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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.

ABSTRACT: 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 thyroid-stimulating 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 (??=?-0.27??g/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.

SUBMITTER: Chevrier J

PROVIDER: S-EPMC6728182 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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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.

Chevrier Jonathan J Rauch Stephen S Obida Muvhulawa M Crause Madelein M Bornman Riana R Eskenazi Brenda B

Environment international 20190705

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 ...[more]

PMID: 31284115

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Project description:BackgroundIndoor residual spraying (IRS) of insecticides, conducted in low- and middle-income countries to control malaria, may result in high exposure to dichlorodiphenyltrichloroethane (DDT), its breakdown product dichlorodiphenyldichloroethylene (DDE), or pyrethroids. Animal studies suggest in utero exposure to these chemicals may increase childhood infection frequency.ObjectivesWe investigated associations between maternal DDT/E and pyrethroid metabolite concentration and child infection associations in an IRS setting in which susceptibility factors are common and infections are leading causes of child morbidity and mortality.MethodsUsing gas chromatography-mass spectrometry, we measured serum DDT/E and urinary pyrethroid metabolite concentrations in peripartum samples from 674 women participating in the Venda Health Examination of Mother, Babies and their Environment (VHEMBE) study. Counts of persistent child fevers, otitis media, and severe sore throat between 1 and 2 y of age were ascertained from maternal interviews. Associations between DDT/E and pyrethroid metabolite concentrations and infections were estimated using zero-inflated Poisson regression. We estimated relative excess risks due to interaction (RERI) with poverty, maternal energy intake, and maternal HIV status.ResultsConcentrations of DDT/E, particularly p,p'-DDE, were associated with higher rates of persistent fevers [IRR=1.21 (95% CI: 1.01, 1.46)], for a 10-fold increase in p,p'-DDE). This association was stronger among children from households below versus above the South African food poverty line [IRR=1.31 (95% CI: 1.08, 1.59) vs. IRR=0.93 (95% CI: 0.69, 1.25), respectively] and for children whose mothers had insufficient versus sufficient caloric intake during pregnancy [IRR=1.30 (95% CI: 1.07, 1.58) vs. IRR=0.96 (95% CI: 0.72, 1.28), respectively].ConclusionsIn utero IRS insecticide exposure may increase childhood infection rates. This was particularly apparent among children from poorer households or whose mothers had low energy intake during pregnancy. https://doi.org/10.1289/EHP2657.

Project description:Background:Pyrethroids are the most widely used insecticides globally for domestic, agricultural, and malaria vector control. In 10 countries, dichlorodiphenyl trichloroethane (DDT) is also used for the latter. Thus, high exposure to pyrethroids and DDT have been reported among women and children from rural and/or malaria-endemic areas. Experimental studies suggest that fetal exposure to pyrethroids, particularly cypermethrin, and DDT may have sex-specific growth effects. However, epidemiologic investigations are scarce and inconsistent and have not considered postnatal environment or susceptibility factors. Methods:In 665 mother-child dyads participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a rural South African birth cohort with high insecticide exposure, we examined associations of maternal peripartum uri-nary pyrethroid metabolites and serum DDT concentrations with child anthropometrics at 3.5 years using multivariable linear regression. We investigated effect modification by child sex, maternal nutrition and HIV status, and household poverty. Results:Pyrethroid metabolites cis-3-(2,2-dibromovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis-DBCA), cis-3-(2,2,-dicholorvinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis-DCCA), trans-DCCA, and 3-phenoxybenzoic acid (3-PBA) were quantified in nearly all mothers. A 10-fold increase in cis-DCCA concentration was associated with 0.21 kg/m2 lower body mass index (95% confidence interval = -0.41, -0.01), with similar estimates for other cypermethrin or permethrin metabolites (trans-DCCA and 3-phenoxybenzoic acid). In stratified analyses, stronger associations were observed with lower weight, body mass index, arm circumference, and weight-for-height among boys relative to girls. Associations with cis-3-(2,2-dibromovinyl)-2,2-dimethyl-cyclopropane carboxylic acid, a metabolite specific to deltamethrin, were weaker or absent. No substantial associations were observed with DDT. Discussion:In a population with ubiquitous pyrethroid exposure, maternal concentrations of metabolites of cypermethrin and permethrin were associated with thinness at 3.5 years.

Project description:BackgroundMultiple mutations in the voltage-gated sodium channel have been associated with knockdown resistance (kdr) to DDT and pyrethroid insecticides in a major human disease vector Aedes aegypti. One mutation, V1016G, confers sodium channel resistance to pyrethroids, but a different substitution in the same position V1016I alone had no effect. In pyrethroid-resistant Ae. aegypti populations, V1016I is often linked to another mutation, F1534C, which confers sodium channel resistance only to Type I pyrethroids including permethrin (PMT), but not to Type II pyrethroids including deltamethrin (DMT). Mosquitoes carrying both V1016G and F1534C exhibited a greater level of pyrethroid resistance than those carrying F1534C alone. More recently, a new mutation T1520I co-existing with F1534C was detected in India. However, whether V1016I or T1520I enhances pyrethroid resistance of sodium channels carrying F1534C remains unknown.Methodology/principal findingsV1016I, V1016G, T1520I and F1534C substitutions were introduced alone and in various combinations into AaNav1-1, a sodium channel from Aedes aegypti. The mutant channels were then expressed in Xenopus oocytes and examined for channel properties and sensitivity to pyrethroids using the two-electrode voltage clamping technique. The results showed that V1016I or T1520I alone did not alter the AaNav1-1 sensitivity to PMT or DMT. However, the double mutant T1520I+F1534C was more resistant to PMT than F1534C, but remained sensitive to DMT. In contrast, the double mutant V1016I+F1534C was resistant to DMT and more resistant to PMT than F1534C. Furthermore, V1016I/G and F1534C channels, but not T1520I, were resistant to dichlorodiphenyltrichloroethane (DDT). Cryo-EM structures of sodium channels suggest that T1520I allosterically deforms geometry of the pyrethroid receptor site PyR1 in AaNav1-1. The small deformation does not affect binding of DDT, PMT or DMT, but in combination with F1534C it increases the channel resistance to PMT and DDT.Conclusions/significanceOur data corroborated the previously proposed sequential selection of kdr mutations in Ae. aegypti. We proposed that mutation F1534C first emerged in response to DDT/pyrethroids providing a platform for subsequent selection of mutations V1016I and T1520I that confer greater and broader spectrum of pyrethroid resistance.

Project description:Although indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) and pyrethroids effectively controls malaria, it potentially increases human exposure to these insecticides. Previous studies suggest that prenatal exposure to these insecticides may impact human neurodevelopment.We aimed to estimate the effects of maternal insecticide exposure and neurodevelopment of toddlers living in a malaria-endemic region currently using IRS.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 maternal exposure to DDT and its breakdown product, dichlorodiphenyldichloroethylene (DDE), in maternal serum, and measured pyrethroid metabolites in maternal urine. We assessed children's neurodevelopment at 1 and 2 y of age using the Bayley Scales of Infant Development, third edition (BSID-III), and examined associations with maternal exposure.DDT and DDE were not associated with significantly lower scores for any BSID-III scale. In contrast, each 10-fold increase in cis-DCCA, trans-DCCA, and 3-phenoxybenzoic acid were associated, respectively, with a -0.63 (95% CI: -1.14, -0.12), -0.48 (95% CI: -0.92, -0.05), and -0.58 (-1.11, -0.06) decrement in Social-Emotional scores at 1 y of age. In addition, each 10-fold increase in maternal cis-DBCA levels was associated with significant decrements at 2 y of age in Language Composite scores and Expressive Communication scores [?=-1.74 (95% CI: -3.34, -0.13) and ?=-0.40 (95% CI: -0.77, -0.04), respectively, for a 10-fold increase]. Significant differences by sex were estimated for pyrethroid metabolites and motor function scores at 2 y of age, with higher scores for boys and lower scores for girls.Prenatal exposure to pyrethroids may be associated at 1 y of age with poorer social-emotional development. At 2 y of age, poorer language development was observed with higher prenatal pyrethroid levels. Considering the widespread use of pyrethroids, these findings deserve further investigation. https://doi.org/10.1289/EHP2129.

Dataset Information

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.

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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.

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