Urban residential pyrethroid insecticide use during pregnancy and effects on infant neurodevelopment

This dissertation is a molecular epidemiologic study designed to assess the extent of prenatal exposure to pyrethroid insecticides resulting from residential pest control among inner-city women from New York City during pregnancy and to examine the relationship between prenatal exposure to pyrethroids and neurodevelopmental outcomes in the child at age 36 months. The study was conducted among the mothers and newborns enrolled in the Columbia Center for Children's Environmental Health (CCCEH) longitudinal birth cohort. The impetus for the study arose from the 2000-2001 U.S. EPA pesticide regulations restricting the applications of two organophosphorous insecticides, chlorpyrifos and diazinon, from residential pest control.;Hypothesis 1. Pyrethroid insecticides are the main active ingredients in spray formulation products marketed for residential pest control in stores located throughout the catchment area of the CCCEH cohort. Results. In 2007, spray products were the most common products sold for residential pest control. The vast majority of spray products contained pyrethroid insecticides. The most common active ingredient contained in spray pesticide products was permethrin. Chlorpyrifos and diazinon have nearly been eliminated from products marketed for residential pest control. This supports my overall hypothesis that pyrethroid insecticides are replacing the organophosphorous insecticides for residential pest control.;Hypothesis 2: It is possible to devise a laboratory methodology to measure pyrethroid and organophosphorous insecticides in human plasma following residential exposure. Results. A novel GC-HRMS methodology was designed and validated to measure a battery of pyrethroids in human plasma or sera. Detection limits of this study proved capable of detecting pyrethroids in 6% to 12% of study participants.;Hypothesis 3. The increase in residential exposure to pyrethroids among subjects enrolled into the CCCEH cohort between 1999-2006 can be demonstrated by measuring levels of pyrethroids and the synergist piperonyl butoxide in personal air samples collected from the mother over 48-hours during the 3 rd trimester of pregnancy and in kitchen dust samples collected from the home during the 3rd trimester of pregnancy. Results. There was widespread exposure to the pyrethroid synergist piperonyl butoxide among subjects enrolled in this cohort between years 2000-2006. Levels and detection of piperonyl butoxide were highly associated with reported use of spray products for residential pest control. Detection of piperonyl butoxide in personal air samples increased in association with the enactment of the 2000-2001 U.S. EPA pesticide regulations. As anticipated, due to the low volatility of pyrethroids, detection frequency of permethrin was relatively low in personal air samples. However, levels and detection frequencies of permethrin were associated with reported use of spray products and increased over time. Permethrin was the most frequently detected pyrethroid in dust samples.;Hypothesis 4. The increase in pyrethroid insecticide exposure to the mother and fetus during pregnancy can be demonstrated by measuring levels in maternal and fetal plasma collected at delivery and in maternal urine samples collected during the 3rd trimester of pregnancy among subjects enrolled between years 1999-2004. Results. Detection of permethrin in maternal plasma was relatively low and levels were only marginally greater than the limit of detection. However, this is the first epidemiologic study to demonstrate a high degree of concordance between detection of permethrin isomers in matched maternal and cord plasma samples. These data confirm the ability of permethrin to cross the placental barrier. The ability to examine changes in permethrin exposure over time was limited by infrequent detections and potential analytical batch effects. Results show a significant increase in the detections of trans-permethrin over years 2000-2006. Detections of cis-permethrin decreased over time in the same plasma samples. Cis- and trans-permethrin were not correlated in either maternal or cord plasma. These results were not expected as cis- and trans-permethrin are isomers of the same insecticide and levels are highly correlated in air. The lack of correlation in plasma could be due to different metabolic pathways or to differences in stabilities during storage. Results of the novel GC-HRMS methodology developed for this dissertation support findings from both the store survey and the environmental monitoring suggesting that permethrin is the predominant pyrethroid used among cohort subjects for residential pest control.;Hypothesis 5 (exploratory aim). Prenatal exposure to permethrin is associated with delayed neurocognitive development in the child age 36-months. Results. Cognitive and motor development at 36 months of age using the Bayley Scales of Infant Development, 2nd Edition was examined as a function of permethrin and piperonyl butoxide measured in personal air collected during the 3rd trimester of pregnancy and maternal and/or cord plasma collected at birth. Adjusting for gender, ethnicity, gestational age at birth, maternal IQ, maternal education, quality of the home environment (HOME) and exposure to ETS, a significant inverse association was between prenatal piperonyl butoxide and 36-month motor developmental scores. (Abstract shortened by UMI.)...