental FLVCR1 expression (n = 49; P < 0.05). Placental FLVCR1 expression was positively associated with placental iron concentration at delivery (n = 61; R(2) = 0.064; P < 0.05). In contrast, placental BCRP expression was not significantly associated with maternal iron status or placental iron content. Both FLVCR1 and BCRP are highly expressed in human placental tissue, but only FLVCR1 was significantly inversely associated with maternal iron status and placental iron concentration. Further analysis is needed to explore potential functional roles of FLVCR1 in human placental iron transport.

Association of Audiometric Measures with plasma long chain polyunsaturated fatty acids in a high-fish eating population: The Seychelles Child Development Study.

OBJECTIVES: To determine if auditory function is associated with current long chain polyunsaturated fatty acids (LCPUFA) concentrations in a cohort of young adults who consume oceanic fish with naturally acquired methylmercury (MeHg). We measured participants plasma LCPUFA concentrations (total n-3, total n-6 and the n-6:n-3 ratio) and looked for an association with Auditory Brain Response (ABR) latencies and Otoacoustic Emissions (OAE) amplitudes. DESIGN: Auditory function of 534 participants from the Seychelles Child Development Study (SCDS) main cohort was examined at 19 years of age. Tests included standard pure-tone audiometry, tympanometry, ABR and both Click-Evoked OAE (CEOAE) and Distortion-Product OAE (DPOAE). Associations of LCPUFA status, measured at the time of examination, and auditory outcomes were examined using covariate-adjusted linear regression models. All models were adjusted for sex, prenatal and current MeHg exposure and hearing status. RESULTS: LCPUFA concentrations were similar for both sexes and when comparing participants with normal hearing (90.4 %) to those who had a sensorineural hearing loss in one or both ears (9.6 %). When looking at a subset of only hearing impaired participants, LCPUFA concentrations were similar in those participants who had a mild sensorineural hearing loss as compared with participants that had a moderate sensorineural hearing loss. LCPUFA concentrations were not correlated with current hair MeHg. LCPUFA concentrations were statistically significantly associated with only 6 of 174 ABR and OAE endpoints examined. Four of the 6 significant associations were present in only one sex. In female participants as n-6 concentrations increased, the ABR wave I absolute latency increased for a 60 dBnHL 19 click/sec stimulus. For male participants the interwave I-III latencies for a 60 dBnHL 69 clicks/sec stimulus increased as the n-6:n-3 LCPUFA ratio increased and the interwave I-V interval decreased for a 60 dBnHL 39 clicks/sec stimulus as the n-6 concentration increased. For both sexes interwave latencies were prolonged for the III-V interwave interval for an 80 dBnHL 39 clicks/sec as n-3 LCPUFA concentration increased. As the n-3 LCPUFA concentrations increased, the amplitude of the 6000 Hz DPOAE in the right ear increased for both sexes. As the n-6:n-3 ratio increased, the amplitude of the 1500 Hz DPOAE in the left ear decreased for females. The amplitude of the CEOAE was not associated with n-3, n-6 LCPUFA concentrations or the n-6:n-3 ratio. CONCLUSION: There was no evidence to suggest LCPUFA status was associated with hearing acuity, ABR latencies or OAE amplitudes, even though our participants tended to have higher LCPUFA concentrations as compared to individuals consuming a more western diet. No association was observed between LCPUFA status and a participants hearing status (normal hearing or hearing loss). Although we found a few associations between current plasma LCPUFA status and ABR and OAE auditory endpoints examined, no clear pattern exists. Some of these associations would be considered detrimental resulting in prolonged ABR latencies or smaller OAE amplitudes, while others would be considered beneficial resulting in shortened ABR latencies or larger OAE amplitudes.

Brainstem maturation after antenatal steroids exposure in premature infants as evaluated by auditory brainstem-evoked response.

OBJECTIVE: Antenatal steroids result in fetal lung maturation, but may retard brain development. Auditory brainstem-evoked response (ABR) is a noninvasive assessment of brainstem maturation. The objective of this study was to determine if antenatal steroids affect brainstem maturation in infants

Associations between prenatal and recent postnatal methylmercury exposure and auditory function at age 19 years in the Seychelles Child Development Study.

OBJECTIVES: The aim of this study was to determine if prenatal or recent postnatal methylmercury (MeHg) exposure from consuming ocean fish and seafood is associated with auditory deficits in young adults. Some investigators have reported adverse associations while others have found no associations. Ocean fish is an important nutrient source for billions of people around the world. Consequently, determining if there is an adverse association with objective auditory measures is important in assessing whether a risk is present or not. DESIGN: The peripheral and central auditory function of 534 subjects in the Seychelles Child Development Study (SCDS) Main Cohort was examined at age of 19 years. The auditory test battery included standard pure-tone audiometry, tympanometry, auditory brainstem response (ABR) latencies, and both click-evoked and distortion product otoacoustic emissions (OAE). Associations with MeHg were evaluated with multiple linear regression models, adjusting for sex, recent postnatal MeHg exposure, and hearing loss. RESULTS: Bilateral hearing loss (defined as a mean pure-tone threshold of greater than 25 dB) was present in 1.1%of the subjects and was not associated with prenatal or recent postnatal MeHg exposure. As expected, absolute and interwave ABR latencies were shorter for women as compared to men, as the stimulus presentation rate decreased from 69.9 to 19.9 clicks/s and as the stimulus intensity increased from 60 to 80 dBnHL. Similarly, larger OAE amplitudes were elicited in women as compared to men and in the right ears as compared to the left. There was no association of prenatal MeHg exposure with hearing loss, ABR absolute and interwave latencies or OAE amplitudes. As recent postnatal MeHg increased, some associations were found with a few ABR absolute and interwave latencies and a few OAE amplitudes. However, the direction of these associations was inconsistent. As recent postnatal MeHg levels increased the wave I absolute latencies were shorter at 80 dBnHL for all three click rates, but the interwave I­V latency was longer for males for the 80 dBnHL 19 clicks/s and for the III­V interwave latencies for males and females for the dBnHL 69 clicks/s. Similarly, smaller OAE amplitudes were found at 1500, 2000, and 4000 Hz for males while larger OAE amplitudes were found for females at 1500 and 2000 Hz as the recent postnatal MeHg levels increased. CONCLUSIONS: No consistent associations were present in this study between prenatal MeHg exposure from consumption of oceanic fish and seafood during pregnancy and auditory functions at 19 years of age. Given the level of prenatal exposure to MeHg, the number of audiologic measures tested, and the presence of the expected sex, click rate, and level dependent findings, it seems unlikely that an association was present and not detected. As recent postnatal MeHg exposure increased, a few associations with ABR latencies and OAE amplitudes were found. The direction of these associations was inconsistent as some showed improved performance as MeHg exposure levels increased while others showed poorer performance. The presence of the inconsistent postnatal MeHg exposure findings are intriguing and deserve further clarification.

Neurophysiologic measures of auditory function in fish consumers: associations with long chain polyunsaturated fatty acids and methylmercury.

BACKGROUND: Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily be quantified, and might be helpful additions to testing. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. OBJECTIVES: We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. METHODS: We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. RESULTS: Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. CONCLUSION: The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants and whether they are associated with children's neurodevelopment.