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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. [ABSTRACT FROM AUTHOR]

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. • Significant associations between maternal blood MMPs with birth outcomes. • Significant inverse associations with gestational age for MMP9 and MMP2 were observed only in mothers carrying male fetuses. • MMP2 was associated with heavier female fetuses, whereas MMP9 was associated with lighter female fetuses. [ABSTRACT FROM AUTHOR]

• Largest study to examine phthalate and eicosanoid associations in single and multipollutant frameworks. • First study to investigate the impact of a recent phthalate replacement on altered levels of eicosanoids during pregnancy. • Metabolites of low molecular phthalates and a recent replacement became prominent in multipollutant analysis. • Weighted sum of phthalate exposure positively associated with multiple eicosanoids, particularly those from the Cytochrome P450 pathway. Humans are exposed to complex mixtures of phthalates. Gestational exposure to phthalates has been linked to preeclampsia and preterm birth through potential pathways such as endocrine disruption, oxidative stress, and inflammation. Eicosanoids are bioactive signaling lipids that are related to a variety of homeostatic and inflammatory processes. We investigated associations between urinary phthalates and their mixtures with plasma eicosanoid levels during pregnancy using the PROTECT cohort in Puerto Rico (N = 655). After adjusting for covariates, we estimated pair-wise associations between the geometric mean of individual phthalate metabolite concentrations across pregnancy and eicosanoid biomarkers using multivariable linear regression. We used bootstrapping of adaptive elastic net regression (adENET) to evaluate phthalate mixtures associated with eicosanoids and subsequently create environmental risk scores (ERS) to represent weighted sums of phthalate exposure for each individual. After adjusting for false-discovery, in single-pollutant analysis, 14 of 20 phthalate metabolites or parent compound indices showed significant and primarily negative associations with multiple eicosanoids. In our mixture analysis, associations with several metabolites of low molecular weight phthalates – DEP, DBP, and DIBP – became prominent. Additionally, MEHHTP and MECPTP, metabolites of a new phthalate replacement, DEHTP, were selected as important predictors for determining the concentrations of multiple eicosanoids from different pathway groups. A unit increase in phthalate ERS derived from bootstrapping of adENET was positively associated with several eicosanoids mainly from Cytochrome P450 pathway. For example, an increase in ERS was associated with 11(S)-HETE (β = 1.6, 95% CI: 0.020, 3.180), (±)11,12-DHET (β = 2.045, 95% CI: 0.250, 3.840), 20(S)-HETE (β = 0.813, 95% CI: 0.147, 1.479), and 9 s-HODE (β = 2.381, 95% CI: 0.657, 4.104). Gestational exposure to phthalates and phthalate mixtures were associated with eicosanoid levels during pregnancy. Results from the mixture analyses underscore the complexity of physiological impacts of phthalate exposure and call for further in-depth studies to examine these relationships. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • There are significant associations between maternal blood metal concentrations and MMPs. • Maternal blood Pb concentration had the greatest positive associations with both MMP1 and MMP2 concentrations. • There are fetal sex-specific differences in the associations between maternal blood metal concentrations and MMPs. [ABSTRACT FROM AUTHOR]

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. • PCPs use did not change between visits in this population of Puerto Rican women. • Household income and education level influenced use of cosmetics and other PCPs. • Use of certain hair products was associated with lower sex steroid hormones levels. • Self-reported PCP use questionnaires are useful complement to biomarker data. [ABSTRACT FROM AUTHOR]

[Display omitted] A growing number of studies have identified both toxic and essential metals which influence fetal growth. However, most studies have conducted single-cohort analyses, which are often limited by narrow exposure ranges, and evaluated metals individually. The objective of the current study was to conduct an environmental mixture analysis of metal impacts on fetal growth, pooling data from three geographically and demographically diverse cohorts in the United States participating in the Environmental Influences on Child Health Outcomes program. The pooled sample (N = 1,002) included participants from the MADRES, NHBCS, and PROTECT cohorts. Associations between seven metals (antimony, cadmium, cobalt, mercury, molybdenum, nickel, tin) measured in maternal urine samples collected during pregnancy (median: 16.0 weeks gestation) and birth weight for gestational age z-scores (BW for GA) were investigated using Bayesian Kernel Machine Regression (BKMR). Models were also stratified by cohort and infant sex to investigate possible heterogeneity. Chromium and uranium concentrations fell below the limits of detection for most participants and were evaluated separately as binary variables using pooled linear regression models. In the pooled BKMR analysis, antimony, mercury, and tin were inversely and linearly associated with BW for GA, while a positive linear association was identified for nickel. The inverse association between antimony and BW for GA was observed in both males and females and for all three cohorts but was strongest for MADRES, a predominantly low-income Hispanic cohort in Los Angeles. A reverse j-shaped association was identified between cobalt and BW for GA, which was driven by female infants. Pooled associations were null for cadmium, chromium, molybdenum, and uranium, and BKMR did not identify potential interactions between metal pairs. Findings suggest that antimony, an understudied metalloid, may adversely impact fetal growth. Cohort- and/or sex-dependent associations were identified for many of the metals, which merit additional investigation. [ABSTRACT FROM AUTHOR]

• A mixture of phthalate metabolites is associated with the oxidative stress biomarker 8-Iso-PGF2α. • Associations differ when 8-Iso-PGF2α results from chemical versus enzymatic lipid peroxidation. • Some phthalates in the mixture are nonlinearly associated with 8-Iso-PGF2α. • Some phthalates interact with one another to impact their associations with 8-Iso-PGF2α. Exposures to phthalate compounds have been linked to adverse birth outcomes, potentially through oxidative stress mechanisms. We explored associations between mixtures of biomarkers of phthalate and phthalate replacement metabolites and oxidative stress using lipid peroxidation biomarker 8-iso-prostaglandin-F2α (8-iso-PGF2α). As 8-iso-PGF2α can be generated via both chemical (nonenzymatic) and enzymatic lipid peroxidation pathways, we calculated the ratio of 8-iso-PGF2α/prostaglandin F2α in an attempt to distinguish the potential contributions of the two pathways. Urinary biomarker measurements were taken from 775 pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) longitudinal birth cohort at up to three time points during gestation (16–20, 20–24, and 24–28 weeks gestation). Adaptive elastic net with pairwise linear interaction terms (adENET-I) was used to determine individual phthalate metabolites and phthalate interactions that were predictive of lipid oxidative stress biomarkers, and to subsequently create environmental risk scores (ERS) to represent weighted sums of phthalate exposure for each individual at each study visit. Repeated ERS were then used in linear mixed effects models to test for associations between biomarkers of phthalate mixtures and biomarkers of oxidative stress. We also used Bayesian kernel machine regression (BKMR) to explore nonlinearity and interactions between phthalate metabolites within the mixture. An increase from the first to fourth quartile of phthalate ERS derived from adENET-I was associated with a 96.7% increase (95% CI: 74.0, 122) in the hypothesized chemical fraction of 8-iso-PGF2α and a 268% increase (95% CI: 139, 465) in the hypothesized enzymatic fraction of 8-iso-PGF2α. BKMR analyses also suggested strong linear associations between the phthalate mixture and biomarkers of lipid oxidative stress. Various phthalates displayed nonlinear relationships with both chemical and enzymatic fractions of 8-iso-PGF2α, and we observed some evidence of interactions between metabolites in the mixture. In conclusion, exposure to phthalate mixtures was strongly associated with linear increases in biomarkers of lipid oxidative stress, and differences observed between hypothesized chemical and enzymatic lipid peroxidation outcomes highlight the need to critically assess pathways of 8-iso-PGF2α generation in relation to environmental exposures. [ABSTRACT FROM AUTHOR]

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. 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. 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, MMB ICC , and MMB WQS 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). 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. 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. [ABSTRACT FROM AUTHOR]

• An extensive panel of blood biomarkers assessing essential and non-essential metals. • A novel example of dimension reduction on the effect modifier space using clustering. • Quantification of interaction between metal exposure and psychosocial stress. • Presence of "poor" psychosocial status intensified vulnerability to manganese exposure. Metal exposure and psychosocial stress in pregnancy have each been associated with adverse birth outcomes, including preterm birth and low birth weight, but no study has examined the potential interaction between them. We examined the modifying effect of psychosocial stress on the association between metals and birth outcomes among pregnant women in Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) birth cohort study. In our analysis of 682 women from the PROTECT study, we measured 16 essential and non-essential metals in blood samples at two time points. We administered questionnaires to collect information on depression, perceived stress, social support, and life experience during pregnancy. Using K-means clustering, we categorized pregnant women into one of two groups: "good" and "poor" psychosocial status. We then evaluated whether the effect of blood metals (geometric average) on adverse birth outcomes (gestational age, preterm birth [overall and spontaneous], birth weight z-score, small for gestation [SGA], large for gestation [LGA]) vary between two clusters of women, adjusting for maternal age, maternal education, pre-pregnancy body mass index (BMI), and second-hand smoke exposure. Blood manganese (Mn) was associated with an increased odds ratio (OR) of overall preterm birth (OR/interquartile range [IQR] = 2.76, 95% confidence interval [CI] = 1.25, 6.12) and spontaneous preterm birth (OR/IQR: 3.68, 95% CI: 1.20, 6.57) only among women with "poor" psychosocial status. The association between copper (Cu) and SGA was also statistically significant only among women having "poor" psychosocial status (OR/IQR: 2.81, 95% CI: 1.20, 6.57). We also observed associations between nickel (Ni) and preterm birth and SGA that were modified by psychosocial status during pregnancy. Presence of "poor" psychosocial status intensified the adverse associations between Mn and preterm birth, Cu and SGA, and protective effects of Ni on preterm. This provides evidence that prenatal psychosocial stress may modify vulnerability to metal exposure. [ABSTRACT FROM AUTHOR]

• First epidemiological study assessing metals and prenatal sex-steroid hormones. • Windows of exposure are important for metals endocrine disruption potential. • CRH is a possible mechanism by which endocrine disruptors impact pregnancy. • Essential metals may be contributors of adverse maternal and fetal outcomes. Metal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes. Pregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal 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 serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations. Arsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4–39.6) and decreased levels in testosterone (%Δ: −16.3, 95%CI: −26.2-−5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3–4.2), E3 (%Δ range: 3.9–8.7) and progesterone (%Δ range: 4.1–6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ −13.3, 95%CI: −18.7-−7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01). Our analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are byproducts of incomplete combustion reactions and are ubiquitous in the environment, leading to widespread human exposure via inhalation and ingestion pathways. PAHs have been implicated as endocrine disrupting compounds in previous animal and in vitro studies, but human studies are currently lacking. Pregnant women and their developing fetuses are particularly susceptible populations to environmental contaminants, in part because alterations in hormone physiology during gestation can have adverse consequences on the health of the pregnancy. We utilized data on 659 pregnant women from the PROTECT longitudinal birth cohort in Puerto Rico to assess associations between repeated measures of 8 urinary hydroxylated PAH (OH-PAH) metabolites and 9 serum hormones during gestation. Urine samples were collected at 3 study visits (median gestational ages of 18, 22, and 26 weeks at each visit, respectively) and serum samples were collected at the first and third study visits. Linear mixed effects models were used to ascertain longitudinal associations between OH-PAHs and hormones, and sensitivity analyses were employed to assess potential nonlinearity and differences in associations on the basis of fetal sex and timing of biomarker measurement. Among the multiple positive associations we observed between OH-PAHs and CRH, estriol, progesterone, T3, and the ratio of T3 to T4, and inverse associations with testosterone, the most notable are a 24.3% increase (95% CI: 13.0, 36.7) in CRH with an interquartile range (IQR) increase in 1-hydroxyphenanthrene and a 17.2% decrease (95% CI: 8.13, 25.4) in testosterone with an IQR increase in 1-hydroxynapthalene. Many associations observed were dependent on fetal sex, and some relationships showed evidence of nonlinearity. These findings demonstrate the importance of studying PAH exposures during pregnancy and highlight the potential complexity of their impacts on the physiology of human pregnancy. Unlabelled Image • Assessed associations between repeated gestational PAH and hormone measurements • PAH exposure resulted in increased concentrations of CRH, estriol and T3. • PAH exposure resulted in decreased concentrations of testosterone and prog/estriol. • Changes in hormone concentrations were dependent on fetal sex and gestational age. • Gestational PAH exposure alters hormones that may result in disruption of labor. [ABSTRACT FROM AUTHOR]

Background: Preterm birth (PTB; gestational age < 37 weeks) is the leading cause of infant morbidity and mortality worldwide. Low and excessive gestational weight gain (GWG) have been previously cited as risk factors for PTB, however the magnitude of association varies across populations. No studies have examined low and excessive GWG as modifiable risk factors for PTB in Puerto Rico, an area with inexplicably high PTB rates.Methods: To examine the relationship between GWG and PTB, we conducted a retrospective analysis using birth certificate data files from the Puerto Rico Department of Health from 2005 to 2012. GWG was standardized to a 40-week gestational duration and was categorized into low, adequate, or excessive for each category of pre-pregnancy body mass index using American College of Obstetricians and Gynecologists guidelines. Logistic regression was used to determine the crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between GWG and PTB.Results: There were 320,695 births included in this analysis; 40.6% with high GWG and 27.3% with low GWG. A greater percentage of women with low GWG were less than 20 years of age, had less than a high school education, and were underweight compared to women with adequate and excessive GWG. Women with low compared to adequate GWG had increased odds of PTB (OR = 1.34, 95% CI = 1.30-1.37). However, excessive compared to adequate GWG was not associated with PTB (OR = 0.99, 95% CI = 0.97-1.02).Conclusions: Among women in Puerto Rico, low GWG was associated with increased odds of PTB. With the exception of obesity, these associations persisted within all strata of pre-pregnancy body mass index, highlighting the importance of maintaining a healthy weight during pregnancy. Future research should examine other factors that may contribute to GWG, such as dietary nutrients, and explore pathways through which GWG may be contributing to PTB. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1], the author mentioned that two additional NIH staff were involved in the development of the protocol who did not receive recognition in the Acknowledgments section in their published article. [ABSTRACT FROM AUTHOR]

Background: Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes.Methods: At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained.Discussion: With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure.Trial Registration: NCT02856984 . Registered August 5, 2016. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Introduction: Prenatal exposure to some phenols and parabens has been associated with adverse birth outcomes. Hormones may play an intermediate role between phenols and adverse outcomes. We examined the associations of phenol and paraben exposures with maternal reproductive and thyroid hormones in 602 pregnant women in Puerto Rico. Urinary triclocarban, phenol and paraben biomarkers, and serum hormones (estriol, progesterone, testosterone, sex-hormone-binding globulin (SHBG), corticotropin-releasing hormone (CRH), total triiodothyronine (T3), total thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH)) were measured at two visits during pregnancy.Methods: Linear mixed models with a random intercept were constructed to examine the associations between hormones and urinary biomarkers. Results were additionally stratified by study visit. Results were transformed to hormone percent changes for an inter-quartile-range difference in exposure biomarker concentrations (%Δ).Results: Bisphenol-S was associated with a decrease in CRH [(%Δ -11.35; 95% CI: -18.71, - 3.33), and bisphenol-F was associated with an increase in FT4 (%Δ: 2.76; 95% CI: 0.29, 5.22). Butyl-, methyl- and propylparaben were associated with decreases in SHBG [(%Δ: -5.27; 95% CI: -9.4, - 1.14); (%Δ: -3.53; 95% CI: -7.37, 0.31); (%Δ: -3.74; 95% CI: -7.76, 0.27)]. Triclocarban was positively associated with T3 (%Δ: 4.08; 95% CI: 1.18, 6.98) and T3/T4 ratio (%Δ: 4.67; 95% CI: -1.37, 6.65), and suggestively negatively associated with TSH (%Δ: -10.12; 95% CI: -19.47, 0.32). There was evidence of susceptible windows of vulnerability for some associations. At 24-28 weeks gestation, there was a positive association between 2,4-dichlorophenol and CRH (%Δ: 9.66; 95% CI: 0.67, 19.45) and between triclosan and estriol (%Δ: 13.17; 95% CI: 2.34, 25.2); and a negative association between triclocarban and SHBG (%Δ: -9.71; 95% CI:-19.1, - 0.27) and between bisphenol A and testosterone (%Δ: -17.37; 95% CI: -26.7, - 6.87).Conclusion: Phenols and parabens are associated with hormone levels during pregnancy. Further studies are required to substantiate these findings. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the racial and ethnic disparities in delivery hospitalizations involving severe maternal morbidity (SMM) by location of residence and community income. We used the 2016 to 2019 Healthcare Cost and Utilization Project National Inpatient Sample. International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to identify delivery hospitalizations with SMM. Using logistic regression models, we examined the association between race and ethnicity and delivery hospitalizations involving SMM. In adjusted analyses, the models were stratified by location of residence and community income and adjusted for patient and hospital characteristics. In rural areas, non-Hispanic Black women (AOR 1.50; 95% CI 1.25-1.79) and women of other races (AOR 1.32; 95% CI 1.03-1.69) had an increased odds of experiencing a delivery hospitalization involving SMM when compared to non-Hispanic White women. In micropolitan areas, non-Hispanic Black women (AOR 1.88; 95% CI 1.79-1.97), non-Hispanic Asian/Pacific Islander women (AOR 1.54; 95% CI 1.16-2.05), and women of other races (AOR 1.31; 95% CI 1.03-1.67) had an increased odds of experiencing a delivery hospitalization involving SMM when compared to non-Hispanic White women. Non-Hispanic Black women also had increased odds of experiencing a delivery hospitalization involving SMM in communities with the lowest income (quartile 1) (AOR 1.59; 95% CI 1.49-1.66), middle income (quartiles 2 and 3) (AOR 1.81; 95% CI 1.72-1.91), and highest income (AOR 2.09; 95% CI 1.90-2.29) when compared to non-Hispanic White women. We found that location of residence and community income are associated with racial and ethnic differences in SMM in the United States. These factors, outside of individual factors assessed in previous studies, provide a better understanding of some of the structural and systemic factors that may contribute to SMM., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 (β:-33.5,95 %CI:-42.9,-22.6) and 15-oxoETE and Sn (β: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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Financial support was provided by the Superfund Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH; grant numbers P42ES017198 and R01ES03220). Additional support was provided from grants P30ES017885 and T32ES007062 from the NIEHS, NIH, and the Environmental influences on Child Health Outcomes (ECHO) program grant number UH3OD023251. ECHO is a nationwide research program supported by the NIH, Office of the Director to enhance child health., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John D. Meeker reports a relationship with University of Michigan that includes: paid expert testimony. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the summer of 2020, SARS-CoV-2 infection rates among the U.S. population aged 20-39 years exceeded other age groups, with the largest increases occurring in the southern US. As many colleges reopened for in-person instruction in August and September, these trends continued among campuses across the country. Our study aimed to identify risk factors (demographic and behavioral) associated with SARS-CoV-2 infection among college students. We used data from a survey administered to students at a southern university in the US. The survey had a total of 765 respondents and this study included the 679 (88.8%) who responded about their SARS-CoV-2 infection status. We examined associations between population characteristics and reported SARS-CoV-2 infection and calculated prevalence ratios along with 95% confidence intervals. SARS-CoV-2 infection was 2.5 times more likely among current users of electronic nicotine delivery systems (ENDS) compared to those who do not use ENDS (95% confidence interval [CI]: (1.76-3.4)) and 2.8 times more likely among those who reported a high frequency of binge drinking compared to those who did not report binge drinking (95% CI: (1.81-4.36)). Current high frequency ENDS users were 2.76 (1.79-4.25) more likely to report SARS-CoV-2 infection than non-users. Current low frequency users of ENDS were 2.27 (1.53-3.37) times more likely to report SARS-CoV-2 infection than nonusers. A trend analysis among ENDS use frequency and SARS-CoV-2 infection was statistically significant, showing a significant dose response with increasing ENDS use. The results of this analysis may assist in providing guidance on policies as well as may serve as a steppingstone for future research concerning SAR-CoV-2 infection among university populations.

Introduction: Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility., Objective: The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework., Methods: We used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure., Results: Only 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P < 0.05) with offspring BMI z-scores at age 2 years in a meta-analytic framework including at least two studies: arabinose (Coef meta  = 0.40 [95% CI 0.10,0.70], P meta  = 9.7 × 10 -3 ), guanidinoacetate (Coef meta  = - 0.28 [- 0.54, - 0.02], P meta  = 0.033), 3-ureidopropionate (Coef meta  = 0.22 [0.017,0.41], P meta  = 0.033), 1-methylhistidine (Coef meta  = - 0.18 [- 0.33, - 0.04], P meta  = 0.011), serine (Coef meta  = - 0.18 [- 0.36, - 0.01], P meta  = 0.034), and lysine (Coef meta  = - 0.16 [- 0.32, - 0.01], P meta  = 0.044). No associations were robust to multiple testing correction., Conclusions: Despite including three cohorts with large sample sizes (N > 100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse., Objectives: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history., Methods: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE., Results: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46)., Conclusions: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States., Objective: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin., Study Design: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F 2α , 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F 2α (F 2 -IsoP-M; the major 8-iso-prostaglandin-F 2α metabolite), and prostaglandin-F 2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models., Results: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F 2 -IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F 2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis., Conclusion: Here, oxidative stress, as measured by 8-iso-prostaglandin-F 2α , F 2 -IsoP-M, and prostaglandin-F 2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: This study examined the relationship between prenatal maternal stress (PREMS) and non-nutritive suck (NNS) and tested its robustness across 2 demographically diverse populations., Methods: The study involved 2 prospective birth cohorts participating in the national Environmental influences on Child Health Outcomes (ECHO) Program: Illinois Kids Development Study (IKIDS) and ECHO Puerto Rico (ECHO-PROTECT). PREMS was measured during late pregnancy via the 10-item Perceived Stress Scale (PSS-10). NNS was sampled from 1- to 8-week-olds using a custom pacifier for ~5 min., Results: Overall, 237 mother-infant dyads completed this study. Despite several significant differences, including race/ethnicity, income, education, and PREMS levels, significant PREMS-NNS associations were found in the 2 cohorts. In adjusted linear regression models, higher PREMS, measured through PSS-10 total scores, related to fewer but longer NNS bursts per minute., Conclusions: A significant association was observed between PREMS and NNS across two diverse cohorts. This finding is important as it may enable the earlier detection of exposure-related deficits and, as a result, earlier intervention, which potentially can optimize outcomes. More research is needed to understand how NNS affects children's neurofunction and development., Impact: In this double-cohort study, we found that higher maternal perceived stress assessed in late pregnancy was significantly associated with fewer but longer sucking bursts in 1- to 8-week-old infants. This is the first study investigating the association between prenatal maternal stress (PREMS) and infant non-nutritive suck (NNS), an early indicator of central nervous system integrity. Non-nutritive suck is a potential marker of increased prenatal stress in diverse populations. Non-nutritive suck can potentially serve as an early indicator of exposure-related neuropsychological deficits allowing for earlier interventions and thus better prognoses., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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.", Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cardona Cordero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother−child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. Phthalate metabolites were measured in multiple maternal urine collected during pregnancy. Neurodevelopment was measured at 6, 12, and 24 months of age using the Battelle Developmental Inventory-2nd edition (BDI), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. Multivariable linear regression was used to examine associations between phthalate metabolite concentrations and BDI scores, adjusting for maternal age, maternal education, child age, and specific gravity. Sex-specificity was assessed with sex X exposure interaction terms and stratified models. Results show that all five domains were significantly associated with mono-3-carboxypropyl phthalate (MCPP) at age 24 months, suggesting a holistic developmental delay related to this metabolite. Sex-specificity existed for all timepoints (p-interaction < 0.2), in general, showing stronger associations among boys. For example, metabolites of a recent phthalate replacement, di-2-ethylhexyl terephthalate (DEHTP), were differentially associated with the adaptive domain (boys −7.53%/IQR, 95% CI: −14.58, −0.48 vs. girls −0.85%/IQR, 95% CI: −5.08, 3.37), and the cognitive domain (boys −6.05%/IQR, 95% CI: −10.88, −1.22 vs. girls −1.93%/IQR, 95%CI: −4.14, 0.28) at 6 months. To conclude, gestational exposure to phthalates and phthalate replacements was associated with neurodevelopmental delay across multiple domains, with differences by sex and child age.

Background/aim: Infant non-nutritive suck (NNS) has been used as an early marker of neonatal brain function. Although there is an established relationship between prenatal exposure to certain metals and brain development, the association between metal exposure and NNS has not been explored. Therefore, in this study we assessed associations between maternal urinary metal(loid) concentrations and NNS measurements among infants from the Puerto Rico PROTECT birth cohort. We hypothesized that maternal urinary metal(loid) concentrations are significantly associated with infant NNS measures in a sex-dependent manner., Methods: We measured urinary concentrations of 14 metal(loid)s in pregnant women at up to three time points in pregnancy. The geometric mean of each metal(loid) for each pregnant woman was calculated and used as an exposure measurement across gestation. NNS measurements (duration, frequency, amplitude, bursts/min, cycles/burst, cycles/min) were collected from infants between 4 and 6 (±2 weeks) weeks of age using our custom research pacifier. Linear regression was used to estimate associations between urinary metal(loid) concentrations across pregnancy and continuous NNS variables. Sex-specific effects were estimated using interaction terms between NNS variables and infant sex., Results: We observed significant positive associations between mercury, manganese, and tin with NNS duration (mercury: %Δ = 1.08, 95% CI: 0.42, 1.74; manganese: %Δ = 0.67, 95% CI: 0.15, 1.20; tin: %Δ = 0.83, 95% CI: 0.17, 1.49) and NNS cycles/burst (mercury: %Δ = 1.85, 95% CI: 0.58, 3.11; manganese: (%Δ = 1.37, 95% CI: 0.40, 2.34; tin: %Δ = 1.68, 95% CI: 0.46, 2.91). Furthermore, the association between NNS cycles/min with cadmium (%Δ = 8.06, 95% CI: 3.33, 12.78), manganese (%Δ = 4.44, 95% CI: 1.40, 7.47), and tin (%Δ = 4.50, 95% CI: 0.81, 8.18) were in the opposite direction from its association with zinc (%Δ = -9.30, 95% CI: -14.71, -3.89), as well as with copper (%Δ = -6.58, 95% CI: -12.06, -1.10). For the sex-stratified analysis, the negative associations between metal(loid)s and NNS duration were predominantly driven by male infants; however, the negative associations between metal(loid)s and NNS bursts/min were mainly driven by female infants., Conclusion: We observed significant associations between prenatal metal(loid) exposure and NNS measurements among infants from the ongoing Puerto Rico PROTECT cohort. Similar to previous studies that have demonstrated associations between NNS and subsequent neurodevelopment, this study highlights the potential of NNS as a quantitative index to measure altered neurodevelopment from prenatal metal(loid) exposures. We believe this study will inform future efforts aimed at reducing health risks related to early life metal exposures, such as developing early identification of metal-induced adverse outcomes in child neurodevelopment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Kim, Zimmerman, Huerta-Montañez, Rosario-Pabón, Vélez-Vega, Alshawabkeh, Cordero, Meeker and Watkins.)

This study examined the relationship between maternal food source and preparation during pregnancy and the duration of breastfeeding among 751 mother-child dyads in the United States. The data collected from the Environmental influences on Child Health Outcomes (ECHO) Program included twelve cohorts of mothers (age ≥ 18) who delivered infant(s). Three categories of maternal food source and preparation including, High, Moderate, or Low Food Source Quality were derived from the mother report. The mean duration of breastfeeding differed strongly across the three categories. The High Food Source Quality group breastfed an average of 41 weeks, while shorter durations were observed for the Moderate (26 weeks) and Low (16 weeks) Food Source Quality groups. Cox proportional hazards models were used to estimate the relative hazard of time to breastfeeding cessation for each participant characteristic. The full model adjusted for clustering/cohort effect for all participant characteristics, while the final model adjusted for the subset of characteristics identified from variable reduction modeling. The hazard of breastfeeding cessation for those in the High Food Source Quality group was 24% less than the Moderate group (RH = 0.76; 95% CI, 0.63-0.92). Pregnant women in the High Food Source Quality group breastfed longer than the Moderate and Low groups. We encourage more detailed studies in the future to examine this relationship longitudinally.

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth., Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US., Design, Setting, and Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included., Exposures: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated., Main Outcomes and Measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth., Results: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively., Conclusions and Relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

To examine postpartum depressive symptom trajectories from birth to age 5 and their risk factors in a national sample of mothers of preterm and full-term infants. The racially and ethnically diverse sample comprised 11,320 maternal participants (M age  = 29; SD = 5.9) in the Environmental influences on Child Health Outcomes (ECHO) Program in the USA with data on newborn gestational age at birth (≥ 22 weeks) and maternal depression symptoms during the first 5 years following childbirth. Growth mixture models determined the number and trajectory of postpartum depression classes among women in the preterm and full-term groups, and we examined predictors of class membership. Five trajectories described depressive symptoms for both groups; however, notable differences were observed. One in 5 mothers of preterm infants developed clinically relevant depressive symptoms over time compared with 1 in 10 mothers of full-term infants. Among women who delivered preterm compared with those who delivered full-term, symptoms were more likely to increase over time and become severe when offspring were older. Distinct subgroups describe mothers' depressive symptom trajectories through 5 years following childbirth. Mild to moderate depressive symptoms may onset or persist for many women beyond the initial postpartum period regardless of newborn gestational age at birth. For women with preterm infants, initially mild symptoms may increase to high levels of severity during the preschool and toddler years., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

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.

Background: Phthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes., Objective: To explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort., Methods: We measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery., Results: After controlling for multiple comparisons, 33 phthalate-lipid associations were identified (False discovery rate adjusted p value < 0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and mono-unsaturated fatty acid chains., Significance: Characterization of associations between lipidomic markers and phthalate metabolites during pregnancy will yield mechanistic insight for maternal and child health outcomes., Impact: This study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1. Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Phthalates are used in the manufacturing of consumer products, resulting in ubiquitous human exposure to phthalate mixtures. Previous work has suggested that phthalates display endocrine-disrupting capabilities, and exposure is associated with early delivery., Objective: To assess mediating effects of hormone concentrations on associations between phthalate mixtures and preterm birth (PTB)., Methods: Repeated urinary phthalates and serum hormones were measured among 1011 women in the PROTECT Puerto Rico birth cohort from 2011-2019. We utilized ridge regression to create phthalate environmental risk scores (ERS), which represent weighted summaries of total phthalate exposure. Mediation analyses were conducted on a subset of 705 women. We additionally conducted fetal sex-specific analyses., Results: Free thyroxine (FT4) mediated 9.6% of the association between high molecular weight (HMW) ERS at 18 weeks and reduced gestational age at delivery (95%CI:1.07-29.9). Progesterone at 26 weeks mediated 21.1% and 16.2% of the association between HMW ERS at 18 and 22 weeks, and spontaneous PTB, respectively. Among male fetuses, corticotropin releasing hormone (CRH) at 18 weeks mediated 28.2% of the association between low molecular weight ERS and spontaneous PTB., Significance: We provide introductory evidence of hormone disruption on the causal pathway between phthalate exposure and early delivery. We also show differences by fetal sex, but larger sample size is necessary to validate our findings., Impact Statement: This study provides introductory evidence that an alteration of hormone concentrations occurs on the causal pathway between gestational phthalate mixture exposure and subsequent PTB. In addition to the novel application of repeated biomarker measurements and mixtures methods in causal mediation analyses, we also explored differences between classes of phthalate compounds and between fetal sexes. We show that differential endocrine pathways may be disrupted with exposures to low versus HMW phthalate compounds, and that pregnancies with a male fetus may be more susceptible to endocrine disruption than those with a female fetus., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Humans are exposed to complex mixtures of phthalate chemicals from a range of consumer products. Previous studies have reported significant associations between individual phthalate metabolites and pregnancy outcomes, but mixtures research is limited., Objectives: We used the Puerto Rico Testsite for Exploring Contamination Threats longitudinal pregnancy cohort to investigate associations between phthalate metabolite mixtures and pregnancy outcomes., Methods: Women ( n = 462 carrying females, n = 540 carrying males) provided up to three urine samples throughout gestation (median 18, 22, and 26 wk), which were analyzed for 13 phthalate metabolites. Pregnancy outcomes including preterm birth (PTB), spontaneous PTB, small and large for gestational age (SGA, LGA), birth weight z -score, and gestational age at delivery were abstracted from medical records. Environmental risk scores (ERS) were calculated as a weighted linear combination of the phthalates from ridge regression and adaptive elastic net, which are variable selection methods to handle correlated predictors. Birth outcomes were regressed on continuous ERS. We assessed gestational average and visit-specific ERS and stratified all analyses by fetal sex. Finally, we used Bayesian kernel machine regression (BKMR) to explore nonlinear associations and interactions between metabolites., Results: Differences in metabolite weights from ridge and elastic net were apparent between birth outcomes and between fetal sexes. An interquartile range increase in gestational average phthalate ERS was associated with increased odds of PTB [male odds   ratio   ( OR ) = 1.56 ; 95% confidence interval (CI): 1.08, 2.27; female OR = 1.91 ; 95% CI: 1.23, 2.98], spontaneous PTB (male OR = 2.32 ; 95% CI: 1.46, 3.68; female OR = 2.00 ; 95% CI: 1.04, 3.82), and reduced gestational age at birth (male β = - 0.39 wk, 95% CI: - 0.62 , - 0.15 ; female β = - 0.29 wk, 95% CI: - 0.52 , - 0.05 ). Analyses by study visit suggested that exposure at ∼ 22 wk (range 20-24 wk) was driving those associations. Bivariate plots from BKMR analysis revealed some nonlinear associations and metabolite interactions that were different between fetal sexes., Discussion: These results suggest that exposure to phthalate mixtures was associated with increased risk of early delivery and highlight the need to study mixtures by fetal sex. We also identified various metabolites displaying nonlinear relationships with measures of birth weight. https://doi.org/10.1289/EHP8990.

Background: Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns' health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 women who experienced preterm birth and 69 controls who underwent full-term labor at 24-28 gestational weeks., Results: A total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows that the fatty acid and carene-enriched module has a significant positive association (P = 8e-04, FDR = 0.006) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among 7 machine-learning classifiers, the application of random forest achieved a highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Additional modeling using only the 19 spontaneous preterm births (sPTB) and controls identifies 16 sPTB markers, with an AUC of 0.89 in testing data. Half of the sPTB overlap with those markers for preterm births. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth., Conclusions: Altogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth., (© The Author(s) 2022. Published by Oxford University Press GigaScience.)

Background: Invasive fungal infections in the United States are chronically underdiagnosed and a lack of coordinated surveillance makes the true burden of disease difficult to determine. The purpose of this analysis was to capture mortality-associated burden of risk conditions and fungal infections., Methods: We analyzed data from the National Vital Statistics System from 1999 through 2018 to estimate the mortality attributed to risk conditions and related fungal disease., Results: The number of risk conditions associated with fungal disease is steadily rising in the United States, with 1 047 422 diagnoses at time of death in 2018. While fungal disease decreased substantially from 1999 to 2010, primarily due to the control of human immunodeficiency virus (HIV) infection, the number of deaths with fungal diagnosis has increased in the non-HIV cohort, with significant increases in patients with diabetes, cancer, immunosuppressive disorders, or sepsis., Conclusions: The landscape of individuals at risk for serious fungal diseases is changing, with a continued decline in HIV-associated incidence but increased diagnoses in patients with cancer, sepsis, immunosuppressive disorders, and influenza. Additionally, there is an overall increase in the number of fungal infections in recent years, indicating a failure to control fungal disease mortality in these new immunocompromised cohorts. Improvement in the prevention and management of fungal diseases is needed to control morbidity and mortality in the rising number of immunocompromised and at-risk patients in the United States., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background/Aim: The association between heavy metal exposure and adverse birth outcomes is well-established. However, there is a paucity of research identifying biomarker profiles that may improve the early detection of heavy metal-induced adverse birth outcomes. Because lipids are abundant in our body and associated with important signaling pathways, we assessed associations between maternal metals/metalloid blood levels with lipidomic profiles among 83 pregnant women in the Puerto Rico PROTECT birth cohort. Methods: We measured 10 metals/metalloid blood levels during 24-28 weeks of pregnancy. Prenatal plasma lipidomic profiles were identified by liquid chromatography-mass spectrometry-based shotgun lipidomics. We derived sums for each lipid class and sums for each lipid sub-class (saturated, monounsaturated, polyunsaturated), which were then regressed on metals/metalloid. False discovery rate (FDR) adjusted p -values ( q -values) were used to account for multiple comparisons. Results: A total of 587 unique lipids from 19 lipid classes were profiled. When controlling for multiple comparisons, we observed that maternal exposure to manganese and zinc were negatively associated with plasmenyl-phosphatidylethanolamine (PLPE), particularly those containing polyunsaturated fatty acid (PUFA) chains. In contrast to manganese and zinc, arsenic and mercury were positively associated with PLPE and plasmenyl-phosphatidylcholine (PLPC). Conclusion: Certain metals were significantly associated with lipids that are responsible for the biophysical properties of the cell membrane and antioxidant defense in lipid peroxidation. This study highlighted lipid-metal associations and we anticipate that this study will open up new avenues for developing diagnostic tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Ashrap, Watkins, Mukherjee, Rosario-Pabón, Vélez-Vega, Alshawabkeh, Cordero and Meeker.)

Background: Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes., Objective: The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI., Methods: Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups., Results: Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients)., Conclusions: Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Loss of basic utilities, such as drinking water and electricity distribution, were sustained for months in the aftermath of Hurricane Maria's (HM) landfall in Puerto Rico (PR) in September 2017. The goal of this study was to assess if there was deterioration in biological quality of drinking water due to these disruptions. This study characterized the microbial composition of drinking water following HM across nine drinking water systems (DWSs) in PR and utilized an extended temporal sampling campaign to determine if changes in the drinking water microbiome were indicative of HM associated disturbance followed by recovery. In addition to monitoring water chemistry, the samples were subjected to culture independent targeted and non-targeted microbial analysis including quantitative PCR (qPCR) and genome-resolved metagenomics. The qPCR results showed that residual disinfectant was the major driver of bacterial concentrations in tap water with marked decrease in concentrations from early to late sampling timepoints. While Mycobacterium avium and Pseudomonas aeruginosa were not detected in any sampling locations and timepoints, genetic material from Leptospira and Legionella pneumophila were transiently detected in a few sampling locations. The majority of metagenome assembled genomes (MAGs) recovered from these samples were not associated with pathogens and were consistent with bacterial community members routinely detected in DWSs. Further, whole metagenome-level comparisons between drinking water samples collected in this study with samples from other full-scale DWS indicated no significant deviation from expected community membership of the drinking water microbiome. Overall, our results suggest that disruptions due to HM did not result in significant and sustained deterioration of biological quality of drinking water at our study sites., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Early delivery remains a significant public health problem that has long-lasting impacts on mother and child. Understanding biological mechanisms underlying timing of labor, including endocrine disruption, can inform prevention efforts., Methods: Gestational hormones were measured among 976 women in PROTECT, a longitudinal birth cohort in Puerto Rico. We evaluated associations between hormone concentrations at 18 and 26 weeks gestation and gestational age at birth, while assessing effect modification by fetal sex. Exploratory analyses assessed binary outcomes of overall preterm birth (PTB, <37 weeks gestation) and the spontaneous PTB subtype, defined as preterm premature rupture of membranes, spontaneous preterm labor, or both. Multivariable logistic and linear regressions were fit using visit-specific hormone concentrations, and fetal sex-specific effects were estimated using interaction terms. Main outcome models were adjusted for maternal age, education, marital status, alcohol consumption, environmental tobacco smoke exposure, and pre-pregnancy body mass index (BMI). Exploratory models adjusted for maternal age and education., Results: We observed reduced gestational age at birth with higher circulating CRH (β: -2.73 days, 95% CI: -4.97, -0.42), progesterone (β: -4.90 days, 95% CI: -7.07, -2.73), and fT4 concentrations (β: -2.73 days, 95% CI: -4.76, -0.70) at 18 weeks specifically among male fetuses. Greater odds of overall and spontaneous PTB were observed among males with higher CRH, estriol, progesterone, total triiodothyronine (T3), and free thyroxine (fT4) concentrations. Greater odds of PTB among females was observed with higher testosterone concentrations., Conclusions: Various associations between hormones and timing of delivery were modified by fetal sex and timing of hormone measurement. Future studies are needed to understand differential mechanisms involved with timing of labor between fetal sexes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cathey, Watkins, Rosario, Vega, Mukherjee, O’Neill, Loch-Caruso, Alshawabkeh, Cordero and Meeker.)

In 2017-2019, the March of Dimes convened a workgroup with biomedical, clinical, and epidemiologic expertise to review knowledge of the causes of the persistent Black-White disparity in preterm birth (PTB). Multiple databases were searched to identify hypothesized causes examined in peer-reviewed literature, 33 hypothesized causes were reviewed for whether they plausibly affect PTB and either occur more/less frequently and/or have a larger/smaller effect size among Black women vs. White women. While definitive proof is lacking for most potential causes, most are biologically plausible. No single downstream or midstream factor explains the disparity or its social patterning, however, many likely play limited roles, e.g., while genetic factors likely contribute to PTB, they explain at most a small fraction of the disparity. Research links most hypothesized midstream causes, including socioeconomic factors and stress, with the disparity through their influence on the hypothesized downstream factors. Socioeconomic factors alone cannot explain the disparity's social patterning. Chronic stress could affect PTB through neuroendocrine and immune mechanisms leading to inflammation and immune dysfunction, stress could alter a woman's microbiota, immune response to infection, chronic disease risks, and behaviors, and trigger epigenetic changes influencing PTB risk. As an upstream factor, racism in multiple forms has repeatedly been linked with the plausible midstream/downstream factors, including socioeconomic disadvantage, stress, and toxic exposures. Racism is the only factor identified that directly or indirectly could explain the racial disparities in the plausible midstream/downstream causes and the observed social patterning. Historical and contemporary systemic racism can explain the racial disparities in socioeconomic opportunities that differentially expose African Americans to lifelong financial stress and associated health-harming conditions. Segregation places Black women in stressful surroundings and exposes them to environmental hazards. Race-based discriminatory treatment is a pervasive stressor for Black women of all socioeconomic levels, considering both incidents and the constant vigilance needed to prepare oneself for potential incidents. Racism is a highly plausible, major upstream contributor to the Black-White disparity in PTB through multiple pathways and biological mechanisms. While much is unknown, existing knowledge and core values (equity, justice) support addressing racism in efforts to eliminate the racial disparity in PTB., Competing Interests: FJ is President of Majaica, LLC. CDC funds supported March of Dime's (MOD's) Prematurity Campaign, which included convening a scientific workgroup. CDC funds were not used to directly support development of this manuscript. MOD funded a small stipend for TD to conduct a comprehensive scientific edit of the initial consensus statement to prepare it as a manuscript of publishable length. MOD funded a small stipend for TH for additional assistance with references. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Braveman, Dominguez, Burke, Dolan, Stevenson, Jackson, Collins, Driscoll, Haley, Acker, Shaw, McCabe, Hay, Thornburg, Acevedo-Garcia, Cordero, Wise, Legaz, Rashied-Henry, Frost, Verbiest and Waddell.)

Introduction: Zika virus is primarily transmitted through mosquito bites. Because Zika virus infection during pregnancy can cause serious birth defects, reproductive-aged women need protection from Zika virus infection. This report describes Zika virus prevention behaviors among women aged 18-49 years and assesses whether pregnancy status and healthcare provider counseling increases Zika virus prevention behaviors., Methods: A population-based cell phone survey of women aged 18-49 years living in Puerto Rico was conducted in July-November 2016. Data were analyzed in 2018-2019. Prevalence estimates and 95% CIs were calculated for Zika virus prevention behaviors. Adjusted prevalence ratios were estimated to examine the association of pregnancy status with healthcare provider counseling on Zika virus prevention behaviors, controlling for age, education, and health insurance status., Results: Most women reported using screens on open doors/windows (87.7%) and eliminating standing water in/around their homes (92.3%). Other Zika virus prevention behaviors were less common (<33%). In adjusted analysis, pregnant women were more likely than women not at risk for unintended pregnancy to report using mosquito repellent every/most days (adjusted prevalence ratio=1.44, 95% CI=1.13, 1.85). Healthcare provider counseling was associated with receiving professional spraying/larvicide treatment (adjusted prevalence ratio=1.42, 95% CI=1.17, 1.74), sleeping under a bed net (adjusted prevalence ratio=2.37, 95% CI=1.33, 4.24), using mosquito repellent (adjusted prevalence ratio=1.57, 95% CI=1.40, 1.77), and wearing long sleeves/pants (adjusted prevalence ratio=1.32, 95% CI=1.12, 1.55)., Conclusions: Receipt of healthcare provider counseling was more consistently associated with Zika virus prevention behaviors than pregnancy status. Healthcare provider counseling is an important strategy for increasing the uptake of Zika virus prevention behaviors among women aged 18-49 years., (Published by Elsevier Inc.)