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Oxidative stress is a biological imbalance in reactive oxygen species and antioxidants. Increased oxidative stress during pregnancy has been associated with adverse birth outcomes. Omega-3 fatty acid (n-3 FA) supplementation may decrease oxidative stress; however, this relationship is seldom examined during pregnancy. This study assessed the association between n-3 FA supplement use during pregnancy and urinary oxidative stress biomarker concentrations. Data came from The Infant Development and the Environment Study (TIDES), a prospective cohort study that recruited pregnant women in 4 US cities between 2010–2012. Third trimester n-3 FA intake was self-reported. Third trimester urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) was measured as an oxidative stress biomarker. Additionally, we measured the major metabolite of 8-iso-PGF2α and Prostaglandin F2α (PGF2α) and utilized the 8-iso-PGF2α to PGF2α ratio to calculate the change in 8-iso-PGF2α reflecting oxidative stress versus inflammation. Adjusted linear models were used to determine associations with control for confounding. Of 725 women, 165 reported n-3 FA supplement use in the third trimester. In adjusted linear models, n-3 FA use was associated with 10.2% lower levels of 8-iso-PGF2α (95% Confidence Interval [CI]: -19.6, 0.25) and 10.3% lower levels of the metabolite (95% CI: -17.1, -2.91). No associations were observed with PGF2α. The lower levels of 8-iso-PGF2α appeared to reflect a decrease in oxidative stress (percent change with supplement use: -18.7, 95% CI: -30.1, -5.32) rather than inflammation. Overall, third trimester n-3 FA intake was associated with lower concentrations of 8-iso-PGF2α and its metabolite, suggesting a decrease in maternal oxidative stress during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult. We aimed to characterize a comprehensive panel of plasma eicosanoids longitudinally across gestation in pregnant women and to determine whether levels differed by infant size at delivery.Methods and Findings: Our data come from a case-control study of 90 pregnant women nested within the LIFECODES prospective birth cohort study conducted at Brigham and Women's Hospital in Boston, Massachusetts. This study included 31 women who delivered small for gestational age (SGA) babies (SGA, ≤10th percentile), 28 who delivered large for gestational age (LGA) babies (≥90th percentile), and 31 who delivered appropriate for gestational age (AGA) babies (controls, >10th to <90th percentile). All deliveries occurred between 2010 and 2017. Most participants were in their early 30s (median age: 33 years), of white (60%) or black (20%) race/ethnicity, and of normal pre-pregnancy BMI (median BMI: 23.5 kg/m2). Women provided non-fasting plasma samples during 3 prenatal study visits (at median 11, 25, and 35 weeks gestation) and were analyzed for a panel of eicosanoids. Eicosanoids were grouped by biosynthetic pathway, defined by (1) the fatty acid precursor, including linoleic acid (LA), arachidonic acid (AA), docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), and (2) the enzyme group, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Additionally, the concentrations of the 4 fatty acids (LA, AA, DHA, and EPA) were measured in maternal plasma. Analytes represent lipids from non-esterified plasma. We examined correlations among eicosanoids and trajectories across pregnancy. Differences in longitudinal concentrations between case groups were examined using Bayesian linear mixed effects models, which included participant-specific random intercepts and penalized splines on gestational age. Results showed maternal plasma levels of eicosanoids and fatty acids generally followed U-shaped curve patterns across gestation. Bayesian models showed that associations between eicosanoids and case status varied by biosynthetic pathway. Eicosanoids derived from AA via the CYP and LOX biosynthetic pathways were positively associated with SGA. The adjusted mean concentration of 12-HETE, a LOX pathway product, was 56.2% higher (95% credible interval 6.6%, 119.1%) among SGA cases compared to AGA controls. Eicosanoid associations with LGA were mostly null, but negative associations were observed with eicosanoids derived from AA by LOX enzymes. The fatty acid precursors had estimated mean concentrations 41%-97% higher among SGA cases and 33%-39% lower among LGA cases compared to controls. Primary limitations of the study included the inability to explore the potential periods of susceptibility of eicosanoids on infant size due to limited sample size, along with the use of infant size at delivery instead of longitudinal ultrasound measures to estimate fetal growth.Conclusions: In this nested case-control study, we found that eicosanoids and fatty acids systematically change in maternal plasma over pregnancy. Eicosanoids from specific inflammation-related pathways were higher in mothers of SGA cases and mostly similar in mothers of LGA cases compared to controls. These findings can provide deeper insight into etiologic mechanisms of abnormal fetal growth outcomes. [ABSTRACT FROM AUTHOR]

Psychosocial stress during pregnancy has been associated with adverse pregnancy outcomes including preterm birth (PTB). This has not been studied in Puerto Rico, an area with high PTB rates. Our objective was to develop a conceptual model describing the interrelationships between measures of psychosocial stress and depression, a result of stress, among pregnant women in Puerto Rico and to examine their associations with PTB. We used data from the Puerto Rico Testsite for Exploring Contamination Threats pregnancy cohort (PROTECT, N = 1,047) to examine associations among depression and different continuous measures of psychosocial stress using path analysis. Psychosocial stress during pregnancy was assessed using validated measures of perceived stress, negative life experiences, neighborhood perceptions and social support. Logistic regression was used to examine associations between psychosocial stress measures in tertiles and PTB. Perceived stress, negative life experiences, and neighborhood perceptions influenced depression through multiple pathways. Our model indicated that perceived stress had the strongest direct effect on depression, where one standard deviation (SD) increase in perceived stress was associated with a 57% SD increase in depression. Negative life experiences were directly but also indirectly, through perceived stress, associated with depression. Finally, neighborhood perceptions directly influenced negative life experiences and perceived stress and consequently had an indirect effect on depression. Psychosocial stress was not associated with PTB across any of the measures examined. Our study examined interrelationships between multiple measures of psychosocial stress and depression among a pregnant Puerto Rican population and identified negative neighborhood perceptions as important upstream factors leading to depression. Our findings highlight the complex relationship between psychosocial stress measures and indicate that psychosocial stress and depression, assessed using 5 different scales, were not associated with PTB. Future research should investigate other environmental and behavioral risk factors contributing to higher rates of PTB in this population. [ABSTRACT FROM AUTHOR]

Preterm birth is a major public health problem, especially in Puerto Rico where the rates are among the highest observed worldwide, reaching 18% in 2011. The Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) study is an ongoing investigation of environmental factors that contribute to this condition. In the present analysis, we sought to examine common risk factors for preterm birth and other adverse birth outcomes which have not been characterized previously in this unique population. Pregnant women from the PROTECT cohort are recruited from the heavily contaminated Northern coast of the island of Puerto Rico and are free of pre-existing conditions like diabetes. We examined associations between basic demographic, behavioral (e.g., tobacco and alcohol use), and pregnancy (e.g., season and year of delivery) characteristics as well as municipality of residence in relation to preterm birth (<37 weeks gestation), postterm birth (≥41 weeks gestation), and small and large for gestational age in univariate and multivariate logistic regression models. Between 2011 and 2017, 1028 live singleton births were delivered as part of the PROTECT cohort. Of these, 107 (10%) were preterm. Preterm birth rates were higher among women with low socioeconomic status, as indicated by education level and income, and among women with high pre-pregnancy body mass index (BMI). Odds ratios of small for gestational age delivery were higher for women who reported tobacco use in pregnancy and lower for women who delivered in the hurricane and dengue season (July-October). Overall, in pregnant women residing in Puerto Rico, socioeconomic status was associated with preterm birth but few other factors were associated with this or other adverse outcomes of pregnancy. Research to understand environmental factors that could be contributing to the preterm birth epidemic in Puerto Rico is necessary. [ABSTRACT FROM AUTHOR]

Introduction: Overt thyroid disease in pregnancy is associated with numerous maternal and neonatal complications including preterm birth. Less is known about the contribution of trimester-specific subclinical alterations in individual thyroid hormones, especially in late gestation, on the risk of preterm birth. Herein, we examined the associations between subclinical changes in maternal thyroid hormone concentrations (TSH, total T3, free and total T4), measured at multiple time points in pregnancy, and the odds of preterm birth in pregnant women without clinical thyroid disease. Participants and Methods: Data were obtained from pregnant women participating in a nested case-control study of preterm birth within on ongoing birth cohort study at Brigham and Women’s Hospital in Boston, MA (N = 439; 116 cases and 323 controls). We measured thyroid hormones in plasma collected at up to four time points in pregnancy (median = 10, 18, 26, and 35 weeks). We used multivariate logistic regression models stratified by study visit of sample collection to examine associations. To reveal potential biological pathways, we also explored these relationships by obstetric presentation of preterm birth (e.g., spontaneous preterm delivery) that have been previously hypothesized to share common underlying mechanisms. Results: In samples collected at median 10 and 26 weeks of gestation, we found inverse associations between FT4 and the odds of overall preterm birth (odds ratio [OR] = 0.57, 95% confidence interval (CI) = 0.33, 1.00; and OR = 0.53, 95% CI = 0.34, 0.84, respectively). Positive associations were detected for total T3 at these same time points (OR = 2.52, 95% CI = 1.20, 5.31; and OR = 3.40, 95% CI = 1.56, 7.40, respectively). These effect estimates were stronger for spontaneous preterm birth. Conclusions: Our results suggest that subclinical alterations in individual maternal thyroid hormones may influence the risk of preterm birth, and the strength of these associations vary by gestational age. [ABSTRACT FROM AUTHOR]

Impaired or suboptimal fetal growth is associated with an increased risk of perinatal morbidity and mortality. By utilizing readily available clinical data on the relative size of the fetus at multiple points in pregnancy, including delivery, future epidemiological research can improve our understanding of the impacts of maternal, fetal, and environmental factors on fetal growth at different windows during pregnancy. This study presents mean and standard deviation ultrasound measurements from a clinically representative US population that can be utilized for creating Z-scores to this end. Between 2006 and 2012, 18, 904 non-anomalous pregnancies that received prenatal care, first and second trimester ultrasound evaluations, and ultimately delivered singleton newborns at Brigham and Women’s hospital in Boston were used to create the standard population. To illustrate the utility of this standard, we created Z-scores for ultrasound and delivery measurements for a cohort study population and examined associations with factors known to be associated with fetal growth. In addition to cross-sectional regression models, we created linear mixed models and generalized additive mixed models to illustrate how these scores can be utilized longitudinally and for the identification of windows of susceptibility. After adjustment for a priori confounders, maternal BMI was positively associated with increased fetal size beginning in the second trimester in cross-sectional models. Female infants and maternal smoking were associated with consistently reduced fetal size in the longitudinal models. Maternal age had a non-significant association with increased size in the first trimester that was attenuated as gestation progressed. As the growth measurements examined here are widely available in contemporary obstetrical practice, these data may be abstracted from medical records by investigators and standardized with the population means presented here. This will enable easy extension of clinical data to epidemiologic studies investigating novel maternal, fetal, and environmental factors that may impact fetal growth. [ABSTRACT FROM AUTHOR]

Phthalate exposure is prevalent in populations worldwide, including pregnant women. Maternal urinary metabolite concentrations have been associated with adverse reproductive outcomes, but underlying mechanisms remain unclear. Here we investigate inflammation as a possible pathway by examining phthalates in association with inflammation biomarkers, including C-reactive protein (CRP) and a panel of cytokines (IL-1β, IL-6, IL-10, and TNF-α) in a repeated measures analysis of pregnant women (N = 480). Urinary phthalate metabolites and plasma inflammation biomarkers were measured from samples collected at up to four visits per subject during gestation (median 10, 18, 26, and 35 weeks). Associations were examined using mixed models to account for within-individual correlation of measures. Few statistically significant associations or clear trends were observed, although in full models mono-carboxypropyl phthalate (MCPP) was significantly (percent change with interquartile range increase in exposure [%Δ] = 8.89, 95% confidence interval [CI] = 3.28, 14.8), and mono-benzyl phthalate (MBzP) was suggestively (%Δ = 6.79, 95%CI = -1.21, 15.4) associated with IL-6. Overall these findings show little evidence of an association between phthalate exposure and peripheral inflammation in pregnant women. To investigate inflammation as a mechanism of phthalate effects in humans, biomarkers from target tissues or fluids, though difficult to measure in large-scale studies, may be necessary to detect effects. [ABSTRACT FROM AUTHOR]