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Prior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse. We quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010–2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively. PFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months. In this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding. [ABSTRACT FROM AUTHOR]

Background: Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent.Objectives: In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns.Methods: We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n = 202) and cord serum at delivery (n = 276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones.Results: With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT4) decreased by 0.52 μg/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT4 (WQS beta = -0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta = -0.11; 95% CI: -0.20, -0.03) and TT4 (WQS beta = -0.53; 95% CI: -0.90, -0.16).Conclusion: Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT4 in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology. [ABSTRACT FROM AUTHOR]

Arsenic exposure during pregnancy may increase the risk for intellectual deficits in children, but limited data exist from prospective epidemiologic studies, particularly at low arsenic exposure levels. We investigated the association between prenatal maternal urinary arsenic concentrations and childhood cognitive abilities in the Health Outcomes and Measures of the Environment (HOME) Study. We used anion exchange chromatography coupled with inductively coupled plasma mass spectrometry detection to measure arsenic species content in pregnant women's urine. The summation of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) refers to ∑As. We assessed children's cognitive function (n = 260) longitudinally at 1-, 2-, and 3-years using Bayley Scales of Infant and Toddler Development, at 5 years using Wechsler Preschool and Primary Scale of Intelligence, and at 8 years using Wechsler Intelligence Scale for Children. We observed a modest decrease in mental development index and full-scale intelligence quotient at ages 3 and 5 years with each doubling of ∑As with estimated score (ß) differences and 95% confidence interval (CI) of -1.8 from -4.1 to 0.5 and -2.5 from -5.1 to 0.0, respectively. This trend was stronger and reached statistical significance among children whose mothers had lower iAs methylation capacity and low urinary arsenobetaine concentrations. Our findings suggest that arsenic exposure levels relevant to the general US population may affect children's cognitive abilities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe ethics consultations at a single Institution that has a mandatory ethics consultation policy. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all adult patients who were admitted to the intensive care unit at Columbia University Medical Center and had an ethics consultation between August 1, 2006, and July 31, 2007. All mandatory and nonmandatory ethics consultations were reviewed. Patient diagnosis, prognosis, presence of do-not-resuscitate order, presence of written advance directives, reason for the ethics consultation, and survival data were collected. The number of ethics consultations hospital-wide from January 1, 2000, to December 31, 2007, was collected. RESULTS: The total number of mandatory and nonmandatory ethics consultations requested was 168. Of these consultations, 108 (64%) were considered mandatory, and 60 (36%) were considered nonmandatory. Between January 1, 2000, and December 31, 2007, the total number of ethics consultations increased 84%. CONCLUSION: The increase in the total number of ethics consultations is interpreted as a positive outcome of the mandatory policy. The mandatory ethics consultation policy has possibly increased exposure to ethics consultant-physician interactions, increased learning for physicians, and raised awareness among physicians and nurses of potential ethics assistance. [ABSTRACT FROM AUTHOR]

Background: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals commonly used in the production of household and consumer goods. While exposure to PFAS has been associated with greater adiposity in children and adults, less is known about associations with gestational weight gain (GWG).Methods: We quantified using mass spectrometry perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfanoate (PFHxS) and perfluorononanoate (PFNA) in maternal serum from 18 ± 5 weeks' gestation (mean ± standard deviation (std)) in a prospective pregnancy and birth cohort (2003-2006, Cincinnati, Ohio) (n = 277). After abstracting weight data from medical records, we calculated GWG from 16 ± 2 weeks' gestation (mean ± std) to the measured weight at the last visit or at delivery, rate of weight gain in the 2nd and 3rd trimesters (GWR), and total weight gain z-scores standardized for gestational age at delivery and pre-pregnancy BMI. We investigated covariate-adjusted associations between individual PFAS using multivariable linear regression; we assessed potential effect measure modification (EMM) by overweight/obese status (pre-pregnancy BMI<25 kg/m2 v. ≥25 kg/m2). Using weighted quantile sum regression, we assessed the combined influence of these four PFAS on GWG and GWR.Results: Each doubling in serum concentrations of PFOA, PFOS, and PFNA was associated with a small increase in GWG (range 0.5-0.8 lbs) and GWR (range 0.03-0.05 lbs/week) among all women. The association of PFNA with GWG was stronger among women with BMI≥25 kg/m2 (β = 2.6 lbs; 95% CI:-0.8, 6.0) than those with BMI<25 kg/m2 (β = -1.0 lbs; 95% CI:-3.8, 1.8; p-EMM = 0.10). We observed associations close to the null between PFAS and z-scores and between the PFAS exposure index (a combined summary measure) and the outcomes.Conclusion: Although there were consistent small increases in gestational weight gain with increasing PFOA, PFOS, and PFNA serum concentrations in this cohort, the associations were imprecise. Additional investigation of the association of PFAS with GWG in other cohorts would be informative and could consider pre-pregnancy BMI as a potential modifier. [ABSTRACT FROM AUTHOR]

Synthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1–2 spot samples during pregnancy and limited diversity of populations. To study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program. While many associations were modest and statistically imprecise, a 1-unit increase in log 10 pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log 10 pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: −67%, −2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: −53%, 8%). In a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life. [ABSTRACT FROM AUTHOR]

We aimed to investigate the joint, class-specific, and individual impacts of (i) PFAS, (ii) toxic metals and metalloids (referred to collectively as "metals"), and (iii) essential elements on birth outcomes in a prospective pregnancy cohort using both established and recent mixture modeling approaches. Participants included 537 mother-child pairs from the New Hampshire Birth Cohort Study. Concentrations of 6 metals and 5 PFAS were measured in maternal toenail clippings and plasma, respectively. Birth weight, birth length, and head circumference at birth were abstracted from medical records. Joint, index-wise, and individual associations of the metals and PFAS concentrations with birth outcomes were evaluated using Bayesian Kernel Machine Regression (BKMR) and Bayesian Multiple Index Models (BMIM). After controlling for potential confounders, the metals-PFAS mixture was associated with a larger head circumference at birth, which was driven by manganese. When using BKMR, the difference in the head circumference z-score when changing manganese from its 25th to 75th percentiles while holding all other mixture components at their medians was 0.22 standard deviations (95% posterior credible interval [CI]: −0.02, 0.46). When using BMIM, the posterior mean of index weight estimates assigned to manganese for head circumference z-score was 0.72 (95% CI: 0, 0.99). Prenatal exposure to the metals-PFAS mixture was not associated with birth weight or birth length by either BKMR or BMIM. Using both traditional and new mixture modeling approaches, prenatal exposure to manganese was associated with a larger head circumference at birth after accounting for exposure to PFAS and multiple toxic and essential metals. [Display omitted] • The essential element class was associated with higher HC. • Mn was the main contributor to the higher HC, accounting for other chemicals. • The positive Mn-HC relationship was driven by male infants. • No class-wise interactions were identified using Bayesian Multiple Index Models. [ABSTRACT FROM AUTHOR]

Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects. We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics. We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008–2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection. Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4′-methylenedianiline, and a composite of o-toluidine and m-toluidine (99–100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4′-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: −11; 95% CI: −19, −1) or time of day, seasonal, and geographic variability. Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects. [Display omitted] • Measured four melamine derivatives and 41 aromatic amines in ECHO pregnant women. • Melamine, cyanuric acid, and ten aromatic amines detected in >60% of women. • Concentrations higher in non-Hispanic Black or Hispanic women for several compounds. • Most chemicals positively associated with the tobacco biomarker cotinine. • Annual, within-day, seasonal, and geographic variability observed. [ABSTRACT FROM AUTHOR]

In primary hyperparathyroidism (PHPT), protracted elevation of serum parathyroid hormone (PTH) is held to be associated with cortical, but not trabecular, bone loss. However, an alternative explanation for the apparent preservation of trabecular bone is fragmentation of the cortex by intracortical remodeling. The cortical fragments resemble trabeculae and so may be erroneously included in the quantification of ‘trabecular’ bone density. To test this hypothesis, we compared bone microarchitecture in 43 patients with untreated PHPT (mean 62.9years, range 31–84) with 47 healthy age-matched controls and 25 patients with surgically treated PHPT (63.6years, 30–82). Images of the distal radius and tibia were acquired using high-resolution peripheral quantitative CT and analysed using StrAx1.0, a new software program that quantifies bone morphology in-vivo. Results were expressed as the mean number of standardized deviations (SD) from the age-specific mean (Z scores, mean±SEM). In subjects with PHPT, total tibial cortical area was reduced −0.26±0.08 SD; p=0.002). Cortical volumetric bone mineral density (vBMD) was reduced (−0.29±0.06 SD; p<0.001) due to higher cortical porosity (0.32±0.06 SD; p<0.001) and lower tissue mineralization density (−0.21±0.06 SD; p=0.002). Medullary area was increased (0.26±0.08 SD; p=0.002) and trabecular vBMD was reduced (−0.14±0.04 SD; p<0.001). In subjects who underwent successful parathyroidectomy, cortical area (−0.18±0.10 SD; NS) and medullary area (0.18±0.10 SD; NS) did not differ from controls. Cortical vBMD was reduced (−0.15±0.05 SD; p=0.003) due to high porosity (0.15±0.05 SD; p=0.006), values numerically lower than in untreated PHPT. Tissue mineralization density (−0.26±0.04 SD; p<0.001) and trabecular vBMD were reduced (−0.16±0.04 SD, p<0.001). The results were similar in the distal radius. In PHPT, chronically elevated endogenous PTH does not spare trabecular bone; it causes bone loss and microarchitectural deterioration in both cortical and trabecular compartments of bone. [ABSTRACT FROM AUTHOR]

Background: Occupational exposure to agrochemicals, some of which are known or suspected carcinogens, is a major health hazard for subsistence agricultural workers and their families. These impacts are more prevalent in low-and-middle income countries (LMIC) due to weak regulations, lack of awareness of the risks of contamination, predominant use of handheld backpack style spraying equipment, general lack of personal protective equipment (PPE), and low literacy about proper agrochemical application techniques. Reducing exposure to agrochemicals was identified as a paramount concern by rural Hondurans working with a community-engaged research initiative. Fluorescent tracer dyes have been described as a means of visualizing and quantifying dermal exposure to agricultural chemicals, and exposure models adapted for LMIC have been developed previously. Tracer dyes have also been used in educational simulations to promote pesticide safety. However, studies evaluating the effectiveness of these educational dye interventions in reducing future exposure have been lacking.Aim: To evaluate whether observing one's own chemical contamination after applying agrochemicals changed the amount of occupational dermal exposure during a subsequent chemical application.Methods: We employed a multi-modal community intervention in a rural village in Honduras that incorporated chemical safety education and use of a fluorescent tracer dye during pesticide application on two consecutive occasions, and compared dermal exposure between the intervention group (previous dye experience and safety education, n = 6) and the control group (safety education only, n = 7).Results: Mean total visual score (TVS) of the tracer dye, which accounts for both extent and intensity of whole-body contamination, was lower among those who had previously experienced the dye intervention (mean TVS = 41.3) than among participants who were dye-naïve (mean TVS = 78.4), with a difference between means of -37.10 (95% CI [-66.26, -7.95], p = 0.02). Stratifying by body part, contamination was significantly lower for the anterior left lower extremity and bilateral feet for the dye-experienced group vs. dye-naïve, with most other segments showing a trend toward decreased contamination as well.Conclusion: Participants who had previously experienced the dye intervention were significantly less contaminated than the dye-naïve control group during a subsequent spraying event. The findings of this small pilot study suggest that a multi-modal, community-based approach that utilizes fluorescence-augmented contamination for individualized learning (FACIL) may be effective in reducing dermal exposure to carcinogenic agrochemicals among subsistence farmers in Honduras and other LMIC. [ABSTRACT FROM AUTHOR]

• NET-C identified a network of features that predict birth weight. It outperforms hierarchical clustering and random forest regression in predicting birth weight in New Hampshire Birth Cohort Study. • NET-C identified a subnetwork of metabolites including lysophosphatidylcholines were nonnegatively associated with birth weight • Net-C confirmed that higher Cu concentrations was related to reduced birth weight Birth weight is a key consequence of environmental exposures and metabolic alterations and can influence lifelong health. While a number of methods have been used to examine associations of trace element (including essential nutrients and toxic metals) concentrations or metabolite concentrations with a health outcome, birth weight, studies evaluating how the coexistence of these factors impacts birth weight are extremely limited. Here, we present a novel algorithm NETwork Clusters (NET-C), to improve the prediction of outcome by considering the interactions of features in the network and then apply this method to predict birth weight by jointly modelling trace element and cord blood metabolite data. Specifically, by using trace element and/or metabolite subnetworks as groups, we apply group lasso to estimate birth weight. We conducted statistical simulation studies to examine how both sample size and correlations between grouped features and the outcome affect prediction performance. We showed that in terms of prediction error, our proposed method outperformed other methods such as (a) group lasso with groups defined by hierarchical clustering, (b) random forest regression and (c) neural networks. We applied our method to data ascertained as part of the New Hampshire Birth Cohort Study on trace elements, metabolites and birth outcomes, adjusting for other covariates such as maternal body mass index (BMI) and enrollment age. Our proposed method can be applied to a variety of similarly structured high-dimensional datasets to predict health outcomes. [ABSTRACT FROM AUTHOR]

• We found that certain clusters and principal components were inversely associated with infant birth length. • Individual chemcial biomarkers in these clusters or PCs were associated with lower birth length. • Cluster, PCs, and individual biomarker were not associated with other birth outcomes. • The consistency of these metrics suggests that these results are not method dependent. Exposure to mixtures of environmental chemicals are prevalent among pregnant women and may be associated with altered fetal growth and gestational age. To date, most research regarding environmental chemicals and neonatal outcomes has focused on the effect of individual agents. In a prospective cohort of 380 pregnant women from Cincinnati, OH (enrolled 2003–2006), we used biomarkers to estimate exposure to 43 phenols, phthalates, metals, organophosphate/pyrethroid/organochlorine pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, perfluoroalkyl substances (PFAS), and environmental tobacco smoke. Using three approaches, we estimated covariate-adjusted associations of chemical mixtures or individual chemicals with gestational-age-specific birth weight z-scores, birth length, head circumference, and gestational age: k-means clustering, principal components (PC), and one-chemical-at-a-time regression. We identified three chemical mixture profiles using k-means clustering. Women in cluster 1 had higher concentrations of most phenols, three phthalate metabolites, several metals, organophosphate/organochlorine pesticides, polychlorinated biphenyls, and several PFAS than women in clusters 2 and 3. On average, infants born to women in clusters 1 (−1.2 cm; 95% CI: −1.9, −0.5) and 2 (−0.5 cm; 95% CI: −1.1, 0.1) had lower birth length than infants in cluster 3. Six PCs explained 50% of the variance in biomarker concentrations and biomarkers with similar chemical structures or from shared commercial/industrial settings loaded onto commons PCs. Each standard deviation increase in PC 1 (organochlorine pesticides, some phenols) and PC 6 (cadmium, bisphenol A) was associated with 0.2 cm (95% CI: −0.4, 0.0) and 0.1 cm (95% CI: −0.4, 0.1) lower birth length, respectively. Organochlorine compounds, parabens, and cadmium were inversely associated with birth length in the one-chemical-at-a-time analysis. Cluster membership, PC scores, and individual chemicals were not associated with other birth outcomes. All three methods of characterizing multiple chemical exposures in this cohort identified inverse associations of select organochlorine compounds, phenols, and cadmium with birth length, but not other neonatal outcomes. [ABSTRACT FROM AUTHOR]