Associations of per- and polyfluoroalkyl substances with maternal metabolic and inflammatory biomarkers in early-to-mid-pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy. METHODS: Pregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation. RESULTS: In linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-α and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with -31.3% lower insulin (95%CI: -45.8, -12.9), -31.9% lower HOMA-IR (95%CI: -46.4, -13.4), and -9.4% lower leptin (95%CI: -17.3, -0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses. IMPLICATIONS: Individual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings.

Urinary oxidative stress biomarkers are associated with preterm birth: an Environmental Influences on Child Health Outcomes program study.

BACKGROUND: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States. OBJECTIVE: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin. STUDY DESIGN: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models. RESULTS: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis. CONCLUSION: Here, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.

Predictors of Water Lead Levels in Drinking Water of Homes With Domestic Wells in 3 Illinois Counties.

CONTEXT: Millions of US homes receive water from private wells, which are not required to be tested for lead (Pb). An approach to prioritizing high-risk homes for water lead level (WLL) testing may help focus outreach and screening efforts, while reducing the testing of homes at low risk. OBJECTIVE: To (1) characterize distribution of WLLs and corrosivity in tap water of homes with private residential wells, and (2) develop and evaluate a screening strategy for predicting Pb detection within a home. DESIGN: Cross-sectional. SETTING: Three Illinois counties: Kane (northern), Peoria (central), and Jackson (southern). PARTICIPANTS: 151 private well users from 3 Illinois counties. INTERVENTION: Water samples were analyzed for WLL and corrosivity. MAIN OUTCOME MEASURES: (1) WLL and corrosivity, and (2) the sensitivity, specificity, and predictive value of a strategy for prioritizing homes for WLL testing. RESULTS: Pb was detected (>0.76 ppb) in tap water of 48.3% homes, and 3.3% exceeded 15 ppb, the US Environmental Protection Agency action level for community water systems. Compared with homes built in/after 1987 with relatively low corrosivity, older homes with more corrosive water were far more likely to contain measurable Pb (odds ratio = 11.07; 95% confidence interval, 3.47-35.31). The strategy for screening homes with private wells for WLL had a sensitivity of 88%, specificity of 42%, positive predictive value of 58%, and negative predictive value of 80%. CONCLUSIONS: Pb in residential well water is widespread. The screening strategy for prioritizing homes with private wells for WLL testing is greater than 85% sensitive.

The relationship of prenatal acetaminophen exposure and attention-related behavior in early childhood.

Acetaminophen is currently the only analgesic considered safe for use throughout pregnancy, but recent studies indicate that prenatal exposure to acetaminophen may be related to poorer neurodevelopmental outcomes. Multiple studies have suggested that it may be associated with attention problems, but few have examined this association by trimester of exposure. The Illinois Kids Development Study is a prospective birth cohort located in east-central Illinois. Exposure data were collected between December 2013 and March 2020, and 535 newborns were enrolled during that period. Mothers reported the number of times they took acetaminophen at six time points across pregnancy. When children were 2, 3, and 4 years of age, caregivers completed the Child Behavior Checklist for ages 1.5-5 years (CBCL). Associations of acetaminophen use during pregnancy with scores on the Attention Problems and ADHD Problems syndrome scales, the Internalizing and Externalizing Behavior composite scales, and the Total Problems score were evaluated. Higher acetaminophen exposure during the second trimester of fetal development was associated with higher Attention Problems, ADHD Problems, Externalizing Behavior, and Total Problems scores at ages 2 and 3. Higher second trimester exposure was only associated with higher Externalizing Behavior and Total Problems scores at 4 years. Higher cumulative exposure across pregnancy was associated with higher Attention Problems and ADHD Problems scores at ages 2 and 3. Findings suggest that prenatal acetaminophen exposure, especially during the second trimester, may be related to problems with attention in early childhood.

Repeated home drinking water sampling to improve detection of particulate lead spikes: a simulation study.

BACKGROUND: Lead can be present in drinking water in soluble and particulate forms. The intermittent release of lead particulates in drinking water can produce highly variable water lead levels (WLLs) in individual homes, a health concern because both particulate and soluble lead are bioavailable. More frequent water sampling would increase the likelihood of identifying sporadic lead "spikes," though little information is available to aid in estimating how many samples are needed to achieve a given degree of sensitivity to spike detection. OBJECTIVE: To estimate the number of rounds of tap water sampling needed to determine with a given level of confidence that an individual household is at low risk for the intermittent release of lead particulates. METHODS: We simulated WLLs for 100,000 homes on 15 rounds of sampling under a variety of assumptions about lead spike release. A Markovian structure was used to describe WLLs for individual homes on subsequent rounds of sampling given a set of transitional probabilities, in which homes with higher WLLs at baseline were more likely to exhibit a spike on repeated sampling. RESULTS: Assuming 2% of homes had a spike on the first round of sampling and a mid-range estimate of transitional probabilities, the initial round of sampling had a 6.4% sensitivity to detect a spike. Seven rounds of sampling would be needed to increase the sensitivity to 50%, which would leave unrecognized the more than 15,000 homes that intermittently exhibit spikes. SIGNIFICANCE: For assessing household risk for lead exposure through drinking water, multiple rounds of water sampling are needed to detect the infrequent but high spikes in WLLs due to particulate release. Water sampling procedures for assessment of lead exposure in individual homes should be modified to account for the infrequent but high spikes in WLL. IMPACT: It has been known for decades that intermittent "spikes" in water lead occur due to the sporadic release of lead particulates. However, conventional water sampling strategies do not account for these infrequent but hazardous events. This research suggests that current approaches to sampling tap water for lead testing identify only a small fraction of homes in which particulate spikes occur, and that sampling procedures should be changed substantially to increase the probability of identifying the hazard of particulate lead release into drinking water.

IEUBK Modeling of Children's Blood Lead Levels in Homes Served by Private Domestic Wells in Three Illinois Counties.

Lead is known to impair neurocognitive development in children. Drinking water is routinely monitored for lead content in municipal systems, but private well owners are not required to test for lead. The lack of testing poses a risk of lead exposure and resulting health effects to rural children. In three Illinois counties, we conducted a cross-sectional study (n = 151 homes) examining water lead levels (WLLs), water consumption, and water treatment status to assess risk of lead exposure among residents using private water wells. Since blood lead levels (BLLs) were not available, EPA's Integrated Exposure Uptake Biokinetic (IEUBK) modeling was used to estimate the incremental contribution of WLL to BLL, holding all other sources of lead at their default values. Nearly half (48.3%) of stagnant water samples contained measurable lead ranging from 0.79 to 76.2 µg/L (median= 0.537 µg/L). IEUBK modeling showed BLLs rose from 0.3 to 0.4 µg/dL when WLLs rose from 0.54 µg/L (the tenth percentile) to 4.88 µg/L (the 90th percentile). Based on IEUBK modeling, 18% of children with a WLL at the 10th percentile would have a BLL above 3.5 µg/dL compared to 27.4% of those with a WLL at the 90th percentile. These findings suggest that the consumption of unfiltered well water likely results in increased blood lead levels in children.

Associations of prenatal phthalate exposure with neurobehavioral outcomes in 4.5- and 7.5-month-old infants.

Phthalates are ubiquitous endocrine-disrupting chemicals, and research indicates that prenatal exposure to some phthalates may affect neurodevelopment. In a prospective birth cohort study, five first-morning urine samples collected across pregnancy were pooled and the following phthalate biomarkers assessed: sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of diisononyl phthalate metabolites (ΣDINP), sum of dibutyl phthalate metabolites (ΣDBP), sum of anti-androgenic metabolites (ΣAA), monoethyl phthalate (MEP), and sum of all phthalate metabolites (ΣAll). The Ages & Stages Questionnaires® (ASQ), a standardized parent-reported, age-adapted screening tool, measured communication, personal-social, problem solving, and motor domains in infants at 4.5 and 7.5 months (n = 123). Adjusting for maternal age, annual household income, gestational age at birth, infant age at assessment, and sex, repeated-measures generalized linear regression models were used to examine associations between prenatal phthalate urine biomarker concentrations and domain scores (assuming a Poisson distribution). Beta estimates were exponentiated back to the domain scale for ease of interpretation. Mothers were mostly white and college-educated, and most reported an annual household income of ≥$60,000. Associations of phthalate concentrations with ASQ outcomes are presented as follows: (1) anti-androgenic phthalate metabolites (ΣDEHP, ΣDINP, ΣDBP, and ΣAA), (2) MEP, which is not anti-androgenic, and (3) ΣAll. Overall, anti-androgenic phthalates were associated with higher (i.e., better) scores. However, there were exceptions, including the finding that a one-unit increase in ΣDBP was associated with a 12% increase in problem solving scores in 4.5-month-old females (ß = 1.12; 95% CI: 0.99, 1.28; p = 0.067) but a 85% decrease for 7.5-month-old females (ß = 0.54; 95% CI: 0.3, 0.99; p = 0.047). In contrast, MEP was associated with poorer scores on several outcomes. Sex- and timepoint-specific estimates demonstrated a one-unit increase in MEP was associated with: a 52% decrease in personal-social scores in 7.5-month-old males (ß = 0.66; 95% CI: 0.46, 0.95; p = 0.02), a 39% decrease in fine motor scores in 7.5-month-old males (ß = 0.72; 95% CI: 0.52, 0.98; p = 0.035), and a 6% decrease in fine motor scores in 4.5-month-old females (ß = 0.94; 95% CI: 0.88, 0.99; p = 0.03). A one-unit increase in ΣAll was associated with a 4% increase in personal-social scores in 4.5-month-old males (ß = 1.04; 95% CI: 0.99, 1.1; p = 0.08) but a 17% decrease in 7.5-month-old males (ß = 0.85; 95% CI: 0.73, 0.99; p = 0.03). These data suggest age- and sex-specific associations of prenatal phthalates with infant neurobehavior. The current findings should be confirmed by longitudinal studies with larger sample sizes.

Prenatal PFAS and psychosocial stress exposures in relation to fetal growth in two pregnancy cohorts: Applying environmental mixture methods to chemical and non-chemical stressors.

BACKGROUND: Prenatal exposure to individual per­ and poly­fluoroalkyl substances (PFAS) and psychosocial stressors have been associated with reductions in fetal growth. Studies suggest cumulative or joint effects of chemical and non-chemical stressors on fetal growth. However, few studies have examined PFAS and non-chemical stressors together as a mixture, which better reflects real life exposure patterns. We examined joint associations between PFAS, perceived stress, and depression, and fetal growth using two approaches developed for exposure mixtures. METHODS: Pregnant participants were enrolled in the Chemicals in Our Bodies cohort and Illinois Kids Development Study, which together make up the ECHO.CA.IL cohort. Seven PFAS were previously measured in 2nd trimester maternal serum samples and were natural log transformed for analyses. Perceived stress and depression were assessed using self-reported validated questionnaires, which were converted to t-scores using validated methods. Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to assess joint associations between PFAS, perceived stress and depression t-scores and birthweight z-scores (N = 876). RESULTS: Individual PFAS, depression and perceived stress t-scores were negatively correlated with birthweight z-scores. Using quantile g-computation, a simultaneous one quartile increase in all PFAS, perceived stress and depression t-scores was associated with a slight reduction in birthweight z-scores (mean change per quartile increase = -0.09, 95% confidence interval = -0.21,0.03). BKMR similarly indicated that cumulative PFAS and stress t-scores were modestly associated with lower birthweight z-scores. Across both methods, the joint association appeared to be distributed across multiple exposures rather than due to a single exposure. CONCLUSIONS: Our study is one of the first to examine the joint effects of chemical and non-chemical stressors on fetal growth using mixture methods. We found that PFAS, perceived stress, and depression in combination were modestly associated were lower birthweight z-scores, which supports prior studies indicating that chemical and non-chemical stressors are jointly associated with adverse health outcomes.

Associations of Maternal Stress, Prenatal Exposure to Per- and Polyfluoroalkyl Substances (PFAS), and Demographic Risk Factors with Birth Outcomes and Offspring Neurodevelopment: An Overview of the ECHO.CA.IL Prospective Birth Cohorts.

BACKGROUND: Infants whose mothers experience greater psychosocial stress and environmental chemical exposures during pregnancy may face greater rates of preterm birth, lower birth weight, and impaired neurodevelopment. METHODS: ECHO.CA.IL is composed of two cohorts, Chemicals in Our Bodies (CIOB; n = 822 pregnant women and n = 286 infants) and Illinois Kids Development Study (IKIDS; n = 565 mother-infant pairs), which recruit pregnant women from San Francisco, CA and Urbana-Champaign, IL, respectively. We examined associations between demographic characteristics and gestational age, birth weight z-scores, and cognition at 7.5 months across these two cohorts using linear models. We also examined differences in biomarkers of exposure to per- and polyfluoroalkyl substances (PFAS), measured in second-trimester serum, and psychosocial stressors by cohort and participant demographics. RESULTS: To date, these cohorts have recruited over 1300 pregnant women combined. IKIDS has mothers who are majority white (80%), whereas CIOB mothers are racially and ethnically diverse (38% white, 34% Hispanic, 17% Asian/Pacific Islander). Compared to CIOB, median levels of PFOS, a specific PFAS congener, are higher in IKIDS (2.45 ng/mL versus 1.94 ng/mL), while psychosocial stressors are higher among CIOB. Across both cohorts, women who were non-white and single had lower birth weight z-scores relative to white women and married women, respectively. Demographic characteristics are not associated with cognitive outcomes at 7.5 months. CONCLUSIONS: This profile of the ECHO.CA.IL cohort found that mothers and their infants who vary in terms of socioeconomic status, race/ethnicity, and geographic location are similar in many of our measures of exposures and cognitive outcomes. Similar to past work, we found that non-white and single women had lower birth weight infants than white and married women. We also found differences in levels of PFOS and psychosocial stressors based on geographic location.

Observations of marketing on food packaging targeted to youth in retail food stores.

There is growing evidence that exposure to food marketing influences dietary preferences among youth. Few studies exploring this association, however, have focused on the retail food store environment where families negotiate the influence of food and beverage marketing on purchasing practices. Consequently, we sought to examine: (i) the extent to which foods marketed on the internet and television to youth are also available and marketed in retail food stores, and (ii) whether differences exist in the marketing practices across store types and by neighborhood racial composition. In 2008, a cross-sectional survey of 118 food stores was conducted in four Midwestern cities in the United States. Results showed that 82% of stores assessed carried items commonly marketed to youth via television or the internet. The items most likely to have some type of marketing technique were noncarbonated drinks (97.7%), fruit and cereal bars (76.9%), and soda (62.2%). Grocery stores were significantly more likely than convenience stores to have marketing for breads and pastries (34.6% vs. 17.9%), breakfast cereals (52.0% vs. 22.9%), cookies and crackers (54.2% vs. 25.3%), dairy (70.8% vs. 42.7%), and ice cream (23.8% vs. 9.8%). Stores located in black neighborhoods were significantly more likely to have marketing, in comparison to white neighborhoods, for breads and pastries (35.7% vs. 17.1%), breakfast cereals (44.4% vs. 25.0%), and cookies and crackers (48.1% vs. 26.3%). Our results highlight the importance of examining food marketing techniques in the retail food store environment, where visual cues from television and the internet may be reinforced.