Prenatal Polychlorinated Biphenyls Exposure Research Articles

Prenatal and postnatal exposure to polychlorinated biphenyls alter follicle numbers, gene expression, and a proliferation marker in the rat ovary

Polychlorinated biphenyls (PCBs) were used in industrial applications until they were banned in the 1970s, but they still persist in the environment. Little is known about the long-term effects of exposure to PCB mixtures on the rat ovary during critical developmental periods. Thus, this study tested whether prenatal and postnatal exposures to PCBs affect follicle numbers and gene expression in the ovaries of F1 offspring. Sprague-Dawley rats were treated with vehicle or Aroclor 1221 (A1221) at 1 mg/kg/day during embryonic days 8–18 and/or postnatal days (PND) 1–21. Ovaries from F1 rats were collected for assessment of follicle numbers and differential expression of estrogen receptor 1 (Esr1), estrogen receptor 2 (Esr2), androgen receptor (Ar), progesterone receptor (Pgr), and Ki-67 (Ki67) at PNDs 8, 32, and 60. Sera were collected for measurement of estradiol concentrations. Prenatal exposure to A1221 significantly decreased the number of primordial follicles and the total number of follicles at PND 32 compared to control. Postnatal PCB exposure borderline increased Ki67 gene expression and significantly increased Ki67 protein levels (PND 60) compared to control. Combined prenatal and postnatal PCB exposure borderline decreased Ar expression (PND 8) compared to control. However, PCB exposure did not significantly affect the expression of Pgr, Esr1, and Esr2 or serum estradiol concentrations compared to control at any time point. In conclusion, these data suggest that PCB exposure affects follicle numbers and levels of the proliferation marker Ki67, but it does not affect expression of some sex steroid hormone receptors in the rat ovary.

Prenatal Environmental Exposure to Persistent Organic Pollutants and Reproductive Hormone Profile and Pubertal Development in Dutch Adolescents.

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), may interfere with hormonal processes. Knowledge about the effects of prenatal exposure to PCBs and their hydroxylated metabolites (OH-PCBs) on pubertal development is limited. Therefore, the aim of the current study was to determine whether prenatal environmental PCB and OH-PCB exposure are associated with reproductive hormone levels and pubertal characteristics in 13- to 15-year-old children. In this Dutch observational cohort study, 194 mother–infant pairs were included (1998–2002). Maternal pregnancy serum levels of PCBs, OH-PCBs, and other POPs were measured. At follow-up (2014–2016), we measured serum or plasma levels of reproductive hormones in their children. We assessed Tanner stages and testicular volume (by clinician or standardized self-assessment), and participants completed questionnaires on pubertal onset. In total, 101 adolescents (14.4 ± 0.8 years; 53.7% of invited) participated, and 55 were boys. In boys, higher prenatal PCB levels were associated with higher testosterone levels, higher pubic hair stage, larger testicular volume, and younger age at onset of growth spurt and voice break. In girls, higher prenatal PCB levels were associated with higher stages for breast development. In conclusion, higher prenatal PCB exposure could be associated with more advanced pubertal development in 13- to 15-year-old children.

In Utero Exposure to 3,3',4,4', 5-Pentachlorobiphenyl Dose-Dependently Induces N-butyl-4-(hydroxybutyl) Nitrosamine in Rats With Urinary Bladder Carcinoma.

Polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants that can accumulate in adipose tissue or be secreted in milk. N-butyl-4-(hydroxy butyl) (BBN), a rat bladder carcinogen, recruits the host metabolism to yield its ultimate carcinogenic form via CYP1s. Since estrogen receptors (ERs) mediate biological responses important for the growth of bladder carcinoma, we investigated PCNA, Cyclin D1, ERs, CYP1s, and AhR expression in BBN rat bladder carcinomas with prenatal PCB exposure. Female SD rats were treated with 7.5 μg, 250 ng, and 2.5 ng of 3,3',4,4',5-pentachlorobiphenyl (PCB126)/kg or vehicle on days 13 to 19 post-pregnancy. Six-week-old male offspring were treated with 0.05% BBN for 10 weeks before being anesthetized and the urinary bladder wall incised to expose the bladder carcinomas. N-butyl-4-(hydroxybutyl) bladder carcinoma incidence increased with prenatal PCB exposure dose-dependently. In bladder carcinoma, PCB126 exposure significantly increased PCNA, D1, ERα, CYPIA1, CYP1B1, and AhR expression dose-dependently, and increased ERα expression was particularly prominent. However, the expression of ERβ was low, independent of the volume of PCB126 given, indicating similarity to the Vehicle group. We conclude that prenatal PCB126 exposure in rats can induce PCB126 to dose-dependently metabolize BBN via CYP1A1, and contribute to bladder carcinogenesis with upregulation of ERα expression.

Perspective on prenatal polychlorinated biphenyl exposure and the development of the progeny nervous system (Review).

The developmental origins of health and disease concept illustrates that exposure in early life to various factors may affect the offspring's long-term susceptibility to disease. During development, the nervous system is sensitive and vulnerable to the environmental insults. Polychlorinated biphenyls (PCBs), which are divided into dioxin-like (DL-PCBs) and non-dioxin-like PCBs (NDL-PCBs), are synthetic persistent environmental endocrine-disrupting chemicals. The toxicological mechanisms of DL-PCBs have been associated with the activation of the aryl hydrocarbon receptor and NDL-PCBs have been associated with ryanodine receptor-mediated calcium ion channels, which affect neuronal migration, promote dendritic growth and alter neuronal connectivity. In addition, PCB accumulation in the placenta destroys the fetal placental unit and affects endocrine function, particularly thyroid hormones and the dopaminergic system, leading to neuroendocrine disorders. However, epidemiological investigations have not achieved a consistent result in different study cohorts. The present review summarizes the epidemiological differences and possible mechanisms of the effects of intrauterine PCB exposure on neurological development.

Transgenerational effects of polychlorinated biphenyls: 2. Hypothalamic gene expression in rats†.

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals (EDCs) with well-established effects on reproduction and behavior in developmentally-exposed (F1) individuals. Because of evidence for transgenerational effects of EDCs on the neuroendocrine control of reproductive physiology, we tested the hypothesis that prenatal PCB exposure leads to unique hypothalamic gene-expression profiles in three generations. Pregnant Sprague-Dawley rats were treated on gestational days 16 and 18 with the PCB mixture Aroclor 1221 (A1221), vehicle (3% DMSO in sesame oil), or estradiol benzoate (EB, 50μg/kg), the latter a positive control for estrogenic effects of A1221. Maternal- and paternal-lineage F2 and F3 generations were bred using untreated partners. The anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), involved in the hypothalamic control of reproduction, were dissected from F1 to F3 females and males, RNA extracted, and gene expression measured in a qPCR array. We detected unique gene-expression profiles in each generation, which were sex- and lineage-specific. In the AVPV, treatment significantly changed 10, 25, and 11 transcripts in F1, F2, and F3 generations, whereas 10, 1, and 12 transcripts were changed in these generations in the ARC. In the F1 AVPV and ARC, most affected transcripts were decreased by A1221. In the F2 AVPV, most effects of A1221 were observed in females of the maternal lineage, whereas only Pomc expression changed in the F2 ARC (by EB). The F3 AVPV and ARC were mainly affected by EB. It is notable that results in one generation do not predict results in another, and that lineage was a major determinant in results. Thus, transient prenatal exposure of F1 rats to A1221 or EB can alter hypothalamic gene expression across three generations in a sex- and lineage-dependent manner, leading to the conclusion that the legacy of PCBs continues for generations.

Evidence for differential thyroid sensitivity from prenatal exposure to polychlorinated biphenyl chemicals in children with autism

Background/Aim: Prenatal exposure to polychlorinated biphenyls (PCBs), persistent organic pollutants, is linked to altered thyroid function and adverse neurodevelopmental outcomes, including autism spectrum disorder (ASD). We examined whether neonatal thyroid-stimulating hormone (TSH) mediates the relationship between prenatal PCB exposure and risk of ASD. Methods: We analyzed data from the Early Markers for Autism (EMA) Study, a case-control study of children born during 2000-2003 in Southern California. Children diagnosed with ASD (n=523), Intellectual disability (ID; n=147), and general population controls (n=405) were identified from birth and Department of Developmental Services records. Eleven PCB congeners were measured above the limit of detection in maternal serum collected during the second trimester and modeled as quartiles. Neonatal TSH levels were obtained from state newborn screening records and ln-transformed. We assessed relationships between PCBs and neonatal TSH in models stratified by neurodevelopmental outcome and TSH mediation of the significant relationships we previously observed in EMA between several PCBs and ASD. Results: In the full sample, correlations between PCB concentrations and neonatal TSH were weak and not significant (ranging from 0 to 0.06). However, among children with ASD, we observed significant increases in neonatal TSH associated with an interquartile increase in prenatal levels of four PCBs, including PCB153 (adj-β: 0.21, 95%CI: 0.02-0.39) and PCB138/158 (adj-β: 0.19, 95%CI: 0.01-0.37). We did not observe associations between neonatal TSH and PCBs among children with ID only or controls. Mediation analyses did not suggest that relationships between these PCBs and ASD were mediated by neonatal TSH. Conclusions: Prenatal exposure to PCBs, particularly congeners previously found to be associated with ASD in EMA, were positively associated with neonatal TSH, but only among children subsequently diagnosed with ASD. These findings, needing replication in larger cohorts, may indicate differential fetal sensitivity to thyroid-disrupting chemicals among individuals born, and later-diagnosed, with ASD.

Prenatal exposure to trichlorinated biphenyls (PCB 18 and 28) is associated with child hyperactivity 8 years later

Background: Polychlorinated biphenyl (PCB) exposure may be associated with neurodevelopmental problems, particularly hyperactivity and attention deficit/hyperactivity disorder (ADHD). In animal studies, exposure to PCBs increased hyperactivity, decreased dopamine in key brain regions, and PCB 28, 47, and 52 were found in those regions. Dopamine has also been implicated in the etiology of ADHD in humans. Most epidemiologic studies have relied on maternal blood rather than newborn blood to quantify prenatal PCB exposure, and neonatal levels might better reflect fetal exposure. Methods: Whole-blood concentrations of PCB congeners #8, 15, 18, 28, 52, 70, 95, 101, 138, and 153 were measured in the Upstate KIDS study, a population-based longitudinal study of children born in New York State between 2008-2010, using newborn dried blood spots (n=2610). PCBs were quantified (ng/mL) using gas chromatography-DFS high resolution mass spectrometry. Individual blood spots provided insufficient volume for assays, so pools of 5 were used, and individual values were derived from pools. Child hyperactivity symptoms (Mean=4.82, SD=5.13) were assessed by maternal report on the Vanderbilt ADHD Parent Rating Scale when children were 8 years of age. Models were adjusted for child age, sex, and plurality, and maternal age, education, race/ethnicity, insurance status, marital status, pre-pregnancy body mass index, gestational weight gain, parity, and pregnancy smoking. Results: Each 1 ng/mL increase in PCB 18 and PCB 28 was associated with 3.63 (95%CI=0.42-6.84) and 4.08 (95%CI=0.61-7.55) more points in hyperactive behavioral ratings, respectively. Except for PCB 15, other PCBs also had positive but imprecise relations with hyperactivity. Conclusions: Levels of PCBs in newborn blood spots were associated with less than 1 standard deviation higher hyperactivity 8 years later. Even low-level prenatal exposure may have long-term behavioral consequences.

Prenatal environmental exposures and associations with teen births.

Background:Children’s prenatal exposure to multiple environmental chemicals may contribute to subsequent deficits in impulse control, predisposing them to risk-taking.Objective:Our goal was to investigate associations between prenatal exposure mixtures and risk of teen birth, a manifestation of high-risk sexual activity, among 5,865 girls (1st generation) born in southeast Massachusetts from 1992-1998.Methods:Exposures included prenatal modeled polychlorinated biphenyls (PCBs), ρ,ρ′-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), lead (Pb), and mercury (Hg). We fit adjusted generalized additive models with multivariable smooths of exposure mixtures, 1st generation infant’s birth year, and maternal age at 1st generation birth. Predicted odds ratios (ORs) for teen birth were mapped as a function of joint exposures. We also conducted sensitivity analyses among 1st generation girls with measured exposure biomarkers (n=371).Results:The highest teen birth risk was associated with a mixture of high prenatal HCB, Hg, Pb, and PCB, but low DDE exposure, with similar associations in sensitivity analyses. The highest OR predicted for girls born in 1995 to mothers of median age (26 years) was at the 95th percentile of the HCB and PCB exposure distributions (OR=3.09; 95% confidence interval: 0.29, 32.4). Additionally, girls born earlier in the study period or to teen mothers were at increased risk of teen birth.Significance:Prenatal environmental chemical exposures and sociodemographic characteristics may interact to substantially increase risk of teen births.

Prenatal exposure to PCBs and neurological and sexual/pubertal development from birth to adolescence

Several chemical compounds are resistant to degradation and end up in the food chain. One group of these chemicals is polychlorinated biphenyls (PCBs) which are used as flame retardants and plasticizers. Although PCBs were banned several decades ago, PCBs are still found in environmental media, including in the body of humans. PCBs are transferred from mother to fetus via the placenta during pregnancy. Considering that the prenatal period is a sensitive period during which essential developmental processes take place, exposure to environmental chemicals might have considerable and permanent consequences for outcomes in later life. The aim of this review is to provide an update on the latest insights on the effects of prenatal exposure to PCBs on neurological, sexual and pubertal development in children. We give an overview of recent literature, and discuss it in the light of the findings in a unique Dutch birth cohort, with data on both neurological and pubertal development into adolescence. The findings in the studies included in this review, together with the findings in the Dutch cohort, demonstrate that prenatal exposure to PCBs can interfere with normal child development, not only during the perinatal period, but up to and including adolescence. Higher prenatal exposure to PCBs was found to be both negatively and positively associated with neurodevelopmental outcomes. Regarding pubertal development, higher prenatal PCB exposure was found to be associated with more advanced pubertal development, also in the Dutch cohort, whereas other studies also found delayed pubertal development. These findings raise concern regarding the effects of man-made chemical compounds on child development. They further contribute to the awareness of how environmental chemical compounds can interfere with child development and negatively influence healthy ageing.

Human prenatal exposure to polychlorinated biphenyls (PCBs) and risk behaviors in adolescence

Polychlorinated biphenyls (PCBs) are chemicals used in a variety of products before they were widely banned due to toxic effects in humans and wildlife. Because of continued persistence and ubiquity of these contaminants, risk of exposure to people living in industrialized countries is still high. Experimental research show that developmental exposure to PCB may alter function of brain pleasure centers and potentially influence disinhibitory behaviors, including tobacco and alcohol use. Yet, the potential effects of developmental PCB exposure on adolescent substance use have not been studied in humans. We used the Child Health and Development Studies (CHDS), a prospective birth cohort study in the Oakland and East Bay areas of California, to investigate associations between prenatal exposure to PCB congeners (66, 74, 99, 118, 138, 153, 170, 180, 187, and 203) and later disinhibitory behaviors in adolescents, specifically alcohol consumption and smoking, in a randomly selected sample (n = 554). Total prenatal PCB exposure was not associated with disinhibitory behaviors, among adolescents. However, the adjusted odds ratio (aOR) for being a current smoker, was higher in subjects within the third quartile of maternal PCB 66 exposure compared to those below the median (aOR = 1.93; 95% CI 1.05, 3.55). The aOR for drinking >2 alcoholic beverages per week, were also higher for adolescents within the third (aOR = 1.46; 95% CI 0.86, 2.47) and fourth quartile of PCB 66 exposure (aOR = 1.39; 95% CI 0.83, 2.35), but the differences did not reach statistical significance. These results suggest that this specific PCB congener may play a role inducing neurodevelopmental alterations that could potentially increase the risk of becoming a long-term user of tobacco and possibly alcohol. There were no notable differences between magnitude or direction of effect between boys and girls. Future replicate analyses with larger longitudinal samples and animal experimental studies of potential underlying mechanisms are warranted.

Neuroimaging signatures of brain plasticity in adults with prenatal exposure to polychlorinated biphenyls: Altered functional connectivity on functional MRI

Prenatal exposure to polychlorinated biphenyls (PCBs), persistent organic pollutants in food chains and environment, exerts negative effects on children's cognitive function. To study the long-term effects, we examined cognitive functions in the male children of women with substantial PCB exposure in Taiwan during 1978–1979 and investigated neural basis of cognitive function changes through structural magnetic resonance imaging (MRI) and functional MRI (fMRI), which included resting-state and task-activated fMRI with two paradigms: a 2-back task and a picture rotation task. Ten men aged 30.0 ± 3.7 years with prenatal exposure to PCBs and 11 unexposed controls aged 28.1 ± 3.1 years participated. Both groups had similar cognitive phenotypes and behavioral results. Structural MRI analysis results showed that the PCB group had increased cortical thickness over the right inferior parietal lobule. In the resting-state study, the PCB group showed alterations in the default mode network. During the tasks, the PCB group showed decreased task-induced deactivation signals in cognition–associated brain areas during the 2-back task but enhanced deactivations during the picture rotation task. This study demonstrated altered structural MRI as well as resting and task-related fMRI in men with prenatal PCB exposure, suggesting altered brain plasticity and compensatory neuropsychological performance.

Prenatal exposure to polychlorinated biphenyls and asthma, eczema/hay fever, and frequent ear infections

ABSTRACTObjectives: The effects of prenatal exposure to Polychlorinated biphenyls (PCBs) on the development of asthma, frequent ear infections, and eczema/hay fever are not well understood. We aim to investigate associations between prenatal PCB exposure and these health outcomes in the offspring of women who worked at the LaSalle Electrical Utilities Company (EUC). Methods: A retrospective cohort with at least one live birth and known employment time at EUC was eligible for this analysis. Exposure was defined and categorized by the number of fiscal quarters worked during the PCB era (1952–1981). A total of 288 women with 800 live births were included. A Chi-Square test was used to compare maternal and child characteristics across exposure groups and repeated measures logistic regression, controlling for clustering among siblings, was used to assess the associations between prenatal PCB exposure and these outcomes. Results: After adjustment for confounding and independent maternal predictors, 1–4 quarters of prenatal exposure to PCBs increased the odds for asthma (OR 3.24[1.30–8.09]), eczema/hay fever (OR 3.29[1.54–7.04]), and frequent ear infections (OR 2.24[1.19–4.22]) when compared with persons unexposed/exposed only to naphthalenes. The significance of the associations varied by exposure period and level of exposure, with the strongest associations in those employed exclusively after 1952 when PCBs were introduced. Conclusions: These results support previous findings of associations of prenatal exposure to PCBs with asthma, eczema/hay fever, and frequent ear infections. Additional prospective studies are needed to confirm these findings. Also required are more precise PCB exposures to separate them from other exposures in occupational settings.

Erratum: "Prenatal PBDE and PCB Exposures and Reading, Cognition, and Externalizing Behavior in Children".

[This corrects the article DOI: 10.1289/EHP478.].

Effects of intrauterine exposures to polychlorinated biphenyls, methylmercury, and lead on birth weight in Japanese male and female newborns

BackgroundThe effects of prenatal exposures to polychlorinated biphenyls (PCBs), methylmercury, and lead on birth weight remain disputable. The aim of this study was to investigate whether these chemicals affect birth weight of Japanese newborns, with special emphasis on determining whether these effects differ between males and females.MethodsThe subjects from Tohoku Study of Child Development, which was designed to examine the developmental effects of prenatal exposures to such hazardous chemicals, were 489 mother-newborn pairs with complete data including smoking habit during pregnancy.ResultsThe mean birth weight of all newborns was 3083 (range, 2412–4240) g. The median values of biomarkers in cord blood were 46.0 (5th and 95th percentiles, 18.6–113.8) ng/g–lipid for total PCBs, 10.1 (4.3–22.4) ng/g for total mercury (THg), and 1.0 (0.6-1.7) μg/dL for lead. The birth weight was significantly heavier in the 252 male newborns than in the 237 female ones. A negative association between total PCBs and birth weight was observed in both male and female newborns, even after adjusting for possible confounders. However, a negative association of THg with birth weight was found only in the male newborns. There was no significant relationship between lead and birth weight in both groups.ConclusionBirth weight appears to be affected by prenatal PCB exposure in Japanese male and female newborns, and the effect of methylmercury exposure on male fetal growth may be stronger than that for females. This implication is that the effects on fetal growth should be assessed in males and females separately.

Polychlorinated biphenyls: New evidence from the last decade.

Millions of pounds of polychlorinated biphenyl (PCB) compounds have been produced in multiple countries for industrial applications over the last several decades. PCB exposure induces various adverse health effects in animals and humans. Environmental and occupational exposures to PCBs have been associated with liver, kidney, endocrine, and neurodevelopmental adverse effects. We have collected and reviewed animal and human data cited in the US National Library of Medicine from 2000 to 2010. In brief, our review shows new evidence, that is, in animal studies, exposure to one of the PCBs, A1221, induces a significant alteration of serum luteinizing hormone. The effects were more profound in the F2 generation, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. Morphological analyses of brain tissue from rats exposed to A1254 confirmed the results of an earlier work which showed that the relative size of the intra- and infrapyramidal (II-P) mossy fibers was smaller than that in the controls and also reduction in growth was selective for the II-P mossy fibers. PCB exposure increased anogenital distance and prostate size but decreased epididymal weight, epididymal sperm count, and motile epididymal sperm count. No effects were observed on testicular weight or size. The epidemiological data showed an association between diabetes mellitus prevalence and elevated concentrations of PCB 153. Additionally, prenatal PCB exposure studies were associated with a smaller thymic index at birth and could adversely affect immune responses to childhood vaccinations and resistance to respiratory infections. PCB exposure was also reported to adversely affect enamel development in children in a dose-dependent manner. Because PCBs and their metabolites are potential health hazards, understanding the risk factors associated with individual PCBs, PCB mixtures, and PCB metabolites is important. PCB exposures of vulnerable populations (pregnant women, fetuses, infants, and children) are of particular concern because of heightened sensitivity during this period of brain development.

Prenatal PBDE and PCB Exposures and Reading, Cognition, and Externalizing Behavior in Children.

Background:Prenatal polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) exposures may influence children’s neurodevelopment.Objective:We examined the association of prenatal PBDE and PCB exposures with children’s reading skills at ages 5 and 8 years, Full-Scale Intelligence Quotient (FSIQ), and externalizing behavior problems at age 8 years.Methods:From 239 mother–child pairs recruited (2003–2006) in Cincinnati, Ohio, we measured maternal serum PBDE and PCB concentrations, assessed child’s reading skills using the Woodcock–Johnson Tests of Achievement III (WJ-III) at age 5 years and the Wide Range Achievement Test-4 (WRAT-4) at age 8 years, tested FSIQ using the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing behavior problems using the Behavioral Assessment System for Children-2 (BASC-2) at age 8 years. We used multiple linear regression to examine the association of prenatal PBDE and PCB concentrations and reading, FSIQ, and externalizing behavior problems after adjusting for covariates.Results:An increase of Sum4PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) by 10 times was not significantly associated with reading scores at age 5 years at the p = 0.05 level but was inversely associated with Reading Composite scores (β: –6.2, 95% CI: –11.7, –0.6) and FSIQ (β: –5.3, 95% CI: –10.6, –0.02) at age 8 years; it was positively associated with the score for externalizing behavior problems (β: 3.5, 95% CI: –0.1, 7.2) at age 8 years. Prenatal Sum4PCBs (PCB-118, -153, -138-158, and -180) was not significantly associated with a child’s reading skills, FSIQ, and externalizing behavior problems.Conclusion:Prenatal PBDE concentration was inversely associated with reading skills and FSIQ and positively associated with externalizing behavior problems at age 8 years. No significant associations were found in prenatal PCB concentration.Citation:Zhang H, Yolton K, Webster GM, Sjödin A, Calafat AM, Dietrich KN, Xu Y, Xie C, Braun JM, Lanphear BP, Chen A. 2017. Prenatal PBDE and PCB exposures and reading, cognition, and externalizing behavior in children. Environ Health Perspect 125:746–752; http://dx.doi.org/10.1289/EHP478

Chaotic time series prediction for prenatal exposure to polychlorinated biphenyls in umbilical cord blood using the least squares SEATR model.

Chaotic time series prediction based on nonlinear systems showed a superior performance in prediction field. We studied prenatal exposure to polychlorinated biphenyls (PCBs) by chaotic time series prediction using the least squares self-exciting threshold autoregressive (SEATR) model in umbilical cord blood in an electronic waste (e-waste) contaminated area. The specific prediction steps basing on the proposal methods for prenatal PCB exposure were put forward, and the proposed scheme’s validity was further verified by numerical simulation experiments. Experiment results show: 1) seven kinds of PCB congeners negatively correlate with five different indices for birth status: newborn weight, height, gestational age, Apgar score and anogenital distance; 2) prenatal PCB exposed group at greater risks compared to the reference group; 3) PCBs increasingly accumulated with time in newborns; and 4) the possibility of newborns suffering from related diseases in the future was greater. The desirable numerical simulation experiments results demonstrated the feasibility of applying mathematical model in the environmental toxicology field.

Estimation of a partially linear additive model for data from an outcome-dependent sampling design with a continuous outcome.

Outcome-dependent sampling (ODS) designs have been well recognized as a cost-effective way to enhance study efficiency in both statistical literature and biomedical and epidemiologic studies. A partially linear additive model (PLAM) is widely applied in real problems because it allows for a flexible specification of the dependence of the response on some covariates in a linear fashion and other covariates in a nonlinear non-parametric fashion. Motivated by an epidemiological study investigating the effect of prenatal polychlorinated biphenyls exposure on children's intelligence quotient (IQ) at age 7 years, we propose a PLAM in this article to investigate a more flexible non-parametric inference on the relationships among the response and covariates under the ODS scheme. We propose the estimation method and establish the asymptotic properties of the proposed estimator. Simulation studies are conducted to show the improved efficiency of the proposed ODS estimator for PLAM compared with that from a traditional simple random sampling design with the same sample size. The data of the above-mentioned study is analyzed to illustrate the proposed method.

Prenatal Exposure To PCBs Differentially Affects Sperm Head And Tail Morphology Among Adult Male Offspring Of The Child Health And Development Studies

Introduction Studies of the association between polychlorinated biphenyls (PCBs) and sperm morphology are contradictory. Two possible reasons are 1) different PCB congeners and congener mixtures may have different effects and 2) the standard measure of percent abnormal sperm combines several outcomes, e.g. abnormal heads and tails. Here we explore the effect of prenatal exposure to PCBs on 3 measures of abnormal sperm morphology. Methods In a follow-up of 196 men from the Child Health and Development Studies cohort, we evaluated associations between prenatal exposure to total PCBs and 15 PCB congeners, both individually and grouped according to chlorination patterns and proposed biological mechanism, and percent abnormal sperm (total, head and tail) at mean age 43. PCBs were measured in stored maternal blood taken immediately postpartum. Sperm morphology was measured in semen collected from adult male offspring and analyzed according to WHO criteria. All analyses adjusted for maternal total lipids, race, income and coffee consumption, and offspring age, smoking, and perceived stress. Results Each ng/mL increase in total PCBs in maternal blood was associated with an increase of 0.92 percent total normal sperm (95% CI: 2.35, -0.51), driven by a reduction in head abnormalities (bhead= -1.30 [-2.31, -0.29] but with contrasting evidence for tail abnormalities (btail=0.49 [-0.38, 1.36]). Among total, grouped and individual PCBs, prenatal exposure was generally associated with fewer head abnormalities and more tail abnormalities and the estimated association was strongest for di ortho substituted PCBs Conclusions Prenatal PCB exposure may have opposite effects on sperm head and tail morphology, warranting further research into the influence of PCBs on the development of fetal Sertoli cells. Prenatal PCB exposure may create an unfavorable environment for production or survival of sperm with head abnormalties. The clinical consequences of this finding are uncertain.

Prenatal Polychlorinated Biphenyls Exposure And Reproductive Hormones In Adult Male Offspring: Results From The Child Health And Development Studies

Introduction: Polychlorinated biphenyls (PCBs) are ubiquitous persistent organic pollutants which act as endocrine disruptors. The effect of in utero exposure to PCBs on hormonal concentrations in md-life remains unclear. Except for three studies, previous research investigating the relationship between PCB exposure and male sex hormones has been cross-sectional. Here, we examine whether in utero PCB exposure is associated with concentrations of testosterone and follicular stimulating hormone (FSH) in adult males. Methods: We used data from the Study of the Environment and Reproduction (SER), a follow up of adult male offspring from the Child Health and Development Study. Of those men who participated, 204 (mean age 43.7 years) gave a blood sample for the measurement of total testosterone and FSH. Prenatal PCB exposure to 15 congeners was measured in maternal blood samples in the immediate postpartum period. Multivariable regression was used to determine the association between prenatal PCB exposure and concentrations of testosterone and FSH, controlling for age, race, total lipids and BMI. PCBs were grouped according to their proposed mechanism of action and according to the degree of chlorination; individual congeners were also assessed as separate exposure measures. Hormone and PCB concentrations were positively skewed and transformed using the natural log function. Results: Mean (standard deviation) concentrations of total testosterone and FSH were 386 (183) ng/dL and 5.83 (3.99) mIU/mL, respectively. We did not find any associations between exposure and FSH. In both unadjusted and adjusted analyses, maternal PCB183 was associated with increased total testosterone. For each log unit increase in maternal PCB183, log total testosterone increased by 0.15 ng/dL (95% confidence interval (-0.01, 0.31). Conclusions: These results suggest that prenatal exposure to specific PCB congeners is associated with testosterone levels in adulthood.