Cohort profile: Beyond birth cohort study - The Korean CHildren's ENvironmental health Study (Ko-CHENS).

The Korean CHildren's ENvironmental health Study (Ko-CHENS) is a nationwide prospective birth cohort showing the correlation between the environmental exposures and the health effects to prevent the environmental diseases in children, and it provides the guidelines for the environmental hazardous factors, applying the life-course approach to the environmental-health management system. The Ko-CHENS consists of 5000 Core and 65,000 Main Cohorts. The children in the Core Cohort are followed up at 6 months, every year before their admission into the elementary school, and every 3 years from the first year after this admission. The children in the Cohort will be followed up through the data links (Statistics Korea, National Health Insurance Service [NHIS], and Ministry of Education). The individual biospecimens will be analyzed for 19 substances. The long-term-storage biological samples will be used for the further substance analysis. The Ko-CHENS will investigate whether the environmental variables including the perinatal outdoor and indoor factors and the greenness contribute causally to the health outcomes in the children and adolescents. In addition to the individual surveys, the assessments of the outdoor exposures and health outcomes will use the national air-quality monitoring data and claim data of the NHIS, respectively. The two big-data forms of the Ko-CHENS are as follows: The Ko-CHENS data that can be linked with the nationally registered NHIS health-related database, including the medical utilization and the periodic health screening, and the birth/mortality database in the Statistics; the other is the Big-CHENS dataset that is based on the NHIS mother delivery code, for which the follow-up of almost 97% of the total birth population is expected. The Ko-CHENS is a very cost-effective study that fully exploits the existing national big-data systems with the data linkage.

Effect of tumour necrosis factor-alpha inhibitors on renal function in patients with rheumatoid arthritis from the KOBIO registry from 2012 to 2016.

OBJECTIVES: The effect of biological disease-modifying anti-rheumatic drugs (bDMARDs) on renal function in patients with rheumatoid arthritis (RA) has not been well established. We assessed whether tumour necrosis factor (TNF) inhibitors could affect renal function in RA. METHODS: A total of 2110 patients with RA enrolled in the Korean College of Rheumatology Biologics (KOBIO) registry were analysed. All patients were taking bDMARDs or conventional synthetic DMARDs (csDMARDs). Renal function was evaluated by calculating the estimated glomerular filter rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. Renal insufficiency was defined as eGFR <60 mL/min/1.73 m2. Differences in eGFR changes between different types of DMARDs were assessed at each follow-up time using the generalised linear model (GLM) method. Risk factors for renal insufficiency were identified using binary logistic regression analysis. RESULTS: The changes of eGFR values in patients treated with TNF inhibitors were not significantly different from those with csDMARDs alone or non-TNF inhibitors in all RA patients regardless of renal function. Among patients with renal insufficiency, GLM analysis revealed that the changes of eGFR values by TNF inhibitors were also compatible to those treated with csDMARDs alone or non-TNF inhibitors. Older age (>55 years), longer disease duration (>5 years), and use of methotrexate were identified as clinical determinants for renal insufficiency. CONCLUSIONS: TNF inhibitors did not influence the change of renal function during RA treatment. TNF inhibitors may be a safe treatment option irrespective of renal function.

Maternal and paternal serum concentrations of persistent organic pollutants and the secondary sex ratio: A population-based preconception cohort study.

Recent declines in the secondary sex ratio (SSR), defined as the ratio of males to females at birth, in some industrialized countries may be attributed to exposure to environmental toxicants such as persistent organic pollutants (POPs). This study aimed to evaluate the association of couples' preconception exposure to POPs with the SSR. The study cohort comprised 235 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and prospectively followed through delivery of a singleton birth. Upon enrollment, couples' serum concentrations (ng/g) were measured for 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, and 36 polychlorinated biphenyls (PCBs). Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of a male birth for each chemical. Of the 56 POPs examined, maternal PCB 128 and paternal hexachlorobenzene were significantly associated with a female excess (RRs, 0.75 [95% CI, 0.60-0.94] and 0.81 [95% CI, 0.68-0.97] per 1SD increase in log-transformed serum chemical concentrations, respectively), whereas maternal mirex and paternal PCB 128 and p,p'-dichlorodiphenyldichloroethylene were significantly associated with a male excess (RR range, 1.10-1.22 per 1SD increase in log-transformed serum chemical concentrations). After adjusting for multiple comparisons, only maternal mirex remained significantly associated with the SSR. This exploratory study on multiple classes of POPs demonstrated no conclusive evidence on the association between parental preconception exposure to POPs and the SSR.

Couples' urinary bisphenol A and phthalate metabolite concentrations and the secondary sex ratio.

With limited research focusing on non-persistent chemicals as exogenous factors affecting human sex selection, this study aimed to evaluate the association of urinary bisphenol A (BPA) and phthalate metabolite concentrations with the secondary sex ratio (SSR), defined as the ratio of male to female live births. The current analysis is limited to singleton live births (n=220, 43.9%) from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, in which couples discontinuing contraception with the intention of becoming pregnant were enrolled and followed while trying for pregnancy and through delivery for those achieving pregnancy. Using modified Poisson regression models accounting for potential confounders, we estimated the relative risks (RRs) of a male birth per standard deviation change in the log-transformed maternal, paternal, and couple urinary BPA and 14 phthalate metabolite concentrations (ng/mL) measured upon enrollment. When maternal and paternal chemical concentrations were modeled jointly, paternal BPA (RR, 0.77; 95% confidence interval [CI], 0.62-0.95) and mono-isobutyl phthalate (RR, 0.82; 95% CI, 0.67-1.00) were significantly associated with a female excess. Contrarily, maternal BPA (RR, 1.16; 95% CI, 1.03-1.31), mono-isobutyl phthalate (RR, 1.28; 95% CI, 1.06-1.54), mono-benzyl phthalate (RR, 1.31; 95% CI, 1.08-1.58), and mono-n-butyl phthalate (RR, 1.24; 95% CI, 1.01-1.51) were significantly associated with a male excess. These findings underscore varying patterns for the SSR in relation to parental exposures. Given the absence of previous investigation, these partner-specific associations of non-persistent chemicals with the SSR need future corroboration.

The effect of coffee, tea, and caffeine consumption on serum uric acid and the risk of hyperuricemia in Korean Multi-Rural Communities Cohort.

Caffeine, a commonly consumed food constituent, is known to exert beneficial physiological effects in humans. There is a lack of comprehensive population data for the effects of caffeine intake on urate metabolism. Therefore, the aim of this study was to determine whether coffee, tea, and caffeine intake influences serum uric acid and the risk of hyperuricemia in the Korean Multi-Rural Communities Cohort. We enrolled 9,400 participants in this study. An assessment of various dietary intake amounts of substances such as coffee and tea was performed using a food frequency questionnaire. The content of caffeine was calculated from coffee (74 mg/cup) and tea (15 mg/cup) intake information from the past year. Multivariate logistic regression models, multiple linear regression models, and analysis of covariance were applied to identify any association of dietary intake with serum uric acid levels or the risk of hyperuricemia. No trends for coffee, tea, or caffeine intake were found according to each quintile with serum uric acid in males, although there were weak, marginally significant trends between the content of coffee and caffeine intake and serum uric acid level in females (p = 0.07 for both). Tea intake in males and caffeine intake in females were significantly different between non-hyperuricemia and hyperuricemia (p = 0.04 and p = 0.04, respectively). In addition, a significant association of serum uric acid level with tea intake in males (ß = 0.0006, p = 0.02) and with tea intake and caffeine intake in females (ß = 0.0003, p = 0.04 and ß = 0.0006, p = 0.02, respectively) was observed. There was no effect of coffee, tea, or caffeine intake on the risk of hyperuricemia in either males or females. This study suggests that caffeine consumption might have an effect on serum uric acid in females. However, coffee, tea, and caffeine intake amounts were not associated with the risk of hyperuricemia.

TNFAIP3 gene polymorphisms associated with differential susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Korean population.

OBJECTIVE: We investigated the relationship between polymorphisms in the TNF-a-induced protein 3 (TNFAIP3) gene and genetic susceptibility to SLE and RA in the Korean population. METHODS: The present case control study included 422 patients with RA, 133 patients with SLE and 422 healthy controls. Genotyping for TNFAIP3 gene polymorphisms rs5029941 (C>T), rs2230926 (T>G), rs5029930 (C>A), rs5029937 (G>T) and rs5029939 (G>C) in TNFAIP3 gene polymorphisms was performed. The status of RA-related autoantibodies, including RF and anti-CCP, in RA and the presence of arthritis and nephritis in SLE were assessed. RESULTS: Significantly different frequencies of minor alleles in two TNFAIP3 polymorphisms were found in patients with SLE compared with healthy controls [odds ratio (OR) 2.13, 95% CI 1.25, 3.65, P= 0.02 for rs5029937; OR 2.17, 95% CI 1.27, 3.72, P= 0.01 for rs5029939). Moreover, patients with SLE showed different frequencies of haplotypes compared with healthy controls (P<0.001). However, no association was found between RA susceptibility and TNFAIP3 polymorphisms (P= 0.28). Interactions between RA-related autoantibody status and TNFAIP3 polymorphisms were not associated with RA susceptibility. Interestingly, arthritis in patients with SLE was marginally associated with TNFAIP3 polymorphisms (P= 0.04). CONCLUSION: The results suggest that TNFAIP3 gene polymorphisms are associated with differential susceptibility to SLE and RA in the Korean population. The relationship between TNFAIP3 gene polymorphisms and RA susceptibility may be dependent on ethnic background.

Performance of Routine Assessment of Patient Index Data 3 (RAPID3) for assessment of rheumatoid arthritis in clinical practice: differential agreement of RAPID3 according to disease activity categories.

To evaluate the performance of Routine Assessment of Patient Index Data 3 (RAPID3) with the disease activity score 28 (DAS28) and the clinical/simplified disease activity index (CDAI/SDAI) in a Korean population with rheumatoid arthritis (RA). Four hundred patients with RA were consecutively enrolled. All patients completed disease activity indices such as RAPID3, DAS28, SDAI, and CDAI. The kappa and/or weighted coefficients were used to assess agreement between RAPID3 and other disease activity indices. ANOVA, Mantel-Haenszel chi-square test, and Spearman's partial correlation analysis were used for analyses. RAPID3 scores were significantly correlated with DAS28 (r = 0.62), SDAI (r = 0.74), and CDAI (r = 0.75; p < 0.0001 for all indices) and other activity measures including swollen/tender joint counts, erythrocyte sediment rate, and C-reactive protein. The weighted kappa coefficients of RAPID3 with DAS28, SDAI, and CDAI among the four disease activity categories were 0.33, 0.34, and 0.33, respectively. Kappa coefficients for RAPID3 in two disease activity categories increased more than four categories (κ = 0.40-0.42) indicating fair agreement. More than 86 % of patients with high-to-moderate disease activity in DAS28, CDAI, and SDAI had high-to-moderate disease activity using RAPID3 criteria. However, approximately 50 % of patients with remission-to-low disease activity in DAS28, CDAI, and SDAI showed remission-to-low disease activity in RAPID3. This study confirms RAPID3 as an informative disease activity index with equivalent values in DAS28, CDAI, and SDAI. RAPID3 reveals differential agreement in patients with lower disease activity.

Association between phthalate exposure and sleep quality in pregnant women: Results from the Korean Children's Environmental Health Study with repeated assessment of exposure.

Background: Evidence linking environmental toxicants to sleep quality is growing; however, these associations during pregnancy remain unclear. We examined the associations of repeated measures of urinary phthalates in early and late pregnancy with multiple markers of sleep quality among pregnant women. Methods: The study population included 2324 pregnant women from the Korean Children's Environmental Health Study. We analyzed spot urine samples collected at two time points during pregnancy for exposure biomarkers of eight phthalate metabolites. We investigated associations between four summary phthalates (all phthalates: ∑Phthalates; di-(2-ethylhexyl) phthalate: ∑DEHP; phthalates from plastic sources: ∑Plastic; and antiandrogenic phthalates: ∑AA) and eight individual phthalates and self-reported sleep measures using generalized ordinal logistic regression and generalized estimating equations models that accounted for repeated exposure measurements. The models were adjusted for age, body mass index, education, gestational age, income, physical activity, smoking, occupation, chronic diseases, depression, and urinary cotinine levels. Results: Multiple individual phthalates and summary measures of phthalate mixtures, including ∑Plastic, ∑DEHP, ∑AA, and ∑Phthalates, were associated with lower sleep efficiency. To illustrate, every 1-unit log increase in ∑AA was associated with a reduction of sleep efficiency by 1.37 % (95% confidence interval [CI] = -2.41, -0.32). ∑AA and ∑Phthalates were also associated with shorter sleep duration and longer sleep latency. Associations between summary phthalate measures and sleep efficiency differed by urinary cotinine levels (P for subgroup difference < 0.05). Conclusions: Findings suggest that higher phthalate exposure may be related to lower sleep efficiency, shorter sleep duration, and prolonged sleep latency during pregnancy.

Ambient particulate matter and surrounding greenness in relation to sleep quality among pregnant women: A nationwide cohort study.

Background: Particulate air pollution and residential greenness are associated with sleep quality in the general population; however, their influence on maternal sleep quality during pregnancy has not been assessed. Objective: This cross-sectional study investigated the individual and interactive effects of exposure to particulate matter (PM) air pollution and residential greenness on sleep quality in pregnant women. Methods: Pregnant women (n = 4933) enrolled in the Korean Children's Environmental Health Study with sleep quality information and residential address were included. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The average concentrations of PM (PM2.5 and PM10) during pregnancy were estimated through land use regression, and residential greenness in a 1000 m buffer area around participants' residences was estimated using the Normalized Difference Vegetation Index (NDVI1000-m). Modified Poisson regression models were used to estimate the associations between PM and NDVI and poor sleep quality (PSQI >5) after controlling for a range of covariates. A four-way mediation analysis was conducted to examine the mediating effects of PM. Results: After adjusting for confounders, each 10 µg/m3 increase in PM2.5 and PM10 exposure was associated with a higher risk of poor sleep quality (relative risk [RR]: 1.06; 95% confidence interval [CI]: 1.01, 1.11; and RR: 1.09; 95% CI: 1.06, 1.13, respectively), and each 0.1-unit increase in NDVI1000-m was associated with a lower risk of poor sleep quality (RR: 0.97; 95% CI: 0.95, 0.99). Mediation analysis showed that PM mediated approximately 37%-56% of the association between residential greenness and poor sleep quality. Conclusions: This study identified a positive association between residential greenness and sleep quality. Furthermore, these associations are mediated by a reduction in exposure to particulate air pollution and highlight the link between green areas, air pollution control, and human health.

Relation of rheumatoid factor and anti-cyclic citrullinated peptide antibody with disease activity in rheumatoid arthritis: cross-sectional study.

To analyze the association of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) with non-remission and with disease activity measures in rheumatoid arthritis (RA). Cross-sectional study of consecutive RA patients. Non-remission was defined as a disease activity score (DAS28) ≥ 2.6 at study enrollment. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were additionally measured. Serum titers of RF and anti-CCP were transformed into incremental levels (100/units) and log-transformed levels. Analysis of association with non-remission was done with logistic regression models, with and without adjustment for age, sex, disease duration, and corticoid use. Multiple regression models, raw and similarly adjusted, were used to measure the association of RF and anti-CCP with the disease activity measures. A total of 385 patients were included, of whom 286 (74 %) were not in remission. Log-transformed RF level was associated with an increased risk of non-remission after adjustment (OR = 1.32, 95 % CI 1.04-1.67). This association was especially evident in patients with less than 10 years of disease duration (OR = 1.51, 95 % CI 1.15-1.99) and in those using steroids (OR = 2.06, 95 % CI 1.22-3.48). Serum RF titers and log-transformed RF levels showed a small but significant association with DAS28 score (adjusted beta coefficients 0.002 and 0.18, respectively; both p ≤ 0.01), but neither with SDAI or CDAI nor with anti-CCP antibody. : Log-transformed RF levels might be associated with non-remission in RA, especially in patients with short disease duration or on steroids.

High-Performance Organic Source-Gated Transistors Enabled by the Indium-Tin Oxide-Diketopyrrolopyrrole Polymer Interface.

Source-gated transistors are a new driver of low-power high-gain thin-film electronics. However, source-gated transistors based on organic semiconductors are not widely investigated yet despite their potential for future display and sensor technologies. We report on the fabrication and modeling of high-performance organic source-gated transistors utilizing a critical junction formed between indium-tin oxide and diketopyrrolopyrrole polymer. This partially blocked hole-injection interface is shown to offer both a sufficient level of drain currents and a strong depletion effect necessary for source pinch-off. As a result, our transistors exhibit a set of outstanding metrics, including an intrinsic gain of 160 V/V, an output resistance of 4.6 GΩ, and a saturation coefficient of 0.2 at an operating voltage of 5 V. Drift-diffusion simulation is employed to reproduce and rationalize the experimental data. The modeling reveals that the effective contact length is significantly reduced in an interdigitated electrode geometry, eventually contributing to the realization of low-voltage saturation.

The relationship between alcohol consumption and knee osteoarthritis in Korean population over 50 years-old: Results from Korea National Health and Nutrition Examination Survey.

ABSTRACT: There is still debate regarding the pathogenic relationship between alcohol intake and osteoarthritis (OA). This study investigated the association between alcohol consumption and knee OA in a Korean population.Among 8058 subjects who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) 2012, a total of 2917 subjects over the age of 50 and taken plain radiography was included in this analysis. Knee OA was classified based on the Kellgren-Lawrence (K-L) grading scale. Multivariate logistic regression analyses were used to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) of variables for knee OA (K-L grade ≥ 2).There were 1022 subjects with knee OA (29.2%). Subjects with knee OA tended to have lower daily alcohol intake (g/day) than did those without knee OA (10.4 [6.2-14.6] vs. 15.8 [12.8-18.8], P = .04). Similarly, those with knee OA demonstrated less makgeolli intake than did those without knee OA (P = .002). Subjects who consumed >0.6 g/day of beer also demonstrated less knee OA than did those who consumed <0.6 g/day of beer (OR 0.68, 95% CI 0.46-0.99). However, knee OA was not associated with the categories of alcohol consumption amount (g/day), including total daily alcohol intake (g/day), soju daily intake (g/day), and makgeolli daily intake (g/day) (P > .05 of all).Alcohol consumption was negatively associated with prevalence of knee OA in a Korean population. This preliminary observation will need to be confirmed in future studies.

Effects of Socio-demographic Factors on the Decreasing Trend in the Sex Ratio at Birth in Korea, 1997-2017.

OBJECTIVES: This study investigated the effects of socio-demographic factors on the decreasing trend in the sex ratio at birth from 1997 to 2017 in Korea. METHODS: Data from 10 349 602 live births registered with Statistics Korea from 1997 to 2017 were analyzed. The secondary sex ratio (SSR), defined as the ratio of male to female live births, during the study period (1997-1999 [phase I], 2000-2002 [phase II], 2003-2005 [phase III], 2006-2008 [phase IV], 2009-2011 [phase V], 2012-2014 [phase VI], and 2015-2017 [phase VII]) was calculated according to selected socio-demographic factors, such as parental age, education, occupation, and birth order. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals for a male birth after adjusting for potential confounders. RESULTS: The SSR gradually decreased from 1.10 (in 1998-2000 and 2002) to 1.05 (in 2013-2016). While a decreasing trend in the SSR was not noted among first births, male-biased sex ratios were prominent among third and higher-order births, for which the highest SSR was 1.46 in 1998. Higher birth order was significantly associated with an excess of male births in phases I-VI (≥third vs. first, OR range, 1.03 to 1.35). Advanced maternal age was significantly associated with an excess of female births in phases II, III, and V (≥40 vs. 20-24 years, OR range, 0.92 to 0.95). CONCLUSIONS: This study demonstrated that advanced maternal age and reduction of the artificially-biased SSR among third and higher-order births may partially explain the decreasing trend in the SSR from 1997 to 2017 in Korea.

Impact of Changes in Maternal Age and Parity Distribution on the Increasing Trends in the Low Birth Weight and Very Low Birth Weight Rates in South Korea, 2005-2015.

OBJECTIVES: The aim of this study was to evaluate the impact of shifts in maternal age and parity on the increasing trends in the low birth weight (LBW) and very low birth weight (VLBW) rates from 2005 to 2015 in South Korea. METHODS: Data from 4 993 041 live births registered with Statistics Korea during the period between 2005 and 2015 were analyzed. Applying a modified standardization method, we partitioned the total increment in the LBW and VLBW rates into (1) the increase in the LBW and VLBW rates due to changes in the maternal age and parity distribution (AP-dis) and (2) the increase due to changes in the age-specific and parity-specific rates (AP-spe) of LBW and VLBW for singleton and multiple births, respectively. RESULTS: During the study period, the total increment in the LBW and VLBW rates was 1.43%p and 0.25%p, respectively. Among singleton births, changes in the AP-dis accounted for 79% (0.34%p) and 50% (0.06%p) of the total increment in the LBW and VLBW rates, respectively. Meanwhile, among multiple births, changes in the AP-dis did not contribute to the increase in the LBW and VLBW rates, with 100% of the increase in the LBW (1.00%p) and VLBW (0.13%p) rates being attributed to changes in the AP-spe. CONCLUSIONS: This study demonstrated that shifts in maternal age and parity were prominent contributors to the increase in the LBW and VLBW rates among singleton births between 2005 and 2015 in South Korea.

Association of head circumference with cognitive decline and symptoms of depression in elderly: a 3-year prospective study.

Background: Brain volume is associated with dementia and depression in the elderly. An easy way to predict relative brain volume is to measure head circumference. In this study, we investigated the relationship between head circumference and cognition as well as depression in a non-demented elderly community. Methods: Baseline and follow-up surveys were conducted in 2007 and 2010. At baseline, community residents aged 65 years or over (n=382) within a rural area of South Korea were screened for dementia and symptoms of depression and were followed using the same screening battery after 3 years (n=279). Data from anthropometric measurements (head circumference, height, and body weight), demographics, and blood tests were gathered. Neuropsychological tests, including the Korean version of mini-mental state examination (K-MMSE), clinical dementia rating (CDR) including the CDR-sum of boxes, the Korean version of instrumental activities of daily living, and geriatric depression scale (GDS), were performed. None of the 279 subjects followed were demented. Results: Baseline performance on the K-MMSE and GDS was poorer for participants with smaller head circumferences. Follow-up performance on the MMSE was also poorer for participants with smaller head circumferences. Interestingly, participants with smaller head circumference showed worse GDS scores at baseline but on follow-up examination, participants with larger head circumference showed rapid worsening than those with smaller head circumference with marginal significance by ANOVA test. In regression coefficient analysis, GDS decline showed significant difference. Conclusion: Head circumference was not associated with cognitive change but was associated with symptoms of depression in non-demented community residents.

Preconception stress and the secondary sex ratio in a population-based preconception cohort.

OBJECTIVE: To examine the association between preconception parental stress and the secondary sex ratio, defined as the ratio of males to females at birth. DESIGN: A population-based preconception cohort. SETTING: Not applicable. PATIENT(S): A total of 235 couples who were enrolled before conception in Michigan and Texas between 2005 and 2009 and who had a singleton birth during the follow-up period. Couples were interviewed separately at baseline to obtain information on perceived stress (Cohen's Perceived Stress Scale) and lifetime history of physician-diagnosed anxiety and/or mood disorders. Female partners were also trained to collect basal saliva samples for the measurement of salivary stress markers, alpha-amylase and cortisol. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each stress marker. RESULT(S): After adjusting for potential confounders, we observed a 76% increase in the risk of fathering a male infant (RR 1.76; 95% confidence interval 1.17-2.65) in men diagnosed with anxiety disorders compared with those who were not diagnosed. When lifetime history of physician-diagnosed anxiety disorders was modeled jointly for the couple, the association was slightly strengthened (RR 2.03; 95% confidence interval 1.46-2.84). CONCLUSION(S): This prospective cohort study suggests that paternal lifetime history of physician-diagnosed anxiety disorders may be associated with an increase in the secondary sex ratio, resulting in an excess of male births.

Human semen quality and the secondary sex ratio.

The aim of this study was to evaluate the association between semen quality and the secondary sex ratio (SSR), defined as the ratio of male to female live births. Our study cohort comprised 227 male partners who were enrolled prior to conception in Michigan and Texas between 2005 and 2009, and prospectively followed through delivery of a singleton birth. The male partners provided a baseline and a follow-up semen sample a month apart. Semen analysis was conducted to assess 27 parameters including five general characteristics, six sperm head measures, 14 morphology measures, and two sperm chromatin stability assay measures. Modified Poisson regression models with a robust error variance were used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of a male birth for each semen parameter, after adjusting for potential confounders. Of the 27 semen parameters, only the percentage of bicephalic sperm was significantly associated with the SSR (2 nd vs 1 st quartile, RR, 0.65, 95% CI, 0.45-0.95, P = 0.03; 4 th vs 1 st quartile, RR, 0.61, 95% CI, 0.38-1.00, P < 0.05 before rounding to two decimal places), suggestive of a higher percentage of bicephalic sperm being associated with an excess of female births. Given the exploratory design of the present study, this preconception cohort study suggests no clear signal that human semen quality is associated with offspring sex determination.

Couples' urinary concentrations of benzophenone-type ultraviolet filters and the secondary sex ratio.

The secondary sex ratio (SSR), defined as the ratio of males to females at birth, has been investigated in relation to endocrine disruptors to search for environmental toxicants perturbing human sex selection. Benzophenone (BP)-type ultraviolet (UV) filters, which are used in sunscreens and personal care products, have been reported to exert estrogenic and anti-androgenic activities. This study aimed to evaluate the association between maternal, paternal, and couple urinary concentrations of BP-type UV filters and the SSR, given the absence of previous investigation. The study cohort comprised 220 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and who had a singleton birth during the follow-up period. Couples' urinary concentrations of five BP-type UV filters (ng/mL) were measured using triple-quadrupole tandem mass spectrometry: 2,4-dihydroxybenzophenone (BP-1), 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), and 4-hydroxybenzophenone (4-OH-BP). Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each BP-type UV filter, after adjusting for potential confounders. When maternal and paternal urinary BP-type UV filter concentrations were modeled jointly, both maternal BP-2 (2nd vs 1st tertile, RR, 0.62, 95% confidence interval [CI], 0.43-0.91) and paternal BP-2 (3rd vs 1st tertile, RR, 0.67, 95% CI, 0.45-0.99; p-trend, 0.04) were significantly associated with an excess of female births. Contrarily, maternal 4-OH-BP was significantly associated with an excess of male births (2nd vs 1st tertile, RR, 1.87, 95% CI, 1.27-2.74; 3rd vs 1st tertile, RR, 1.80, 95% CI, 1.13-2.87; p-trend, 0.02). Our findings provide the first evidence suggesting that BP-type UV filters may affect the SSR. However, future corroboration is needed, given the exploratory design of this study.

Influence of asthma on the longitudinal trajectories of cigarette use behaviors from adolescence to adulthood using latent growth curve models.

OBJECTIVES: While epidemiologic research indicates that the prevalence of risk-taking behaviors including cigarette smoking among young people with asthma is substantial, the longitudinal patterns of cigarette smoking in this vulnerable population have received little attention. The aim of this study was to evaluate differences in the longitudinal trajectories of cigarette use behaviors from adolescence to adulthood between young people with and without asthma. METHODS: Data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) during the years 1994 to 1995 (Wave I, adolescence), 2001 to 2002 (Wave III, young adulthood), and 2007 to 2008 (Wave IV, adulthood) were analyzed (n=12 244). Latent growth curve models were used to examine the longitudinal trajectories of cigarette use behaviors during the transition to adulthood according to asthma status. RESULTS: Regardless of asthma status, the trajectory means of cigarette use behaviors were found to increase, and then slightly decrease from adolescence to adulthood. In total participants, there were no statistically significant differences in initial levels and changes in cigarette use behaviors according to asthma status. However, in select sex and race subgroups (i.e., females and non-whites), former asthmatics showed greater escalation in cigarette use behaviors than did non-asthmatics or current asthmatics. CONCLUSIONS: This study indicated that the changing patterns of cigarette use behaviors during the transition to adulthood among young people with asthma are comparable to or even more drastic than those among young people without asthma.

Urinary concentrations of benzophenone-type ultraviolet light filters and semen quality.

OBJECTIVE: To assess benzophenone-type ultraviolet (UV) filter concentrations, chemicals used in sunscreen and personal care products, and semen endpoints. DESIGN: Cohort. SETTING: Not applicable. PATIENT(S): A total of 413 men provided semen and urine samples, 2005-2009. Five UV filters were quantified (ng/mL) in urine using liquid chromatography-triple quadrupole mass spectrometry: BP-1 (2,4-dihydroxybenzophenone), BP-2 (2,2',4,4'-tetrahydroxybenzophenone), BP-3 (2-hydroxy-4-methoxybenzophenone), BP-8 (2,2'-dihydroxy-4-methoxybenzophenone), and 4-OH-BP (4-hydroxybenzophenone). Using linear regression, ß-coefficients (ß) and 95% confidence intervals (CIs) for each chemical dichotomized at the 75th percentile and Box-Cox transformed semen endpoint were estimated, after adjusting for age, body mass index, cotinine, season, and site. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Thirty-five semen endpoints. RESULT(S): BP-2 was associated with diminished sperm concentration (ß = -0.74; 95% CI -1.41, -0.08), straight (ß = -4.57; 95% CI -8.95, -0.18) and linear movement (ß = -3.15; 95% CI -6.01, -0.30), more immature sperm (ß = 0.38; 95% CI 0.15, 0.62), and a decreased percentage of other tail abnormalities (ß = -0.16; 95% CI -0.31, -0.01). BP-8 was associated with decreased hypo-osmotic swelling (ß = -2.57; 95% CI -4.86, -0.29) and higher acrosome area (ß = 1.14; 95% CI 0.01, 2.26). No associations were observed for BP-1, BP-3, or 4OH-BP. CONCLUSION(S): The findings suggest that specific UV filters may be associated with some aspects of semen endpoints, but await future corroboration.