There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n = 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether subgroups of our study population are disproportionately impacted by COVID-19. Many gay men and other MSM not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. These consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socioeconomically disadvantaged groups. These findings highlight the urgent need to mitigate the negative impacts of COVID-19 among gay men and other MSM. Keywords COVID-19 • Economic impact • Mental health • HIV • AIDS • Gay • Men who have sex with men Resumen Existe una necesidad urgente para medir los impactos de COVID-19 entre hombres gay y otros hombres que tienen sexo con hombres (HSH). Hemos conducido una encuesta multifuncional con una prueba mundial de hombres gay y otros HSH (n = 2732) desde el 16 de Abril hasta el 4 de Mayo del 2020, a través de una aplicación de red social. Nosotros caracterizamos los impactos económicos, de salud mental, prevención del VIH y tratamiento del VIH e impactos a COVID-19 y la respuesta de COVID-19, y examinamos si subgrupos de nuestra población de estudio fueron impactados desproporcionadamente por COVID-19. Muchos hombres no tan solo reportaron consecuencias económicas y de salud mental, sino también interrupciones de prevención y de pruebas de VIH, y cuidado del VIH y servicios de tratamiento. Encontramos consecuencias más significantes entre personas viviendo con VIH, grupos raciales/etnicos, migrantes, sexo servidores, y groupos socioeconomicamente disfavorecidos. Los resultados subrayan la necesidad crucial de mitigar los impactos multifacéticos de COVID-19 entre los hombres homosexuales y otros HSH, especialmente para aquellos con vulnerabilidades entrelazadas.

There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n= 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether subgroups of our study population are disproportionately impacted by COVID-19. Many men not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. Consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socio-economically disadvantaged groups. Findings underscore the crucial need to mitigate the multifaceted impacts of COVID-19 among gay men and other MSM, especially for those with intersecting vulnerabilities.

Endogenous signaling molecules derived from lipids, peptides, and DNA, are important regulators of physiological processes during pregnancy. The effect of their collective impact on preterm birth (delivery < 37 weeks gestation) is understudied. We aimed to characterize the associations and predictive capacity of an extensive panel of eicosanoids, immune biomarkers, oxidative stress markers, and growth factors towards preterm birth and its subtypes. We conducted a cross-sectional study of pregnant women (recruited < 15 weeks gestation) in the LIFECODES birth cohort, which included 58 cases of preterm birth and 115 controls that delivered term. Among the cases there were 31 cases who had a spontaneous preterm birth (cases who had spontaneous preterm labor and/or preterm premature rupture of membranes) and 25 that had preterm birth associated with aberrant placentation (cases who had preeclampsia and/or intrauterine growth restriction) and 2 cases that could not be sufficiently categorized as either. We analyzed single biomarker associations with each preterm birth outcome using multiple logistic regression. Adaptive elastic-net was implemented to perform a penalized multiple logistic regression on all biomarkers simultaneously to identify the most predictive biomarkers. We then organized biomarkers into biological groups and by enzymatic pathways and applied adaptive elastic-net and random forest to evaluate the accuracy of each group for predicting preterm birth cases. The majority of associations we observed were for spontaneous preterm birth, and adaptive elastic-net identified 5-oxoeicosatetraenoic acid, resolvin D1, 5,6-epoxy-eicsatrienoic acid, and 15-deoxy-12,14-prostaglandin J2 as most predictive. Overall, lipid biomarkers performed the best at separating cases from controls compared to other biomarker categories (adaptive elastic-net AUC = 0.78 [0.62, 0.94], random forest AUC = 0.84 [0.72, 0.96]). Among the enzymatic pathways that differentiate eicosanoid metabolites, we observed the highest prediction of overall preterm birth by lipoxygenase metabolites using random forest (AUC = 0.83 [0.69, 0.96]), followed by cytochrome p450 metabolites using adaptive elastic-net (AUC = 0.74 [0.52, 0.96]). In this study we translate biological hypothesis into the language of modern machine learning. Many lipid biomarkers were highly associated with overall and spontaneous preterm birth. Among eicosanoids, lipoxygenase and cytochrome p450 products performed best in identifying overall and spontaneous preterm birth. The combination of lipid biomarkers may have good utility in clinical settings to predict preterm birth.

Background: Maternal immune system regulation is critical for maintenance of a healthy pregnancy and fetal development. Exposure to phenols and parabens is widespread, and may be linked to systemic inflammation and alteration of circulating immunological biomarkers. Objective: We sought to characterize associations between repeated measures of individual urinary phenols, parabens and plasma inflammatory markers across pregnancy. Methods: In the LIFECODES prospective birth cohort, we conducted a nested preterm birth case-control study, including 130 cases and 352 controls. In urine samples collected from each participant at up to four study visits during pregnancy, we measured concentrations of six phenols and four parabens, as well as five plasma inflammatory markers. We used multivariable linear mixed models to analyze repeated measures of exposures on inflammatory markers. We created and applied inverse probability weights to account for the sampling approach. Results: We observed bidirectional associations between select phenols and parabens and inflammatory markers. An interquartile range increase in triclosan (55.2 ng/mL) was associated *

Introduction: Preterm birth continues to be a significant public heath concern and is a leading cause of perinatal and infant mortality. Environmental exposures to phenols and parabens are suspected to potentially contribute to the pathology of preterm birth, yet limited human studies have characterized the extent to which these toxicants are associated with birth outcomes. Methods:We examined the associations between phenols, parabens, and preterm birth, within pregnant women who were recruited early in gestation into the LIFECODES cohort at Brigham and Women's Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points in pregnancy and analyzed for phenols and parabens. We selected 130 cases of preterm birth (defined as delivery before 37 weeks gestation), and 350 random controls. We categorized preterm birth subtypes based on clinical presentation and identified 75 cases of spontaneous preterm birth (characterized by spontaneous preterm labor and/or preterm premature rupture of membranes), and 37 cases of placental preterm birth (characterized by preeclampsia and/or intrauterine growth restriction). We used multivariate logistic regression with visit specific and geometric averages of phenols and parabens to determine associations with preterm birth. Results:We observed moderate variability in urinary phenol and paraben concentrations over pregnancy with intraclass correlation coefficients ranging between 0.45 -0.68. Regression analyses indicated mostly null associations. We observed inverse associations, notably between 2,5-dichlorophenol and overall preterm birth (adjusted odds ratio [95% confidence interval, CI]: 0.79 [0.67 -0.94]), and this relationship was consistent by study visit. Conversely, ethyl paraben was associated with increased risk for placental preterm birth (adjusted odds ratio [95% CI]: 1.47

One in ten infants born in the United States is born preterm, or prior to 37 weeks gestation. Exposure to elevated levels of metals, such as lead and arsenic, has been linked to higher risk of preterm birth (PTB), but consequences of lower levels of exposure and less studied metals are unclear. We examined the associations between 17 urinary trace metals individually and in mixtures in relation to PTB. The LIFECODES birth cohort enrolled pregnant women at <15 weeks gestation at Brigham and Women’s Hospital in Boston. We selected cases of PTB (n=99) and unmatched controls (n=291) and analyzed urine samples for a panel of trace metals (median: 26 weeks gestation). We used logistic regression models to calculate the odds ratio (OR) for PTB and subtypes of PTB based on presentation at delivery. Subtypes included spontaneous and placental PTB. We used elastic net (ENET) regularization to identify individual metals or pairwise interactions that had the strongest associations with PTB, and principal components analysis (PCA) to identify classes of exposures associated with the outcome. We observed increased odds of PTB (OR: 1.41, 95% Confidence Interval [CI]: 1.12, 1.78) in association with an interquartile range difference in urinary copper (Cu). We also observed an increased OR for selenium (OR: 1.33, 95% CI:0.98, 1.81). ENET selected Cu as the most important trace metal associated with PTB. PCA identified 3 principal components (PCs) that roughly reflected exposure to toxic metals, essential metals, and metals with seafood as a common source of exposure. PCs reflecting essential metals were associated with an increased odds of overall and spontaneous PTB. Maternal urinary copper in the third trimester was associated with increased risk of PTB, and statistical analyses for mixtures indicated that after accounting for correlation this metal was the most important statistical predictor of the outcome.

Diverse toxicological mechanisms may mediate the impact of environmental toxicants (phthalates, phenols, polycyclic aromatic hydrocarbons, and metals) on pregnancy outcomes. In this study, we introduce an analytical framework for multivariate mediation analysis to identify mediation pathways (q = 61 mediators) in the relationship between environmental toxicants (p = 38 analytes) and gestational age at delivery. Our analytical framework includes: (1) conducting pairwise mediation for unique exposure-mediator combinations, (2) exposure dimension reduction by estimating environmental risk scores, and (3) multivariate mediator analysis using either Bayesian shrinkage mediation analysis, population value decomposition, or mediation pathway penalization. Dimension reduction demonstrates that a one-unit increase in phthalate risk score is associated with a total effect of 1.07 lower gestational age (in weeks) at delivery (95% confidence interval: 0.48–1.67) and eicosanoids from the cytochrome p450 pathway mediated 26% of this effect (95% confidence interval: 4–63%). Eicosanoid products derived from the cytochrome p450 pathway may be important mediators of phthalate toxicity.

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