Maternal Polychlorinated Biphenyls Research Articles

Prenatal organochlorine pollutant exposure and risk of schizophrenia in a national birth cohort

Non-genetic prenatal exposures have been associated with schizophrenia risk. However, the role of prenatal exposure to environmental neurotoxicants in offspring schizophrenia risk has been studied in only limited instances. Polychlorinated biphenyls (PCBs) and the pesticide metabolite p,p′-dichlorodiphenyl dichloroethylene (DDE) have been linked to neurodevelopmental outcomes, including impairments implicated in schizophrenia. To determine whether prenatal maternal levels of organochlorine pollutants including PCBs or DDE are associated with schizophrenia in the offspring, an investigation was conducted in the Finnish Prenatal Study of Schizophrenia (FIPS-S), a case-control study nested in a national birth cohort. Cases were born in 1987–1991 and had at least two diagnoses of schizophrenia (ICD-10 F20; ICD-9 295) or schizoaffective disorder (ICD-10 F25; ICD-9 295.7) recorded in the national Care Register for Health Care. Each case was individually matched to a control on sex, date of birth, and residence in Finland on the date of case diagnosis. In 500 case-control pairs, PCB congeners 74, 99, 118, 138, 153, 156, 170, 180, 183, 187, and some widespread organochlorine pesticides or their metabolites including DDE were measured in archived prenatal maternal sera using gas chromatography - high triple quadrupole mass spectrometry. Maternal total PCBs were quantified as the sum of concentrations of the measured congeners. Associations with schizophrenia were examined using conditional logistic regression. Maternal PCB or DDE levels greater than the 75th percentiles of the control distributions showed no evidence of association with offspring schizophrenia (PCBs: adjusted odds ratio (aOR) = 1.13, 95 % CI = 0.85–1.50), p = 0.41; DDE: aOR = 1.08, 95 % CI = 0.80–1.45; p = 0.63). Maternal levels of either pollutant dichotomized at the 90th percentile or considered as a continuous variable also did not show evidence for association with offspring schizophrenia. This study found a lack of evidence that prenatal maternal levels of the organochlorine pollutants DDE and PCBs are associated with offspring risk of schizophrenia.

Maternal polychlorinated biphenyl 126 (PCB 126) exposure modulates offspring gut microbiota irrespective of diet and exercise

The gut microbiota plays an important role throughout the lifespan in maintaining host health, and several factors can modulate microbiota composition including diet, exercise, and environmental exposures. Maternal microbiota is transferred to offspring during early life; thus, environmental exposures before gestation may also modulate offspring microbiota. Here we aimed to investigate the effects of maternal exposure to dioxin-like polychlorinated biphenyls (PCBs) on the microbiota of aged offspring and to determine if lifestyle factors, including maternal exercise or offspring high-fat feeding alter these associations. To test this, dams were exposed to PCB 126 (0.5 μmole/kg body weight) or vehicle oil by oral gavage during preconception, gestation, and during lactation. Half of each group was allowed access to running wheels for ≥ 7 days before and during pregnancy and up through day 14 of lactation. Female offspring born from the 4 maternal groups (PCB exposure or not, with/without exercise) were subsequently placed either on regular diet or switched to a high-fat diet during adulthood. Microbiota composition was quantified in female offspring at 49 weeks of age by 16 S rRNA sequencing. Maternal exposure to PCB 126 resulted in significantly reduced richness and diversity in offspring microbiota regardless of diet or exercise. Overall compositional differences were largely driven by offspring diet, but alterations in specific taxa due to maternal PCB 126 exposure, included the depletion of Verrucomicrobiaceae and Akkermansia muciniphila, and an increase in Anaeroplasma. Perturbation of microbiota due to PCB 126 may predispose offspring to a variety of chronic diseases later in adulthood.

Evolution of pace-of-life syndrome under conditions of maternal PCB contamination and global warming in early life stages of cold stenothermic fish (Arctic char)

The end of the 20th century was characterised by rapid modifications of ecosystem functioning under different pressures (such as eutrophication and toxic pollution). Increasing temperatures in the context of global warming could have indirect consequences, such as increased bioavailability of hydrophobic organic pollutants amongst aquatic species. According to the “pace-of-life syndrome” (POLS) theory, these stressors could lead to covariations in many life traits. Lake Bourget is the largest natural lake in France and has been highly polluted from the fifties to the eighties both with a high load of nutrients (wastewater discharge) and polychlorinated biphenyls (PCBs) (industrial effluent discharge). Despite improvements in water quality since the 21st century, PCB levels are still higher than the United States Environmental Protection Agency cut-off for wildlife protection. The population of Arctic char, a cold stenothermic salmonid, has remained low in Lake Bourget for the last ten years despite restocking efforts and complete re-oligotrophication. We hypothesised that PCB pollution can affect the Arctic char population and that the increase in water temperature could magnify the effects of PCB. Thus, this study aimed to investigate the effects of maternal PCB contamination on offspring using a multiparametric and multiscale approach. Female Arctic char were contaminated with PCB before spawning, and each fertilised spawn was incubated at two temperatures (4 and 8.5 °C). The results showed that co-exposure to increased temperature and maternal PCB contamination influenced biodemographic, physiological, and behavioural parameters. The effects were highly dependant on the developmental stage. Based on the POLS theory, a continuum of life traits that may reflect potential physiological and behavioural modifications in response to these concurrent stressors is highlighted

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment

BackgroundGestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes. ObjectivesWe aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort. MethodsWe measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits. ResultsPCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure. ConclusionsPlacental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.

Standardised regression coefficient as an effect size index in summarising findings in epidemiological studies


 Background: a major problem in evaluating and reviewing the published findings of studies on the association between a quantitative explanatory variable and a quantitative dependent variable is that the results are analysed and reported in many different ways. To achieve an effective review of different studies, a consistent presentation of the results is necessary. This paper aims to exemplify the main topics related to summarising and pooling research findings from multivariable models with a quantitative response variable.
 Methods: we outline the complexities involved in synthesising associations. We describe a method by which it is possible to transform the findings into a common effect size index which is based on standardised regression coefficients. To describe the approach we searched original research articles published before January 2012 for findings of the relationship between polychlorinated biphenyls (PCBs) and birth weight of new-borns. Studies with maternal PCB measurements and birth weight as a continuous variable were included.
 Results: the evaluation of 24 included articles reveled that there was variation in variable measurement methods, transformations, descriptive statistics and inference methods. Research syntheses were performed summarizing regression coefficients to estimate the effect of PCBs on birth weight. A birth weight decline related to increase in PCB level was found.
 Conclusions: the proposed method can be useful in quantitatively reviewing published studies when different exposure measurement methods are used or differential control of potential confounding factors is not an issue.

Association between telomere length in human umbilical cord tissues and polychlorinated biphenyls in maternal and cord serum

Environmental exposure to persistent organic pollutants during pregnancy has potential adverse health effects on the fetus. One of the environmental pollutants is polychlorinated biphenyl (PCB). Earlier, we reported the presence of PCBs in fetal tissues such as the umbilical cord. Telomere length (TL) is a biomarker of aging because it shortens with each cell division. According to the Developmental Origins of Health and Disease hypothesis, fetal exposure to environmental pollutants during pregnancy affects the occurrence of non-communicable diseases in later life. In the current study, we investigated the association between cord tissue TL and serum levels of PCBs. The subjects were 114 mother-child pairs participating in a birth cohort study, the Chiba Study of Mother and Child Health (C-MACH). Maternal serum was collected during pregnancy, and cord serum and tissue were obtained at birth. TL was assessed by qPCR using genomic DNA extracted from the cord tissue. Maternal and cord serum PCB congener levels were assessed using gas chromatography and negative ion chemical ionization qMS. In male fetuses, serum levels of PCB74 in the cord blood were significantly associated with TL following covariate adjustment, but no significant association was found in female fetuses. These data suggest that the TL of the umbilical cord is affected by fetal exposure to PCBs.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013–2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and “Dana Dwek” Children’s Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4–6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes—allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Maternal serum persistent organic pollutant exposure and offspring diagnosed ADHD in a national birth cohort

BackgroundEvidence implicates environmental factors in attention-deficit/hyperactivity disorder (ADHD) risk. Prenatal exposures to polychlorinated biphenyls (PCBs) and the pesticide metabolite p,p’-dichlorodiphenyl dichloroethylene (DDE) have been linked to lower cognitive ability, increased impulsivity, and attention related deficits in the offspring. However, information on the relationship of these exposures to the risk of clinically diagnosed ADHD is limited. ObjectivesTo determine whether prenatal maternal levels of PCBs or DDE are associated with ADHD diagnosis in the offspring. MethodsThe investigation was conducted in the Finnish Prenatal Study of ADHD (FIPS-ADHD), a case-control study nested in a national birth cohort. Cases were born in 1998 or 1999 and diagnosed with ADHD (ICD-9 314x or ICD-10 F90. x) according to the national Care Register for Health Care. Each case was individually matched to a control on sex, date, and place of birth. PCB congeners (PCB 74, 99, 118, 138, 153, 156, 170, 180, 183, 187) and DDE were quantified from archived prenatal maternal sera from 359 matched case-control pairs using gas chromatography - high triple quadrupole mass spectrometry. Maternal total PCBs were quantified as the sum of concentrations of the measured congeners. Associations with ADHD were examined using conditional logistic regression. ResultsMaternal PCB or DDE levels greater than the 75th percentiles of the control distributions showed no evidence of association with offspring ADHD (PCBs: adjusted odds ratio (aOR) = 1.01, 95% CI = 0.63, 1.60), p = 0.98; DDE: aOR = 1.13, 95% CI = 0.71, 1.81; p = 0.60). Maternal levels of either pollutant dichotomized at the 90th percentile or considered as a continuous variable also did not show evidence for association with offspring ADHD diagnosis. DiscussionThis study did not find evidence for association of maternal prenatal levels of PCBs or DDE with clinical diagnosis of offspring ADHD; however, this does not rule out the possibility of an impact on subclinical phenotypes.

Comparison of the PCB serum levels among mother-child pairs in areas of Eastern Japan and Central Taiwan

Polychlorinated biphenyls (PCBs) have been prohibited for two decades in Japan and Taiwan. The aim of this study was to compare the PCB congeners in maternal and cord serum between two countries. Our study subjects were 248 and 100 mother-child pairs in Japan and Taiwan. The measured levels of 23 serum PCB congeners between two countries were analyzed using gas chromatography–electron capture negative ionization quadrupole mass spectrometry (GC-NICI-qMS). The statistical comparisons were conducted by Student's t-test and principal component analysis with further stratification by maternal age and parity. The maternal total PCBs levels in Japan (426 ± 244 pg/g wet wt) were significantly higher than those in Taiwan (254 ± 155 pg/g wet wt), and the similar results were found in cord total PCBs levels (97 ± 76 and 58 ± 87 pg/g wet wt). It showed different distributions of PCB congeners between two countries. Whether in maternal or cord serum, the CB138, CB153 and CB180 were the highest detectable congeners whether in Japan or Taiwan. And, the CB66, CB99, CB206 and CB209 were only detected in maternal serum of Taiwan. The women of advanced maternal age had higher levels of PCB congeners, especially in Taiwan, and the primiparous women had higher levels of PCB congeners in two countries. In summary, the PCB congeners in Japan's mother-child pairs were with higher levels and different distributions when compared to those in Taiwan, and the maternal age and parity were important factors associated with the PCB levels.

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring.Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns.Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders.Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83–68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70–8.23) μIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27–13.53) μg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36–12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6–24.9) μg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19–24.9).Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

Persistent organic pollutants in pregnant women potentially affect child development and thyroid hormone status

BackgroundPotentially harmful effects of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) on prenatal development and the endocrine system have been controversially discussed.MethodsWorking with a German cohort of 324 pregnant women, we assessed POP levels and used robust linear regression models to determine potential associations between maternal POP concentrations and pre- and postnatal development in the children, as well as the thyroid hormone status of the mother and child.ResultsMaternal p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and most measured PCBs positively correlated with postnatal weight gain. We detected no correlation between newborn birth weight and head circumference, respectively, and maternal PCB and p,p′-DDE serum levels, while body length at birth was negatively associated with the maternal serum concentration of PCB 183. Maternal p,p′-DDE and nearly all PCB serum levels showed a negative correlation with maternal free triiodothyronine (FT3). p,p′-DDE and PCB 74 and 118 were negatively associated with maternal thyroid-stimulating hormone levels. In addition, we identified significant associations between maternal POP levels and thyroid hormone parameters of the child.ConclusionsThese results indicate that POP exposure likely affects different aspects of pre- and postnatal development and impacts the thyroid hormone status of both mother and child.ImpactPregnant women in a German cohort display a substantial accumulation of POPs.Body mass index and age influence maternal serum POP levels.Maternal POP levels show correlations with the child’s length at birth and weight gain, and FT3 levels in the mother and child.Our data provide additional evidence for the potentially harmful influence of POPs.Our data indicate that POPs influence pre- and postnatal development.

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus.This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns.Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables.Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns.This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.

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.

The relationship of maternal PCB, toxic, and essential trace element exposure levels with birth weight and head circumference in Chiba, Japan.

Maternal exposure to high levels of persistent organic pollutants (POPs) and trace elements is an important concern for fetal growth. In our previous study, we showed the polychlorinated biphenyl (PCB) levels in maternal serum from the Chiba Study of Mother and Child Health (C-MACH) cohort and their relationships between PCB levels in cord serum with birth weight of newborn. Various reports on the relationship between chemical exposure and birth status have been published; however, studies that analyze the effects of both PCB and metal exposure together in one cohort are still limited. In this study, we aimed to determine the relationship of maternal serum levels of PCBs and toxic and essential trace elements [mercury (Hg), manganese (Mn), selenium (Se), and cadmium (Cd)], with birth weight and head circumference, in the C-MACH cohort. The median concentration of total PCBs in maternal serum around 32 gestational weeks (n = 62) was 360pgg-1 wet wt (41ngg-1 lipid wt). The levels of Hg, Mn, Se, and Cd in maternal serum were 0.89, 0.84, 100, and 0.024ngg-1, respectively. In this study, the Bayesian linear model determined the relationships of the birth weight and head circumference with combinations of PCB levels, toxic and essential trace elements, and questionnaire data. We found that PCB concentrations in maternal serum were weakly and negatively related to birth weight, whereas trace elements were not associated with birth weight. Serum PCB and Mn levels were negatively associated with head circumference, whereas other trace elements were not associated with head circumference. These results showed that maternal exposure to PCBs may be related to birth weight and head circumference, while maternal exposure to Mn is related to head circumference, even when adjusted based on the exposure levels of other contaminants, and maternal and fetal characteristics. Therefore, our findings indicate that maternal exposure to PCBs and Mn might be negatively related with birth weight and head circumference.

Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort.

Autism is a complex neurodevelopmental disorder with a largely unknown etiology. To date, few studies have investigated prenatal exposure to toxins and risk of autism by using maternal biomarkers of exposure. Persistent organic pollutants are lipophilic halogenated organic compounds and include the insecticide dichlorodiphenyltrichloroethane (DDT), as well as its metabolite p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE), and polychlorinated biphenyls (PCBs). The objective of this study was to test whether elevated maternal levels of persistent organic pollutants are associated with autism among offspring. The investigation was derived from the Finnish Prenatal Study of Autism, a national birth cohort study based on a nested case-control design. Cases of autism among children born between 1987 and 2005 were ascertained by national registry linkages. In cases of childhood autism and matched control subjects (778 matched case-control pairs), maternal serum specimens from early pregnancy were assayed for levels of p,p'-DDE and total levels of PCBs. The odds of autism among offspring were significantly increased with maternal p,p'-DDE levels that were in the highest 75th percentile, with adjustment for maternal age, parity, and history of psychiatric disorders (odds ratio=1.32, 95% CI=1.02, 1.71). The odds of autism with intellectual disability were increased by greater than twofold with maternal p,p'-DDE levels above this threshold (odds ratio=2.21, 95% CI=1.32, 3.69). There was no association between total levels of maternal PCBs and autism. These findings provide the first biomarker-based evidence that maternal exposure to insecticides is associated with autism among offspring. Although further research is necessary to replicate this finding, this study has implications for the prevention of autism and may provide a better understanding of its pathogenesis.

Prenatal exposure to polychlorinated biphenyls and fetal growth in British girls

Polychlorinated biphenyls (PCBs) are synthetic chemicals that bioaccumulate in the food chain. PCBs were used primarily for industrial applications due to their insulating and fire retardant properties, but were banned in the 1970s in the United States and in the 1980s in the United Kingdom, as adverse health effects following exposure were identified. Previous studies of populations with high PCB exposure have reported inverse associations with birth weight and gestational length. Birth weight is a powerful predictor of infant survival, and low birth weight can predispose infants to chronic conditions in adult life such as diabetes and cardiovascular diseases.Using data from the Avon Longitudinal Study of Parents and Children, we investigated the association between prenatal exposure to PCBs and fetal growth in a sample of 448 mother-daughter dyads. Concentrations of three common PCB analytes, PCB-118, PCB-153 and PCB-187, were measured in maternal serum collected during pregnancy, and fetal growth was measured by birth weight and birth length. Multivariable linear regression was used to examine the associations between PCB analytes and measures of fetal growth, after adjusting for parity, maternal age, pre-pregnancy BMI, educational status, tobacco use and gestational age of infant at sample collection. Birth length, ponderal index and gestational age were not associated with any of the PCB analytes. Mothers' educational status modified associations for PCB analytes with birthweight. We observed significant inverse associations with birth weight only among daughters of mothers with less education. Daughter's birth weight was −138.4 g lower (95% CI: −218.0, −58.9) for each 10 ng/g lipid increase in maternal serum PCB-118. Similarly, every 10 ng/g lipid increase in maternal serum PCB-153 was associated with a −41.9 g (95% CI: −71.6, −12.2) lower birth weight. Every 10 ng/g lipids increase in maternal serum PCB-187, was associated with a −170.4 g (95% CI: −306.1, −34.7) lower birth weight, among girls with mothers in the lowest education group.Our findings suggest that prenatal exposure to PCBs is inversely associated with daughters' birth weight and that mothers' education, which is a possible marker for socioeconomic status, significantly modified the association between maternal PCB concentrations and birth weight in female newborns.

Gestational 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) exposure disrupts fetoplacental unit: Fetal thyroid-cytokines dysfunction

Exposure to polychlorinated biphenyls (PCBs) is related to several endocrine disorders. This study examined the effect of maternal exposure of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on the fetoplacental unit and fetal thyroid-cytokine axis during the pregnancy. Pregnant albino rats received PCB 126 (20 or 40μg/kgb.wt.) by oral gavage from gestation day (GD) 1 to 20. Potential effects of PCB 126 were evaluated by following the histopathological changes in the placenta by Haematoxylin and Eosin (H&E) stain and measuring the maternofetal thyroid axis (ELIZA), maternofetal body weight, and fetal growth markers (ELIZA), and cytokines (ELIZA) at embryonic day (ED) 20. Placental tissues of both treated groups showed hyperemia, hemorrhage, degeneration and apoptosis in labyrinth layer and spiral artery at GD 20. Both administrations of PCB 126 elevated serum thyrotropin (TSH) concentration, and decreased free thyroxine (FT4) and free triiodothyronine (FT3) concentrations, resulting in a maternofetal hypothyroidism. The presence of hypothyroidism increased fetal serum concentration of transforming growth factor-β (TGF-β), leptin (LEP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and decreased the fetal serum insulin growth factor-I (IGF-I), IGF-II, insulin, adiponectin (ADP), and growth hormone (GH) in both treated groups at ED 20. However, the increase in resistin (RETN) and interferon-γ (IFN-γ) was non-significant in low-dose group and highly significant in high-dose group. Simultaneously, the reduction in body weight of the dams and fetuses was observed in both PCB 126 groups of examined day with respect to the control group. The maternal PCB 126 distorted the fetoplacental unit might disrupt the fetal thyroid-cytokines axis and prenatal development.

Maternal and paternal serum concentrations of persistent organic pollutants and the secondary sex ratio: A population-based preconception cohort study

Recent declines in the secondary sex ratio (SSR), defined as the ratio of males to females at birth, in some industrialized countries may be attributed to exposure to environmental toxicants such as persistent organic pollutants (POPs). This study aimed to evaluate the association of couples’ preconception exposure to POPs with the SSR. The study cohort comprised 235 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and prospectively followed through delivery of a singleton birth. Upon enrollment, couples’ serum concentrations (ng/g) were measured for 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, and 36 polychlorinated biphenyls (PCBs). Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of a male birth for each chemical. Of the 56 POPs examined, maternal PCB 128 and paternal hexachlorobenzene were significantly associated with a female excess (RRs, 0.75 [95% CI, 0.60–0.94] and 0.81 [95% CI, 0.68–0.97] per 1SD increase in log-transformed serum chemical concentrations, respectively), whereas maternal mirex and paternal PCB 128 and p,p′-dichlorodiphenyldichloroethylene were significantly associated with a male excess (RR range, 1.10–1.22 per 1SD increase in log-transformed serum chemical concentrations). After adjusting for multiple comparisons, only maternal mirex remained significantly associated with the SSR. This exploratory study on multiple classes of POPs demonstrated no conclusive evidence on the association between parental preconception exposure to POPs and the SSR.

Perinatal Polychlorinated Biphenyl 126 Exposure Alters Offspring Body Composition.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants whose exposure levels are associated with various health hazards. We hypothesized that in utero and lactational exposure to PCBs can cause changes in body composition and obesity in a mouse model. Pregnant mice were exposed biweekly to two concentrations of PCB 126 via oral gavage. Maternal PCB exposure did not result in heavier offspring, however, dose-dependent and sex specific changes in body composition were observed. Female offspring displayed the most susceptibility to PCB-induced alterations in body composition, having less percent lean body mass and increased adiposity compared to females born to control dams, and these effects were largely dose-dependent. In contrast to females, and independent of the exposure level of PCB 126, male offspring had reduced lean body mass but no change in fat mass compared to males born to control dams. In conclusion, perinatal PCB 126 exposure did not affect body weight, but rather modulated body composition in a dose-dependent and gender-specific manner.

Maternal body burdens of PCDD/Fs and PBDEs are associated with maternal serum levels of thyroid hormones in early pregnancy: a cross-sectional study.

BackgroundThyroid hormones (THs) regulate many biological functions in the human body and are essential for normal brain development. Epidemiological studies have observed diverging associations between halogenated persistent organic pollutant (POP) exposure and concentrations of THs in pregnant women and their infants. We investigated whether background exposure to polybrominated diphenyl ethers (PBDEs) is related to TH status in a Swedish population of pregnant women and their infants. Furthermore, we examined associations between polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) and TH status in early pregnancy as an extension of an earlier study focusing on late pregnancy TH status.MethodsFree thyroxine (T4), total triiodo-thyronine (T3) and thyroid stimulating hormone (TSH) were analysed in serum from first-time mothers (N = 220-281) in the first and third trimester, and in infants (N = 115-150) 3 weeks and 3 months after delivery. Antibodies to thyroid peroxidase (anti-TPO) (N = 260) were measured in maternal third trimester serum. Maternal body burdens of PCBs (N = 281) were estimated from serum lipid PCB concentrations in late pregnancy, and PCDD/F (N = 97) and PBDE (N = 186) body burdens were estimated from concentrations in mother’s milk lipids 3 weeks after delivery. Linear regression models allowed for covariate adjustment of the associations between ln-transformed POP body burdens and concentrations of TH and anti-TPO.ResultsMaternal body burden of BDE-153 was inversely associated with first trimester total T3, otherwise no associations between PBDEs and first and second trimester THs were observed. No associations were found between maternal PBDE body burdens and infant THs. Maternal body burden of PCDD/Fs were inversely associated with first trimester total T3. No associations were observed between PCBs and first trimester THs. Third trimester anti-TPO was not associated with maternal PCBs, PCDD/Fs and PBDEs.ConclusionsOur results suggest that maternal PCDD/F and BDE-153 body burdens influence maternal TH status in early pregnancy, which is a critical period when maternal TH status influences fetal development.