Dataset Information

Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort.

ABSTRACT:

Background

Indoor 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.

Objectives

We 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.

Methods

Using 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.

Results

Concentrations 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].

Conclusions

In 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.

SUBMITTER: Huang J

PROVIDER: S-EPMC6108579 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort.

Huang Jonathan J Eskenazi Brenda B Bornman Riana R Rauch Stephen S Chevrier Jonathan J

Environmental health perspectives 20180614 6

<h4>Background</h4>Indoor 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 <i>in utero</i> exposure to these chemicals may increase childhood infection frequency.<h4>Objectives</h4>We investigated associations between maternal DDT/E and pyrethroid metabolite concentratio ...[more]

PMID: 29906263

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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: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.

Project description:BackgroundPrenatal phthalate exposure has been associated with behavioral problems and lower performance on measures of cognitive ability in children. However, the potential effect of phthalate exposure during the sensitive preconception period is unknown.ObjectivesTo estimate the association of maternal and paternal preconception urinary phthalate metabolite concentrations with child behavior and evaluate potential modification by child sex.MethodsWe used data from 166 children (111 singletons, 26 pairs of twins, and 1 set of triplets) born to 134 mothers and 100 fathers participating in a prospective preconception cohort study of subfertile couples from the Massachusetts General Hospital Fertility Center. We estimated mean maternal and paternal preconception exposures by averaging individual phthalate metabolite concentrations in multiple urine samples collected before pregnancy. We assessed children's behavior at 2-9 years of age by parent report using the Behavior Assessment System for Children-2 (BASC-2). We estimated the covariate-adjusted association between individual phthalate metabolite concentrations and the sum of di(2-ethylhexyl) phthalate metabolites (∑ DEHP) and behavior scores, and evaluated differences in associations by child sex using linear regression with Generalized Estimating Equations. Models were further adjusted for prenatal phthalate concentrations in sensitivity analyses.ResultsEach loge-unit increase in maternal and paternal preconception concentrations of ∑DEHP was associated with a 2.0 (95% CI: - 3.2, - 0.7) and 1.8 (95% CI: - 3.1, - 0.4) point decrease in BASC-2 internalizing behavior scores among all children, respectively. We observed sex-specific associations for some phthalate biomarkers: among boys, maternal monoisobutyl phthalate (MiBP) was positively associated with externalizing behaviors, and paternal MiBP and mono-n-butyl phthalate were positively associated with internalizing behaviors.ConclusionsIn this cohort, paternal and maternal preconception concentrations of some phthalate biomarkers were associated with specific aspects of child behavior, even after adjustment for prenatal concentrations. While additional research is warranted to confirm these results, our findings suggest that the preconception period of exposure may be a critical window for offspring neurodevelopment.

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.

Project description:BACKGROUND:Prenatal phthalate exposure has been inconsistently associated with fetal growth and infant birth weight. However, the effect of exposure during the paternal and maternal preconception period remains understudied. OBJECTIVES:To investigate associations of paternal and maternal preconception and maternal prenatal urinary phthalate metabolite concentrations with birth weight. METHODS:The study comprised 364 singletons born to 364 mothers and 195 fathers (195 couples) from the EARTH Study, a prospective cohort of couples from Boston, MA. Births were categorized by mode of conception: in-vitro fertilization based (IVF) (n=208) or non-IVF based (n=156, intrauterine insemination or non-medically assisted/natural conception). We measured urinary concentrations of eleven phthalate metabolites in maternal (n=1425) and paternal (n=489) preconception and maternal prenatal (n=781) samples. Birth weight was abstracted from delivery records. Covariate-adjusted associations between loge-phthalate metabolite concentrations and birth weight were evaluated separately by mode of conception using multivariable linear regression. RESULTS:Each loge-unit increase in paternal urinary concentration of the sum of di(2-ethylhexyl) phthalate (?DEHP) metabolites was associated with a 90 gram (95% CI: -165, -15) decrease in birth weight among IVF singletons, but not among non-IVF singletons (18g; 95% CI: -76, 113). Additional adjustment for maternal prenatal ?DEHP concentrations modestly strengthened findings among IVF singletons. While few associations were found with maternal preconception phthalate metabolites, we observed an inverse relationship between several maternal prenatal urinary phthalate metabolite concentrations and birth weight among IVF singletons in covariate-adjusted models. However, with further adjustment for specific paternal phthalate metabolite concentrations, these associations were attenuated and no longer significant. CONCLUSIONS:Paternal preconception urinary concentration of ?DEHP metabolites was associated with a decrease in birth weight among IVF-conceived singletons. These results, if replicated, highlight the importance of preconception health, especially among subfertile couples.

Project description:BACKGROUND:Organophosphate esters (OPEs) are synthetic chemicals used as flame retardants and plasticizers in a variety of goods. Despite ubiquitous human exposures and laboratory evidence that prenatal OPE exposures may disrupt offspring metabolism, perinatal studies of OPE health effects are limited. The objectives of this study were to: 1) Determine predictors and reproducibility of urinary OPE biomarker concentrations during pregnancy, and 2) Estimate the relation of prenatal OPE exposures with birth outcomes and cord blood adipokine and insulin concentrations. METHODS:We analyzed five OPE metabolites in urine samples collected at up to three visits during pregnancy from 90 women enrolled in the ORigins of Child Health And Resilience in Development (ORCHARD) pregnancy cohort in Baltimore, MD from 2017 to 2019. To quantify the variability of metabolite concentrations during pregnancy, we calculated intraclass correlation coefficients (ICCs) for each metabolite using mixed effects regression models. Using self-reported questionnaire data collected during gestation, we assessed possible sociodemographic and environmental/behavioral predictors of each OPE metabolite using generalized estimating equations to account for repeated exposure measures. We ascertained birth outcomes of 76 offspring from medical records, including weight-for-gestational age, length, ponderal index, and gestational age. In a subset of 37 infants, we measured cord blood concentrations of leptin, adiponectin, and insulin. To account for repeated exposure measures, we used linear structural equation models to assess the relations of standard deviation (SD) increases in prenatal OPE metabolite factor scores with continuous birth outcomes and cord blood biomarker concentrations. RESULTS:ICCs ranged from 0.09 for isopropylphenyl-phenyl phosphate (ip-PPP) to 0.59 for bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We observed little consistency in environmental or behavioral predictors of OPE exposures, although concentrations were generally lower for samples collected in the afternoon compared to morning and winter compared to other seasons. In adjusted analyses, a SD increase in BDCIPP concentration was associated with a 0.06?g/cm3 (95% CI: 0.00, 0.12) greater ponderal index. A SD increase in BDCIPP was associated with a 0.37 (95% CI: -?0.62, -?0.13) SD lower insulin concentration and 0.24 (95% CI: -?0.39, -?0.08) SD lower leptin concentration. Other OPEs were not associated with infant outcomes. CONCLUSIONS:These findings suggest some OPEs may be metabolic disruptors warranting investigation in larger studies.

Dataset Information

Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort.

Background

Objectives

Methods

Results

Conclusions

Publications

Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort.

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