Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included

Determinants of organophosphate pesticide exposure in pregnant women: A population-based cohort study in the Netherlands

Background: In the Netherlands organophosphate (OP) pesticides are frequently used for pest control in agricultural settings. Despite concerns about the potential health impacts of low-level OP pesticides exposure, particularly in vulnerable populations, the primary sources of exposure remain unclear. The present study was designed to investigate the levels of DAP metabolites concentrations across pregnancy and to examine various determinants of DAP metabolite concentrations among an urban population of women in the Netherlands. Method: Urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined at 25 weeks of pregnancy in 784 pregnant women participating in the Generation R Study (between 2004 and 2006), a large population-based birth cohort in Rotterdam, the Netherlands. Questionnaires administered prenatally assessed demographic and lifestyle characteristics and maternal diet. Linear mixed models, with adjustment for relevant covariates, were used to estimate associations between the potential exposure determinants and DAP metabolite concentrations expressed as molar concentrations divided by creatinine levels. Results: The median DAP metabolite concentration was 311 nmol/g creatinine for the first trimester, 317 nmol/g creatinine for the second trimester, and 310 nmol/g creatinine for the third trimester. Higher maternal age, married/living with a partner, underweight or normal weight (BMI of <18.5 and 18.5-<25), high education, high income, and non-smoking were associated with higher DAP metabolite concentrations, and DAP metabolite concentrations tended to be higher during the summer. Furthermore, fruit intake was associated with increased DAP metabolite concentrations. Each 100 g/d difference in fruit consumption was associated with a 7% higher total DAP metabolite concentration across pregnancy. Other food groups were not associated with higher DAP metabolite concentrations. Conclusions: The DAP metabolite concentrations measured in the urine of pregnant women in the Netherlands were higher than those in most other studies previously conducted. Fruit intake was the main dietary source of exposure to OP pesticides in young urban women in the Netherlands. The extent to which DAP metabolite concentrations reflect exposure to the active parent pesticide rather than to less toxic metabolites remains unclear. Further research will be undertaken to investigate the possible effects of this relatively high level OP pesticides exposure on offspring health

Effects of sample handling and analytical procedures on thyroid hormone concentrations in pregnant women's plasma

Background: Maternal thyroid function is a critical mediator of fetal brain development. Pregnancy-related physiologic changes and handling conditions of blood samples may influence thyroid hormone biomarkers. We investigated the reliability of thyroid hormone biomarkers in plasma of pregnant women under various handling conditions. Methods: We enrolled 17 pregnant women; collected serum and plasma were immediately frozen. Additional plasma aliquots were subjected to different handling conditions before the analysis of thyroid biomarkers: storage at room temperature for 24 or 48 hours before freezing and an extra freeze-Thaw cycle. We estimated free thyroid hormone indices in plasma based on T3 uptake. Results: High correlations between plasma and serum (>0.94) and intraclass correlation coefficients for plasma handling conditions (0.96 to 1.00) indicated excellent reliability for all thyroid hormone biomarkers. Conclusion: Delayed freezing and freeze-Thaw cycles did not affect reliability of biomarkers of thyroid function in plasma during pregnancy. See video abstract at, http://links.lww.com/EDE/B180

Maternal Thyroid Function during Pregnancy or Neonatal Thyroid Function and Attention Deficit Hyperactivity Disorder: A Systematic Review

Background: Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children, yet its etiology is poorly understood. Early thyroid hormone disruption may contribute to the development of ADHD. Disrupted maternal thyroid hormone function has been associated with adverse neurodevelopmental outcomes in children. Among newborns, early-treated congenital hypothyroidism has been consistently associated with later cognitive deficits. Methods: We systematically reviewed literature on the association between maternal or neonatal thyroid hormones and ADHD diagnosis or symptoms. We searched Embase, Pubmed, Cinahl, PsycInfo, ERIC, Medline, Scopus, and Web of Science for articles published or available ahead of print as of April 2018. Results: We identified 28 eligible articles: 16 studies of maternal thyroid hormones, seven studies of early-treated congenital hypothyroidism, and five studies of neonatal thyroid hormones. The studies provide moderate evidence for an association between maternal thyroid hormone levels and offspring ADHD, some evidence for an association between early-treated congenital hypothyroidism and ADHD, and little evidence for an association between neonatal thyroid hormone levels and later ADHD. Conclusions: The reviewed articles suggest an association between maternal thyroid function and ADHD, and possibly between early-treated congenital hypothyroidism and ADHD. Study limitations, however, weaken the conclusions in our systematic review, underlining the need for more research. Importantly, there was much variation in the measurement of thyroid hormone function and of ADHD symptoms. Recommendations for future research include using population-based designs, attending to measurement issues for thyroid hormones and ADHD, considering biologically relevant covariates (e.g., iodine intake), and assessing nonlinear dose-responses

Response to “Comment on ‘optimal exposure biomarkers for nonpersistent chemicals in environmental epidemiology’”

We appreciate the opportunity to respond to the letter from Stahlhut et al. regarding our Brief Communication. We stressed the importance of biospecimen integrity and the potential danger of unrecognized contamination of convenience samples, particularly with ubiquitous environmental chemicals such as bisphenol A (BPA) and phthalates

Gestational thyroid hormone concentrations and risk of attention-deficit hyperactivity disorder in the Norwegian Mother, Father and Child Cohort Study

Background: Maternal thyroid function plays an important role in foetal brain development; however, little consensus exists regarding the relationship between normal variability in thyroid hormones and common neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD). Objective: We sought to examine the association between mid-pregnancy maternal thyroid function and risk of clinically diagnosed ADHD in offspring. Methods: We conducted a nested case–control study in the Norwegian Mother, Father and Child Cohort Study. Among children born 2003 or later, we randomly sampled singleton ADHD cases obtained through linkage with the Norwegian Patient Registry (n = 298) and 554 controls. Concentrations of maternal triiodothyronine (T3), thyroxine (T4), T3-Uptake, thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) were measured in maternal plasma, collected at approximately 17 weeks' gestation. Indices of free T4 (FT4i) and free T3 (FT3i) were calculated. We used multivariable adjusted logistic regression to calculate odds ratios and accounted for missing covariate data using multiple imputation. We used restricted cubic splines to assess non-linear trends and provide flexible representations. We examined effect measure modification by dietary iodine and selenium intake. In sensitivity analyses, we excluded women with clinically significant thyroid disorders (n = 73). Results: High maternal T3 was associated with increased risk of ADHD (5th vs 1st quintile odds ratio 2.27, 95% confidence interval 1.21, 4.26). For FT4i, both the lowest and highest quintiles were associated with an approximate 1.6-fold increase in risk of ADHD, with similar trends found for T4. The FT4i association was modified by dietary iodine intake such that the highest risk strata were confined to the low intake group. Conclusions: Both high and low concentrations of maternal thyroid hormones, although within population reference ranges, increase the risk of ADHD in offspring. Increased susceptibility may be found among women with low dietary intake of iodine and selenium