Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

Association of educational attainment with cancer mortality in a national cohort study of black and white adults: A mediation analysis.

Background: Low educational attainment is associated with excess cancer mortality. However, the mechanisms driving this association remain unknown. Methods: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated the associations of participant and parental/caregiver education with cancer mortality using Cox proportional hazards models, adjusting for socio-demographic characteristics and health conditions. We used principal components analysis to generate indices of measures representing the social determinants of health (SDOH) and health behaviors. We used structural equation modeling to determine if the association between educational attainment and cancer mortality was mediated by these domains. Results: Among 30,177 REGARDS participants included in this analysis, 3798 (12.6%) had less than a high school degree. In fully adjusted models, those without a high school education experienced about 50% greater risk of death than high school graduates and higher (White participants HR: 1.47; 95% CI: 1.23, 1.76 and Black HR: 1.54; 95% CI: 1.33, 1.79). There was evidence of a modest mediation effect for the association between education and cancer mortality by the SDOH domain score (White total effect HR: 1.25; 95% CI: 1.18, 1.33, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.21; 95% CI: 1.14, 1.28 and Black total effect HR: 1.24; 95% CI: 1.18, 1.29, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.19; 95% CI: 1.14, 1.24). There was no evidence of mediation by the health behaviors score. No significant associations were found for female caregiver/mother's or male caregiver/father's education (N = 13,209). Conclusions: In conclusion, participant education was strongly associated with cancer mortality, and this association was partially mediated by the SDOH domain score.

Association Between Change in Physical Activity During Pregnancy and Infant Birth Weight.

OBJECTIVE: We assessed whether total, recreational, and non-recreational physical activity (PA) assessed twice during pregnancy, and its change, were associated with infant birth weight and small for gestational age (SGA). METHODS: We included 1467 Pregnancy, Infection, and Nutrition 3 Study participants who self-reported PA at time 1 (T1: 17-22 weeks' gestation) and time 2 (T2: 27-30 weeks' gestation). We assessed last week absolute intensities of PA (moderate: 4.7-7.1 METs; and vigorous: > 7.1 METs) and perceived intensities. Change in hours/week of PA was assessed continuously or categorically (increase or decrease ≥ 1 hour, and no change). Associations of continuous PA hours/week at T1, T2, and its change, with sex-specific z-scores of birth weight, were assessed using multivariable linear robust regressions. We used logistic regressions to assess categorical PA measures with SGA. Models were adjusted for adequacy of maternal weight gain, general health, maternal age, parity, race/ethnicity, and smoking. RESULTS: Hours/week of total and recreational absolute intensities of PA at T1, T2, and its change were generally not associated with birth weight, although two measures of non-recreational PA at T2 and its change were associated with increased birth weight. Perceived intensities of PA (at T1, T2, and its change) were largely not associated with sex-specific z-scores of infant birth weight. Absolute and perceived intensity PA were not associated with SGA. CONCLUSIONS FOR PRACTICE: In this observational cohort, increases and decreases in PA during pregnancy were not associated with differential changes in birthweight or SGA.

The association of prenatal phthalates, organophosphorous pesticides, and organophosphate esters with early child language ability in Norway.

BACKGROUND: Prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides have been associated with neurodevelopmental deficits including language ability, however, few studies consider the effect of exposure mixtures and the potential longitudinal detriments over time. OBJECTIVE: This study examines the influence of prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides, on children's language ability from toddlerhood to the preschool period. METHODS: This study includes 299 mother-child dyads from Norway in the Norwegian Mother, Father and Child Cohort Study (MoBa). Prenatal exposure to chemicals were assessed at 17 weeks' gestation, and child language skills were assessed at 18 months using the Ages and Stages Questionnaire communication subscale and at preschool age using the Child Development Inventory. We ran two structural equation models to examine the simultaneous influences of chemical exposures on parent-reported and teacher-reported child language ability. RESULTS: Prenatal organophosphorous pesticides were negatively associated with preschool language ability through language ability at 18 months. Additionally, there was a negative association between low molecular weight phthalates and teacher-reported preschool language ability. There was no effect of prenatal organophosphate esters on child language ability at either 18 months or preschool age. CONCLUSIONS: This study adds to the literature on prenatal exposure to chemicals and neurodevelopment and highlights the importance of developmental pathways in early childhood.

Prenatal Exposure to Organophosphorus Pesticides and Preschool ADHD in the Norwegian Mother, Father and Child Cohort Study.

Prenatal organophosphorus pesticide (OPP) exposure has been associated with child attention-deficit/hyperactivity disorder (ADHD) in agricultural communities and those that are exposed to residentially applied insecticides. To examine this association in populations that are exposed primarily through diet, we estimate the associations between prenatal OPP exposure and preschool ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa), and describe modification by paraoxonase 1 (PON1) gene variants. We used participants from the MoBa Preschool ADHD Sub-study (n = 259 cases) and a random sample of MoBa sub-cohort participants (n = 547) with birth years from 2004 to 2008. Prenatal urinary dialkylphosphate (DAP) metabolites (total diethylphosphate [∑DEP] and total dimethylphosphate [∑DMP]) were measured by an ultra-performance liquid chromatography-time-of-flight system and summed by molar concentration. Maternal DNA was genotyped for coding variants of PON1 (Q192R and L55M). We used a multivariable logistic regression to calculate the odds ratios (OR) and 95% confidence intervals, adjusted for maternal education, parity, income dependency, age, marital status, ADHD-like symptoms, pesticide use, produce consumption, and season. We found no associations between DAP metabolite concentrations and preschool ADHD. The adjusted ORs for exposure quartiles 2-4 relative to 1 were slightly inverse. No monotonic trends were observed, and the estimates lacked precision, likely due to the small sample size and variation in the population. We found no evidence of modification by PON1 SNP variation or child sex. Maternal urinary DAP concentrations were not associated with preschool ADHD.

Maternal Physical Activity at Term and Spontaneous Labor: A Case-Crossover Study.

BACKGROUND: This study assessed associations between antenatal physical activity and the onset of spontaneous labor (SL). METHODS: Data were taken from 541 participants in the third pregnancy, infection, and nutrition study who had no contraindications to antenatal physical activity. An interviewer-administered questionnaire assessed labor triggers, gestational age at birth, and physical activity within the week (24 h to 7 d) and the 24-hour period (0-24 h) prior to SL. A case-crossover design examined the association between physical activity (recreational, occupational, or any) and the risk of onset of SL within the subsequent 24 hours. RESULTS: Overall, 21% (any), 26% (recreational), and 14% (occupational) of participants reported physical activity during the week; whereas 5% (any), 7% (recreational), and 3% (occupational) reported physical activity during the 24-hour period, prior to SL onset. Participants who reported any or occupational physical activity during the 24-hour period had a decreased likelihood of SL within the subsequent 24 hours, while participants who reported at least 30 minutes of recreational physical activity had an increased likelihood. Results remained consistent among early, full, or postterm participants. CONCLUSION: Recreational, but not occupational, physical activity at term may increase the likelihood of SL; however, the authors cannot rule out reverse causality.

Urine gastrin-releasing peptide in the first week correlates with bronchopulmonary dysplasia and post-prematurity respiratory disease.

RATIONALE: Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin-releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. OBJECTIVE: We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. METHODS: Extremely low gestational age infants (23-28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post-PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). RESULTS: A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03-3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35-4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8-hydroxydeoxyguanosine. CONCLUSIONS: Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.

Maternal diabetes and hypertensive disorders in association with autism spectrum disorder.

Previous studies have shown complications of pregnancy, often examined in aggregate, to be associated with autism spectrum disorder (ASD). Results for specific complications, such as maternal diabetes and hypertension, have not been uniformly consistent and should be investigated independently in relation to ASD in a large community-based sample. The Study to Explore Early Development (SEED), a US multisite case-control study, enrolled children born in 2003-2006 at 2-5 years of age. Children were classified into three groups based on confirmation of ASD (n = 698), non-ASD developmental delay (DD; n = 887), or controls drawn from the general population (POP; n = 979). Diagnoses of any diabetes or hypertensive disorder during pregnancy were identified from prenatal medical records and maternal self-report. Logistic regression models estimated adjusted odds ratios (aOR) and confidence intervals (CI) adjusting for maternal age, race/ethnicity, education, smoking during pregnancy, and study site. Models for hypertension were additionally adjusted for parity and plurality. Among 2,564 mothers, we identified 246 (9.6%) with any diabetes and 386 (15.1%) with any hypertension in pregnancy. After adjustment for covariates, any diabetes during pregnancy was not associated with ASD (aOR = 1.10 [95% CI 0.77, 1.56]), but any hypertension was associated with ASD (aOR = 1.69 [95% CI 1.26, 2.26]). Results were similar for DD, and any diabetes (aOR = 1.29 [95% CI 0.94, 1.78]) or any hypertension (aOR = 1.71 [95% CI 1.30, 2.25]). Some pregnancy complications, such as hypertension, may play a role in autism etiology and can possibly serve as a prompt for more vigilant ASD screening efforts. Autism Res 2019, 12: 967-975. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied if common complications in pregnancy are associated with autism spectrum disorder (ASD) in a large sample of mothers and children. Our results show an association between conditions marked by high blood pressure and ASD, but no association with conditions marked by high blood sugar and ASD. Associations were similar for children who had a developmental disorder that was not ASD, suggesting that this relationship may not be specific to ASD.

Screening for Pregnancy Status in a Population-Based Sample: Characteristics Associated with Item Nonresponse.

OBJECTIVES: Population-based recruitment of a cohort of women who are currently pregnant or who may become pregnant in a given timeframe presents challenges unique to identifying pregnancy status or the likelihood of future pregnancy. Little is known about the performance of individual eligibility items on pregnancy screeners although they are critical to participant recruitment. This paper examined the patterns and respondent characteristics of key pregnancy screener items used in a large national study. METHODS: Cross-sectional analyses were conducted. Descriptive statistics and multivariable logistic regression models were used to examine nonresponse patterns to three questions (currently pregnant, trying to get pregnant and able to get pregnant). The questions were asked of 50,529 women in 17 locations across the US, as part of eligibility screening for the National Children's Study Vanguard Study household-based recruitment. RESULTS: Most respondents were willing to provide information about current pregnancy, trying, and able to get pregnant: 99.3% of respondents answered all three questions and 97.4% provided meaningful answers. Nonresponse ranged from 0.3 to 2.5% for individual items. Multivariable logistic regression results identified small but statistically significant differences in nonresponse by respondent age, marital status, race/ethnicity-language, and household-based recruitment group. CONCLUSIONS FOR PRACTICE: The high levels of response to pregnancy-related items are impressive considering that the eligibility questions were fairly sensitive, were administered at households, and were not part of a respondent-initiated encounter.

Associations between Personal Care Product Use Patterns and Breast Cancer Risk among White and Black Women in the Sister Study.

BACKGROUND: Many personal care products include chemicals that might act as endocrine disruptors and thus increase the risk of breast cancer. OBJECTIVE: We examined the association between usage patterns of beauty, hair, and skin-related personal care products and breast cancer incidence in the Sister Study, a national prospective cohort study (enrollment 2003-2009). METHODS: Non-Hispanic black (4,452) and white women (n=42,453) were examined separately using latent class analysis (LCA) to identify groups of individuals with similar patterns of self-reported product use in three categories (beauty, skin, hair). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between product use and breast cancer incidence. RESULTS: A total of 2,326 women developed breast cancer during follow-up (average follow-up=5.4y). Among black women, none of the latent class hazard ratios was elevated, but there were <100 cases in any category, limiting power. Among white women, those classified as "moderate" and "frequent" users of beauty products had increased risk of breast cancer relative to "infrequent" users [HR=1.13 (95% CI: 1.00, 1.27) and HR=1.15 (95% CI: 1.02, 1.30), respectively]. Frequent users of skincare products also had increased risk of breast cancer relative to infrequent users [HR=1.13 (95% CI: 1.00, 1.29)]. None of the hair product classes was associated with increased breast cancer risk. The associations with beauty and skin products were stronger in postmenopausal women than in premenopausal women, but not significantly so. CONCLUSIONS: This work generates novel hypotheses about personal care product use and breast cancer risk. Whether these results are due to specific chemicals or to other correlated behaviors needs to be evaluated. https://doi.org/10.1289/EHP1480.

Adherence to gender-typical behavior and high frequency substance use from adolescence into young adulthood.

Substance use is prevalent among adolescents in the U.S., especially males. Understanding the cross-sectional and longitudinal associations between gender norms and substance use is necessary to tailor substance use prevention messages and efforts appropriately. This study investigates the relationship between adherence to gender-typical behavior (AGB) and substance use from adolescence into young adulthood. Participants in the National Longitudinal Study of Adolescent to Adult Health completed self-report measures on the frequency of binge drinking, cigarette smoking and marijuana use as well as various behaviors and emotional states that captured the latent construct of AGB. Sex-stratified logistic regression models revealed cross-sectional and longitudinal relationships between AGB and high frequency substance use. For example, an adolescent male who is more gender-adherent, compared to less adherent males, has 75% higher odds of high frequency binge drinking in adolescence and 22% higher odds of high frequency binge drinking in young adulthood. Sex-stratified multinomial logistic regression models also revealed cross-sectional and longitudinal relationships between AGB and patterns of use. For example, a more gender-adherent adolescent male, compared to one who is less adherent, is 256% more likely to use all three substances in adolescence and 66% more likely to use all three in young adulthood. Cross-sectional and longitudinal results for females indicate greater gender-adherence is associated with lower odds of high frequency substance use. These findings indicate adherence to gender norms may influence substance use behaviors across the developmental trajectory, and inform strategies for prevention efforts.

Early Life Characteristics and Neurodevelopmental Phenotypes in the Mount Sinai Children's Environmental Health Center.

Neurodevelopmental outcomes including behavior, executive functioning, and IQ exhibit complex correlational structures, although they are often treated as independent in etiologic studies. We performed a principal components analysis of the behavioral assessment system for children, the behavior rating inventory of executive functioning, and the Wechsler scales of intelligence in a prospective birth cohort, and estimated associations with early life characteristics. We identified seven factors: (1) impulsivity and externalizing, (2) executive functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6) processing speed, and (7) verbal intelligence. Prenatal fish consumption, maternal education, preterm birth, and the home environment were important predictors of various neurodevelopmental factors. Although maternal smoking was associated with more adverse externalizing, executive functioning, and adaptive composite scores in our sample, of the orthogonally-rotated factors, smoking was only associated with the impulsivity and externalizing factor ([Formula: see text] - 0.82, 95% CI - 1.42, - 0.23). These differences may be due to correlations among outcomes that were accounted for by using a phenotypic approach. Dimension reduction may improve upon traditional approaches by accounting for correlations among neurodevelopmental traits.

Impact of sample collection participation on the validity of estimated measures of association in the National Birth Defects Prevention Study when assessing gene-environment interactions.

To better understand the impact that nonresponse for specimen collection has on the validity of estimates of association, we examined associations between self-reported maternal periconceptional smoking, folic acid use, or pregestational diabetes mellitus and six birth defects among families who did and did not submit buccal cell samples for DNA following a telephone interview as part of the National Birth Defects Prevention Study (NBDPS). Analyses included control families with live born infants who had no birth defects (N = 9,465), families of infants with anorectal atresia or stenosis (N = 873), limb reduction defects (N = 1,037), gastroschisis (N = 1,090), neural tube defects (N = 1,764), orofacial clefts (N = 3,836), or septal heart defects (N = 4,157). Estimated dates of delivery were between 1997 and 2009. For each exposure and birth defect, odds ratios and 95% confidence intervals were calculated using logistic regression stratified by race-ethnicity and sample collection status. Tests for interaction were applied to identify potential differences between estimated measures of association based on sample collection status. Significant differences in estimated measures of association were observed in only four of 48 analyses with sufficient sample sizes. Despite lower than desired participation rates in buccal cell sample collection, this validation provides some reassurance that the estimates obtained for sample collectors and noncollectors are comparable. These findings support the validity of observed associations in gene-environment interaction studies for the selected exposures and birth defects among NBDPS participants who submitted DNA samples.

Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age.

Importance: Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. Objective: To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. Design, Setting, and Participants: Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area. Exposures: Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. Main Outcomes and Measures: The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result. Results: A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n = 69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n = 737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Conclusions and Relevance: Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.

Flavored little cigar smoke induces cytotoxicity and apoptosis in airway epithelia.

Addition of flavors reduces the harsh taste of tobacco, facilitating the initiation and maintenance of addiction among youths. Flavored cigarettes (except menthol) are now banned. However, the legislation on little cigars remains unclear and flavored little cigars are currently available for purchase. Since inhaled tobacco smoke directly exerts toxic effects on the lungs, we tested whether non-flavored and flavored little cigar smoke exposure had the potential for harm in cultured pulmonary epithelia. We cultured Calu-3 lung epithelia on both 96-well plates and at the air-liquid interface and exposed them to smoke from non-flavored Swisher Sweets and flavored (sweet cherry, grape, menthol, peach and strawberry) Swisher Sweets little cigars. Irrespective of flavor, acute little cigar smoke exposure (10×35 ml puffs) significantly increased cell death and decreased the percentage of live cells. Chronic exposure (10×35 ml puffs per day for 4 days) of smoke to Calu-3 cultures significantly increased lactate dehydrogenase release, further indicating toxicity. To determine whether this exposure was associated with increased cell death/apoptosis, a protein array was used. Chronic exposure to smoke from all types of little cigars induced the activation of the two major apoptosis pathways, namely the intrinsic (mitochondrial-mediated) and the extrinsic (death receptor-mediated) pathways. Both flavored and non-flavored little cigar smoke caused similar levels of toxicity and activation of apoptosis, suggesting that flavored and non-flavored little cigars are equally harmful. Hence, the manufacture, advertisement, sale and use of both non-flavored and flavored little cigars should be strictly controlled.

The association between urbanization and reduced renal function: findings from the China Health and Nutrition Survey.

BACKGROUND: While chronic kidney disease (CKD) is a growing public health concern in low- and middle-income countries, such as China, few studies have investigated the association between urbanization and the occurrence of CKD in those countries. METHODS: We investigated the association between urbanization and estimated glomerular filtration rate (eGFR), an important CKD risk marker. Data came from the China Health and Nutrition Survey wave 2009, in which we collected fasting serum, individual and household data along with community level urbanization data, which was used to derive a study-specific urbanization measure, in 218 communities across nine provinces. A total of 3644 men and 4154 women participants aged 18 years or older were included in the analysis. Reduced renal function was defined as eGFR of less than 60 mL/min/1.73 m2 measured using serum creatinine concentration (mg/dL). RESULTS: After adjusting for socio-demographic (e.g., age, education and household income), a sex-stratified multilevel logistic model revealed that living in a more urbanized community was associated with higher odds of reduced eGFR (odds ratio [OR] = 1.38 per one-standard deviation [SD] increase in the CHNS specific urbanization index, 95% confidence interval [CI] = 1.11-1.73 for men; OR = 1.35, 95% CI = 1.11-1.62 for women). After adjusting for behavioral variables (i.e., alcohol consumption, smoking, physical activity and diet), as well as obesity and cardiometabolic risk factors, the association was attenuated in men (OR = 1.25, 95% CI = 0.98-1.59), but remained statistically significant in women (OR = 1.24, 95% CI = 1.01-1.52). CONCLUSION: Our findings suggest that living in an urban environment is linked with higher odds of reduced renal function independently of behavioral and cardiometabolic risk factors, which have been shown to increase along with urbanization.

Longitudinal associations of away-from-home eating, snacking, screen time, and physical activity behaviors with cardiometabolic risk factors among Chinese children and their parents.

Background: Little is known about intergenerational differences in associations of urbanization-related lifestyle behaviors with cardiometabolic risk factors in children and their parents in rapidly urbanizing China.Objective: We tested the intergenerational differences in longitudinal associations of away-from-home eating, snacking, screen time, and leisure-time sports with high waist-to-height ratio (WHtR), elevated blood pressure (BP), elevated glycated hemoglobin (HbA1c), and elevated C-reactive protein (CRP) among Chinese children and their parents.Design: We studied children enrolled in the longitudinal China Health and Nutrition Survey (1991-2009, 7 surveys) aged 7-17 y in ≥2 surveys (average follow-up: 2.3 surveys out of a possible 4 surveys with the age restriction; n = 3875, including 1175 siblings) and their parents (2947 mothers, 2632 fathers) living in the same household. We used 3 consecutive interviewer-administered 24-h dietary recalls to derive a 3-d average for away-from-home eating (nonconsumer, >0 and <1 meal/d, or ≥1 meals/d) and consumption of fruit or vegetable snacks (any or none) and other snacks (any or none) and a self-reported 7-d physical activity recall for screen time (≤1, >1 and ≤2, or >2 h/d) and leisure-time sports (any or none). Random-effects logistic regression was used to examine the associations of lagged (average: 3 y) behaviors with cardiometabolic risk factors (WHtR, BP, HbA1c, and CRP).Results: We detected intergenerational differences in associations between lagged behaviors and risk factors (P-interaction < 0.1). Generation-specific models showed that lagged away-from-home eating of ≥1 meal/d (compared with none) was negatively associated with parents' high WHtR (OR: 0.68; 95% CI: 0.53, 0.88) but positively associated with children's high WHtR (OR: 1.46; 95% CI: 1.01, 2.12). Lagged fruit and vegetable snack consumption was negatively related to parents' (OR: 0.76; 95% CI: 0.59, 0.97) and children's (OR: 0.58; 95% CI: 0.33, 1.00) high WHtR. Lagged screen time (>2 compared with ≤1 h/d) was positively associated with parents' (OR: 2.58; 95% CI: 1.56, 4.28) and children's high WHtR (OR: 2.26; 95% CI: 1.06, 4.83).Conclusion: Parent-offspring differences in associations between lifestyle behaviors and cardiometabolic risk factors provide insight into intergenerational differences in cardiometabolic risk with urbanization.

Cardiometabolic Correlates of Physical Activity and Sedentary Patterns in U.S. Youth.

INTRODUCTION: Daily or weekly averages of physical activity and sedentary behavior could mask patterns of behavior throughout the week that independently affect cardiovascular health. We examined associations between day-to-day physical activity and sedentary behavior latent classes and cardiovascular disease (CVD) risk factors in U.S. youth. METHODS: Data were from 3984 youth ages 6-17 yr from the National Health and Nutrition Examination Survey (2003-2006) and from previously published accelerometry latent classes characterizing average counts per minute and percent of wear time in moderate-to-vigorous physical activity (MVPA) and sedentary behavior. Multiple linear regression was used to examine associations of the classes with waist circumference, systolic and diastolic blood pressure, HDL-C and LDL-C, triglycerides, glucose, and insulin. RESULTS: Participants spent 50.4% of the day in sedentary behavior and 5.3% of the day in moderate-to-vigorous physical activity. Average counts per minute were 516.4 for a 7-d period. Significant differences in CVD risk factors were between extreme classes with few differences observed in intermediate classes. Youth in latent class 4 (highest average counts per minute) had lower systolic blood pressure (-4.11 mm Hg, 95% confidence interval [CI] = -7.74 to -0.55), lower glucose (-4.25 mg·dL, 95% CI = -7.84 to -0.66]), and lower insulin (-6.83 µU·mL, 95% CI = -8.66 to -4.99]) compared with youth in class 1 (lowest average counts per minute). Waist circumference was lower for the least sedentary class (-2.54 cm, 95% CI = -4.90 to -0.19) compared with the most sedentary class. Some associations were attenuated when classes were adjusted for mean physical activity or sedentary level. CONCLUSIONS: There is some indication that patterns, in addition to the total amount of physical activity and sedentary behavior, may be important for cardiovascular health in youth. Longitudinal studies are needed to examine associations between physical activity and sedentary behavior patterns and changes in CVD risk factors.

Little Cigars are More Toxic than Cigarettes and Uniquely Change the Airway Gene and Protein Expression.

Little cigars (LCs) are regulated differently than cigarettes, allowing them to be potentially targeted at youth/young adults. We exposed human bronchial epithelial cultures (HBECs) to air or whole tobacco smoke from cigarettes vs. LCs. Chronic smoke exposure increased the number of dead cells, lactate dehydrogenase release, and interleukin-8 (IL-8) secretion and decreased apical cilia, cystic fibrosis transmembrane conductance regulator (CFTR) protein levels, and transepithelial resistance. These adverse effects were significantly greater in LC-exposed HBECs than cigarette exposed cultures. LC-exposure also elicited unique gene expression changes and altered the proteomic profiles of airway apical secretions compared to cigarette-exposed HBECs. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that LCs produced more chemicals than cigarettes, suggesting that the increased chemical load of LCs may be the cause of the greater toxicity. This is the first study of the biological effects of LCs on pulmonary epithelia and our observations strongly suggest that LCs pose a more severe danger to human health than cigarettes.

Flavored e-cigarette liquids reduce proliferation and viability in the CALU3 airway epithelial cell line.

E-cigarettes are generally thought of as a safer smoking alternative to traditional cigarettes. However, little is known about the effects of e-cigarette liquids (e-liquids) on the lung. Since over 7,000 unique flavors have been identified for purchase in the United States, our goal was to conduct a screen that would test whether different flavored e-liquids exhibited different toxicant profiles. We tested the effects of 13 different flavored e-liquids [with nicotine and propylene glycol/vegetable glycerin (PG/VG) serving as controls] on a lung epithelial cell line (CALU3). Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as an indicator of cell proliferation/viability, we demonstrated a dose-dependent decrease of MTT metabolism by all flavors tested. However, a group of four flavors consistently showed significantly greater toxicity compared with the PG/VG control, indicating the potential for some flavors to elicit more harmful effects than others. We also tested the aerosolized "vapor" from select e-liquids on cells and found similar dose-dependent trends, suggesting that direct e-liquid exposures are a justifiable first-pass screening approach for determining relative e-liquid toxicity. We then identified individual chemical constituents for all 13 flavors using gas chromatography-mass spectrometry. These data revealed that beyond nicotine and PG/VG, the 13 flavored e-liquids have diverse chemical constituents. Since all of the flavors exhibited some degree of toxicity and a diverse array of chemical constituents with little inhalation toxicity available, we conclude that flavored e-liquids should be extensively tested on a case-by-case basis to determine the potential for toxicity in the lung and elsewhere.