Metabolomic Alterations Associated with Phthalate Exposures among Pregnant Women in Puerto Rico.

Although phthalate exposure has been linked with multiple adverse pregnancy outcomes, their underlying biological mechanisms are not fully understood. We examined associations between biomarkers of phthalate exposures and metabolic alterations using untargeted metabolomics in 99 pregnant women and 86 newborns [mean (SD) gestational age = 39.5 (1.5) weeks] in the PROTECT cohort. Maternal urinary phthalate metabolites were quantified using isotope dilution high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), while metabolic profiles in maternal and cord blood plasma were characterized via reversed-phase LC-MS. Multivariable linear regression was used in metabolome-wide association studies (MWAS) to identify individual metabolic features associated with elevated phthalate levels, while clustering and correlation network analyses were used to discern the interconnectedness of biologically relevant features. In the MWAS adjusted for maternal age and prepregnancy BMI, we observed significant associations between specific phthalates, namely, di(2-ethylhexyl) phthalate (DEHP) and mono(3-carboxypropyl) phthalate (MCPP), and 34 maternal plasma metabolic features. These associations predominantly included upregulation of fatty acids, amino acids, purines, or their derivatives and downregulation of ceramides and sphingomyelins. In contrast, fewer significant associations were observed with metabolic features in cord blood. Correlation network analysis highlighted the overlap of features associated with phthalates and those identified as differentiating markers for preterm birth in a previous study. Overall, our findings underscore the complex impact of phthalate exposures on maternal and fetal metabolism, highlighting metabolomics as a tool for understanding associated biological processes. Future research should focus on expanding the sample size, exploring the effects of phthalate mixtures, and validating identified metabolic features in larger, more diverse populations.

Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Gestational glyphosate exposure and early childhood neurodevelopment in a Puerto Rico birth cohort.

INTRODUCTION: N-(phosphonomethyl)glycine, or glyphosate, is a non-selective systemic herbicide widely used in agricultural, industrial, and residential settings since 1974. Glyphosate exposure has been inconsistently linked to neurotoxicity in animals, and studies of effects of gestational exposure among humans are scarce. In this study we investigated relationships between prenatal urinary glyphosate analytes and early childhood neurodevelopment. METHODS: Mother-child pairs from the PROTECT-CRECE birth cohort in Puerto Rico with measures for both maternal urinary glyphosate analytes and child neurodevelopment were included for analysis (n = 143). Spot urine samples were collected 1-3 times throughout pregnancy and analyzed for glyphosate and aminomethylphosphonic acid (AMPA), an environmental degradant of glyphosate. Child neurodevelopment was assessed at 6, 12, and 24 months using the Battelle Developmental Inventory, 2nd edition Spanish (BDI-2), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. We used multivariable linear regression to examine associations between the geometric mean of maternal urinary glyphosate analytes across pregnancy and BDI-2 scores at each follow-up. Results were expressed as percent change in BDI-2 score per interquartile range increase in exposure. RESULTS: Prenatal AMPA concentrations were negatively associated with communication domain at 12 months (%change = -5.32; 95%CI: 9.04, -1.61; p = 0.007), and communication subdomain scores at 12 and 24 months. At 24 months, four BDI-2 domains were associated with AMPA: adaptive (%change = -3.15; 95%CI: 6.05, -0.25; p = 0.038), personal-social (%change = -4.37; 95%CI: 7.48, -1.26; p = 0.008), communication (%change = -7.00; 95%CI: 11.75, -2.26; p = 0.005), and cognitive (%change = -4.02; 95%CI: 6.72, -1.32; p = 0.005). Similar trends were observed with GLY concentrations, but most confidence intervals include zero. We found no significant associations at 6 months. CONCLUSIONS: Our results suggest that gestational exposure to glyphosate is associated with adverse early neurodevelopment, with more pronounced delays at 24 months. Given glyphosate's wide usage, further investigation into the impact of gestational glyphosate exposure on neurodevelopment is warranted.

Maternal blood metal concentrations are associated with matrix metalloproteinases (MMPs) among pregnant women in Puerto Rico.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) are important regulators of uterine remodeling, a critical process for healthy pregnancies, and studies have revealed a link between an imbalance in MMPs and adverse birth outcomes. Toxicological studies have indicated that exposure to heavy metals can alter the levels of inflammatory cytokines, including MMPs. Despite growing evidence, the clear association between heavy metal exposure and MMPs has yet to be explored extensively in human populations. To have a better understanding of the association, in this study, we assessed associations between maternal blood metal levels with MMPs among 617 pregnant women in the Puerto Rico PROTECT birth cohort. METHODS: We measured blood concentrations for 11 metals in the first and/or second trimester of pregnancy using ICP-MS. MMPs (MMP1, MMP2, and MMP9) were quantified using a customized Luminex assay. Linear mixed effects models (LMEs) were used to regress MMPs on metals and included random intercepts for study participants to account for correlated repeated outcome measures. Fetal sex effects were estimated using interaction terms between metal exposure variables and fetal sex indicators. RESULTS: We observed significant associations between cesium, manganese, and zinc with all the MMPs that were measured. We also observed differences in metal-MMPs associations by fetal sex. Cobalt was positively associated with MMP1 only in women with male fetuses, and cesium was negatively associated with MMP1 only in women with female fetuses. MMP2 had significant associations with maternal blood metal concentrations only in women with female fetuses. CONCLUSION: Certain metals were significantly associated with MMPs that are responsible for uterine remodeling and healthy pregnancies. Most of these associations differed by fetal sex. This study highlighted significant metal-MMPs associations that may inform research on new avenues for understanding heavy metal-induced adverse birth outcomes and the development of diagnostic tools.

Personal care products: Demographic characteristics and maternal hormones in pregnant women from Puerto Rico.

Personal care products (PCPs) refer to a wide variety of items commonly characterized as health or beauty products. PCPs contain a number of ingredients, often including a wide range of endocrine disrupting chemicals such as phthalates and parabens. The present study examines the association between self-reported PCP use and prenatal sex-steroids and thyroid hormones levels in women from Puerto Rico. We recruited pregnant women (n = 1070) through the Puerto Rico PROTECT Cohort and collected blood, demographic and pregnancy-related data at recruitment and subsequent visits. PCP use in the 48-h preceding the blood sample was collected through self-reported questionnaires. Nine hormones (corticotropin-releasing hormone [CRH], sex-hormone binding globulin [SHBG], estriol [E3], progesterone, testosterone, thyroid-stimulating hormone [TSH], total triiodothyronine [T3], total thyroxine [T4], and free thyroxine [fT4]) were measured in maternal serum samples at two points during pregnancy. Linear mixed models with random intercepts were used to examine associations between PCP use and serum hormone levels. Use of cosmetics significantly increased with age, household income and education level (p < 0.01). Use of hair products, such as hair dyes and bleach, relaxers, and mousse, was associated with lower levels of all sex steroid hormones compared to non-use: SHBG (%Δ = -7.1, 95%CI: -12.4,-1.8), E3 (%Δ = -23.2, 95%CI: -32.2,-13.0), progesterone (%Δ = -21.5, 95%CI: -29.4,-12.9) and testosterone (%Δ = -21.5, 95%CI: -33.1,-7.8) adjusted for maternal age, education and pre-pregnancy body mass index. Our findings suggest that household income and education level influence PCP use among pregnant women in this study. Use of certain hair products was associated with lower concentrations of sex steroid hormones. Although there are limitations to questionnaire data, characterizing PCP use is inexpensive and may represent exposure from multiple classes of chemicals, including chemicals that may not specifically appear on product labels and/or have not been tested for endocrine disrupting potential, making it a useful complement to chemical biomarker data.

The association between urinary glyphosate and aminomethyl phosphonic acid with biomarkers of oxidative stress among pregnant women in the PROTECT birth cohort study.

BACKGROUND: Glyphosate is a widely used herbicide in global agriculture. Glyphosate and its primary environmental degradate, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress in in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may be indicative of health effects caused by previous exposure via multiple mechanisms including oxidative stress. METHODS: Glyphosate and AMPA were measured in 347 urine samples collected between 16 and 20 weeks gestation and 24-28 weeks gestation from pregnant women in the PROTECT birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2α (8-iso-PGF2α), its metabolite 2,3-dinor-5,6-dihydro-15-F2 t-isoprostane (8-isoprostane metabolite) and prostaglandin-F2α (PGF2α), were also measured. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Potential nonlinear trends were also assessed using tertiles of glyphosate and AMPA exposure levels. RESULTS: No significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5-19.3%) higher 8-iso-PGF2α metabolite concentrations. Significant linear trends were also identified when examining tertiles of exposure variables. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6-26.5%) and 15.2% (1.8-30.3%) higher 8-isoprostane metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (-0.9 to 10.7%) higher 8-iso-PGF2α. CONCLUSIONS: Urinary concentrations of the main environmental degradate of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.

Performance of urine, blood, and integrated metal biomarkers in relation to birth outcomes in a mixture setting.

BACKGROUND: Studies on the health effects of metal mixtures typically utilize biomarkers measured in a single biological medium, such as blood or urine. However, the ability to evaluate mixture effects are limited by the uncertainty whether a unified medium can fully capture exposure for each metal. Therefore, it is important to compare and assess metal mixtures measured in different media in epidemiology studies. OBJECTIVES: The aim of this study was to examine the mixture predictive performance of urine and blood metal biomarkers and integrated multi-media biomarkers in association with birth outcomes. METHODS: In our analysis of 847 women from the Puerto Rico PROTECT Cohort, we measured 10 essential and non-essential metals in repeated and paired samples of urine and blood during pregnancy. For each metal, we integrated exposure estimates from paired urine and blood biomarkers into multi-media biomarkers (MMBs), using intraclass-correlation coefficient (ICC) and weighted quantile sum (WQS) approaches. Using Ridge regressions, four separate Environmental risk scores (ERSs) for metals in urine, blood, MMBICC, and MMBWQS were computed as a weighted sum of the 10 metal concentrations. We then examined associations between urine, blood, and multi-media biomarker ERSs and birth outcomes using linear and logistic regressions, adjusting for maternal age, maternal education, pre-pregnancy body mass index (BMI), and second-hand smoke exposure. The performance of each ERS was evaluated with continuous and tertile estimates and 95% confidence intervals of the odds ratio of preterm birth using area under the curve (AUC). RESULTS: Pb was the most important contributor of blood ERS as well as the two integrated multi-media biomarker ERSs. Individuals with high ERS (3rd tertile) showed increased odds of preterm birth compared to individuals with low ERS (1st tertile), with 2.8-fold (95% CI, 1.49 to 5.40) for urine (specific gravity corrected); 3.2- fold (95% CI, 1.68 to 6.25) for blood; 3.9-fold (95% CI, 1.72 to 8.66) for multi-media biomarkers composed using ICC; and 5.2-fold (95% CI, 2.34 to 11.42) for multi-media biomarkers composed using WQS. The four ERSs had comparable predictive performances (AUC ranging from 0.64 to 0.68) when urine is examined with specific gravity corrected concentrations. CONCLUSIONS: Within a practical metal panel, measuring metals in either urine or blood may be an equally good approach to evaluate the metals as a mixture. Applications in practical study design require validation of these methods with other cohorts, larger panels of metals and within the context of other adverse health effects of interest.

Attitudes Toward the Environment and Use of Information and Communication Technologies to Address Environmental Health Risks in Marginalized Communities: Prospective Cohort Study.

BACKGROUND: Information and communication technologies, including mobile health (mHealth), can help isolated communities address environmental health challenges. The Puerto Rican island of Culebra has faced multiple sociopolitical and economic factors that have distressed the island's environment and health. Culebrenses are technologically engaged and have demonstrated a use of technology that transcends socioeconomic barriers. As a result, technological interventions could potentially help manage environmental risks on the island. OBJECTIVE: This study aims to test and evaluate the potential benefits of an mHealth tool, termed ¡mZAP! (Zonas, Acción y Protección), for engaging communities with environmental risks through technology. METHODS: Participants using ¡mZAP! (N=111) were surveyed. Bivariate analyses were used to examine associations of mHealth use with sociodemographics, technology use, an adapted environmental attitudes inventory, and the multidimensional health locus of control. Logistic regression was used to examine associations between attitudes toward environmental health risks and mHealth use. RESULTS: Higher positive attitudes toward the environment were significantly associated with the use of ¡mZAP! (odds ratio 5.3, 95% CI 1.6-17.0). Environmental attitudes were also associated with the multidimensional health locus of control powerful others subscale (P=.02), indicating that attitudes toward the environment become more negative as feelings controlled by others increase. Participants felt that the authorities would resolve the challenges (63/111, 56.7%). CONCLUSIONS: Perceived lack of control could present barriers to collective actions to address salient environmental health challenges in communities. The ongoing dependency on government-based solutions to community problems is worrisome, especially after the hurricane experiences of 2017 (which may potentially continue to be an issue subsequent to the more recent 2020 earthquakes).

Impact of Hurricane Maria on Drinking Water Quality in Puerto Rico.

This study performed a comprehensive assessment of the impact of Hurricane Maria (HM) on drinking water quality in Puerto Rico (PR) by integrating targeted chemical analysis of both inorganic (18 trace elements) and organic trace pollutants (200 micropollutants) with high-throughput quantitative toxicogenomics and in vitro biomarkers-based toxicity assays. Average concentrations of 14 detected trace elements and 20 organic micropollutants showed elevation after HM. Arsenic, sucralose, perfluorooctanoic acid (PFOA), atrazine-2-hydroxy, benzotriazole, acesulfame, and prometon were at significantly (p < 0.05) higher levels in the post-HM than in the pre-HM samples. Thirteen micropollutants, including four pesticides, were only detected in posthurricane samples. Spatial comparison showed higher pollutant and toxicity levels in the samples from northern PR (where eight Superfund sites are located) than in those from southern PR. Distinctive pathway-specific molecular toxicity fingerprints for water extracts before and after HM and at different locations revealed changes in toxicity nature that likely resulted from the impact of HM on drinking water composition. Correlation analysis and Maximum Cumulative Ratio assessment suggested that metals (i.e., arsenic) and PFOA were the top ranked pollutants that have the potential to cause increased risk after HM, providing a possible direction for future water resource management and epidemiological studies.

Predictors of urinary and blood Metal(loid) concentrations among pregnant women in Northern Puerto Rico.

Given the potential adverse health effects related to toxic trace metal exposure and insufficient or excessive levels of essential trace metals in pregnant women and their fetuses, the present study characterizes biomarkers of metal and metalloid exposure at repeated time points during pregnancy among women in Puerto Rico. We recruited 1040 pregnant women from prenatal clinics and collected urine, blood, and questionnaire data on demographics, product use, food consumption, and water usage at up to three visits. All samples were analyzed for 16 metal(loid)s: arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), cesium (Cs), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), titanium (Ti), uranium (U), vanadium (V), and zinc (Zn). Urine samples were additionally analyzed for molybdenum (Mo), platinum (Pt), antimony (Sb), tin (Sn), and tungsten (W). Mean concentrations of most metal(loid)s were higher among participants compared to the general US female population. We found weak to moderate correlations for inter-matrix comparisons, and moderate to strong correlations between several metal(loid)s measured within each biological matrix. Blood concentrations of Cu, Zn, Mn, Hg, and Pb were shown to reflect reliable biomarkers of exposure. For other metals, repeated samples are recommended for exposure assessment in epidemiology studies. Predictors of metal(loid) biomarkers included fish and rice consumption (urinary As), fish and canned food (blood Hg), drinking public water (blood Pb), smoking (blood Cd), and iron/folic acid supplement use (urinary Cs, Mo, and Sb). Characterization of metal(loid) biomarker variation over time and between matrices, and identification of important exposure sources, may inform future epidemiology studies and exposure reduction strategies.

Impact of Hurricanes Irma and Maria on Puerto Rico Maternal and Child Health Research Programs.

Puerto Rico was hit by two major hurricanes in September 2017 causing great devastation, losing over 90% of the power grid, wireless communication and access to potable water, and destroying many homes. Our research programs: Puerto Rico Testsite for Exploring Contamination Threats (PROTECT), Center for Research on Early Childhood Exposure and Development in Puerto Rico (CRECE), Zika in Infants and Pregnancy (ZIP), and Environmental Influences on Child Health Outcomes (ECHO) are ongoing observational cohort studies that have been investigating environmental risk factors for perinatal health outcomes among Puerto Rican mothers and infants. Our projects paused operations for about two weeks, to begin recovery process and become a source of assistance, retaining 95% of study participants across all research programs. We joined with various groups to ensure the safety and welfare of team members, study participants, community health center partners, and members of the surrounding communities. We learned important lessons about the impact of these hurricanes and the difficulties of the recovery. Major challenges post-hurricanes were access to care and nutrition, maternal stress, and environmental damage. We understood the need to integrate disaster preparedness into our programs' operating procedures and future applications, recognizing that these events will recur. We will grow resilience among our staff, maternal and child health partners, and participants by building on the experience of these two storms.

Qualitative Assessment of Environmental Health Risk Perceptions and Community Challenges in a Puerto Rican Community: Change and Continuity in Response to Hurricanes Irma and María.

Culebra, a geographically isolated island located 17 miles from the eastern coast of Puerto Rico's main island, suffers from an amalgam of significant environmental health risk and associated social determinants of health that are affecting the community. In 2017, two major Hurricanes (Irma and María) impacted Culebra, resulting in an increase of preexisting environmental health risk. The present study's primary aim was to explore community attitudes, beliefs, and perceptions of environmental health risk, and to describe the social priorities of Culebrenses in relation to these risks and challenges. Semi-structured interview guide and Rapid Qualitative Inquiry (RQI) focused on topics of environmental health risk was followed. Qualitative focus groups and individual interviews were conducted among community members in Culebra before and shortly after Hurricanes Irma and María affected the island. Environmental health factors identified included: presence of mosquitoes, trash disposal, water quality and tourism. Additionally, a strong sentiment of island pride was found potentially generating a sense of community that could facilitate solutions to the existing environmental health challenges. Preexisting environmental health risk magnified after the pass of Hurricanes Irma and María. Sustainable and community engagement approaches are needed to develop strategies that can assist in the mitigation and resolution of the identified environmental health risk and challenges, including factors associated with threats such as disasters and pollution.

Investigating the impact of Hurricane Maria on an ongoing birth cohort in Puerto Rico.

Prior to Hurricane Maria, Puerto Rico already had 200+ hazardous waste sites, significant contamination of water resources, and among the highest rates of preterm birth in the US. To address these issues, the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) Center was formed in 2010 to investigate prenatal environmental exposures, particularly phthalates, and adverse birth outcomes. Recent work from the PROTECT study confirms that in utero exposure to certain phthalates is associated with shorter gestation and increased risk of preterm birth. However, previous research also suggests that pregnant women who experience a natural disaster such as Hurricane Maria are at higher risk of adverse birth outcomes, but it is unknown whether this is due to stress, hazardous exposures, or a combination of factors. Thus, the aim of this analysis was to characterize hurricane-related changes in phthalate exposures and experiences within the PROTECT cohort. Among 176 participants who were pregnant during or within 5 months after Maria, 122 completed a questionnaire on hurricane-related experiences. Questionnaire results and biomarkers of exposure suggest that participants did not have regular access to fresh foods and water during hurricane recovery, and almost half reported structural damage to their home. In addition, biomarker concentrations of phthalates commonly used in food packaging were higher among participants post-hurricane, while phthalates commonly used in personal care products were lower compared to pre-hurricane levels. Hurricane-related increases in phthalate exposure, as well as widespread structural damage, food and water shortages, and long-term absence of electricity and cell phone service, likely increased the risk of adverse birth outcomes among this already vulnerable population.

The association of urinary organophosphate ester metabolites and self-reported personal care and household product use among pregnant women in Puerto Rico.

BACKGROUND: Organophosphate esters (OPEs) are widely detected among U.S. pregnant women. OPEs, some of which are present in nail polish, have been associated with adverse reproductive health outcomes. More research is needed to investigate associations with OPEs and personal care products (PCP) use. METHODS: Pregnant women (18-40 years) were recruited from two hospitals and five prenatal clinics in Northern Puerto Rico (n = 148 women) between 2011 and 2015. Concentrations of bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), di-benzyl phosphate (DBzP), di-cresyl phosphate (DCP), DPHP, and 2,3,4,5-tetrabromobenzoic acid (TBBA) were measured twice during pregnancy. Participants completed questionnaires on PCP and household products (HP) use. Associations among products and metabolite concentrations (n = 296 observations) were assessed using linear mixed models. RESULTS: BCEtP, BCPP, BDCPP and DPHP were detected frequently (≥77%). Correlations among metabolites (0.16 ≤ r ≤ 0.35) and Intraclass correlation coefficients (ICCs) (0.03 ≤ ICC≤0.34) were weak-to-moderate. Suntan lotion was associated with a 110% increase in BDCPP. DPHP increased with perfume (51%) and nail polish (49%) use. BCPP increased 46% with pesticide use in home. CONCLUSION: Biomarkers of OPEs were often detected among pregnant women. Associations with PCP and HP use suggest OPEs may be used in such products, specifically in perfume and nail polish. Further investigation into these products is warranted.

Discrimination and Health among Lesbian, Gay, Bisexual and Trans People in Puerto Rico.

OBJECTIVE: To identify the experiences of discrimination among and the perceived priorities for the health of lesbian, gay, bisexual, and trans (LGBT) people in Puerto Rico (PR). METHODS: Data were collected during the 2013 LGBT Pride Parade in San Juan, using a brief self-administered survey that included questions on sociodemographic characteristics, the disclosure of sexual orientation/gender identity, experiences of discrimination, experiences while receiving social and health services, and perceived healthcare priorities and needs. RESULTS: Most participants reported that they had disclosed their sexual orientation to at least one person. Discrimination due to sexual orientation/gender identity was most frequently reported to have occurred in school settings. At least 25% of the sample reported regular or negative experiences based on sexual orientation/gender identity when receiving government services and when looking for support from relatives. HIV/AIDS, mental health, and sexual health were identified as healthcare priorities. In bivariate analyses, mental health services and aging were the priorities most frequently reported among older participants. HIV/AIDS was the main priority only for gay men; sexual health was the main priority for bisexuals; and mental health was the main priority for lesbians. Most participants reported that their preferred modalities for health service provision were support groups and health education. CONCLUSION: The experiences of discrimination among LGBT people in PR were consistent across age groups and sexual orientation/gender identity. Policies and interventions to address discrimination in different settings are necessary. The findings also suggest the need to prioritize HIV services among gay men and to address mental and sexual health needs among lesbian and bisexual people.

Associations of maternal blood metal concentrations with plasma eicosanoids among pregnant women in Puerto Rico.

BACKGROUND/AIM: Heavy metals are known to induce oxidative stress and inflammation, and the association between metal exposure and adverse birth outcomes is well established. However, there lacks research on biomarker profiles linking metal exposures and adverse birth outcomes. Eicosanoids are lipid molecules that regulate inflammation in the body, and there is growing evidence that suggests associations between plasma eicosanoids and pregnancy outcomes. Eicosanoids may aid our understanding of etiologic birth pathways. Here, we assessed associations between maternal blood metal concentrations with eicosanoid profiles among 654 pregnant women in the Puerto Rico PROTECT birth cohort. METHODS: We measured concentrations of 11 metals in whole blood collected at median 18 and 26 weeks of pregnancy, and eicosanoid profiles measured in plasma collected at median 26 weeks. Multivariable linear models were used to regress eicosanoids on metals concentrations. Effect modification by infant sex was explored using interaction terms. RESULTS: A total of 55 eicosanoids were profiled. Notably, 12-oxoeicosatetraenoic acid (12-oxoETE) and 15-oxoeicosatetraenoic acid (15-oxoETE), both of which exert inflammatory activities, had the greatest number of significant associations with metal concentrations. These eicosanoids were associated with increased concentrations of Cu, Mn, and Zn, and decreased concentrations of Cd, Co, Ni, and Pb, with the strongest effect sizes observed for 12-oxoETE and Pb (ß:-33.5,95 %CI:-42.9,-22.6) and 15-oxoETE and Sn (ß:43.2,95 %CI:11.4,84.1). Also, we observed differences in metals-eicosanoid associations by infant sex. Particularly, Cs and Mn had the most infant sex-specific significant associations with eicosanoids, which were primarily driven by female fetuses. All significant sex-specific associations with Cs were inverse among females, while significant sex-specific associations with Mn among females were positive within the cyclooxygenase group but inverse among the lipoxygenase group. CONCLUSION: Certain metals were significantly associated with eicosanoids that are responsible for regulating inflammatory responses. Eicosanoid-metal associations may suggest a role for eicosanoids in mediating metal-induced adverse birth outcomes.

Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort.

BACKGROUND: Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. OBJECTIVES: We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among N=1,433 Puerto Rico PROTECT study participants. METHODS: We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. RESULTS: We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture odds ratio(OR)=1.57 (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB ß=0.78 (95% CI: 0.17, 1.38) and adjusted P-PB ß=0.85 (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted ß=-0.57; 95% CI: -1.09, -0.05). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. CONCLUSIONS: Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.

Associations between urinary hydroxylated polycyclic aromatic hydrocarbon biomarker concentrations and measures of timing of delivery and infant size at birth.

Preterm birth is a leading cause of neonatal mortality and presents significant public health concerns. Environmental chemical exposures during pregnancy may be partially to blame for disrupted delivery timing. Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion, exposure to which occurs via inhalation of cigarette smoke and automobile exhaust, and ingestion of charred meats. Exposure to PAHs in the US population is widespread, and pregnant women represent a susceptible population to adverse effects of PAHs. We aimed to investigate associations between gestational exposure to PAHs and birth outcomes, including timing of delivery and infant birth size. We utilized data from the PROTECT birth cohort where pregnant women provided spot urine samples at up to three study visits (median 16, 20, and 24 weeks gestation). Urine samples were assayed for eight hydroxylated PAH concentrations. Associations between PAHs and birth outcomes were calculated using linear/logistic regression models, with adjustment for maternal age, education, pre-pregnancy BMI, and daily exposure to environmental tobacco smoke. Models accounted for urine dilution using specific gravity. We also explored effect modification by infant sex. Interquartile range (IQR) increases in all averaged PAH exposures during the second trimester were associated with reduced gestational age at delivery and increased odds of overall PTB, although these associations were not statistically significant (p > 0.05). Most PAHs at the second study visit were most strongly associated with earlier delivery and increased odds of overall and spontaneous PTB, with visit 2 2-hydroxynapthalene (2-NAP) being significantly associated with increased odds of overall PTB (OR:1.55; 95 %CI: 1.05,2.29). Some PAHs resulted in earlier timing of delivery among only female fetuses, specifically 2-NAP on overall PTB (female OR:1.52 95 %CI: 1.02,2.27; male OR:0.78, 95 %CI: 0.53,1.15). Future work should more deeply investigate differential physiological impacts of PAH exposure between pregnancies with male and female fetuses, and on varying developmental processes occurring at different points through pregnancy.

Prenatal polycyclic aromatic hydrocarbon exposure and neurodevelopment among children in Puerto Rico.

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants produced through the combustion of organic matter, with sources ranging from traffic pollution to diet. Although PAH exposure has been associated with adverse health effects, few studies have examined its impact on neurodevelopmental delay (NDD). Thus, our study aims to investigate the effect of prenatal PAH exposure on the odds of NDD. We measured 7 hydroxylated PAH metabolites in spot urine samples collected up to three times during pregnancy in the PROTECT birth cohort. NDD was identified using score cutoffs from the Ages and Stages Questionnaire, 3rd edition offered in Spanish, across five domains at 12, 24, 36, and 48 months. We utilized logistic regression and mixed effects logistic regression models to assess associations between prenatal PAH concentrations and NDD. Our results showed mostly lower odds of NDD with higher PAH exposure (p < 0.05). However, male children showed higher odds of NDD in relation to PAH exposure, particularly in the Fine Motor domain. For example, 1-hydroxypyrene was associated with 1.11 (1.01, 1.23) times odds of delay in fine motor function in male children versus 0.91 (0.82, 1.00) times odds in female children. Our preliminary sex-specific results suggest that PAH exposure may impact neurodevelopment in male children and prompt further investigation into the potential sex-specific mechanisms of PAHs on motor function.

Urinary phenol and paraben concentrations in association with markers of inflammation during pregnancy in Puerto Rico.

Exposure to phenols and parabens may contribute to increased maternal inflammation and adverse birth outcomes, but these effects are not well-studied in humans. This study aimed to investigate relationships between concentrations of 8 phenols and 4 parabens with 6 inflammatory biomarkers (C-reactive protein (CRP); matrix metalloproteinases (MMP) 1, 2, and 9; intercellular adhesion molecule-1 (ICAM-1); and vascular cell adhesion molecule-1 (VCAM-1)) measured at two time points in pregnancy in the PROTECT birth cohort in Puerto Rico. Linear mixed models were used, adjusting for covariates of interest. Results are expressed as the percent change in outcome per interquartile range (IQR) increase in exposure. Particularly among phenols, numerous significant negative associations were found, for example, between benzophenone-3 and CRP (-11.21 %, 95 % CI: -17.82, -4.07) and triclocarban and MMP2 (-9.87 %, 95 % CI: -14.05, -5.5). However, significant positive associations were also detected, for instance, between bisphenol-A (BPA) and CRP (9.77 %, 95 % CI: 0.67, 19.68) and methyl-paraben and MMP1 (10.78 %, 95 % CI: 2.17, 20.11). Significant interactions with female fetal sex and the later study visit (at 24-28 weeks gestation) showed more positive associations compared to male fetal sex and the earlier study visit (16-20 weeks gestation). Our results suggest that phenols and parabens may disrupt inflammatory processes pertaining to uterine remodeling and endothelial function, with important implications for pregnancy outcomes. More research is needed to further understand maternal inflammatory status in an effort to improve reproductive and developmental outcomes.