The Cross-Sectional Association Between Tinnitus and Actigraphy-Estimated Sleep in a Population-Based Cohort of Middle-Aged and Elderly Persons.

OBJECTIVES: Tinnitus is a common and burdensome disease, often accompanied by complaints of poor sleep. However, associations of tinnitus with objective estimates of sleep remain unclear, particularly in the general population. We assessed these associations in a population-based cohort of middle-aged and elderly persons. DESIGN: This study included 1456 participants (mean age: 65.0 ± 7.1 years, 52% women) from the population-based Rotterdam Study. Tinnitus was self-reported and in those who reported tinnitus daily, symptom severity was assessed with the Tinnitus Handicap Inventory. We used actigraphy to estimate sleep and 24-hour activity rhythms objectively and sleep diaries to assess self-reported sleep. We estimated the difference in sleep and 24-hour activity rhythms first between those with and those without tinnitus and secondly with tinnitus severity. RESULTS: Tinnitus, reported by 341 (23%) participants, and tinnitus severity, assessed in 194 participants with daily tinnitus, were not associated with actigraphy-estimated sleep or 24-hour activity rhythms, but were associated with a longer self-reported sleep onset latency (adjusted difference tinnitus = 2.36, 95% confidence interval [CI] = 0.95-3.78, adjusted difference tinnitus severity = 0.27, 95% CI = 0.013-0.54). After stratification for hearing loss, tinnitus was associated with longer self-reported sleep onset latency (adjusted difference = 2.26, 95% CI = 0.98-3.53) and less stable 24-hour activity rhythms (adjusted difference = -0.02, 95% CI = -0.04 to -0.00) in those with hearing loss. In those without hearing loss, tinnitus was associated with more stable rhythms (adjusted difference = 0.03, 95% CI = 0.01-0.05). CONCLUSIONS: Having tinnitus is associated with a longer self-reported sleep onset latency, but not with objective estimates of sleep, suggesting that the subjective experience of sleep may be particularly disturbed in those with tinnitus. In addition, hearing loss may modify the association of tinnitus and 24-hour activity rhythms.

Risk Factors For Hearing Decline From Childhood To Early Adolescence.

OBJECTIVE: To identify risk factors of hearing decline between 9 and 13 years of age. The risk factors examined included sociodemographic, health, and lifestyle-related factors. METHODS: This study was embedded within a population-based prospective cohort study from fetal life onwards in the Netherlands. Pure-tone audiometry and tympanometry were performed at the age of 9 and 13 years. The hearing decline was defined as an increase in low-frequency or high-frequency pure-tone average of at least 5 dB in one of both ears. Multivariable logistic regression was performed to examine the association of possible risk factors with hearing decline. The study was conducted from April 2012 to October 2015, and from April 2016 to September 2019. RESULTS: Of the 3,508 participants included, 7.8% demonstrated a hearing decline in the low frequencies, and 11.3% in the high frequencies. Participants who reported alcohol consumption were more likely to have a hearing decline in the low frequencies (OR 1.5, 95% CI 1.1; 2.0). Moreover, a lower educational level was associated with an increased odds of having a hearing decline in the high frequencies (OR 1.4, 95% CI 1.0; 1.8). Age, sex, household income, personal music player use, and body mass index were not associated with hearing decline. CONCLUSION: Educational level and risky behavior were significantly associated with hearing decline from childhood to early adolescence. The findings of the present study can help in the design of public health interventions to prevent hearing loss at a young age. LEVEL OF EVIDENCE: 2 (prospective cohort study) Laryngoscope, 133:389-395, 2023.

The association between exposure to antibiotics in the first week of life and later otitis media: The INCA study.

Otitis media (OM) is one of the most common diagnoses in preschool-age children. Its pathophysiology is poorly understood, but is associated with changes in the nasopharyngeal microbiome, immune system, and presence of allergies. These, in turn, can be affected by early-life antibiotic exposure. Therefore, this study aimed to determine if antibiotic treatment in the first week of life in children born at term was associated with acute otitis media (AOM) and otitis media with effusion (OME) in the first 4-6 years of life. METHODS: A prospective birth cohort of 436 term-born infants was followed up at 4-6 years of age. Parents reported (recurrent) AOM and OME through online questionnaires, sent to parents of 418 eligible children. Doctors' diagnoses of AOM and OME were collected after additional informed consent. Multivariate logistic regression analyses were used to study the association between antibiotic exposure and AOM and OME. RESULTS: Of the 436 infants, 151 infants received antibiotics in the first week of life. In total, 341 (82%) questionnaires were collected. The parental-reported prevalence was 45% (155/341) for AOM. Of these 155 children, 33 children also had OME (10% of the total cohort). Doctor's diagnoses were obtained from 308 (74%) children, of which 30% (91/308) had AOM. Of these 91 children, 12 children also had OME and 8 children had OME without a diagnosis of AOM (6% of the total obtained diagnoses). Antibiotic treatment in the first week of life was not significantly associated with parent-reported nor doctor-diagnosed (recurrent) AOM and OME in the first 4-6 years of life in the regression models. CONCLUSION: Antibiotic treatment in the first week of life was not associated with AOM and OME in the first 4-6 years of life in this prospective cohort of Dutch infants. More insight into the pathophysiology of OM is warranted to determine whether antibiotic-induced microbiome changes play a role in the susceptibility to OM.

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss.

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.

Neonatal Antibiotics and Food Allergy Are Associated With FGIDs at 4-6 Years of Age.

OBJECTIVES: Antibiotics may contribute to the development of functional gastrointestinal disorders (FGIDs). This study aimed to determine whether antibiotics during the first week of life, infantile colic in the first year of life, gut-associated immune markers at 1 year of age, and allergies at 4-6 years of age in term-born children were associated with a higher prevalence of FGIDs at 4-6 years of age. METHODS: A prospective observational cohort of 436 term-born infants was followed up at the age of 4-6 years; 151 received broad-spectrum antibiotics (AB+), and 285 healthy controls (AB-). Validated Questionnaire On Pediatric Gastrointestinal Symptoms-Rome III and International Study of Asthma and Allergy in Childhood questionnaires were sent to parents of 418 available children. The independent t-test, chi-squared test or non-parametric test and logistic multivariate regression analyses were used. RESULTS: In total, 340 of 418 (81%) questionnaires were completed. Only the presence of functional abdominal pain was significantly higher in AB+ than AB- (4% vs 0.4%, respectively, P  = 0.045). Children with food allergy fulfilled significantly more often the criteria for irritable bowel syndrome (IBS) and abdominal migraine (26% vs 9%, P  = 0.002 and 7% vs 1%, P  = 0.043, respectively) compared to non-allergic children. No differences in FGIDs existed at the age of 4-6 years between children with and without a history of infantile colic. There were significant differences in gut-associated immune markers between children with and without FGIDs. CONCLUSION: Antibiotics during the first week of life resulted in a higher risk for functional abdominal pain at 4-6 years. Furthermore, food allergy was associated with IBS and abdominal migraine at 4-6years.

Hearing Function: Identification of New Candidate Genes Further Explaining the Complexity of This Sensory Ability.

To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, and high frequencies) collected in nine cohorts from Europe, South-Eastern USA, Caucasus, and Central Asia, for an overall number of ~9000 subjects. Three hundred seventy-five genes across all nine analyses were tagged by single nucleotide polymorphisms (SNPs) reaching a suggestive p-value (p < 10-5). Amongst these, 15 were successfully replicated using a gene-based approach in the independent Italian Salus in the Apulia cohort (n = 1774) at the nominal significance threshold (p < 0.05). In addition, the expression level of the replicated genes was assessed in published human and mouse inner ear datasets. Considering expression patterns in humans and mice, eleven genes were considered particularly promising candidates for the hearing function: BNIP3L, ELP5, MAP3K20, MATN2, MTMR7, MYO1E, PCNT, R3HDM1, SLC9A9, TGFB2, and YTHDC2. These findings represent a further contribution to our understanding of the genetic basis of hearing function and its related diseases.

Macrolide-associated ototoxicity: a cross-sectional and longitudinal study to assess the association of macrolide use with tinnitus and hearing loss.

BACKGROUND: Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity. OBJECTIVES: To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population. METHODS: Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action. RESULTS: In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07-1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found. CONCLUSIONS: Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.

Cross-sectional and Longitudinal Associations Between Tinnitus and Mental Health in a Population-Based Sample of Middle-aged and Elderly Persons.

Importance: Tinnitus is a common disorder, but its impact on daily life varies widely in population-based samples. It is unclear whether this interference in daily life is associated with mental health problems that are commonly detected in clinical populations. Objective: To investigate the association of tinnitus and its interference in daily life with symptoms of depression and anxiety and poor sleep quality in a population-based sample of middle-aged and elderly persons in a cross-sectional analysis and during a 4-year follow-up. Design, Setting, and Participants: This cohort study evaluated data from the population-based Rotterdam Study of individuals 40 years or older living in Rotterdam, the Netherlands. Between 2011 and 2016, data on tinnitus were obtained during a home interview at least once for 6128 participants. Participants with information on depressive and anxiety symptoms and self-rated sleep quality, with Mini-Mental State Examination scores indicating unimpaired cognition, and with repeatedly obtained tinnitus and mental health outcome data were included. Data analyses were conducted between September 2019 and April 2020. Main Outcomes and Measures: The presence of tinnitus and its interference with daily life were assessed during a home interview. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression, anxiety symptoms with the Hospital Anxiety and Depression Scale, and sleep quality with the Pittsburgh Sleep Quality Index. Linear regression analyses and linear mixed models adjusted for relevant confounders were used to assess the cross-sectional and longitudinal association of tinnitus with mental health. Results: Of 5418 complete-case participants (mean [SD] age, 69.0 [9.8] years; 3131 [57.8%] women), 975 (mean [SD] age, 71.7 [4.5] years; 519 [53.2%] women) had repeated measurements available for follow-up analyses. Compared with participants without tinnitus and participants with nonbothersome tinnitus, participants with tinnitus interfering with daily life reported more depressive (difference, 0.20; 95% CI, 0.11-0.28) and anxiety (difference, 0.15; 95% CI, 0.08-0.22) symptoms and poorer sleep quality (difference, 0.10; 95% CI, 0.03-0.16). Compared with participants without tinnitus, participants with nonbothersome tinnitus also reported more depressive (difference, 0.06; 95% CI, 0.03-0.09) and anxiety (difference, 0.05; 95% CI, 0.02-0.07) symptoms and poorer sleep quality (difference, 0.05; 95% CI, 0.03-0.08). Individuals indicating more interference with daily life reported having more mental health problems. During a mean follow-up of 4.4 years (range, 3.5-5.1 years), participants with tinnitus reported more anxiety symptoms and poorer sleep quality than those without tinnitus. Conclusions and Relevance: Findings of this population-based cohort study indicate that tinnitus was associated with more mental health problems in middle-aged and elderly persons in the general population, in particular when tinnitus interfered with daily life but not solely. Over time, more severe tinnitus was associated with an increase in anxiety symptoms and poor sleep quality. This outcome suggests that mental health problems may be part of the burden of tinnitus, even among individuals who do not report their tinnitus interfering with daily life.

Tinnitus and Its Central Correlates: A Neuroimaging Study in a Large Aging Population.

OBJECTIVES: To elucidate the association between tinnitus and brain tissue volumes and white matter microstructural integrity. DESIGN: Two thousand six hundred sixteen participants (mean age, 65.7 years [SD: 7.5 years]; 53.9% female) of the population-based Rotterdam Study underwent tinnitus assessment (2011 to 2014) and magnetic resonance imaging of the brain (2011 to 2014). Associations between tinnitus (present versus absent) and total, gray, and white matter volume and global white matter microstructure were assessed using multivariable linear regression models adjusting for demographic factors, cardiovascular risk factors, depressive symptoms, Mini-Mental State Examination score, and hearing loss. Finally, potential regional gray matter density and white matter microstructural volume differences were assessed on a voxel-based level again using multivariable linear regression. RESULTS: Participants with tinnitus (21.8%) had significantly larger brain tissue volumes (difference in SD, 0.09; 95% confidence interval, 0.06 to 0.13), driven by larger white matter volumes (difference, 0.12; 95% confidence interval, 0.04 to 0.21) independent of hearing loss. There was no association between tinnitus and gray matter volumes nor with global white matter microstructure. On a lobar level, tinnitus was associated with larger white matter volumes in each lobe, not with gray matter volume. Voxel-based results did not show regional specificity. CONCLUSIONS: We found that tinnitus in older adults was associated with larger brain tissue volumes, driven by larger white matter volumes, independent of age, and hearing loss. Based on these results, it may be hypothesized that tinnitus potentially has a neurodevelopmental origin in earlier life independent of aging processes.

Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses in Preterm Pigs.

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS-lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1 ± 0.0 to 9.7 ± 1.9, p < 0.001), docosahexaenoic acid, DHA (day 0 = 2.5 ± 0.7 to 13.6 ± 2.9, p < 0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1ß increased at the first hour of LPS infusion (296.6 ± 308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p < 0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit the initial LPS-induced inflammatory responses in preterm pigs.

Prevalence of Tinnitus in an Aging Population and Its Relation to Age and Hearing Loss.

OBJECTIVES: Tinnitus is a common hearing-related disorder, which may have a large impact on daily life. With aging populations worldwide, it is important to gain insight in the occurrence of tinnitus at older ages and to understand its relationship with age-related hearing loss. We investigated the prevalence of tinnitus among a general aging population, across age strata and hearing status. STUDY DESIGN: Cross-sectional. SETTING: The population-based Rotterdam Study. METHODS: A total of 6098 participants underwent tinnitus assessment, and 4805 had additional hearing assessment. We determined tinnitus prevalence per 5-year age groups. Hearing impairment was defined as ≥25-dB HL worse ear pure tone average (0.5, 1, 2, 4 kHz). We investigated with multivariable logistic regression the association between hearing impairment and tinnitus. Tinnitus handicap was assessed in 663 participants with daily tinnitus via the Tinnitus Handicap Inventory-screening version (THI-s). RESULTS: Tinnitus was prevalent in 21.4% (n = 1304). Prevalent tinnitus was evenly distributed over 5-year age groups. Participants with hearing impairment were more likely to have tinnitus (odds ratio, 2.27; 95% CI, 1.92-2.69) as compared with those without hearing impairment. The median THI-s score was 4 (interquartile range, 0-10), indicating a slight handicap, and 14.6% of the participants reported a moderate or severe handicap (THI-s ≥16). CONCLUSIONS: In a general elderly population, 1 in 5 persons has tinnitus. Of those with tinnitus, for 1 per 10 persons, the presence of tinnitus interfered with daily life. Participants with hearing impairment were twice as likely to have tinnitus. Despite the age-dependent occurrence of hearing impairment, no such age dependency was found for tinnitus.

Tinnitus Affects Speech in Noise Comprehension in Individuals With Hearing Loss.

BACKGROUND: Tinnitus is a prevalent auditory disorder that frequently co-occurs with hearing loss. It is suggested that tinnitus might have negative impact on speech perception. However, studies thus far have not been able to disentangle tinnitus, hearing loss, and speech in noise intelligibility. We therefore investigated whether there is an association between tinnitus and speech understanding in noise, independent of hearing loss. METHODS: Of 4,211 participants from the population-based Rotterdam Study (mean age 67.8 [SD 8.9], 57.3% female) data was available on tinnitus, pure-tone audiometry, and digits in noise test. We compared the speech reception threshold in noise (SRTn) in participants with and without tinnitus for the whole population as well as for subgroups stratified for average hearing threshold in 10-dB strata. Additionally, we regressed tinnitus on SRTn with a multivariable regression model, adjusting for sex, age, highest achieved education, and cognitive function. RESULTS: Participants with tinnitus (20.8%) had a higher SRTn (-3.6 dB [SD 3.7] versus -4.6 dB [SD 3.1]). This difference remained only in the subgroups of participants with hearing loss, between 0.6 and 0.8 dB difference in the SRTn for the different subgroups. In the fully adjusted model tinnitus was associated with 0.2 dB (95% CI 0.00, 0.39) SRTn increase. CONCLUSION: We have shown that tinnitus is associated with speech intelligibility in noise, but it is a small effect, only found in people with co-occurring hearing loss.

Association of Speech Recognition Thresholds With Brain Volumes and White Matter Microstructure: The Rotterdam Study.

OBJECTIVES: Brain volumetric declines may underlie the association between hearing loss and dementia. While much is known about the peripheral auditory function and brain volumetric declines, poorer central auditory speech processing may also be associated with decreases in brain volumes. METHODS: Central auditory speech processing, measured by the speech recognition threshold (SRT) from the Digits-in-Noise task, and neuroimaging assessments (structural magnetic resonance imaging [MRI] and fractional anisotropy and mean diffusivity from diffusion tensor imaging), were assessed cross-sectionally in 2,368 Rotterdam Study participants aged 51.8 to 97.8 years. SRTs were defined continuously and categorically by degrees of auditory performance (normal, insufficient, and poor). Brain volumes from structural MRI were assessed on a global and lobar level, as well as for specific dementia-related structures (hippocampus, entorhinal cortex, parahippocampal gyrus). Multivariable linear regression models adjusted by age, age-squared, sex, educational level, alcohol consumption, intracranial volume (MRI only), cardiovascular risk factors (hypertension, diabetes, obesity, current smoking), and pure-tone average were used to determine associations between SRT and brain structure. RESULTS: Poorer central auditory speech processing was associated with larger parietal lobe volume (difference in mL per dB increase= 0.24, 95% CI: 0.05, 0.42), but not with diffusion tensor imaging measures. Degrees of auditory performance were not associated with brain volumes and white matter microstructure. CONCLUSIONS: Central auditory speech processing in the presence of both vascular burden and pure-tone average may not be related to brain volumes and white matter microstructure. Longitudinal follow-up is needed to explore these relationships thoroughly.

Discrimination of degrees of auditory performance from the digits-in-noise test based on hearing status.

OBJECTIVE: To discriminate among degrees of auditory performance of the Digits-in-Noise (DIN) test. DESIGN: We performed Pearson's correlations and age- and sex-adjusted linear regression models to examine the correlation between pure-tone average (PTA) from pure-tone audiometric tests and speech recognition thresholds (SRT) from the DIN test. Then, optimal SRT cut-points by PTA-defined hearing status (0-25 dB HL [normal], 26-40 dB HL [mild hearing loss], 41-50 dB HL [moderate hearing loss]) were compared across three methods: Youden, Nearest, and Liu. SRT-defined categories of auditory performance were compared to PTA-defined hearing categories to examine the convergence of similar categories. Study Sample: 3422 Rotterdam Study participants aged 51-98 years between 2011 and 2014. RESULTS: The correlation between SRT and PTA was 0.65 (95% Confidence Interval: 0.63, 0.67) in the overall sample. The variability of SRT explained by PTA after age and sex adjustment was 54%. Optimal cut-points for the overall sample across the three methods were: ≤ -5.55 dB SNR (normal); > -5.55 to ≤ -3.80 dB SNR (insufficient performance); > -3.80 dB SNR (poor performance). When comparing the SRT- or PTA-defined categories, 59.8% had concordant hearing categories and 40.2% had discordant hearing categories. CONCLUSIONS: Discrimination of degrees of auditory performance may add greater utility of the DIN test.

Assessing hearing loss in older adults with a single question and person characteristics; Comparison with pure tone audiometry in the Rotterdam Study.

INTRODUCTION: Hearing loss (HL) is a frequent problem among the elderly and has been studied in many cohort studies. However, pure tone audiometry-the gold standard-is rather time-consuming and costly for large population-based studies. We have investigated if self-reported hearing loss, using a multiple choice question, can be used to assess HL in absence of pure tone audiometry. METHODS: This study was performed within 4,906 participants of the Rotterdam Study. The question (in Dutch) that was investigated was: 'Do you have any difficulty with your hearing (without hearing aids)?'. The answer options were: 'never', 'sometimes', 'often' and 'daily'. Mild hearing loss or worse was defined as PTA0.5-4(Pure Tone Average 0.5, 1, 2 & 4 kHz) ≥20dBHL and moderate HL or worse as ≥35dBHL. A univariable linear regression model was fitted with the PTA0.5-4 and the answer to the question. Subsequently, sex, age and education were added in a multivariable linear regression model. The ability of the question to classify HL, accounting for sex, age and education, was explored through logistic regression models creating prediction estimates, which were plotted in ROC curves. RESULTS: The variance explained (R2) by the univariable regression was 0.37, which increased substantially after adding age (R2 = 0.60). The addition of sex and educational level, however, did not alter the R2 (0.61). The ability of the question to classify hearing loss, reflected in the area under the curve (AUC), was 0.70 (95% CI 0.68, 0.71) for mild hearing loss or worse and 0.86 (95% CI 0.85, 0.87) for moderate hearing loss or worse. The AUC increased substantially when sex, education and age were taken into account (AUC mild HL: 0.73 (95%CI 0.71, 0.75); moderate HL 0.90 (95%CI 0.89, 0.91)). CONCLUSION: Self-reported hearing loss using a single question has a good ability to detect hearing loss in older adults, especially when age is accounted for. A single question cannot substitute audiometry, but it can assess hearing loss on a population level with reasonable accuracy.

Antibiotic Treatment in the First Week of Life Impacts the Growth Trajectory in the First Year of Life in Term Infants.

OBJECTIVE: Antibiotic treatment in early life appears to increase the risk for childhood overweight and obesity. So far, the association between antibiotics administrated specifically during the first week of life and growth has not been studied. Therefore, we studied the association between growth and antibiotics, given in the first week of life and antibiotic courses later in the first year of life. METHOD: A prospective observational birth cohort of 436 term infants with 151 receiving broad-spectrum antibiotics for suspected neonatal infection (AB+), and 285 healthy controls (AB-) was followed during their first year. Weight, height, and additional antibiotic courses were collected monthly. A generalized-additive-mixed-effects model was used to fit the growth data. Growth curve estimation was controlled for differences in sex, gestational age, delivery mode, exclusive breast-feeding, tobacco exposure, presence of siblings, and additional antibiotic courses. RESULTS: Weight-for-age and length-for-age increase was lower in AB+ compared with AB- (P < 0.0001), resulting in a lower weight and length increase 6.26 kg (standard error [SE] 0.07 kg) and 25.4 cm (SE 0.27 cm) versus 6.47 kg (SE 0.06 kg) and 26.4 cm (SE 0.21 cm) (P < 0.05 and P < 0.005, respectively) in the first year of life. Approximately 30% of the children in both groups received additional antibiotic course(s) in their first year, whereafter additional weight gain of 76 g per course was observed (P = 0.0285). CONCLUSIONS: Decreased growth was observed after antibiotics in the first week of life, whereas increased growth was observed after later antibiotic course(s) in term born infants in the first year of life. Therefore, timing of antibiotics may determine the association with growth.

Neonatal Antibiotic Treatment Is Associated With an Altered Circulating Immune Marker Profile at 1 Year of Age.

Background: Neonatal antibiotics disturb the developing gut microbiome and are therefore thought to influence the developing immune system, but exact mechanisms and health consequences in later life still need to be elucidated. Therefore, we investigated whether neonatal antibiotics influence inflammatory markers at 1 year of age. In addition, we determined whether health problems during the first year of life, e.g., allergic disorders (eczema and wheezing) or infantile colics, were associated with changes in the circulating immune marker profile at 1 year of age. Methods: In a subgroup (N = 149) of the INCA-study, a prospective birth-cohort study, a blood sample was drawn from term born infants at 1 year of age and analyzed for 84 immune related markers using Luminex. Associations of antibiotic treatment, eczema, wheezing, and infantile colics with immune marker concentrations were investigated using a linear regression model. The trial is registered as NCT02536560. Results: The use of broad-spectrum antibiotics in the first week of life, was significantly associated with different levels of inflammatory markers including sVCAM-1, sCD14, sCD19, sCD27, IL-1RII, sVEGF-R1, and HSP70 at 1 year of age. Eczema was associated with decreased concentrations of IFNα, IFNγ, TSLP, CXCL9, and CXCL13, but increased concentrations of CCL18 and Galectin-3. Wheezing, independent of antibiotic treatment, was positively associated to TNF-R2 and resistin. Infantile colics were positively associated to IL-31, LIGHT, YKL-40, CXCL13, sPD1, IL1RI, sIL-7Ra, Gal-1, Gal-9, and S100A8 at 1 year of age, independent of early life antibiotic treatment. Conclusion: In this explorative study, we identified that neonatal antibiotics are associated with immunological alterations at 1 year of age and that, independent of the antibiotic treatment, infantile colics were associated with alterations within gut associated markers. These findings support the importance of the first host microbe interaction in early life immune development.