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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Gray, Kimberly A
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University of Michigan Ann Arbor
Public Health & Prev Medicine
Schools of Public Health
Ann Arbor
United States
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Watkins, Deborah J; Ferguson, Kelly K; Anzalota Del Toro, Liza V et al. (2015) Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico. Int J Hyg Environ Health 218:212-9
Ferguson, Kelly K; McElrath, Thomas F; Chen, Yin-Hsiu et al. (2015) Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth. Am J Obstet Gynecol 212:208.e1-8
Ferguson, Kelly K; Cantonwine, David E; Rivera-González, Luis O et al. (2014) Urinary phthalate metabolite associations with biomarkers of inflammation and oxidative stress across pregnancy in Puerto Rico. Environ Sci Technol 48:7018-25
Ferguson, Kelly K; McElrath, Thomas F; Ko, Yi-An et al. (2014) Variability in urinary phthalate metabolite levels across pregnancy and sensitive windows of exposure for the risk of preterm birth. Environ Int 70:118-24
Watkins, Deborah J; Téllez-Rojo, Martha Maria; Ferguson, Kelly K et al. (2014) In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation. Environ Res 134:233-41
Ferguson, Kelly K; McElrath, Thomas F; Meeker, John D (2014) Environmental phthalate exposure and preterm birth. JAMA Pediatr 168:61-7
LaRocca, Jessica; Binder, Alexandra M; McElrath, Thomas F et al. (2014) The impact of first trimester phthalate and phenol exposure on IGF2/H19 genomic imprinting and birth outcomes. Environ Res 133:396-406
Ferguson, Kelly K; McElrath, Thomas F; Chen, Yin-Hsiu et al. (2014) Longitudinal profiling of inflammatory cytokines and C-reactive protein during uncomplicated and preterm pregnancy. Am J Reprod Immunol 72:326-36
Cantonwine, David E; Cordero, Jose F; Rivera-Gonzalez, Luis O et al. (2014) Urinary phthalate metabolite concentrations among pregnant women in Northern Puerto Rico: distribution, temporal variability, and predictors. Environ Int 62:1-11
Colacino, Justin A; Arthur, Anna E; Ferguson, Kelly K et al. (2014) Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress. Environ Res 131:6-12

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