Sex and poverty modify associations between maternal peripartum concentrations of DDT/E and pyrethroid metabolites and thyroid hormone levels in neonates participating in the VHEMBE study, South Africa

Indoor Residual Spraying (IRS), the application of insecticides on the inside walls of dwellings, is used by 84 countries for malaria control. Although effective in preventing malaria, this practice results in elevated insecticide exposure to>100 million people, most of whom are Africans. Pyrethroid insecticides and dichlorodiphenyl trichloroethane (DDT) are currently used for IRS. Animal and in vitro studies suggest that pyrethroids and DDT interfere with thyroid hormone homeostasis but human studies are inconsistent and no prior study has investigated this question in a population residing in an area where IRS is conducted. Our objective was thus to evaluate whether prenatal exposure to pyrethroids, DDT or DDT's breakdown product dichlorodiphenyl dichloroethylene (DDE) is associated with altered thyroid hormone levels among neonates from Limpopo, South Africa, where pyrethroids and DDT are used annually to control malaria. We measured serum DDT/E and urinary pyrethroid metabolite concentrations in maternal peripartum samples from 717 women participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study conducted in Limpopo's Vhembe district. We measured total thyroxine (T4) and thyroidstimulating hormone (TSH) in dried blood spots collected via heel stick. We found that all pyrethroid metabolites were positively associated with TSH; trans-DCCA and 3-PBA showed the strongest associations with a 12.3% (95%CI=3.0, 22.3) and 14.0% (95%CI=0.5, 30.2) change for each 10-fold increase in biomarker concentration, respectively. These associations were substantially stronger among children from households below the South African food poverty line. DDT and DDE were associated with lower total T4 among boys only (β=−0.27 μg/dL per 10-fold increase; 95%CI=−0.47, −0.04). Results suggest that prenatal exposure to DDT, DDE and pyrethroid insecticides is associated with changes in neonatal thyroid hormones consistent with hypothyroidism/hypothyroxinemia and that sex and poverty modify associations. Further research is needed to confirm these findings and examine whether they have implications for child development.The U.S. National Institute of Environmental Health Sciences (1R01ES020360) and a Canada Research Chair in Environmental Health Sciences.http://www.elsevier.com/locate/envintam2020School of Health Systems and Public Health (SHSPH

Prenatal exposure to insecticides and weight trajectories among South African children in the VHEMBE birth cohort

DATA AVAILABLITY STATEMENT : Access to data and computing may be discussed by contacting the corresponding author.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.The VHEMBE study was funded by the Canadian Institutes of Health Research and the US National Institute of Environmental Health Sciences; a Canada Research Chair in Global Environmental Health and Epidemiology; a Doctoral Award from the Fonds de recherche du Québec—Santé, with prior fund- ing from McGill University’s Faculty of Medicine.hj2023School of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

Association between prenatal exposure to multiple insecticides and child body weight and body composition in the VHEMBE South African birth cohort

BACKGROUND : Pregnant women may be co-exposed to multiple insecticides in regions where both pyrethroids and dichlorodiphenyltrichloroethane (DDT) are used for indoor residual spraying (IRS) for malaria control. Despite the potential for adverse effects on offspring, there are few studies in areas where IRS is currently used and little is known about the effects of pyrethroids on children's health. METHODS : We investigated the relationship between concentrations of four urinary pyrethroid metabolites in urine and organochlorine pesticide concentrations in maternal blood collected near delivery on body weight and body composition among children ≤2 years old participating in the prospective South Africa VHEMBE birth cohort (N = 708). We used measurements of length/height and weight collected at 1 and 2 years of age to calculate body mass index (BMI)-for-age, weight-for-age, and weight-for-height z-scores based on World Health Organization standards. We fit separate single-pollutant mixed effects models for each exposure of interest and also stratified by sex. We also fit all analyte concentrations jointly by using a Bayesian kernel machine regression (BKMR) statistical method to assess variable importance of each analyte and to explore the potential for joint effects of the multiple exposures. RESULTS : Single-pollutant linear mixed effects models showed that, among girls only, p,p′-DDT was associated with higher BMI-for-age (adjusted [a]β = 0.22 [95% CI: 0.10, 0.35]; sex interaction p-value = 0.001), weight-for-height (aβ = 0.22 [95% CI: 0.09, 0.34]; sex interaction p-value = 0.002), and weight-for-age (aβ = 0.17 [95% CI: 0.05, 0.29], sex interaction p-value = 0.01). Although single-pollutant models suggested that p,p′-DDT and dichlorodiphenyldichloroethylene (p,p′-DDE) were also associated with these outcomes in girls, p,p′-DDE was no longer associated in multi-pollutant models with BKMR. The pyrethroid metabolites cis-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylicacid (cis-DBCA) and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA) were inversely related to BMI-for-age and weight-for-height overall; however, results suggested that weight-for-age and weight-for-height associations for trans-DCCA (sex interaction p-valueweight-for-age = 0.02; p-valueweight-for-height = 0.13) and cis-DCCA (sex interaction p-valueweight-for-age = 0.02; p-valueweight-for-height = 0.08) were strongest and most consistent in boys relative to girls. BKMR also revealed joint effects from the chemical mixture. For instance, with increased concentrations of p,p′-DDE, the negative exposure-response relationship for cis-DBCA on BMI-for-age became steeper. CONCLUSIONS : Our single-pollutant and multi-pollutant model results show that maternal serum p,p′-DDT concentration was consistently and positively associated with body composition and body weight in young girls and that maternal urinary pyrethroid metabolite concentrations (particularly cis-DBCA and trans-DCCA) were negatively associated with body weight and body composition in young boys. Joint effects of the insecticide exposure mixture were also apparent, underscoring the importance of using advanced statistical methods to examine the health effects of chemical mixtures.The National Institute of Environmental Health Sciences (Award ID: 1R01ES020360), the Health Resources and Services Administration, Maternal and Child Health Bureau (Award ID: T76MC00002), and the Global Health Equity Scholars Program, Fogarty International CenterTW009338.http://www.elsevier.com/locate/envint2019-04-30hj2018School of Health Systems and Public Health (SHSPH

Maternal exposure to DDT, DDE, and pyrethroid insecticides for malaria vector control and hypospadias in the VHEMBE birth cohort study, Limpopo, South Africa

Hypospadias is the ectopic opening of the urethra on the penis or scrotum. Exposure to estrogenic and/or anti-androgenic chemicals in utero may play an etiologic role. DDT and the pyrethroids cypermethrin and deltamethrin, are used to control malaria. DDT is estrogenic and its breakdown product DDE is anti-androgenic; cypermethrin and deltamethrin can also disrupt androgen pathways. We examined the relationship between maternal exposure to these insecticides during pregnancy and hypospadias among boys participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) in Limpopo Province, South Africa. We measured peripartum levels of p,p'-DDT and p,p'-DDE in maternal serum and urinary pyrethroid metabolites. We conducted urogenital examination on 359 one-year-old boys. A total of 291 (81.0 %) had phimosis, which prevented full urogenital examination, leaving a final sample of 68 boys for determination of the presence of hypospadias. Diagnosis was based on concordance of two independent physicians. We identified hypospadias in 23 of the 68 boys (34 %). Maternal urinary concentrations of cis-DCCA and trans-DCCA metabolites of cypermethrin and other pyrethroids, were associated with an increased risk for hypospadias, but the other metabolite 3-PBA was not (adjusted relative risk per 10-fold increase = 1.58, 95 % CI 1.07–2.34; 1.61, 95 % CI 1.09–2.36; and 1.48, 95 % CI 0.78–2.78, respectively). No associations were found between p,p'-DDT, p,p'-DDE, 3-PBA or cis-DBCA and hypospadias. We observed a high prevalence of hypospadias among boys without phymosis. Boys with higher prenatal exposure to pyrethroid insecticides were at higher risk of hypospadias. Our findings may have global implications given that pyrethroid insecticides are widely used for malaria control, in agriculture and for home use.http://www.elsevier.com/locate/scitotenvhj2023School of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

Undisturbed dust as a metric of long-term indoor insecticide exposure : residential DDT contamination from indoor residual spraying and its association with serum levels in the VHEMBE cohort

Although approximately 123 million people may be exposed to high levels of insecticides through the use of indoor residual spraying (IRS) for malaria control, fewstudies exist on indoor insecticide contamination due to IRS and its relationship with human exposure. In the present study, we developed a sampling method to collect undisturbed dust from50 homes in Limpopo, South Africa, a region where dichlorodiphenyltrichloroethane (DDT) has been used in IRS programs to preventmalaria for ~70 years.WequantifiedDDT and its degradation products, dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyldichloroethane (DDD) in dust samples to determine dust loading levels and compared these levels to paired serum concentrations of p,p′-DDT and p,p′-DDE in women residents. p,p′-DDT and p,p′-DDE had the highest detection frequencies in both dust (58% and 34% detection, respectively) and serumsamples (98% and 100% detection, respectively). Significantly higher detection frequencies for o,p′-DDT, p,p′-DDE, and p,p′-DDDwere observed in dust samples collected in buildings that had been previously sprayed for malaria control.We also observed a significant, positive association between dust loading and serumconcentrations of p,p′-DDT and p,p′-DDE (Spearman's rho=0.68 and 0.54, respectively). Despite the lowdetection frequency in dust, our results indicate that undisturbed dustmay be a goodmetric to quantify longterm home exposure to DDT-related compounds and that contamination of the home environment may be an important determinant/source of DDT and DDE exposure.National Institute of Environmental Health Sciences, Award ID: R01ES020360-01, the University of California Berkeley's Center for Occupational and Environmental Health Suzanne Llewellyn Student Award, and the Center for Global Public Health Research Fellowship.http://www.elsevier.com/locate/envint2016-12-31hb2016School of Health Systems and Public Health (SHSPH

Seasonality of antenatal care attendance, maternal dietary intake, and fetal growth in the VHEMBE birth cohort, South Africa.

BackgroundSeasonality of food availability, physical activity, and infections commonly occurs within rural communities in low and middle-income countries with distinct rainy seasons. To better understand the implications of these regularly occurring environmental stressors for maternal and child health, this study examined seasonal variation in nutrition and health care access of pregnant women and infants in rural South Africa.MethodsWe analyzed data from the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort study of 752 mother-infant pairs recruited at delivery from August 2012 to December 2013 in the Vhembe District of Limpopo Province, the northernmost region of South Africa. We used truncated Fourier series regression to assess seasonality of antenatal care (ANC) attendance, dietary intake, and birth size. We additionally regressed ANC attendance on daily rainfall values. Models included adjustment for sociodemographic characteristics.ResultsMaternal ANC attendance, dietary composition, and infant birth size exhibited significant seasonal variation in both unadjusted and adjusted analyses. Adequate frequency of ANC attendance during pregnancy (≥ 4 visits) was highest among women delivering during the gardening season and lowest during the lean (rainy) season. High rainfall during the third trimester was also negatively associated with adequate ANC attendance (adjusted OR = 0.59, 95% CI: 0.40, 0.86). Carbohydrate intake declined during the harvest season and increased during the vegetable gardening and lean seasons, while fat intake followed the opposite trend. Infant birth weight, length, and head circumference z-scores peaked following the gardening season and were lowest after the harvest season. Maternal protein intake and ANC ≤ 12 weeks did not significantly vary by season or rainfall.ConclusionsSeasonal patterns were apparent in ANC utilization, dietary intake, and fetal growth in rural South Africa. Interventions to promote maternal and child health in similar settings should consider seasonal factors

Seasonality of antenatal care attendance, maternal dietary intake, and fetal growth in the VHEMBE birth cohort, South Africa

Background Seasonality of food availability, physical activity, and infections commonly occurs within rural communities in low and middle-income countries with distinct rainy seasons. To better understand the implications of these regularly occurring environmental stressors for maternal and child health, this study examined seasonal variation in nutrition and health care access of pregnant women and infants in rural South Africa. Methods We analyzed data from the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort study of 752 mother-infant pairs recruited at delivery from August 2012 to December 2013 in the Vhembe District of Limpopo Province, the northernmost region of South Africa. We used truncated Fourier series regression to assess seasonality of antenatal care (ANC) attendance, dietary intake, and birth size. We additionally regressed ANC attendance on daily rainfall values. Models included adjustment for sociodemographic characteristics. Results Maternal ANC attendance, dietary composition, and infant birth size exhibited significant seasonal variation in both unadjusted and adjusted analyses. Adequate frequency of ANC attendance during pregnancy (≥ 4 visits) was highest among women delivering during the gardening season and lowest during the lean (rainy) season. High rainfall during the third trimester was also negatively associated with adequate ANC attendance (adjusted OR = 0.59, 95% CI: 0.40, 0.86). Carbohydrate intake declined during the harvest season and increased during the vegetable gardening and lean seasons, while fat intake followed the opposite trend. Infant birth weight, length, and head circumference z-scores peaked following the gardening season and were lowest after the harvest season. Maternal protein intake and ANC ≤ 12 weeks did not significantly vary by season or rainfall. Conclusions Seasonal patterns were apparent in ANC utilization, dietary intake, and fetal growth in rural South Africa. Interventions to promote maternal and child health in similar settings should consider seasonal factors

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

BackgroundIndoor 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.MethodsA 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.ResultsApproximately 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% (β = 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.ConclusionsA 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

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.The U.S. National Institute of Environmental Health Sciences, a Canada Research Chair in Global Environmental Health and Epidemiology and a scholarship by the McGill University Department of Epidemiology, Biostatistics and Occupational Health.http://www.elsevier.com/locate/envreshj2021School of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

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