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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.

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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.

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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.

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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.

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Matrix metalloproteinases (MMPs) are major extracellular matrix (ECM) remodeling proteinases and regulate uterine remodeling, which is a critical process for healthy pregnancies. The goal of this study was to investigate associations between maternal blood MMPs during pregnancy and birth outcomes among 898 pregnant women in the Puerto Rico PROTECT birth cohort. MMPs (MMP1, MMP2, and MMP9) were quantified using a customized Luminex assay in blood samples collected at two gestational study visits (around 18 and 26 weeks gestation). Linear and logistic regression models were used to regress continuous and binary birth outcomes, respectively, on MMPs at each study visit separately. Sensitivity analyses were conducted to test for effect modification by fetal sex on associations between MMPs and birth outcomes. We observed significant associations between MMP2 at visit 1 and newborn length that were in the opposite direction from the associations between MMP9 at visit 3 and newborn length. MMPs were associated with increased odds of preeclampsia and gestational diabetes mellitus, though case numbers were low. We also observed significant inverse associations with gestational age for MMP9 and MMP2 at visit 1 and visit 3, respectively, and these associations were observed only in mothers carrying male fetuses. Further, MMP2 was associated with heavier female fetuses, whereas MMP9 was associated with lighter female fetuses. We observed significant associations between birth outcomes and MMPs, and the majority of these associations differed by fetal sex. This study highlighted significant MMPs-birth outcomes associations that may provide a basis to explore the impact of MMPs on endometrium health and physiology.

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OBJECTIVE: To describe the importance of community engagement from research projects and research centers in times of disasters or emergencies, using the case of Puerto Rico in recent years (2017 - 2022) as an example. METHODS: First, research participants and stakeholders from local community and health organizations were contacted via email and phone calls after each emergency to assess their immediate needs. Second, needs were classified in categories (materials, educational resources, service referrals, and collaborations). Finally, delivery of support was coordinated in a timely manner whether in person or online. RESULTS: Activities were conducted such as handing out materials, providing educational resources, contacting participants, and stakeholders, as well as coordinating collaboration with community and organizations. CONCLUSION: Several lessons were learned from our experiences related to Puerto Rico's recent emergencies as well as some relevant recommendations for future disasters. The efforts presented illustrate the importance of community engagement from academic institutions in disasters. Research centers and research projects, particularly those with community engagement components, should consider providing support in the preparedness phase as well as the recovery phase if necessary. Community engagement in emergencies is crucial to recovery efforts as well as fostering empowerment and making an impact on individual and societal levels.

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BACKGROUND: The PROTECT Center is a multi-project initiative that studies the relationship between exposure to environmental contaminants and preterm births during the prenatal and postnatal period among women living in Puerto Rico. PROTECT's Community Engagement Core and Research Translation Coordinator (CEC/RTC) play a key role in building trust and capacity by approaching the cohort as an engaged community that provides feedback about processes, including how personalized results of their exposure to chemicals should be reported back. The goal of the Mi PROTECT platform was to create a mobile-based application of DERBI (Digital Exposure Report-Back Interface) for our cohort that provides tailored, culturally appropriate information about individual contaminant exposures as well as education on chemical substances and approaches to exposure reduction. METHODS: Participants (N = 61) were presented with commonly used terms in environmental health research related to collected samples and biomarkers, followed by a guided training on accessing and exploring the Mi PROTECT platform. Participants evaluated the guided training and Mi PROTECT platform answering a Likert scale in separated surveys that included 13 and 8 questions, respectively. RESULTS: Participants provided overwhelmingly positive feedback on the clarity and fluency of presenters in the report-back training. Most participants reported that the mobile phone platform was both accessible and easy to navigate (83% and 80%, respectively) and that images included in the platform facilitated comprehension of the information. Overall, most participants (83%) reported that language, images, and examples in Mi PROTECT strongly represented them as Puerto Ricans. CONCLUSIONS: Findings from the Mi PROTECT pilot test informed investigators, community partners and stakeholders by demonstrating a new way to promote stakeholder participation and foster the "research right-to-know."

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Phthalates are ubiquitous environmental exposures that may be implicated in inflammatory processes, as demonstrated by previous in vivo and in vitro studies. Few human studies have substantiated these observations. This study sought to examine whether maternal phthalate exposures impact inflammatory processes, as measured by circulating inflammatory biomarkers, in the PROTECT cohort in northern Puerto Rico. Inflammatory biomarkers included matrix metalloproteinases 1, 2, and 9 (MMPs), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM), and intercellular cell adhesion molecule-1 (ICAM). Biomarkers were measured in maternal serum samples collected during pregnancy. 19 phthalate metabolites were assessed in urinary samples collected at three study visits across pregnancy. Phthalates with <50 % of measurements above the limit of detection were excluded from analysis. We utilized linear mixed effect models to estimate associations between interquartile range increases in phthalate metabolite concentrations and percent changes in inflammatory biomarkers. Our results revealed significant associations between mono-n-butyl phthalate (MBP) and higher MMP1 by 7.86 % (95 % CI: 0.49, 15.76) and between mono oxononyl phthalate (MONP) and higher MMP2 by 8.30 % (95 % CI: 2.22, 14.75). We observed negative or null associations between phthalate metabolites and MMP2, MMP9, ICAM, VCAM, and CRP. Many results were significantly modified by fetal sex, particularly those between di-2-ethylhexyl phthalate (DEHP) metabolites and MMP1 (p-interaction: MEHHP = 0.01, MEOHP = 0.04, MECPP = 0.01) and MMP2 (p-interaction: MEHHP = 0.03, MEOHP = 0.01, MECPP = 0.01), for which associations were positive among only women carrying female fetuses. MMPs have been previously associated with preeclampsia and hypertensive pregnancy disorders as mediators of artery remodeling. Hence, our findings suggest a potential role for phthalates in mediating the maternal inflammatory response, as well as significant sexual dimorphism in these relationships, which has implications for several adverse pregnancy outcomes.

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Studies have revealed a link between aberrant levels of maternal C-reactive protein (CRP) and cell adhesion molecules (CAMs) with adverse birth outcomes. Some epidemiologic studies have indicated that long-term metal exposures can modulate the levels of CRP and CAMs, but the associations between prenatal metal exposures and the levels of CRP and CAMs have yet to be studied more extensively. In this study, we assessed associations between maternal blood metal levels and CRP/CAMs among 617 pregnant women in the Puerto Rico PROTECT birth cohort. Methods: Blood samples were collected from participants at 16-20 (visit 1) and 24-28 (visit 3) weeks gestation. We measured concentrations of 11 metals using inductively coupled plasma mass spectrometry (ICP-MS). From the blood samples, CRP and CAMs intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) were also quantified using a customized Luminex assay. Linear-mixed effects models (LMEs) were used to regress CRP and CAMs on metals and included random intercepts for study participants to account for correlated repeated outcome measures. Fetal sex and visit effects were estimated using interaction terms between metal exposure variables and fetal sex, as well as visit indicators, respectively. Results: We observed significant positive associations between nickel and CRP (Δ: 7.04, 95% CI = 0.75, 13.73) and between lead and VCAM (Δ: 4.57, 95% CI = 1.36, 7.89). The positive associations were mainly driven by mothers carrying male fetuses. We also observed various visit-specific associations. The significant associations between metals and CRP were predominantly driven by visit 3; however, the significant associations between metals and VCAM were mainly driven by visit 1. Conclusion: Certain maternal blood metal levels were significantly associated with CRP and CAMs and most of these associations were differentially driven by fetal sex, as well as by timing in pregnancy. Future studies should further explore metal-CRP/CAMs associations for a better understanding of the underlying mechanism of metal-induced adverse birth outcomes.

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The PROTECT research Center funded by the NIH's National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program was launched in 2010 to explore the impact of exposure to pollutants on the high rate of premature births in Puerto Rico. In September 2017, Hurricanes Irma and María devastated the archipelago, which caused: collapse of the electrical system, collapse of the communication system, limited access to clean water, food, gas, and health services, destruction of public (e.g., hospitals) and private property (e.g., houses) and more than 4500 deaths. Pregnant and postpartum individuals are especially vulnerable to natural disasters. They face difficulty obtaining adequate pre- and post-natal care, are exposed to increased risk of miscarriage, premature delivery, and giving birth to low birth weight babies during and after disasters and are also more likely to suffer physical and mental health problems compared to the general population during and after disasters. A face-to-face questionnaire was administered to PROTECT participants who were pregnant during hurricanes Irma or Maria or who became pregnant shortly after in order to identify hurricane-related sources of stress and other adverse effects. This paper is based on the answers to the open-ended question at the end of the questionnaire where participants were asked to share their experiences during and after the hurricanes. Among the 375 participants who completed the survey, 76 answers to the open-ended question were considered due to data saturation. The answers to the open-ended question were transcribed into a document in order to facilitate the coding process. The transcribed text was analyzed first to identify emerging categories and then coded to identify common themes as well as divergence among participants. The following themes were identified: pregnancy and birth challenges, lack of access to basic services, housing conditions, stressful working conditions, concerns about health, concerns about their children, and positive or protective aspects. The results indicate how the disruption in access to basic services has a unique impact on the physical and mental health of pregnant and post-partum women in an emergency situation. These findings point to the potential benefit of developing specific protocols designed for emergency preparedness aimed at this population, which can inform healthcare providers and community organizations in case of future events.