Dataset Information

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 (ResultsThe 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.

SUBMITTER: Boss J

PROVIDER: S-EPMC6011420 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores.

Boss Jonathan J Zhai Jingyi J Aung Max T MT Ferguson Kelly K KK Johns Lauren E LE McElrath Thomas F TF Meeker John D JD Mukherjee Bhramar B

Environmental health : a global access science source 20180620 1

<h4>Background</h4>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.<h4>Methods</h4> ...[more]

PMID: 29925380

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Project description:BACKGROUND:Maintaining thyroid homeostasis during pregnancy is essential for normal fetal growth and development. Growing evidence suggests that phthalates interfere with normal thyroid function. Few human studies have investigated the degree to which phthalates may affect thyroid hormone levels in particularly susceptible populations such as pregnant women. OBJECTIVES:We examined the associations between repeated measures of urinary phthalate metabolites and plasma thyroid hormone levels in samples collected at up to four time points per subject in pregnancy. Additionally, we investigated the potential windows of susceptibility to thyroid hormone disturbances related to study visit of sample collection. METHODS:Data were obtained from pregnant women (n = 439) participating in a nested case-control study of preterm birth with 116 cases and 323 controls. We measured 9 phthalate metabolite concentrations in urine samples collected at up to four study visits per subject during pregnancy (median = 10, 18, 26, and 35 weeks of gestation, respectively). We also measured a panel of thyroid function markers in plasma collected at the same four time points per subject during pregnancy. RESULTS:Although our results were generally null, in repeated measures analyses we observed that phthalate metabolites were largely inversely associated with thyrotropin and positively associated with free and total thyroid hormones. Cross-sectional analyses by study visit revealed that the magnitude and/or direction of these relationships varied by timing of exposure during gestation. CONCLUSIONS:These results support previous reports showing the potential for environmental phthalate exposure to alter circulating levels of thyroid hormones in pregnant women. Citation: Johns LE, Ferguson KK, McElrath TF, Mukherjee B, Meeker JD. 2016. Associations between repeated measures of maternal urinary phthalate metabolites and thyroid hormone parameters during pregnancy. Environ Health Perspect 124:1808-1815;?http://dx.doi.org/10.1289/EHP170.

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Project description:Study questionAre urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting?Summary answerHigher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care.What is known alreadyExperimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown.Study design, size, durationWe examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study.Participants/materials, setting, methodsWe quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking.Main results and the role of chanceWe observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated.Limitations, reasons for cautionWe demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals.Wider implications of the findingsEnvironmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development.Study funding/competing interestsWork supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare.

Dataset Information

Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores.

Background

Methods

Conclusions

Publications

Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores.

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