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

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 add...

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Autores principales: Boss, Jonathan, Zhai, Jingyi, Aung, Max T., Ferguson, Kelly K., Johns, Lauren E., McElrath, Thomas F., Meeker, John D., Mukherjee, Bhramar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011420/
https://www.ncbi.nlm.nih.gov/pubmed/29925380
http://dx.doi.org/10.1186/s12940-018-0400-3
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author Boss, Jonathan
Zhai, Jingyi
Aung, Max T.
Ferguson, Kelly K.
Johns, Lauren E.
McElrath, Thomas F.
Meeker, John D.
Mukherjee, Bhramar
author_facet Boss, Jonathan
Zhai, Jingyi
Aung, Max T.
Ferguson, Kelly K.
Johns, Lauren E.
McElrath, Thomas F.
Meeker, John D.
Mukherjee, Bhramar
author_sort Boss, Jonathan
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12940-018-0400-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-60114202018-07-05 Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores Boss, Jonathan Zhai, Jingyi Aung, Max T. Ferguson, Kelly K. Johns, Lauren E. McElrath, Thomas F. Meeker, John D. Mukherjee, Bhramar Environ Health Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12940-018-0400-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-20 /pmc/articles/PMC6011420/ /pubmed/29925380 http://dx.doi.org/10.1186/s12940-018-0400-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Boss, Jonathan
Zhai, Jingyi
Aung, Max T.
Ferguson, Kelly K.
Johns, Lauren E.
McElrath, Thomas F.
Meeker, John D.
Mukherjee, Bhramar
Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
title Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
title_full Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
title_fullStr Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
title_full_unstemmed Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
title_short Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
title_sort associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011420/
https://www.ncbi.nlm.nih.gov/pubmed/29925380
http://dx.doi.org/10.1186/s12940-018-0400-3
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