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Introduction Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent synthetic chemicals found in consumer products, firefighting foam, and contaminated food and water. (1) Routes of exposure include ingestion, inhalation, and [...]

BackgroundA causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose-response relation.ObjectiveWe investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia.MethodsWe searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model.ResultsWe found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels.DiscussionOverall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381.

Background: Dietary factors, including high sugar intake, may have adverse effects on male reproduction. Studies of the association between sugar‐sweetened beverage (SSB) intake and semen quality have reported inconsistent results. Objective: We estimated the effects of SSB consumption on semen quality in a North American preconception cohort study. Methods: We analyzed baseline data from 690 males (n = 1,247 samples) participating in Pregnancy Study Online (PRESTO) during 2015–2022. Participants aged ≥21 years completed a baseline questionnaire on which they reported information about intake of SSBs, including sodas, energy drinks, sports drinks, and fruit juices. After enrollment, we invited U.S. participants to a semen testing substudy, in which they collected and analyzed two samples using an at‐home semen testing kit. We used linear regression models to estimate adjusted percent differences (%D) and 95% confidence intervals (CI) for associations of SSB intake with semen volume, sperm concentration, total sperm count (TSC), motility, and total motile sperm count (TMSC). We used modified Poisson regression models to estimate adjusted risk ratios (RRs) and 95% CIs for the association of SSB intake with World Health Organization semen parameter cut points. Results: Relative to non‐consumers of SSBs, those who consumed ≥7 SSBs/week had lower semen volume (%D = −6, 95% CI: −13, 0), sperm concentration (%D = −22, 95% CI: −38, 0), TSC (%D = −22, 95% CI: −38, −2), motility (%D = −4, 95% CI: −10, 2), and TMSC (%D = −25, 95% CI: −43, −2). High SSB consumers also had greater risks of low sperm concentration (≤16 million/mL; RR = 1.89, 95% CI: 1.11, 3.21), low TSC (≤39 million; RR = 1.75, 95% CI: 0.92, 3.33), low motility (≤42%; RR = 1.23, 95% CI: 0.87, 1.75) and low TMSC (≤21 million; RR = 1.95, 95% CI: 1.12, 3.38). Associations were stronger among participants with body mass index ≥ 25 kg/m2. Conclusion: Greater SSB consumption was associated with reduced semen quality in a North American preconception cohort. [ABSTRACT FROM AUTHOR]

We examined the association between childhood adversity and fecundability (the per-cycle probability of conception), and the extent to which childhood social support modified this association. We used data from 6318 female participants aged 21-45 years in Pregnancy Study Online (PRESTO), a North American prospective preconception cohort study (2013-2022). Participants completed a baseline questionnaire, bimonthly follow-up questionnaires (until pregnancy or a censoring event), and a supplemental questionnaire on experiences across the life course including adverse childhood experiences (ACEs) and social support (using the modified Berkman-Syme Social Network Index [SNI]). We used proportional probabilities regression models to compute fecundability ratios (FRs) and 95% CIs, adjusting for potential confounders and precision variables. Adjusted FRs for ACE scores 1-3 and ≥4 vs 0 were 0.91 (95% CI, 0.85-0.97) and 0.84 (95% CI, 0.77-0.91), respectively. The FRs for ACE scores ≥4 vs 0 were 0.86 (95% CI, 0.78-0.94) among participants reporting high childhood social support (SNI ≥4) and 0.78 (95% CI, 0.56-1.07) among participants reporting low childhood social support (SNI <4). Our findings confirm results from 2 previous studies and indicate that high childhood social support slightly buffered the effects of childhood adversity on fecundability. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate associations between oil and gas development (OGD) and mental health using cross-sectional data from a preconception cohort study, Pregnancy Study Online. Methods. We analyzed baseline data from a prospective cohort of US and Canadian women aged 21 to 45 years who were attempting conception without fertility treatment (2013–2023). We developed residential proximity measures for active OGD during preconception, including distance from nearest site. At baseline, participants completed validated scales for perceived stress (10-item Perceived Stress Scale, PSS) and depressive symptoms (Major Depression Inventory, MDI) and reported psychotropic medication use. We used log-binomial regression and restricted cubic splines to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). Results. Among 5725 participants across 37 states and provinces, residence at 2 km versus 20 to 50 km of active OGD was associated with moderate to high perceived stress (PSS ≥ 20 vs < 20: PR = 1.08; 95% CI = 0.98, 1.18), moderate to severe depressive symptoms (MDI ≥ 20 vs < 20: PR = 1.27; 95% CI = 1.11, 1.45), and psychotropic medication use (PR = 1.11; 95% CI = 0.97, 1.28). Conclusions. Among North American pregnancy planners, closer proximity to OGD was associated with adverse preconception mental health symptomatology. (Am J Public Health. 2024;114(9):923–934. https://doi.org/10.2105/AJPH.2024.307730) [ABSTRACT FROM AUTHOR]

BackgroundThe synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts.MethodsThe Cape Cod Family Health Study is a retrospective cohort study designed to examine the reproductive and developmental health effects of exposure to PCE-contaminated drinking water. Our analysis included 1565 women who reported 3826 planned pregnancies from 1949 to 1990. Women completed self-administered questionnaires that ascertained TTP for each of her pregnancies, regardless of the outcome, as well as residential history and demographic information. We utilized EPANET water distribution system modeling software and a leaching and transport model to assess PCE exposure for each pregnancy. We used log-binomial regression models to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for potential confounders. We performed a probabilistic bias analysis to examine the effect of outcome misclassification on our results.ResultsAny cumulative PCE exposure before pregnancy was associated with a 15% reduction in risk of TTP > 12 months (RR = 0.85, 95% CI: 0.70, 1.03). However, women with the highest average monthly PCE exposure around the time of the pregnancy attempt (≥ 2.5 g) had increased risk of TTP > 12 months (RR = 1.36, 95% CI: 1.06, 1.76).ConclusionsWe found little evidence for long-term, cumulative adverse effects of PCE exposure on TTP, but high levels of PCE exposure around the time of the pregnancy attempt were associated with longer TTP. These associations may be underestimated due to the exclusion of unsuccessful pregnancy attempts from our study population, and may be biased by outcome and exposure misclassification given the long-term recall of TTP and use of a leaching and transport model to estimate PCE exposure.

Background: Residential green space can have positive physiological effects on human health through various mechanisms, including reducing stress and/or depression or facilitating physical activity. Although green space has been consistently associated with improved birth outcomes in several studies, there has been limited study of its effect on other reproductive outcomes, including fertility. Objective: We examined associations between residential green space and fecundability, the per-cycle probability of conception. Methods: We analyzed data from 8,563 female participants enrolled between 2013 and 2019 in Pregnancy Study Online (PRESTO), a prospective preconception cohort study of North American couples attempting conception. Participants completed a baseline questionnaire on sociodemographic, behavioral, and reproductive factors, and bimonthly follow-up questionnaires for up to 12 months to ascertain pregnancies. Using geocoded addresses, we calculated residential green space exposure using the Normalized Difference Vegetation Index (NDVI) within 50-, 100-, 250-, and 500-m buffers across multiple temporal scales: annual maximum, seasonal maximum, and seasonal mean. We used proportional probabilities regression models to estimate fecundability ratios (FRs), adjusting for sociodemographic, behavioral, and neighborhood characteristics. We also evaluated the extent to which associations were mediated by reductions in perceived stress or depressive symptoms and increased physical activity. Results: When comparing the highest ([greater than or equal to]0.8) with the lowest ( Discussion: In this cohort, greater residential green space was associated with a modest increase in fecundability. https://doi.org/10.1289/EHP10648, Introduction A growing body of literature examines the positive physiological impacts of green space on human health. (1,2) Hypothesized pathways by which exposure to green space improves health include increased [...]

STUDY QUESTION Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle? SUMMARY ANSWER Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis. WHAT IS KNOWN ALREADY About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses. STUDY DESIGN, SIZE, DURATION This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income. MAIN RESULTS AND THE ROLE OF CHANCE Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91–1.04); CIN1, 1.04 (0.96–1.13); CIN2+ no surgery, 1.00 (0.82–1.22); and CIN2+ with surgery 0.99 (0.89–1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86–1.11) for other cervical lesions; 1.13 (0.99–1.29) for CIN1; 0.89 (0.62–1.26) for CIN2+ no surgery and 0.91 (0.75–1.10) for CIN2+ with surgery compared with the no lesion group. LIMITATIONS, REASONS FOR CAUTION In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1. WIDER IMPLICATIONS OF THE FINDINGS Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by The Danish Cancer Society (R167-A11036-17-S2). The overall cohorts were funded by the National Institute of Child Health and Human Development (R01-HD086742 and R03-HD094117). The authors report no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Simple Summary: Females prenatally exposed to diethylstilbestrol have an elevated risk of severe cervical dysplasia and some cancers, while testicular cancer is increased in males. We assessed these associations in the prenatally exposed female's offspring (third generation). Based on third-generation females' self-reports, diethylstilbestrol exposure was not associated with risks of overall cancer, breast cancer, or severe cervical dysplasia. Borderline ovarian cancer risk in exposed vs. unexposed was elevated but compatible with chance. Based on mothers' reports, diethylstilbestrol exposure did not increase the risk of overall or other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated but compatible with chance. Testicular cancer risk was not elevated in exposed males, and there were no prostate cancers reported. These data do not provide evidence that diethylstilbestrol is associated with cancer risk in third-generation females or males. The third generation is relatively young and requires follow-up to assess risk as the cohort ages. Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36–1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37–32.42). Based on mothers' reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49–1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70–2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed. [ABSTRACT FROM AUTHOR]