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BACKGROUND: Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. OBJECTIVES: We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among N = 1,433 Puerto Rico PROTECT study participants. METHODS: We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. RESULTS: We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture oddsratio(OR) = 1:57 (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB [beta] = 0:78 (95% CI: 0.17, 1.38) and adjusted P-PB [beta] = 0:85 (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted [beta]= -0:57; 95% CI: -1:09, -0:05). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. CONCLUSIONS: Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008, Introduction Phenols and parabens are two classes of high production volume chemicals that are ubiquitous in consumer and personal care products (1,2) and have been associated with reproductive and developmental [...]

BACKGROUND: Organophosphate esters (OPEs), used ubiquitously as flame retardants and plasticizers in consumer products, are suspected of having developmental toxicity. OBJECTIVES: Our study aimed to estimate associations between prenatal exposure to OPEs and fetal growth, including both ultrasound (head circumference, abdominal circumference, femur length, and estimated fetal weight) and delivery [birth weight z-score, small-for-gestational age (SGA), and large-for-gestational age (LGA)] measures of growth. METHODS: In the LIFECODES Fetal Growth Study (2008-2018), an enriched case--cohort of 900 babies born at the small and large ends of the growth spectrum, we quantified OPE biomarkers in three urine samples per pregnant participant and abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-averaged log-transformed OPE biomarkers and repeated ultrasound measures of fetal growth using linear mixed-effects models, and delivery measures of fetal growth using linear (birth weight) and logistic (SGA and LGA) regression models. RESULTS: Most OPE biomarkers were positively associated with at least one ultrasound measure of fetal growth, but associations with delivery measures were largely null. For example, an interquartile range (IQR; 1.31 ng=mL) increase in bis(2-chloroethyl) phosphate concentration was associated with larger z-scores in head circumference [mean difference (difference): 0.09; 95% confidence interval (CI): 0.01, 0.17], abdominal circumference (difference: 0.10; 95% CI: 0.02, 0.18), femur length (difference: 0.11; 95% CI: 0.03, 0.19), and estimated fetal weight (difference: 0.13; 95% CI: 0.04, 0.22) but not birth weight (difference: 0.04; 95% CI: -0.08, 0.17). At delivery, an IQR (1.00 ng=mL) increase in diphenyl phosphate (DPHP) concentration was associated with an SGA birth (odds ratio: 1.46; 95% CI: 1.10, 1.94). CONCLUSIONS: In a large prospective cohort, gestational OPE exposures were associated with larger fetal size during pregnancy, but associations at delivery were null. DPHP concentrations were associated with heightened risk of an SGA birth. These findings suggest that OPE exposure may affect fetal development. https://doi.org/10.1289/EHP14647, Introduction Organophosphate esters (OPEs) are high-production chemicals in widespread global use. (1) They are organic esters of phosphoric acid--containing alkyl chains or aryl groups, which may be halo-genated or nonhalogenated. [...]

BackgroundNovel interventions tailored to blue collar workers are needed to reduce the disparities in smoking rates among occupational groups. ObjectiveThe main objective of this study was to evaluate the efficacy and usage of the Web-enhanced “Tobacco Tactics” intervention targeting operating engineers (heavy equipment operators) compared to the “1-800-QUIT-NOW” telephone line. MethodsOperating engineers (N=145) attending one of 25 safety training sessions from 2010 through 2012 were randomized to either the Tobacco Tactics website with nurse counseling by phone and access to nicotine replacement therapy (NRT) or to the 1-800-QUIT-NOW telephone line, which provided an equal number of phone calls and NRT. The primary outcome was self-reported 7-day abstinence at 30-day and 6-month follow-up. The outcomes were compared using chi-square tests, t tests, generalized mixed models, and logistic regression models. ResultsThe average age was 42 years and most were male (115/145, 79.3%) and white (125/145, 86.2%). Using an intent-to-treat analysis, the Tobacco Tactics website group showed significantly higher quit rates (18/67, 27%) than the 1-800-QUIT NOW group (6/78, 8%) at 30-day follow-up (P=.003), but this difference was no longer significant at 6-month follow-up. There were significantly more positive changes in harm reduction measures (quit attempts, number of cigarettes smoked per day, and nicotine dependence) at both 30-day and 6-month follow-up in the Tobacco Tactics group compared to the 1-800-QUIT-NOW group. Compared to participants in the 1-800-QUIT NOW group, significantly more of those in the Tobacco Tactics website group participated in the interventions, received phone calls and NRT, and found the intervention helpful. ConclusionsThe Web-enhanced Tobacco Tactics website with telephone support showed higher efficacy and reach than the 1-800-QUIT-NOW intervention. Longer counseling sessions may be needed to improve 6-month cessation rates. Trial RegistrationClinicaltrials.gov NCT01124110; http://clinicaltrials.gov/ct2/show/NCT01124110 (Archived by WebCite at http://www.webcitation.org/6TfKN5iNL).

Background: Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results. Objectives: We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. Methods: We included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as [log.sub.2]-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex. Results: Three OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis (1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect= 1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-forgestational-age z-scores (b for detect vs. nondetect = 0.04-0.07); other chemicals showed null associations. Discussion: In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182, Introduction Organophosphate esters (OPEs) have been increasingly used as flame retardants over the last decade as polybrominated diphenyl ether (PBDE) flame retardants were phased out in the mid-2000s over concerns [...]

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate- adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/ Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity- stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831, Introduction Preterm birth is a major cause of neonatal mortality and morbidity that may perpetuate impacts on intergenerational health. (1) In the United States, preterm birth rates increased over the [...]

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. Objectives: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. Results: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log- normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of [beta] = -0.15 [95% confidence interval (CI): -0.27, -0.03], [beta] = -0.14 (95% CI: -0.28, -0.002), [beta] = -0.22 (95% CI: -0.23, -0.10), [beta] = -0.06 (95% CI: -0.18, 0.06), and [beta] = -0.25 (95% CI: -0.37, -0.14), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: ORpfna = 0.56 (95% CI: 0.38, 0.83), [OR.sub.PFDA] = 0.52 (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z- score [-0.28; 95% highest posterior density (HPD): -0.44, -0.14] and decreased odds of large-for-gestational-age (OR = 0.49; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. Discussion: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723, Introduction Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in nonstick and stain- and water-resistant consumer products, as well as in industrial processes. PFAS are persistent [...]

AbstractBackgroundRecent research indicates that 35 percent of blue-collar workers in the US currently smoke while only 20 percent of white-collar workers smoke. Over the last year, we have been working with heavy equipment operators, specifically the Local 324 Training Center of the International Union of Operating Engineers, to study the epidemiology of smoking, which is 29% compared to 21% among the general population. For the current study funded by the National Cancer Institute (1R21CA152247-01A1), we have developed the Tobacco Tactics website which will be compared to the state supported 1-800-QUIT-NOW telephone line. Outcome evaluation will compare those randomized to the Tobacco Tactics web-based intervention to those randomized to the 1-800-QUIT-NOW control condition on: a) 30-day and 6-month quit rates; b) cotinine levels; c) cigarettes smoked/day; d) number of quit attempts; and e) nicotine addiction. Process evaluation will compare the two groups on the: a) contacts with intervention; b) medications used; c) helpfulness of the nurse/coach; and d) willingness to recommend the intervention to others.Methods/DesignThis will be a randomized controlled trial (N = 184). Both interventions will be offered during regularly scheduled safety training at Local 324 Training Center of the International Union of Operating Engineers and both will include optional provision of over-the-counter nicotine replacement therapy and the same number of telephone contacts. However, the Tobacco Tactics website has graphics tailored to Operating Engineers, tailored cessation feedback from the website, and follow up nurse counseling offered by multimedia options including phone and/or email, and/or e-community. Primary Analysis of Aim 1 will be conducted by using logistic regression to compare smoking habits (e.g., quit rates) of those in the intervention arm to those in the control arm. Primary analyses for Aim 2 will compare process measures (e.g., medications used) between the two groups by linear, logistic, and Poisson regression.DiscussionDissemination of an efficacious work-site, web-based smoking cessation intervention has the potential to substantially impact cancer rates among this population. Based on the outcome of this smaller study, wider scale testing in conjunction with the International Environment Technology Testing Center which services Operating Engineers across North America (including US, Mexico, and Canada) will be conducted.Trial registrationNCT01124110