Association of plasma trans fatty acid concentrations with blood pressure and hypertension in U.S. adults.

Objective: The present study aimed to evaluate the association of plasma trans fatty acids (TFAs) biomarkers with the risk of hypertension. Methods: Using data from the National Health and Nutrition Examination Surveys (NHANES 2009-2010), we conducted a thorough analysis using both the traditional regression model and the Bayesian Kernel Machine Regression (BKMR) model to investigate the associations of individual TFAs and their mixtures with systolic blood pressure (SBP), diastolic blood pressure (DBP), and the risk of hypertension in a sample of 1,970 American adults. Results: The concentrations of TFAs were natural logarithms (ln) transformed to approximate a normal distribution. Multivariate linear regression models showed that each 1-unit increase in ln-transformed plasma concentrations of palmitelaidic, elaidic, vaccenic, and linolelaidic acids was associated with separate 2.94-, 3.60-, 2.46- and 4.78-mm Hg and 2.77-, 2.35-, 2.03-, and 3.70- mm Hg increase in SBP and DBP, respectively (P < 0.05). The BKMR model showed positive associations between the four TFAs mixtures and SBP and DBP. In addition, linolelaidic acid contributed the most to an increased blood pressure. Similar results were observed with the threshold of hypertension (≥130/80 mm Hg). Conclusion: Our findings provide preliminary evidence that plasma TFA concentrations are associated with increased blood pressure and the risk of hypertension in US adults. This study also suggests that linolelaidic acid might exhibit more deleterious effects on hypertension than other TFAs. Further studies should be conducted to validate these results.

Associations between organophosphate esters and bone mineral density in adults in the United States: 2011-2018 NHANES.

BACKGROUND: Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans. OBJECTIVES: We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). METHODS: Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender. RESULTS: A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (ß = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; ß = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; ß=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models. CONCLUSIONS: This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings.

Tranexamic acid in patients with post-traumatic elbow stiffness: protocol for a randomised, double-blind, placebo-controlled trial investigating the effectiveness of tranexamic acid at reducing the recurrence of heterotopic ossification after open elbow arthrolysis.

INTRODUCTION: Exaggerated inflammatory response is one of the main mechanisms underlying heterotopic ossification (HO). It has been suggested that the antifibrinolytic drug tranexamic acid (TXA) can exert a significant anti-inflammatory effect during orthopaedic surgery. However, no prospective studies have yet investigated the effects of TXA on HO recurrence in patients following open elbow arthrolysis (OEA). METHODS AND ANALYSIS: Here, we present a protocol for a single-centre, randomised, double-blind, placebo-controlled trial to investigate the effectiveness of TXA on HO recurrence after OEA in a single hospital. A minimum sample size of 138 eligible and consenting participants randomised into treatment and control groups in a 1:1 manner will be included. Patients will receive 2 g of intravenous TXA (experimental group) or placebo (normal saline, control group) administered before skin incision. The primary outcome is HO recurrence rate within 12 months after surgery. The secondary outcomes are the serum immune-inflammatory cytokines including erythrocyte sedimentation rate, C reactive protein, interleukin (IL)-6, IL-1ß, IL-13 at the first and third day postoperatively, and elbow range of motion and functional score at 1.5, 6, 9 and 12 months after surgery. After completion of the trial, the results will be reported in accordance with the extensions of the Consolidated Standards of Reporting Trials Statement for trials. The results of this study should determine whether TXA can reduce the rates of HO occurrence after OEA. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (reference number 2022-123-(1)). The results of this study will be disseminated through presentations at academic conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300068106.

Temporal Trend in Suicide Mortality for Chinese Adolescents, 2008 to 2021.

This study aims to evaluate the temporal trend in suicide mortality for Chinese adolescents aged 10 to 19 years from 2008 to 2021.

Rheumatoid arthritis and the risk of postpartum psychiatric disorders: a Nordic population-based cohort study.

BACKGROUND: Postpartum psychiatric disorders (PPD) are common complications of childbirth. A common explanation for their development is that the psychological, hormonal, and immune changes associated with pregnancy and parturition may trigger psychiatric symptoms postpartum. Rheumatoid arthritis (RA) is characterized by abnormalities in the activity of the hypothalamic-pituitary-adrenal axis and of the immune system, but its association with PPD is unknown. We analyzed whether women with RA before childbirth have an increased risk of PPD. METHODS: We conducted a large population-based cohort study including mothers of singleton births in the Danish (1995-2015), Finnish (1997-2013), and Swedish Medical Birth Registers (2001-2013) (N = 3,516,849). We linked data from the Medical Birth Registers with data from several national socioeconomic and health registers. Exposure was defined as having a diagnosis of RA before childbirth, while the main outcome was a clinical diagnosis of psychiatric disorders 90 days postpartum. We analyzed the association between RA and PPD using Cox proportional hazard models, stratified by a personal history of psychiatric disorders. RESULTS: Among women without a history of psychiatric disorders, the PPD incidence rate was 32.2 in the exposed and 19.5 per 1000 person-years in the unexposed group; women with RA had a higher risk of overall PPD than their unexposed counterparts [adjusted hazard ratio (HR) = 1.52, 95% confidence intervals (CI) 1.17 to 1.98]. Similar associations were also observed for postpartum depression (HR = 1.65, 95% CI 1.09 to 2.48) and other PPD (HR = 1.59, 95% CI 1.13 to 2.24). Among women with a history of psychiatric disorders, the incidence rate of overall PPD was 339.6 in the exposed and 346.6 per 1000 person-years in the unexposed group; RA was not associated with PPD. We observed similar associations between preclinical RA (RA diagnosed after childbirth) and PPD to those corresponding to clinical RA. CONCLUSIONS: Rheumatoid arthritis was associated with an increased PPD risk in women without, but not in those with a psychiatric history. If our findings are confirmed in future studies, new mothers with RA may benefit from increased surveillance for new-onset psychiatric disorders postpartum.

Gestational exposure to organophosphate esters and adiposity measures of children up to 6 years: Effect modification by breastfeeding.

Organophosphate esters (OPEs) are synthetic chemicals used in various commercial products. Accumulating evidence has shown that they may act as metabolic disruptors. However, no study has investigated the long-term effects of gestational OPEs exposure on childhood adiposity. Breast milk represents the optimal nutritional form of feeding for infants and may protect against the adverse effects of gestational OPEs exposure on offspring development. Using data from the Shanghai-Minhang birth cohort study, we investigated the associations of gestational OPEs exposure with adiposity measures in children up to 6 years of age, and whether breastfeeding could modify these associations. A total of 733 mother-child pairs with available data on OPE concentrations and child anthropometry were included. Eight OPE metabolites were assessed in maternal urine samples collected at 12-16 weeks of pregnancy. Information on children's weight, height, arm circumference, and waist circumference was collected at birth and 0.5, 1, 4, and 6 years of age. Weight-for-age and body mass index-for-age z scores were calculated. The duration of children's breastfeeding was categorized as ≤4 months or >4 months. The generalized estimate equation and Bayesian Kernel Machine Regression models were used to examine the associations of OPEs exposure with children's adiposity measures. Selected OPEs exposure was associated with higher children's adiposity measures. Particularly, we found stronger associations of bis(1-chloro-2-propyl) phosphate (BCIPP), bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), and di-o-cresyl phosphate and di-p-cresyl phosphate (DCP) with higher adiposity measures in children breastfed for ≤4 months, while little evidence of associations was found among those breastfed for >4 months. Our study suggested that gestational OPEs exposure could alter children's adiposity measures, but the potential effects were attenuated if children were breastfed for >4 months.

Prenatal exposure to organophosphate esters is associated with decreased anogenital distance in offspring.

BACKGROUND: Evidence from in vitro and rodent studies suggests that organophosphate esters (OPEs) may disrupt sex steroid hormone homeostasis, but no human studies, to date, have examined the effects of in utero exposure to OPEs on offspring reproductive development. OBJECTIVE: Anogenital distance (AGD) is a sensitive biomarker of fetal hormonal milieu and has been used to assess reproductive toxicity. We evaluated the longitudinal effects of prenatal exposure to OPEs on the AGD of offspring from birth to 4 years. METHODS: Based on Shanghai-Minhang Birth Cohort Study, pregnant women provided urine samples at a gestational age of 12-16 weeks, which were analyzed for eight OPE metabolites. AGD was measured in offspring at birth and 0.5, 1, and 4 years of age. We used generalized estimating equations (GEE) and Bayesian kernel machine regression (BKMR) models to estimate the associations of prenatal exposure to individual OPE metabolites and OPE mixtures with AGD stratified by sex. RESULTS: A total of 733 mother-infant pairs were analyzed. Prenatal exposure to diphenyl phosphate and bis-(2-ethylhexyl) phosphate was associated with decreased AGD in boys in GEE models. Bis-(1-chloro-2-propyl) phosphate (BCIPP) showed a similar but marginally significant effect. Prenatal exposure to most OPE metabolites was associated with decreased AGD in girls, with the most profound association observed for bis (2-butoxyethyl) phosphate (BBOEP) and alkyl-OPEs. The OPE mixture was also inversely associated with AGD in both sexes. The single-exposure effects of BKMR models were largely consistent with those observed in the GEE models. In addition, alkyl-OPEs, particularly BBOEP, contributed the most to the decreased AGD in girls, while BCIPP contributed the most to the decreased AGD in boys. CONCLUSIONS: This study provides the first human evidence that prenatal exposure to OPEs is associated with decreased AGD in offspring. The magnitude of these effects may vary depending on the structure of OPEs.

Associations of single and multiple perfluoroalkyl substances exposure with folate among adolescents in NHANES 2007-2010.

BACKGROUND: The accumulation of perfluoroalkyl substances (PFAS) in human body has raised concerns about the potential health impacts on children and adolescents. However, no study has evaluated the associations of PFAS exposure with folate concentrations among adolescents. METHODS: In the present study, we mainly used three statistical approaches, namely multiple linear regression, Bayesian Kernel Machine Regression (BKMR), and quantile-based g-computation (Q-gcomp) models, to evaluate associations of individual PFAS and their mixtures with serum and red blood cell (RBC) folate concentrations in a sample of 721 adolescents from the NHANES 2007-2010. RESULTS: In multiple linear regression models, for per unit increase in ln-transformed perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) concentrations, RBC folate concentrations decreased by 72.4 (95% confidence interval (CI): -112.7, -32.2), 58.3 (95% CI: -115.0, -1.6), 60.7 (95% CI: -107.5, -13.8), and 76.5 (95% CI: -119.0, -33.9) nmol/L, respectively. A similar significant inverse association was also observed between ln-transformed PFDA and serum folate. BKMR models further confirmed inverse associations of serum PFOS and PFDA with RBC folate, and serum PFDA with serum folate. However, the inverse associations of PFOA and PFNA with RBC folate shown in multiple linear regression model were not observed or less evident in BKMR analyses. We observed interactions of PFOA with PFOS, PFNA, and PFDA on RBC folate in BKMR models, with the negative slopes for PFOS, PFNA, and PFDA increased when PFOA concentration increased from the 10th percentile to the 90th percentile. Both BKMR and Q-gcomp models suggested that the mixtures of five PFAS showed inverse overall associations with RBC folate concentration. CONCLUSIONS: The present study revealed that adolescent exposure to PFAS might affect serum and RBC folate concentrations.

Association of prenatal exposure to polybrominated diphenyl ethers at low levels with adiposity measures in children up to 6 years.

The effects of prenatal PBDEs exposure, especially at low levels, on childhood obesity are scarce. No previous studies have investigated the effect modification by breastfeeding on the associations of PBDEs exposure with childhood obesity. We aimed to investigate the associations of prenatal PBDEs exposure with adiposity measures in children up to 6 years, and the effect modification by breastfeeding. Participants were mother-child pairs from the Shanghai-Minhang Birth Cohort study. Nine PBDE congeners were assessed in cord blood plasma. We obtained information about child weight (0-6 years), height (0.5-6 years), arm circumference (0-6 years), and waist circumference (0-6 years) at each follow-up visit. Breastfeeding duration was collected when children were aged 1 year and was categorized as short (≤6 months) and adequate (>6 months). Multiple linear regression models were used to examine the associations of PBDE concentrations with adiposity measures of the children at each age. Generalized estimating equation (GEE) models were used to estimate the overall associations of PBDEs exposure with adiposity measures. We examined the effect modification by breastfeeding using stratified analyses and by including interaction terms into GEE models. For boys, there was a general profile of positive associations of several PBDE congeners exposure with adiposity measures. Especially, boys with higher BDE-153 concentration had higher adiposity measures at each time point. For girls, we also found positive associations of BDE-100 and -153 exposure with adiposity measures. The GEE models showed consistent patterns for BDE-153 in boys and for BDE-100 and -153 in girls. In breastfeeding-stratified analyses, stronger associations of PBDEs exposure with adiposity measures were generally found in children who were shortly breastfed. Our findings suggest that prenatal exposure to PBDEs at low levels may influence childhood adiposity measures, and the potential effects of PBDEs were attenuated by adequate breastfeeding.

Preconceptional paternal alcohol consumption and the risk of child behavioral problems: a prospective cohort study.

Animal studies demonstrated that paternal alcohol exposure before conception increases the risk of adverse neurodevelopment in offspring, but limited evidence is known in humans. Based on Shanghai-Minhang Birth Cohort Study, we aimed to examine associations between preconceptional paternal alcohol consumption and child behavioral problems. Paternal alcohol consumption during the last 3 months before conception was obtained by maternal report. Children born to fathers who drank alcohol at least once a week were classified as exposed. Child behavioral problems were assessed using the Child Behavior Checklist (CBCL) at age of 2, 4, and 6. Negative binomial regression was used to estimate the rate ratio (RR) of CBCL raw scores in 796 offspring. The risks of rating scores on anxious/depressed were increased by 33% (RR 1.33, 95% CI 1.09, 1.61) and 37% (RR 1.37, 95% CI 1.02, 1.84) among boys in the exposed group at age of 4 and 6, respectively. We also found that risks of somatic complaints were increased by 18% (RR 1.18, 95%CI 1.00, 1.40) and 65% (RR 1.65, 95%CI 1.14, 2.38) among girls in the exposed group at age of 4 and 6. The increased risks of sleep problems (RR 1.25, 95% CI 1.00, 1.55) in girls at age 4, thought problems (RR 1.32, 95% CI 1.01, 1.73) in girls at age 6, rule-breaking behaviors (RR 1.35, 95% CI 1.09, 1.67) in boys at age 6 were also found. The risks of CBCL scores on anxious/depressed and sleep problems in girls at age 4, as well as the risks of somatic complaints and rule-breaking behaviors in boys at age 6 increased with the level of exposure to paternal alcohol consumption. Our findings provided preliminary evidence that preconceptional paternal alcohol consumption may increase risks of child behavioral problems.

Association Between Neonatal Thyroid Function and Anogenital Distance from Birth to 48 Months of Age.

Background: Evidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study. Methods: Concentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGDAP [anus-penis] and AGDAS [anus-scrotum] for boys and AGDAC [anus-clitoris] and AGDAF [anus-fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI. Results: Multiple linear regression models showed inverse associations of TT4, FT3, and FT4 with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT4 and FT4 concentrations were associated with lower AGIAC (TT4: ß = -0.27, 95% CI: -0.50, -0.03 for middle vs. lowest tertile; FT4: ß = -0.38, 95% CI: -0.61, -0.16 for middle and ß = -0.30, 95% CI: -0.55, -0.04 for highest vs. lowest tertile). Besides, girls with the highest tertile of FT3 concentrations had lower AGIAF than those with the lowest tertile (the highest vs. lowest tertile: ß = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys. Conclusions: This study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.

Differential methylation of genes in the human placenta associated with bisphenol A exposure.

Prenatal exposure to bisphenol A (BPA) is associated with numerous adverse health outcomes among offspring. Although DNA methylation is considered one of the underlying causes of these associations, few studies have focused on the association between prenatal BPA exposure and DNA methylation in the human placenta. In this study, we examined the association between prenatal BPA exposure and DNA methylation in the placenta of 146 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study. BPA concentrations in maternal urine samples were measured using high-performance liquid chromatography. Six placenta samples were selected for whole-genome methylation analysis using Infinium Human Methylation 450K Beadchip, followed by pyrosequencing-based methylation analysis of three selected genes in 146 placentas. Among 282 differentially methylated CpGs, representing 208 genes, 127 were hypermethylated, and 155 were hypomethylated in the BPA exposure group. Prenatal BPA exposure was associated with a higher methylation level of HLA-DRB6 in individuals as determined using pyrosequencing, which was consistent with the whole-genome methylation analysis results. Compared with that subjects with low BPA exposure, the methylation level (ln-transformed) of HLA-DRB6 in placentas from those with high BPA exposure increased by 0.29% (95% confidence interval[CI]: 0.02%, 0.56%) at the CpG2 site, and the average methylation level (ln-transformed) of the three CpG sites increased by 0.30% (95%CI: -0.03%, 0.63%). Our findings provide evidence that prenatal BPA exposure might alter DNA methylation levels in the placenta.

Association between prenatal exposure to polybrominated diphenyl ethers and anogenital distance in girls at ages 0-4 years.

Anogenital distance (AGD) is a sensitive marker for the effect of in utero hormonal disturbance. However, studies on the associations between prenatal exposure to polybrominated diphenyl ethers (PBDEs), a group of endocrine disruptors, and AGD are limited. We examined the associations between prenatal PBDE exposure and AGD in girls at ages 0-4 years in the Shanghai-Minhang Birth Cohort Study. We measured PBDE in cord plasma collected from 148 girls at birth. Of them, two AGD metrics (AGDAC: from the anterior surface of the clitoral hood to the center of the anus; AGDAF: from the posterior end of the fourchette to the center of the anus) were measured in 142, 114, 104 and 120 of girls at birth, 6, 12, and 48 months of age, respectively. Linear regression models and linear mixed models were used to evaluate the associations between PBDE exposure and AGD at ages 0-4 years. We found positive associations of PBDE exposure with AGDAF and AGDAC in linear regression models, although some associations only reached significance at 6 and 48 months of age. For AGDAF, the associations were statistically significant for BDE-47, -99, and -100 at 6 months of age (ß = 2.34, 95% CI (0.21, 4.48) for BDE-47; ß = 2.21, 95% CI (0.05, 4.36) for BDE-99; ß = 2.12, 95% CI (0.01, 4.23) for BDE-100), and for BDE-99 and -100 at 48 months of age (ß = 4.49, 95% CI (1.27, 7.71) for BDE-99; ß = 5.04, 95% CI (1.87, 8.22) for BDE-100), while statistically significant associations with AGDAC were only observed for BDE-99, -100, -153, and ∑5PBDEs at 48 months of age (ß = 7.62, 95% CI (2.59, 12.64) for BDE-99; ß = 7.04, 95% CI (2.01, 12.07) for BDE-100; ß = 5.41, 95% CI (0.45, 10.38) for BDE-153; ß = 5.05 mm, 95% CI (0.09, 10.01 for ∑5PBDEs). A consistent pattern of positive associations between prenatal exposure to PBDEs and AGD was also observed in linear mixed models. The finding provided further insights into the adverse effects of PBDEs on reproductive development at low dose exposure.

Prenatal polybrominated diphenyl ethers exposure and anogenital distance in boys from a Shanghai birth cohort.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are major brominated flame retardant (BFR) chemicals with endocrine-disrupting properties. One small-scale study on humans has suggested that prenatal exposure to PBDEs is adversely related to anogenital distance (AGD) a sensitive marker for prenatal androgen exposure. The aim of the present study was to examine the associations between prenatal exposure to PBDEs and AGD among boys 0-4 years of age in a cohort study. METHODS: In the Shanghai-Minhang Birth Cohort Study (S-MBCS), nine PBDE congeners were measured in cord plasma of 192 male infants. We measured anopenile distance (AGDAP) and anoscrotal distance (AGDAS) at birth, 6 months, 12 months, and 48 months of age. A total of 190 boys with neonatal concentrations of PBDEs (ng/g lipid) who had at-least one AGD measurement were included in our study. Information on potential confounding variables were collected through in-person interviews. Multiple linear regression models and generalized estimating equation (GEE) models were used to evaluate the associations between prenatal PBDEs concentrations and AGD. RESULTS: Among the nine congeners, BDE-47 had the highest detection rate (83.68%) and the highest median concentration (0.18 ng/g lipid). Boys who had neonatal concentration of BDE-47 or Σ4PBDEs (sum of BDE-47, BDE-99, BDE-100, and BDE-153) in the higher quartile generally had shorter AGDAP and AGDAS than those in the first quartile. Significant inverse associations were found between AGDAS and fourth quartile BDE-47 levels among boys 12 months and 48 months of age (ß = -5.57, 95% confidence interval (CI): -9.89, -1.25 for 12 month of age; ß = -4.32, 95% CI: -8.18, -0.46 for 48 month of age). Inverse associations were also observed between AGDAS and fourth quartile Σ4PBDEs levels among boys 12 months of age (ß = -5.13, 95% CI: -9.89, -1.25). In GEE models, similar patterns of association were also observed between BDE-47 and AGDAS. CONCLUSIONS: Our findings provide preliminary evidence that prenatal exposure to BDE-47 and Σ4PBDEs, even at low environmental levels, may be associated with shorter AGD in boys. This data suggest that prenatal exposure to PBDEs may have adverse effects on male reproductive development. Further studies should be conducted to validate these results.