Search

BackgroundPhthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.ObjectivesWe 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.MethodsWe 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.ResultsIn 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.ConclusionsPhthalate 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.

BackgroundPrenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure.ObjectiveWe assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3-6 years of age).MethodsWithin The Infant Development and the Environment Study (TIDES), a prospective pregnancy cohort, we analyzed a panel of phthalate metabolites in urine collected at two visits from early and late gestation (N=780). We estimated average phthalate metabolite associations with child weight z-scores from ∼20wk gestation (estimated by ultrasound), birth, and 1, 3, 4, and 6 years of age using linear mixed-effects (LME) models. We also modeled associations with adiposity z-scores from birth (weight for length) and 1, 3, 4, and 6 years of age [body mass index (BMI)] using LME models.ResultsFor weight, we observed inverse associations between several phthalate metabolites and birth weight z-scores, but no associations were observed with postnatal weight z-scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length z-scores at birth, but positive associations were observed with BMI z-scores at 3-4 years of age in LME models. For example, mono-ethyl phthalate was associated with a 0.17-unit decrease in birth weight-for-length z-score [95% confidence interval (CI): -0.29, -0.05] and a 0.18-unit increase in 4-years-of-age BMI z-score (95% CI: 0.04, 0.32).DiscussionWe observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3-4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. https://doi.org/10.1289/EHP10077.

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.

BackgroundUrinary phthalate metabolites and psychosocial stress in pregnancy have each been associated with preterm birth (PTB), but no study has examined the joint impact of these two environmental exposures. We hypothesized that there would be stronger associations between phthalate exposure and PTB in mothers with higher stress in pregnancy compared to mothers with lower stress.MethodsWe addressed this question using data from The Infant Development and the Environment Study (TIDES), a prospective birth cohort conducted at four US sites (N = 783). We examined urinary phthalate metabolite concentrations measured in samples collected from up to three trimesters of pregnancy. Mothers reported their exposure to stressful life events (SLE) in each trimester in a questionnaire administered in the third trimester. PTB was defined as delivery before 37 weeks completed gestation (n = 71, 9.1%). We examined associations between urinary phthalate metabolite concentrations (individual time points and on average) and PTB using logistic regression models adjusted for maternal race, age, pre-pregnancy body mass index, education, specific gravity, and gestational age at sample collection. In addition, we created models stratified by whether or not mothers were exposed to any or no SLE in pregnancy.ResultsSummed di-2-ethylhexyl phthalate (ΣDEHP) metabolites measured in urine samples from the third trimester, but not the first trimester, were associated with an increased odds ratio (OR) of PTB (OR = 1.44, 95% confidence interval [CI] = 1.06, 1.95). In models stratified by SLE, associations between third trimester ΣDEHP concentrations and PTB were significant only for women experiencing one or more SLE during pregnancy (OR for ΣDEHP: 2.09, 95% CI: 1.29, 3.37) but not for women with no SLE during pregnancy (OR for ΣDEHP: 1.04, 95% CI: 0.66, 1.63) (p for interaction = 0.07).ConclusionsWe observed an association between urinary ΣDEHP levels and PTB that was modified by whether a mother was exposed to one or more psychosocial stressors during pregnancy. Additional research to understand the joint impacts of chemical and non-chemical exposures, with an emphasis on timing of exposure, is needed in order to advance the state of the science on how the environment influences pregnancy.

BackgroundOxidative stress has been implicated in numerous birth outcomes, including spontaneous preterm birth. However, the relationship with presentation at delivery has been less well studied. We assessed the relationship between oxidative stress biomarkers and gestational duration with a focus on spontaneous presentation for delivery.MethodsOur sample included 740 women from a multi-center prospective cohort study, recruited from 2010 to 2012. Resultant measures of oxidative stress in pregnancy prostaglandin F2α (PGF2α), 8-iso-prostaglandin F2α (8-iso-PGF2α), and the primary 8-iso-PGF2α metabolite were measured in third trimester urine samples. Information on presentation for delivery was abstracted from medical records. We examined associations with preterm birth using adjusted logistic models. Time to event (overall delivery and spontaneous delivery) was examined using adjusted accelerated failure time models.ResultsThe 8-iso-PGF2α metabolite was associated with increased odds of overall preterm birth (OR: 1.44 [95% CI: 1.00, 2.06]), and the association with spontaneous preterm birth was similar in magnitude but not statistically significant (OR: 1.45 [95% CI: 0.96, 2.20]). We did not detect associations between other biomarkers and preterm birth, or between biomarkers and timing of overall or spontaneous delivery in accelerated failure time models.ConclusionsOur data suggest that increased oxidative stress, as indicated by the 8-iso-PGF2α metabolite, may be associated with preterm birth. In contrast to previous studies, associations were similar among individuals with spontaneous versus non-spontaneous presentation for delivery.