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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 (IRR 10 ) = 1.4; 95 % Confidence Interval (CI) = 1.0, 2.1) and persistent diarrhea (IRR 10  = 2.1; 95 % CI = 1.2, 3.9), trans-DCCA was associated with increased rates of colds in children (IRR 10  = 1.3; 95 % CI = 1.0, 1.6) and persistent fever (IRS 10  = 1.4; 95 % CI = 1.0, 2.0), and 3-PBA was associated with increased rates of persistent fever (IRR 10  = 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Half the world's population is at risk for malaria. Indoor residual spraying (IRS) with insecticides has been effective in controlling malaria, yet the potential neurotoxicity of these insecticides is of concern, particularly for infants exposed in utero., Objectives: To determine the association of prenatal exposure to DDT/DDE and pyrethroid insecticides and behavioral/emotional problems in two-year-old children., Methods: The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort in South Africa, measured concentrations of p,p'-DDT and p,p'-DDE in maternal serum and pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, and 3-PBA) in maternal urine collected during pregnancy. At 2 years, 683 mothers were interviewed about their children's behavior and emotional development, using the Child Behavior Checklist (CBCL). We examined associations between behavioral or emotional problems and biomarkers of prenatal insecticide exposure., Results: Maternal serum p,p'-DDT concentrations were associated with heightened withdrawn behavior in 2-year olds, with a 0.24 increase in raw scores (95%CI = 0.00, 0.49) and a 12% increase (95%CI = 1.01, 1.23) in risk of being at or above the borderline-clinical level, per 10-fold increase in concentrations. Ten-fold increases in p,p'-DDT and p,p'-DDE were related to 30% (RR = 1.30; 95%CI = 1.01, 1.67) and 39% (RR = 1.39; 95%CI =1.01, 1.91) higher risks, respectively, for increased oppositional-defiant behavior. p,p'-DDE concentrations were also related to increased risk of ADHD-related problems (RR = 1.30; 95%CI = 0.98, 1.72). Maternal urinary concentrations of cis-DBCA and 3-PBA were associated with increased risk of externalizing behaviors (RR = 1.30; 95%CI = 1.05, 1.62; RR = 1.35, 95%CI = 1.03, 1.78 per 10-fold increase, respectively), with some evidence of an association between cis-DBCA and affective disorders (RR = 1.25; 95%CI = 0.99, 1.56). Some associations with maternal pyrethroid concentrations were stronger in girls than boys., Conclusions: Prenatal exposure to DDT and pyrethroid insecticides may be associated with maternally-reported behavioral problems in two-year-old children. Given their long history and continued use, further investigation is warranted., (Copyright © 2022. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.