Semiparametric partial linear modeling of risk factors for ear infections: the Early Childhood Longitudinal Study.

The Early Childhood Longitudinal Study-Kindergarten Class of 2010-2011 (ECLS-K:2011) ascertained timing of ear infections within age specified intervals and parent's/caregiver's report of medically diagnosed hearing loss. In this nationally representative, school-based sample of children followed from kindergarten entry through fifth grade, academic performance in reading, mathematics, and science was assessed longitudinally. Prior investigations of this ECLS-K:2011 cohort showed that age has a non-linear, monotonically increasing functional relationship with academic performance. Because of this knowledge, a semiparametric partial linear model is proposed, in which the effect of age is modeled by an unknown monotonically increasing function along with other regression parameters. The parameters are estimated by a semiparametric maximum likelihood estimator. A test of a constant effect of age is also proposed. Simulation studies are conducted to evaluate the performance of the proposed method, as compared with the commonly used linear model; the former outperforms the latter based on several criteria. We then analyzed ECLS-K:2011 data to compare results of the partial linear parametric model estimation with that of classical linear regression models.

In Utero Antiretroviral Exposure and Risk of Neurodevelopmental Problems in HIV-Exposed Uninfected 5-Year-Old Children.

Studies have observed neurodevelopmental (ND) challenges among young children perinatally HIV-exposed yet uninfected (CHEU) with in utero antiretroviral (ARV) exposure, without clear linkage to specific ARVs. Atazanavir (ATV) boosted with ritonavir has been a preferred protease inhibitor recommended for pregnant women, yet associations of ATV with ND problems in CHEU have been reported. Studies among early school-age children are lacking. The pediatric HIV/AIDS cohort study (PHACS) surveillance monitoring for antiretroviral therapy (ART) toxicities (SMARTT) study evaluated 5-year-old monolingual English-speaking CHEU using the behavior assessment system for children, Wechsler preschool and primary scales of intelligence, and test of language development-primary. A score ≥1.5 standard deviations worse than population norms defined a signal within each domain. Analyses of risk for signals were stratified by timing of any ARV initiation. Associations between ARV exposure and risk of ND signals were assessed using proportional odds models, adjusting for confounders. Among 230 children exposed to ARVs at conception, 15% had single and 8% had multiple ND problems; ATV exposure was not associated with higher risk of signals [adjusted cumulative odds ratio (cOR) = 0.66, confidence interval (CI): 0.28-1.56]. However, among 461 children whose mothers initiated ARVs during pregnancy, 21% had single and 12% had multiple ND problems; ATV exposure was associated with higher risk of signals (cOR = 1.70, CI: 0.82-3.54). The specific regimen tenofovir/emtricitabine/ATV was associated with higher risk (cOR = 2.31, CI: 1.08-4.97) relative to regimens using a zidovudine/lamivudine backbone combined with non-ATV ARVs. It remains important to monitor neurodevelopment of CHEU during early childhood and investigate the impact and the role of timing of in utero exposure to specific ARVs.

Auditory Function in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol Up Young Adults: A Pilot Study.

BACKGROUND: To collect and compare selected hearing measures in a pilot study of young adults with perinatally acquired HIV (YAPHIV) and those with perinatal HIV exposure who are uninfected young adults with PHEU (YAPHEU). SETTING: Cross-sectional hearing measures in YAPHIV and YAPHEU enrolled in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) for Participants 18 Years of Age and Older (AMP Up). METHODS: Pure-tone air conduction audiometry and distortion product otoacoustic emission (DPOAE) data were collected in 1 visit. A low-frequency pure-tone average (PTA) (LFPTA, at 0.25, 0.5, 1, and 2 kHz), a speech-frequency PTA (SFPTA, at 0.5, 1, 2, and 4 kHz), and a high-frequency PTA (HFPTA, at 3, 4, 6, and 8 kHz) were calculated. Hearing loss was defined as worse ear SFPTA of ≥20 dB HL. Separate linear regression models were fit for worse ear LFPTA, SFPTA, and HFPTA to assess associations with PHIV status. DPOAE signal-to-noise ratios (SNRs) were obtained at 3 frequencies in each ear. RESULTS: Forty-seven YAPHIV and 9 YAPHEU completed hearing testing. All adjusted mean PTAs were similar between YAPHIV and YAPHEU. Hearing loss occurred more in YAPHIV (7/47, 15.2%; 95% CI: 6.3%-28.9%), compared with YAPHEU (0/9, 0%). No associations were detected between HIV disease severity measures and worse ear SFPTA. DPOAE SNRs were similar between YAPHIV and YAPHEU. CONCLUSIONS: In this pilot study, peripheral hearing (ie, PTAs) and cochlear function (ie, DPOAEs) were similar between YAPHIV and YAPHEU. A larger study is warranted to confirm these findings.

Gap detection responses modelled using the Hill equation in adults with well-controlled HIV.

OBJECTIVE: This study's objective was determining whether gap detection deficits are present in a longstanding cohort of people living with HIV (PLWH) compared to those living without HIV (PLWOH) using a new gap detection modelling technique (i.e. fitting gap responses using the Hill equation and analysing the individual gap detection resulting curves with non-linear statistics). This approach provides a measure of both gap threshold and the steepness of the gap length/correct detection relationship. DESIGN: The relationship between the correct identification rate at each gap length was modelled using the Hill equation. Results were analysed using a nonlinear mixed-effect regression model. STUDY SAMPLE: 45 PLWH (age range 41-78) and 39 PLWOH (age range 38-79) were enrolled and completed gap detection testing. RESULTS: The likelihood ratio statistic comparing the full regression model with the HIV effects to the null model, assuming one population curve for both groups, was highly significant (p < 0.001), suggesting a less precise relationship between gap length and correct detection in PLWH. CONCLUSIONS: PLWH showed degraded gap detection ability compared to PLWOH, likely due to central nervous system effects of HIV infection or treatment. The Hill equation provided a new approach for modelling gap detection ability.

A Missense Variant in COMT Associated with Hearing Loss among Young Adults: The National Longitudinal Study of Adolescent to Adult Health (Add Health).

Hearing loss is a major public problem with a heritability of up to 70%. Catechol-O-methyltransferase (COMT) encodes an enzyme that is highly expressed in sensory hair cells of the inner ear. The association between COMT and hearing loss has not been reported previously in nationally representative population-based studies. A regression linear model was used to estimate associations between the allele/genotype of COMT and self-reported hearing loss based on 13,403 individuals from Wave IV of the Add Health study, a nationally representative sample of multiethnic U.S. young adults. The inverse variance-weighted effect magnitude was estimated using a genetic meta-analysis model. The "A" allele frequency of rs6480 (a missense variant in COMT) was 0.44. The prevalence of hearing loss was 7.9% for individuals with the "A" allele and 6.5% for those with the "G" allele. The "A" allele was significantly associated with increased hearing loss (p = 0.01). The prevalence of hearing loss was 6.0%, 7.2%, and 8.7% for individuals with GG, AG, and AA genotypes, respectively, which was consistent with a genetic additive model. The genotypic association model showed that rs4680 was significantly associated with increased hearing loss (p = 0.006). A missense variant of rs4680 in COMT was significantly associated with increased hearing loss among young adults in a multi-racial/ethnic U.S. population-based cohort.

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.

Self-Reported Olfactory Dysfunction and Diet Quality: Findings from the 2011-2014 National Health and Nutrition Examination Survey (NHANES).

We identified associations between self-reported olfactory dysfunction (OD) and dietary attributes in participants aged ≥40 years (n = 6,356) from the nationally representative 2011-2014 National Health and Nutrition Examination Survey (NHANES). The chemosensory questionnaire and 24-h dietary recalls were administered by trained interviewers. OD was defined as self-report of either smell problems in the last year, worse smell relative to age 25, or perceiving phantom odors. Dietary outcomes included Healthy Eating Index 2015 score (HEI) with adequacy and moderation components (higher scores indicated higher diet quality), dietary diversity, energy density, and intake of major food groups. Survey-weighted linear regression models estimated OD-diet associations, adjusting for socio-demographic, lifestyle, and clinical factors. Adjusted mean difference (95% CI) between those with versus without OD, showed that adults with OD had significantly lower HEI moderation score (-0.67 (-1.22, -0.11)) and diets higher in energy density (0.06 (0.00, 0.11)), and percent energy from saturated fat (0.47 (0.12, 0.81)), total fat (0.96 (0.22, 1.70)), and added sugar (1.00 (0.33, 1.66)). Age and sex-stratified analyses showed that younger females (40-64 years) primarily accounted for the associations with diet quality and total/saturated fat intake. These findings inform dietary screening and recommendations for adults who report OD, including those experiencing transient or persistent smell loss with COVID-19.

Prenatal Exposure to Tobacco and Alcohol Alters Development of the Neonatal Auditory System.

Prenatal exposures to alcohol (PAE) and tobacco (PTE) are known to produce adverse neonatal and childhood outcomes including damage to the developing auditory system. Knowledge of the timing, extent, and combinations of these exposures on effects on the developing system is limited. As part of the physiological measurements from the Safe Passage Study, Auditory Brainstem Responses (ABRs) and Transient Otoacoustic Emissions (TEOAEs) were acquired on infants at birth and one-month of age. Research sites were in South Africa and the Northern Plains of the U.S. Prenatal information on alcohol and tobacco exposure was gathered prospectively on mother/infant dyads. Cluster analysis was used to characterize three levels of PAE and three levels of PTE. Repeated-measures ANOVAs were conducted for newborn and one-month-old infants for ABR peak latencies and amplitudes and TEOAE levels and signal-to-noise ratios. Analyses controlled for hours of life at test, gestational age at birth, sex, site, and other exposure. Significant main effects of PTE included reduced newborn ABR latencies from both ears. PTE also resulted in a significant reduction of ABR peak amplitudes elicited in infants at 1-month of age. PAE led to a reduction of TEOAE amplitude for 1-month-old infants but only in the left ear. Results indicate that PAE and PTE lead to early disruption of peripheral, brainstem, and cortical development and neuronal pathways of the auditory system, including the olivocochlear pathway.

Association of Prenatal Exposure to Maternal Drinking and Smoking With the Risk of Stillbirth.

Importance: Prenatal smoking is a known modifiable risk factor for stillbirth; however, the contribution of prenatal drinking or the combination of smoking and drinking is uncertain. Objective: To examine whether prenatal exposure to alcohol and tobacco cigarettes is associated with the risk of stillbirth. Design, Setting, and Participants: The Safe Passage Study was a longitudinal, prospective cohort study with data collection conducted between August 1, 2007, and January 31, 2015. Pregnant women from Cape Town, South Africa, and the Northern Plains region of the US were recruited and followed up throughout pregnancy. Data analysis was performed from November 1, 2018, to November 20, 2020. Exposure: Maternal consumption of alcohol and tobacco cigarettes in the prenatal period. Main Outcomes and Measures: The main outcomes were stillbirth, defined as fetal death at 20 or more weeks' gestation, and late stillbirth, defined as fetal death at 28 or more weeks' gestation. Self-reported alcohol and tobacco cigarette consumption was captured at the recruitment interview and up to 3 scheduled visits during pregnancy. Participants were followed up during pregnancy to obtain delivery outcome. Results: Of 11663 pregnancies (mean [SD] gestational age at enrollment, 18.6 [6.6] weeks) in 8506 women for whom the pregnancy outcome was known by 20 weeks' gestation or later and who did not terminate their pregnancies, there were 145 stillbirths (12.4 per 1000 pregnancies) and 82 late stillbirths (7.1 per 1000 pregnancies). A total of 59% of pregnancies were in women from South Africa, 59% were in multiracial women, 23% were in White women, 17% were in American Indian women, and 0.9% were in women of other races. A total of 8% were older than 35 years. In 51% of pregnancies, women reported no alcohol or tobacco cigarette exposure (risk of stillbirth, 4 per 1000 pregnancies). After the first trimester, 18% drank and smoked (risk of stillbirth, 15 per 1000 births), 9% drank only (risk of stillbirth, 10 per 1000 pregnancies), and 22% smoked only (risk of stillbirth, 8 per 1000 pregnancies). Compared with the reference group (pregnancies not prenatally exposed or without any exposure after the first trimester), the adjusted relative risk of late stillbirth was 2.78 (98.3% CI, 1.12-6.67) for pregnancies prenatally exposed to drinking and smoking, 2.22 (98.3% CI, 0.78-6.18) for pregnancies prenatally exposed to drinking only after the first trimester, and 1.60 (98.3% CI, 0.64-3.98) for pregnancies prenatally exposed to smoking only after the first trimester. The adjusted relative risk for all stillbirths was 1.75 (98.3% CI, 0.96-3.18) for dual exposure, 1.26 (98.3% CI, 0.58-2.74) for drinking only, and 1.27 (98.3% CI, 0.69-2.35) for smoking only compared with the reference group. Conclusions and Relevance: These results suggest that combined drinking and smoking after the first trimester of pregnancy, compared with no exposure or quitting before the end of the first trimester, may be associated with a significantly increased risk of late stillbirth.

Associations between chronic cigarette smoking and taste function: Results from the 2013-2014 national health and nutrition examination survey.

We identified associations between cigarette-smoking and taste function in the U.S. NHANES 2013-2014. Adults ≥ 40 years (n = 2849, nearly half former or current smokers) rated whole-mouth and tongue-tip bitter (1 mM quinine) and salt (1 M NaCl, 0.32 M NaCl) intensities and reported smoking history (pack years, PY), dependence (time to first cigarette, TTFC) and menthol/non-menthol use. Perceived intensity on the tongue-tip averaged just below moderate for quinine and moderate to strong for 1 M NaCl. Current chronic smokers (≥ 20 PY) reported lower bitter and salty intensities on the tongue-tip (ß: -2.0, 95% CI: -3.7 to -0.4 and ß: -3.6, 95% CI: -6.9 to -0.3, respectively) than never smokers. Similarly, compared to never smokers, dependent current smokers (TTFC ≤ 30 min) and dependent chronic smokers (≥ 20 PY, TTFC ≤ 30 min) rated less bitter (ß: -2.0, 95% CI: -4.0 to 0.1 and ß: -2.9, 95% CI: -4.5 to -1.3, respectively) and salty (ß: -5.3, 95% CI: -9.3 to -1.4 and ß: -4.7, 95% CI: -8.6 to -0.7, respectively) intensities on the tongue-tip. Depressed tongue-tip intensity in dependent smokers (with/without chronicity) versus never smokers was significant in younger (40-65 years), but not older (> 65 years) adults. Former smokers, non-chronic/less dependent smokers, and menthol smokers were more likely to report elevated whole-mouth quinine and 1 M NaCl intensities. Tongue-tip and whole-mouth taste intensity concordance varied between smokers and never smokers-current dependent smokers were more likely to rate tongue-tip quinine and NaCl lower than their respective whole-mouth tastants (OR: 1.8, 95% CI: 1.0 to 3.1 and OR: 1.8, 95% CI: 1.1 to 2.8, respectively). In summary, these U.S. nationally-representative data show that current smoking with chronicity and/or dependence associates with lower tongue-tip intensity for bitter and salty stimuli. Smokers with greater exposure to nicotine and/or dependence showed greater risk of taste alterations, with implications for diet- and smoking-related health outcomes.

Vestibular and oculomotor abnormalities among HIV-infected and HIV-uninfected men and women: A pilot study.

OBJECTIVE: To determine if middle-aged and aging men and women with HIV disease (HIV+) should be screened for vestibular and oculomotor dysfunction. METHODS: Age- and sociodemographically matched HIV+ and HIV- men and women were tested on vestibular evoked myogenic potential (VEMP), bi-thermic caloric testing, Dix-Hallpike maneuvers and saccades. RESULTS: HIV+ men had more caloric weakness than HIV- men. HIV+ subjects had more saccade abnormalities than HIV- subjects. A saccade abnormality was positively associated with being HIV+. Among the HIV+ sample, abnormalities were associated with increasing age, being male, ever taking monotherapy, and having an undetectable viral load. Only being male and having an undetectable viral load were statistically significant. Unilateral caloric weakness had a decreased prevalence with age per 10 years, and being HIV+ showed an increased prevalence. In HIV+ subjects only, these abnormalities decreased with age and being male but increased with undetectable viral load and ever taking antiretroviral monotherapy. No statistically significant differences were found. CONCLUSION: Women are at greater risk of vestibular and oculomotor abnormalities than men. HIV+ adults are at greater risk than HIV- adults. Physicians who care for HIV+ men and women should monitor the symptoms of vestibular and oculomotor impairment.

Concurrent prenatal drinking and smoking increases risk for SIDS: Safe Passage Study report.

BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality. Although the rate has plateaued, any unexpected death of an infant is a family tragedy thus finding causes and contributors to risk remains a major public health concern. The primary objective of this investigation was to determine patterns of drinking and smoking during pregnancy that increase risk of SIDS. METHODS: The Safe Passage Study was a prospective, multi-center, observational study with 10,088 women, 11,892 pregnancies, and 12,029 fetuses, followed to 1-year post delivery. Subjects were from two sites in Cape Town, South Africa and five United States sites, including two American Indian Reservations. Group-based trajectory modeling was utilized to categorize patterns of drinking and smoking exposure during pregnancy. FINDINGS: One-year outcome was ascertained in 94·2% infants, with 28 SIDS (2·43/1000) and 38 known causes of death (3·30/1000). The increase in relative risk for SIDS, adjusted for key demographic and clinical characteristics, was 11·79 (98·3% CI: 2·59-53·7, p < 0·001) in infants whose mothers reported both prenatal drinking and smoking beyond the first trimester, 3.95 (98·3% CI: 0·44-35·83, p = 0·14), for drinking only beyond the first trimester and 4·86 (95% CI: 0·97-24·27, p = 0·02) for smoking only beyond the first trimester as compared to those unexposed or reported quitting early in pregnancy. INTERPRETATION: Infants prenatally exposed to both alcohol and cigarettes continuing beyond the first trimester have a substantially higher risk for SIDS compared to those unexposed, exposed to alcohol or cigarettes alone, or when mother reported quitting early in pregnancy. Given that prenatal drinking and smoking are modifiable risk factors, these results address a major global public health problem. FUNDING: National Institute on Alcohol Abuse and Alcoholism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Deafness and Other Communication Disorders.

Words-in-Noise Test Performance in Young Adults Perinatally HIV Infected and Exposed, Uninfected.

Purpose The purpose of this study was to compare Words-in-Noise (WIN) data between young adults with perinatal HIV (PHIV) infection and those with PHIV exposure but uninfected (PHEU) and to evaluate associations between antiretroviral therapy (ART) exposures and WIN data. Method The WIN test and cognitive function were assessed in participants of the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol Up. Impaired WIN (IWIN) performance was defined as a signal-to-babble ratio of > +10 dB. Cognitive function was determined based on fluid cognition composite scores (FCCSs) and crystallized cognition composite scores, and < 70 was considered a fluid or crystallized cognitive impairment. Log binomial models were used to calculate the relative risks of IWIN between PHIV and PHEU. Results PHIV (n = 334) and PHEU (n = 52) participants had similar WIN thresholds and IWIN percentages. For young adults with FCCS ≥ 70, participants with PHIV were less likely to have IWIN for the better ear and worse ear as compared to participants with PHEU. For young adults with FCCS < 70, there was no association between HIV status and risk of IWIN for the better ear or worse ear. For those adults with crystallized cognition composite score of ≥ 70, young adults with PHIV were less likely to have IWIN for the better ear than young adults with PHEU; there was no association between HIV status and IWIN for the worse ear. For young adults with PHIV without a Centers for Disease Control and Prevention Class C diagnosis, a longer combination ART duration was associated with a higher risk of IWIN for the better ear. Conclusions For those without cognitive impairment, young adults with PHEU had poorer WIN thresholds than those young adults with PHIV. In young adults with PHIV who had no prior Centers for Disease Control and Prevention Class C diagnosis, a longer combination ART duration was associated with IWIN only in the better ear.

Associations of olfactory dysfunction with anthropometric and cardiometabolic measures: Findings from the 2013-2014 national health and nutrition examination survey (NHANES).

We examined associations of olfactory dysfunction with anthropometric and cardiometabolic measures in a nationally representative sample of US adults. In the 2013-2014 National Health and Nutrition Examination Survey (NHANES), 3,815 participants, 40 years and older, completed a standardized taste and smell protocol, which consisted of an 8-item odor identification test and a chemosensory questionnaire. Measured dysfunction was incorrect identification of ≥3 of 8 odors; self-reported dysfunction was affirmative response to either a recent smell problem, worse ability since age 25, or phantosmia. Survey-weighted linear regression models tested associations of olfactory dysfunction with body mass index (BMI), waist circumference (WC), blood pressure, serum total cholesterol (TC) with fractions, triglycerides, and glucose levels. Models were adjusted for age, race, education, physical activity, self-reported general health condition, smoking history, and income-to-poverty ratio, stratifying by sex and age group (middle-age 40-64 years; older ≥65 years). Relative to normal, measured olfactory dysfunction was associated with lower BMI [ß=-1.6 (95% CI: -3.2, -0.01)] in older men. In middle-age women, dysfunction was associated with higher BMI and WC, whether assessed by examination [ß's for BMI=3.1 (0.6, 5.5), WC=5.0 (0.3, 9.8)] or self-report [ß's for BMI=2.5 (0.6, 4.3), WC=6.1 (2.2, 9.9)]. Measured dysfunction was associated with significantly higher TC [ß=12.8 (7.5, 18.1)] and LDL [ß=18.1 (9.1, 27.2)] among older men, but significantly lower TC [ß=-15.0 (-25.0, -5.7)] and marginally lower LDL [ß=-12.0 (-25.0, 1.2)] among older women. Between measured dysfunction and fasting glucose, the association was inverse [ß=-7.9 (-13.0, -2.6)] among middle-age men, but positive [ß=15.6 (1.5, 29.7)] among older women. No significant associations were observed with blood pressure levels. In conclusion, among US adults ≥40 years, olfactory dysfunction is associated with anthropometric and glucose and lipid levels, with associations varying by sex and age group.

Association between vertigo, cognitive and psychiatric conditions in US children: 2012 National Health Interview Survey.

OBJECTIVES: Small studies have suggested an association between vertigo and psychiatric comorbidity. The purpose of this study is to evaluate the associations between vertigo and cognitive and psychiatric conditions among a large sample of U.S. children. METHODS: We conducted a cross-sectional analysis of the 2012 National Health Interview Survey (NHIS) Child Balance Supplement administered to parents/caregivers of children aged 3-17 years. Multivariable logistic regression models were used to evaluate the association between vertigo and specific cognitive and psychiatric conditions. RESULTS: The 1-year prevalence of vertigo was 1.56% in this nationally-representative sample (N = 10,823) of U.S. children aged 3-17 years. After adjusting for demographic and confounding health variables (otitis media and headaches/migraine), children with vertigo had significantly higher odds of attention deficit disorder (OR = 1.73, 95%CI: 1.06-2.81), learning disability (OR = 3.45, CI: 2.18), developmental delay (OR = 2.59, CI: 1.34-4.98), intellectual disability (OR = 6.60, CI: 2.60-16.79), and are more likely to utilize special education services (OR = 2.46, CI: 1.48-4.10) relative to the rest of U.S. children. Children with vertigo also had higher odds of having difficulty with emotions, concentration, or behavior (OR = 2.92, CI 1.85-4.61), and having a poor attention span (OR = 1.68, CI: 1.01-2.80). CONCLUSIONS: Vertigo is associated with significantly increased odds of cognitive and psychiatric comorbidity in U.S. children. These findings support the hypothesis that the vestibular system is important for normal cognitive and psychiatric development in children.

Birth Prevalence of Congenital Cytomegalovirus Infection in HIV-Exposed Uninfected Children in the Era of Combination Antiretroviral Therapy.

OBJECTIVES: To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. STUDY DESIGN: The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. RESULTS: Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/µL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. CONCLUSIONS: Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment.

Previous research has shown that genes play a substantial role in determining a person's susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden.

Poorer outcomes of all low birth weight groups at age 10: Missouri statewide case-control study.

BACKGROUND: In 1989-1991, a population-based cohort of every Missouri birth weighing < 1500 g was identified over a 16-month period. Infants born moderately low birth weight (MLBW, 1500-2499 g) and normal birth weight (NBW, ≥ 2500 g), were matched to < 1500 g infants by delivery date, race, maternal age, and residence. AIMS: To compare outcomes of extremely low birth weight (ELBW, < 1000 g), very low birth weight (VLBW, 1000-1499 g), and MLBW, to NBW infants at age 10. STUDY DESIGN: A population-based cohort and matched case-control study OUTCOME MEASURES: A Child Health and Development Questionnaire developed for this study collected social, medical, educational and special services history. The Conners' Parent Rating Scale-Revised was also completed by parents/caregivers. RESULTS: As birth weight declined, the prevalence of adverse outcomes increased. Children in all LBW groups were more likely than NBW children to have problems in speech and language, vision, fine and gross motor tasks, illnesses, attention, school performance, and increased requirements for therapy and accommodation. Repetition of a grade was three times higher for MLBW children and over three times higher for the other LBW groups. CONCLUSION: In this statewide population-based study, controlling for child's sex, mother's age, race, residence, education, marital status, Medicaid assistance, and smoking or alcohol use during pregnancy, failed to eliminate the strong effect of decreasing birth weight. Problems were most frequent in ELBW, however, VLBW and MLBW also had many significantly greater problems than NBW children. All LBW groups of children experienced greater adverse health and developmental outcomes resulting in significant habilitation and educational challenges.