Exposure to Per- and Polyfluoroalkyl Substances and Mortality in U.S. Adults: A Population-Based Cohort Study

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants associated with diseases such as cancer and dyslipidemia. However, few studies have investigated the association between PFAS mixture exposure and mortality in general populations.Objectives: This study aimed to explore the association between PFAS mixture, perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS) and mortality in U.S. adults by a nationally representative cohort.Methods: Adults ≥18 years of age who were enrolled in the National Health and Nutrition Examination Survey (NHANES) (1999–2014) were included in our study. Baseline serum concentrations of seven PFAS were measured and individuals were followed up to 31 December 2015. Hazard ratios (HRs) and confidence intervals (CIs) were estimated using Cox proportional hazards models. Association between PFAS mixture exposure and mortality was analyzed using the k-means method by clustering PFAS mixtures into subgroups. Association between PFOA/PFOS exposure and mortality was subsequently analyzed in both continuous and categorical models.Results: During the follow-up period, 1,251 participants died. In the mixture analysis, the k-means algorithm clustered participants into low-, medium-, and high-exposure groups. Compared with the low-exposure group, participants in the high-exposure group showed significantly higher risks for all-cause mortality (HR=1.38; 95% CI: 1.07, 1.80), heart disease mortality (HR=1.58; 95% CI: 1.05, 2.51), and cancer mortality (HR=1.70; 95% CI: 1.08, 2.84). In single PFAS analysis, PFOS was found to be positively associated with all-cause mortality (third vs. first tertile HR=1.57; 95% CI: 1.22, 2.07), heart disease mortality (third vs. first tertile HR=1.65; 95% CI: 1.09, 2.57), and cancer mortality (third vs. first tertile HR=1.75; 95% CI: 1.10, 2.83), whereas PFOA exposure had no significant association with mortality. Assuming the observed association is causal, the number of deaths associated with PFOS exposure (≥17.1 vs. <7.9 ng/mL) was ∼382,000 (95% CI: 176,000, 588,000) annually between 1999 and 2015, and it decreased to 69,000 (95% CI: 28,000, 119,000) annually between 2015 and 2018. The association between PFOS and mortality was stronger among women and people without diabetes.Discussion: We observed a positive association between PFAS mixture exposure and mortality among U.S. adults. Limitations of this study include the potential for unmeasured confounding, selection bias, a relatively small number of deaths, and only measuring PFAS at one point in time. Further studies with serial measures of PFAS concentrations and longer follow-ups are necessary to elucidate the association between PFAS and mortality from specific causes. https://doi.org/10.1289/EHP10393     

Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study

Background: DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.Objectives: We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003–2006; Cincinnati, Ohio).Methods: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children’s age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999–2002; Boston, Massachusetts) to replicate significant associations.Results: After adjusting for covariates, 435 cytosine–guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q<0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children’s age.Discussion: In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118     

Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis

Background: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver.Objective: The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies.Methods: PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human studies, at least three observational studies per PFAS were used to conduct a weighted z-score meta-analysis to determine the direction and significance of associations. For rodent studies, data were synthesized to qualitatively summarize the direction and significance of effect.Results: Our search yielded 85 rodent studies and 24 epidemiological studies, primarily of people from the United States. Studies focused primarily on legacy PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid. Meta-analyses of human studies revealed that higher ALT levels were associated with exposure to PFOA (z-score= 6.20, p<0.001), PFOS (z-score= 3.55, p<0.001), and PFNA (z-score= 2.27, p=0.023). PFOA exposure was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in humans. In rodents, PFAS exposures consistently resulted in higher ALT levels and steatosis.Conclusion: There is consistent evidence for PFAS hepatotoxicity from rodent studies, supported by associations of PFAS and markers of liver function in observational human studies. This review identifies a need for additional research evaluating next-generation PFAS, mixtures, and early life exposures. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10092","term_id":"372009472","term_text":"EHP10092"}}EHP10092     

Per- and Polyfluoroalkyl Substances and Risk of Myocardial Infarction and Stroke: A Nested Case–Control Study in Sweden

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been associated with elevated cholesterol levels. However, data on incident cardiovascular disease (CVD) is lacking.Objectives: We investigated the association of exposure to PFAS with risk of myocardial infarction and stroke and, subsidiary, with baseline blood lipids.Methods: This population-based nested case–control study included first incident myocardial infarction and stroke cases with matched controls from two Swedish cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-year-olds (60YO). Baseline blood sampling occurred during 2003–2009 and 1997–1999 with follow-up through 2017 and 2014 for the SMC-C and the 60YO, respectively. Eight plasma PFAS concentrations were measured using targeted liquid chromatography–triple quadrupole mass spectrometry. Five of these were quantifiable in both cohorts; individual values and their standardized sum were categorized into tertiles based on the controls. First incident myocardial infarction (n=345) and ischemic stroke (n=354) cases were ascertained via linkage to the National Inpatient Register and the Cause of Death Register. Controls were randomly selected from each cohort after matching for age, sex, and sample date. Baseline blood lipids were measured in plasma or serum after overnight fasting.Results: Among the 1,528 case–control subjects, the mean (standard deviation) age was 66 (7.7) y and 67% of them were women. In multivariable-adjusted analyses, the third tertile of the standardized sum of five PFAS associated with higher cholesterol and lower triglyceride levels among controls at baseline (n=631). The corresponding results were odds ratios=0.70 [95% confidence interval (CI): 0.53, 0.93] for CVD, 0.60 (95% CI: 0.39, 0.92) for myocardial infarction, and 0.83 (95% CI: 0.46, 1.50) for stroke.Discussion: This study indicated that exposure to PFAS, although associated with increased cholesterol levels, did not associate with an increased risk of myocardial infarction, stroke, or their composite end point. The findings improve our knowledge on potential health effects of environmental contaminants in the CVD context. https://doi.org/10.1289/EHP9791     

Long-Term Associations between Disaster-Related Home Loss and Health and Well-Being of Older Survivors: Nine Years after the 2011 Great East Japan Earthquake and Tsunami

Background: Little research has examined associations between disaster-related home loss and multiple domains of health and well-being, with extended long-term follow-up and comprehensive adjustment for pre-disaster characteristics of survivors.Objectives: We examined the longitudinal associations between disaster-induced home loss and 34 indicators of health and well-being, assessed ∼9y post-disaster.Methods: We used data from a preexisting cohort study of Japanese older adults in an area directly impacted by the 2011 Japan Earthquake (n=3,350 and n=2,028, depending on the outcomes). The study was initiated in 2010, and disaster-related home loss status was measured in 2013 retrospectively. The 34 outcomes were assessed in 2020 and covered dimensions of physical health, mental health, health behaviors/sleep, social well-being, cognitive social capital, subjective well-being, and prosocial/altruistic behaviors. We estimated the associations between disaster-related home loss and the outcomes, using targeted maximum likelihood estimation and SuperLearner. We adjusted for pre-disaster characteristics from the wave conducted 7 months before the disaster (i.e., 2010), including prior outcome values that were available.Results: After Bonferroni correction for multiple testing, we found that home loss (vs. no home loss) was associated with increased posttraumatic stress symptoms (standardized difference=0.50; 95% CI: 0.35, 0.65), increased daily sleepiness (0.38; 95% CI: 0.21, 0.54), lower trust in the community (−0.36; 95% CI: −0.53, −0.18), lower community attachment (−0.60; 95% CI: −0.75, −0.45), and lower prosociality (−0.39; 95% CI: −0.55, −0.24). We found modest evidence for the associations with increased depressive symptoms, increased hopelessness, more chronic conditions, higher body mass index, lower perceived mutual help in the community, and decreased happiness. There was little evidence for associations with the remaining 23 outcomes.Discussion: Home loss due to a disaster may have long-lasting adverse impacts on the cognitive social capital, mental health, and prosociality of older adult survivors. https://doi.org/10.1289/EHP10903     

Biomarkers of Exposure to Phthalate Mixtures and Adverse Birth Outcomes in a Puerto Rico Birth Cohort

Background: Humans are exposed to complex mixtures of phthalate chemicals from a range of consumer products. Previous studies have reported significant associations between individual phthalate metabolites and pregnancy outcomes, but mixtures research is limited.Objectives: We used the Puerto Rico Testsite for Exploring Contamination Threats longitudinal pregnancy cohort to investigate associations between phthalate metabolite mixtures and pregnancy outcomes.Methods: Women (n=462 carrying females, n=540 carrying males) provided up to three urine samples throughout gestation (median 18, 22, and 26 wk), which were analyzed for 13 phthalate metabolites. Pregnancy outcomes including preterm birth (PTB), spontaneous PTB, small and large for gestational age (SGA, LGA), birth weight z-score, and gestational age at delivery were abstracted from medical records. Environmental risk scores (ERS) were calculated as a weighted linear combination of the phthalates from ridge regression and adaptive elastic net, which are variable selection methods to handle correlated predictors. Birth outcomes were regressed on continuous ERS. We assessed gestational average and visit-specific ERS and stratified all analyses by fetal sex. Finally, we used Bayesian kernel machine regression (BKMR) to explore nonlinear associations and interactions between metabolites.Results: Differences in metabolite weights from ridge and elastic net were apparent between birth outcomes and between fetal sexes. An interquartile range increase in gestational average phthalate ERS was associated with increased odds of PTB [male oddsratio(OR)=1.56; 95% confidence interval (CI): 1.08, 2.27; female OR=1.91; 95% CI: 1.23, 2.98], spontaneous PTB (male OR=2.32; 95% CI: 1.46, 3.68; female OR=2.00; 95% CI: 1.04, 3.82), and reduced gestational age at birth (male β=−0.39 wk, 95% CI: −0.62, −0.15; female β=−0.29 wk, 95% CI: −0.52, −0.05). Analyses by study visit suggested that exposure at ∼22 wk (range 20–24 wk) was driving those associations. Bivariate plots from BKMR analysis revealed some nonlinear associations and metabolite interactions that were different between fetal sexes.Discussion: These results suggest that exposure to phthalate mixtures was associated with increased risk of early delivery and highlight the need to study mixtures by fetal sex. We also identified various metabolites displaying nonlinear relationships with measures of birth weight. https://doi.org/10.1289/EHP8990     

Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood

Background: Metal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants.Objectives: We evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress.Methods: We measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn (n=898) and TL (n=893) in second-trimester maternal blood and mtDNAcn (n=419) and TL (n=408) in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions.Results: A 2-fold increase in maternal magnesium was associated with lower maternal [β=−0.07, 95% confidence interval (CI): −0.10, −0.01] and cord blood (β=−0.08, 95% CI: −0.20, −0.01) mtDNAcn. Lead was associated with higher maternal mtDNAcn (β=0.04, 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL (β=0.30, 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn (β=0.04, 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium.Discussion: Maternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294     

Maternal Phthalate and Bisphenol Urine Concentrations during Pregnancy and Early Markers of Arterial Health in Children

Background: Fetal exposure to endocrine-disrupting chemicals such as phthalates and bisphenols might lead to fetal cardiovascular developmental adaptations and predispose individuals to cardiovascular disease in later life.Objectives: We examined the associations of maternal urinary bisphenol and phthalate concentrations in pregnancy with offspring carotid intima-media thickness and distensibility at the age of 10 y.Methods: In a population-based, prospective cohort study of 935 mother–child pairs, we measured maternal urinary phthalate and bisphenol concentrations at each trimester. Later, we measured child carotid intima-media thickness and distensibility in the children at age 10 y using ultrasound.Results: Maternal urinary average or trimester-specific phthalate concentrations were not associated with child carotid intima-media thickness at age 10 y. Higher maternal average concentrations of total bisphenol, especially bisphenol A, were associated with a lower carotid intima-media thickness [differences −0.15 standard deviation score and 95% confidence interval (CI): −0.24, −0.09 and −0.13 (95% CI: −0.22, −0.04) per interquartile range (IQR) increase in maternal urinary total bisphenol and bisphenol A concentration]. Trimester-specific analysis showed that higher maternal third-trimester total bisphenol and bisphenol A concentrations were associated with lower child carotid intima-media thickness [differences −0.13 (95% CI: −0.22, −0.04) and −0.13 (95% CI: −0.22, −0.05) per IQR increase in maternal urinary bisphenol concentration]. Maternal urinary bisphenol or phthalate concentrations were not associated with child carotid distensibility.DISCUSSION: In this large prospective cohort, higher maternal urinary bisphenols concentrations were associated with smaller childhood carotid intima-media thickness. Further studies are needed to replicate this association and to identify potential underlying mechanisms. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10293","term_id":"372009678","term_text":"EHP10293"}}EHP10293     

Prenatal Exposure to Air Pollution and Autism Spectrum Disorder: Sensitive Windows of Exposure and Sex Differences

Background: Studies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters.Objective: We identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort.Methods: This population-based retrospective cohort study included 294,937 mother–child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of ≤2.5μm (PM2.5)], nitrogen dioxide (NO2), and ozone (O3) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season.Results: There were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive PM2.5 exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1–27 wk of gestation, cumulative hazard ratio (HR)=1.14 [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) (7.4-μg/m3) increase]. O3 exposure during 34–37 wk of gestation was associated with increased risk [HR=1.06 (95% CI: 1.01, 1.11) per IQR (17.4 ppb) increase] but with reduced risk during 20–28 wk of gestation [HR=0.93 (95% CI: 0.89, 0.98)]. No associations were observed with NO2. Sex-stratified early gestational PM2.5 associations were stronger among boys [boys HR=1.16 (95% CI: 1.08, 1.26); girls HR=1.06 (95% CI: 0.89, 1.26)]. O3 associations in later gestation were observed only in boys [boys HR=1.10 (95% CI: 1.04, 1.16); girls HR=0.94 (95% CI: 0.84, 1.05)].Conclusions: Exposures to PM2.5 in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of O3 exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509     

Prenatal Exposure to Nonpersistent Chemical Mixtures and Fetal Growth: A Population-Based Study

Background: Prenatal exposure to mixtures of nonpersistent chemicals is universal. Most studies examining these chemicals in association with fetal growth have been restricted to single exposure models, ignoring their potentially cumulative impact.Objective: We aimed to assess the association between prenatal exposure to a mixture of phthalates, bisphenols, and organophosphate (OP) pesticides and fetal measures of head circumference, femur length, and weight.Methods: Within the Generation R Study, a population-based cohort in Netherlands (n=776), urinary concentrations of 11 phthalate metabolites, 3 bisphenols, and 5 dialkylphosphate (DAP) metabolites were measured at <18, 18–25, and >25 weeks of gestation and averaged. Ultrasound measures of head circumference, femur length, and estimated fetal weight (EFW) were taken at 18–25 and >25 weeks of gestation, and measurements of head circumference, length, and weight were performed at delivery. We estimated the difference in each fetal measurement per quartile increase in all exposures within the mixture with quantile g-computation.Results: The average EFW at 18–25 wk and >25wk was 369 and 1,626g, respectively, and the average birth weight was 3,451g. Higher exposure was associated with smaller fetal and newborn growth parameters in a nonlinear fashion. At 18–25 wk, fetuses in the second, third, and fourth quartiles of exposure (Q2–Q4) had 26g [95% confidence intervals (CI):−38, −13], 35g (95% CI: −55, −15), and 27g (95% CI: −54, 1) lower EFW compared with those in the first quartile (Q1). A similar dose–response pattern was observed at >25wk, but all effect sizes were smaller, and no association was observed comparing Q4 to Q1. At birth, we observed no differences in weight between Q1–Q2 or Q1–Q3. However, fetuses in Q4 had 91g (95% CI: −258, 76) lower birth weight in comparison with those in Q1. Results observed at 18–25 and >25wk were similar for femur length; however, no differences were observed at birth. No associations were observed for head circumference.Discussion: Higher exposure to a mixture of phthalates, bisphenols, and OP pesticides was associated with lower EFW in the midpregnancy period. In late pregnancy, these differences were similar but less pronounced. At birth, the only associations observed appeared when comparing individuals from Q1 and Q4. This finding suggests that even low levels of exposure may be sufficient to influence growth in early pregnancy, whereas higher levels may be necessary to affect birth weight. Joint exposure to nonpersistent chemicals may adversely impact fetal growth, and because these exposures are widespread, this impact could be substantial. https://doi.org/10.1289/EHP9178     

Associations of Childhood and Perinatal Blood Metals with Children’s Gut Microbiomes in a Canadian Gestation Cohort

Background: The gut microbiome is important in modulating health in childhood. Metal exposures affect multiple health outcomes, but their ability to modify bacterial communities in children is poorly understood.Objectives: We assessed the associations of childhood and perinatal blood metal levels with childhood gut microbiome diversity, structure, species, gene family-inferred species, and potential pathway alterations.Methods: We assessed the gut microbiome using 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing in stools collected from 6- to 7-year-old children participating in the GESTation and Environment (GESTE) cohort study. We assessed blood metal concentrations [cadmium (Cd), manganese (Mn), mercury (Hg), lead (Pb), selenium (Se)] at two time points, namely, perinatal exposures at delivery (N=70) and childhood exposures at the 6- to 7-y follow-up (N=68). We used multiple covariate-adjusted statistical models to determine microbiome associations with continuous blood metal levels, including linear regression (Shannon and Pielou alpha diversity indexes), permutational multivariate analysis of variance (adonis; beta diversity distance matrices), and multivariable association model (MaAsLin2; phylum, family, species, gene family-inferred species, and pathways).Results: Children’s blood Mn and Se significantly associated with microbiome phylum [e.g., Verrucomicrobiota (coef=−0.305, q=0.031; coef=0.262, q=0.084, respectively)] and children’s blood Mn significantly associated with family [e.g., Eggerthellaceae (coef=−0.228, q=0.052)]-level differences. Higher relative abundance of potential pathogens (e.g., Flavonifractor plautii), beneficial species (e.g., Bifidobacterium longum, Faecalibacterium prausnitzii), and both potentially pathogenic and beneficial species (e.g., Bacteriodes vulgatus, Eubacterium rectale) inferred from gene families were associated with higher childhood or perinatal blood Cd, Hg, and Pb (q<0.1). We found significant negative associations between childhood blood Pb and acetylene degradation pathway abundance (q<0.1). Finally, neither perinatal nor childhood metal concentrations were associated with children’s gut microbial inter- and intrasubject diversity.Discussion: Our findings suggest both long- and short-term associations between metal exposure and the childhood gut microbiome, with stronger associations observed with more recent exposure. Future epidemiologic analyses may elucidate whether the observed changes in the microbiome relate to children’s health. https://doi.org/10.1289/EHP9674     

Maternal Levels of Perfluoroalkyl Substances (PFAS) during Early Pregnancy in Relation to Preeclampsia Subtypes and Biomarkers of Preeclampsia Risk

Background: Prenatal exposure to perfluoroalkyl substances (PFAS) has been previously associated with preeclampsia, although findings are mixed with respect to the direction and magnitude of effect. To our knowledge, no studies have examined associations between PFAS and preeclampsia subtypes, which may have distinct etiologies.Objective: We examined associations between PFAS, any preeclampsia diagnosis, and early- and late-onset preeclampsia. In addition, we estimated associations between PFAS and the angiogenic biomarkers soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF), which provide an estimate of pro- and anti-angiogenic activity within the placenta.Methods: This case–control study (n=75 cases, n=75 controls) was sampled from the LIFECODES birth cohort. Nine legacy PFAS were quantified in maternal plasma from early pregnancy (median= 10 wk) and angiogenic biomarkers were quantified in maternal plasma from four study visits (median= 10, 18, 26, and 35 wk). Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the association between an interquartile range (IQR)-increase in PFAS and preeclampsia outcomes. Linear regression was used to estimate associations between an IQR-increase in PFAS and concentrations of angiogenic biomarkers.Results: Both perfluorodecanoic acid (OR= 1.64, 95% CI: 1.08, 2.47) and perfluorooctanesulfonic acid (OR= 1.60, 95% CI: 1.06, 2.43) were associated with higher odds of late-onset preeclampsia. Associations tended to be below the null for early-onset preeclampsia, although findings were imprecise. Few associations were noted between PFAS and angiogenic biomarkers.Discussion: Maternal PFAS concentrations were associated with higher odds of late-onset preeclampsia. Heterogeneity of preeclampsia should be considered in future studies because populations may have different distributions of disease subtypes. https://doi.org/10.1289/EHP9091     

Sociodemographic Patterns of Exposure to Civil Aircraft Noise in the United States

Background: Communities with lower socioeconomic status and higher prevalence of racial/ethnic minority populations are often more exposed to environmental pollutants. Although studies have shown associations between aircraft noise and property values and various health outcomes, little is known about how aircraft noise exposures are sociodemographically patterned.Objective: Our aim was to describe characteristics of populations exposed to aviation noise by race/ethnicity, education, and income in the United States.Methods: Aircraft noise contours characterized as day–night average sound level (DNL) were developed for 90 U.S. airports in 2010 for DNL ≥45 dB(A) in 1-dB(A) increments. We compared characteristics of exposed U.S. Census block groups at three thresholds (≥45, ≥55, and ≥65 dB(A)), assigned on the basis of the block group land area being ≥50% within the threshold, vs. unexposed block groups near study airports. Comparisons were made across block group race/ethnicity, education, and income categories within the study areas (n=4,031–74,253). We performed both multinomial and other various multivariable regression approaches, including models controlling for airport and models with random intercepts specifying within-airport effects and adjusting for airport-level means.Results: Aggregated across multiple airports, block groups with a higher Hispanic population had higher odds of being exposed to aircraft noise. For example, the multinomial analysis showed that a 10-percentage point increase in a block group’s Hispanic population was associated with an increased odds ratio of 39% (95% CI: 25%, 54%) of being exposed to ≥65 dB(A) compared with block groups exposed to <45 dB(A). Block groups with higher proportions of residents with only a high school education had higher odds of being exposed to aircraft noise. Results were robust across multiple regression approaches; however, there was substantial heterogeneity across airports.Discussion: These results suggest that across U.S. airports, there is indication of sociodemographic disparities in noise exposures. https://doi.org/10.1289/EHP9307     

Estimating the Effects of Soil Remediation on Children’s Blood Lead near a Former Lead Smelter in Omaha,Nebraska, USA

Background: Lead exposures from legacy sources threaten children’s health. Soil in Omaha, Nebraska, was contaminated by emissions from a lead smelter and refinery. The U.S. Environmental Protection Agency excavated and replaced contaminated soil at the Omaha Lead Superfund Site between 1999 and 2016.Objectives: The goal of this study was to assess the association of soil lead level (SLL) and soil remediation status with blood lead levels (BLLs) in children living near or on the site.Methods: We linked information on SLL at residential properties with children’s BLLs and assigned remediation status to children’s BLL measurements based on whether their measurements occurred during residence at remediated or unremediated properties. We examined the association of SLL and remediation status with elevated BLL (EBLL). We distinguished the roles of temporal trend and the intervention with time-by-intervention-status interaction contrasts. All analyses estimated odds ratios (ORs) with a generalized estimating equations approach to ensure robustness under the complex correlations among BLL measurements. All analyses controlled for relevant covariates including children’s characteristics.Results: EBLL (>5μg/dL) was associated with both residential SLL [e.g., OR=2.00; 95% confidence interval (CI): 1.83, 2.19; >400–800 vs. ≤200 ppm] and neighborhood SLL [e.g., OR=1.85 (95% CI: 1.62, 2.11; >400–800 vs. ≤200 ppm)] before remediation but only with neighborhood SLL after remediation. The odds of EBLL were higher before remediation [OR 1.52 (95% CI: 1.34, 1.72)]. Similarly, EBLL was positively associated with preremediation status in our interaction analysis [interaction OR=1.18 (95%CI: 1.02, 1.37)].Discussion: Residential and neighborhood SLLs were important predictors of EBLLs in children residing near or on this Superfund site. Neighborhood SLL remained a strong predictor following remediation. Our data analyses showed the benefit of soil remediation. Results from the interaction analyses should be interpreted cautiously due to imperfect correspondence of remediation times between remediation and comparison groups. https://doi.org/10.1289/EHP8657     

Efficacy of Air Filtration and Education Interventions on Indoor Fine Particulate Matter and Child Lower Respiratory Tract Infections among Rural U.S. Homes Heated with Wood Stoves: Results from the KidsAIR Randomized Trial

Background: Millions of rural U.S. households are heated with wood stoves. Wood stove use can lead to high indoor concentrations of fine particulate matter [airborne particles ≤2.5μm in aerodynamic diameter (PM2.5)] and is associated with lower respiratory tract infection (LRTI) in children.Objectives: We assessed the impact of low-cost educational and air filtration interventions on childhood LRTI and indoor PM2.5 in rural U.S. homes with wood stoves.Methods: The Kids Air Quality Interventions for Reducing Respiratory Infections (KidsAIR) study was a parallel three-arm (education, portable air filtration unit, control), post-only randomized trial in households from Alaska, Montana, and Navajo Nation (Arizona and New Mexico) with a wood stove and one or more children <5 years of age. We tracked LRTI cases for two consecutive winter seasons and measured indoor PM2.5 over a 6-d period during the first winter. We assessed results using two analytical frameworks: a) intervention efficacy on LRTI and PM2.5 (intent-to-treat), and b) association between PM2.5 and LRTI (exposure–response).Results: There were 61 LRTI cases from 14,636 child-weeks of follow-up among 461 children. In the intent-to-treat analysis, children in the education arm [odds ratio (OR)=0.98; 95% confidence interval (CI): 0.35, 2.72] and the filtration arm (OR=1.23; 95% CI: 0.46, 3.32) had similar odds of LRTI vs. control. Geometric mean PM2.5 concentrations were similar to control in the education arm (11.77% higher; 95% CI: −16.57, 49.72) and air filtration arm (6.96% lower; 95% CI: −30.50, 24.55). In the exposure–response analysis, odds of LRTI were 1.45 times higher (95% CI: 1.02, 2.05) per interquartile range (25μg/m3) increase in mean indoor PM2.5.Discussion: We did not observe meaningful differences in LRTI or indoor PM2.5 in the air filtration or education arms compared with the control arm. Results from the exposure–response analysis provide further evidence that biomass air pollution adversely impacts childhood LRTI. Our results highlight the need for novel, effective intervention strategies in households heated with wood stoves. https://doi.org/10.1289/EHP9932