Prenatal metal(loid) mixtures and birth weight for gestational age: A pooled analysis of three cohorts participating in the ECHO program

Background: 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. Methods: 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. Results: 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. Conclusions: 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

Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. OBJECTIVES: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. RESULTS: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of formula presented [95% confidence interval (CI): formula presented ], formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented , 0.06), and formula presented (95% CI: formula presented ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: formula presented (95% CI: 0.38, 0.83), formula presented (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [formula presented ; 95% highest posterior density (HPD): formula presented ] and decreased odds of large-for-gestational-age (formula presented ; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. DISCUSSION: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723

Associations between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

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

Menstrual cycle variations in gray matter density, white matter volume and functional connectivity: critical impact on parietal lobe

Health and self-regulatio

Brain responses to painful electrical stimuli and cognitive tasks interact in the precuneus, posterior cingulate cortex, and inferior parietal cortex and do not vary across the menstrual cycle

INTRODUCTION: Bidirectional effects between cognition and pain have been extensively reported. Although brain regions involved in cognitive and pain processing seem to partly overlap, it is unknown what specific brain regions are involved in the interaction between pain and cognition. Furthermore, the role of gonadal hormones on these interacting effects has not been examined. This study investigated brain activation patterns of the interaction between pain and cognition over different phases of the naturally occurring menstrual cycle. METHODS: Fifteen healthy normally cycling females were examined over the course of 4 different cycle phases. Sensory stimulation was applied using electrical pulses and cognitive performance was assessed using the Multi‐Source Interference Task. Brain imaging consisted of functional magnetic resonance imaging using a repeated measures ANOVA group analysis approach. RESULTS: Sensory stimulation was found to interact with task performance in the left precuneus, left posterior cingulate cortex and right inferior parietal lobule. No effects of cycle phase were observed to interact with main effects of stimulation, task or interaction effects between task performance and sensory stimulation. CONCLUSION: Potential neural correlates of shared resources between pain and cognition were demonstrated providing further insights into the potential mechanisms behind cognitive performance difficulties in pain patients and opening avenues for new treatment options including targeting specific cognitive factors in pain treatment such as cognitive interference

Temporal trends and predictors of phthalate, phthalate replacement, and phenol biomarkers in the LIFECODES Fetal Growth Study

Background: Exposure to many phthalates and phenols is declining as replacements are introduced. There is little information on temporal trends or predictors of exposure to these newer compounds, such as phthalate replacements, especially among pregnant populations. Objective: Examine temporal trends and predictors of exposure to phthalates, phthalate replacements, and phenols using single- and multi-pollutant approaches. Methods: We analyzed data from 900 singleton pregnancies in the LIFECODES Fetal Growth Study, a nested case-cohort with recruitment from 2007 to 2018. We measured and averaged concentrations of 12 phthalate metabolites, four phthalate replacement metabolites, and 12 phenols in urine at three timepoints during pregnancy. We visualized and analyzed temporal trends and predictors of biomarker concentrations. To examine chemical mixtures, we derived clusters of individuals with shared exposure profiles using a finite mixture model and examined temporal trends and predictors of cluster assignment. Results: Exposure to phthalates and most phenols declined across the study period, while exposure to phthalate replacements (i.e., di(isononyl) cyclohexane-1,2-dicarboxylic acid, diisononyl ester [DINCH] and di-2-ethylhexyl terephthalate [DEHTP]) and bisphenol S (BPS) increased. For example, the sum of DEHTP biomarkers increased multiple orders of magnitude, with an average concentration of 0.92 ng/mL from 2007 to 2008 and 61.9 ng/mL in 2017–2018. Biomarkers of most chemical exposures varied across sociodemographic characteristics, with the highest concentrations observed in non-Hispanic Black or Hispanic participants relative to non-Hispanic White participants. We identified five clusters with shared exposure profiles and observed temporal trends in cluster membership. For example, at the end of the study period, a cluster characterized by high exposure to phthalate replacements was the most prevalent. Significance: In a large and well-characterized pregnancy cohort, we observed exposure to phthalate replacements and BPS increased over time while exposure to phthalates and other phenols decreased. Our results highlight the changing nature of exposure to consumer product chemical mixtures