159 research outputs found
Oxytocin and oxytocinase in the obese and nonobese parturients during induction and augmentation of labor
Abstract
Objective To investigate differences in oxytocin (OXT) biodistribution between nonobese and obese parturients during labor.
Study Design Patients with body mass index (BMI) of either ≥ 18 ≤ 24.9 kg/m2 (“nonobese”) or ≥ 30 kg/m2 (“obese”) undergoing elective induction of labor were included (N = 25 each). Blood samples were collected at baseline (T0), and 20 minutes after maximal OXT augmentation or adequate uterine contractions (T1) for OXT and oxytocinase assays. A mixed-model repeated-measures analysis of variance was used to test for group versus time interaction and analysis of covariance to detect a difference in OXT level at T1. Data presented as mean ± standard deviation or median (interquartile range), with p < 0.05 considered significant.
Results The mean BMIs (kg/m2) were 22.1 ± 1.6 and 35.9 ± 5.1 in the nonobese and obese groups, respectively. No differences were observed in either the duration of OXT infusion, total dose of OXT, or plasma OXT (pg/mL) either at T0 or T1. However, plasma oxytocinase (ng/mL) was significantly lower at T0 (1.41 [0.67, 3.51] vs. 0.40 [0.29, 1.12]; p = 0.03) in the obese group.
Conclusion We provide preliminary evidence that the disposition of OXT may not be different between obese and nonobese women during labor
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Prenatal Vitamin Use and Vitamin D Status during Pregnancy, Differences by Race and Overweight Status
Objective: We aimed to study whether prenatal vitamin (PNV) use protects against low 25(OH)D levels in all women and particularly in obese and black women who are both at risk of vitamin D deficiency and poor pregnancy outcomes. Study design We studied 1019 women enrolled in a prospective study at Brigham and Women’s Hospital in Boston, 2007–2009. We used multivariable logistic regression to analyze associations of PNV use and odds of vitamin D deficiency defined as 25(OH)D levels < 50 nmol/L. Results: 56% of black and 86% of white women reported pre- and/or post-conceptional PNV use. 75% of black and 19% of white women were vitamin D deficient in the first trimester. PNV use among black women was not associated with vitamin D deficiency (adjusted OR 1.0, 95%CI 0.4, 2.3) but was among white women (3.5, 95%CI 2.1, 5.8)(Interaction P<0.01). Conclusions: Ongoing trials of vitamin D supplementation during pregnancy should consider potential effect modification by race/ethnicity
Inflammatory and oxidative stress markers associated with decreased cervical length in pregnancy
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134275/1/aji12545_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134275/2/aji12545.pd
Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146468/1/aji13017_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146468/2/aji13017.pd
First-Trimester Urine Concentrations of Phthalate Metabolites and Phenols and Placenta miRNA Expression in a Cohort of U.S. Women
Background: There is increasing concern that early-life exposure to endocrine-disrupting chemicals (EDCs) can influence the risk of disease development. Phthalates and phenols are two classes of suspected EDCs that are used in a variety of everyday consumer products, including plastics, epoxy resins, and cosmetics. In utero exposure to EDCs may affect disease propensity through epigenetic mechanisms. Objective: The objective of this study was to determine whether prenatal exposure to multiple EDCs is associated with changes in miRNA expression of human placenta, and whether miRNA alterations are associated with birth outcomes. Methods: Our study was restricted to a total of 179 women co-enrolled in the Harvard Epigenetic Birth Cohort and the Predictors of Preeclampsia Study. We analyzed associations between first-trimester urine concentrations of 8 phenols and 11 phthalate metabolites and expression of 29 candidate miRNAs in placenta by qRT-PCR. Results: For three miRNAs—miR-142-3p, miR15a-5p, and miR-185—we detected associations between Σphthalates or Σphenols on expression levels (p < 0.05). By assessing gene ontology enrichment, we determined the potential mRNA targets of these microRNAs predicted in silico were associated with several biological pathways, including the regulation of protein serine/threonine kinase activity. Four gene ontology biological processes were enriched among genes significantly correlated with the expression of miRNAs associated with EDC burden. Conclusions: Overall, these results suggest that prenatal phenol and phthalate exposure is associated with altered miRNA expression in placenta, suggesting a potential mechanism of EDC toxicity in humans. Citation LaRocca J, Binder AM, McElrath TF, Michels KB. 2016. First-trimester urine concentrations of phthalate metabolites and phenols and placenta miRNA expression in a cohort of U.S. women. Environ Health Perspect 124:380–387; http://dx.doi.org/10.1289/ehp.140840
Pregnancy complications as markers for subsequent maternal cardiovascular disease: Validation of a maternal recall questionnaire
Background: We designed and tested the validity of a questionnaire to characterize maternal recall of pregnancy complications associated with increased future cardiovascular disease risk, based on the 2011 American Heart Association (AHA) guidelines. Methods: A maternal recall questionnaire of pregnancy history was administered to 971 patients who had participated in a previous cohort study of 1,608 pregnant women. Medical records from the study pregnancy served as the gold standard. Prevalence, sensitivity (sens), specificity (spec), positive predictive value (PPV), negative predictive value (NPV), and/or Spearman's correlation coefficients (r) were calculated for each question. Results: A total of 526 (54%) individuals recontacted responded. Respondents were more likely to be older, white, educated, and nulliparous and were less likely to deliver low-birthweight infants in the study pregnancy than were individuals who did not respond. Mean length of recall was 4.35 years (standard deviation [SD] 0.46) postpartum. Maternal recall was most accurate for gestational diabetes (sens: 92%, spec: 98%, PPV: 79%, NPV: 99%), infant birthweight (r=0.95), and gestation length (r=0.85). Maternal recall was modest for preeclampsia (sens: 79%, spec: 97%, PPV: 68%, NPV: 98%) and pregnancy-associated hypertension, including preeclampsia or gestational hypertension (sens: 60%, spec: 95%, PPV: 64%, NPV: 94%). Conclusions: This validation study demonstrated that the majority of women could accurately recall a history of gestational diabetes, infant birthweight, and gestational age at delivery, 4 years postpartum on average. Recall of preeclampsia and pregnancy-associated hypertension overall was modest. Maternal report of these pregnancy conditions may help clinicians identify women at increased risk for cardiovascular disease
Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
Abstract
Background
Preterm birth is a significant public health concern and exposure to phthalates has been shown to be associated with an increased odds of preterm birth. Even modest reductions in gestational age at delivery could entail morbid consequences for the neonate and analyzing data with this additional information may be useful. In the present analysis, we consider gestational age at delivery as our outcome of interest and examine associations with multiple phthalates.
Methods
Women were recruited early in pregnancy as part of a prospective, longitudinal birth cohort at the Brigham and Women’s Hospital in Boston, Massachusetts. Urine samples were collected at up to four time points during gestation for urinary phthalate metabolite measurement, and birth outcomes were recorded at delivery. From this population, we selected all 130 cases of preterm birth (< 37 weeks of gestation) as well as 352 random controls. We conducted analysis with both geometric average of the exposure concentrations across the first three visits as well as using repeated measures of the exposure. Two different time to event models were used to examine associations between nine urinary phthalate metabolite concentrations and time to delivery. Two different approaches to constructing a summative phthalate risk score were also considered.
Results
The single-pollutant analysis using a Cox proportional hazards model showed the strongest association with a hazard ratio (HR) of 1.21 (95% confidence interval (CI): 1.09, 1.33) per interquartile range (IQR) change in average log-transformed mono-2-ethyl-5-carboxypentyl phthalate (MECPP) concentration. Using the accelerated failure time model, we observed a 1.19% (95% CI: 0.26, 2.11%) decrease in gestational age in association with an IQR change in average log-transformed MECPP. We next examined associations with an environmental risk score (ERS). The fourth quartile of ERS was significantly associated with a HR of 1.44 (95% CI: 1.19, 1.75) and a reduction of 2.55% (95% CI: 0.76, 4.30%) in time to delivery (in days) compared to the first quartile.
Conclusions
On average, pregnant women with higher urinary metabolite concentrations of individual phthalates have shorter time to delivery. The strength of the observed associations are amplified with the risk scores when compared to individual pollutants.https://deepblue.lib.umich.edu/bitstream/2027.42/144517/1/12940_2018_Article_400.pd
A Hierarchical Integrative Group LASSO (HiGLASSO) Framework for Analyzing Environmental Mixtures
Environmental health studies are increasingly measuring multiple pollutants
to characterize the joint health effects attributable to exposure mixtures.
However, the underlying dose-response relationship between toxicants and health
outcomes of interest may be highly nonlinear, with possible nonlinear
interaction effects. Existing penalized regression methods that account for
exposure interactions either cannot accommodate nonlinear interactions while
maintaining strong heredity or are computationally unstable in applications
with limited sample size. In this paper, we propose a general shrinkage and
selection framework to identify noteworthy nonlinear main and interaction
effects among a set of exposures. We design hierarchical integrative group
LASSO (HiGLASSO) to (a) impose strong heredity constraints on two-way
interaction effects (hierarchical), (b) incorporate adaptive weights without
necessitating initial coefficient estimates (integrative), and (c) induce
sparsity for variable selection while respecting group structure (group LASSO).
We prove sparsistency of the proposed method and apply HiGLASSO to an
environmental toxicants dataset from the LIFECODES birth cohort, where the
investigators are interested in understanding the joint effects of 21 urinary
toxicant biomarkers on urinary 8-isoprostane, a measure of oxidative stress. An
implementation of HiGLASSO is available in the higlasso R package, accessible
through the Comprehensive R Archive Network.Comment: 29 pages, 6 figure
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Urinary Concentrations of Bisphenol A and Phthalate Metabolites Measured during Pregnancy and Risk of Preeclampsia
Background: Preeclampsia represents a major cause of maternal mortality and morbidity worldwide. Although it is known that the placenta plays a central role in development of preeclampsia, investigation into the contribution of environmental toxicants to the risk of preeclampsia has been sparse. Objectives: In the present study we examined the relationship between longitudinally measured urinary BPA and phthalate metabolite concentrations during gestation and preeclampsia. Methods: A nested case–control study of preterm birth was performed in 2011 from women enrolled in a prospective birth cohort study at Brigham and Women’s Hospital in Boston. There were 50 cases of preeclampsia as part of this study. Urine samples were analyzed for concentrations of BPA and nine phthalate metabolites several times during pregnancy. Adjusted Cox proportional hazard models were used to calculate hazard ratios of preeclampsia in association with an interquartile range increase in BPA and phthalate concentrations and were weighted to reflect results generalizable to the base population. Results: Adjusted hazard ratios indicated that an interquartile range increase of urinary concentrations of BPA (1.53; 95% CI: 1.04, 2.25) and MEP (monoethyl phthalate) (1.72; 95% CI: 1.28, 2.30) at 10 weeks gestation was associated with onset of preeclampsia, whereas significantly elevated hazard ratios were found across gestation for all DEHP [di(2-ethylhexyl) phthalate] metabolites. These relationships differed based on infant sex. Conclusions: Urinary concentrations of BPA and several phthalate metabolites were significantly associated with increased risk of preeclampsia. If validated, these results indicate an environmental contribution of endocrine-disrupting chemicals to preeclampsia and suggest a modifiable means to reduce the mortality and morbidity associated with this condition. Citation: Cantonwine DE, Meeker JD, Ferguson KK, Mukherjee B, Hauser R, McElrath TF. 2016. Urinary concentrations of bisphenol A and phthalate metabolites measured during pregnancy and risk of preeclampsia. Environ Health Perspect 124:1651–1655; http://dx.doi.org/10.1289/EHP18
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Urinary BPA and Phthalate Metabolite Concentrations and Plasma Vitamin D Levels in Pregnant Women: A Repeated Measures Analysis
Background: In addition to its well-established role in maintaining skeletal health, vitamin D has essential regulatory functions in female reproductive and pregnancy outcomes. Phthalates and bisphenol A (BPA) are endocrine disruptors, and previous research has suggested that these chemical agents may disrupt circulating levels of total 25(OH)D in adults. Objectives: We investigated the relationships between repeated measures of urinary phthalate metabolites and BPA and circulating total 25(OH)D in a prospective cohort of pregnant women. Methods: The present study population includes participants (n=477) in a nested case–control study of preterm birth drawn from a prospective birth cohort of pregnant women at Brigham and Women’s Hospital in Boston, Massachusetts. Urine and blood samples were collected for biomarker measurements at median 10 wk and 26 wk of gestation. Results: In repeated measures analysis, we observed that an interquartile range (IQR) increase in urinary mono-3-carboxypropyl phthalate (MCPP) was associated with a 4.48% decrease [95% confidence interval (CI): −7.37, −1.58] in total 25(OH)D. We also detected inverse associations for metabolites of di(2-ethylhexyl) phthalate (DEHP) [percent difference (%Δ)=−2.83 to −2.16]. For BPA, we observed a nonsignificant inverse association with total 25(OH)D in the overall population. Our sensitivity analysis revealed that the associations for some metabolites (e.g., MEHP) varied by race/ethnicity, which may reflect potential differences in susceptibility. In agreement with findings from repeated measures analysis, we reported that DEHP metabolites and BPA were significantly associated with an approximate 20% increase in the odds of vitamin D deficiency (≤20 ng/mL) [odds ratio (95% CI): 1.19 (1.06, 1.35) for molar sum of DEHP metabolites and 1.22 (1.01, 1.47) for BPA] at median 10 wk and 26 wk, respectively. Conclusions: Our results provide suggestive evidence of the potential for environmental exposure to phthalates and/or BPA to disrupt circulating vitamin D levels in pregnancy. https://doi.org/10.1289/EHP117
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