Prenatal toxic metal mixture exposure and newborn telomere length: Modification by maternal antioxidant intake.

BACKGROUND: Telomere length (TL) predicts the onset of cellular senescence and correlates with longevity and age-related disease risk. While telomeres erode throughout life, adults display fixed ranking and tracking of TL, supporting the importance of the early environment in determining inter-individual variability across the life course. Given their guanine-rich structure, telomeres are highly susceptible to oxidative stress (OS). We examined maternal metal exposure, which can induce OS, in relation to newborn TL. We also considered the modifying role of maternal antioxidant intake. METHODS: Analyses included 100 mother-newborn pairs enrolled in the Boston and New York City-based PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. We measured As, Ba, Cd, Ni, and Pb in maternal late-pregnancy urine by ICP-MS and quantified relative leukocyte TL (rLTL) in cord blood using qPCR. We used Weighted Quantile Sum (WQS) regression to estimate the metal mixture - rLTL association and conducted repeated holdout validation to improve the stability of estimates across data partitions. We examined models stratified by high (>median) versus low (≤median) maternal antioxidant intake, estimated from Block98 Food Frequency Questionnaires. We considered urinary creatinine, week of urine collection, maternal age, and race/ethnicity as covariates. RESULTS: In adjusted models, urinary metals were inversely associated with newborn rLTL (ßWQS = -0.50, 95% CI: -0.78, -0.21). The top metals contributing to the negative association included Ba (weight: 35.4%), Cd (24.5%) and Pb (26.9%). In models stratified by antioxidant intake, the significant inverse association between metals and rLTL remained only among mothers with low antioxidant intake (low: ßWQS = -0.92, 95% CI: -1.53, -0.30; high: ßWQS = -0.03, 95% CI: -0.58, 0.52). Results were similar in unadjusted models. CONCLUSIONS: Relative LTL was shorter among newborns of mothers with higher exposure to metals during pregnancy. Higher maternal antioxidant intake may mitigate the negative influence of metals on newborn rLTL.

Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven.

BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time. OBJECTIVES: To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures. METHODS: Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother's education, mother's IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique. RESULTS: Using repeated holdout validation, IQ scores were 1.9-points (CI = -3.6, -0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation. CONCLUSION: Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.

A longitudinal study of polychlorinated biphenyls and neuropsychological function among older adults from New York State.

BACKGROUND: Cross-sectional studies have linked greater polychlorinated biphenyl (PCB) exposure to adverse neuropsychological effects in older adults, including learning, memory, and depressive symptoms. However, no studies among older adults have evaluated the association over time. OBJECTIVES: To assess the effect of serum PCB levels on neuropsychological function over a 14-year period in a cohort of older men and women from a PCB-contaminated area of New York State. METHODS: In 2000-2002, we assessed serum PCB levels and neuropsychological function (including the California Verbal Learning Test Trial 1 (CVLTT1) for verbal memory and learning, and the Beck Depression Index (BDI) for depressive symptoms) in 253 men and women, ages 55-74 years. A total of 116 (46%) persons repeated the PCB and neuropsychological assessment 14 years later. To assess the association over time, we used generalized estimating equations with clustering variables time, total PCB (∑PCB), and ∑PCB × time, and adjusted for baseline age, sex, smoking, and total serum-lipids. For statistically significant ∑PCB × time interactions, we evaluated the association between PCBs and either verbal memory and learning or depressive symptoms while holding ∑PCB constant at the 10th and 90th percentiles to clarify the direction of the interaction. RESULTS: Over the study period, serum ∑PCB levels (wet-weight) declined by 22%, and were associated with different patterns of change over time for memory (∑PCB × Time ß = 0.08 p = 0.009) and depressive symptoms (∑PCB × Time ß = -0.16 p = 0.013). Specifically, verbal memory and learning decreased (ß = -0.08 p = 0.008) and depressive symptoms increased (ß = 0.17 p = 0.008) among persons with low exposure (∑PCB levels at the 10th percentile), while persons with high exposure (90th percentile) showed non-significant improvements. DISCUSSION: In this cohort, declining ∑PCB levels were likely due at least in part to low rates of local fish consumption in recent decades, given the ban since 1976. The decreased verbal memory and learning and increased depressive symptoms over time among persons with low serum ∑PCB levels is consistent with studies of normative aging. However, the small improvements in those outcomes among those with high serum ∑PCB levels was unexpected. Healthy survivor selection bias or uncontrolled confounding may explain this result. It may also indicate that the neurotoxic impacts of PCBs in older adults are not permanent, but future studies are needed to confirm this possibility.

Occupational exposure to perfluoroalkyl substances and serum levels of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in an aging population from upstate New York: a retrospective cohort study.

PURPOSE: Perfluoroalkyl substances (PFASs) are environmentally persistent amphiphilic compounds. Exposure to two PFASs, perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) is linked to specific occupations and industries. This study examines the contribution of past occupational PFAS exposure to serum PFOS and PFOA levels among 154 older adults in New York State. METHODS: Serum PFOS and PFOA levels were compared to data from the National Health and Nutrition Examination Survey (NHANES). Potential occupational exposure to any PFAS was determined from work histories, reviewed by an industrial hygienist, and assessed in relation to current serum PFOS and PFOA levels using exposure probability, duration and cumulative exposure. RESULTS: We observed 25% higher serum PFOS and 80% higher PFOA levels in study participants compared to NHANES. No participants reported PFAS chemical manufacturing work, but n = 68 reported work in occupations and industries known to use PFASs. We found that participants with high cumulative workplace exposure had 34% higher serum PFOS levels compared to participants without occupational exposure, adjusted for age, sex and income. Serum PFOS levels were 26% higher for participants with longer occupational exposure durations. The probability of occupational PFAS exposure metric was not associated with serum PFOS. Serum PFOA was not associated with any measure of occupational exposure. CONCLUSION: Occupational exposure may contribute to total PFOS body burden in this study population, even among workers not directly involved in manufacturing PFASs. PFAS exposure assessments should evaluate the workplace as a potential source, even when workplace exposures are assumed to be low or moderate.