•Phthalate exposure as well as psychosocial stress have been associated with preterm birth.•We categorized women based on stressful life events experienced in pregnancy (yes/no).•Among stressed ...women, some phthalate metabolites were associated with preterm birth.•In non-stressed women, we observed no associations.•Phthalate and stress exposure in pregnancy may have a joint effect on preterm birth.
Urinary 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.
We 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.
Summed 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).
We 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.
Polyketides are a diverse class of molecules sought after for their valuable properties, including as potential pharmaceuticals. Previously, we demonstrated that the oleaginous yeast Yarrowia ...lipolytica is an optimal host for production of the simple polyketide, triacetic acid lactone (TAL). We here expand the capacities of this host by overcoming previous media challenges and enabling production of more complex polyketides. Specifically, we employ a β-oxidation related strategy to improve polyketide production directly from defined media. Beyond TAL production, we establish biosynthesis of the 4-coumaroyl-CoA derived polyketides: naringenin, resveratrol, and bisdemethoxycurcumin, as well as the diketide intermediate, (E)-5-(4-hydroxyphenyl)-3-oxopent-4-enoic acid. In this background, we enable high-level de novo production of naringenin through import of both a heterologous pathway and a mutant Y. lipolytica allele. In doing so, we generated an averaged maximum titer of 898 mg/L naringenin, the highest titer reported to date in any host. These results demonstrate that Y. lipolytica is an ideal polyketide production host for more complex 4-coumaroyl-CoA derived products.
•Established TAL production from defined media to generate 8.6 ± 0.8 g/L TAL.•Expanded Y. lipolytica polyketide palette to include 4-coumaroyl-CoA derived products.•Acid supplemented production of resveratrol, bisdemethoxycurcumin and a diketide intermediate.•Bioreactor scale-up enabled the highest reported naringenin production: 898 ± 19 mg/L.
Human exposure to glyphosate-based herbicides (GBH) is increasing rapidly worldwide. Most existing studies on health effects of glyphosate have focused on occupational settings and cancer outcomes ...and few have examined this common exposure in relation to the health of pregnant women and newborns in the general population. We investigated associations between prenatal glyphosate exposure and length of gestation in The Infant Development and the Environment Study (TIDES), a multi-center US pregnancy cohort. Glyphosate and its primary degradation product aminomethylphosphonic acid (AMPA) were measured in urine samples collected during the second trimester from 163 pregnant women: 69 preterm births (<37 weeks) and 94 term births, the latter randomly selected as a subset of TIDES term births. We examined the relationship between exposure and length of gestation using multivariable logistic regression models (dichotomous outcome; term versus preterm) and with weighted time-to-event Cox proportional hazards models (gestational age in days). We conducted these analyses in the overall sample and secondarily, restricted to women with spontaneous deliveries (n = 90). Glyphosate and AMPA were detected in most urine samples (>94 %). A shortened gestational length was associated with maternal glyphosate (hazard ratio (HR): 1.31, 95 % confidence interval (CI) 1.00–1.71) and AMPA (HR: 1.32, 95%CI: 1.00–1.73) only among spontaneous deliveries using adjusted Cox proportional hazards models. In binary analysis, glyphosate and AMPA were not associated with preterm birth risk (<37 weeks). Our results indicate widespread exposure to glyphosate in the general population which may impact reproductive health by shortening length of gestation. Given the increasing exposure to GBHs and the public health burden of preterm delivery, larger confirmatory studies are needed, especially in vulnerable populations such as pregnant women and newborns.
•Glyphosate/AMPA are commonly detected in urine samples from pregnant women.•Glyphosate/AMPA are associated with shorter gestational length in spontaneous deliveries.•Further research should assess the impact of glyphosate/AMPA in reproductive health.
Exposure to environmental chemicals such as phthalates has been linked to numerous adverse pregnancy outcomes, potentially through an oxidative stress mediated mechanism. Most research examined ...urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) as the oxidative stress biomarker. However, 8-iso-PGF2α also originates from enzymatic sources linked to inflammation. Therefore, associations between phthalates and 8-iso-PGF2α could have been misinterpreted. To clarify this, the 8-iso-PGF2α/prostaglandin F2α ratio approach was used to quantitatively distinguish between inflammation or oxidative stress derived 8-iso-PGF2α and estimate their associations with phthalate metabolites in a cohort of 758 pregnant women from The Infant Development and Environment Study (TIDES). Most urinary phthalate metabolites were associated with a significant increase in 8-iso-PGF2α. For example, a 22.4% higher 8-iso-PGF2α concentration (95% confidence interval = 14.4, 30.9) was observed with an interquartile range increase in mono-n-butyl phthalate. For most metabolites, associations were observed solely with oxidative stress derived 8-iso-PGF2α. In contrast, monocarboxy-isononyl phthalate and monoisononyl phthalate (MNP) were associated with both sources of 8-iso-PGF2α. Metabolites of the phthalate alternative 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH), were only associated with inflammation-derived 8-iso-PGF2α, which is interesting because DINCH metabolites and MNP have structural similarities.In conclusion, phthalates metabolites are not exclusively associated with oxidative stress derived 8-iso-PGF2α. Depending on the metabolite structure, some are also associated with inflammation derived sources, which provides interesting insights in the toxicology of phthalates.
Phthalates are common plasticizer chemicals that have been linked to glucose intolerance in the general population, but there is only limited research on their association with gestational diabetes ...(GDM).
We evaluated the association between 11 urinary phthalate metabolites and GDM, impaired glucose tolerance (IGT), and continuous blood glucose concentration during pregnancy in The Infant Development and Environment Study (TIDES). Based on prior study results, our primary analyses focused on monoethyl phthalate (MEP) in relation to our outcomes of interest.
We used multi-variable logistic regression to examine the odds of GDM and IGT in relation to an interquartile-range (IQR) increase in natural log (ln)-transformed, specific gravity (SG)-adjusted first trimester (T1) and average of T1 and third trimester (T3) (“T1T3avg”) phthalate metabolite concentrations. We fit linear regression models to examine the percent change in blood glucose per IQR increase in ln-transformed, SG-adjusted T1 and T1T3avg phthalates. In sensitivity analyses, we examined interactions between exposure and race. We adjusted for maternal age, maternal body mass index, study center, race/ethnicity, parity, and gestational age at glucose testing.
In our sample of 705 pregnant women, we observed 60 cases of GDM, 90 cases of IGT, and an average GLT blood glucose of 113.6 ± 27.7 mg/dL. In our primary analysis, T1T3avg MEP was positively associated with GDM (OR (95% CI) per IQR increase T1T3avg MEP: 1.61 (1.10, 2.36)). In secondary analyses, most other phthalates were not found to be related to study outcomes, though some associations were noted. Sensitivity analyses indicated possible strong race-specific associations in Asians, though these results are based on a small sample size (n = 35).
In alignment with our a priori selection, we documented an association between T1T3avg MEP and GDM. Additional phthalate metabolites were also found to be linked to glucose intolerance, with possible stronger associations in certain racial/ethnic subgroups. Given the prevalence of phthalate exposures and the growing evidence of associations with metabolic outcomes, future studies should continue to examine this question in diverse cohorts of pregnant women, particularly in those who may be at higher risk for GDM and IGT.
•Limited studies have suggested a possible link between phthalates and impaired glucose tolerance during pregnancy•In agreement with prior studies, we observed an association between mono-ethyl phthalate (MEP) and gestational diabetes•Secondary analyses link other phthalates to glucose intolerance, with possible stronger associations in certain subgroups
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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Prenatal phthalate exposure has been linked to reductions in fetal growth in animal and laboratory studies, but epidemiologic evidence is equivocal.
Examine the association between ...prenatal phthalate metabolite mixtures and fetal growth and evaluate whether that association is modified by fetal sex or omega-3 intake during pregnancy.
Analyses included 604 singleton pregnancies from TIDES, a prospective pregnancy cohort with spot urine samples and questionnaires collected in each trimester. Pregnancy-averaged phthalate exposure estimates were calculated as the geometric means of specific-gravity corrected phthalate metabolites. Fetal growth outcomes included birthweight and length, and ultrasound-derived size and velocity of estimated fetal weight, femur length, abdominal and head circumferences in the second and third trimesters. We used a novel application of quantile g-computation to estimate the joint association between pregnancy-averaged phthalate exposure and fetal growth, and to examine effect modification of that association by infant sex or omega-3 intake during pregnancy.
There were few statistically significant differences in birth size and fetal growth by exposure. A one-quartile increase in the phthalate mixture was modestly associated with reduced birthweight(β 95% confidence interval): −54.6 −128.9, 19.7 grams; p = 0.15) and length (−0.2 −0.6, 0.2 centimeters; p = 0.40). A one-quartile increase in the phthalate mixture was associated with reduced birth length in males (−0.5 −1.0, 0.0 centimeters) but not for females (0.1 −0.2, 0.3 centimeters); interaction p = 0.05. The phthalate metabolite mixture was inversely associated with ultrasound-derived fetal growth among those with adequate omega-3 intake. For example, a one-quartile increase in the phthalate mixture was associated with reduced abdominal circumference in the third trimesters in those with adequate omega-3 intake (−3.3 −6.8, 0.1 millimeters) but not those with inadequate omega-3 intake (1.8 −0.8, 4.5 millimeters); interaction p = 0.01.
Prenatal phthalate exposure was not significantly associated with fetal growth outcomes, with some exceptions for certain subgroups.
Prenatal 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.
We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3-6 years of age).
Within 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 (
). We estimated average phthalate metabolite associations with child weight
-scores from
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
-scores from birth (weight for length) and 1, 3, 4, and 6 years of age body mass index (BMI) using LME models.
For weight, we observed inverse associations between several phthalate metabolites and birth weight
-scores, but no associations were observed with postnatal weight
-scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length
-scores at birth, but positive associations were observed with BMI
-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
-score 95% confidence interval (CI):
,
and a 0.18-unit increase in 4-years-of-age BMI
-score (95% CI: 0.04, 0.32).
We 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.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
OBJECTIVES:To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART).
...DESIGN:Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother–infant pairs through 12–18 months postpartum.
SETTING:Peri-urban community, Cape Town, South Africa.
PARTICIPANTS:HEU (n = 215) and HIV-unexposed (n = 306) children.
MAIN OUTCOME MEASURES:Cognitive, motor and language development at median 13 (interquartile range 12–14) months of agecontinuous and dichotomous Bayley Scales of Infant and Toddler Development Third Edition (delay defined as composite score <85).
RESULTS:Incidence of preterm delivery (<37 weeks) was similar among HEU and HIV-unexposed children (11 vs. 9%, P = 0.31; median gestation 39 weeks); 48% were boys. Median breastfeeding duration was shorter among HEU vs. HIV-unexposed children (6 vs. 10 months). All HIV-infected mothers initiated lifelong ART (tenofovir–emtricitabine–efavirenz) antenatally. HEU (vs. HIV-unexposed) children had higher odds of cognitive delay odds ratio (OR) 2.28 (95% confidence interval (CI) 1.13–4.60) and motor delay OR 2.10 (95% CI 1.03–4.28), but not language delay, in crude and adjusted analysis. Preterm delivery modified this relationship for motor developmentcompared with term HIV-unexposed children, term HEU children had similar odds of delay, preterm HIV-unexposed children had five-fold increased odds of delay (adjusted OR 4.73, 95% CI 1.32; 16.91) and preterm HEU children, 16-fold increased odds of delay (adjusted OR 16.35, 95% CI 5.19; 51.54).
CONCLUSION:Young HEU children may be at increased risk for cognitive and motor delay despite universal maternal ART and breastfeeding; those born preterm may be particularly vulnerable.
Lower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy ...outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers.
Leveraging four pregnancy cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program spanning multiple geographic regions across the United States (U.S.) (N = 2082), we measured biomarkers of oxidative stress in urine samples at up to three time points during pregnancy, including 8-isoprostane-prostaglandin F2α (8-isoPGF2α), its major metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane, and prostaglandin F2α (PGF2α). Maternal age, pre-pregnancy body mass index, marital/partnered status, parity, and smoking status were included as biological and behavioral factors while race/ethnicity, maternal education, and stressful life events were considered social factors. We examined associations between each individual biological, behavioral, and social factor with oxidative stress biomarkers using multivariable-adjusted linear mixed models.
Numerous biological, behavioral, and social factors were associated with elevated levels of 8-isoPGF2α, its major metabolite, and PGF2α. Pregnant people who were current smokers relative to non-smokers or had less than a high school education relative to a college degree had 11.04% (95% confidence interval CI = −1.97%, 25.77%) and 9.13% (95% CI = -1.02%, 20.32%) higher levels of 8-isoPGF2α, respectively.
Oxidative stress biomarkers are elevated among pregnant people with higher socioeconomic disadvantage and may represent one pathway linking biological, behavioral, and social factors to adverse pregnancy and child health outcomes, which should be explored in future work.
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•Oxidative stress biomarkers were elevated among pregnant people with higher socioeconomic disadvantage.•Associations were strongest for the chemical fraction of 8-iso-PGF2α.•Oxidative stress may link socioeconomic status to adverse pregnancy outcomes.
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