Feasibility and acceptability of collecting umbilical cord tissue for prenatal cannabis research: A mixed-methods research study.

BACKGROUND: Large-scale longitudinal studies with biological samples are needed to examine the associations between prenatal cannabis use and birth and developmental outcomes. OBJECTIVES: The aim of this study was to understand the feasibility and acceptability of collecting umbilical cord tissue for the purpose of cannabis use testing in a community sample. DESIGN: This is a mixed methods research study consisted of a prospective cohort study and a qualitative descriptive study. METHODS: This study was conducted in Vancouver, British Columbia between January 2021 and August 2022. Participants were recruited during pregnancy, and the umbilical cord tissues were collected at birth and tested for the presence of cannabinoids. After the completion of the study, participants completed an online open-ended questionnaire about their overall experience. Data were analyzed using descriptive and thematic analyses. RESULTS: Among the 85 eligible individuals, 57 people (67%) consented to the study. The cord tissue was collected for 39 participants (68.4%). The collection rates for participants with vaginal, elective, and emergency cesarean delivery were 73.0%, 71.4%, and 53.8%, respectively, and for those with spontaneous and induced labor were 81.5% and 50%, respectively. Four (7.0%) and seven participants (12.3%) reported prenatal cannabis use in direct and probing self-report questions, respectively. The agreement between any self-report and cord tissue test was moderate (kappa 0.53, 95% confidence interval 0.06-0.99). Qualitative findings were classified into five themes. CONCLUSION: The collection of cord tissue was perceived acceptable by most participants. Implementation of collection protocols for complex labors, a central hospital unit to liaise direct communications and active participants' involvement might increase the feasibility of future studies.

Feasibility issues impacting optimal levels of maternity care in rural communities: implementing the Rural Birth Index in British Columbia.

INTRODUCTION: The continued attrition of maternity services across rural communities in high resource countries demands a rigorous, systematic approach to determining population level need, including a clear understanding of feasibility issues that may constrain achieving and sustaining recommended levels of services. The Rural Birth Index (RBI) proposes a robust and objective methodology to determine such need along with attention to the feasibility of implementation. BACKGROUND: Predictions of appropriate levels of maternity care in rural communities require consideration of the feasibility of implementation. Although previous work has focused on essential considerations that impact feasibility, there is little research documenting the barriers to implementation from the perspective of rural care providers and administrators. METHODS: We conducted in-depth, qualitative research interviews with rural community health care administrators and providers (n = 14) to understand the challenges of offering maternity care in 10 rural communities across British Columbia (BC). RESULTS: Participants articulated three thematic challenges to providing maternity services in their communities: maintaining clinical skills and financial stability in the context of low procedural volume, recruitment and retention of care providers and challenges with patient transport. CONCLUSIONS: Current models of compensation for maternity care are inadequate and inflexible and underscore many of the challenges to implementing a level of care that is based on population need. Re-thinking provision of care as a social obligation to actualize our system commitment to equity instead of working to achieve economies of scale is the first step to use equitable care. Addressing remuneration will provide the groundwork for solving other barriers to sustainable care.

Childhood exposure to per- and polyfluoroalkyl substances (PFAS) and neurobehavioral domains in children at age 8 years.

BACKGROUND: Toxicological studies have raised concerns regarding the neurotoxic effects of per- and polyfluoroalkyl substances (PFAS). However, observational evidence from human studies investigating the association between childhood PFAS and neurobehavior is limited and remains unclear. OBJECTIVES: To examine whether childhood PFAS concentrations are associated with neurobehavior in children at age 8 years and whether child sex modifies this relationship. METHODS: We used data from 208 mother-child dyads in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort (Cincinnati, OH, USA). We quantified PFAS in child serum at 3 and 8 years. We assessed neurobehavioral domains using the Behavior Assessment System for Children-2 at 8 years. We used multiple informant models to estimate score changes per ln-increase in repeated PFAS concentrations. RESULTS: Childhood PFAS were not associated with Externalizing or Internalizing Problems at 8 years. However, we noted effect measure modification by sex, with higher scores in Externalizing Problems among males per ln-unit increase in perfluorononanoate (PFNA) at 3 years (ß = 4.3 points, 95% CI: 1.0, 7.7) while females had lower scores (ß = -2.8 points, 95% CI: -4.7, -1.0). More Internalizing Problems were observed among males per ln-unit increase in concurrent PFNA concentrations (ß = 3.7 points, 95% CI: 0.7, 6.8), but not in females (ß = -1.7 points, 95% CI: -4.6, 1.2). Childhood PFNA concentrations were associated with lower scores for attention problems and activity of daily living. CONCLUSION: While findings do not consistently support an association between childhood PFAS serum concentrations and neurobehavior, child sex may play a role in this relationship.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and neurobehavior in US children through 8 years of age: The HOME study.

BACKGROUND: Studies of prenatal per- and polyfluoroalkyl substances (PFAS) and attention deficit hyperactivity disorder (ADHD)-related behaviors in children are inconsistent. OBJECTIVES: To examine associations between maternal serum PFAS concentrations and child behavior in 241 mother-child dyads within the Health Outcomes and Measures of the Environment (HOME) Study. METHODS: We quantified perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) in maternal serum collected during pregnancy or at delivery. We evaluated a total of 17 outcomes of child behavior using the Behavioral Assessment System for Children-2 (BASC-2) at 5 and 8 years (n = 240) and ADHD diagnostic symptoms and criteria with the Diagnostic Interview Schedule for Children-Young Child (DISC-YC) at 5 years (n = 190). We used linear mixed models and logistic regression with generalized estimating equations to assess associations between PFAS and continuous or dichotomous "at risk" BASC-2 scores; negative binomial regression to calculate incident rate ratios for counts of ADHD symptoms; and Poisson regression with robust standard errors to calculate relative risks of meeting ADHD diagnostic criteria. RESULTS: Each ln-unit increase in PFOS, PFHxS, and PFNA was associated with higher BASC-2 scores and increased odds of "at-risk" scores for externalizing behaviors, including hyperactivity (PFOS: odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2, 5.9; PFHxS: OR 2.5, 95% CI 1.5, 4.3; PFNA: OR 3.2, 95% CI 1.3, 8.0). PFHxS was also associated with internalizing problems (OR 2.0, 95% CI 1.1, 3.4) and somatization (OR 2.2, 95% CI 1.2, 4.0). PFOS and PFNA were significantly associated with 50-80% more DISC-YC symptoms and diagnostic criteria related to hyperactive-impulsive type ADHD. Prenatal PFNA was associated with increased risk of any-type ADHD. CONCLUSIONS: Prenatal PFOS and PFNA were consistently associated with measures related to hyperactive-impulsive type ADHD across two validated assessment instruments. PFHxS was associated with increased problems with both externalizing and internalizing behaviors. No associations were noted between PFOA and child neurobehavior.

Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.

BACKGROUND: The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation. METHODS: We enrolled 2,001 women>18 years of age during the first trimester of pregnancy between 2008 and 2011 from 10 cities in Canada. At 3-4 years of age, 610 children underwent neuropsychological assessments including the Social Responsiveness Scale-II (SRS-2) as a measure of autistic traits and social impairment. We measured 11 phthalate metabolites in maternal first trimester urine samples and assessed folic acid supplementation from reported intakes. We estimated covariate-adjusted differences in SRS-2 T-scores with a doubling in phthalate concentrations in 510 children with complete data. RESULTS: Mean total SRS T-score was 45.3 (SD=6.1). Children with higher gestational exposure to mono-n-butyl (MBP) and mono-3-carboxypropyl (MCPP) concentrations exhibited significantly higher total SRS T-scores, indicating greater overall social impairment, as well as higher scores on subdomains, indicating deficits in social cognition, social communication, social motivation, and restricted interests/repetitive behaviors. A doubling in MBP or MCPP concentrations was associated with 0.6 (95% CI: 0.1, 1.0) and 0.5 (95% CI: 0.1, 0.8) higher total SRS T-scores. Associations were consistently and significantly stronger in boys (ßMBP=1.0; 95% CI: 0.4, 1.6; n=252) compared with girls (ßMBP=0.1; 95% CI: -0.6, 0.7; n=258) and among children who had lower prenatal folic acid supplementation (<400µg/d) (ßMBP=1.3; 95% CI: 0.4, 2.3; n=59) compared with those who had adequate folic acid supplementation (≥400µg/d) (ßMBP=0.4; 95% CI: -0.1, 0.8; n=451). CONCLUSIONS: Higher gestational concentrations of some phthalate metabolites were associated with higher scores of autistic traits as measured by the SRS-2 in boys, but not girls; these small size effects were mitigated by first trimester-of-pregnancy folic acid supplementation. https://doi.org/10.1289/EHP5621.

Coal smoke, gestational cadmium exposure, and fetal growth.

BACKGROUND: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. METHODS: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. RESULTS: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) µg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. CONCLUSIONS: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.

Prenatal and childhood exposure to poly- and perfluoroalkyl substances (PFAS) and cognitive development in children at age 8 years.

BACKGROUND: Toxicological studies indicate that poly- and perfluoroalkyl substances (PFAS) may be neurotoxic, but human studies have yet to provide compelling evidence for PFAS' impact on cognitive abilities. OBJECTIVE: To test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations. METHODS: We included 221 mother-child pairs from the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort in Cincinnati, OH (USA). We quantified PFAS in maternal serum at 16 ±â€¯3 weeks gestation and in child serum at 3 and 8 years. We used the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) at age 8 years, assessing Full Scale IQ (FSIQ), verbal comprehension, perceptual reasoning, working memory, and processing speed. We used multiple informant models to estimate covariate-adjusted differences in WISC-IV scores by repeated ln-transformed PFAS. RESULTS: Prenatal and childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were not associated with WISC-IV measures. We observed an increase of 4.1-points (95% CI 0.3, 8.0) and 5.7-points (95% CI 1.2, 10.2) in working memory with 1-ln unit increase in prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA), respectively. In addition, PFNA at 3 years was associated with better FSIQ and perceptual reasoning. Child sex modified the relationship between prenatal PFOA and FSIQ; the association was positive in females only. Sex also modified the association between concurrent PFOS and FSIQ, with males having higher scores. CONCLUSION: We did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years.

Evaluation of random forest regression and multiple linear regression for predicting indoor fine particulate matter concentrations in a highly polluted city.

BACKGROUND: Indoor and outdoor fine particulate matter (PM2.5) are both leading risk factors for death and disease, but making indoor measurements is often infeasible for large study populations. METHODS: We developed models to predict indoor PM2.5 concentrations for pregnant women who were part of a randomized controlled trial of portable air cleaners in Ulaanbaatar, Mongolia. We used multiple linear regression (MLR) and random forest regression (RFR) to model indoor PM2.5 concentrations with 447 independent 7-day PM2.5 measurements and 87 potential predictor variables obtained from outdoor monitoring data, questionnaires, home assessments, and geographic data sets. We also developed blended models that combined the MLR and RFR approaches. All models were evaluated in a 10-fold cross-validation. RESULTS: The predictors in the MLR model were season, outdoor PM2.5 concentration, the number of air cleaners deployed, and the density of gers (traditional felt-lined yurts) surrounding the apartments. MLR and RFR had similar performance in cross-validation (R2 = 50.2%, R2 = 48.9% respectively). The blended MLR model that included RFR predictions had the best performance (cross validation R2 = 81.5%). Intervention status alone explained only 6.0% of the variation in indoor PM2.5 concentrations. CONCLUSIONS: We predicted a moderate amount of variation in indoor PM2.5 concentrations using easily obtained predictor variables and the models explained substantially more variation than intervention status alone. While RFR shows promise for modelling indoor concentrations, our results highlight the importance of out-of-sample validation when evaluating model performance. We also demonstrate the improved performance of blended MLR/RFR models in predicting indoor air pollution.

Organophosphate esters in house dust: A comparative study between Canada, Turkey and Egypt.

Organophosphate esters (OPEs) are commonly used as flame retardants (FRs) and plasticizers. The usage of OPEs has increased recently due to the ban of several brominated flame retardants, but information on levels in the environment, including the indoor environment is still limited. We investigated the occurrence and distribution of 12 OPEs in urban house dust from Vancouver, Canada; Istanbul, Turkey; and Cairo, Egypt. The median ∑OPE concentration was 41.4 µg/g in the Vancouver samples while median levels in Istanbul and Cairo were significantly lower. The median composition profiles of OPEs in Vancouver and Cairo were dominated by tris (2-butoxyethyl) phosphate (TBOEP), accounting for 56 and 92% of total OPEs respectively while it showed a detection frequency of only 14% in Istanbul. Tris (2-chloropropyl) phosphate (TCPP) was the most abundant chlorinated OPE representing 20 and 36% of the total OPEs in Vancouver and Istanbul respectively, but was below the detection limit in the Cairo dust samples. Consistent with other studies, ΣOPE concentrations were ~1 to 2 orders of magnitude higher than PBDEs and currently used flame retardants in the same dust samples. The mean estimated daily intakes (EDI) of ΣOPE from dust were 115, 38 and 9 ng/kg/bw/day in Vancouver, Cairo and Istanbul respectively for toddlers where adults were ~10 times lower. The total toddler OPE intake ranged from 115 to 2900, 38 to 845 and from 9 to 240 ng/kg bw/day across the three cities. TBOEP had the largest contribution to the EDI in both toddler and adults, where toddler TBOEP exposures via dust represented 4% to 80%, 2% to 44% and 0.1% to 6% of the Reference Doses (RfD) in the mean and high intake scenarios for toddlers in Vancouver, Cairo and Istanbul respectively.

Exposure to polybrominated diphenyl ethers (PBDEs) during childhood and adiposity measures at age 8 years.

BACKGROUND: Animal studies suggest polybrominated diphenyl ethers (PBDEs) may be obesogens. However, epidemiologic studies investigating childhood exposure to PBDEs and adiposity are limited, with several reporting an inverse association. OBJECTIVES: To investigate associations between repeated childhood PBDE concentrations and adiposity measures at age 8 years. METHODS: We examined 206 children from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (2003-2006). Serum PBDEs were measured at ages 1, 2, 3, 5, and 8 years. We used multiple imputation to estimate missing PBDE concentrations. At 8 years, we measured weight, height, waist circumference, and body fat percentage. We used multiple informant models to estimate age-specific associations between PBDEs and adiposity measures. RESULTS: We observed significant inverse associations between BDE-153 with all adiposity measures that became increasingly stronger with later childhood measurements. A 10-fold increase in BDE-153 at ages 1 and 8 years was associated with 2% (95% CI -3.9, -0.1) and 7% (95% CI -9.1, -4.7) lower body fat, respectively. No statistically significant associations were found with BDE-28, -47, -99, or -100. Child sex modified some associations; inverse associations between BDE-153 and body fat were stronger among boys, while positive and null associations were noted among girls. CONCLUSIONS: Childhood BDE-153 concentrations were inversely associated with adiposity measures and these associations became stronger as BDE-153 measurements were more proximal to adiposity measures. Inverse associations could be attributed to reverse causality arising from greater storage of PBDEs in adipose tissue of children with higher adiposity.

Childhood polybrominated diphenyl ether (PBDE) serum concentration and reading ability at ages 5 and 8 years: The HOME Study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment and human beings. PBDE concentrations are higher in children than adults. A previous study found that prenatal PBDE exposure was associated with decreased reading skills in children; however, evidence is limited on the potential impact of childhood exposure to PBDEs. The study examined the association between childhood PBDE exposures and reading ability in children at ages 5 and 8 years. METHODS: The study included 230 children from an ongoing prospective pregnancy and birth cohort study, the Health Outcomes and Measures of Environment (HOME) Study, conducted in Cincinnati, Ohio. Children's serum concentrations of eleven PBDE congeners were measured at 1, 2, 3, 5, and 8 years. The Woodcock-Johnson Tests of Achievement - III and the Wide Range Achievement Test - 4 were administered to assess children's reading skills at ages 5 and 8 years, respectively. We used multiple informant models to examine the associations between repeated measures of PBDEs and reading scores at ages 5 and 8 years. We also estimated the ßs and 95% CIs of the association of PBDE measure at each age by including interaction terms between PBDE concentrations and child age in the models. RESULTS: All childhood BDE-153 concentrations were inversely associated with reading scores at 5 and 8 years, but associations were not statistically significant after covariate adjustment. For example, a 10-fold increase in BDE-153 concentrations at ages 3 and 5 years was associated with a -5.0 (95% confidence interval (CI): -11.0, 1.0) and -5.5 (95% CI: -12.5, 1.4) point change in Basic Reading score at age 5 years, respectively. Similarly, the estimates for Brief Reading score at age 5 years were -4.5 (95% CI: -10.5, 1.5) and -5.2 (95% CI: -12.2, 1.7) point changes, respectively. Serum concentration of BDE-47, -99, -100, and Sum4PBDEs (sum of BDE-47, 99, 100, and 153) at every age were inversely associated with reading scores at ages 5 and 8 years in unadjusted analyses. While the adjusted estimates were much attenuated and became non-significant, the direction of most of the associations was not altered. CONCLUSION: Our study has shown a suggestive but non-significant trend of inverse associations between childhood PBDE serum concentrations, particularly BDE-153, and children's reading skills. Future studies with a larger sample size are needed to examine these associations.

The effect of portable HEPA filter air cleaner use during pregnancy on fetal growth: The UGAAR randomized controlled trial.

BACKGROUND: Fine particulate matter (PM2.5) exposure may impair fetal growth. AIMS/OBJECTIVES: Our aim was to assess the effect of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy on fetal growth. METHODS: The Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study is a single-blind randomized controlled trial conducted in Ulaanbaatar, Mongolia. Non-smoking pregnant women recruited at ≤18 weeks gestation were randomized to an intervention (1-2 air cleaners in homes from early pregnancy until childbirth) or control (no air cleaners) group. Participants were not blinded to their intervention status. Demographic, health, and birth outcome data were obtained via questionnaires and clinic records. We used unadjusted linear and logistic regression and time-to-event analysis to evaluate the intervention. Our primary outcome was birth weight. Secondary outcomes were gestational age-adjusted birth weight, birth length, head circumference, gestational age at birth, and small for gestational age. The study is registered at ClinicalTrials.gov (NCT01741051). RESULTS: We recruited 540 participants (272 control and 268 intervention) from January 9, 2014 to May 1, 2015. There were 465 live births and 28 losses to follow up. We previously reported a 29% (95% CI: 21, 37%) reduction in indoor PM2.5 concentrations with portable HEPA filter air cleaner use. The median (25th, 75th percentile) birth weights for control and intervention participants were 3450 g (3150, 3800 g) and 3550 g (3200, 3800 g), respectively (p = 0.34). The intervention was not associated with birth weight (18 g; 95% CI: -84, 120 g), but in a pre-specified subgroup analysis of 429 term births the intervention was associated with an 85 g (95% CI: 3, 167 g) increase in mean birth weight. CONCLUSIONS: HEPA filter air cleaner use in a high pollution setting was associated with greater birth weight only among babies born at term.

Childhood perfluoroalkyl substance exposure and executive function in children at 8 years.

BACKGROUND: Toxicological studies highlight the potential neurotoxicity of perfluoroalkyl substances (PFAS) during fetal development. However, few epidemiological studies have examined the impact of childhood PFAS on neurodevelopment. METHODS: We employed data from 208 children in the Health Outcomes and Measures of the Environment Study, a birth cohort (Cincinnati, OH), to examine associations of six serum PFAS concentrations measured at 3 and 8 years with executive function assessed at 8 years using the validated parent-completed Behavior Rating Inventory of Executive Function survey. We used multiple informant models to identify susceptible windows of neurotoxicity to PFAS and executive function. We investigated trajectories of PFAS concentrations and whether sex modified these associations. RESULTS: Each ln-increase in perfluorononanoate (PFNA) at 8 years was associated with a 3.4-point increase (95% CI 0.4, 6.3) in metacognition score, indicating poorer function. Children with PFNA above the median at 8 years had poorer global executive functioning compared to children with concentrations consistently below median levels (ß = 6.5, 95% CI 0.2, 12.9). Higher concurrent PFNA was associated with poorer behavior regulation among males, while associations among females were null (pPFNA×sex = 0.018). Children with higher concurrent perfluorooctanoate (PFOA) had increased odds of being at risk of having clinical impairments in metacognition (OR = 3.18, 95% CI 1.17, 8.60). There were no associations between perfluorooctane sulfonate and perfluorohexane sulfonate and executive function. CONCLUSIONS: PFNA and PFOA at 8 years, but not 3 years, may be related to poorer executive function at 8 years. Results need to be confirmed in cohort studies with larger sample sizes.

Prenatal and childhood exposure to perfluoroalkyl substances (PFAS) and measures of attention, impulse control, and visual spatial abilities.

BACKGROUND: Despite evidence from toxicological studies describing the potential neurotoxicity of perfluoroalkyl substances (PFAS), their role in neurodevelopment remains uncertain amid inconsistent findings from epidemiological studies. METHODS: Using data from 218 mother-child dyads from the Health Outcomes and Measures of the Environment Study, we examined prenatal and childhood (3 and 8 years) serum concentrations of four PFAS and inattention, impulsivity, and visual spatial abilities. At 8 years, we used the Conners' Continuous Performance Test-II to assess attention and impulse control and the Virtual Morris Water Maze (VMWM) to measure visual spatial abilities. RESULTS: In multiple informant models, there was no evidence to indicate that prenatal or childhood PFAS are associated with attention. However, there was an inverse association between prenatal ln-perfluorooctanoate (PFOA) and errors of commission (ß = -2.0, 95% Confidence Interval [CI] -3.8, -0.3). Ln-perfluorononanoate (PFNA) at 3 years was associated with longer (poorer) VMWM completion times of 3.6 seconds (CI 1.6, 5.6). However, higher concurrent concentrations of ln-perfluorohexane sulfonate (PFHxS) (ß = -2.4 s, 95% CI -4.4, -0.3) were associated with shorter (better) times. Higher prenatal PFHxS was positively associated with percentage of traveling distance in the correct quadrant (ß = 4.2%, 95% CI 0.8, 7.7), indicating better performance. CONCLUSION: Findings were mixed for prenatal and childhood PFAS concentrations and visual spatial abilities. There is not enough evidence to support that PFAS are associated with visual spatial abilities as assessed by the VMWM or CPT-II measures of inattention or impulsivity in children at age 8 years.

Polybrominated diphenyl ether (PBDE) exposures and thyroid hormones in children at age 3 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. METHODS: We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ±â€¯3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. RESULTS: Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT3). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T4 (FT4) in males. Prenatal ∑PBDEs were not associated with TT4, FT4, or total T3. CONCLUSIONS: These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males.

The effect of portable HEPA filter air cleaners on indoor PM2.5 concentrations and second hand tobacco smoke exposure among pregnant women in Ulaanbaatar, Mongolia: The UGAAR randomized controlled trial.

BACKGROUND: Portable HEPA filter air cleaners can reduce indoor fine particulate matter (PM2.5), but their use has not been adequately evaluated in high pollution settings. We assessed air cleaner effectiveness in reducing indoor residential PM2.5 and second hand smoke (SHS) exposures among non-smoking pregnant women in Ulaanbaatar, Mongolia. METHODS: We randomized 540 participants to an intervention group receiving 1 or 2 HEPA filter air cleaners or a control group receiving no air cleaners. We followed 259 intervention and 253 control participants to the end of pregnancy. We measured one-week indoor residential PM2.5 concentrations in early (~11weeks gestation) and late (~31weeks gestation) pregnancy and collected outdoor PM2.5 data from centrally-located government monitors. We assessed blood cadmium in late pregnancy. Hair nicotine was quantified in a subset (n=125) to evaluate blood cadmium as a biomarker of SHS exposure. We evaluated air cleaner effectiveness using mixed effects and multiple linear regression models and used stratified models and interaction terms to evaluate potential modifiers of effectiveness. RESULTS: The overall geometric mean (GM) one-week outdoor PM2.5 concentration was 47.9µg/m3 (95% CI: 44.6, 51.6µg/m3), with highest concentrations in winter (118.0µg/m3; 110.4, 126.2µg/m3). One-week indoor and outdoor PM2.5 concentrations were correlated (r=0.69). Indoor PM2.5 concentrations were 29% (21, 37%) lower in intervention versus control apartments, with GMs of 17.3µg/m3 (15.8, 18.8µg/m3) and 24.5µg/m3 (22.2, 27.0µg/m3), respectively. Air cleaner effectiveness was greater when air cleaners were first deployed (40%; 31, 48%) than after approximately five months of use (15%; 0, 27%). Blood cadmium concentrations were 14% (4, 23%) lower among intervention participants, likely due to reduced SHS exposure. CONCLUSIONS: Portable HEPA filter air cleaners can lower indoor PM2.5 concentrations and SHS exposures in highly polluted settings.

Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

BACKGROUND: Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS exposures. The composition of PFASs in human sera reflects the complexity of exposure sources but source identification can be confounded by differences in toxicokinetics affecting uptake, distribution, and elimination. Common PFASs, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects. METHODS: We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands) to explore whether chemical fingerprints in human sera provide insights into predominant exposure sources. We compare serum PFAS profiles from Faroese individuals to other North American populations to investigate commonalities in potential exposure sources. We compare individuals with similar demographic and physiological characteristics and samples from the same years to reduce confounding by toxicokinetic differences and changing environmental releases. RESULTS: Using principal components analysis (PCA) confirmed by hierarchical clustering, we assess variability in serum PFAS concentrations across three Faroese groups. The first principal component (PC)/cluster consists of C9-C12 perfluoroalkyl carboxylates (PFCAs) and is consistent with measured PFAS profiles in consumed seafood. The second PC/cluster includes perfluorohexanesulfonic acid (PFHxS) and the PFOS precursor N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same exposure sources in two North American populations, suggesting generalizability of results from the Faroese population. CONCLUSIONS: We conclude that PFAS homologue profiles in serum provide valuable information on major exposure sources. It is essential to compare samples collected at similar time periods and to correct for demographic groups that are highly affected by differences in physiological processes (e.g., pregnancy). Information on PFAS homologue profiles is crucial for attributing adverse health effects to the proper mixtures or individual PFASs.

Prenatal and childhood perfluoroalkyl substances exposures and children's reading skills at ages 5 and 8years.

BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may impact children's neurodevelopment. OBJECTIVE: To examine the association of prenatal and early childhood serum PFAS concentrations with children's reading skills at ages 5 and 8years. METHODS: We used data from 167 mother-child pairs recruited during pregnancy (2003-2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16±3weeks of gestation and childhood sera at ages 3 and 8years. We assessed children's reading skills using Woodcock-Johnson Tests of Achievement III at age 5years and Wide Range Achievement Test-4 at age 8years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility. RESULTS: Median serum PFASs concentrations were PFOS>PFOA>PFHxS>PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children's reading scores at ages 5 and 8years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children's scores in Reading Composite (ß: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (ß: 4.2, 95% CI: 0.5, 8.0) at age 8years; b) 3-year PFOA was positively associated with higher children's scores in Brief Reading (ß: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (ß: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (ß: 5.9, 95% CI: 1.5, 10.2) at age 5years; c) 8-year PFOA was positively associated with higher children's Word Reading scores (ß: 5.8, 95% CI: 0.8, 10.7) at age 8years. Prenatal PFOS and PFNA were positively associated with children's reading abilities at age 5years, but not at age 8years; 3-year PFOS and PFNA were positively associated with reading scores at age 5years. But PFHxS concentrations, at any exposure windows, were not associated with reading skills. CONCLUSION: Prenatal and childhood serum PFOA, PFOS and PFNA concentrations were positively associated with better children's reading skills at ages 5 and 8years, but no association was found between serum PFHxS and reading skills.

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study.

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (ß=4.6, 95% CI 0.5, 8.7) and BDE-153 (ß=4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.

Prenatal and postnatal polybrominated diphenyl ether (PBDE) exposure and measures of inattention and impulsivity in children.

Exposure to polybrominated diphenyl ethers (PBDEs) during fetal development may be associated with deficits in attention and impulse control. However, studies examining postnatal PBDE exposures and inattention and impulsivity have been inconsistent. Using data from 214 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort with enrollment from 2003 to 2006 in the Greater Cincinnati Area, we investigated the relationship of both prenatal and postnatal PBDE exposures with attention and impulse control. Serum PBDEs were measured at 16±3weeks of gestation and during childhood at 1, 2, 3, 5, and 8years. We assessed children's attention and impulse control using the Conners' Continuous Performance Test-Second Edition (CPT-II) at 8years. We used multiple informant models to estimate associations of repeated PBDE measures with inattention and impulsivity. There was a pattern of associations between PBDEs and poorer performance on CPT-II measures of attention. For BDE-153, adverse associations extended to exposures at preschool and kindergarten ages; ten-fold increases in exposure were associated with higher omission errors (BDE-153 at 3years: ß=4.0 [95% CI: -2.4, 10.5]; at 5years: ß=4.6 [95% CI: -2.8, 12.0]; at 8years: ß=4.1 [95% CI: -3.4, 11.5]). Longer hit reaction times, indicated by the exponential part of the hit reaction curve, were also observed with 10-fold increases in BDE-153 during the prenatal period and throughout childhood (Prenatal: ß=15.0 milliseconds (ms) [95% CI: -15.8, 45.8]; 5years: ß=20.6ms [95% CI: -20.8, 61.9]; 8years: ß=28.6ms [95% CI: -12.1, 69.4]). Significant impairment in discriminability, as indicated by detectability (d'), between targets and non-targets was also noted with 5 and 8-year PBDE concentrations. Associations between PBDEs and inattention significantly differed by child sex, with males performing more poorly than females with regard to omission errors and measures of reaction times. Collectively, these results do not strongly support that PBDEs are associated with poorer impulse and attention control among 8year old children. However, there may be a possible relationship between prenatal and concurrent PBDEs and inattention, which requires additional research.