Prenatal Polybrominated Diphenyl Ethers Research Articles

Prenatal exposure to polybrominated diphenyl ether (PBDE) and child neurodevelopment: The role of breastfeeding duration

BackgroundPrenatal and early-life exposure to polybrominated diphenyl ethers (PBDEs) is associated with detrimental and irreversible neurodevelopmental health outcomes during childhood. Breastfeeding may be a child's largest sustained exposure to PBDE— potentially exacerbating their risk for adverse neurodevelopment outcomes. However, breastfeeding has also been associated with positive neurodevelopment. Our study investigates if breastfeeding mitigates or exacerbates the known adverse effects of prenatal exposure to PBDEs and child neurodevelopment. MethodsParticipants included 321 mother-infant dyads from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort in California. PBDE concentrations were measured in maternal serum blood samples collected during pregnancy or at delivery. Using generalized estimated equations (GEE), we estimated associations of PBDE concentrations with children's attention, executive function, and cognitive scores assessed longitudinally between 7 and 12 years of age, stratified by duration of exclusive and complementary breastfeeding. ResultsWe observed that higher maternal prenatal PBDE concentrations were associated with poorer executive function among children who were complementary breastfed for a shorter duration compared to children breastfed for a longer duration; preservative errors (β for 10-fold increase in complementary breastfeeding <7 months = −6.6; 95 % Confidence Interval (CI): −11.4, −1.8; β ≥ 7 months = −5.1; 95 % CI: −10.2, 0.1) and global executive composition (β for 10-fold increase <7 months = 4.3; 95 % CI: 0.4, 8.2; β for 10-fold increase ≥7 months = 0.6; 95 % CI: −2.8, 3.9). ConclusionsProlonged breastfeeding does not exacerbate but may mitigate some previously observed negative associations of prenatal PBDE exposure and child neurodevelopment.

Prenatal exposure to phthalates and polybrominated diphenyl ethers on neonatal health: A birth cohort study in Guangxi, China

Few epidemiological studies have focused on prenatal phthalates (PAEs) and polybrominated diphenyl ethers (PBDEs) exposure to neonatal health in China. This study aimed to assess the associations between prenatal PAEs and PBDEs exposure and neonatal health in Guangxi, a Zhuang autonomous region of China. Concentrations of 4 PAEs metabolites (mPAEs) and 5 PBDEs congeners were measured in the serum of 267 healthy pregnant women. Birth outcomes and clinical data of neonates were collected after delivery. Mono-(2-Ethylhexyl) phthalate (MEHP) (81.52%) and BDE47 (35.21%) were the mPAEs and PBDEs congeners with the highest detection rate in serum. Prenatal exposures to mono-n-butyl phthalate (MBP), MEHP, and ΣmPAEs were negatively associated with birth weight (BW), birth length (BL), and gestational age (GA). Higher exposures to MBP, MEHP, and ΣmPAEs were associated with an increased odds ratio (OR) for low birth weight (LBW), but exposure to BDE28 exhibited the opposite effect. Moreover, higher exposures to MBP, MEHP, ΣmPAEs, BDE99, and ΣPBDEswere associated with an increased OR for premature birth (PTB) (P < 0.05). In contrast to MBP exposure, BDE28 exposure was associated with a higher OR for neonatal jaundice (NNJ) (P < 0.05). The interaction analysis showed a positive interaction between monoethyl phthalate (MEP) and BDE28 on the risk of NNJ and positive interaction between ΣmPAEs and BDE47 on the risk of NNJ. In addition, there are ethnicity-specific associations of prenatal PBDEs exposure with neonatal health in individuals of Zhuang and Han nationalities, and boy neonates were more sensitive to prenatal PBDEs exposure than girl neonates. The results revealed that prenatal exposure to mPAEs and PBDEs might have adverse effects on neonatal development, and the effects might be ethnicity- and sex-specific.

Associations between prenatal exposure to polybrominated diphenyl ethers and physical growth in a seven year cohort study.

Although evidence suggests that prenatal exposure to polybrominated diphenyl ethers (PBDEs) alter offspring's physical growth, most studies rely upon physical growth at a single timepoint, and little is known regarding their longitudinal effects over time. In the current study, we determined the associations between prenatal PBDEs exposure and child physical growth by following up 207 mother-child pairs from the Laizhou Wan Birth Cohort (LWBC) from pregnancy until the children were seven years old. Child physical growth including weight, height, and body mass index (BMI) was assessed at birth, and at one, two and seven years of age. Prenatal exposure to PBDEs was quantified by measuring eight PBDE congeners (BDE-28, BDE-47, BDE-85, BDE-99, BDE-100, BDE-153, BDE-154, and BDE-183) in maternal serum samples collected upon hospital admission for delivery. Linear mixed models were applied to examine the associations between prenatal PBDEs exposure and repeated measures of child physical growth, and to determine whether these associations were modified by child's sex. Our findings indicated that BDE-28, BDE-85, BDE-153, BDE-183, and Σ7PBDEs were positively associated with child weight z-score; and that BDE-28, BDE-47, BDE-85, BDE-99, BDE-153, and Σ7PBDEs were positively associated with child height z-score. In addition, these associations were modified by the child's sex as reflected by pronounced positive associations among boys, while negative associations were noted among girls. In conclusion, our findings indicated the sex-specific associations between prenatal PBDE exposures and child physical growth during the first seven years of life.

Gestational exposure to BDE-209 induces placental injury via the endoplasmic reticulum stress-mediated PERK/ATF4/CHOP signaling pathway

Several epidemiological studies have reported significant associations between prenatal polybrominated diphenyl ethers (PBDEs) exposure and adverse birth outcomes. Placental injury is thought to mediate these associations. However, few study has investigated the adverse effects of PBDEs exposure on placental growth and development. We examined the impacts of gestational exposure to BDE-209, the most abundant PBDE conger detected in human samples, on placental structure and function, and its model of action in vivo and in vitro. Pregnant mice were exposed to 0, 2, 20, 200 mg/kg/day of BDE-209 by gavages from gestational day (GD) 0 to GD18. Results showed that gestational BDE-209 exposure significantly reduced placental weight, impaired placental vascular development and induced placental cell apoptosis. In addition, gestational BDE-209 exposure impaired placental transport and endocrine function as demonstrated by markedly downregulated expression of Glut1, Znt1, Pgf and Igf2 in BDE-209-treated placentas. Mechanistically, gestational exposure to BDE-209 upregulated the expression of GRP78, and 3 downstream proteins (p-eIF2α, ATF4 and CHOP) of the PERK signaling, suggesting the activation of endoplasmic reticulum (ER) stress and PERK signaling pathway in mouse placentas. Further in vitro study showed that PERK siRNA pretreatment markedly reversed BDE-209-induced cell apoptosis in human JEG-3 cells. Collectively, our results suggest that the activation of the ER stress-mediated PERK/ATF4/CHOP signaling pathway played a role in BDE-209-induced placental injury. Our findings provide new insight into the mechanisms of BDE-209 induced reproductive and developmental toxicity.

Prenatal exposure to persistent organic pollutants and childhood obesity: A systematic review and meta-analysis of human studies.

We conducted a systematic review and meta-analysis of the associations between prenatal exposure to persistent organic pollutants (POPs) and childhood obesity. We focused on organochlorines (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB], and polychlorinated biphenyls [PCBs]), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and polybrominated diphenyl ethers (PBDEs) that are the POPs more widely studied in environmental birth cohorts so far. We search two databases (PubMed and Embase) through July/09/2021 and identified 33 studies reporting associations with prenatal organochlorine exposure, 21 studies reporting associations with prenatal PFAS, and five studies reporting associations with prenatal PBDEs. We conducted a qualitative review. Additionally, we performed random-effects meta-analyses of POP exposures, with data estimates from at least three prospective studies, and BMI-z. Prenatal DDE and HCB levels were associated with higher BMI z-score in childhood (beta: 0.12, 95% CI: 0.03, 0.21; I2 : 28.1% per study-specific log increase of DDE and beta: 0.31, 95% CI: 0.09, 0.53; I2 : 31.9% per study-specific log increase of HCB). No significant associations between PCB-153, PFOA, PFOS, or pentaPBDEs with childhood BMI were found in meta-analyses. In individual studies, there was inconclusive evidence that POP levels were positively associated with other obesity indicators (e.g., waist circumference).

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 (β=2.34, 95% CI (0.21, 4.48) for BDE-47; β=2.21, 95% CI (0.05, 4.36) for BDE-99; β=2.12, 95% CI (0.01, 4.23) for BDE-100), and for BDE-99 and -100 at 48 months of age (β=4.49, 95% CI (1.27, 7.71) for BDE-99; β=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 (β=7.62, 95% CI (2.59, 12.64) for BDE-99; β=7.04, 95% CI (2.01, 12.07) for BDE-100; β=5.41, 95% CI (0.45, 10.38) for BDE-153; β=5.05mm, 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.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study

ObjectiveTo explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes. MethodsBased on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records. ResultsA total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑19PBDEs were detected in FGR cases than in controls. Increased BDE-207, -208, -209, and ∑19PBDEs levels in maternal serum were related to decreased placental length, breadth, surface area, birth weight, birth length, gestational age, and Quetelet index of newborns. After adjusting for confounders, BDE-207 and ∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR. ConclusionA negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) and cognitive ability in early childhood

BackgroundPrenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with adverse neurodevelopmental outcomes in children, but evidence remains mixed regarding sex differences in this association. ObjectiveTo examine the prospective association between prenatal PBDE exposure and cognitive ability in young children, as well as potential sex differences. MethodsThe study was conducted in a multi-site Canadian pregnancy cohort recruited in 2008–11. PBDEs were measured in maternal plasma samples collected early in pregnancy. Cognitive ability was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) in children at age 3 years (mean = 3.4). Multiple linear regression was used to analyze the association between maternal PBDE plasma concentrations (lipid-standardized and log10-transformed) and Verbal, Performance, and Full Scale IQ scores on the whole sample and stratified by sex, adjusting for confounders. ResultsThe sample was composed of 592 children (291 boys and 301 girls). A tenfold increase in maternal blood PBDE concentration (sum of BDE-47, −99, −100, and −153) was associated with lower Full Scale scores in boys (−3.4 points; 95% CI: −7.0, 0.1), after adjusting for confounders. BDE-47 was the congener with the highest concentrations in maternal blood and a tenfold increase in exposure was associated with significantly lower Full Scale IQ scores in boys (−4.4 points; 95% CI: −7.9, −0.9), after adjusting for confounders. Verbal and Performance IQ scores were similarly associated with PBDE exposure. Maternal blood PBDE concentrations were not associated with IQ scores in girls. ConclusionsPrenatal exposure to background levels of PBDEs, especially BDE-47, was associated with lower IQ scores in boys, but not in girls. Our results support that exposure to PBDEs during early development may be sex-dependent and detrimental to a child’s neurodevelopmental trajectory.

Effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on the second to fourth digit ratio in children aged 4 years.

The second to fourth digit ratio (2D:4D) is assumed to be a biomarker of prenatal sex steroid exposure, correlating negatively with prenatal testosterone and positively with prenatal estrogen. The ratio has been suggested to be influenced by endocrine disrupting chemicals (EDCs). However, evidence regarding effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on 2D:4D of children was sparse. We investigated the associations between prenatal exposure to PBDEs and 2D:4D of children aged 4 years. Participants were mother-child pairs from the Shanghai-Minhang Birth Cohort Study (S-MBCS) which enrolled pregnant women at 12-16 weeks of gestation from April to December 2012. Nine PBDE congeners in venous umbilical cord plasma of 340 children were measured. Digit lengths were measured using a vernier caliper in children aged 4 years and 2D:4D for left and right hands and average 2D:4D value of both hands were calculated. A total of 281 children (160 boys and 121 girls) who had data on both 2D:4D and PBDE concentrations were included in the final analysis. Associations between prenatal PBDE exposures and 2D:4D were investigated using multiple linear regression models. Among the nine congeners, BDE-47 had the highest detection rate of 86.12% with the highest median concentration of 0.20ng/ml lipid. Five PBDE congeners with detection rates greater than or close to 50% (BDE-28, -47, -99, -100 and -153) and Σ5PBDEs (the sum of them) were included in final analysis. For girls, a consistent pattern for the positive associations between prenatal PBDE exposures and 2D:4D of children was observed mainly for the left hand, where those in the highest exposure groups had higher 2D:4D compared to the lowest exposure groups (a feminizing effect), with statistically significant associations observed for BDE-47 (β=0.0247, 95% confidence interval (CI): 0.0017, 0.0477), -100 (β=0.0264, 95% CI: 0.0087, 0.0441) and Σ5PBDEs (β=0.0201, 95% CI: 0.0027, 0.0374). For boys, compared with the lowest exposure groups, statistically significantly higher (feminized) 2D:4D for both hands was observed in those with the highest exposure levels of BDE-100 (β=0.0147, 95% CI: 0.0005, 0.0289 for the left hand; β=0.0182, 95% CI: 0.0046, 0.0318 for the right hand) and those with the middle and the highest exposure levels of BDE-153 (middle vs. undetected, β=0.0215, 95% CI: 0.0072, 0.0358 for the left hand; β=0.0155, 95% CI: 0.0015, 0.0295 for the right hand; highest vs. undetected, β=0.0162, 95% CI: 0.0017, 0.0307 for the left hand; β=0.0152, 95% CI: 0.0011, 0.0294 for the right hand). Our study provides preliminary evidence that prenatal exposure to PBDEs might be associated with higher 2D:4D in boys and girls.

Prenatal Exposure to Polybrominated Diphenyl Ethers (PBDEs) Flame Retardants and Breast Tissue Composition among Adolescents Girls

Exposure to endocrine-disrupting chemicals including PBDEs during the prenatal period may affect breast development and composition and the risk of developing breast cancer in adulthood. We examined the association between prenatal exposure to PBDEs and breast tissue composition in adolescent girls. We used data from the Columbia’s Breast Cancer and the Environment Research Project (BCERP), part of the Columbia Center for Children's Environmental Health birth cohort. Prenatal PBDE concentrations were measured in cord blood from African-American or Dominican neonates, born between 1998 and 2006 (prior to PBDE phase out). After longitudinal follow-up, breast tissue composition was measured using optical spectroscopy (OS) in adolescent girls between 2016 and 2020. OS is a non-invasive device that uses visible and near infrared light to provide a broad compositional view of the breast by capturing variation in the amount of water, lipid, oxy-hemoglobin, deoxy-hemoglobin (HbO2), and collagen, and cellular and connective tissue density. Spectral data was reduced using principal component analysis and principal component (PC) scores were generated for each girl (averaged over both breasts). Associations between lipid-adjusted PBDE concentrations (ln) and PC scores were evaluated using linear regression. The analysis included 94 daughters (ages 12.6 to 19.9 years, median=16.9 years). Five PCs explained 99.9% of the variation in OS data. When examining PBDE as continuous, PC2 scores were lower on average for girls with higher prenatal concentrations of BDE-47 (overall sample geometric mean = 11.82 ng/g lipid; βBDE-47 = -0.05, 95% CI:-0.09, -0.005) after adjusting for age and body mass index. Results were consistent when examining PBDEs using median cut-points. PC2 covered 3.8% of the spectral variations and was related to overall lower HbO2 and higher water. Associations were attenuated in fully adjusted models. We found evidence suggesting that prenatal exposure to PBDEs may be associated with breast tissue composition in adolescent girls.

Racial/ethnic and geographic differences in polybrominated diphenyl ether (PBDE) levels across maternal, placental, and fetal tissues during mid-gestation

Prenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal–fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014–16). Maternal–fetal PBDE levels were compared to population characteristics using censored Kendall’s tau correlation and linear regression. PBDEs were commonly detected in all biomatrices. Before lipid adjustment, wet-weight levels of all four PBDE congeners were highest in the fetal liver (p < 0.001), whereas median PBDE levels were significantly higher in maternal serum than in the fetal liver or placenta after lipid-adjustment (p < 0.001). We also found evidence of racial/ethnic disparities in PBDE exposures (Non-Hispanic Black > Latina/Hispanic > Non-Hispanic White > Asian/Pacific Islander/Other; p < 0.01), with higher levels of BDE-100 and BDE-153 among non-Hispanic Black women compared to the referent group (Latina/Hispanic women). In addition, participants living in Fresno/South Central Valley had 34% (95% CI: − 2.4 to 84%, p = 0.07) higher wet-weight levels of BDE-47 than residents living in the San Francisco Bay Area. PBDEs are widely detected and differentially distributed in maternal–fetal compartments. Non-Hispanic Black pregnant women and women from Southern Central Valley geographical populations may be more highly exposed to PBDEs. Further research is needed to identify sources that may be contributing to differential exposures and associated health risks among these vulnerable populations.

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

Prenatal exposure to persistent organic pollutants (POPs) may affect child neurobehavior; however, exposures to mixtures of POPs have rarely been examined. 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. 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. 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.

Functional connectivity of the reading network is associated with prenatal polybrominated diphenyl ether concentrations in a community sample of 5 year-old children: A preliminary study

Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N = 33). Maternal serum PBDE concentrations (∑PBDE) were measured at 12.2 ± 2.8 weeks gestation (mean ± SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between ∑PBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher ∑PBDE showed reduced GE of the RN; ∑PBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, ∑PBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between ∑PBDE concentrations and reading problems observed previously in older children.

Associations of prenatal exposures to low levels of Polybrominated Diphenyl Ether (PBDE) with thyroid hormones in cord plasma and neurobehavioral development in children at 2 and 4 years

BackgroundNeurotoxic effects of Polybrominated Diphenyl Ethers (PBDEs) at low levels have not been well studied in human population, and whether the associations can be explained by thyroid hormones (THs) remains unclear. ObjectivesWe examined the associations of prenatal PBDE exposures with THs in cord plasma and neurobehavior of children at 2 and 4 years among general population in China. MethodsParticipants were mother-child pairs in the Shanghai-Minhang Birth Cohort Study. Nine PBDE congeners and THs (thyroid stimulating hormone, total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine) were determined in cord plasma. Child Behavior Checklist (CBCL/1.5-5) were completed by caregivers to assess children's neurobehavioral development at 2 and 4 years. In the final analyses, 199 and 307 mother-child pairs at 2 and 4 years were included to examine associations of PBDEs with CBCL scores using Pearson-scale-adjusted Poisson regressions, and 339 subjects were included in linear regression models to investigate the associations between PBDEs and THs. ResultsBDE-47 had the highest detection rate of 83.82% with the median concentration of 0.19 ng/g lipid, followed by BDE-28, −99, −100 and −153 with detection rates nearly 50%. We found positive associations between prenatal PBDE concentrations and children's neurobehavior, including Somatic Complaints, Withdrawn, Sleep Problems and Internalizing Problems in girls, and Somatic Complaints and Attention Problems in boys. We also observed inverse associations of the sum of BDE-47, −28, −99, −100 and −153 with THs. However, by adding THs to the models examining associations between PBDEs and CBCL, the main results didn't measurably change. ConclusionsThis study adds new knowledge that prenatal PBDEs at low levels may be related to long-lasting behavioral abnormalities in children and reduced THs in cord plasma. However, the hypothesis that the neurotoxic impact of PBDEs may be explained by alterations in cord THs was not supported.

A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood.

The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood. In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using agraph-theoretical approach) in 5-year-old children (n=34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n=106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems. Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (β's=.01, FDR-corrected p's≤.05); (b) more reported EF problems (β's=.001, FDR-corrected p's≤.05). Higher global efficiency of brain areas involved in visual attention was associated with more EF problems (β's=.01, FDR-corrected p's<.05). Intrinsic functional network organization of visual attention brain areas linked prenatal PBDE concentrations to EF problems in childhood. Visual attention may contribute to the development of higher-order cognitive functions, such as EF, which could be explored in future studies.

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

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. 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. 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 (β = -5.57, 95% confidence interval (CI): -9.89, -1.25 for 12 month of age; β = -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 (β = -5.13, 95% CI: -9.89, -1.25). In GEE models, similar patterns of association were also observed between BDE-47 and AGDAS. 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.

Childhood polybrominated diphenyl ether (PBDE) serum concentration and reading ability at ages 5 and 8 years: The HOME Study

BackgroundPolybrominated diphenyl ethers (PBDEs) exist extensively in the environment and human beings. PBDE concentrations are higher in children than adults. A previous study found that prenatal PBDE exposure was associated with decreased reading skills in children; however, evidence is limited on the potential impact of childhood exposure to PBDEs. The study examined the association between childhood PBDE exposures and reading ability in children at ages 5 and 8 years. MethodsThe study included 230 children from an ongoing prospective pregnancy and birth cohort study, the Health Outcomes and Measures of Environment (HOME) Study, conducted in Cincinnati, Ohio. Children's serum concentrations of eleven PBDE congeners were measured at 1, 2, 3, 5, and 8 years. The Woodcock-Johnson Tests of Achievement - III and the Wide Range Achievement Test - 4 were administered to assess children's reading skills at ages 5 and 8 years, respectively. We used multiple informant models to examine the associations between repeated measures of PBDEs and reading scores at ages 5 and 8 years. We also estimated the βs and 95% CIs of the association of PBDE measure at each age by including interaction terms between PBDE concentrations and child age in the models. ResultsAll childhood BDE-153 concentrations were inversely associated with reading scores at 5 and 8 years, but associations were not statistically significant after covariate adjustment. For example, a 10-fold increase in BDE-153 concentrations at ages 3 and 5 years was associated with a −5.0 (95% confidence interval (CI): −11.0, 1.0) and −5.5 (95% CI: −12.5, 1.4) point change in Basic Reading score at age 5 years, respectively. Similarly, the estimates for Brief Reading score at age 5 years were −4.5 (95% CI: −10.5, 1.5) and −5.2 (95% CI: −12.2, 1.7) point changes, respectively. Serum concentration of BDE-47, -99, -100, and Sum4PBDEs (sum of BDE-47, 99, 100, and 153) at every age were inversely associated with reading scores at ages 5 and 8 years in unadjusted analyses. While the adjusted estimates were much attenuated and became non-significant, the direction of most of the associations was not altered. ConclusionOur study has shown a suggestive but non-significant trend of inverse associations between childhood PBDE serum concentrations, particularly BDE-153, and children's reading skills. Future studies with a larger sample size are needed to examine these associations.

Prenatal Polybrominated Diphenyl Ether (PBDE) Concentrations and Functional Connectivity of the Reading Network in a Community Sample of 5 Year-Old Children

Objective:Examine associations between PBDE concentrations and functional connectivity of the reading network (RN) in a community sample.Method:Resting State fMRI data (rsfMRI) were acquired from 3...

Relationship between Polybrominated Diphenyl Ether (PBDE) Levels in Maternal Serum and Fetal Tissues during Mid-Gestation of Pregnancy and Associations with Placental Biomarkers of Growth and Development

Polybrominated diphenyl ether (PBDE) compounds are flame retardant chemicals with adverse effects on brain development, which may be mediated by placental effects. Pharmacokinetic factors may lead to disproportionate exposure in the developing fetus, yet the maternal-fetal relationship is not well understood. We examined whether PBDE concentrations vary between mother and fetus during early-to-mid pregnancy and identified placental biomarkers of PBDE exposure that may influence placental growth and function using statistical methods that account for left censored PBDE data. We calculated correlations between levels of 19 PBDE congeners across three biological matrices (maternal serum, placenta tissue, and fetal liver) in 130 maternal-fetal units. We conducted an exploratory analysis in a subset of samples to identify biomarkers of PBDE exposures that may influence placental development and function. Detection frequency was highest for BDE-47 (&amp;gt; 93% across matrices). Congener BDE-28 was more highly detected in placental and fetal liver tissues than maternal serum (&amp;gt; 60% compared to &amp;lt; 20%). PBDE levels were similar or higher in maternal compared to placental and fetal tissues before and after lipid adjustment for most congeners. The median BDE-47 concentration in serum was 0.24 ng/g (95% CI: 0.22, 0.28), more than twice as high as the placental value of 0.10 ng/g (95% CI: 0.09, 0.12). The difference was more pronounced after lipid adjustment, with 35.5 ng/g lipid BDE-47 found in serum compared to 10.8 ng/g in the placenta. Lipid-adjusted BDE-28, -99, and -153 levels were ~ two times higher in the placenta and fetal liver. Biomarker changes were observed in a subset of 12 placental tissues. Prenatal PBDE exposures are correlated with maternal levels. Molecular biomarkers related to placental development and function may be informative measures of PBDE exposure in future studies.

Prenatal Polybrominated Diphenyl Ether Serum Concentrations Are Associated with Intrinsic Functional Network Organization and Executive Functioning in Childhood

Prenatal Polybrominated Diphenyl Ether Serum Concentrations Are Associated with Intrinsic Functional Network Organization and Executive Functioning in Childhood