Blood trihalomethane and urinary haloacetic acid concentrations in relation to hypertension: An observational study among 1162 healthy men.

Disinfection byproducts (DBPs) have demonstrated cardiovascular and reproductive toxicity. However, the associations and mechanisms of DBP exposure in relation to hypertension among healthy young men, which are critical for gaining new insights into the prevention and treatment of male subfertility, remain unclear. In 2017-2018, we recruited 1162 healthy Chinese men. A single blood sample was collected and measured for trihalomethane (THM) concentrations (n = 956). Up to 2930 repeated urinary samples were collected at baseline and during follow-up periods and determined for haloacetic acid concentrations. Oxidative stress (OS) biomarkers were measured in within-subject pooled urinary samples (n = 1003). In total, 403 (34.68 %) participants were diagnosed with stage 1-2 hypertension (≥130/80 mmHg) and 108 (9.29 %) stage 2 hypertension (≥140/90 mmHg). In adjusted models, blood bromodichloromethane (BDCM) concentrations were positively associated with the risk of stage 1-2 and stage 2 hypertension [ORs= 1.48 (95 % CI: 1.15, 1. 91) and 1.65 (95 % CI: 1.08, 2.51), respectively, per 2.7-fold increase in BDCM concentrations]. Additionally, we found positive associations between DBP exposure biomarkers and urinary concentrations of 4-hydroxy-2-nonenal-mercapturic acid and 8-hydroxy-2-deoxyguanosine. However, these OS biomarkers were unrelated to hypertension. Our results suggest that BDCM exposure may be associated with a greater risk of hypertension among healthy young men.

Per- and polyfluoroalkyl substances exposure is associated with polycystic ovary syndrome risk among women attending a fertility clinic.

Previous studies reported that exposures to per- and polyfluoroalkyl substances (PFAS), largely in higher exposed populations, were associated with elevated risk of polycystic ovary syndrome (PCOS). However, studies evaluating PCOS risk in populations with lower background exposures to PFAS are limited. This study aimed to examine the associations between serum PFAS concentrations and PCOS risk among women attending a U.S. academic fertility clinic during 2005-2019. A total of 502 females who sought fertility evaluation and assisted reproduction treatments were included. Nine PFAS were quantified in non-fasting serum samples collected at study entry. Diagnosis of PCOS was based on the Rotterdam criteria. We used logistic regression to examine the odds ratio (OR) of PCOS in relation to individual PFAS concentrations (continuous and by tertiles) and quantile g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) to examine the joint associations of PFAS mixture with PCOS. Most participants were White and had a graduate degree or higher. Per doubling of serum perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) concentrations were associated with higher odds of PCOS [OR (95%CI): 1.70 (1.06, 2.81) and 1.45 (1.02, 2.08) for PFOS and PFHxS respectively]. There was a dose-response relationship of PFOS with PCOS risk (p of trend by PFOS tertiles = 0.07). Both QGC and BKMR identified PFOS as the most important contributor among the mixture to PCOS risk. No clear joint effects were found for other PFAS or PFAS mixtures on PCOS risk. Our findings are consistent with existing evidence in populations with higher background PFAS concentrations and highlight the adverse effects of PFAS exposure on reproductive health. Findings can inform public health measures and clinical care to protect populations vulnerable to PCOS, in part, due to environmental exposures.

Prenatal Exposure to Ambient Air Pollution and Cerebral Palsy.

Importance: Air pollution is associated with structural brain changes, disruption of neurogenesis, and neurodevelopmental disorders. The association between prenatal exposure to ambient air pollution and risk of cerebral palsy (CP), which is the most common motor disability in childhood, has not been thoroughly investigated. Objective: To evaluate the associations between prenatal residential exposure to ambient air pollution and risk of CP among children born at term gestation in a population cohort in Ontario, Canada. Design, Setting, and Participants: Population-based cohort study in Ontario, Canada using linked, province-wide health administrative databases. Participants were singleton full term births (≥37 gestational weeks) born in Ontario hospitals between April 1, 2002, and March 31, 2017. Data were analyzed from January to December 2022. Exposures: Weekly average concentrations of ambient fine particulate matter with a diameter 2.5 µm (PM2.5) or smaller, nitrogen dioxide (NO2), and ozone (O3) during pregnancy assigned by maternal residence reported at delivery from satellite-based estimates and ground-level monitoring data. Main outcome and measures: CP cases were ascertained by a single inpatient hospitalization diagnosis or at least 2 outpatient diagnoses for children from birth to age 18 years. Results: The present study included 1 587 935 mother-child pairs who reached term gestation, among whom 3170 (0.2%) children were diagnosed with CP. The study population had a mean (SD) maternal age of 30.1 (5.6) years and 811 745 infants (51.1%) were male. A per IQR increase (2.7 µg/m3) in prenatal ambient PM2.5 concentration was associated with a cumulative hazard ratio (CHR) of 1.12 (95% CI, 1.03-1.21) for CP. The CHR in male infants (1.14; 95% CI, 1.02-1.26) was higher compared with the CHR in female infants (1.08; 95% CI, 0.96-1.22). No specific window of susceptibility was found for prenatal PM2.5 exposure and CP in the study population. No associations or windows of susceptibility were found for prenatal NO2 or O3 exposure and CP risk. Conclusions and relevance: In this large cohort study of singleton full term births in Canada, prenatal ambient PM2.5 exposure was associated with an increased risk of CP in offspring. Further studies are needed to explore this association and its potential biological pathways, which could advance the identification of environmental risk factors of CP in early life.

Urinary haloacetic acid concentrations in relation to sex and thyroid hormones among reproductive-aged men.

Sex and thyroid hormones are critical for male reproductive health. However, the associations between haloacetic acid (HAA) exposure - a known endocrine disruptor - and sex and thyroid hormones in humans remains unclear. We thus recruited 502 male participants seeking fertility evaluation from a reproductive center. We measured concentrations of sex and thyroid hormones in a single blood sample and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in repeated urine samples. Multivariable linear regression models were constructed to evaluate the associations between HAA concentrations and hormone measurements. After adjusting for potential confounders and urinary creatinine concentrations, urinary concentrations of TCAA were inversely associated with serum levels of sex hormone-binding globulin (SHBG), testosterone (T), T/luteinizing hormone ratio (T/LH), and thyroid stimulating hormone (TSH) (all P for trend < 0.10). Compared with participants in the lowest quartile of TCAA concentrations, those in the highest quartile had reduced serum levels of SHGB by 14.2 % (95% CI: -26.7, -3.0 %), T by 11.1 % (95% CI: -21.7, -1.3 %), T/LH by 21.0 % (95% CI: -36.7, -7.1 %), and TSH by 19.1 % (95% CI: -39.7, -1.5 %). Additionally, we observed inverse associations between continuous measurements of urinary HAAs and serum levels of free T, bioactive T, and estradiol. Our findings suggest that male HAA exposure may be associated with disrupted sex and thyroid function.

Predictors of Serum Per- and Polyfluoroalkyl Substances Concentrations among U.S. Couples Attending a Fertility Clinic.

Previous studies have examined the predictors of PFAS concentrations among pregnant women and children. However, no study has explored the predictors of preconception PFAS concentrations among couples in the United States. This study included 572 females and 279 males (249 couples) who attended a U.S. fertility clinic between 2005 and 2019. Questionnaire information on demographics, reproductive history, and lifestyles and serum samples quantified for PFAS concentrations were collected at study enrollment. We examined the PFAS distribution and correlation within couples. We used Ridge regressions to predict the serum concentration of each PFAS in females and males using data of (1) socio-demographic and reproductive history, (2) diet, (3) behavioral factors, and (4) all factors included in (1) to (3) after accounting for temporal exposure trends. We used general linear models for univariate association of each factor with the PFAS concentration. We found moderate to high correlations for PFAS concentrations within couples. Among all examined factors, diet explained more of the variation in PFAS concentrations (1-48%), while behavioral factors explained the least (0-4%). Individuals reporting White race, with a higher body mass index, and nulliparous women had higher PFAS concentrations than others. Fish and shellfish consumption was positively associated with PFAS concentrations among both females and males, while intake of beans (females), peas (male), kale (females), and tortilla (both) was inversely associated with PFAS concentrations. Our findings provide important data for identifying sources of couples' PFAS exposure and informing interventions to reduce PFAS exposure in the preconception period.

Association between per- and polyfluoroalkyl substances exposure and thyroid function biomarkers among females attending a fertility clinic.

Per- and polyfluoroalkyl substances (PFAS) exposure was associated with changes in thyroid function in pregnant mothers and the general population. Limited such evidence exists in other susceptible populations such as females with fertility problems. This cross-sectional study included 287 females seeking medically assisted reproduction at a fertility clinic in Massachusetts, United States, between 2005 and 2019. Six long-alkyl chain PFAS, thyroid hormones, and autoimmune antibodies were quantified in baseline serum samples. We used generalized linear models and quantile g-computation to evaluate associations of individual PFAS and their total mixture with thyroid biomarkers. Most females were White individuals (82.7%), had graduate degrees (57.8%), and nearly half had unexplained subfertility (45.9%). Serum concentrations of all examined PFAS and their mixture were significantly associated with 2.6%-5.6% lower total triiodothyronine (TT3) concentrations. Serum concentrations of perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluoroundecanoate (PFUnDA), and of the total mixture were associated with higher ratios of free thyroxine (FT4) to free triiodothyronine (FT3). No associations were found for PFAS and TSH or autoimmune antibodies. Our findings support the thyroid-disrupting effect of long alkyl-chain PFAS among a vulnerable population of subfertile females.

Mendelian randomization reveals apolipoprotein B shortens healthspan and possibly increases risk for Alzheimer's disease.

Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein cholesterol (LDL) and has been implicated in conditions that end healthspan (the interval between birth and onset of chronic disease). However, APOB's direct relationship with healthspan remains uncertain. With Mendelian randomization, we show that higher levels of APOB and LDL shorten healthspan in humans. Multivariable Mendelian randomization of APOB and LDL on healthspan suggests that the predominant trait accounting for the relationship is APOB. In addition, we provide preliminary evidence that APOB increases risk for Alzheimer's disease, a condition that ends healthspan. If these relationships are causal, they suggest that interventions to improve healthspan in aging populations could include strategies targeting APOB. Ultimately, given that more than 44 million people currently suffer from Alzheimer's disease worldwide, such interventions are needed.

Maternal and Paternal Preconception Serum Concentrations of Per and Polyfluoroalkyl Substances in Relation to Birth Outcomes.

Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.S. clinic. PFAS were quantified in serum samples collected before conception. Gestational age (GA) and birthweight (BW) were abstracted from delivery records. We also assessed low birthweight (BW < 2500 g) and preterm birth (GA < 37 completed weeks). We utilized multivariable linear regression, logistic regression, and quantile-based g computation to examine maternal or paternal serum concentrations of individual PFAS and mixture with birth outcomes. Maternal serum concentrations of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), and the total PFAS mixture were inversely associated with birthweight. Maternal PFOS concentration was associated with a higher risk of low birthweight. Conversely, paternal PFOS and PFHxS concentrations were imprecisely associated with higher birthweight. No associations were found for gestational age or preterm birth. The findings have important implications for preconception care. Future research with larger sample sizes would assist in validating these findings.

Exposure to Trihalomethanes and Bone Mineral Density in US Adolescents: A Cross-Sectional Study (NHANES).

Animal and human studies have suggested that trihalomethane (THM) has toxicity to bone. In this study, we included adolescents from the National Health and Nutrition Examination Survey who had quantified blood and tap water THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and lumbar spine or total body less head (TBLH) bone mineral density (BMD). A 2.7-fold increase in concentrations of blood TCM, DBCM, chlorinated THMs (the sum of TCM, BDCM, and DBCM), and total THMs (the sum of 4 THMs) was associated with lower lumbar spine BMD z-scores by -0.06 [95% confidence interval (CI): -0.12, -0.01], -0.06 (95% CI: -0.11, -0.003), -0.08 (95% CI: -0.14, -0.02), and -0.07 (95% CI: -0.13, -0.003), respectively, in adjusted models. Similarly, a 2.7-fold increase in blood BDCM, DBCM, and chlorinated THM concentrations was associated with lower TBLH BMD z-scores by -0.10 (95% CI: -0.17, -0.02), -0.10 (95% CI: -0.17, -0.03), and -0.11 (95% CI: -0.20, -0.01), respectively. Low-to-moderate predictive power was attained when tap water THM concentrations were used to predict blood THM measurements. Notably, the inverse associations for blood THMs persisted exclusively between water concentrations of DBCM and Br-THMs and the TBLH BMD z-scores. Our findings suggest that exposure to THMs may adversely affect the adolescent BMD.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

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.

Effects of armed conflict on maternal and infant health: a mixed-methods study of Armenia and the 2020 Nagorno-Karabakh war.

INTRODUCTION: Armed conflict worldwide and across history has harmed the health of populations directly and indirectly, including generations beyond those immediately exposed to violence. The 2020 war between Armenia and Azerbaijan over Nagorno-Karabakh, inhabited by an ethnically Armenian population, provides an example of how conflict harmed health during COVID-19. We hypothesised that crises exposure would correspond to decreased healthcare utilisation rates and worse health outcomes for the maternal and infant population in Armenia, compounded during the pandemic. METHODS: Following a mixed-methods approach, we used ecological data from 1980 to 2020 to evaluate health trends in conflict, measured as battle-related deaths (BRDs), COVID-19 cases, and maternal and infant health indicators during periods of conflict and peace in Armenia. We also interviewed 10 key informants about unmet needs, maternal health-seeking behaviours and priorities during the war, collecting recommendations to mitigate the effects of future crisis on maternal and infant health. We followed a deductive coding approach to analyse transcripts and harvest themes. RESULTS: BRDs totalled more in the 2020 war compared with the previous Nagorno-Karabakh conflicts. Periods of active conflict between 1988-2020 were associated with increased rates of sick newborn mortality, neonatal mortality and pre-eclampsia or eclampsia. Weekly average COVID-19 cases increased sevenfold during the 2020 Nagorno-Karabakh war. Key informants expressed concerns about the effects of stress and grief on maternal health and pregnancy outcomes and recommended investing in healthcare system reform. Participants also stressed the synergistic effects of the war and COVID-19, noting healthcare capacity concerns and the importance of a strong primary care system. CONCLUSIONS: Maternal and infant health measures showed adverse trends during the 2020 Nagorno-Karabakh war, potentially amplified by the concurrent COVID-19 pandemic. To mitigate effects of future crises on population health in Armenia, informants recommended investments in healthcare system reform focused on primary care and health promotion.

Blood Trihalomethane Concentrations and Osteoarthritis among U.S. Population Aged over 50 Years.

Exposure to trihalomethanes (THMs) has been associated with inflammation and oxidative stress, which are implicated in osteoarthritis. However, the association of THM exposure with osteoarthritis is unknown. Therefore, we pooled seven independent National Health and Nutrition Examination Survey cycles (1999-2012) among participants aged over 50 years who had quantified blood concentrations of chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM). Among 4,077 adults aged over 50 years, 781 (21.3%) reported osteoarthritis. Logistic regression models showed increased odds of osteoarthritis across the categories of blood BDCM, DBCM, and brominated THM (Br-THM, which was the sum of BDCM, DBCM, and TBM) concentrations [odds ratios = 1.46 (95% CI 1.09-1.94), 1.53 (95% CI 1.15-2.04), and 1.35 (95% CI 0.97-1.88), respectively], comparing highest versus lowest exposure categories (quartiles or tertiles). Additionally, we found positive dose-response relationships between blood BDCM, DBCM, and Br-THM concentrations and serum markers of oxidative stress (i.e., gamma-glutamyltransferase). In summary, blood Br-THM concentrations were associated with elevated serum levels of gamma-glutamyltransferase as well as an increased risk of osteoarthritis among U.S. adults aged over 50 years. However, more prospective population studies are needed to verify these findings and explore the underlying mechanisms.

Folate concentrations and serum perfluoroalkyl and polyfluoroalkyl substance concentrations in adolescents and adults in the USA (National Health and Nutrition Examination Study 2003-16): an observational study.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a family of highly fluorinated aliphatic compounds, which are widely used in commercial applications, including food packaging, textiles, and non-stick cookware. Folate might counteract the effects of environmental chemical exposures. We aimed to explore the relationship between blood folate biomarker concentrations and PFAS concentrations. METHODS: This observational study pooled cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2016 cycles. NHANES is a population-based national survey that measures the health and nutritional status of the US general population every 2 years by means of questionnaires, physical examination, and biospecimen collection. Folate concentrations in red blood cells and in serum, and perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) concentrations in serum were examined. We used multivariable regression models to assess the percentage change in serum PFAS concentrations in relation to changes in folate biomarker concentrations. We additionally used models with restricted cubic splines to investigate the shape of these associations. FINDINGS: This study included 2802 adolescents and 9159 adults who had complete data on PFAS concentrations, folate biomarkers, and covariates, were not pregnant, and had never had a cancer diagnosis at the time of the survey. The mean age was 15·4 years (SD 2·3) for adolescents and 45·5 years (17·5) for adults. The proportion of male participants was slightly higher in adolescents (1508 [54%] of 2802 participants) than in adults (3940 [49%] of 9159 participants). We found negative associations between red blood cell folate concentrations and serum concentrations of PFOS (percentage change for a 2·7 fold-increase in folate level -24·36%, 95% CI -33·21 to -14·34) and PFNA (-13·00%, -21·87 to -3·12) in adolescents, and PFOA (-12·45%, -17·28 to -7·35), PFOS (-25·30%, -29·67 to -20·65), PFNA (-21·65%, -26·19 to -16·82), and PFHxS (-11·70%, -17·32 to 5·70) in adults. Associations for serum folate concentrations and PFAS were in line with those found for red blood cell folate levels, although the magnitude of the effects was lower. Restricted cubic spline models suggested linearity of the observed associations, particularly for associations in adults. INTERPRETATION: In this large-scale, nationally representative study, we found consistent inverse associations for most examined serum PFAS compounds in relation to folate concentrations measured in either red blood cells or serum among both adolescents and adults. These findings are supported by mechanistic in-vitro studies that show the potential of PFAS to compete with folate for several transporters implicated in PFAS toxicokinetics. If confirmed in experimental settings, these findings could have important implications for interventions to reduce the accumulated PFAS body burden and mitigate the related adverse health effects. FUNDING: United States National Institute of Environmental Health Sciences.

Association of Early Pregnancy Perfluoroalkyl and Polyfluoroalkyl Substance Exposure With Birth Outcomes.

Importance: Prenatal perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. Previous research showed that higher folate concentrations are associated with lower blood PFAS concentrations in adolescents and adults. Further studies are needed to explore whether prenatal folate status mitigates PFAS-related adverse birth outcomes. Objective: To examine whether prenatal folate status modifies the negative associations between pregnancy PFAS concentrations, birth weight, and gestational age previously observed in a US cohort. Design, Setting, and Participants: In a prospective design, a prebirth cohort of mothers or pregnant women was recruited between April 1999 and November 2002, in Project Viva, a study conducted in eastern Massachusetts. Statistical analyses were performed from May 24 and October 25, 2022. Exposure: Plasma concentrations of 6 PFAS compounds were measured in early pregnancy (median gestational week, 9.6). Folate status was assessed through a food frequency questionnaire and measured in plasma samples collected in early pregnancy. Main Outcomes and Measures: Birth weight and gestational age, abstracted from delivery records; birth weight z score, standardized by gestational age and infant sex; low birth weight, defined as birth weight less than 2500 g; and preterm birth, defined as birth at less than 37 completed gestational weeks. Results: The cohort included a total of 1400 mother-singleton pairs. The mean (SD) age of the mothers was 32.21 (4.89) years. Most of the mothers were White (73.2%) and had a college degree or higher (69.1%). Early pregnancy plasma perfluorooctanoic acid concentration was associated with lower birth weight and birth weight z score only among mothers whose dietary folate intake (birth weight: ß, -89.13 g; 95% CI, -166.84 to -11.42 g; birth weight z score: -0.13; 95% CI, -0.26 to -0.003) or plasma folate concentration (birth weight: -87.03 g; 95% CI, -180.11 to 6.05 g; birth weight z score: -0.14; 95% CI, -0.30 to 0.02) were below the 25th percentile (dietary: 660 µg/d, plasma: 14 ng/mL). No associations were found among mothers in the higher folate level groups, although the tests for heterogeneity did not reject the null. Associations between plasma perfluorooctane sulfonic acid and perfluorononanoate (PFNA) concentrations and lower birth weight, and between PFNA and earlier gestational age were noted only among mothers whose prenatal dietary folate intake or plasma folate concentration was in the lowest quartile range. No associations were found among mothers in higher folate status quartile groups. Conclusions and Relevance: In this large, US prebirth cohort, early pregnancy exposure to select PFAS compounds was associated with adverse birth outcomes only among mothers below the 25th percentile of prenatal dietary or plasma folate levels.

Trauma and female reproductive health across the lifecourse: motivating a research agenda for the future of women's health.

The aetiology behind many female reproductive disorders is poorly studied and incompletely understood despite the prevalence of such conditions and substantial burden they impose on women's lives. In light of evidence demonstrating a higher incidence of trauma exposure in women with many such disorders, we present a set of interlinked working hypotheses proposing relationships between traumatic events and reproductive and mental health that can define a research agenda to better understand reproductive outcomes from a trauma-informed perspective across the lifecourse. Additionally, we note the potential for racism to act as a traumatic experience, highlight the importance of considering the interaction between mental and reproductive health concerns, and propose several neuroendocrinological mechanisms by which traumatic experiences might increase the risk of adverse health outcomes in these domains. Finally, we emphasize the need for future primary research investigating the proposed pathways between traumatic experiences and adverse female reproductive outcomes.

Blood trihalomethane concentrations and allergic sensitization: A nationwide cross-sectional study.

BACKGROUND: Exposure to disinfection by-products has been associated with several allergic diseases, but its association with allergen-specific immunoglobulin E (IgE) antibodies remains inconclusive. METHODS: We included 932 U.S. adolescents and 2187 adults from the National Health and Nutrition Examination Survey 2005-2006 who had quantified blood THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and 19 allergen-specific IgE antibodies. The odds ratios (ORs) of allergen-specific sensitization per 2.7-fold increment in blood THM concentrations were estimated by multivariable logistic regression models. RESULTS: Blood THM concentrations were unrelated to any allergen-specific sensitization in adults. Among adolescents, however, we found positive associations between blood TCM and chlorinated THMs (Cl-THMs: sum of TCM, BDCM, and DBCM) concentrations and the odds of pet sensitization [OR = 1.28 (95 % CI: 1.05, 1.55) and 1.38 (1.15, 1.65), respectively, per each 2.7-fold increment], between blood BDCM concentrations and the odds of mold [OR = 1.47 (1.24, 1.74)], plant [OR = 1.25 (1.09, 1.43)], pet [OR = 1.27 (1.07, 1.52)], and food sensitization [OR = 1.18 (1.03, 1.36)], and between blood brominated THM (Br-THMs: sum of BDCM, DBCM, and TBM) and total THM (TTHMs: sum of 4 THMs) concentrations and the odds of mold [OR = 1.52 (1.30 1.78) and 1.30 (1.03, 1.65), respectively], dust mite [OR = 1.39 (1.06, 1.82) and 1.45 (1.06, 1.98), respectively], and pet sensitization [OR = 1.42 (1.05, 1.92) and 1.54 (1.19, 1.98), respectively]. CONCLUSION: Higher blood concentrations of THMs were associated with a greater risk of allergic sensitization among U.S. adolescents but not in adults.

Red Blood Cell Folate Modifies the Association between Serum Per- and Polyfluoroalkyl Substances and Antibody Concentrations in U.S. Adolescents.

Per- and polyfluoroalkyl substances (PFAS) exposure has been associated with reduced antibody levels. Higher red blood cell (RBC) folate was previously associated with lower serum PFAS concentrations in adolescents. This study included 819 adolescents aged 12-19 years who had detectable rubella and measles antibody levels in serum from the U.S. National Health and Nutrition Examination Survey 2003-2004 and 2009-2010 cycles. We found inverse associations between serum PFOS and PFHxS and rubella antibodies, between PFOA and mumps antibodies, and between PFAS mixtures and rubella and mumps antibodies, only among adolescents with RBC folate concentrations <66th percentile (lower folate group) while not among adolescents with higher RBC folate levels (upper folate group). Specifically, per quartile increase in serum concentrations of the total PFAS mixture was associated with a 9.84% (95% CI: -15.57%, -3.74%) decrease in rubella antibody and an 8.79% (95% CI: -14.39%, -2.82%) decrease in the mumps antibody concentrations only in the lower folate group, while null associations were found for the upper folate group. If confirmed in mechanistic studies or prospective epidemiologic studies, these findings may have important implications for using folate as a mitigation measure against immune-related PFAS effects.

Sperm mitochondrial DNA copy number mediates the association between seminal plasma selenium concentrations and semen quality among healthy men.

Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn.

Blood trihalomethane concentrations in relation to sperm mitochondrial DNA copy number and telomere length among 958 healthy men.

BACKGROUND: In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood. OBJECTIVE: To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men. METHODS: We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0-9, 10-14, 15-69, or >69 days) to explore potential windows of susceptibility. RESULTS: After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend≤0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15-69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations. CONCLUSION: Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction.