Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE).

BACKGROUND: Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area. METHODS: We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. At 3.5-year and 5-year follow-up visits, caregivers of 647 and 620 children, respectively, were queried about children's respiratory allergy symptoms based on validated instruments. We applied marginal structural models for repeated outcomes to estimate associations between biomarker concentrations and asthma diagnosis as well as respiratory allergy symptoms at ages 3.5 and 5 years. RESULTS: We found that a10-fold increase in maternal urinary cis-DCCA, trans-DCCA and 3-PBA concentrations were associated with more than a doubling in the risk of doctor-diagnosed asthma (cis-DCCA: RR = 2.1, 95% CI = 1.3, 3.3; trans-DCCA: RR = 2.1, 95% CI = 1.1, 3.9; 3-PBA: RR = 2.4, 95% CI = 1.0, 5.8) and an about 80% increase in the risk of wheezing or whistling in the chest (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.0; trans-DCCA: RR = 1.7, 95% CI = 1.1, 2.6; 3-PBA: RR = 1.8, 95% CI = 1.0, 3.3) and suspected asthma (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.1; trans-DCCA: RR = 1.8, 95% CI = 1.1, 2.8). We also observed that higher concentrations of cis-DBCA and 3-PBA were related to increases in the risks of dry cough at night (RR = 3.5, 95% CI = 1.3, 9.5) and seasonal rhinoconjunctivitis (RR = 2.0, 95% CI = 1.1, 3.9), respectively. CONCLUSION: Maternal exposure to pyrethroids may increase the risk of asthma and other respiratory allergy symptoms among preschool children from an IRS area.

Prenatal Exposure to Insecticides and Weight Trajectories Among South African Children in the VHEMBE Birth Cohort.

BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides are sprayed inside dwellings for malaria vector control, resulting in high exposure to millions of people, including pregnant women. These chemicals disrupt endocrine function and may affect child growth. To our knowledge, few studies have investigated the potential impact of prenatal exposure to DDT or pyrethroids on growth trajectories. METHODS: We investigated associations between gestational insecticide exposure and child growth trajectories in the Venda Health Examination of Mothers, Babies and their Environment, a birth cohort of 751 children born between 2012 and 2013 in South Africa. Based on child weight measured at follow-up and abstracted from medical records, we modeled weight trajectories from birth to 5 years using SuperImposition, Translation and Rotation, which estimated two child-specific parameters: size (average weight) and tempo (age at peak weight velocity). We estimated associations between peripartum maternal concentrations of serum DDT, dichlorodiphenyldichloroethylene, or urinary pyrethroid metabolites and SuperImposition, Translation and Rotation parameters using marginal structural models. RESULTS: We observed that a 10-fold increase in maternal concentrations of the pyrethroid metabolite trans-3-(2,2,-dicholorvinyl)-2,2-dimethyl-cyclopropane carboxylic acid was associated with a 21g (95% confidence interval = -40, -1.6) smaller size among boys but found no association among girls (Pinteraction = 0.07). Estimates suggested that pyrethroids may be associated with earlier tempo but were imprecise. We observed no association with serum DDT or dichlorodiphenyldichloroethylene. CONCLUSIONS: Inverse associations between pyrethroids and weight trajectory parameters among boys are consistent with hypothesized disruption of androgen pathways and with our previous research in this population, and support the endocrine-disrupting potential of pyrethroids in humans.

Breastmilk, Stool, and Meconium: Bacterial Communities in South Africa.

Human milk optimizes gut microbial richness and diversity, and is critical for proper immune development. Research has shown differing microbial composition based on geographic location, providing evidence that diverse biospecimen data is needed when studying human bacterial communities. Yet, limited research describes human milk and infant gut microbial communities in Africa. Our study uses breastmilk, stool, and meconium samples from a South African birth cohort to describe the microbial diversity, identify distinct taxonomic units, and determine correlations between bacterial abundance in breastmilk and stool samples. Mother-infant dyads (N = 20) were identified from a longitudinal birth cohort in the Vhembe district of Limpopo Province, South Africa. Breastmilk, meconium, and stool samples were analyzed using 16S ribosomal RNA sequencing of the V4-V5 gene region using the MiSeq platform for identification and relative quantification of bacterial taxa. A non-metric multidimensional scaling using Bray-Curtis distances of sample Z-scores showed that meconium, stool, and breastmilk microbial communities are distinct with varying genus. Breastmilk was mostly comprised of Streptococcus, Staphylococcus, Veillonella, and Corynebacterium. Stool samples showed the highest levels of Bifidobacterium, Faecalibacterium, Bacteroides, and Streptococcus. Alpha diversity measures found that stool samples have the highest Shannon index score compared to breastmilk and meconium. The abundance of Bifidobacterium (r = 0.57), Blautia (r = 0.59), and Haemophilus (r = 0.69) was correlated (p < 0.1) between breastmilk and stool samples. Despite the importance of breastmilk in seeding the infant gut microbiome, we found evidence of distinct bacterial communities between breastmilk and stool samples from South African mother-infant dyads.

Assessing the External Exposome Using Wearable Passive Samplers and High-Resolution Mass Spectrometry among South African Children Participating in the VHEMBE Study.

Children in low- and middle-income countries are often exposed to higher levels of chemicals and are more vulnerable to the health effects of air pollution. Little is known about the diversity, toxicity, and dynamics of airborne chemical exposures at the molecular level. We developed a workflow employing state-of-the-art wearable passive sampling technology coupled with high-resolution mass spectrometry to comprehensively measure 147 children's personal exposures to airborne chemicals in Limpopo, South Africa, as part of the Venda Health Examination of Mothers, Babies, and Their Environment (VHEMBE). 637 environmental exposures were detected, many of which have never been measured in this population; of these 50 airborne chemical exposures of concern were detected, including pesticides, plasticizers, organophosphates, dyes, combustion products, and perfumes. Biocides detected in wristbands included p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), propoxur, piperonyl butoxide, and triclosan. Exposures differed across the assessment period with 27% of detected chemicals observed to be either higher or lower in the wet or dry seasons.

Associations between prenatal exposure to DDT and DDE and allergy symptoms and diagnoses in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), South Africa.

Dichlorodiphenyl trichloroethane (DDT) is an organochlorine insecticide that is banned internationally except for use as part of Indoor Residual Spraying (IRS) programs to control malaria. Although animal studies show that DDT and its breakdown product dichlorodiphenyl dichloroethylene (DDE) affect the immune system and may cause allergies, no studies have examined this question in populations where IRS is conducted. The aim of our study was to investigate whether prenatal exposure to DDT and DDE is associated with allergy symptoms and diagnose among South African children living in an area where IRS is conducted. To accomplish this aim, we used data from the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), an ongoing birth cohort study of 752 children born between 2012 and 2013 in the rural Vhembe district of Limpopo, South Africa. We measured maternal peripartum serum concentrations of DDT and DDE, and administered a questionnaire to the caregivers of 658 children aged 3.5 years to collect information on allergy symptoms and diagnoses as well as potential confounders using validated instruments. Using multiple logistic regression models, we found positive associations between DDT and DDE serum concentrations and most of the allergy symptoms and diagnoses. Maternal DDT (Odds Ratio [OR] = 1.5 per 10-fold increase, 95% Confidence interval, CI = 1.0, 2.3) and DDE (OR = 1.4, 95% CI = 0.8, 2.4) serum concentrations were most strongly associated with caregiver report of wheezing or whistling in the chest. Concentrations of DDT and/or DDE were also associated with increased odds of children's chests sounding wheezy during or after exercise, itchy rashes coming and going for at least six months, diagnosis of food allergy, and diagnosis of dust or dust mites allergy but confidence intervals crossed the null. Results suggest that prenatal exposure to DDT, and possibly DDE, is associated with elevated odds of wheezing among children from an IRS area.

Exposure to lead and vaccine-specific IgG titers in South African children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE): A longitudinal study.

BACKGROUND: While successes have been achieved in reducing global exposure to lead, few studies have investigated the potential health effects of low-level exposure (e.g. blood lead levels [BLLs] below the CDC reference level of 5 µg/dL), particularly among children from low- and middle-income countries. In addition, lead is immunotoxic in animals but human data on immune response to vaccines is limited. Our aim was to determine whether low-level exposure to lead is associated with humoral response to vaccines among rural South African children. METHODS: We used data from the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study conducted in Limpopo, South Africa. BLLs were measured in whole blood collected at age 1 year and IgG titers for measles, tetanus and Haemophilus influenzae type B (Hib) were determined at age 3.5 years among 425 fully-vaccinated children. RESULTS: BLLs were low (median = 1.90 µg/dL) and 94% of children had a BLL below 5 µg/dL. Overall, BLLs were associated with higher risks of having IgG titers below the protective limit for tetanus (RR = 1.88 per 10-fold increase; 95%CI = 1.08, 3.24) but not measles (RR = 1.02; 95%CI = 0.26, 3.95) or Hib (RR = 0.96; 95%CI = 0.54, 1.71). BLLs were also associated with low Hib IgG titers among children exposed to HIV in utero and with low measles IgG titers among females. In contrast, the association with measles IgG titers was positive among males. CONCLUSION: Low-level exposure to lead may compromise the humoral response to vaccines. Children exposed to HIV in utero and females may be particularly susceptible.

Impacts of food contact chemicals on human health: a consensus statement.

Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.

Associations of Maternal Exposure to Dichlorodiphenyltrichloroethane and Pyrethroids With Birth Outcomes Among Participants in the Venda Health Examination of Mothers, Babies and Their Environment Residing in an Area Sprayed for Malaria Control.

Although effective in controlling malaria, indoor residual spraying results in elevated exposure to insecticides such as dichlorodiphenyltrichloroethane (DDT) and pyrethroids. These chemicals cross the placenta, but no studies have examined their associations with birth outcomes in populations residing in indoor residual spraying areas. We investigated this question in the Venda Health Examination of Mothers, Babies and Their Environment (VHEMBE), a birth cohort study of 751 South African children born between 2012 and 2013. We measured maternal peripartum serum DDT and urine pyrethroid metabolite concentrations and collected data on birth weight, length, head circumference, and duration of gestation. We analyzed the data using marginal structural models with inverse-probability-of-treatment weights, generalized propensity scores, and standard conditional linear regression. Using all 3 analytical methods, p,p'-DDT, o,p'-DDT, and to a lesser extent p,p'-dichlorodiphenyldichloroethylene were related to elevated birth weight, birth length, and head circumference among girls. Changes in gestational duration did not mediate this relationship, suggesting that these exposures accelerate fetal growth, which is consistent with the known estrogenic properties of o,p'-DDT and p,p'-DDT. No associations with pyrethroid metabolites were found. Results suggest that prenatal exposure to DDT is related to elevated birth size. Further studies are needed to elucidate the implications of these findings.

A community-based education programme to reduce insecticide exposure from indoor residual spraying in Limpopo, South Africa.

BACKGROUND: Indoor residual spraying (IRS), the coating of interior walls of houses with insecticides, is common in malaria-endemic areas. While important in malaria control, IRS potentially exposes residents to harmful insecticides. The World Health Organization recommends steps to minimize exposure; however, no programme has focused on educating populations. METHODS: A dramatic presentation and song were developed by study personnel and performed by lay performers in order to spread awareness of the importance of IRS and to minimize insecticide exposure. Performances were staged at 16 sprayed villages in the Vhembe District of Limpopo, South Africa, at which 592 attendees completed short questionnaires before and after the performance about behaviors that might limit insecticide exposure. Overall indices of the attendees' change in knowledge of precautions to take prior to and after spraying to prevent insecticide exposure were analyzed using hierarchical mixed models to assess the effect of the performance on change in participants' knowledge. RESULTS: Approximately half of attendees lived in homes that had been sprayed for malaria and 62% were female. Over 90% thought it better to allow IRS prior to the presentation, but knowledge of proper precautions to prevent exposure was low. The proportion answering correctly about proper distance from home during spraying increased from 49.4% pre-performance to 62.0% post-performance (RR = 1.26, 95% CI = 1.13, 1.41), and the proportion reporting correctly about home re-entry interval after spraying increased from 58.5 to 91.1% (RR = 1.54, 95% CI 1.35, 1.77). Attendees improved in their knowledge about precautions to take prior to and after spraying from mean of 57.9% correct to a mean of 69.7% (ß = 12.1%, 95% CI 10.9, 13.4). Specifically, increased knowledge in closing cupboards, removing food and bedding from the home, covering immoveable items with plastic, and leading animals away from the home prior to spraying were observed, as was increased knowledge in sweeping the floors, proper disposal of dead insects, and discarding dirty washrags after spraying. CONCLUSIONS: A dramatic presentation and song were able to increase the attendees' knowledge of precautions to take prior to and after spraying in order to limit their insecticide exposure resulting from IRS. This approach to community education is promising and deserves additional study.

Determinants of Exposure to Pyrethroid Insecticides in the VHEMBE Cohort, South Africa.

Exposure to pyrethroid insecticides has been linked to adverse health effects, and can originate from several sources, including indoor residual spraying (IRS) for malaria control, home pest control, food contamination, and occupational exposure. We aimed to explore the determinants of urinary pyrethroid metabolite concentrations in a rural population with high pesticide use. The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort of 752 mother-child pairs in Limpopo, South Africa. We measured pyrethroid metabolites in maternal urine and collected information on several factors possibly related to pesticide exposure, including IRS, home pesticide use, and maternal factors (e.g., dietary habits and body composition). We performed statistical analysis using both conventional bivariate regressions and Bayesian variable selection methods. Urinary pyrethroid metabolites are consistently associated with pesticide factors around homes, including pesticide application in yards and food stocks, and IRS in the home during pregnancy, while more distant factors such as village spraying are not. High fat intake is associated with higher metabolite concentrations, and women from homes drawing water from wells or springs had marginally higher levels. Home pesticide use is the most consistent correlate of pyrethroid metabolite concentrations, but IRS, dietary habits, and household water source may also be important exposure determinants.

Exposure to DDT and hypertensive disorders of pregnancy among South African women from an indoor residual spraying region: The VHEMBE study.

Indoor Residual Spraying (IRS), the use of insecticides inside residences for malaria control, may cause elevated exposure to insecticides such as dichlorodiphenyl trichloroethane (DDT). Evidence suggests that DDT exposure may increase blood pressure but no study has investigated associations with hypertensive disorders of pregnancy (HDP) in an IRS area. We measured the serum concentration of DDT and its breakdown product dichlorodiphenyl trichloroethylene (DDE) at the time of delivery among 733 rural South African women participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE). We also collected data on HDP diagnosis through questionnaires administered to participants and medical record abstraction. We used multiple logistic regression models to examine the relation between DDT/E and HDP. p,p'-DDT and p,p'-DDE serum concentrations were associated with HDP based on self-report (OR = 1.50; 95%CI = 1.10, 2.03 for p,p'-DDT and OR = 1.58; 95%CI = 1.09, 2.28 for p,p'-DDE) and medical records (OR = 1.32; 95%CI = 0.99, 1.75 for p,p'-DDT and OR = 1.47; 95%CI = 1.03, 2.09 for p,p'-DDE). p,p'-DDE was also associated with gestational hypertension (OR = 1.44; 95% CI = 1.00, 2.07). Exposure to DDT and DDE may be associated with elevated risks of HDP in South African women residing in an area sprayed for malaria control.

Associations of maternal exposure to triclosan, parabens, and other phenols with prenatal maternal and neonatal thyroid hormone levels.

Environmental phenols and parabens are commonly used in personal care products and other consumer products and human exposure to these chemicals is widespread. Although human and animal studies suggest an association between exposure to phenols and parabens and thyroid hormone levels, few studies have investigated the association of in utero exposure to these chemicals and thyroid hormones in pregnant women and their neonates. We measured four environmental phenols (triclosan, benzophenone-3, and 2,4- and 2,5-dichlorophenol), and three parabens (methyl-, propyl-, and butyl paraben) in urine collected from mothers at two time points during pregnancy as part of the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in serum of the pregnant women (N = 454) and TSH in their neonates (N = 365). We examined potential confounding by a large number of additional chemical exposures and used Bayesian Model Averaging (BMA) to select the most influential chemicals to include in regression models. We observed negative associations of prenatal urinary concentrations of propyl paraben and maternal TSH (ß for two-fold increase = -3.26%, 95% CI: -5.55, -0.90) and negative associations of 2,4-dichlorophenol and maternal free T4 (ß for two-fold increase = -0.05, 95% CI: -0.08, -0.02), after controlling for other chemical exposures. We observed negative associations of triclosan with maternal total T4 after controlling for demographic variables, but this association became non-significant after controlling for other chemicals (ß for two-fold increase = -0.05, 95% CI: -0.11, 0.00). We found evidence that environmental phenols and parabens are associated with lower TSH and free T4 in pregnant women after controlling for related chemical exposures.

Associations between pesticide use and respiratory symptoms: A cross-sectional study in Southern Ghana.

BACKGROUND: Indiscriminate use of pesticides is a common practice amongst farmers in Low and Middle Income Countries (LMIC) across the globe. However, there is little evidence defining whether pesticide use is associated with respiratory symptoms. OBJECTIVES: This cross-sectional study was conducted with 300 vegetable farmers in southern Ghana (Akumadan). Data on pesticide use was collected with an interviewed-administered questionnaire. The concentration of seven organochlorine pesticides and 3 pyrethroid pesticides was assayed in urine collected from a sub-population of 100 vegetable farmers by a gas chromatograph equipped with an electron capture detector (GC-ECD). RESULTS: A statistically significant exposure-response relationship of years per day spent mixing/applying fumigant with wheezing [30-60 days/year: prevalence ratio (PR)=1.80 (95% CI 1.30, 2.50); >60days/year: 3.25 (1.70-6.33), p for trend=0.003] and hours per day spent mixing/applying fumigant with wheezing [1-2h/day: 1.20 (1.02-1.41), 3-5h/day: 1.45 (1.05-1.99), >5h/day: 1.74 (1.07-2.81), p for trend=0.0225]; days per year spent mixing/applying fungicide with wheezing [30-60 days/year: 2.04 (1.31-3.17); >60days/year: 4.16 (1.72-10.08), p for trend=0.0017] and h per day spent mixing/applying fungicide with phlegm production [1-2h/day: 1.25 (1.05-1.47), 3-5h/day: 1.55 (1.11-2.17), >5h/day: 1.93 (1.17-3.19), p for trend=0.0028] and with wheezing [1-2h/day: 1.10 (1.00-1.50), 3-5h/day: 1.20 (1.11-1.72), >5h/day: 1.32 (1.09-2.53), p for trend=0.0088]; h per day spent mixing/applying insecticide with phlegm production [1-2h/day: 1.23 (1.09-1.62), 3-5h/day: 1.51 (1.20-2.58), >5h/day: 1.85 (1.31-4.15), p for trend=0.0387] and wheezing [1-2h/day: 1.22 (1.02-1.46), 3-5h/day: 1.49 (1.04-2.12), >5h/day: 1.81 (1.07-3.08), p for trend=0.0185] were observed. Statistically significant exposure-response association was also observed for a combination of activities that exposes farmers to pesticide with all 3 respiratory symptoms. Furthermore, significant exposure-response associations for 3 organochlorine insecticides: beta-HCH, heptachlor and endosulfan sulfate were noted. CONCLUSIONS: In conclusion, vegetable farmers in Ghana may be at increased risk for respiratory symptoms as a result of exposure to pesticides.

Increasing sample size in prospective birth cohorts: back-extrapolating prenatal levels of persistent organic pollutants in newly enrolled children.

Study sample size in prospective birth cohorts of prenatal exposure to persistent organic pollutants (POPs) is limited by costs and logistics of follow-up. Increasing sample size at the time of health assessment would be beneficial if predictive tools could reliably back-extrapolate prenatal levels in newly enrolled children. We evaluated the performance of three approaches to back-extrapolate prenatal levels of p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE) and four polybrominated diphenyl ether (PBDE) congeners from maternal and/or child levels 9 years after delivery: a pharmacokinetic model and predictive models using deletion/substitution/addition or Super Learner algorithms. Model performance was assessed using the root mean squared error (RMSE), R2, and slope and intercept of the back-extrapolated versus measured levels. Super Learner outperformed the other approaches with RMSEs of 0.10 to 0.31, R2s of 0.58 to 0.97, slopes of 0.42 to 0.93 and intercepts of 0.08 to 0.60. Typically, models performed better for p,p'-DDT/E than PBDE congeners. The pharmacokinetic model performed well when back-extrapolating prenatal levels from maternal levels for compounds with longer half-lives like p,p'-DDE and BDE-153. Results demonstrate the ability to reliably back-extrapolate prenatal POP levels from levels 9 years after delivery, with Super Learner performing best based on our fit criteria.

Serum dioxin concentrations and thyroid hormone levels in the Seveso Women's Health Study.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Although experimental evidence suggests that TCDD alters thyroid hormone levels in rodents, human data are inconsistent. In 1976, a trichlorophenol plant exploded in Seveso, Italy. Women living in highly exposed areas were followed through the Seveso Women's Health Study. TCDD concentrations were measured in 1976 (n = 981) and 1996 (n = 260), and levels of total thyroxine, free thyroxine, free triiodothyronine, and thyroid-stimulating hormone were measured in 1996 (n = 909) and 2008 (n = 724). We used conditional multiple linear regression and marginal structural models with inverse-probability-of-treatment weights to evaluate associations and causal effects. TCDD concentration in 1976 was inversely associated with total thyroxine level in 1996 but not in 2008. Associations were stronger among women who had been exposed before menarche. Among these women, associations between total thyroxine and concurrent 1996 TCDD were slightly weaker than those with 1976 TCDD. A model including both 1976 and 1996 measurements strengthened the relationship between 1976 TCDD and total thyroxine but drove the association with 1996 TCDD to the null. TCDD exposure was not associated with levels of other thyroid hormones. TCDD exposure, particularly exposure before menarche, may have enduring impacts on women's total thyroxine levels. Initial exposure appears to be more influential than remaining body burden.

Hypothetical interventions to limit metalworking fluid exposures and their effects on COPD mortality: G-estimation within a public health framework.

BACKGROUND: Current recommendations for limits on metalworking fluids may provide insufficient protection from workplace-related illness. Chronic obstructive pulmonary disease (COPD) is a challenging outcome in occupational cohorts because its long period of worsening pulmonary function allows sicker workers to reduce exposure, causing a healthy worker survivor bias. G-estimation is a statistical method that reduces this bias. We introduce a public health approach using g-estimation to compare a series of potential exposure-reducing interventions. METHODS: Autoworkers at three General Motors plants in Michigan were followed for COPD mortality from 1 January 1941 to 31 December 1994. For each of the three fluid types (straight, soluble, synthetic), a series of binary variables indicated whether exposure exceeded a series of potential limits. Separate g-estimation analyses for each limit yielded results expressed as the total number of years of life that could have been saved among those who died from COPD had that exposure limit been enforced. RESULTS: Lower limits would have had greater effect than higher limits. A ban on soluble fluids (the most common type) would have had the greatest effect, saving an estimated 1550 years of life. Corresponding estimates were 737 and 260 years for straight and synthetic fluids, respectively. Few workers were exposed to synthetic fluids, limiting analytic power. CONCLUSIONS: This application of g-estimation suggests that limiting exposure to metalworking fluids could have saved many years of life lost to COPD in this cohort. The approach permits comparison of different interventions. Separate limits should be considered for different types of fluids.

Association between prenatal exposure to indoor residual spraying insecticides and infection rates among South African children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE).

In 2021, 53 countries conducted indoor residual spraying (IRS), the application of insecticides such as dichlorodiphenyl trichloroethane (DDT) or pyrethroids to the walls of homes to control malaria. Animal studies show that these insecticides can increase susceptibility to infections but only one human study was conducted in a population from an area where IRS is applied. The aim of the present study was thus to investigate whether maternal exposure to DDT, its breakdown product dichlorodiphenyl dichloroethylene (DDE) or pyrethroid insecticides is associated with symptoms of infection among children living in a region of South Africa were IRS is conducted annually. As part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) we measured maternal serum concentrations of DDT and DDE, and urinary concentrations of four pyrethroid metabolites in peripartum samples. Poisson regression models with robust variance estimates were used to investigate associations with the rates of infection symptoms between ages 3.5-5 years among 629 children as assessed based on caregiver interviews. Multiple pyrethroid metabolites were associated with infection symptoms. For instance, cis-DBCA was associated with increased rates of ear infection (Incidence Rate Ratio for a 10-fold increase (IRR10) = 1.4; 95 % Confidence Interval (CI) = 1.0, 2.1) and persistent diarrhea (IRR10 = 2.1; 95 % CI = 1.2, 3.9), trans-DCCA was associated with increased rates of colds in children (IRR10 = 1.3; 95 % CI = 1.0, 1.6) and persistent fever (IRS10 = 1.4; 95 % CI = 1.0, 2.0), and 3-PBA was associated with increased rates of persistent fever (IRR10 = 1.8; 95 % CI = 1.0, 3.0). We found limited evidence of association between maternal DDE and DDT serum concentrations and infection symptoms. Results suggest that prenatal exposure to pyrethroid insecticides may be associated with infections among children from an area where IRS is conducted.

Fluoride exposure and thyroid hormone levels in pregnancy: The MIREC cohort.

BACKGROUND: Fluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce. OBJECTIVES: We examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects. METHODS: We measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder. RESULTS: A 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: -0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05-0.32 mg/L), those with levels in the third quartile (0.49-0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13-0.52 mg/L) and third (0.52-0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04-0.13 mg/L). Adjustment for maternal iodine status did not change the results. DISCUSSION: Fluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.

Preschooler Screen Time During the Pandemic Is Prospectively Associated With Lower Achievement of Developmental Milestones.

OBJECTIVE: The aim of this study was to assess the developmental risks associated with total screen time, and specifically newer mobile devices, in the context of the pandemic. METHODS: This study uses parent-reported data from a prospective cohort of Canadian preschool-age children. The exposure variable is child daily screen time measured at the age of 3.5 years categorized as light (<1 hr/d), moderate (1-4 hr/d), or intensive (>4 hr/d) use (N = 315). Time spent on mobile devices was considered separately as a continuous variable. Our outcome is child global development scores, which combine assessments of communication, cognitive, personal-social, and motor skills measured at the age of 4.5 years using the Ages and Stages Questionnaire (ASQ) (N = 249, 79% retained). ASQ scores were dichotomized to distinguish children at risk of developmental delays (below the 15th percentile) from those not at risk. We estimate associations between child screen time and later global development using multiple regressions adjusted for child sex and temperament, and parent education. We also examine whether associations are moderated by child and parent characteristics. RESULTS: Logistic regressions revealed that intensive users were more at risk of global developmental delays compared with light users (OR = 4.29, p = 0.020). Mobile device use was also associated with lower global scores (ß = -3.064; p = 0.028), but not with risk of delays. We found no evidence that associations were moderated by child sex and temperament, or parent education. CONCLUSION: The findings suggest that intensive screen time may be associated with delays in child global development. Early childhood professionals should encourage families with preschoolers to prioritize screen-free activities to promote optimal cognitive, language, social, and motor development.