Background/Aim: Phthalate exposures are ubiquitous in pregnant women and may be obesogenic. Although excess adolescent adiposity predicts obesity and cardiometabolic diseases during adulthood, few studies have examined associations between prenatal phthalate exposures and anthropometric outcomes during adolescence. We investigated the relationships between prenatal phthalate exposures and anthropometry at age 12 years.Methods: We used data from 219 mother-child pairs enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003-2006. We measured monobutyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and four metabolites of di-2-ethylhexyl phthalate (DEHP) in maternal urine samples collected at 16 and 26 weeks of pregnancy. At age 12 years, we measured child weight and height. We used multivariable linear regression to estimate covariate-adjusted associations of a 10-fold increase in average maternal urinary phthalate metabolite concentrations with age- and sex- standardized height, weight, and BMI z-scores. We assessed effect measure modification (EMM) by child sex using stratified models.Results: In adjusted analyses, maternal urinary phthalate metabolite concentrations were not associated with height, weight, or BMI z-scores in the overall sample. However, associations of MBzP concentrations with all anthropometry z-scores were modified by child sex, with lower z-scores among girls, but not boys. For example, a 10-fold increase in MBzP concentrations was associated with lower BMI z-scores in girls (β=-0.4; 95% CI: -0.9, 0.0) but not boys (β=0.2; 95% CI: -0.3, 0.7; EMM p-value=0.09). Additionally, a 10-fold increase in MiBP was associated with increased height z-scores among boys (β=0.7; 95% CI: 0.1, 1.3), but not girls (β=0.0; 95% CI: -0.6, 0.5; EMM p-value=0.09).Conclusions: In this prospective cohort study, higher prenatal phthalate exposures were not associated with adolescent anthropometry, but there may be sex-specific effects.

Background/Aim: Per- and polyfluoroalkyl substances (PFAS) exposures in pregnancy and childhood have been associated with lower sex hormones levels in children, but few prospective studies have estimated the effect of PFAS on secondary sex characteristics. We examined the associations of prenatal and peripubertal exposure to PFAS with sexual maturation. Methods: We used data from a prospective pregnancy and birth cohort study in Cincinnati, OH (the HOME Study, enrolled: 2003-2006). We quantified serum concentrations of four PFAS—perfluorooctane sulfonate, perfluorooctanoate (PFOA), perfluorononanoate, and perfluorohexane sulfonate—in mothers at ~16 weeks gestation and their children at age ~12 years (120 girls and 96 boys). At age ~12 years, we collected pubertal data by self-reported Tanner staging of pubic hair growth (boys and girls) and breast growth (girls), as well as age at menarche in girls. We estimated covariate-adjusted associations between PFAS and stages of breast and pubic hair growth (stage 1 to 5) using ordinal regression models. We evaluated age at menarche using Cox proportional-hazard models that account for censored data. Results: Mean age at menarche was 11.6 years; 82% and 97% of boys and girls, respectively, were stage 2+ for pubic hair development; and 96% of girls were stage 2+ for breast growth. We observed that higher peripubertal serum concentrations of all PFAS were associated with later puberty among girls. For example, one IQR increase in PFOA (3.5 ng/mL) was inversely associated with breast (OR=0.47, 95%CI:0.22-0.98) and pubic hair (OR=0.84, 95%CI:0.45-1.58) growth, and age at menarche (HR=0.66, 95%CI:0.37-1.18). We found no clear pattern in males or for prenatal concentrations. Conclusions: These data suggest that higher peripubertal PFAS concentrations may be associated with later pubertal development in girls, but not boys.

Background/Aim: Perfluoroalkyl substances (PFAS) may impair bone health via endocrine disruption and nuclear hormone receptor activation. Bone mineral accrual during adolescence is important for long-term bone health, but human studies of PFAS and bone mineral density are primarily in adults or use a cross-sectional study design. We estimated associations of gestational PFAS exposures with early adolescent areal bone mineral density (aBMD) in a prospective cohort study. Methods: We examined 225 pregnant mothers enrolled from 2003-2006 in Cincinnati, OH and their children in the HOME Study. We measured concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononaoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) in maternal serum collected at 16 weeks gestation. When children were 12 years old, we measured lean body mass and total body, spine, total hip, femoral neck, and distal forearm (1/3 radius) aBMD with dual x-ray absorptiometry and calculated height-, age-, sex-, and race-specific aBMD z-scores. Using linear regression, we estimated covariate-adjusted associations in aBMD z-scores per doubling of gestational PFAS concentrations overall and stratified by sex. We estimated the proportion of total effects that were mediated by lean mass using structural equation modeling. Results: In adjusted models, higher PFOA concentrations were associated with lower aBMD z-scores of the forearm (β: -0.28, 95% CI: -0.49, -0.08), total hip (β: -0.28, 95% CI: -0.54, -0.02), and spine (β: -0.34, 95% CI: -0.61, -0.06) in males but not females. Lean mass mediated 29-50% of these associations. Higher PFHxS and PFNA concentrations were associated with lower aBMD z-scores of the forearm (PFHxS β: -0.11, 95% CI: -0.23, 0.00; PFNA β: -0.14, 95% CI: -0.35, 0.06), with no modification by sex or mediation by lean mass. PFOS was not associated with aBMD measures in either sex. Conclusions: Gestational PFAS exposures may reduce bone accrual in early adolescence, possibly in a sex-dependent manner.

BACKGROUND AND AIM: Optimizing bone mineral density (BMD) in adolescence is critical for life-long bone health. Organophosphate esters (OPEs) are synthetic flame retardants and plasticizers that may have osteotoxic effects via endocrine disruption or nuclear receptor agonism. Animal studies suggest that gestation may be a critical period of susceptibility for the impact of OPEs on bone health, but human studies are lacking. We assessed the relation of maternal urinary OPE metabolite concentrations during pregnancy with early adolescent BMD in a prospective birth cohort study. METHODS: We used data from 223 mother-child dyads enrolled in the HOME Study from Cincinnati, OH area, 2003-2006. We measured bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in maternal urine collected at 16- and 26-weeks gestation, and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry in children at age 12 years and calculated height-, age-, sex-, and population ancestry-specific Z-scores for whole body (excluding head), total hip, femoral neck, distal radius, and ultradistal radius areal BMD (aBMD) and spine bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per 2-fold increase in maternal urinary OPE concentrations and assessed effect measure modification by child sex. RESULTS:In adjusted analyses, BDCIPP concentrations were positively associated with aBMD and BMAD Z-scores at most skeletal sites. Z-score differences were between 0.11 and 0.15 and greatest for total hip (β = 0.15, 95% CI: 0.02, 0.29). Associations of DPHP with femoral neck and total hip aBMD differed by child sex. Associations among males were null while DPHP concentrations were inversely associated with femoral neck (β = -0.15, 95% CI: -0.29, -0.02) and total hip (β = -0.15, 95% CI: -0.29, 0.00) aBMD Z-scores among females. CONCLUSIONS:Maternal OPE exposures during gestation may affect early adolescent BMD in a metabolite-, sex-, and bone site-specific manner. KEYWORDS: Chemical exposures, Children's environmental health, Endocrine disrupting chemicals

Background/Aim: Some epidemiological studies suggest that per- and polyfluoroalkyl substances (PFAS) exposure may increase adiposity and obesity risk in children. However, we are unaware of any studies extending these findings into adolescence or identifying potential periods of heightened susceptibility. Thus, we estimated associations of five repeated measures of pre- and postnatal PFAS exposure with body composition in adolescence.Methods: We studied 212 mother-offspring pairs from the HOME Study, a prospective pregnancy and birth cohort study that enrolled pregnant women in Cincinnati, OH from 2003-2006. We quantified serum perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) concentrations in mothers at ~16 weeks gestation and their children at birth and ages 3, 8, and 12 years. At 12 years, we assessed children's adiposity using anthropometry and dual X-ray absorptiometry (DXA). We used multiple informant models to estimate covariate-adjusted associations of ln-transformed PFAS with adiposity measures for each exposure period, and tested the difference in these associations.Results: Prenatal serum concentrations of all four PFAS were positively associated with body fat, but there was no clear pattern for postnatal PFAS exposures. For instance, each ln-transformed increase in prenatal PFOA and PFHxS was associated with higher android (PFOA: β=1.9%, 95%CI: 0.0, 3.8; PFHxS: β=2.0%, 95%CI: 0.2, 3.9) and visceral fat percent (PFOA: β=1.9%, 95%CI: -0.2, 3.9; PFHxS: β=2.4%, 95%CI: 0.5, 4.4). Associations were generally stronger for central adiposity measures compared to peripheral ones. In multipollutant models, prenatal PFOA and PFHxS were more strongly associated with body fat than PFOS and PFNA. We observed evidence suggesting that prenatal PFOA was more strongly associated with greater adiposity in girls, but not boys.Conclusions: Prenatal, but not postnatal, serum concentrations of PFAS, particularly PFOA and PFHxS, were positively associated with measures of central body fat in adolescence.

Background: Lead exposure is associated with behavioral problems in children, but the ages when children are most susceptible to lead toxicity are unclear. Our objective was to evaluate the association of repeated blood lead concentrations with parent-reported behaviors and identify periods of heightened susceptibility.Methods: Between 2003-2006, we recruited pregnant women (n=389) living in homes built pre-1978 from Cincinnati, Ohio (HOME Study) and followed their children until age 8 years. We quantified lead in whole blood samples collected from children at ages 1, 2, 3, 4, 5, and 8 years. We assessed parent-reported child behavior using the Behavioral Assessment System for Children-2 (BASC-2) when children were ages 2, 3, 4, 5, and 8 years. Using linear regression with generalized estimating equations adjusted for covariates, we estimated associations of time-varying blood lead concentrations (ln-transformed, g/L) with behavioral profiles using the BASC-2 composite scales. We used multiple informant models to assess heterogeneity in these associations across exposure periods (n=241).Results: The median blood lead concentration peaked at 15 g/L around age 2 years (25th, 75th=10, 22 g/L) and gradually decreased to 6 g/L around age 8 years (25th, 75th=4, 9) g/L). Higher time-varying blood lead concentrations were associated with more externalizing problems (β:1.8-point; 95% CI= 0.3, 3.2). The association between blood lead levels and externalizing problems varied by exposure timing (lead x period interaction p-value=0.11), with heightened susceptibility around ages 3 (β:2.1-point; 95% CI= 0.6, 3.6) and 8 (β:3.5-point; 95% CI= 1.2, 5.7) years compared with other ages. Conclusion: Children with higher blood lead levels had more parent-reported hyperactive and aggressive behaviors. Future research could investigate if the periods of heightened susceptibility around ages 3 and 8 years are due to unique neurodevelopmental processes.

Background/Aim: Gestational exposure to perfluoroalkyl substances (PFAS), a class of ubiquitous and persistent endocrine disrupting chemicals, is associated with increased risk of obesity and cardiometabolic disorders in children. However, it is unclear if PFAS exposure is associated with childhood adiposity trajectories. We examined if prenatal PFAS exposure was associated with children's body mass index (BMI) trajectories from 4 weeks to 12 years of age.Methods: In 295 mother-child pairs from Cincinnati, OH (enrolled 2003-2006), we measured perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid, perfluorononaoic acid, and perfluorohexanesulfonic acid concentrations in maternal serum collected at 16-weeks gestation. At ages 4 weeks and 1, 2, 3, 4, 5, 8, and 12 years, we measured weight and length/height and calculated child BMI (1,827 repeated measures). Using linear mixed models and splines to account for repeated BMI measures and non-linear BMI patterns, respectively, we estimated BMI trajectories as a function of child age for PFAS terciles, adjusting for covariates.Results: BMI trajectories varied by prenatal PFOA in a non-monotonic fashion. Compared with children in the 1st PFOA tercile, children in the 2nd tercile had lower BMI at age 4 weeks, an earlier adiposity nadir (-0.5 years, 95% CI:-1.1, 0.1), and higher BMI at age 12 years (2.2 kg/m2, 95% CI:1.0, 3.4). In contrast, children in the 3rd tercile had on average 0.3 to 0.5 kg/m2 lower BMI values in the first five years of life, accelerated BMI gains between 8 and 12 years, and an earlier adiposity nadir (-0.3 years, 95% CI:-0.3, 0.0). We observed similar patterns for perfluorononaoic acid, but not other PFAS.Conclusion: These results suggest that higher gestational PFOA exposure is associated with BMI patterns in children that have been linked to later life obesity and cardiometabolic disease.

Background/Aim: Bisphenol-A (BPA) is a suspected endocrine disrupting compound (EDC) that may adversely affect human health. In rodent studies, prenatal BPA exposure alters maternal behavior, including reduced caregiving behavior towards their pups. These rodent behaviors may be correlates of maternal postpartum depressive symptoms that include feeling withdrawn, numb/disconnected from their offspring, or in doubt of their caregiving ability.Methods: We analyzed data from the Health Outcomes and Measures of the Environment (HOME) Study (n=346), a cohort of pregnant women and their children in Cincinnati, Ohio, enrolled between March 2003 and January 2006. We measured BPA concentrations in urine samples collected at ~16 and 26 weeks gestation. Mothers self-reported depressive symptoms at approximately four weeks post-partum using the Beck Depression Inventory-II (BDI-II). Using linear and logistic regression, we estimated changes in continuous and categorical (>mild vs. minimal symptoms) BDI-II scores, respectively, per interquartile range (IQR) increase in log10-transformed urinary BPA concentrations, adjusting for sociodemographic and perinatal factors.Results: The mean BDI-II score was 8.3 (25th and 75th percentiles: 5, 11). A total of 25 (7.2%), 13 (3.8%), and 6 (1.7%) women reported mild (scores: 14-19), moderate (scores: 20-28), and severe (scores: 29-63) depressive symptoms, respectively. Each IQR increase in log10-transformed urinary BPA concentration was associated with a 0.85-point increase in BDI-II score (95% CI: 0.2, 1.6). In addition, each IQR increase in BPA concentrations was associated with a 50% increased odds of having > minimal depressive symptoms (95% CI: 1.0, 2.2).Conclusion: Higher maternal urinary BPA concentrations during pregnancy were associated with more postpartum depressive symptoms at four weeks among mothers in this study.

PDS 73: Neurological effects, Johan Friso Foyer, Floor 1, August 26, 2019, 10:30 AM - 12:00 PM Background/Aim: Phthalate exposures may adversely affect child behavior via hormonal disruption. Because few studies have examined the impact of both gestational and childhood phthalate exposure on behavior, we estimated these associations. Methods: Using data from 228 mother-child pairs in the HOME Study (Cincinnati, Ohio), we quantified concentrations of 11 phthalate metabolites in urine samples collected twice during pregnancy and 6 times during childhood (ages 1-8 years). We assessed children's behaviors at age 8-years via parent report using the Behavior Assessment System for Children-2; higher scores indicate more problem behaviors. We first estimated associations between urinary phthalate metabolite concentrations at each visit and behavior, testing for differences in associations across visits using multiple informant models. Then, we estimated associations of average creatinine-standardized phthalate metabolite concentrations during pregnancy and childhood separately with behavior using linear regression. Finally, we quantified the cumulative association between childhood phthalate metabolite concentrations and behavior using weighted quantile sum regression. We adjusted for demographic, perinatal, and child factors. Results: Phthalate-behavior associations did not differ across visits; thus we report associations using average pregnancy or childhood phthalate metabolite concentrations. Gestational mono(3-carboxypropyl) phthalate and monobenzyl phthalate (MBzP) concentrations were positively associated with internalizing and externalizing problems scores, respectively. Childhood sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), MBzP, and mono-n-butyl phthalate (MnBP) concentrations were positively associated with externalizing scores. For example, each 1-standard deviation increase in childhood MBzP was associated with a 1.8-point increase in externalizing scores (95%CI=0.6, 3.1). Childhood ΣDEHP, MBzP, MnBP, and monocarboxynonyl phthalate were both individually and cumulatively associated with higher behavioral symptom index scores (weighted phthalate index β=1.1, 95%CI=0.1, 2.0). Conclusions: In this cohort, urinary concentrations of several phthalate metabolites during pregnancy or childhood were individually or cumulatively associated with higher behavior problem scores. We did not identify specific periods of heightened susceptibility during pregnancy or childhood. Maternal Exposure to High Magnetic Field Non-Ionizing Radiation During Pregnancy and the Risk of Headaches and Migraines in Offspring:

PDS 62: Chemicals and metals: exposure and biomarkers, Johan Friso Foyer, Floor 1, August 28, 2019, 10:30 AM - 12:00 PM Background: Polybrominated diphenyl ethers, suspected endocrine disruptors, have been replaced by organophosphate (OPFR) and novel brominated flame retardants (NBFR). OPFRs and NBFRs readily migrate from consumer products, including furniture and electronics, into dust where humans are exposed via accidental ingestion and inhalation. Toxicological studies have found potential carcinogenicity, endocrine disruption, and neurobehavioral alterations from these alternative flame retardants. However, no comprehensive assessments of exposure to OPFRs and NBFRs have been completed in a longitudinal cohort. Methods: We quantified concentrations of OPFRs and NBFRs in house dust samples (n=317) collected from pregnant women (~20 weeks) enrolled in the Health Outcomes and Measures of the Environment (HOME) Study in Cincinnati, Ohio (2003-2006). We used multiple regression modeling to identify personal characteristics that were associated with concentrations of individual chemicals and summary concentrations for each class. Finally, we estimated personal daily dust exposure for each participant based on dust concentration and cross-sectional weight data. Results: Tris(1-chloro-2-propyl)phosphate (TCIPP) (median: 1860 ng/g, range: 70.1-166,000 ng/g), tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) (median: 1860 ng/g, range: 55.2-228,000 ng/g), triphenyl phosphate (TPHP) (median: 995 ng/g, range: 34.1-62,100 ng/g), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) (median: 45.8 ng/g, range: 2.82-7,800 ng/g), and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) (median: 115 ng/g, range 2.17-13,600 ng/g) were all detected in over 90% of dust samples; tris(2-chloroethyl)phosphate (TCEP) (median: 759.4 ng/g, range: 56.8-160,000 ng/g) was detected in 80.1% of samples. Concentrations of individual chemicals, ∑OPFRs, and ∑NBFRs were associated with the number of people living in the home, race, education, floor type, and visible cleanliness of the room. Daily exposure to ∑OPFRs from dust was 2.1 ng/kg/day based on average dust ingestion and 6.3 ng/kg/day among women in the 95th percentile of dust ingestion. Conclusions: This study shows that OPFRs and NBFRs are ubiquitous in childbearing women's house dust, and justifies more research on the consequences of exposure in these concentration ranges.

TPS 771: Diet and lifestyle, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background/Aim: Maternal nutrition during gestation may modify the effect of toxicants on child neurodevelopment. Caffeine, most notable for its stimulation of the central nervous system, may affect offspring neurodevelopment. However, little is known about the relationship between gestational caffeine intake and autistic behaviors. We aimed to assess the relation between daily maternal caffeine intake and children's behavior traits associated with Autism Spectrum Disorders (ASD), measured by the Social Responsiveness Scale (SRS). Methods: We harmonized data from two pregnancy cohorts, the Health Outcomes and Measures of the Environment (HOME) (n= 269), a general population cohort, and Early Autism Risk Longitudinal Investigation (EARLI) (n=120), an enriched-risk autism cohort of mothers who previously had child with autism. Caffeine-containing food and beverage intake was assessed twice during pregnancy via maternal report. Parent-reported SRS scores were ascertained when children were ages 3-8 years, with higher scores indicating greater ASD severity. We estimated changes in continuous SRS scores per interquartile range increase in maternal caffeine intake, adjusting for sociodemographic and perinatal factors. Results: Median maternal caffeine intake during pregnancy was 18 mg/day (25th and 75th quartiles: 44, 56) in the pooled and individual cohorts (HOME 25th, 75th percentile: 44, 56; EARLI 25th, 75th percentile: 43, 55). In the pooled sample there was a positive association between caffeine intake and SRS scores (β: 1.1; 95%CI: 0.5, 2.2). However, the association was significantly different in each cohort (cohort x caffeine interaction p-value<0.05), where increasing caffeine intake was associated with increased SRS scores in EARLI (β: 2.7; 95%CI: 1.2, 4.2), but not in HOME (β: 0.3; 95%CI: -0.8, 1.3). Conclusion: Higher levels of maternal caffeine intake during pregnancy were associated with increases in ASD-related traits among children in EARLI, but not in HOME. We speculate differences between these two cohorts could be due to underlying genetic susceptibilities.

PDS 62: Chemicals and metals: exposure and biomarkers, Johan Friso Foyer, Floor 1, August 28, 2019, 10:30 AM - 12:00 PM Background: Exclusive breastfeeding is the recommended practice for the first 6 months following birth. Previous studies have detected phthalates and phenols in breast milk, but the contribution of breastfeeding to an infant's exposure to these chemicals is unknown. We hypothesized that breastfed children would have higher urinary phthalate metabolite and phenol concentrations compared with non-breastfed children. Methods: We used data from 295 mother-child pairs in the HOME Study (Cincinnati, Ohio, enrolled: 2003-2006). Research assistants assessed breastfeeding duration via maternal report when infants were approximately 12 months old. We also quantified concentrations of eight phthalate metabolites and three phenols (bisphenol A, triclosan, and benzophenone-3) in infants' urine collected at the same time. We estimated geometric mean (GM) phthalate metabolite and phenol concentrations by breastfeeding status, after adjusting for sociodemographic and perinatal factors, as well as urinary creatinine. Results: Eighty-two (28%) infants were breastfeeding at age 12 months. After adjusting for covariates, GM phthalate metabolite and phenol concentrations were 4-25% higher in children who were breastfed at 12 months than those who were not being breastfed. However, the 95% CIs of these estimates included the null and were imprecise. For example, urinary concentrations of bisphenol A and di-2-ethylhexyl phthalate metabolites were 13% (95% CI: -12, 46) and 4% (95% CI: -18, 31) higher, respectively, in breastfed children compared to non-breastfed children. Conclusion: In this cohort, we found little evidence to suggest that breastfeeding is a major source of exposure to phthalates and phenols in nursing infants. Future studies could consider examining whether plastic feeding bottles or pumped milk are potential sources of phthalate and phenol exposures among infants.