Racialized experience, biomarkers of lead exposure, and later-life cognition: a mediation analysis.

We evaluated the role of the neurotoxicant lead (Pb) in mediating racial disparities in later-life cognition in 1,085 non-Hispanic Black and 2,839 non-Hispanic white participants in NHANES (1999-2002, 2011-2014) 60+ years of age. We operationalized Black race as a marker for the experience of racialization and exposure to systemic racism. We estimated patella bone Pb via predictive models using blood Pb and demographics. Concurrent cognition (processing speed, sustained attention, working memory) was measured by the Digit Symbol Substitution Test (DSST) and a global measure combining four cognitive tests. To obtain the portion mediated, we used regression coefficients (race on Pb * Pb on cognitive score)/(race on cognitive score), adjusting for age, NHANES cycle, and sample weights. Other confounder adjustment (education, poverty income ratio, smoking) was limited to the mediator-outcome (i.e., Pb-cognition) pathway because these factors do not lie upstream of race and so cannot confound associations with race. Pb was estimated to mediate 0.6% of the association between race and global cognition, and 4% of the DSST. Our results suggest that later-life cognitive health disparities may be impacted by avoidable lead exposure driven by environmental injustice, noting that a large proportion of the pathway of systemic racism harming cognition remains.

Association between objective measures and parent-reported measures of child tobacco smoke exposure: A secondary data analysis of four trials.

INTRODUCTION: Tobacco smoke exposure (TSE) harms children and adults. Studies of childhood TSE exposure often relies on parental reports, but may benefit from objective measures. The objective of our study was to study the relationship between reported and objective measures of TSE. METHODS: We analyzed data from four intervention trials, conducted in clinical or community settings, to identify objective measures most closely associated with parent-reported measures and the optimal set of parent-reported measures for predicting objective measures. We also assessed whether there was a learning curve in reported exposure over time, and the importance of replicate biomarker measures. RESULTS: Correlations between objective and parent-reported measures of child TSE were modest at best, ranging from zero to 0.41. Serum cotinine and urinary cotinine were most strongly associated with parental reports. Parental questions most closely related to biomarkers were number of cigarettes and home smoking rules; together these formed the best set of predictive questions. No trial included all objective measures and all questions, precluding definitive statements about relative advantages. Within-subject repeatability of biomarker measures varied across studies, suggesting that direct pilot data are needed to assess the benefit of replicate measurements. CONCLUSIONS: Improvements in objective and parent-reported child exposure measurements are needed to accurately monitor child TSE, evaluate efforts to reduce such exposure, and better protect child health.

Maternal smoking during pregnancy and offspring intellectual disability: sibling analysis in an intergenerational Danish cohort.

BACKGROUND: Maternal smoking has known adverse effects on fetal development. However, research on the association between maternal smoking during pregnancy and offspring intellectual disability (ID) is limited, and whether any associations are due to a causal effect or residual confounding is unknown. METHOD: Cohort study of all Danish births between 1995 and 2012 (1 066 989 persons from 658 335 families after exclusions), with prospectively recorded data for cohort members, parents and siblings. We assessed the association between maternal smoking during pregnancy (18.6% exposed, collected during prenatal visits) and offspring ID (8051 cases, measured using ICD-10 diagnosis codes F70-F79) using logistic generalised estimating equation regression models. Models were adjusted for confounders including measures of socio-economic status and parental psychiatric diagnoses and were adjusted for family averaged exposure between full siblings. Adjustment for a family averaged exposure allows calculation of the within-family effect of smoking on child outcomes which is robust against confounders that are shared between siblings. RESULTS: We found increased odds of ID among those exposed to maternal smoking in pregnancy after confounder adjustment (OR 1.35, 95% CI 1.28-1.42) which attenuated to a null effect following adjustment for family averaged exposure (OR 0.91, 95% CI 0.78-1.06). CONCLUSIONS: Our findings are inconsistent with a causal effect of maternal smoking during pregnancy on offspring ID risk. By estimating a within-family effect, our results suggest that prior associations were the result of unmeasured genetic or environmental characteristics of families in which the mother smokes during pregnancy.

Associations Between Early Low-Level Tobacco Smoke Exposure and Executive Function at Age 8 Years.

OBJECTIVE: To investigate whether exposure to tobacco smoke during early brain development is linked with later problems in behavior and executive function. STUDY DESIGN: We studied 239 children in a prospective birth cohort. We measured tobacco exposures by caregiver report and serum cotinine 3 times during pregnancy and 4 times during childhood. We used linear regression to examine the association between prenatal and childhood serum cotinine concentrations and behavior (the Behavior Assessment System for Children-2) and executive function (the Behavior Rating Inventory of Executive Function) at age 8 years while adjusting for important covariates. RESULTS: Neither prenatal nor child serum cotinine were associated with behavior problems measured by the Behavior Assessment System for Children-2. On the Behavior Rating Inventory of Executive Function, prenatal and childhood exposure was associated with poorer task initiation scores (B = 0.44; 95% CI, 0.03-0.85 and B = 0.69, 95% CI, 0.06-1.32 respectively). Additionally, in a subset of 208 children with nonsmoking mothers, prenatal exposure was associated with task initiation scores (B = 1.17; 95% CI, 0.47-1.87) and additional components of the metacognition index (eg, working memory, B = 1.20; 95% CI, 0.34-2.06), but not components of the behavioral regulation index. CONCLUSIONS: Tobacco exposures during pregnancy (including low-level second-hand smoke) and childhood were associated with deficits in some domains of children's executive function, especially task initiation and metacognition. These results highlight that decreasing early exposure to tobacco smoke, even second-hand exposure, may support ideal brain functioning.

Familial confounding of the association between maternal smoking in pregnancy and autism spectrum disorder in offspring.

Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub-phenotypes, we conducted a whole-population cohort study in Denmark. We followed births 1991-2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012. Autism, with and without attention deficit hyperactivity disorder (ADHD) and with and without intellectual disability (ID) were based on ICD-8 and ICD-10 codes from Danish national health registers, including 3,319 autism + ADHD, 10,228 autism - no ADHD, 2,205 autism + ID, and 11,342 autism - no ID. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) between any maternal smoking (from birth records) and autism (or sub-phenotypes) using survival models with robust standard errors, stratifying by birth year and adjusting for child sex, parity, and parental age, education, income, and psychiatric history. To additionally address confounding using family designs, we constructed a maternal cluster model (adjusting for the smoking proportion within the family), and a stratified sibling model. Associations with maternal smoking and autism were elevated in conventional adjusted analyses (HR of 1.17 [1.13-1.22]) but attenuated in the maternal cluster (0.98 [0.88-1.09]) and sibling (0.86 [0.64-1.15]) models. Similarly, risks of autism sub-phenotypes with maternal smoking were attenuated in the family-based models. Together these results support that smoking in pregnancy is not linked with autism or select autism comorbid sub-phenotypes after accounting for familial confounding. Autism Res 2020, 13: 134-144. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Smoking during pregnancy has many harmful impacts, which may include harming the baby's developing brain. However, in a study of thousands of families in Denmark, it does not appear that smoking in pregnancy leads to autism or autism in combination with intellectual problems or attention deficits, once you account for the way smoking patterns and developmental disabilities run in families.

Early Life Exposure to Air Pollution and Autism Spectrum Disorder: Findings from a Multisite Case-Control Study.

BACKGROUND: Epidemiologic studies have reported associations between prenatal and early postnatal air pollution exposure and autism spectrum disorder (ASD); however, findings differ by pollutant and developmental window. OBJECTIVES: We examined associations between early life exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone in association with ASD across multiple US regions. METHODS: Our study participants included 674 children with confirmed ASD and 855 population controls from the Study to Explore Early Development, a multi-site case-control study of children born from 2003 to 2006 in the United States. We used a satellite-based model to assign air pollutant exposure averages during several critical periods of neurodevelopment: 3 months before pregnancy; each trimester of pregnancy; the entire pregnancy; and the first year of life. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for study site, maternal age, maternal education, maternal race/ethnicity, maternal smoking, and month and year of birth. RESULTS: The air pollution-ASD associations appeared to vary by exposure time period. Ozone exposure during the third trimester was associated with ASD, with an OR of 1.2 (95% CI: 1.1, 1.4) per 6.6 ppb increase in ozone. We additionally observed a positive association with PM2.5 exposure during the first year of life (OR = 1.3 [95% CI: 1.0, 1.6] per 1.6 µg/m increase in PM2.5). CONCLUSIONS: Our study corroborates previous findings of a positive association between early life air pollution exposure and ASD, and identifies a potential critical window of exposure during the late prenatal and early postnatal periods.

Environmental chemical exposures and autism spectrum disorders: a review of the epidemiological evidence.

In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms.

Maternal smoking during pregnancy and the prevalence of autism spectrum disorders, using data from the autism and developmental disabilities monitoring network.

BACKGROUND: Reported associations between gestational tobacco exposure and autism spectrum disorders (ASDs) have been inconsistent. OBJECTIVE: We estimated the association between maternal smoking during pregnancy and ASDs among children 8 years of age. METHODS: This population-based case-cohort study included 633,989 children, identified using publicly available birth certificate data, born in 1992, 1994, 1996, and 1998 from parts of 11 U.S. states subsequently under ASD surveillance. Of these children, 3,315 were identified as having an ASD by the active, records-based surveillance of the Autism and Developmental Disabilities Monitoring Network. We estimated prevalence ratios (PRs) of maternal smoking from birth certificate report and ASDs using logistic regression, adjusting for maternal education, race/ethnicity, marital status, and maternal age; separately examining higher- and lower-functioning case subgroups; and correcting for assumed under-ascertainment of autism by level of maternal education. RESULTS: About 13% of the source population and 11% of children with an ASD had a report of maternal smoking in pregnancy: adjusted PR (95% confidence interval) of 0.90 (0.80, 1.01). The association for the case subgroup autistic disorder (1,310 cases) was similar: 0.88 (0.72, 1.08), whereas that for ASD not otherwise specified (ASD-NOS) (375 cases) was positive, albeit including the null: 1.26 (0.91, 1.75). Unadjusted associations corrected for assumed under-ascertainment were 1.06 (0.98, 1.14) for all ASDs, 1.12 (0.97, 1.30) for autistic disorder, and 1.63 (1.30, 2.04) for ASD-NOS. CONCLUSIONS: After accounting for the potential of under-ascertainment bias, we found a null association between maternal smoking in pregnancy and ASDs, generally. The possibility of an association with a higher-functioning ASD subgroup was suggested, and warrants further study.

Variability and predictors of urinary bisphenol A concentrations during pregnancy.

BACKGROUND: Prenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy. OBJECTIVE: Our goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy. METHODS: We measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log10-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models. RESULTS: Geometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 µg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 µg/g) compared with those consuming no canned vegetables (GM = 1.6 µg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations. CONCLUSIONS: These results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures.

Determinants of serum cotinine and hair cotinine as biomarkers of childhood secondhand smoke exposure.

Understanding the determinants of childhood secondhand smoke (SHS) exposure is important in measuring and preventing exposure to this widespread environmental contaminant. We evaluated the ability of a broad set of factors to explain variability in serum cotinine, reflecting recent exposure, and hair cotinine, reflecting longer-term exposure. We included repeated measures from 223 elementary-school-age asthmatic children residing with a smoker. We used a manual model-building approach and likelihood ratio tests to select a model predicting each biomarker, and also compared the predictive ability of determinants using Akaike Information Criteria. Potential determinants included a comprehensive parent questionnaire, household nicotine, home ventilation characteristics, exposure in vehicles and others' homes, child demographics, and family social class. Variables in each of these categories remained in the final model for both serum (R(2) of 0.61) and hair cotinine (R(2) of 0.45). A comprehensive set of factors was required to best predict cotinine. Studies should use biomarkers for the best quantitative assessment of SHS exposure. Hair cotinine may be a problematic measure because it was highly influenced by racial differences that were unexplained by SHS exposure. When biospecimen collection is not possible, a household nicotine measurement is warranted. If only questionnaires are available, multiple questions are required to best characterize exposure, such as number of cigarettes, hours spent in a room with concurrent smoking, maternal smoking, and approximate home size.