The Transcriptional Landscape of Coding and Noncoding RNAs in Recurrent and Nonrecurrent Colon Cancer.

A number of patients with colon cancer with local or local advanced disease suffer from recurrence and there is an urgent need for better prognostic biomarkers in this setting. Here, the transcriptomic landscape of mRNAs, long noncoding RNAs, snRNAs, small nucleolar RNAs (snoRNAs), small Cajal body-specific RNAs, pseudogenes, and circular RNAs, as well as RNAs denoted as miscellaneous RNAs, was profiled by total RNA sequencing. In addition to well-known coding and noncoding RNAs, differential expression analysis also uncovered transcripts that have not been implicated previously in colon cancer, such as RNA5SP149, RNU4-2, and SNORD3A. Moreover, there was a profound global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in more advanced tumors. A global down-regulation of circular RNAs in tumors relative to normal tissues was observed, although only a few were expressed differentially between tumor stages. Many previously undescribed transcripts, including RNU6-620P, RNU2-20P, VTRNA1-3, and RNA5SP60, indicated strong prognostic biomarker potential in receiver operating characteristics analyses. In summary, this study unveiled numerous differentially expressed RNAs across various classes between recurrent and nonrecurrent colon cancer. Notably, there was a significant global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in advanced tumors. Many of these newly discovered candidates demonstrate a strong prognostic potential for stage II colon cancer.

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

Spatial Profiling of Circular RNAs in Cancer Reveals High Expression in Muscle and Stromal Cells.

Circular RNAs (circRNA) are covalently closed molecules that can play important roles in cancer development and progression. Hundreds of differentially expressed circRNAs between tumors and adjacent normal tissues have been identified in studies using RNA sequencing or microarrays, emphasizing a strong translational potential. Most previous studies have been performed using RNA from bulk tissues and lack information on the spatial expression patterns of circRNAs. Here, we showed that the majority of differentially expressed circRNAs from bulk tissue analyses of colon tumors relative to adjacent normal tissues were surprisingly not differentially expressed when comparing cancer cells directly with normal epithelial cells. Manipulating the proliferation rates of cells grown in culture revealed that these discrepancies were explained by circRNAs accumulating to high levels in quiescent muscle cells due to their high stability; on the contrary, circRNAs were diluted to low levels in the fast-proliferating cancer cells due to their slow biogenesis rates. Thus, different subcompartments of colon tumors and adjacent normal tissues exhibited striking differences in circRNA expression patterns. Likewise, the high circRNA content in muscle cells was also a strong confounding factor in bulk analyses of circRNAs in bladder and prostate cancers. Together, these findings emphasize the limitations of using bulk tissues for studying differential circRNA expression in cancer and highlight a particular need for spatial analysis in this field of research. SIGNIFICANCE: The abundance of circRNAs varies systematically between subcompartments of solid tumors and adjacent tissues, implying that differentially expressed circRNAs discovered in bulk tissue analyses may reflect differences in cell type composition between samples.

Early childhood lead exposure is not reflected in adult bone lead: Results of a sub-cohort of African American women in the Cincinnati lead study.

INTRODUCTION: Pb in bone may serve as a biomarker for cumulative Pb dose over decades. We hypothesized that adult female bone Pb concentrations (BoPb) would be significantly associated with average childhood blood Pb levels (BlPb) in a birth cohort exposed to relatively high levels of Pb from Pb paint residues. METHODS: 94 African American women with a mean age of 32.7 years were recruited from the Cincinnati Lead Study (CLS) cohort. Subjects were born to women residing where there had been a high incidence of childhood Pb poisoning. Biomarkers of Pb exposure were serial BlPb concentrations spanning the prenatal period to approximately 6.5 years of age. BoPb was assessed in the tibia using the McMaster 109Cd K-XRF fourth generation system. Covariates included nutritional variables related to bone health. RESULTS: BlPb concentrations began to rise around 6 months of age and declined at later ages. Study participants were obese with a mean Body Mass Index of 34.4 and suboptimal vitamin D status as indicated by a mean 25-OH-D of 18.5 ng/ml. Average tibia Pb was -2.0 ± 8.6 µgPb/g bone mineral. In multiple linear regression, there was no significant association between BoPb at approximately age 30 and childhood cumulative BlPb(CumBlPb). DISCUSSION: Collectively, BoPb of this group of subjects was not detectable. We suggest that the reason these subjects' BoPb did not reflect their early exposure was that a significantly smaller proportion of Pb body burden resides in bone in young children. As the child grows what Pb there was in bone is diluted and any remaining signal is weak. It has been claimed that BoPb in older children, adolescents, and adults can recapitulate historical exposure to Pb during earlier development; however, in some populations, BoPb at later ages may not be an adequate biomarker to capture childhood exposure to Pb.

The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis.

Peritubular cells of the human testis form a small compartment surrounding the seminiferous tubules. They are crucial for sperm transport, and they emerge as contributors to the spermatogonial stem cell niche. They are among the least known cell types of the human body. We employed single-cell RNA sequencing of cultured human testicular peritubular cells (HTPCs), which had been isolated from testicular samples of donors with normal spermatogenesis. The significant overlap between our results and recently published ex vivo data indicates that HTPCs are a highly adequate cellular model to define and study these cells. Thus, based on the expression of several markers, HTPCs can be classified as testicular smooth muscle cells. Small differences between the in vivo/in vitro expressed genes may be due to cellular plasticity. Plasticity was also shown upon addition of FCS to the culture medium. Based on transcriptome similarities, four cellular states were identified. Further analyses confirmed the presence of known stem cell niche-relevant factors (e.g., GDNF) and identified unknown functions, e.g., the ability to produce retinoic acid. Therefore, HTPCs allow us to define the signature(s) and delineate the functions of human testicular peritubular cells. The data may also serve as a resource for future studies to better understand male (in)fertility.

Prenatal exposure to a mixture of organophosphate esters and intelligence among 8-year-old children of the HOME Study.

Many environmental chemicals are being identified as suspected neurotoxicants based on the findings of both experimental and epidemiological studies. Organophosphate esters (OPEs), which are among the chemicals that have replaced neurotoxic polybrominated diphenyl ethers (PBDEs) after 2004, have also become an important public health topic as evidence regarding their potential for early-life neurotoxicity is growing. In 233 mother child pairs from Cincinnati, OH, we measured concentrations of the OPE metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP) in the urine of pregnant women at 16 and 26 weeks gestation and at delivery. At age 8 years, we assessed children's cognition using the Wechsler Intelligence Scale for Children-IV. In models adjusted for maternal race, income, body mass index, and IQ, maternal urinary BCEP was associated with a modest increase in child full-scale IQ (ß: 0.81 per a ln-unit BCEP increase; 95 % CI: 0.00, 1.61) while other OPEs were not associated with changes in full-scale IQ or any IQ subscales. Maternal serum PBDE concentrations did not confound the relationships between urinary OPE metabolites and child IQ. Using Bayesian kernel machine regression, we did not find that concentrations of a mixture of OPE metabolites during gestation was associated with any child cognition measures. The results of this study are not consistent with other published work, and a larger sample size would be beneficial to explore potential associations more fully. Therefore, additional studies are necessary to continue studying prenatal OPE exposure and child neurodevelopment and behavior.

Childhood exposure to per- and polyfluoroalkyl substances (PFAS) and neurobehavioral domains in children at age 8 years.

BACKGROUND: Toxicological studies have raised concerns regarding the neurotoxic effects of per- and polyfluoroalkyl substances (PFAS). However, observational evidence from human studies investigating the association between childhood PFAS and neurobehavior is limited and remains unclear. OBJECTIVES: To examine whether childhood PFAS concentrations are associated with neurobehavior in children at age 8 years and whether child sex modifies this relationship. METHODS: We used data from 208 mother-child dyads in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort (Cincinnati, OH, USA). We quantified PFAS in child serum at 3 and 8 years. We assessed neurobehavioral domains using the Behavior Assessment System for Children-2 at 8 years. We used multiple informant models to estimate score changes per ln-increase in repeated PFAS concentrations. RESULTS: Childhood PFAS were not associated with Externalizing or Internalizing Problems at 8 years. However, we noted effect measure modification by sex, with higher scores in Externalizing Problems among males per ln-unit increase in perfluorononanoate (PFNA) at 3 years (ß = 4.3 points, 95% CI: 1.0, 7.7) while females had lower scores (ß = -2.8 points, 95% CI: -4.7, -1.0). More Internalizing Problems were observed among males per ln-unit increase in concurrent PFNA concentrations (ß = 3.7 points, 95% CI: 0.7, 6.8), but not in females (ß = -1.7 points, 95% CI: -4.6, 1.2). Childhood PFNA concentrations were associated with lower scores for attention problems and activity of daily living. CONCLUSION: While findings do not consistently support an association between childhood PFAS serum concentrations and neurobehavior, child sex may play a role in this relationship.

Co-exposure to manganese and lead and pediatric neurocognition in East Liverpool, Ohio.

Exposure to metal mixtures may lead to health impacts greater than the effects associated with singular exposures. Two common childhood environmental exposures, manganese (Mn) and lead (Pb), are associated with similar adverse neurodevelopmental effects; however, the effects surrounding concurrent exposure to both metals remain unclear. We study the impact of joint exposure to Mn and Pb on cognitive performance in school-aged children participating in the Communities Actively Researching Exposure Study (CARES) based in East Liverpool, Ohio. Blood Pb levels were measured for each child (geometric mean (GM) = 1.13 µg/dL, range 0.30 µg/dL - 6.64 µg/dL). Mn was measured in participant blood, hair, and toenails with GMs of 10.1 µg/L, 360 ng/g, 0.974 µg/g, respectively. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV) to assess intelligence quotient (IQ). The WISC-IV provides scores for Full Scale IQ, Perceptual Reasoning, Processing Speed, Working Memory, and Verbal Comprehension. Interactions between blood Pb and all Mn biomarkers were tested in linear models adjusted for child sex, household income, and serum cotinine. Separate regression models were run for each of the Mn biomarkers. The cohort was comprised of 106 children with a mean age of 8.4 years. Interactions between blood Pb and hair Mn were significant (p < 0.05) for four out of the five IQ domains. The effect of blood Pb on IQ was more pronounced at higher levels of hair and toenail Mn. No significant associations were observed when characterizing the main effect of Mn using blood. Uncovering the health impacts associated with exposure mixtures is critical to understanding the impact of real-life conditions. Our findings suggest that joint exposure to Mn and Pb may produce heightened neurocognitive impacts even at blood Pb levels below the CDC reference concentration of 5 µg/dL.

Criminal arrests associated with reduced regional brain volumes in an adult population with documented childhood lead exposure.

Childhood lead exposure interferes with brain maturation, which adversely impacts cognitive and behavioral development. Lower intelligence scores, impairments in decision making, and increased rates of delinquent and criminal behavior are adverse outcomes linked to childhood lead absorption. The present study examined the relationships between childhood blood lead concentrations, structural brain volume, and measures of adult criminality. We hypothesized that increased rates of criminal arrests in adulthood would be inversely correlated with regional gray and white matter volumes, especially prefrontal areas responsible for decision making and self-control. We obtained childhood blood lead histories and anatomical magnetic resonance imaging from a subset of the longitudinally followed birth cohort known as the Cincinnati Lead Study. Criminality data for cohort participants were extracted from public databases. Voxel based morphometry was used to examine spatial differences in regional gray and white matter volumes associated with childhood blood lead concentrations and measures of adult criminality, respectively. Conjunction analyses allowed for the exploratory evaluation of common regions of volume change. Childhood blood lead concentrations were inversely associated with gray and white matter volume in the frontal, parietal and temporal lobes. Gray matter volumes were also inversely associated with criminal arrests with key regions within the cingulate, precuneus, several frontal gyri and the supplementary motor area. Conjunction analyses identified regions in the anterior cingulate, frontal gray matter and supplementary motor area associated with childhood lead absorption and criminality. The results from this study suggest that reduced brain volumes in regions responsible for cognition and emotional regulation are associated with childhood lead exposure and criminal arrests.

Maternal Urinary Organophosphate Esters and Alterations in Maternal and Neonatal Thyroid Hormones.

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003-2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose-response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di-n-butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed.

Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors.

Sirtuins (SIRTs) are NAD+-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1-7 was not correlated with the survival of the patients; however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs, these SIRTs may represent novel drug targets.

Developmental lead exposure and adult criminal behavior: A 30-year prospective birth cohort study.

Using a variety of research designs and measures of lead absorption, numerous studies link childhood lead exposure to a range of cognitive and behavioral deficits, including low IQ, impulsivity, juvenile delinquency, and criminal behavior in adolescence and early adulthood. In this study, we tested the association between multiple measures of blood lead concentration assessed in childhood with criminal behavior in adulthood and across the life-course. Prospective data from the Cincinnati Lead Study (CLS) included blood lead measures quarterly across the first 78 months of life and the number of times a person was arrested across the life-course (from age 18 to 33 years) and in later adulthood (age 27 to 33 years). Childhood blood lead concentration prospectively predicted variation in adult arrests and arrests over the life-course, indicating lead absorption is implicated in the etiology of crime-especially in geographic areas where environmental sources of lead are more prevalent and concentrated. Efforts to decrease lead exposure in both developed and developing countries should be part of a comprehensive strategy to reduce social dislocation and crime.

Proximity to traffic and exposure to polycyclic aromatic hydrocarbons in relation to Attention Deficit Hyperactivity Disorder and conduct disorder in U.S. children.

BACKGROUND: Traffic related air pollution (TRAP) and its component polycyclic aromatic hydrocarbons (PAHs) may be neurotoxic in children. There is limited research on postnatal exposure to TRAP and PAHs and child neurodevelopment. METHODS: We linked data from the U.S. NHANES 2001-2004 with the National Highway Planning Network 2005 to examine the proximity to major roads (highway or urban/rural principal arterials), urinary PAH metabolites, and diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) based on Diagnostic Interview Schedule for Children (C-DISC) in 1253 children aged 8-15 years. We calculated odds ratios (ORs) and 95% Confidence Intervals (CIs) for ADHD and CD by traffic proximity and PAH exposures using logistic regression adjusted for confounders. RESULTS: Higher ADHD prevalence was observed among children living <500 m (9.86%) compared to those ≥500 m (3.84%) from a major road. Prevalence of children with CD was comparable (<500 m: 2.51% and ≥500 m: 2.43%). We found little difference in urinary PAH metabolite levels between children living near major roads and those who did not. Children living <500 m from a major road had a non-significant OR of 2.06 (95% CI 0.85-5.03) for ADHD diagnosis. Children living on ≥2 major roads within 500 m of a highway had a non-significant OR of 2.27 (95% CI 0.71-7.26) for ADHD diagnosis. There was no association between proximity to major roads and CD diagnosis. CONCLUSION: We found living close to a major road was not associated with increased PAH levels. We did not find statistically significant relation between proximity to a major road or urinary PAH metabolite levels and ADHD or CD diagnosis in this cross-sectional analysis. Prospective studies are needed for the investigation of postnatal TRAP exposure and ADHD and CD diagnosis.

Palmitic Acid Targets Human Testicular Peritubular Cells and Causes a Pro-Inflammatory Response.

Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. Human testicular peritubular cells (HTPCs) can be isolated from men and cultured. They have contractile properties but also produce Interleukin 6 (IL6), express the inflammasome member NLRP3, and via glia cell line derived neurotrophic factor (GDNF), they contribute to the spermatogonial stem cell niche. We found that PA at 100 µM significantly increased the levels of IL6, while NLRP3 or the related Interleukin 1 beta (IL1beta) were not affected. The contractility marker calponin (CNN1) and the growth factor GDNF were likewise not affected. ELISA studies confirmed the stimulatory PA actions on IL6. Hence, PA derived from diet and/or endogenous sources may be able to foster a pro-inflammatory milieu in the testis. A possible link of these results to diet and high fat intake and obesity is indicated by the about 12-fold elevated testicular levels of IL6 in testes of obese rhesus monkeys (n = 3), fed with a Western Style diet. They had elevated 2-5-fold increased body fat and increased circulating triglyceride levels. Further consequences of PA and obesity for testicular functions remain to be evaluated.

Maternal cadmium exposure and neurobehavior in children: The HOME study.

BACKGROUND: It is unclear whether cadmium (Cd) exposure during fetal brain development is associated with child neurobehavior. OBJECTIVE: To examine the potential associations between Cd exposure during pregnancy and neurobehavior among children. METHODS: We used data from 276 children in the Health Outcomes and Measures of the Environment (HOME) Study, a well-established prospective pregnancy and birth cohort. We measured maternal urinary Cd concentrations at 26 weeks of gestation. For cognitive function, we assessed Mental Development Index (MDI) and Full-Scale Intelligence Quotient (FSIQ) using the Bayley Scales of Infant Development-II, the Wechsler Preschool and Primary Scales of Intelligence-III, or the Wechsler Intelligence Scales for Children-IV at ages 1, 2, 3, 5, and 8 years. We assessed child behaviors using the Behavior Assessment System for Children-2 at ages 2, 3, 4, 5, and 8 years, yielding four composite measures: Externalizing Problems, Internalizing Problems, Behavioral Symptoms Index, and Adaptive Skills. We used linear mixed models with covariate adjustment to estimate the associations between maternal urinary Cd concentrations and child neurobehavior. RESULTS: We categorized study participants into three groups based on maternal urinary Cd concentrations (Group 1: < limit of detection (LOD), Group 2: 0.06-0.22 µg/g creatinine, Group 3: ＞0.22 µg/g creatinine). In linear mixed models adjusting for maternal and child characteristics, maternal urinary Cd levels were not significantly associated with cognitive function at ages 1, 2, 3, 5, and 8 years or with behavioral composite measures at 2, 3, 4, 5, and 8 years. CONCLUSIONS: No significant associations were observed between maternal urinary Cd and cognitive or behavioral measures in children at 1-8 years of age in this study.

Prenatal exposure to a mixture of persistent organic pollutants (POPs) and child reading skills at school age.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may affect child neurobehavior; however, exposures to mixtures of POPs have rarely been examined. METHODS: We estimated associations of prenatal serum concentrations of 17 POPs, namely 5 polybrominated diphenyl ethers (PBDEs), 6 polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and 4 per- and polyfluoroalkyl substances (PFAS), with Wide Range Achievement Test-4 reading composite scores at age 8 years in 161 children from a pregnancy and birth cohort (Health Outcomes and Measures of the Environment [HOME] Study, 2003-present) in Cincinnati, OH. We applied 6 statistical methods: least absolute shrinkage and selection operator (LASSO), elastic net (ENET), Sparse Principal Component Analysis (SPCA), Weighted Quantile Sum (WQS) regression, Bayesian Kernel Machine Regression (BKMR), and Bayesian Additive Regression Trees (BART), to estimate covariate-adjusted associations with individual and their mixtures in multi-pollutant models. RESULTS: Both LASSO and ENET models indicated inverse associations with reading scores for BDE-153 and BDE-28, and positive associations for CB-118, CB-180, perfluoroctanoate (PFOA), and perfluorononanoate (PFNA). The SPCA identified inverse associations for BDE-153 and BDE-100 and positive associations for perfluorooctane sulfonate (PFOS), PFOA, and PFNA, as parts of different principal component scores. The WQS regression showed the highest weights for BDE-100 (0.35) and BDE-28 (0.16) in the inverse association model and for PFNA (0.29) and CB-180 (0.21) in the positive association model. The BKMR model identified BDE-100 and BDE-153 for inverse associations and CB-118, CB-153, CB-180, PFOA, and PFNA for positive associations. The BART method found dose-response functions similar to the BKMR model. No interactions between POPs were identified. CONCLUSIONS: Despite some inconsistency among biomarkers, these analyses revealed inverse associations between prenatal PBDE concentrations and children's reading scores. Positive associations of PCB congeners and PFAS with reading skills were also found.

Polybrominated diphenyl ether (PBDE) and poly- and perfluoroalkyl substance (PFAS) exposures during pregnancy and maternal depression.

BACKGROUND: Experimental studies in rodents suggest that polybrominated diphenyl ethers (PBDEs) and poly- and perfluoroalkyl substances (PFAS) may contribute to depressive symptoms. Few studies have examined the impact of these chemicals on depression in adults. OBJECTIVE: To examine the associations between serum PBDE and PFAS concentrations during pregnancy and repeated measures of depressive symptoms in women assessed from pregnancy to 8 years postpartum. METHODS: This study was based on 377 women from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (USA). PBDEs (BDE-28, -47, -99, -100, -153, and ∑PBDEs) and PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorohexane sulfonate [PFHxS], perfluorononanoate [PFNA]) were quantified in maternal serum at 16 ± 3 weeks gestation. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI-II) at ~20 weeks gestation and up to seven times during postpartum visits (4 weeks, 1, 2, 3, 4, 5, and 8 years). We used linear mixed models to estimate covariate-adjusted associations between chemical concentrations and repeated measures of BDI-II. Multinomial logistic regression models were used to estimate the relative risk ratios of having a medium or high depression trajectory. RESULTS: We found that a 10-fold increase in BDE-28 at 16 ± 3 weeks gestation was associated with significantly increased BDI-II scores (ß = 2.5 points, 95% confidence interval [CI] 0.8, 4.2) from pregnancy to 8 years postpartum. Significant positive associations were also observed with BDE-47, -100, -153, and ∑PBDEs. A 10-fold increase in ∑PBDEs was associated with a 4.6-fold increased risk (95% CI 1.8, 11.8) of a high trajectory for BDI-II compared to a low trajectory. We observed no significant associations between PFAS and BDI-II scores. CONCLUSION: PBDEs during pregnancy were associated with more depressive symptoms among women in this cohort.

Organophosphate esters in a cohort of pregnant women: Variability and predictors of exposure.

Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks' gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5-2.3 µg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75-0.99 µg/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72-0.97 µg/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25-0.28 µg/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (rs: 0.23-0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16-0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility.

Birth outcomes associated with maternal exposure to metals from informal electronic waste recycling in Guiyu, China.

BACKGROUND: Informal electronic waste (e-waste) recycling is a rapidly growing industry. Informal e-waste recycling creates a mixture of chemicals that can be harmful to humans, especially vulnerable populations like pregnant women and young children. OBJECTIVES: We aimed to analyze the associations between birth outcomes and living in a community with a history of informal e-waste recycling. METHODS: The e-waste Recycling Exposure and Community Health (e-REACH) Study enrolled pregnant women in Guiyu, an informal e-waste recycling site (n = 314), and an unexposed control site (Haojiang) (n = 320) at delivery. We analyzed maternal whole blood samples for lead (Pb), cadmium (Cd), chromium (Cr), and manganese (Mn). We captured data in newborns on birth weight, birth length, head circumference, body mass index (BMI), and Ponderal Index (PI). We compared the birth outcomes between sites after adjustment for covariates, and examined the associations with individual and the mixture of metals. RESULTS: The neonates from Guiyu had smaller head circumference (adj ß -1.96 cm, 95% CI -2.39, -1.52), BMI (adj ß -0.77 kg/m2, 95% CI -1.03, -0.51), and PI (adj ß -2.01 kg/m3, 95% CI -2.54, -1.47). Birth weights were lower in Guiyu compared to Haojiang, but the difference was not significant (ß -51, 95% CI -132, 29). Cumulative exposure to metals was related to lower head circumference, BMI, and PI, but not related to birth weight. DISCUSSION: We observed slight and statistically significant differences in the head size, BMI, and PI of neonates, but not birth weight, from Guiyu when compared to neonates from Haojiang. Cumulative metal exposure may partially account for the findings.