Table of Contents

Abstract

Background: Many personal care products include chemicals that might act as endocrine disruptors and thus increase the risk of breast cancer.

Objective: We examined the association between usage patterns of beauty, hair, and skin-related personal care products and breast cancer incidence in the Sister Study, a national prospective cohort study (enrollment 2003–2009).

Methods: Non-Hispanic black (4,452) and white women ($n=\mathrm{42,453}$) were examined separately using latent class analysis (LCA) to identify groups of individuals with similar patterns of self-reported product use in three categories (beauty, skin, hair). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between product use and breast cancer incidence.

Results: A total of 2,326 women developed breast cancer during follow-up ($\text{average}\text{follow}\text{-up}=5.4\mathrm{y}$). Among black women, none of the latent class hazard ratios was elevated, but there were $<100$ cases in any category, limiting power. Among white women, those classified as “moderate” and “frequent” users of beauty products had increased risk of breast cancer relative to “infrequent” users [$\text{HR}=1.13$ (95% CI: 1.00, 1.27) and $\text{HR}=1.15$ (95% CI: 1.02, 1.30), respectively]. Frequent users of skincare products also had increased risk of breast cancer relative to infrequent users [$\text{HR}=1.13$ (95% CI: 1.00, 1.29)]. None of the hair product classes was associated with increased breast cancer risk. The associations with beauty and skin products were stronger in postmenopausal women than in premenopausal women, but not significantly so.

Conclusions: This work generates novel hypotheses about personal care product use and breast cancer risk. Whether these results are due to specific chemicals or to other correlated behaviors needs to be evaluated. https://doi.org/10.1289/EHP1480

Abstract

Background: Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema.

Objectives: We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals.

Methods: Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children’s ages of 1–5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother–son pairs with adjusted multiple logistic regression and Cox’s survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment.

Results: At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0–24 mo of age) eczema (15.7%) and late-onset (24–60 mo of age) eczema (14.7%). Applying the Cox’s model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di-n-butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio $\left(\text{HR}\right)=1.67$ [95% confidence interval (CI): 1.10, 2.54], $p=0.01$ and $\text{HR}=1.87$ (95% CI: 1.01, 3.48), $p=0.04$, respectively}.

Conclusions: Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. https://doi.org/10.1289/EHP1829

Abstract

Background: Proponents of the biophilia hypothesis believe that contact with nature, including green spaces, has a crucial role in brain development in children. Currently, however, we are not aware of evidence linking such exposure with potential effects on brain structure.

Objective: We determined whether lifelong exposure to residential surrounding greenness is associated with regional differences in brain volume based on 3-dimensional magnetic resonance imaging (3D MRI) among children attending primary school.

Methods: We performed a series of analyses using data from a subcohort of 253 Barcelona schoolchildren from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project. We averaged satellite-based normalized difference vegetation index (NDVI) across $100\text{-}\mathrm{m}$ buffers around all residential addresses since birth to estimate each participant’s lifelong exposure to residential surrounding greenness, and we used high-resolution 3D MRIs of brain anatomy to identify regional differences in voxel-wise brain volume associated with greenness exposure. In addition, we performed a supporting substudy to identify regional differences in brain volume associated with measures of working memory (d′ from computerized n-back tests) and inattentiveness (hit reaction time standard error from the Attentional Network Task instrument) that were repeated four times over one year. We also performed a second supporting substudy to determine whether peak voxel tissue volumes in brain regions associated with residential greenness predicted cognitive function test scores.

Results: Lifelong exposure to greenness was positively associated with gray matter volume in the left and right prefrontal cortex and in the left premotor cortex and with white matter volume in the right prefrontal region, in the left premotor region, and in both cerebellar hemispheres. Some of these regions partly overlapped with regions associated with cognitive test scores (prefrontal cortex and cerebellar and premotor white matter), and peak volumes in these regions predicted better working memory and reduced inattentiveness.

Conclusion: Our findings from a study population of urban schoolchildren in Barcelona require confirmation, but they suggest that being raised in greener neighborhoods may have beneficial effects on brain development and cognitive function. https://doi.org/10.1289/EHP1876

Abstract

Background: It has been proposed that interactions between selenium and arsenic in the body may affect their kinetics and toxicity. However, it is unknown how the elements influence each other in humans.

Objectives: We aimed to investigate potential interactions in the methylation of selenium and arsenic.

Methods: Urinary selenium (U-Se) and arsenic (U-As) were measured using inductively coupled plasma mass spectrometry (ICPMS) in samples collected from pregnant women ($n=226$) in rural Bangladesh at gestational weeks (GW) 8, 14, 19, and 30. Urinary concentrations of trimethyl selenonium ion (TMSe) were measured by HPLC–vapor generation–ICPMS, as were inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA). Methylation efficiency was assessed based on relative amounts (%) of arsenic and selenium metabolites in urine. Genotyping for the main arsenite and selenium methyltransferases, AS3MT and INMT, was performed using TaqMan probes or Sequenom.

Results: Multivariable-adjusted linear regression analyses indicated that %TMSe (at GW8) was positively associated with %MMA ($\mathrm{\beta }=1.3$, 95% CI: 0.56, 2.0) and U-As, and inversely associated with %DMA and U-Se in producers of TMSe (INMT rs6970396 $\text{AG}+\text{AA}$, $n=74$), who had a wide range of urinary TMSe (12–42%). Also, %TMSe decreased in parallel to %MMA during pregnancy, especially in the first trimester ($-0.58$ %TMSe per gestational week). We found a gene–gene interaction for %MMA ($p-\text{interaction}=0.076$ for haplotype 1). In analysis stratified by INMT genotype, the association between %MMA and both AS3MT haplotypes 1 and 3 was stronger in women with the INMT GG (TMSe nonproducers, 5th–95th percentile: 0.2–2%TMSe) vs. $\text{AG}+\text{AA}$ genotype.

Conclusions: Our findings for Bangladeshi women suggest a positive association between urinary %MMA and %TMSe. Genes involved in the methylation of selenium and arsenic may interact on associations with urinary %MMA. https://doi.org/10.1289/EHP1912

Abstract

Background: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain this association.

Objectives: Our main aim was to study the association between long-term air pollution exposure and DNA methylation.

Methods: We performed a genome-wide methylation study using robust linear regression models in 1,017 subjects from the LifeLines cohort study to analyze the association between exposure to nitrogen dioxide ( ${\text{NO}}_2$) and particulate matter ( ${\mathrm{PM}}_{2.5}$, fine particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$; ${\mathrm{PM}}_{10}$, particulate matter with aerodynamic diameter $\le 10\mathrm{\mu }\mathrm{m}$) and ${\mathrm{PM}}_{2.5\text{absorbance}}$, indicator of elemental carbon content (estimated with land-use-regression models) with DNA methylation in whole blood (Illumina® HumanMethylation450K BeadChip). Replication of the top hits was attempted in two independent samples from the population-based Cooperative Health Research in the Region of Augsburg studies (KORA).

Results: Depending on the p-value threshold used, we found significant associations between ${\text{NO}}_2$ exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold $p<1.19\times {10}^{-7}$) or for 4,980 CpG sites (False Discovery $\text{Rate}<0.05$). The top associated CpG site was annotated to the PSMB9 gene (i.e., cg04908668). None of the seven Bonferroni significant CpG-sites were significantly replicated in the two KORA-cohorts. No associations were found for PM exposure.

Conclusions: Long-term ${\text{NO}}_2$ exposure was genome-wide significantly associated with DNA methylation in the identification cohort but not in the replication cohort. Future studies are needed to further elucidate the potential mechanisms underlying ${\text{NO}}_2-\text{exposure}$–related respiratory disease. https://doi.org/10.1289/EHP2045

Abstract

Background: Although epidemiologic studies have shown associations between particle mass and daily mortality, evidence on other particle metrics is weak.

Objectives: We investigated associations of size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) with cause-specific daily mortality in contrast to ${\mathrm{PM}}_{10}$.

Methods: We used time-series data (March 2009–December 2014) on daily natural, cardiovascular, and respiratory mortality (NM, CVM, RM) of three adjacent cities in the Ruhr Area, Germany. Size-specific PNC (electric mobility diameter of $13.3–750\text{nm}$), PSC, and ${\mathrm{PM}}_{10}$ were measured at an urban background monitoring site. In single- and multipollutant Poisson regression models, we estimated percentage change (95% confidence interval) [% (95% CI)] in mortality per interquartile range (IQR) in exposure at single-day (0–7) and aggregated lags (0–1, 2–3, 4–7), accounting for time trend, temperature, humidity, day of week, holidays, period of seasonal population decrease, and influenza.

Results: ${\text{PNC}}_{100–750}$ and PSC were highly correlated and had similar immediate (lag0–1) and delayed (lag4–7) associations with NM and CVM, for example, 1.12% (95% CI: 0.09, 2.33) and 1.56% (95% CI: 0.22, 2.92) higher NM with IQR increases in ${\text{PNC}}_{100–750}$ at lag0–1 and lag4–7, respectfully, which were slightly stronger then associations with IQR increases in ${\mathrm{PM}}_{10}$. Positive associations between PNC and NM were strongest for accumulation mode particles (PNC $100–500\text{nm}$), and for larger UFPs (PNC $50–100\text{nm}$). Associations between NM and ${\text{PNC}}_{<100}$ changed little after adjustment for ${\mathrm{O}}_3$ or ${\mathrm{PM}}_{10}$, but were more sensitive to adjustment for ${\text{NO}}_2$.

Conclusion: Size-specific PNC ($50–500\text{nm}$) and lung-deposited PSC were associated with natural and cardiovascular mortality in the Ruhr Area. Although associations were similar to those estimated for an IQR increase in ${\mathrm{PM}}_{10}$, particle number size distributions can be linked to emission sources, and thus may be more informative for potential public health interventions. Moreover, PSC could be used as an alternative metric that integrates particle size distribution as well as deposition efficiency. https://doi.org/10.1289/EHP2054

Abstract

Background: Increasing evidence links higher particulate matter (PM) air pollution exposure to late-life cognitive impairment. However, few studies have considered associations between direct estimates of long-term past exposures and brain MRI findings indicative of neurodegeneration or cerebrovascular disease.

Objective: Our objective was to quantify the association between brain MRI findings and PM exposures approximately 5 to 20 y prior to MRI in the Atherosclerosis Risk in Communities (ARIC) study.

Methods: ARIC is based in four U.S. sites: Washington County, Maryland; Minneapolis suburbs, Minnesota; Forsyth County, North Carolina; and Jackson, Mississippi. A subset of ARIC participants underwent 3T brain MRI in 2011–2013 ($n=\mathrm{1,753}$). We estimated mean exposures to PM with an aerodynamic diameter less than 10 or $2.5\mathrm{\mu }\mathrm{m}$ (${\mathrm{PM}}_{10}$ and ${\mathrm{PM}}_{2.5}$) in 1990–1998, 1999–2007, and 1990–2007 at the residential addresses of eligible participants with MRI data. We estimated site-specific associations between PM and brain MRI findings and used random-effect, inverse variance–weighted meta-analysis to combine them.

Results: In pooled analyses, higher mean ${\mathrm{PM}}_{2.5}$ and ${\mathrm{PM}}_{10}$ exposure in all time periods were associated with smaller deep-gray brain volumes, but not other MRI markers. Higher ${\mathrm{PM}}_{2.5}$ exposures were consistently associated with smaller total and regional brain volumes in Minnesota, but not elsewhere.

Conclusions: Long-term past PM exposure in was not associated with markers of cerebrovascular disease. Higher long-term past PM exposures were associated with smaller deep-gray volumes overall, and higher ${\mathrm{PM}}_{2.5}$ exposures were associated with smaller brain volumes in the Minnesota site. Further work is needed to understand the sources of heterogeneity across sites. https://doi.org/10.1289/EHP2152

Abstract

Background: Electronic cigarettes (e-cigarettes) generate an aerosol by heating a solution (e-liquid) with a metallic coil. Whether metals are transferred from the coil to the aerosol is unknown.

Objective: Our goal was to investigate the transfer of metals from the heating coil to the e-liquid in the e-cigarette tank and the generated aerosol.

Methods: We sampled 56 e-cigarette devices from daily e-cigarette users and obtained samples from the refilling dispenser, aerosol, and remaining e-liquid in the tank. Aerosol liquid was collected via deposition of aerosol droplets in a series of conical pipette tips. Metals were reported as mass fractions ($\mathrm{\mu }\mathrm{g}/\mathrm{kg}$) in liquids and converted to mass concentrations (${\mathrm{mg}/\mathrm{m}}^3$) for aerosols.

Results: Median metal concentrations ($\mathrm{\mu }\mathrm{g}/\mathrm{kg}$) were higher in samples from the aerosol and tank vs. the dispenser (all $p<0.001$): 16.3 and 31.2 vs. 10.9 for Al; 8.38 and 55.4 vs. $<0.5$ for Cr; 68.4 and 233 vs. 2.03 for Ni; 14.8 and 40.2 vs. 0.476 for Pb; and 515 and 426 vs. 13.1 for Zn. Mn, Fe, Cu, Sb, and Sn were detectable in most samples. Cd was detected in 0.0, 30.4, and 55.1% of the dispenser, aerosol, and tank samples respectively. Arsenic was detected in 10.7% of dispenser samples (median $26.7\mathrm{\mu }\mathrm{g}/\mathrm{kg}$) and these concentrations were similar in aerosol and tank samples. Aerosol mass concentrations (${\mathrm{mg}/\mathrm{m}}^3$) for the detected metals spanned several orders of magnitude and exceeded current health-based limits in close to 50% or more of the samples for Cr, Mn, Ni, and Pb.

Conclusions: Our findings indicate that e-cigarettes are a potential source of exposure to toxic metals (Cr, Ni, and Pb), and to metals that are toxic when inhaled (Mn and Zn). Markedly higher concentrations in the aerosol and tank samples versus the dispenser demonstrate that coil contact induced e-liquid contamination. https://doi.org/10.1289/EHP2175

Abstract

Background: Few epidemiologic studies have investigated health effects of water-soluble fractions of ${\mathrm{PM}}_{2.5}$ metals, the more biologically accessible fractions of metals, in their attempt to identify health-relevant components of ambient ${\mathrm{PM}}_{2.5}$.

Objectives: In this study, we estimated acute cardiovascular effects of ${\mathrm{PM}}_{2.5}$ components in an urban population, including a suite of water-soluble metals that are not routinely measured at the ambient level.

Methods: Ambient concentrations of criteria gases, ${\mathrm{PM}}_{2.5}$, and ${\mathrm{PM}}_{2.5}$ components were measured at a central monitor in Atlanta, Georgia, during 1998–2013, with some ${\mathrm{PM}}_{2.5}$ components only measured during 2008–2013. In a time-series framework using Poisson regression, we estimated associations between these pollutants and daily counts of emergency department (ED) visits for cardiovascular diseases in the five-county Atlanta area.

Results: Among the ${\mathrm{PM}}_{2.5}$ components we examined during 1998–2013, water-soluble iron had the strongest estimated effect on cardiovascular outcomes [$\widehat{RR}=1.012$ (95% CI: 1.005, 1.019), per interquartile range increase ($20.46\text{ng}/{\mathrm{m}}^3$)]. The associations for ${\mathrm{PM}}_{2.5}$ and other ${\mathrm{PM}}_{2.5}$ components were consistent with the null when controlling for water-soluble iron. Among ${\mathrm{PM}}_{2.5}$ components that were only measured during 2008–2013, water-soluble vanadium was associated with cardiovascular ED visits [$\widehat{RR}=1.012$ (95% CI: 1.000, 1.025), per interquartile range increase ($0.19\text{ng}/{\mathrm{m}}^3$)].

Conclusions: Our study suggests cardiovascular effects of certain water-soluble metals, particularly water-soluble iron. The observed associations with water-soluble iron may also point to certain aspects of traffic pollution, when processed by acidifying sulfate, as a mixture harmful for cardiovascular health. https://doi.org/10.1289/EHP2182

Abstract

Background: Limited evidence links air pollution exposure to chronic cough and sputum production. Few reports have investigated the association between long-term exposure to air pollution and classically defined chronic bronchitis.

Objectives: Our objective was to estimate the association between long-term exposure to particulate matter (diameter $<10\mathrm{\mu }\mathrm{m}$, ${\mathrm{PM}}_{10}$; $<2.5\mathrm{\mu }\mathrm{m}$, ${\mathrm{PM}}_{2.5}$), nitrogen dioxide $\left({\text{NO}}_2\right)$, and both incident and prevalent chronic bronchitis.

Methods: We estimated annual average ${\mathrm{PM}}_{2.5}$, ${\mathrm{PM}}_{10}$, and ${\text{NO}}_2$ concentrations using a national land-use regression model with spatial smoothing at home addresses of participants in a prospective nationwide U.S. cohort study of sisters of women with breast cancer. Incident chronic bronchitis and prevalent chronic bronchitis, cough and phlegm, were assessed by questionnaires.

Results: Among 47,357 individuals with complete data, 1,383 had prevalent chronic bronchitis at baseline, and 647 incident cases occurred over 5.7-y average follow-up. No associations with incident chronic bronchitis were observed. Prevalent chronic bronchitis was associated with ${\mathrm{PM}}_{10}$ [adjusted odds ratio (aOR) per interquartile range (IQR) difference $\left(5.8{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3\right)=1.07$; 95% confidence interval (CI): 1.01, 1.13]. In never-smokers, ${\mathrm{PM}}_{2.5}$ was associated with prevalent chronic bronchitis ( $\text{aOR}=1.18$ per IQR difference; 95% CI: 1.04, 1.34), and ${\text{NO}}_2$ was associated with prevalent chronic bronchitis ( $\text{aOR}=1.10$; $95\%\text{CI}=1.01,1.20$), cough ( $\text{aOR}=1.10$; 95% CI: 1.05, 1.16), and phlegm ( $\text{aOR}=1.07$; 95% CI: 1.01, 1.14); interaction p-values (nonsmokers vs. smokers) $<0.05$.

Conclusions: ${\mathrm{PM}}_{10}$ exposure was related to chronic bronchitis prevalence. Among never-smokers, ${\mathrm{PM}}_{2.5}$ and ${\text{NO}}_2$ exposure was associated with chronic bronchitis and component symptoms. Results may have policy ramifications for ${\mathrm{PM}}_{10}$ regulation by providing evidence for respiratory health effects related to long-term ${\mathrm{PM}}_{10}$ exposure. https://doi.org/10.1289/EHP2199

Abstract

Background: Exposure to ambient fine particulate matter (${\mathrm{PM}}_{2.5}$) is associated with cardiovascular mortality, but underlying pathophysiologic mechanisms are not fully understood. Hypothalamic inflammation, characterized by the activation of Inhibitor kappaB kinase 2/Nuclear factor kappaB ($\text{IKK}2/\text{NF}-\mathrm{\kappa }\mathrm{B}$) signaling pathway, may play an important role in the pathogenesis of cardiovascular diseases. We recently demonstrated that hypothalamic inflammation is increased in mice exposed to concentrated ambient ${\mathrm{PM}}_{2.5}$ (CAP).

Objectives: In the present study, we used a neuron-specific IKK2 knockout mouse model to examine the role of neural IKK2 expression and hypothalamic inflammation in the pathophysiologic effects of ${\mathrm{PM}}_{2.5}$.

Methods: We assessed inflammatory and vascular responses in $\text{Nestin}-\text{creIKK}{2}^{\text{flox}/\text{flox}}$ ($\text{IKK}{2}^{\text{Neu}-\text{KO}}$) and littermate $\text{Nestin}-\text{creIKK}{2}^{\text{flox}/+}$ (control) mice after 4 mo of exposure to filtered air (FA) or CAP.

Results: CAP exposure was associated with significantly higher tumor necrosis factor-$\mathrm{\alpha }$ $\left(\text{TNF}\mathrm{\alpha }\right)$ and interleukin (IL)-6 mRNA in the hypothalamus of control mice, but not $\text{IKK}{2}^{\text{Neu}-\text{KO}}$ mice. In addition, CAP exposure–induced increases in bronchoalveolar lavage fluid (BALF) leukocytes, pulmonary macrophage infiltration and IL-6 expression, plasma $\text{TNF}\mathrm{\alpha }$ and $\text{IL}-1\mathrm{\beta }$ levels, adipose macrophage infiltration and $\text{IL}-1\mathrm{\beta }$ expression, and endothelial dysfunction were reduced or absent in $\text{IKK}{2}^{\text{Neu}-\text{KO}}$ mice compared with controls.

Conclusions: Our findings support a role of neural IKK2 in CAP exposure–induced local and systemic pro-inflammatory cytokine expression, pulmonary and adipose inflammation, and endothelial dysfunction, thus providing insight into pathophysiologic mechanisms that may mediate effects of ${\mathrm{PM}}_{2.5}$ exposure. https://doi.org/10.1289/EHP2311

Abstract

Background: Prenatal exposure to some per- and polyfluoroalkyl substances (PFASs) may disrupt maternal and neonatal thyroid function, which is critical for normal growth and neurodevelopment.

Objectives: We examined associations of PFAS exposure during early pregnancy with maternal and neonatal thyroid hormone levels.

Methods: We studied 732 mothers and 480 neonates in Project Viva, a longitudinal prebirth cohort in Boston, Massachusetts. We quantified six PFASs, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), and maternal thyroid hormones [thyroxine (${\mathrm{T}}_4$), Free ${\mathrm{T}}_4$ Index (${\text{FT}}_4\mathrm{I}$), thyroid stimulating hormone (TSH)] in plasma samples collected at a median 9.6 wk gestation and neonatal ${\mathrm{T}}_4$ levels from postpartum heel sticks. We estimated associations of PFAS concentrations with thyroid hormone levels using covariate-adjusted linear regression models and explored effect measure modification by maternal thyroid peroxidase antibody (TPOAb) status and infant sex.

Results: PFAS concentrations were not associated with maternal ${\mathrm{T}}_4$, but PFOA, perfluorohexane sulfonate (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) were inversely associated with maternal ${\text{FT}}_4\mathrm{I}$ [e.g., $-1.87\%$ (95% confidence interval (CI): $-3.40$, $-0.31$) per interquartile (IQR) increase in PFOA]. PFAS concentrations [PFOA, PFOS, and perfluorononanoate (PFNA)] were inversely associated with TSH levels in TPOAb-positive women only. Prenatal PFOS, PFOA, and PFHxS concentrations were inversely associated with ${\mathrm{T}}_4$ levels in male [e.g., PFHxS, quartile 4 vs.1: $-2.51\mathrm{\mu }\mathrm{g}/\text{dL}$ (95% CI: $-3.99$, $-1.04$ )], but not female neonates [$0.40\mathrm{\mu }\mathrm{g}/\text{dL}$ (95% CI: $-0.98$, 1.79)].

Conclusions: In this study, prenatal exposure to some PFASs during early pregnancy was inversely associated with maternal ${\text{FT}}_4\mathrm{I}$ and neonatal ${\mathrm{T}}_4$ in male infants. These results support the hypothesis that prenatal exposure to PFASs influences thyroid function in both mothers and infants. https://doi.org/10.1289/EHP2534

Abstract

Background: Several studies have reported that cadmium (Cd) is associated with type 2 diabetes. However, little is known about Cd exposure and the risk of gestational diabetes mellitus (GDM).

Objective: We examined the association between Cd body burden in early pregnancy and the risk of GDM.

Methods: We conducted a prospective study of 2,026 pregnant women from a single tertiary medical center between 2013 and 2016 in Wuhan, China. Cd body burden was reflected by Cd concentrations in urine samples collected between gestational weeks 8 and 14. GDM was diagnosed according to International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations.

Results: The geometric mean of Cd concentrations in maternal urine of all pregnant women was $0.59\mathrm{\mu }\mathrm{g}/\mathrm{L}$. A total of 198 (9.8%) women were diagnosed with GDM. After adjustment for potential confounders, the risk ratios (RRs) of GDM were 1.04 (95% CI: 0.74, 1.44) for the middle tertile of Cd levels and 1.36 (95%: CI: 0.98, 1.90) for the top tertile compared with the bottom tertile. In addition, we found a significant interaction between fetal sex and maternal Cd levels on the risk of GDM ($p\text{for}\text{interaction}=0.03$). Among women carrying male fetuses, the RR of GDM was 1.86 (95% CI: 1.14, 2.93) for the top tertile of Cd levels compared with the bottom tertile.

Conclusions: To our knowledge, this is the first report of an association between urinary Cd levels in early pregnancy and GDM. Our findings suggest that Cd body burden increases the risk of GDM and that the association may be modified by fetal sex. https://doi.org/10.1289/EHP2716

Abstract

Background: Community-led total sanitation (CLTS) is a widely applied rural behavior change approach for ending open defecation. However, evidence of its impact is unclear.

Objectives: We conducted a systematic review of journal-published and gray literature to a) assess evidence quality, b) summarize CLTS impacts, and c) identify factors affecting implementation and effectiveness.

Methods: Eligible studies were systematically screened and selected for analysis from searches of seven databases and 16 websites. We developed a framework to appraise literature quality. We qualitatively analyzed factors enabling or constraining CLTS, and summarized results from quantitative evaluations.

Discussion: We included 200 studies (14 quantitative evaluations, 29 qualitative studies, and 157 case studies). Journal-published literature was generally of higher quality than gray literature. Fourteen quantitative evaluations reported decreases in open defecation, but did not corroborate the widespread claims of open defecation–free (ODF) villages found in case studies. Over one-fourth of the literature overstated conclusions, attributing outcomes and impacts to interventions without an appropriate study design. We identified 43 implementation- and community-related factors reportedly affecting CLTS. This analysis revealed the importance of adaptability, structured posttriggering activities, appropriate community selection, and further research on combining and sequencing CLTS with other interventions.

Conclusions: The evidence base on CLTS effectiveness available to practitioners, policy makers, and program managers to inform their actions is weak. Our results highlight the need for more rigorous research on CLTS impacts as well as applied research initiatives that bring researchers and practitioners together to address implementation challenges to improve rural sanitation efforts. https://doi.org/10.1289/EHP1965