BACKGROUND: Folate plays a critical role during pregnancy, preventing neural tube defects and possibly adverse neurodevelopment. Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that may decrease folate levels. Although some studies have found associations between PFAS and folate, we are unaware of studies conducted in pregnant women. To address this knowledge gap, we evaluated associations between PFAS and whole blood folate (WBF) in pregnant women. METHODS: We used data from 288 pregnant women in the Health Outcomes and Measures of the Environment (HOME) Study, a pregnancy and birth cohort in the Cincinnati Ohio area. We measured eight serum PFAS and WBF concentrations at 16 weeks' gestation. We used linear regression to estimate the effect of each PFAS on WBF, and quantile-based g-computation and Bayesian kernel machine regression (BKMR) to investigate the joint effect of PFAS on WBF, adjusting for parity, prenatal vitamin intake, maternal race/ethnicity, household income, maternal age, and second trimester smoking status in all models. In addition, we investigated interactions between PFAS using BKMR. RESULTS: We did not observe inverse associations of individual PFAS or their mixture with WBF, nor interactions between PFAS in the BKMR model in pregnant women. CONCLUSION: Future studies could consider WBF measures in late pregnancy to evaluate other periods of susceptibility. Furthermore, as people are exposed to multiple PFAS, future studies should continue to consider joint PFAS exposure.

BACKGROUND: Phthalate exposure during pregnancy has been associated with preterm birth, but mechanisms of action may depend on the timing of exposure. OBJECTIVE: Investigate critical periods of susceptibility during pregnancy for associations between urinary phthalate metabolite concentrations and preterm birth. METHODS: Individual-level data were pooled from 16 US cohorts (N = 6045, n = 539 preterm births). We examined trimester-averaged urinary phthalate metabolite concentrations. Most phthalate metabolites had 2248, 3703, and 3172 observations in the first, second, and third trimesters, respectively. Our primary analysis used logistic regression models with generalized estimating equations (GEE) under a multiple informant approach to estimate trimester-specific odds ratios (ORs) of preterm birth and significant (p < 0.20) heterogeneity in effect estimates by trimester. Adjusted models included interactions between each covariate and trimester. RESULTS: Differences in trimester-specific associations between phthalate metabolites and preterm birth were most evident for di-2-ethylhexyl phthalate (DEHP) metabolites. For example, an interquartile range increase in mono (2-ethylhexyl) phthalate (MEHP) during the first and second trimesters was associated with ORs of 1.15 (95 % confidence interval [CI]: 0.99, 1.33) and 1.11 (95 % CI: 0.97, 1.28) for preterm birth, respectively, but this association was null in the third trimester (OR = 0.91 [95 % CI: 0.76, 1.09]) (p-heterogeneity = 0.03). CONCLUSION: The association of preterm birth with gestational biomarkers of DEHP exposure, but not other phthalate metabolites, differed by the timing of exposure. First and second trimester exposures demonstrated the greatest associations. Our study also highlights methodological considerations for critical periods of susceptibility analyses in pooled studies.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), synthetic chemicals previously used as flame retardants in commercial products, impact human behaviors, mood symptoms and cognitive abilities. OBJECTIVE: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported ratings of executive function in a prospective pregnancy and birth cohort. METHODS: We measured gestational serum concentrations of five PBDE congeners and created a summary exposure variable (∑(5)BDE: 28, -47, -99, -100 and -153). At age 12 years, we assessed executive function for 237 adolescents using self- and caregiver-reports with the Behavior Rating Inventory of Executive Functioning (BRIEF-2). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log(10)-transformed gestational PBDE concentrations with BRIEF-2 T-scores. We evaluated potential effect measure modification (EMM) of sex by examining sex-stratified regression models. RESULTS: As higher scores indicate greater deficits in executive function, gestational PBDE concentrations were positively associated with adolescent-reported BRIEF-2 T-scores for Global Executive Composite (BDE-28: β = 6.31 (95%CI: 2.59, 10.03), BDE-47: (β = 3.32 (95%CI: 0.1, 6.54), ∑(5)BDE: (β = 3.70 (95%CI: 0.37, 7.03), Behavior Regulation Index (BDE-28: β = 5.36 (95%CI: 1.56, 9.15), BDE-99: β = 3.53 (95%CI: 0.33, 6.74), ∑(5)BDE: β = 3.93 (95%CI: 0.57, 7.3), Emotion Regulation Index (BDE-28: β = 4.76 (95%CI: 0.88, 8.64) and the Cognitive Regulation Index (BDE-28: β = 6.69 (95%CI: 3.08, 10.31), BDE-47: β = 3.45 (95%CI: 0.3, 6.59), ∑(5)BDE: β = 3.57 (95%CI: 0.32, 6.82) and several other scales. We observed stronger associations with gestational PBDE concentrations for all congeners among males, especially for the caregiver-rated scales (all EMM p-values <0.1). DISCUSSION: This study provides evidence that gestational PBDE serum concentrations may adversely influence offspring executive function during adolescence.

BACKGROUND: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery. METHODS: This study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways. RESULTS: We observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways. CONCLUSION: Maternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.

BACKGROUND: Environmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures. METHODS: In 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004 and 2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6-15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n = 179), paternal preconception (n = 121), and maternal pregnancy (n = 177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors. RESULTS: The mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (β(maternal_precon) = -1.6, 95% CI -2.7; -0.4; β(paternal_precon) = -2.9, 95% CI -4.6; -1.2) for each log(e) increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations. CONCLUSIONS: Urinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

BACKGROUND: Evidence from toxicological studies indicate organophosphate esters (OPEs) are neurotoxic, but few epidemiological studies investigated associations between gestational OPEs and executive function. OBJECTIVE: To examine the associations between gestational concentrations of OPE urinary metabolites and executive function at 12 years METHODS: We used data from 223 mother-adolescent dyads from the Health Outcomes of Measures of the Environment (HOME) Study. Women provided spot urine samples at 16 weeks gestation, 26 weeks gestation, and at delivery for quantification of bis(1,3-dichloro-2-propyl) phosphate, bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP). Executive function was assessed at age 12 years using the parent- and self-report Behavior Rating Inventory of Executive Function (BRIEF2). Covariate-adjusted associations between specific gravity-corrected OPEs and BRIEF2 scores were estimated using multiple informant models. Bayesian Kernel Machine Regression (BKMR) was used to assess the impact of all OPEs simultaneously. RESULTS: Parent- and self-report BRIEF2 indices and composite scores were weakly to moderately correlated (r(s)=0.32-0.41). A natural-log unit increase in BCEP at 26 weeks was associated with approximately a 1-point increase on the self-report Cognitive Regulation Index [CRI] (95% CI 0.4, 2.3), the Emotion Regulation Index [ERI] (95% CI 0.3, 2.2), and the Global Executive Composite [GEC] (95% CI 0.4, 2.2), indicating poorer performance. Higher DPHP at 16 weeks was associated with lower parent-report GEC score (β=-1.1, 95% CI -2.3, -0.003). BKMR identified BCEP and DNBP at 26 weeks as important contributors to CRI and ERI, respectively. CONCLUSION: OPE metabolites during gestational development, particularly BCEP, may influence adolescent executive function. However, since the FDR p-values failed to reach statistical significance, additional studies would benefit from using larger cohorts.

BACKGROUND AND OBJECTIVES: Diet plays critical roles in modulating maternal metabolic health in pregnancy, but is also a source of metabolic-disrupting phthalates and their replacements. We aimed to evaluate whether the effects of better diet quality on favorable maternal metabolic outcomes could be partially explained by lower exposure to phthalates/replacements. METHODS: At 13 weeks gestation, 295 Illinois women (enrolled 2015-2018) completed a three-month food frequency questionnaire that we used to calculate the Alternative Healthy Eating Index (AHEI)-2010 diet quality index. We quantified 19 metabolites, reflecting exposure to 10 phthalates/replacements, in a pool of five first-morning urine samples collected monthly across pregnancy. We measured 15 metabolic biomarkers in fasting plasma samples collected at 17 weeks gestation, which we reduced to five uncorrelated principal components (PCs), representing adiposity, lipids, cholesterol, inflammation, and growth. We used linear regression to estimate associations of diet quality with [1] phthalates/replacements and [2] metabolic PCs, as well as [3] associations of phthalates/replacements with metabolic PCs. We estimated the proportion of associations between diet quality and metabolic outcomes explained by phthalates/replacements using a causal mediation framework. RESULTS: Overall, every 10-point improvement in AHEI-2010 score was associated with -0.15 (95% CI: -0.27, -0.04) lower adiposity scores, reflecting lower glucose, insulin, C-peptide, leptin, C-reactive protein, but higher adiponectin biomarker levels. Every 10-point increase in diet quality was also associated with 18% (95%CI: 7%, 28%) lower sum of di-2-ethylhexyl terephthalate urinary metabolites (∑DEHTP). Correspondingly, each 18% increase in ∑DEHTP was associated with 0.03 point (95% CI: 0.01, 0.05) higher adiposity PC scores. In mediation analyses, 21% of the inverse relationship between diet quality and adiposity PC scores was explained by lower ∑DEHTP. CONCLUSIONS: The favorable impact of diet quality on maternal adiposity biomarkers may be partially attributed to lower metabolite concentrations of DEHTP, a plasticizer allowed to be used in food packaging materials.

BACKGROUND: Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations. METHOD: This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways. RESULTS: Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta. CONCLUSION: Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43682-024-00027-7.

OBJECTIVE: To examine trends, characteristics, and outcomes of donor oocyte embryo transfer cycles by original oocyte and resultant embryo state and determine whether oocyte state (fresh or frozen) is differentially associated with clinical pregnancy, live birth, and term, normal birthweight neonates among singleton live births. DESIGN: Retrospective cohort study SUBJECTS: Patients undergoing donor oocyte embryo transfer cycles in the United States reporting to National Assisted Reproductive Technology Surveillance System (NASS) from 2013-2020 EXPOSURE: Original donor oocyte and resultant embryo state (fresh or frozen) MAIN OUTCOME MEASURES: Annual numbers and proportions of total donor oocyte embryo transfer cycles stratified by oocyte and embryo state and single embryo transfer cycles resulting in live birth of term (≥37 weeks gestation), normal birthweight (≥2500g) singletons during 2013-2020. Rates of live birth and term, normal birthweight neonates among singleton live births for 2018-2020 are also reported. Relative risks (RR) examine associations between donor oocyte state and live birth and term, normal birthweight neonates among singleton live births resulting from donor oocyte embryo transfer cycles. RESULTS: From 2013-2020, there were 135,085 donor oocyte embryo transfer cycles, of which the proportions increased for frozen embryos (42.3% to 76.6%), fresh embryos using frozen donor oocytes (19.9% to 68.3%) and single embryo transfer (SET) (36.4% to 85.5%). During 2018-2020, there were 48,679 donor oocyte embryo transfer cycles. Rates of live birth were lower with frozen compared to fresh donor oocytes for both fresh (46.2%, 55.9%; aRR 0.83 [95% CI 0.79-0.87]) and frozen (41.3%, 45.8%; aRR 0.94 [95% CI 0.91-0.98]) embryo transfer cycles. Among singleton live births, rates of delivering a term, normal birthweight neonate were similar for frozen compared to fresh donor oocyte transfer cycles among fresh (77.3, 77.2%; aRR 1.01 [95% CI 0.98-1.03]) and frozen (75.6, 75.1%; aRR 1.02 [95% CI 0.99-1.04]) embryos. CONCLUSION: In this national study of donor oocyte embryo transfer cycles, frozen embryo transfers, fresh embryo transfers using frozen oocytes, and SET increased. Although frozen compared to fresh oocytes were associated with a slightly reduced rate of live birth, rates of term, normal birthweight neonates among singleton live births were comparable between donor oocyte states.

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a life-threatening, costly, and common preventable complication associated with hospitalization. Although VTE prevention strategies such as risk assessment and prophylaxis are available, they are not applied uniformly or systematically across US hospitals and healthcare systems. Hospital-level performance measurement has been used nationally to promote standardized approaches for VTE prevention and incentivize the adoption of guideline-based care management. Though most measures reflect care processes rather than outcomes, certain domains including diagnosis, treatment, and continuity of care remain unmeasured. In this article, we describe the development of VTE prevention measures from various stakeholders, measure strengths and limitations, publicly reported rates, the impact of technology and health policy on measure use, and perspectives on future options for surveillance and performance monitoring.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. OBJECTIVE: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. METHODS: We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑(5)BDE: 28, -47, -99, -100 and -153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log(10)-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. RESULTS: Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, -99, -100, ∑(5)BDE), internalizing problems (BDE-28, -47, -99), functional impairment (BDE-28, ∑(5)BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, -99, -100, -153, ∑(5)BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, -99, -100, ∑(5)BDE). DISCUSSION: Gestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers.

BACKGROUND: Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage. METHODS: We quantified urinary triclosan concentrations twice during pregnancy and seven times between birth and 12 years in participants recruited from Cincinnati, OH (2003-2006). We averaged concentrations across pregnancy and childhood and separately considered individual exposure periods in multiple informant models. At 12 years, we measured serum hormone concentrations (males [n = 72] and females [n = 84]-dehydroepiandrosterone-sulfate, luteinizing hormone, follicle-stimulating hormone; males-testosterone; females-estradiol). Also at age 12 years, participants self-reported physical development and menarchal timing. We estimated associations (95% confidence interval) of triclosan with hormone concentrations, more advanced physical development, and age at menarche. RESULTS: For females, each doubling of childhood triclosan was associated with 16% lower estradiol concentrations (-29%, 0%), with stronger associations for measures closer to adolescence. We found suggestive evidence that higher triclosan at any age was associated with ~10% (for gestational triclosan: -18%, -2%) lower follicle-stimulating hormone concentrations among males and early postnatal (1-3 years) triclosan was associated with 63% (5%, 96%) lower odds of advanced pubic hair development in females. In multiple informant models, each doubling of gestational triclosan concentrations was associated with 5% (0%, 9%) earlier age at menarche, equivalent to 5.5 months. CONCLUSION: Gestational and childhood triclosan concentrations were related to some pubertal outcomes including hormone concentrations and age at menarche. Our findings highlight the relevance of elucidating potential sex-specific and time-dependent actions of triclosan.

BACKGROUND: Eating behaviors are controlled by the neuroendocrine system. Whether endocrine disrupting chemicals have the potential to affect eating behaviors has not been widely studied in humans. We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-A (BPA) concentrations were associated with children's eating behaviors. METHODS: We used data from mother-father-child triads in the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-13 years whose parent(s) previously enrolled in a fertility clinic-based prospective preconception study. We quantified urinary concentrations of 11 phthalate metabolites and BPA in parents' urine samples collected preconceptionally and during pregnancy. Parents rated children's eating behavior using the Child Eating Behavior Questionnaire (CEBQ). Using multivariable linear regression, accounting for correlation among twins, we estimated covariate-adjusted associations of urinary phthalate biomarkers and BPA concentrations with CEBQ subscale scores. RESULTS: This analysis included 195 children (30 sets of twins), 160 mothers and 97 fathers; children were predominantly non-Hispanic white (84%) and 53% were male. Paternal and maternal preconception monobenzyl phthalate (MBzP) concentrations and maternal preconception mono-n-butyl phthalate (MnBP) were positively associated with emotional overeating, food responsiveness, and desire to drink scores in children (β(')s= 0.11 [95% CI: 0.01, 0.20]-0.21 [95% CI: 0.10, 0.31] per log(e) unit increase in phthalate biomarker concentration). Paternal preconception BPA concentrations were inversely associated with scores on food approaching scales. Maternal pregnancy MnBP, mono-isobutyl phthalate (MiBP) and MBzP concentrations were associated with increased emotional undereating scores. Maternal pregnancy monocarboxy-isononyl phthalate concentrations were related to decreased food avoiding subscale scores. CONCLUSIONS: In this cohort, higher maternal and paternal preconception urinary concentrations of some phthalate biomarkers were associated with increased food approaching behavior scores and decreased food avoiding behavior scores, which could lead to increased adiposity in children.

BACKGROUND/OBJECTIVES: Pregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. METHODS: Illinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8-40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. RESULTS: In women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with -5.65% (95% CI: -9.79, -1.28) lower testosterone and -0.09 μIU/mL (95% CI: -0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: -0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with -1.77% (95% CI: -4.08, 0.58) lower TT4 and -0.18 μIU/mL (95% CI: -0.33, -0.03) lower TSH. We also identified select chemical interactions. CONCLUSION: Some biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.

BACKGROUND: Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment. OBJECTIVE: We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior. METHODS: We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6-13 years and their parents. We estimated covariate-adjusted associations of log(e) -transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g-computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 and Behavior Rating Inventory of Executive Function T-scores (higher scores indicate more problem behaviors). RESULTS: This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non-Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T-scores (propyl paraben β = 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β = 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T-scores (propyl paraben β = 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β = 1.6; 95% confidence interval: -0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T-scores respectively. Higher paternal preconception ( β = 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception ( β = 1.1 95% confidence interval: -0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T-scores in children, but the paraben mixtures was not. CONCLUSION: In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent-reported child behaviors.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): - 34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: - 19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

BACKGROUND: Epidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health. OBJECTIVE: We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior. METHODS: We analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors). RESULTS: This analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-log(e) unit increase; 95 % CI: -0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: -1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: -2.1, -0.4). CONCLUSION: In this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores.

BACKGROUND: Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure. OBJECTIVE: We aimed to examine the exposure pattern of urinary OPE metabolites in children. METHODS: We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership. RESULTS: Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66-0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44-3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13-0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory. SIGNIFICANCE: The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure. IMPACT STATEMENT: In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1-8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1-3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood.

University settings have demonstrated potential for COVID-19 outbreaks, as they can combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin (UW)–Madison. During August – October 2020, 3,485 students tested positive, including 856/6,162 students living in residence halls. Case counts began rising during move-in week for on-campus students (August 25-31, 2020), then rose rapidly during September 1-11, 2020. UW-Madison initiated multiple prevention efforts, including quarantining two residence halls; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, where UW-Madison is located, did not find evidence of transmission from a large cluster of cases in the two residence halls quarantined during the outbreak. Coordinated implementation of prevention measures can effectively reduce SARS-CoV-2 spread in university settings and may limit spillover to the community surrounding the university.Competing Interest StatementThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention.Clinical TrialN/A.Funding StatementG.K.M. is supported by an NLM training grant to the Computation and Informatics in Biology and Medicine Training Program (NLM 5T15LM007359). This work was funded in part by the U.S. Centers for Disease Control and Prevention Contract #75D30120C09870: Defining the Role of College Students in SARS-CoV-2 Spread in the Upper Midwest.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:A waiver of HIPAA Authorization was obtained by the Western Institutional Review Board (WIRB #1-1290953-1) to obtain the clinical specimens for whole genome sequencing. This analysis was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. These activities were determined to be non-research public health surveillance by the Institutional Review Board at UW-Madison.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll sequencing data is available on www.gisaid.org. Scripts for sequence data analysis is available at https://github.com/gagekmoreno/SARS-CoV-2-at-UW_Madison. https://github.com/gagekmoreno/SARS-CoV-2-at-UW_Madison

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

BACKGROUND: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks. RESULTS: In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings. SUMMARY: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester.

The associations between urinary phenol concentrations and markers of thyroid function and autoimmunity among potentially susceptible subgroups, such as subfertile women, have been understudied, especially when considering chemical mixtures. We evaluated cross-sectional associations of urinary phenol concentrations, individually and as a mixture, with serum markers of thyroid function and autoimmunity. We included 339 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2009-2015). We quantified four phenols in urine using isotope dilution high-performance liquid chromatography-tandem mass spectrometry, and biomarkers of thyroid function (thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4), and triiodothyronine (fT3, TT3)), and autoimmunity (thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (Ab)) in serum using electrochemoluminescence assays. We fit linear and additive models to investigate the association between urinary phenols-both individually and as a mixture-and serum thyroid function and autoimmunity, adjusted for confounders. As a sensitivity analysis, we also applied Bayesian Kernel Machine Regression (BKMR) to investigate non-linear and non-additive interactions. Urinary bisphenol A was associated with thyroid function, in particular, fT(3) (mean difference for a 1 log unit increase in concentration: -0.088; 95% CI [-0.151, -0.025]) and TT(3) (-0.066; 95% CI [-0.112, -0.020]). Urinary methylparaben and triclosan were also associated with several thyroid hormones. The overall mixture was negatively associated with serum fT(3) concentrations (mean difference comparing all four mixture components at their 75th vs. 25th percentiles: -0.19, 95% CI [-0.35, -0.03]). We found no evidence of non-linearity or interactions. These results add to the current literature on phenol exposures and thyroid function in women, suggesting that some phenols may alter the thyroid system.

BACKGROUND: Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with lower reproductive hormones and later puberty, but epidemiological studies evaluating these associations are scarce. OBJECTIVES: We examined associations of PFAS concentrations assessed from pregnancy to adolescence with pubertal development and reproductive hormones at age 12 years. METHODS: We studied 200 mother-child pairs from the HOME Study in Cincinnati, OH (enrolled: 2003-2006). We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in pregnant women and their children at age 3, 8 and 12 years. At age 12 years, children self-assessed pubertal development using Tanner staging of pubic hair growth (males and females) and breast growth (females), and age at menarche. We quantified serum concentrations of dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in both sexes; estradiol in females; testosterone in males. We estimated associations of PFAS with pubertal outcomes and reproductive hormones using a combination of ordinal regression, Cox proportional-hazard regression, and linear regression. Quantile-based g-computation was used for PFAS mixture. RESULTS: In females, adolescent PFAS concentrations and their mixture were associated with later pubic hair growth, breast maturation, and age at menarche, but there was no pattern for prenatal or other postnatal concentrations. For instance, in females, each doubling in adolescent PFAS concentrations was associated with 79 % (PFOA), 63 % (PFOS), 56 % (PFNA), and 47 % (PFHxS) lower odds of attaining a higher stage for breast growth. In addition, adolescent PFAS concentrations were consistently associated with lower estradiol concentrations in females. No pattern was observed for associations of PFAS concentrations with pubic hair growth or reproductive hormones in males. CONCLUSIONS: We observed associations between PFAS concentrations in adolescence and later pubertal development in females, but this could be due to reverse causation induced by excretion of PFAS through menstrual fluid.

BACKGROUND: Beginning in October 2016, the Centers for Medicare & Medicaid Services (CMS) issued expanded guidance requiring accrediting organizations and state survey agencies to report serious infection control breaches to relevant state health departments. This project sought to characterize and summarize The Joint Commission's early experiences and findings in applying this guidance to facilities accredited under the ambulatory and office-based surgery programs in 2017. METHODS: Surveyor notes were retrospectively reviewed to identify individual breaches, and then the Centers for Disease Control and Prevention's Infection Prevention Checklist for Outpatient Settings was used to categorize and code documented breaches. RESULTS: Of 845 ambulatory organizations, 39 (4.6%) had breaches observed during the survey process and reported to health departments. Within these organizations, surveyors documented 356 breaches, representing 52 different breach codes. Common breach domains were sterilization of reusable devices, device reprocessing observation, device reprocessing, disinfection of reusable devices, and infection control program and infrastructure. Eight of the 39 facilities (20.5%) were cited for not performing the minimum level of reprocessing based on the items' intended use, reusing single-use devices, and/or not using aseptic technique to prepare injections. CONCLUSION: The CMS infection control breach reporting requirement has helped highlight some of the challenges faced by ambulatory facilities in providing a safe care environment for their patients. This analysis identified numerous opportunities for improved staff training and competencies as well as leadership oversight and investment in necessary resources. More systematic assessments of infection control practices, extending to both accredited and nonaccredited ambulatory facilities, are needed to inform oversight and prevention efforts.

BACKGROUND: Phenol exposure during pregnancy has been associated with preterm birth, but the potential effect of preconception exposure in either parent is unknown. There is a growing body of evidence to suggest that the preconception period is a critical window of vulnerability for adverse pregnancy outcomes. OBJECTIVE: We examined whether maternal and paternal preconception urinary concentrations of select phenols were associated with the risk of preterm birth among couples attending fertility care. METHODS: The analysis included 417 female and 229 male participants of the Environment and Reproductive Health (EARTH) Study who gave birth to 418 singleton infants between 2005 and 2018 and for whom we had phenol biomarkers quantified in at least one urine sample collected before conception. Mothers and fathers provided an average of 4 and 3 urine samples during the preconception period, respectively. We calculated the geometric mean of bisphenol A (BPA), bisphenol S (BPS), benzophenone-3, triclosan, and the molar sum of parabens (ΣParabens) urinary concentrations to estimate each participant's preconception exposure. Risk ratios (RRs) of preterm birth (live birth before 37 completed weeks' gestation) were estimated using modified Poisson regression models adjusted for covariates. RESULTS: The mean (SD) gestational age among singletons was 39.3 (1.7) weeks with 8% born preterm. A natural log-unit increase in maternal preconception BPA (RR 1.94; 95% CI: 1.20, 3.14) and BPS (RR 2.42; 95% CI: 1.01, 5.77) concentration was associated with an increased risk of preterm birth. These associations remained after further adjustment for maternal prenatal and paternal preconception biomarker concentrations. Paternal preconception ΣParabens concentrations showed a possible elevated risk of preterm birth (RR 1.36; 95% CI: 0.94, 1.96). No consistent pattern of association was observed for benzophenone-3 or triclosan biomarkers in either parent. DISCUSSION: Maternal preconception urinary BPA and BPS concentrations, as well as paternal preconception urinary parabens concentrations were prospectively associated with a higher risk of preterm birth. Subfertile couples' exposure to select phenols during the preconception period may be an unrecognized risk factor for adverse pregnancy outcomes.

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers for commercial and residential purposes, are suspected of being neurotoxic. We aimed to assess exposure to an OPE mixture in early life and its relationship to parent-reported child behavior. We measured urinary concentrations of three OPE metabolites, bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and diphenyl phosphate (DPHP), at pregnancy (16 and 26 weeks of gestation and delivery) and postnatal time points (ages 1, 2, 3, and 5 years) in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort in Cincinnati, Ohio, USA (enrolled 2003-2006, n = 219). We used latent variable analysis in structural equations models and quantile g-computation to investigate associations of a mixture of the three OPE metabolites with parent-reported child behaviors at 3 and 8 years, measured using the Behavioral Assessment System for Children, Second Edition. Higher log-transformed urinary OPE latent variable values at 16 weeks were associated with fewer externalizing problem behaviors (ß = -5.74; 95% CI = -11.24, -0.24) and fewer overall behavioral problems at age 3 years (ß = -5.26; 95% CI = -10.33, -0.19), whereas having higher OPEs at delivery was associated with poorer overall behavioral problems at age 3 years (ß = 2.87; 95% CI = 0.13, 5.61). OPE latent variable values at 16 weeks, 26 weeks, and delivery were not associated with child behavior at 8 years. However, higher OPE latent variable values at 3 years were associated with fewer externalizing behaviors at 8 years (ß = -2.62; 95% CI = -5.13, -0.12). The quantile g-computation estimates had directions largely consistent with the latent variable analysis results. Pregnancy and postnatal urinary OPE metabolite mixtures were associated with child internalizing, externalizing, and overall negative behaviors at 3 and 8 years, but we did not identify a consistent pattern in terms of the direction of the effects or a particularly sensitive time point.

BACKGROUND: Early-life phthalate exposures may disrupt metabolic processes; however few prospective studies have assessed whether these associations extend to cardiometabolic outcomes during adolescence. METHODS: Among 183 mother-adolescent pairs in a prospective cohort study that enrolled pregnant women in Cincinnati, OH (2003-2006), we quantified nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children. At age 12 years, we assessed triglycerides, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, insulin, and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Using multiple informant models, we estimated covariate-adjusted associations between urinary phthalate concentrations at each time period and cardiometabolic biomarkers at age 12 years, including modification by child sex. RESULTS: Although most associations were weak or null, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and monobenzyl phthalate (MBzP) concentrations were generally associated with lower LDL at age 12 years. A 10-fold increase in 4- and 12-year MEP was associated with -15.3mg/dL (95% CI: 27.5, -3.13mg/dL) and -11.8mg/dL (-22.0, -1.51mg/dL) lower LDL, respectively. Discrepant associations were observed in females versus males: a 10-fold increase in 3-year MEP concentrations was associated with 12.0mg/dL (95% CI: 7.11, 31.1mg/dL) higher LDL levels in males and -30.4mg/dL (95% CI: 50.9, -9.8mg/dL) lower LDL levels in females. Some urinary phthalate concentrations were cross-sectionally associated with HOMA-IR. CONCLUSIONS: Early-life phthalate biomarker concentrations may be inversely associated with LDL during early adolescence in an exposure-period and sex-dependent manner.

BACKGROUND: Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health. METHODS: We used data from 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, OH; 2003-2006). We quantified benzophenone-3, bisphenol A (BPA), 2,5-dichlorophenol, and triclosan in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry at age 12 years and calculated Z-scores for whole body (less head), total hip, femoral neck, and 1/3rd distal radius bone mineral content (BMC) and areal bone mineral density (aBMD) as well as ultra-distal radius aBMD and spine BMC and bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per doubling of maternal urinary environmental phenol concentrations in linear regression models. We also examined effect measure modification by child's sex and estimated associations of the environmental phenol mixture with BMC and aBMD using quantile g-computation. RESULTS: We observed generally null associations for all analytes and bone measures. Yet, in adjusted models, higher urinary 2,5-dichlorophenol concentrations were associated with higher 1/3rd distal radius BMC (: 0.09; 95% CI: 0.02, 0.17) and aBMD (: 0.09; 95% CI: 0.02, 0.17) Z-scores in the overall sample. In sex-stratified analyses, the magnitude of the BMC association was positive for females (: 0.16; 95% CI: 0.06, 0.26) and null for males (: 0.02; 95% CI: 0.08, 0.13). The environmental phenol mixture was associated with greater 1/3rd distal radius BMC and aBMD Z-scores in both sexes, which was mostly driven by benzophenone-3 in males and 2,5-dichlorophenol in females. CONCLUSION: In this prospective cohort study, we observed generally null associations for environmental phenols with BMC and aBMD at age 12 years. While there was a positive association of 2,5-dichlorophenol concentrations during fetal development with distal radius BMC and aBMD at age 12 years, future studies utilizing methods capable of differentiating cortical and trabecular bone are needed to elucidate potential mechanisms and implications for bone strength and microarchitecture.

Organophosphate esters (OPEs) are developmental toxicants in experimental studies of animals, but limited evidence is available in humans. We included 340 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) for the analysis. We evaluated gestational exposure to OPEs with gestation age at birth and newborn anthropometric measures. We quantified four OPE urinary metabolites at 16 weeks and 26 weeks of gestation. We extracted gestational age at birth, newborn weight, length, and head circumference from the chart review. We calculated z-scores for these anthropometric measures and the ponderal index. We used multiple informant models to examine the associations between repeated OPE measurements and the outcomes. We used modified Poisson regression to estimate the association of gestational exposure to OPEs with preterm birth. We also explored effect modification by infant sex and the potential mediation effect by the highest maternal blood pressure and glucose levels. We found that bis(2-chloroethyl) phosphate (BCEP) at 16 weeks and diphenyl phosphate at 26 weeks of pregnancy were positively associated with gestational age and inversely associated with preterm birth. In female newborns, BCEP at 16 weeks was inversely related to birth weight and length z-scores. In male newborns, we observed negative associations of 26-week di-n-butyl phosphate with the ponderal index at birth. No mediation by the highest maternal blood pressure or glucose levels during pregnancy was identified. In this cohort, gestational exposure to some OPEs was associated with gestational age, preterm birth, and neonatal anthropometric measures. Certain associations tended to be window- and infant sex-specific.

OBJECTIVE: To determine the proportion of hospitals that implemented 6 leading practices in their antimicrobial stewardship programs (ASPs). Design: Cross-sectional observational survey. SETTING: Acute-care hospitals. PARTICIPANTS: ASP leaders. METHODS: Advance letters and electronic questionnaires were initiated February 2020. Primary outcomes were percentage of hospitals that (1) implemented facility-specific treatment guidelines (FSTG); (2) performed interactive prospective audit and feedback (PAF) either face-to-face or by telephone; (3) optimized diagnostic testing; (4) measured antibiotic utilization; (5) measured C. difficile infection (CDI); and (6) measured adherence to FSTGs. RESULTS: Of 948 hospitals invited, 288 (30.4%) completed the questionnaire. Among them, 82 (28.5%) had <99 beds, 162 (56.3%) had 100-399 beds, and 44 (15.2%) had ≥400+ beds. Also, 230 (79.9%) were healthcare system members. Moreover, 161 hospitals (54.8%) reported implementing FSTGs; 214 (72.4%) performed interactive PAF; 105 (34.9%) implemented procedures to optimize diagnostic testing; 235 (79.8%) measured antibiotic utilization; 258 (88.2%) measured CDI; and 110 (37.1%) measured FSTG adherence. Small hospitals performed less interactive PAF (61.0%; P = .0018). Small and nonsystem hospitals were less likely to optimize diagnostic testing: 25.2% (P = .030) and 21.0% (P = .0077), respectively. Small hospitals were less likely to measure antibiotic utilization (67.8%; P = .0010) and CDI (80.3%; P = .0038). Nonsystem hospitals were less likely to implement FSTGs (34.3%; P < .001). CONCLUSIONS: Significant variation exists in the adoption of ASP leading practices. A minority of hospitals have taken action to optimize diagnostic testing and measure adherence to FSTGs. Additional efforts are needed to expand adoption of leading practices across all acute-care hospitals with the greatest need in smaller hospitals.