Grantee Research Project Results
Final Report: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
EPA Grant Number: R834513C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834513
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
Investigators: Eskenazi, Brenda
Institution: University of California - Berkeley
EPA Project Officer: Hahn, Intaek
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2017)
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Over the past 20 years, the Center for Children’s Environmental Health Research at the University of California, Berkeley has successfully created and coordinated a transdisciplinary research program that addresses the unique environmental health needs of children living in a predominantly Latino farmworker community. Below is a summary of our many accomplishments since 2010 for the three Projects and an update on Cores.
Summary/Accomplishments (Outputs/Outcomes):
Our data collection work on this grant is complete, but we continue to work with data generated from this funding. We are currently preparing a manuscript for publication showing striking, sex-differentiated associations between prenatal OP pesticide exposures and children’s executive functioning and attention between ages 7 and 12. These indicate that boys experience pronounced deficits in maternally-reported executive function and child-assessed working memory in association with in utero OP exposure. We are also beginning work on analyses focused on the timing and tempo of puberty in CHAMACOS boys and girls, both as an outcome of early childhood adversity and as a predictor of risk-taking behavior in later adolescence. We expect to continue working with these data for years to come.
This portion of our Center grant set out to assess effects on boys’ neurodevelopment and pubertal development of prenatal and early life exposure to environmental exposures with wide U.S. and global relevance. We recognized that our Center was well poised to address societal concerns that environmental exposures could contribute to apparent increases in neurobehavioral issues like attention problems and a shifting age at puberty, and through our specific aims, we intended to do so. We have made important progress towards these aims. With regards to neurodevelopment, we have presented evidence of association between multiple early-life exposures and adverse neurobehavioral outcomes at this age point, particularly for boys. While prenatal PBDE exposure, prenatal methyl bromide and chloropicrin and early postnatal Mn exposure show similarly adverse associations with attention, executive functioning, and/or behavior for boys and girls, we provide evidence that prenatal Mn exposure and OP pesticide exposure (not yet published) may be particularly detrimental to boys. In so far as WISC Processing Speed and Working Memory Indices reflect attention and executive functioning capacities, respectively, our research suggests that prenatal DDT exposure and exposure to alternate flame retardants (Firemaster 500 or OP-based formulations) may also exert detrimental impacts on these outcomes. With regards to timing of puberty, we have provided evidence that PBDES, PCB, and DDT/E are associated with either earlier physical manifestations of male puberty or higher levels of male sex hormones at age 12. Early Mn exposure appears to be associated with slightly later genital development in boys, but was not associated with age 12 sex hormones (not published). In our parallel analyses of female pubertal timing, prenatal DDT exposure and early Mn exposure were associated with earlier menarche and earlier pubarche, respectively (not yet published). By contrast, prenatal PBDEs were associated with later menarche.
As noted above, the data collected under this grant and previous EPA funding have also enabled important research on other health outcomes of widespread interest in the U.S.: respiratory health and obesity. With regards to respiratory health, we observed associations between higher average urinary OP metabolite concentrations during childhood and increased respiratory symptoms and poorer lung function at 7-years of age. We also observed relationships between higher agricultural use of sulfur within 1 km of the child’s residence during the year prior to the 7-year visit and increased odds of reporting respiratory symptoms and poorer lung function. An important difference between the associations that we have observed with respiratory health and those with neurodevelopment is that postnatal pesticide exposures during early childhood appear to be more strongly related to adverse respiratory outcomes, whereas prenatal exposures consistently show stronger associations with neurodevelopmental outcomes. We did not observe any adverse relationship between prenatal or postnatal residential proximity to agricultural fumigant use and respiratory health in the CHAMACOS cohort. With regards to obesity, we’ve shown differential impacts of prenatal exposure to PBDEs and DDT/E based on child sex. Boys with higher prenatal exposure to PBDEs, DDT, and/or DDE all showed higher BMI in middle childhood, whereas girls with higher PBDE exposure tended to have a lower BMI in middle childhood (and showed no change in BMI linked to DDT/E exposure). One PBDE congener (BDE-153) as measured at age 7 was associated with lower BMI for both sexes at this age.
Novel epigenetic findings on the molecular mechanisms associated with environmental exposures in newborns and children resulting from the CHAMACOS Project C were only possible because of the existing CHAMACOS birth cohort data and banked biological samples collected over the children’s lifetime going back 18 years to the time when CHAMACOS children were in utero. This project required a careful examination of existing methodological and analytical approaches. We conducted a direct comparison of DNA methylation in different cell types that demonstrated that the commonly used minfi procedure may not be appropriate for newborns that have a different blood cell composition than adults. We developed novel methods of data normalization of high-dimensional genome-wide methylation data that was submitted to the public domain. We employed state-of the art analytical tools such as SuperLearner for statistical analyses and are now applying these methods in other studies.
Our data show striking differences in genome-wide DNA methylation by age and sex, not limited to CpG sites located in sex chromosomes. These findings provide additional evidence for the need to expand research on environmental epigenetics to a wide variety of sub-populations, including fetuses and pregnant women and minority cohorts (e.g. CHAMACOS) in order to explain differential risks and health effects. We first reported data from our birth cohort demonstrating that prenatal exposure to POPs such as PBDE and DDT that are still common in California and many other parts of the world and may be linked to hypomethylation in fetal blood. Importantly, we showed that accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies. These findings are immediately relevant to the EPA priority science question “What chemicals and combinations of chemicals… pose the greatest risk to children’s health”.
In short, within our Center, we have been able to trace important linkages between children’s early environmental exposures and multiple facets of their health and development in childhood. Beyond our Center, we’ve sought opportunities to contribute to collaborative investigations of these issues. In 2016, the CHAMACOS Study was selected to participate in the NIH-funded ECHO program (ECHO stands for Environmental influences on Child Health Outcomes), which has set out to construct a “synthetic cohort” of 50,000 US children by combining and harmonizing data collected from a large number of new and extant birth cohort studies around the country. Our participation in ECHO will facilitate use of CHAMACOS data – including data collected under this EPA funding – in any number of analyses related to children’s health and development.
Conclusions:
In Project A, we have examined the association of pesticide exposure (e.g. to DDT, Mn-containing pesticides, OP pesticides) and PBDE flame retardants with neurodevelopment, pubertal development, and respiratory outcomes in CHAMACOS children. Although this award specifically funded data collection related to boys, DDT and PBDEs, and neurodevelopmental and pubertal outcomes, we report here on the full breadth of pediatric environmental health research we have been able to conduct with the help of this funding. Please note that while this progress report officially covers our work through May 2016, we are also presenting the work we’ve done since that point to provide our funders a clear picture of our work. We also present findings that relate to earlier phases of our study and to other health outcomes.
Project A Specific Aims:
- To maintain and expand the CHAMACOS cohort as children begin the critical transition to puberty, assessing neurodevelopment and pubertal development in 300 boys form 9 to 13 years of age.
- To determine whether prenatal and childhood exposure to DDT/E, PBDEs, and Mn are associated with neurobehavioral functioning at age 9, 10 1/2, and 12 years.
- To determine whether prenatal and childhood exposure to DDT/E, PBDEs, and Mn are associated with timing of pubertal development in boys between age 9 and 13 years.
- To determine whether prenatal and childhood exposure to DDT/E, PBDEs, and Mn are associated with hormone levels in boys at age 12.
1. Maintain and expand the CHAMACOS cohort: We successfully met our goal of expanding the CHAMACOS cohort to 300 boys. We assessed 326 boys at age 9 years, 310 boys at age 10½, 304 boys at age 12, and 241 boys at age 12¾. Under separate funding sources, we have also been able to assess over 300 girls during this period, as well as to repeat pubertal development assessments at age 14 years. The findings presented below reflect our work with boys and girls.
2. Exposure to DDT/E and neurobehavioral functioning: For both DDT/E and PBDEs, measured maternal pregnancy serum concentrations were used as the exposure variable for the majority of CHAM1 participants (i.e., members of the original CHAMACOS cohort followed since pregnancy), while back-extrapolated pregnancy concentrations were used for all CHAM2 participants (i.e., members of the CHAMACOS cohort enrolled at child age 9) as well as for CHAM1 participants who were missing pregnancy or delivery serum samples. Prenatal concentrations were back-extrapolated from DDT/E and/or PBDE levels measured in maternal serum collected when the child was 9 years old using the SuperLearner algorithm, which is an ensemble machine learning technique that uses the weighted combination of algorithms to return a prediction function that minimizes the cross-validated mean squared error (see Project B). In validation models, which used maternal serum concentrations to back-extrapolate values in women for whom measured pregnancy values were also available, the model R2 for models comparing extrapolated and measured values was 0.95 for both p,p’-DDT and p,p’-DDE, and ranged from 0.58-0.84 for the four highest-detected PBDE congeners in this population (Verner et al 2015). In an article published in 2015, we reported on analyses of children’s IQ at ages 7 and 10.5 years in association with prenatal exposure to DDT and DDE. We found no associations between these exposure and any WISC IQ outcomes in general models incorporating both 7 and 10.5 year endpoints. However, we did observe an inverse association between prenatal DDT levels and children’s Processing Speed subscale scores at age 7 only. In separate models by sex, we also noted inverse associations between prenatal DDE exposure and girl’s Processing Speed and Full Scale IQ at age 7 years (Gaspar et al 2015).
3. Exposure to PBDEs and neurobehavioral functioning: In a second article published in 2015, we reported on analyses of children’s attention and executive functioning at ages 9-12 years in association with prenatal exposure to PBDEs. Prenatal exposures were associated with impaired performance on both direct assessments and parent reports of children’s attention and executive functioning at these ages. For example, a 10-fold increase in prenatal ΣPBDE was associated with poorer response consistency on the Conners' Continuous Performance Test II (β=2.9; 95% CI: 0.9, 4.8) and poorer working memory on the Behavioral Rating Inventory of Executive Function (β=2.5; 95% CI: 0.5, 4.4). Child age 9 ΣPBDE levels were associated with poorer parent-reported attention and executive function for girls but not boys (Sagiv et al 2015).
4. Exposure to Mn and neurobehavioral functioning: We measured Mn levels in prenatal (Mnpre) (n=197) and postnatal (Mnpost) dentin (n=193) from children’s shed teeth using laser ablation inductively coupled plasma mass spectroscopy and examined the relationship with children’s scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) on the Bayley Scales of Infant Development at 6, 12, and 24-months (Gunier et al. 2015). We explored non-linear associations and interactions by sex, blood lead concentrations and maternal iron status during pregnancy. We observed that a two-fold increase of Mnpost levels in dentin was associated with small decreases in MDI at 6-months and 12-months of age. We also observed a non-linear relationship between Mnpost levels and PDI at 6-months. There was evidence of effect modification by sex for Mnpost levels and neurodevelopment at 6-months with stronger effects among girls for both MDI (-1.5 points; 95% Confidence Interval (CI): -2.4, -0.6) and PDI (-1.8 points; 95% CI: -3.3, -0.3). Girls whose mothers had lower hemoglobin levels experienced larger decreases in MDI and PDI associated with Mnpre levels than girls whose mothers had higher hemoglobin levels (pinteraction=0.007 and 0.09, respectively). We did not observe interactions with blood lead concentrations or any relationships with neurodevelopment at 24-months.
In another manuscript published in 2015, we reported on analyses of children’s behavior, memory, motor skills, and IQ at ages 7, 9, and 10.5 years in association with prenatal and early postnatal manganese (Mn) exposure, as assessed in tooth dentine formed in utero and early infancy and assayed in children’s shed teeth. Mn was associated adverse behavioral outcomes. Prenatal Mn exposure showed adverse associations with maternally-reported internalizing, externalizing, and hyperactivity problems at age 10½ for boys but not girls, whereas postnatal Mn exposure was associated with these outcomes for both boys and girls. For boys only, MN was associated with improved memory, motor, and IQ scores. When MN exposure occurred in conjunction with elevated lead levels, it was associated with poorer visuospatial memory at age 9 as well as lower IQ scores at 7 and 10.5 (Mora et al 2015).
In preliminary, unpublished analyses, we did not observe an association between hair Mn concentrations and 10.5 year IQ or behavior in models adjusted for child’s exact age, maternal education, poverty status, language of assessment and HOME score.
5. Exposure to DDT/E, PBDEs, and Mn and pubertal development in boys: In 2017, we published a manuscript regarding children’s prenatal and childhood (age 9) PBDE exposure and in association with age at onset of physical manifestations of puberty (genital and public hair development in boys; breast and public hair development in girls, and menarche in girls). Prenatal PBDE exposure was associated with later menarche in girls but earlier pubic hair development in boys. No associations were seen between either prenatal or age 9 exposures and any other indicators of age at pubertal onset (Harley et al 2017).
We have not yet published on DDT/E and the physical manifestations of puberty, though we have published on pubertal sex hormones (see Aim 4). Our preliminary analyses on DDT/E suggest that prenatal DDT concentrations are associated with earlier genital development in boys and with earlier menarche in girls.
We have not yet published on Mn and puberty. Results of our preliminary analyses were as follows. Among 103 boys with available exposure and outcome data, our preliminary analyses indicate a marginally significant association of prenatal Mn with later onset of genital development (HR=0.6, 95% CI=0.4, 1.0). Among girls (N=113), higher postnatal (i.e. infancy) Mn exposure was associated with significantly earlier onset of pubic hair development (HR=1.4, 95% CI=1.1, 1.9).
6. Exposure to DDT/E, PBDEs, and Mn and hormone levels in boys:
In 2016, we published a manuscript presenting associations between PBDE, DDT/E, and PCB exposures in utero and at age 9 on adolescent boys’ production of sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T)] at age 12. In utero exposure to BDE-153 (a PBDE congener) was associated with substantial increases in levels of all three sex hormones measured. BDE-100 (another PBDE congener was associated with increases in boys’ LH levels only, and total PCB concentrations were associated with increased FSH levels. DDT/E was not associated with hormone levels in boys at this age (Eskenazi et al 2017).
We ran preliminary analyses of prenatal and postnatal Mn exposure in association with hormones in boys. Among 78 boys included in these analyses, we observed no association between either prenatal or postnatal Mn exposure and LH, T, or FSH at age 12. These data have been presented at scientific conferences but given the small numbers of boys with Mn measured, we will likely not submit this as a separate manuscript.
7. OTHER CHAMACOS STUDIES
- OP Metabolites and neurodevelopment: We presented evidence that early childhood adversity may modify associations between prenatal OP pesticide exposures as reflected by maternal urinary DAP metabolites and child IQ as assessed using the WISC. Boys, for example, displayed the most negative associations between OP exposure and IQ when they had experienced high adversity in the early learning environment (Stein et al 2016).
- Agricultural pesticides and neurodevelopment: We also published manuscripts based on California’s Pesticide Use Reporting (PUR) database, which we used to estimate CHAMACOS mothers’ ambient exposure to agricultural use pesticides during pregnancy based on their residential address at that time. In the first of these, we demonstrated that children of mothers who had experienced highest (top quartile) versus lowest (bottom quartile) prenatal residential exposure to a toxicity-weighted quantity of OP and carbamate pesticides through nearby agricultural applications performed significantly worse on Perceptual Reasoning (4 pt decrease) and Working Memory (2.8 point decrease) indices of the WISC at age 10.5, resulting in a 3 point decrease in Full Scale IQ score (Rowe et al 2016). In the second such analysis, we assessed continuous associations of a number of prenatal pesticide exposures in association with WISC scores at age 7. We demonstrated that each standard deviation increase in toxicity-weighted organophosphate (OP) pesticides was associated with a 2.2 point decrease on Full-Scale IQ and a 2.9 point decrease in Verbal Comprehension at child age 7. We observed similar decrements in association with each of two specific OPs (acephate and oxydemeton-methyl) as well as with three other pesticide groups (pyrethroids, neonicotinoids, and manganese fungicides) (Gunier et al 2016).
In a third analysis, we assessed prenatal exposure to fumigant pestcides (methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene) with child IQ and parent-reported hyperactivity or attention problems at age 7. We observed decreases of 2.6 points (95% Confidence Interval (CI): -5.2, 0.0) and 2.4 points (95% CI: -4.7, -0.2) in Full-Scale intelligence quotient for each ten-fold increase in methyl bromide and chloropicrin use within 8km of the child's residences from birth to 7-years of age, respectively. There were no associations between residential proximity to use of other fumigants and cognition or proximity to use of any fumigant and hyperactivity or attention problems. (Gunier et al 2017). In the most recent of such analysis, we applied Bayesian profile regression (BFR) to characterize the combined impact of various groups of pesticides to which women tended to experience simultaneous exposure. BFR techniques revealed 8 distinct exposure profiles in this region in 1999-2000 (when CHAMACOS children were in utero). Offspring of women in the two most highly-exposed profile groupings experienced substantial deficits (6.9 points and 6.4 points respectively) in WISC Full Scale IQ at age 7 relative to offspring of women in the lowest-exposed profile grouping. This novel analytic technique revealed new insight on the spatial patterning of local exposure groupings, and of sub-additive effects of multiple exposures (Coker et al 2017).
- OP Metabolites and respiratory health: We investigated the relationship between early-life exposure to OPs and respiratory outcomes. Participants included 359 mothers and children from the CHAMACOS birth cohort. Dialkyl phosphate (DAP) metabolites of OP pesticides, specifically diethyl (DE) and dimethyl (DM) phosphate metabolites, were measured in urine from mothers twice during pregnancy (mean = 13 and 26 weeks gestation) and from children five times during childhood (0.5-5 years). Childhood DAP concentrations were estimated by the area under curve (AUC). Mothers reported their child's respiratory symptoms at 5 and 7 years of age. We used generalized estimating equations (GEE) to examine associations of prenatal and childhood DAP concentrations with repeated measures of respiratory symptoms and exercise-induced coughing at 5 and 7 years of age, adjusting for child's sex and age, maternal smoking during pregnancy, secondhand tobacco smoke, season of birth, PM2.5, breastfeeding, mold and cockroaches in home, and distance from highway. Higher prenatal DAP concentrations, particularly DE, were non-significantly associated with respiratory symptoms in the previous 12 months at 5 or 7 years of age [adjusted odds ratio (aOR) per 10-fold increase = 1.44; 95% CI: 0.98, 2.12]. This association was strongest with total DAP and DE from the second half of pregnancy (aOR per 10-fold increase = 1.77; 95% CI: 1.06, 2.95; and 1.61; 95% CI: 1.08, 2.39, respectively). Childhood DAP, DE, and DM concentrations were associated with respiratory symptoms and exercise-induced coughing in the previous 12 months at 5 or 7 years of age (total DAPs: aOR per 10-fold increase = 2.53; 95% CI: 1.32, 4.86; and aOR = 5.40; 95% CI: 2.10, 13.91, respectively). Early-life exposure to OP pesticides was associated with respiratory symptoms consistent with possible asthma in childhood. This work was published in Environmental Health Perspectives (Raanan et al. 2015).
We also evaluated associations between early-life organophosphate exposure and lung function of children living in an agricultural community. In this analysis, participants were 279 children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal birth cohort. The area under the curve for organophosphate exposure was determined by urinary diethyl and dimethyl dialkylphosphate metabolites of organophosphate pesticides, which were measured five times during childhood (6-60 months). Spirometry was performed at age 7 years. Regression models controlled for maternal smoking during pregnancy, season of birth, particulate matter concentrations with aerodynamic diameter ≤2.5 μm (PM2.5), breast feeding duration, mold and pets at home, distance of home from a highway, food insecurity, maternal education, season of spirometry, sex, height and technician. We found that childhood diethyl, dimethyl and total dialkylphosphate concentrations were associated with significant decreases in lung function at age 7. Specifically, we found lower FEV1, (L/s) (ß=-0.16, 95% CI -0.30 to -0.02, p=0.03) and FVC (L) (ß=-0.17, 95% CI -0.34 to 0.01, p=0.06) per 10-fold increase of total dialkylphosphate levels. Early-life organophosphate exposure as assessed by dialkylphosphate concentrations was adversely associated with 7-year-old children's lung function. This work was published in Thorax (Raanan et al. 2016).
- Agricultural pesticides and respiratory health: We evaluated associations between residential proximity to elemental sulfur applications and respiratory symptoms and spirometry of children living in an agricultural community. Participants were enrolled in the CHAMACOS longitudinal birth cohort. We collected respiratory symptomatology for 347 children at 7 y of age and measured spirometry on a subset of 279. Of these, estimations of proximity to sulfur application and relevant covariate data were available for 237 and 205 children for whom we had symptomatology information and FEV1 measurements, respectively. Data from the California Pesticide Use Reporting System were used to estimate the amount of elemental sulfur applied within 0.5, 1, and 3km of a child's residence during the week, month, and 12 mo prior to pulmonary evaluation. Regression models controlled for maternal smoking during pregnancy; season of birth; PM2.5 (particulate matter ≤2.5mm in aerodynamic diameter); breast feeding duration; child's sex, age, and height; technician; and other covariates. We observed adverse associations with respiratory outcomes were found for sulfur applications within 0.5- and 1-km radii. Specifically, asthma medication usage and respiratory symptoms increased [OR=3.51; 95% confidence interval (CI): 1.50, 8.23, p=0.004; OR=2.09; 95% CI: 1.27, 3.46, p=0.004, respectively] and FEV1 decreased (β=−0.143; 95% CI: −0.248, −0.039, p=0.008) per 10-fold increase in the estimated amount of sulfur used within 1 km of child residence during the year prior to pulmonary evaluation. This study suggests that elemental sulfur use, allowed in both organic and conventional farming, in close proximity to residential areas, may adversely affect children's respiratory health. This study was published in Environmental Health Perspectives (Raanan et al. 2017).
We examined the relationship between residential proximity to agricultural fumigant use and respiratory symptoms and lung function in 7-year old children. We obtained information on respiratory symptoms and asthma medication use from maternal questionnaires and children performed spirometry to determine the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25–75% (FEF25-75) at 7-years of age. We estimated agricultural fumigant use within 3, 5 and 8 km of residences during pregnancy and from birth to age 7 using California’s Pesticide Use Report data. We evaluated the association between prenatal and postnatal residential proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene with respiratory symptoms and use of asthma medication with logistic regression models and continuous lung function measurements with linear regression models adjusted for confounders. We observed no significant associations between residential proximity to use of fumigants and respiratory symptoms or use of asthma medication. We did not observe any adverse relationships between residential proximity to fumigant use and lung function measurements. Unexpectedly, we observed suggestive evidence of improved FEV1 and FEF25-75 with higher use of methyl bromide and chloropicrin during the prenatal period. For example, for each 10-fold increase in methyl bromide use during the prenatal development period we observed higher FEV1 (β=0.06 L/s; 95% CI: 0.00, 0.12) and higher FEF25-75 (β=0.15 L/s; 95% CI: 0.03, 0.27). Residential proximity to agricultural fumigant use during pregnancy and childhood did not adversely affect respiratory health in the children through 7 years of age (Gunier et al. 2018).
- PBDEs and body mass index: In 2015, we published on manuscript investigating associations of prenatal and childhood exposures to PBDE flame retardants in association with children’s body mass index (BMI) at age 7 years. Prenatal PBDE exposure was associated with higher BMI in boys but with lower BMI in girls. Childhood exposure to one specific PBDE congener (BDE-153) as measured at age 7 were associated with lower BMI for both boys and girls (Erkin-Cakmak et al 2015).
- DDT/E and body mass index: We recently published a manuscript investigating prenatal DDT/E exposures with children’s BMI at age 12 years. Results indicated different associations for males and females. Among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased BMI z-score (o,p'-DDT, adj-β=0.37, 95% CI: 0.08, 0.65; p,p'-DDT, adj-β = 0.26, 95% CI: 0.03, 0.48; p,p'-DDE, adj-β = 0.31, 95% CI: 0.02, 0.59). Results for girls were nonsignificant. The difference by sex persisted after considering pubertal status (Warner et al 2017).
- Contemporary flame retardant chemicals and neurodevelopment: We recently published the first manuscript on flame retardant chemicals used as alternatives to PBDEs – specifically, Firemaster 550® (FM 550®) and organophosphate flame retardants (PFRs) – in association with child IQ at age 7 years. We measured urinary metabolites of FM 550 and four PFRs from CHAMACOS women during pregnancy. Metabolites of tris(1,3- dichloro-2-propyl) phosphate (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and triphenyl phosphate (DPHP: diphenyl phosphate) were detected in >75% of urine samples, and isopropylphenyl phenyl phosphate (ip-PPP), a metabolite of one component of FM 550®, was detected in 72% of urine samples. We observed decreases of 2.9 points (95% Confidence Interval (CI): -6.3, 0.5) and 3.9 points (95% CI: -7.3,-0.5) in Full-Scale intelligence quotient and Working Memory, respectively, for each ten-fold increase in DPHP in adjusted regression models (Castorina et al 2017).
- OP Metabolites pooling study of early neurodevelopment: We participated in a pooling study with four birth cohorts examining the relationship between prenatal organophosphorus pesticide exposure and child neurodevelopment at 24-months (Engel et al. 2016). Using general linear models, site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (ΣDMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) were computed and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype.There was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.
- OP Metabolites pooling study of fetal growth: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight, length, and head circumference. Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall (Harley et al. 2016). However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations.
- Children’s autonomic nervous system reactivity and sleep problems: We assessed the cross-sectional relations among family demographics (education, marital status), adversities, routines, major life events (MLE)], and biological sensitivity as measured by autonomic nervous system (ANS) reactivity associated with parent-rated sleep problems when the children were 5 years old. The children completed a 15-min standardized protocol while continuous cardiac measures of the ANS [respiratory sinus arrhythmia (RSA), preejection period (PEP)] were collected during resting and four challenge conditions. Reactivity was defined as the mean of the responses to the four challenge conditions minus the first resting condition. Logistic regression models showed there were significant main effects for children living in families with fewer daily routines having more sleep problems than for children living in families with daily routines. There were significant interactions for children with low PEP reactivity and for children with the reciprocal, low reactivity profiles who experienced major family life events in predicting children's sleep problems. Children who had a reciprocal, low reactivity ANS profile had more sleep problems if they also experienced MLE than children who experienced fewer MLE. These findings suggest that children who experience family adversities have different risks for developing sleep problems depending on their biological sensitivity (Alkon et al. 2017).
- Worry about deportation and cardiovascular disease risk factors among adult women: We estimated the associations between worry about deportation and clinically measured cardiovascular risk factors. In multivariable models, reporting a lot of worry about deportation was significantly associated with higher body mass index (BMI), an increased risk of obesity (relative to normal weight), larger waist circumference, and higher pulse pressure. Reporting moderate deportation worry was significantly associated with an increased risk of overweight (relative to normal weight) and higher systolic blood pressure. Significant associations between worry about deportation and higher BMI, waist circumference, and pulse pressure, respectively, held after correcting for multiple testing at p<0.05. Worry about deportation may be an important cardiovascular risk factor for ethnic minority populations in the U.S.
Journal Articles:
No journal articles submitted with this report: View all 148 publications for this subprojectSupplemental Keywords:
RFA, Scientific Discipline, Health, INTERNATIONAL COOPERATION, Health Risk Assessment, Biochemistry, Children's Health, Environmental Policy, Biology, farmworkers, pesticide exposure, flame retardants, PBDE, children's vulnerablity, neurochemical effects, harmful environmental agents, biological markers, agricultural communityProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834513 Center for Research on Early Childhood Exposure and Development in Puerto Rico Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834513C001 CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
R834513C002 Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
R834513C003 Epigenetics Project
R834513C004 Community Outreach and Translation Core
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- 2016 Progress Report
- 2015 Progress Report
- 2014 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
- 2010 Progress Report
- Original Abstract
76 journal articles for this subproject
Main Center: R834513
694 publications for this center
166 journal articles for this center