Preterm birth is the leading cause of infant mortality worldwide, and also greatly increases the risk of developing serious health complications in childhood and throughout life. Preterm birth, as well as low birth weight infants, are significant public health challenges due to the increased prevalence in these adverse birth outcomes in recent decades. In the US, rates of preterm birth have increased over 30 percent since 1981 and 18 percent since 1990, and now accounts for nearly 13 percent of all live births. Conditions that contribute to preterm birth remain unclear, though the influence of environmental exposures has been immensely understudied. There is recent preliminary evidence that human exposure to bisphenol A (BPA) and phthalates, chemicals used in plastics, personal care products, and other consumer goods may be associated with increased risk of preterm birth and adverse effects on fetal development. In animal studies, BPA and phthalates have been shown to cause oxidative stress, inflammation, and endocrine disruption, mechanism that may contribute to increased risk of altered fetal growth and adverse pregnancy outcomes. This is of particular concern since most of the general population, including pregnant women, are exposed to these classes of compounds on a daily basis. This application proposes to study environmental risk factors for adverse effects on fetal growth and preterm birth among 700 mother/infant pairs selected from a large ongoing cohort study of live born singletons in Boston, MA. The study will utilize state-of-the-art methods for measuring urinary BPA and phthalate concentrations, and for assessing molecular epidemiologic mechanistic pathway markers (oxidative stress, inflammation and endocrine disruption), in biological samples collected during each trimester of pregnancy. Innovative measures of fetal growth and placental function from repeated ultrasound scans during pregnancy will also be explored. The study will utilize patient data and biological samples from an ongoing study and is thus a highly cost-efficient use of research funds. In addition, the proposed study will provide new information on phthalate and BPA metabolism and individual exposure susceptibility among pregnant women, a highly vulnerable segment of the population. The study will also explore whether associations between BPA and phthalates differs based on an innovative classification system to disaggregate preterm births according to underlying etiology. Finally, the study will provide data on the interaction of phthalates and BPA with genetic markers of interest in relation to fetal development and risk of preterm birth.

Public Health Relevance

The rising rates of preterm birth and low birth weight infants in the U.S. represents a significant public health challenge. Increased population-wide exposures to the biologically active compounds bisphenol A and phthalates are also of great public health concern. This epidemiological project will use state-of-the-art methods and an innovative study design to provide much needed information on environmental, demographic, and biological factors that contribute to adverse effects on fetal growth and preterm birth risk.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES018872-04
Application #
8501464
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Gray, Kimberly A
Project Start
2010-08-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$489,126
Indirect Cost
$97,277
Name
University of Michigan Ann Arbor
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Ferguson, Kelly K; Cantonwine, David E; McElrath, Thomas F et al. (2016) Repeated measures analysis of associations between urinary bisphenol-A concentrations and biomarkers of inflammation and oxidative stress in pregnancy. Reprod Toxicol 66:93-98
Cantonwine, David E; Ferguson, Kelly K; Mukherjee, Bhramar et al. (2016) Utilizing Longitudinal Measures of Fetal Growth to Create a Standard Method to Assess the Impacts of Maternal Disease and Environmental Exposure. PLoS One 11:e0146532
Ferguson, Kelly K; Meeker, John D; Cantonwine, David E et al. (2016) Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth. Environ Int 94:531-7
James-Todd, Tamarra M; Meeker, John D; Huang, Tianyi et al. (2016) Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors. Environ Int 96:118-126
Johns, Lauren E; Ferguson, Kelly K; Meeker, John D (2016) Relationships Between Urinary Phthalate Metabolite and Bisphenol A Concentrations and Vitamin D Levels in U.S. Adults: National Health and Nutrition Examination Survey (NHANES), 2005-2010. J Clin Endocrinol Metab 101:4062-4069
LaRocca, Jessica; Binder, Alexandra M; McElrath, Thomas F et al. (2016) First-Trimester Urine Concentrations of Phthalate Metabolites and Phenols and Placenta miRNA Expression in a Cohort of U.S. Women. Environ Health Perspect 124:380-7
Johns, Lauren E; Ferguson, Kelly K; McElrath, Thomas F et al. (2016) Associations between Repeated Measures of Maternal Urinary Phthalate Metabolites and Thyroid Hormone Parameters during Pregnancy. Environ Health Perspect 124:1808-1815
Cantonwine, David E; Meeker, John D; Ferguson, Kelly K et al. (2016) Urinary Concentrations of Bisphenol A and Phthalate Metabolites Measured during Pregnancy and Risk of Preeclampsia. Environ Health Perspect 124:1651-1655
Cantonwine, David E; Zhang, Zhen; Rosenblatt, Kevin et al. (2016) Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth. Am J Obstet Gynecol 214:631.e1-631.e11
Chen, Yin-Hsiu; Ferguson, Kelly K; Meeker, John D et al. (2015) Statistical methods for modeling repeated measures of maternal environmental exposure biomarkers during pregnancy in association with preterm birth. Environ Health 14:9

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