Impact of Skin Care Products on Phthalates and Phthalate Replacements in Children: the ECHO-FGS.

BACKGROUND: Phthalates and their replacements have been implicated as developmental toxicants. Young children may be exposed to phthalates/replacements when using skin care products (SCPs). OBJECTIVES: Our objective is to assess the associations between use of SCPs and children's urinary phthalate/replacement metabolite concentrations. METHODS: Children (4-8 years old) from the Environmental Influences on Child Health Outcomes-Fetal Growth Study (ECHO-FGS) cohort provided spot urine samples from 2017 to 2019, and mothers were queried about children's SCP use in the past 24 h (n=906). Concentrations of 16 urinary phthalate/replacement metabolites were determined by liquid chromatography-tandem mass spectrometry (n=630). We used linear regression to estimate the child's use of different SCPs as individual predictors of urinary phthalate/replacement metabolites, adjusted for urinary specific gravity, age, sex assigned at birth, body mass index, and self-reported race/ethnic identity, as well as maternal education, and season of specimen collection. We created self-organizing maps (SOM) to group children into "exposure profiles" that reflect discovered patterns of use for multiple SCPs. RESULTS: Children had lotions applied (43.0%) frequently, but "2-in-1" hair-care products (7.5%), sunscreens (5.9%), and oils (4.3%) infrequently. Use of lotions was associated with 1.17-fold [95% confidence interval (CI): 1.00, 1.34] greater mono-benzyl phthalate and oils with 2.86-fold (95% CI: 1.89, 4.31) greater monoethyl phthalate (MEP), 1.43-fold (95% CI: 1.09, 1.90) greater monobutyl phthalate (MBP), and 1.40-fold (95% CI: 1.22, 1.61) greater low-molecular-weight phthalates (LMW). Use of 2-in-1 haircare products was associated with 0.84-fold (95% CI: 0.72, 0.97) and 0.78-fold (95% CI: 0.62, 0.98) lesser mono(3-carboxypropyl) phthalate (MCPP) and MBP, respectively. Child's race/ethnic identity modified the associations of lotions with LMW, oils with MEP and LMW, sunscreen with MCPP, ointments with MEP, and hair conditioner with MCPP. SOM identified four distinct SCP-use exposure scenarios (i.e., profiles) within our population that predicted 1.09-fold (95% CI: 1.03, 1.15) greater mono-carboxy isononyl phthalate, 1.31-fold (95% CI: 0.98, 1.77) greater mono-2-ethyl-5-hydroxyhexyl terephthalate, 1.13-fold (95% CI: 0.99, 1.29) greater monoethylhexyl phthalate, and 1.04-fold (95% CI: 1.00, 1.09) greater diethylhexyl phthalate. DISCUSSION: We found that reported SCP use was associated with urinary phthalate/replacement metabolites in young children. These results may inform policymakers, clinicians, and parents to help limit children's exposure to developmental toxicants. https://doi.org/10.1289/EHP13937.

Posttraumatic Stress Disorder Among Adults in Communities With Mass Violence Incidents.

Importance: Mass violence incidents (MVIs) are prevalent in the US and can have profound and long-lasting psychological consequences on direct survivors, but their outcomes among the broader communities where the MVI occurred are unknown. Objective: To investigate the prevalence of and factors associated with past-year and current posttraumatic stress disorder (PTSD) among adults in communities that experienced an MVI. Design, Setting, and Participants: This cross-sectional survey was completed between February and September 2020 with a household probability sample of adults from 6 communities that had experienced an MVI between 2015 and 2019: Dayton, Ohio; El Paso, Texas; Parkland, Florida; Pittsburgh, Pennsylvania; San Bernadino, California; and Virginia Beach, Virginia. Address-based sampling was used to identify randomly selected households, mail invitations, and select 1 adult per household to complete a self-administered paper or online survey. Data analysis was performed from September to November 2023. Main Outcomes and Measures: The primary outcome was presumptive diagnostic-level past-year PTSD and current (past month) PTSD determined using American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) PTSD criteria. Results: A total of 6867 adults aged 18 years or older accessed the website with a description of the study and consent materials. Of these, 5991 (87.2%) agreed to participate and completed the survey, 343 (6.3%) partially completed the survey, and 443 (6.5%) did not meet eligibility criteria or refused to participate. Most of the 5991 respondents were female (3825 individuals [53.5%]) and had a mean (SD) age of 45.56 (17.58) years. A total of 1261 of 5931 individuals (21.0%) reported high exposure to the MVI (either they or a close friend and/or family member was on site during the shooting). Nearly one-quarter (23.7%; 1417 of 5977 participants reporting PTSD) met presumptive DSM-5 diagnostic criteria for past-year PTSD, with 8.9% (530 participants) meeting the criteria for current PTSD. Regression analyses found that being female (odds ratio, 2.32; 95% CI, 2.01-2.68) and having a history of both physical or sexual assault and other potentially traumatic events (odds ratio, 9.68; 95% CI, 7.48-12.52) were associated with the greatest risk of past-year PTSD. Conclusions and Relevance: In this survey study of 5991 participants, presumptive PTSD was quite prevalent long after the MVI among adults in communities that have experienced an MVI, suggesting that MVIs have persistent and pervasive public health impacts on communities, particularly among those with prior exposure to physical or sexual assault and other potentially traumatic events. Focusing exclusively on direct exposure to MVIs is not sufficient. Incorporating these findings into screening should improve efforts to identify the individuals most in need of prevention or mental health service after MVIs.

Phthalate and phthalate replacement concentrations in relationship to adiposity in a multi-racial cohort of children.

BACKGROUND/OBJECTIVE: Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children. SUBJECTS/METHODS: A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI. RESULTS: All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [ß = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [ß = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [ß = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity. CONCLUSIONS: We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

OBJECTIVE: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. METHODS: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. RESULTS: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). CONCLUSION: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Glyphosate exposure and preterm birth: A nested case-control pilot study.

Preterm birth (PTB) is associated with a high risk of infant mortality and long-term adverse health effects. Glyphosate is a broad-spectrum herbicide applied in agricultural and non-agricultural settings. Studies suggested an association between maternal exposure to glyphosate and PTB among mostly racially homogenous populations, though results were inconsistent. The objective of this pilot study was to inform the design of a larger and more definitive study of glyphosate exposure and adverse birth outcomes in a racially-diverse population. Urine was obtained from 26 women with a PTB as cases and 26 women with a term birth as controls, from participants enrolled in a birth cohort in Charleston, South Carolina. We used binomial logistic regression to estimate associations between urinary glyphosate and the odds of PTB, and multinomial regression to estimate associations between maternal racial identity and urinary glyphosate among controls. Glyphosate was unrelated to PTB (odds ratio (OR) = 1.06, 95% CI: 0.61, 1.86). Women who identified as Black had greater odds (OR = 3.83, 95% CI: 0.13, 111.33) of having categorical "high" glyphosate (> 0.28 ng/mL) and lesser odds (OR = 0.79, 95% CI: 0.05, 12.21) of "low" glyphosate (< 0.03 ng/mL) relative to women who identified as white, suggesting a potential racial disparity, although the effect estimates were imprecise and included the null. Given concerns of potential reproductive toxicity of glyphosate, the results merit confirmation in a larger investigation to determine specific sources of glyphosate exposure, incorporating longitudinal urinary glyphosate measures during pregnancy and a comprehensive measure of diet.

Prevalence of Depression and Posttraumatic Stress Disorder in Flint, Michigan, 5 Years After the Onset of the Water Crisis.

Importance: Environmental disasters, such as the Flint, Michigan, water crisis, are potentially traumatic events (PTEs) that may precipitate long-term psychiatric disorders. The water crisis was associated with acute elevations in mental health problems in the Flint community, but long-term psychiatric sequelae have not yet been evaluated using standardized diagnostic measures. Objective: To investigate the prevalence of and factors associated with current presumptive diagnostic-level major depression and posttraumatic stress disorder (PTSD) among Flint residents 5 years after the onset of the crisis. Design, Setting, and Participants: In this cross-sectional study, a household probability sample of 1970 adults living in Flint, Michigan, during the crisis were surveyed about their crisis experiences, their psychological symptoms 5 years later, and their access to and use of mental health services in the intervening years. Analyses were weighted to produce population-representative estimates. Main Outcomes and Measures: Presumptive Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnostic-level past-year major depression and PTSD. Results: Among 1970 respondents, 1061 of 1946 reporting sex (54.5%) were women; 1043 of 1951 reporting race (53.5%) were Black or African American and 829 (42.5%) were White; and 1895 of 1946 reporting ethnicity (97.4%) were non-Hispanic. Overall, 435 (22.1%) met DSM-5 criteria for presumptive past-year depression, 480 (24.4%) for presumptive past-year PTSD, and 276 (14.0%) for both disorders. Residents who believed that their or their family's health was harmed by contaminated water (eg, risk ratio [RR] for depression: 2.23; 95% CI, 1.80-2.76), who had low confidence in public-official information (eg, RR for PTSD, 1.44; 95% CI, 1.16-1.78), who had previous exposure to PTEs (eg, RR for both disorders: 5.06; 95% CI, 2.99-8.58), or who reported low social support (eg, RR for PTSD, 2.58; 95% CI, 1.94-3.43) had significantly higher risk for depression, PTSD, and comorbidity. PTEs involving prior physical or sexual assault were especially potent risk factors (eg, both disorders: RR, 7.30; 95% CI, 4.30-12.42). Only 685 respondents (34.8%) were ever offered mental health services to assist with water-crisis-related psychiatric symptoms; most (543 [79.3%]) who were offered services utilized them. Conclusions and Relevance: In this cross-sectional study of psychiatric disorder in Flint, Michigan, presumptive depression and PTSD were highly prevalent 5 years after the onset of the water crisis. These findings suggest that public-works environmental disasters have large-scale, long-term psychological sequelae. The Flint community may require expanded mental health services to meet continued psychiatric need. National disaster preparedness and response programs should consider psychiatric outcomes.

Association of Accelerometer-Measured Sedentary Time and Physical Activity With Risk of Stroke Among US Adults.

Importance: The amount and intensity of physical activity required to prevent stroke are yet to be fully determined because of previous reliance on self-reporting measures. Furthermore, the association between objectively measured time spent being sedentary as an independent risk factor for stroke is unknown. Objective: To investigate the associations of accelerometer-measured sedentary time and physical activity of varying intensity and duration with the risk of incident stroke. Design, Setting, and Participants: This cohort study involved participants who were enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from February 5, 2003, to October 30, 2007. Accelerometer data were collected from 7607 Black and White adults 45 years or older in the contiguous US between May 12, 2009, and January 5, 2013. Data on other races and ethnicities were not collected for scientific and clinical reasons. By design, Black adults and residents of the southeastern US stroke belt and stroke buckle were oversampled. Data were analyzed from May 5, 2020, to November 11, 2021. Exposures: Sedentary time, light-intensity physical activity (LIPA), and moderate- to vigorous-intensity physical activity (MVPA) were measured using a hip-mounted accelerometer worn for 7 consecutive days and stratified by tertile for the analyses. Main Outcomes and Measures: Incident stroke. Results: Among 7607 participants, the mean (SD) age was 63.4 (8.5) years; 4145 participants (54.5%) were female, 2407 (31.6%) were Black, and 5200 (68.4%) were White. A total of 2523 participants (33.2%) resided in the stroke belt, and 1638 (21.5%) resided in the stroke buckle. Over a mean (SD) of 7.4 (2.5) years of follow-up, 286 incident stroke cases (244 ischemic [85.3%]) occurred. The fully adjusted hazard ratios (HRs) for incident stroke in the highest tertile compared with the lowest tertile were 0.74 (95% CI, 0.53-1.04; P = .08) for LIPA and 0.57 (95% CI, 0.38-0.84; P = .004) for MVPA. Higher sedentary time was associated with a 44% greater risk of incident stroke (HR, 1.44; 95% CI, 0.99-2.07; P = .04). When comparing the highest with the lowest tertile, mean sedentary bout duration was associated with a significantly greater risk of incident stroke (HR, 1.53; 95% CI, 1.10-2.12; P = .008). After adjustment for sedentary time, the highest tertile of unbouted MVPA (shorter bouts [1-9 minutes]) was associated with a significantly lower risk of incident stroke compared with the lowest tertile (HR, 0.62; 95% CI, 0.41-0.94; P = .02); however, bouted MVPA (longer bouts [at least 10 minutes]) was not (HR, 0.78; 95% CI, 0.53-1.15; P = .17). When expressed as continuous variables, sedentary time was positively associated with incident stroke risk (HR per 1-hour/day increase in sedentary time: 1.14; 95% CI, 1.02-1.28; P = .02), and LIPA was negatively associated with incident stroke risk (HR per 1-hour/day increase in LIPA: 0.86; 95% CI, 0.77-0.97; P = .02). Conclusions and Relevance: In this cohort study, objectively measured LIPA, MVPA, and sedentary time were significantly and independently associated with incident stroke risk. Longer sedentary bout duration was also independently associated with an increased risk of incident stroke. These findings suggest that replacing sedentary time with LIPA, or even very short bouts of MVPA, may lower stroke risk, supporting the concept of moving more and sitting less as a beneficial stroke risk reduction strategy among adults.

Associations of Maternal Prenatal Stress and Depressive Symptoms With Childhood Neurobehavioral Outcomes in the ECHO Cohort of the NICHD Fetal Growth Studies: Fetal Growth Velocity as a Potential Mediator.

OBJECTIVE: Maternal prenatal stress and mood symptoms are associated with risk for child psychopathology. Within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies (ECHO-FGS), a racially and ethnically diverse cohort, we studied associations between prenatal stress and depressive symptoms with child neurobehavior, and potential mediation by fetal growth velocity (FGV) in low-risk pregnancies. METHOD: For 730 mother-child pairs, we had serial ultrasound measurements, self-reports of prenatal stress and depression, observations of child executive functions and motor skills from 4 to 8 years, and maternal reports of child psychiatric problems. We tested associations between prenatal stress and depressive symptoms with child neurobehavior in regression analyses, and associations with FGV in mixed effect models. Post hoc we tested severity of prenatal symptoms; FGV at 25th, 50th, and 75th percentiles; and moderation by biological sex and by race and ethnicity. RESULTS: Prenatal stress and depressive symptoms were associated with child psychiatric problems, and prenatal depressive symptoms with decrements in executive functions and motor skills, especially in biological male children. Neither prenatal stress nor depressive symptoms were associated with FGV. CONCLUSION: In one of the largest cohorts with observed child outcomes, and the first with broad representation of race and ethnicity in the United States, we found that prenatal stress and depressive symptoms were associated with greater reports of child psychiatric symptoms. Only prenatal depressive symptoms were associated with observed decrements in cognitive abilities, most significantly in biological male children. Stress during low-risk pregnancies may be less detrimental than theorized. There was no mediation by FGV. These findings support the need to attend to even small changes in prenatal distress, as these may have long-lasting implications.

The association between maternal pre-pregnancy BMI, gestational weight gain and child adiposity: A racial-ethnically diverse cohort of children.

BACKGROUND: The prevalence of obesity in US children has more than tripled in the past 40 years; hence, it is critical to identify potentially modifiable factors that may mitigate the risk. OBJECTIVES: To examine the association between maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and child adiposity as measured by BMI, waist circumference and percent body fat in a racial-ethnically diverse cohort. METHODS: In a prospective cohort study of healthy women without chronic disease, we examined the association between pre-pregnancy BMI, GWG and child adiposity. Children ages 4-8 years (n = 816) in the Environmental Influences on Child Health Outcomes-NICHD Fetal Growth Studies were assessed. Trained study staff ascertained maternal pre-pregnancy BMI, GWG and child adiposity. RESULTS: The odds of child obesity (≥95th BMI percentile) increased independently for each unit increase in maternal pre-pregnancy BMI [OR = 1.12 (95% CI: 1.08, 1.17)] and for each 5-kg increase in GWG [OR = 1.25 (95% CI: 1.07, 1.47)]. The odds of child waist circumference (≥85th percentile) also increased independently for pre-pregnancy BMI [OR = 1.09 (95% CI: 1.05, 1.12)] and GWG [OR = 1.18 (95% CI: 1.04, 1.34)]. CONCLUSIONS: Maternal pre-pregnancy BMI and GWG were each independently and positively associated with child obesity and high child waist circumference.

Early Exposure to Animals and Childhood Body Mass Index Percentile and Percentage Fat Mass.

INTRODUCTION: A few studies have identified childhood animal exposure as associated with adiposity, but results are inconsistent and differ in timing. METHODS: We conducted an observational cohort study of children ages 4-8 in the Environmental Influences on Child Health Outcomes [ECHO] study. The main exposure was having a dog in the home and/or regular contact with farm animals during the first year of life. Outcomes of interest were child BMI percentile (adjusted for gender and age) categorized as normal/underweight (<85th percentile), overweight (85th to <95th), and obese (≥95th), and percent fat mass (continuous). Associations were analyzed using multinomial logistic regression and multivariable linear regression, respectively, with and without multiple imputation. RESULTS: First year animal exposure occurred in 245 of 770 (31.8%) children. Children with early animal exposure had 0.53 (95% CI: 0.28, 0.997) times the odds of being in the obese BMI category compared to those exposed to animals after controlling for covariates: maternal pre-pregnancy BMI, race/ethnicity, reported child activity level, receiving food assistance, age child began daycare (<1 year vs 1+), exclusively breastfed x6 months, and NICU admission (n=721). Children with early animal exposure had, on average, 1.5% (95% CI: -3.0, -0.1) less fat mass than exposed children after adjustment for maternal BMI, race/ethnicity, activity, food assistance, breastfeeding, and maternal education (n=548). Multiple imputation did not alter either result. CONCLUSION: These results provide evidence that exposure to dogs or farm animals in the first year of life is associated with lower odds of obesity and lower percent fat mass in childhood.

Breastfeeding Associations with Childhood Obesity and Body Composition: Findings from a Racially Diverse Maternal-Child Cohort.

Background: Studies suggest breastfeeding lowers obesity risk in childhood, but generalizability of existing evidence is limited. We examined associations of breastfeeding with childhood overweight, obesity, and percentage body fat, in a racially diverse maternal-child cohort. Methods: This cross-sectional study included 823 children, ages 4-8 years, enrolled in the Environmental Exposures and Child Health Outcomes (ECHO) cohort, a subset of the National Institute of Child Health and Human Development Fetal Growth Studies cohort. Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for overweight [BMI (kg/m2) 85th to <95th percentile] and obesity (BMI ≥95th percentile) in relation to breastfeeding including duration of exclusive and total breastfeeding. Linear regression was used to evaluate association between breastfeeding and percentage body fat measured by bioelectrical impedance analysis. Results: Fifty-two percent of children were male, 32% non-Hispanic Black, 29% Hispanic, 27% non-Hispanic White, and 13% Asian; 16% were overweight and 13% obese. Six months of exclusive breastfeeding, compared with no breastfeeding, was associated with 60% lower odds of obesity (95% CI 0.18-0.91) adjusting for age, gender, race, socioeconomic status, maternal BMI, and child's activity. Percentage body fat was inversely associated with breastfeeding duration. For none, <6, and ≥6 months of exclusive breastfeeding, adjusted mean percentage body fat was 16.8, 14.5, and 13.4, respectively. Results did not differ by gender, race/ethnicity, or maternal BMI status. Conclusions: Exclusive breastfeeding for the first 6 months of life is inversely and significantly associated with obesity and percentage body fat at ages 4-8 years. These findings support current breastfeeding guidelines.

Association between gestational PFAS exposure and Children's adiposity in a diverse population.

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4-8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p < 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (ß = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (ß = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (ß = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.

Using Bayesian time-stratified case-crossover models to examine associations between air pollution and "asthma seasons" in a low air pollution environment.

Many areas of the United States have air pollution levels typically below Environmental Protection Agency (EPA) regulatory limits. Most health effects studies of air pollution use meteorological (e.g., warm/cool) or astronomical (e.g., solstice/equinox) definitions of seasons despite evidence suggesting temporally-misaligned intra-annual periods of relative asthma burden (i.e., "asthma seasons"). We introduce asthma seasons to elucidate whether air pollutants are associated with seasonal differences in asthma emergency department (ED) visits in a low air pollution environment. Within a Bayesian time-stratified case-crossover framework, we quantify seasonal associations between highly resolved estimates of six criteria air pollutants, two weather variables, and asthma ED visits among 66,092 children ages 5-19 living in South Carolina (SC) census tracts from 2005 to 2014. Results show that coarse particulates (particulate matter <10 µm and >2.5 µm: PM10-2.5) and nitrogen oxides (NOx) may contribute to asthma ED visits across years, but are particularly implicated in the highest-burden fall asthma season. Fine particulate matter (<2.5 µm: PM2.5) is only associated in the lowest-burden summer asthma season. Relatively cool and dry conditions in the summer asthma season and increased temperatures in the spring and fall asthma seasons are associated with increased ED visit odds. Few significant associations in the medium-burden winter and medium-high-burden spring asthma seasons suggest other ED visit drivers (e.g., viral infections) for each, respectively. Across rural and urban areas characterized by generally low air pollution levels, there are acute health effects associated with particulate matter, but only in the summer and fall asthma seasons and differing by PM size.

Objectively Measured Physical Activity and Sedentary Time Among Adults With and Without Stroke: A National Cohort Study.

Background and Purpose: We examined differences in the volume and pattern of physical activity (PA) and sedentary behavior between adults with and without stroke. Methods: We studied cohort members with an adjudicated or self-reported stroke (n=401) and age-, sex-, race-, region of residence-, and body mass index-matched participants without a history of stroke (n=1203) from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Sedentary behavior (total volume and bouts), light-intensity PA, and moderate-to-vigorous-intensity PA were objectively measured for 7 days via hip-worn accelerometer. Results: Sedentary time (790.5±80.4 versus 752.4±81.9 min/d) and mean sedentary bout duration (15.7±12.6 versus 11.9±8.1 min/d) were higher and PA (light-intensity PA: 160.5±74.6 versus 192.9±73.5 min/d and moderate-to-vigorous-intensity PA: 9.0±11.9 versus 14.7±17.0 min/d) lower for stroke survivors compared with controls (P<0.001). Stroke survivors also accrued fewer activity breaks (65.5±21.9 versus 73.31±18.9 breaks/d) that were shorter (2.4±0.7 versus 2.7±0.8 minutes) and lower in intensity (188.4±60.8 versus 217.9±72.2 counts per minute) than controls (P<0.001). Conclusions: Stroke survivors accrued a lower volume of PA, higher volume of sedentary time, and exhibited accrual patterns of more prolonged sedentary bouts and shorter, lower intensity activity breaks compared with persons without stroke.

Reproductive Health Risks Associated with Occupational and Environmental Exposure to Pesticides.

A marked reduction in fertility and an increase in adverse reproductive outcomes during the last few decades have been associated with occupational and environmental chemical exposures. Exposure to different types of pesticides may increase the risks of chronic diseases, such as diabetes, cancer, and neurodegenerative disease, but also of reduced fertility and birth defects. Both occupational and environmental exposures to pesticides are important, as many are endocrine disruptors, which means that even very low-dose exposure levels may have measurable biological effects. The aim of this review was to summarize the knowledge collected between 2000 and 2020, to highlight new findings, and to further interpret the mechanisms that may associate pesticides with infertility, abnormal sexual maturation, and pregnancy complications associated with occupational, environmental and transplacental exposures. A summary of current pesticide production and usage legislation is also included in order to elucidate the potential impact on exposure profile differences between countries, which may inform prevention measures. Recommendations for the medical surveillance of occupationally exposed populations, which should be facilitated by the biomonitoring of reduced fertility, is also discussed.

Exploring associations between prenatal exposure to multiple endocrine disruptors and birth weight with exposure continuum mapping.

BACKGROUND: Improved understanding of how prenatal exposure to environmental mixtures influences birth weight or other adverse outcomes is essential in protecting child health. OBJECTIVE: We illustrate a novel exposure continuum mapping (ECM) framework that combines the self-organizing map (SOM) algorithm with generalized additive modeling (GAM) in order to integrate spatially-correlated learning into the study mixtures of environmental chemicals. We demonstrate our method using biomarker data on chemical mixtures collected from a diverse mother-child cohort. METHODS: We obtained biomarker concentrations for 16 prevalent endocrine disrupting chemicals (EDCs) collected in the first-trimester from a large, ethnically/racially diverse cohort of healthy pregnant women (n = 604) during 2009-2012. This included 4 organochlorine pesticides (OCPs), 4 polybrominated diphenyl ethers (PBDEs), 4 polychlorinated biphenyls (PCBs), and 4 perfluoroalkyl substances (PFAS). We applied a two-stage exposure continuum mapping (ECM) approach to investigate the combined impact of the EDCs on birth weight. First, we analyzed our EDC data with SOM in order to reduce the dimensionality of our exposure matrix into a two-dimensional grid (i.e., map) where nodes depict the types of EDC mixture profiles observed within our data. We define this map as the 'exposure continuum map', as the gridded surface reflects a continuous sequence of exposure profiles where adjacent nodes are composed of similar mixtures and profiles at more distal nodes are more distinct. Lastly, we used GAM to estimate a joint-dose response based on the coordinates of our ECM in order to capture the relationship between participant location on the ECM and infant birth weight after adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index (BMI), education, serum cotinine, total plasma lipids, and infant sex. Single chemical regression models were applied to facilitate comparison. RESULTS: We found that an ECM with 36 mixture profiles retained 70% of the total variation in the exposure data. Frequency analysis showed that the most common profiles included relatively low concentrations for most EDCs (~10%) and that profiles with relatively higher concentrations (for single or multiple EDCs) tended to be rarer (~1%) but more distinct. Estimation of a joint-dose response function revealed that lower birth weights mapped to locations where profile compositions were dominated by relatively high PBDEs and select OCPs. Higher birth weights mapped to locations where profiles consisted of higher PCBs. These findings agreed well with results from single chemical models. CONCLUSIONS: Findings from our study revealed a wide range of prenatal exposure scenarios and found that combinations exhibiting higher levels of PBDEs were associated with lower birth weight and combinations with higher levels of PCBs and PFAS were associated with increased birth weight. Our ECM approach provides a promising framework for supporting studies of other exposure mixtures.

Recruitment of population-based controls for ALS cases from the National ALS Registry.

Objective: In 2010, the United States Agency for Toxic Substances and Disease Registry (ATSDR) created the National ALS Registry (Registry) to examine the epidemiology of ALS and potential risk factors. We are currently recruiting population-based controls for an epidemiologic case-control study to examine ALS environmental risk factors using this Registry. To date, we have recruited 181 non-diseased, population-based controls for comparison to Registry cases (n = 280). Here we report our recruitment methods for controls and the associated response rates and costs. Methods: Eligible ALS cases had complete risk factor survey data, DNA analysis, and blood concentrations of persistent organic pollutants (POPs). Age, sex, and county-matched controls were identified from commercial/consumer databases using a targeted landline phone sample. Eligible controls were consented, surveyed, and mailed the POPs' blood analysis consent form. Once consented, phlebotomy was scheduled. Results: We mailed 3760 recruitment letters for 181 potential case-matches across 42 states between 9/2018 and 3/2020. After making phone contact and determining eligibility, 146 controls agreed to participate (response rate = 11.4%, cooperation rate = 22.8%). To date, 127 controls completed the survey and bloodwork. Though controls were matched to cases on age, sex, and county, unmatched characteristics (e.g. smoking) did not differ statistically. Interviewing and incentive costs are estimated at $211.85 per complete participation. Conclusions: Recruiting matched population-based controls for comparison to cases from the Registry for a study involving completion of a detailed survey and blood specimen provision is relatively feasible and cost effective. This recruitment method could be useful for case-control studies of other rare disorders.

Mediation of the association between maternal pre-pregnancy overweight/obesity and childhood overweight/obesity by birth anthropometry.

The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother-child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.

Reported Neighborhood Traffic and the Odds of Asthma/Asthma-Like Symptoms: A Cross-Sectional Analysis of a Multi-Racial Cohort of Children.

Asthma in children poses a significant clinical and public health burden. We examined the association between reported neighborhood traffic (a proxy for traffic-related air pollution) and asthma among 855 multi-racial children aged 4-8 years old who participated in the Environmental Influences on Child Health Outcomes (ECHO) cohort. We hypothesized that high neighborhood traffic density would be associated with the prevalence of asthma. Asthma/asthma-like symptoms (defined as current and/or past physician diagnosed asthma, past wheezing, or nighttime cough or wheezing in the past 12 months) was assessed by parental report. The relationship between neighborhood traffic and asthma/asthma-like symptoms was assessed using logistic regression. The prevalence of asthma/asthma-like symptoms among study participants was 23%, and 15% had high neighborhood traffic. Children with significant neighborhood traffic had a higher odds of having asthma/asthma-like symptoms than children without neighborhood traffic [adjusted OR = 2.01 (95% CI: 1.12, 3.62)] after controlling for child's race-ethnicity, age, sex, maternal education, family history of asthma, play equipment in the home environment, public parks, obesity and prescribed asthma medication. Further characterization of neighborhood traffic is needed since many children live near high traffic zones and significant racial/ethnic disparities exist.