Stephanie M Eick1, Kelly K Ferguson2, Ginger L Milne3, Rafael Rios-McConnell4, Carmen Vélez-Vega4, Zaira Rosario4, Akram Alshawabkeh5, José F Cordero6, John D Meeker7. 1. Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Services, University of California San Francisco, San Francisco, CA, United States. 2. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States. 3. Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, United States. 4. University of Puerto Rico Graduate School of Public Health, UPR Medical Sciences Campus, San Juan, PR, United States. 5. College of Engineering, Northeastern University, Boston, MA, United States. 6. Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, United States. 7. Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States. Electronic address: meekerj@umich.edu.
Abstract
BACKGROUND: Preterm birth (PTB; gestational age <37 weeks), the leading cause of infant morbidity and mortality worldwide, is of particular concern in Puerto Rico. Rates of PTB in Puerto Rico peaked at 20% in 2006, which are historically some of the highest in the world. Oxidative stress and inflammation have been implicated as contributors to adverse birth outcomes, including PTB, and these associations have not been explored in Puerto Rico. Our objective was to examine associations between urinary oxidative stress biomarkers and PTB in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort (N = 469). METHODS: 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite, and prostaglandin F2α (PGF2α) were included as biomarkers of oxidative stress or inflammation. Biomarkers were measured in urine samples collected at up to 3 timepoints across pregnancy (mean 18, 24, 28 weeks gestation). We quantified the proportion of 8-iso-PGF2α originating from oxidative stress and inflammation pathways with a formula based on the ratio of 8-iso-PGF2α to PGF2α. Logistic regression models were used to calculate adjusted odds ratios (OR) for associations between average biomarker concentrations from each woman (visits 1-3) and PTB. Associations between biomarker concentrations at each study visit and PTB were analyzed in separate models. RESULTS: Averaged levels of 8-iso-PGF2α, its primary metabolite, and PGF2α were associated with increased odds of PTB (OR = 1.64, 95% confidence interval [CI] = 1.07-2.54; OR = 1.79, 95% CI = 1.14-2.84; OR = 1.98, 95% CI = 1.32-3.02, respectively). Odds ratios for PTB were greater in magnitude in association with oxidative stress biomarkers measured later in pregnancy. The fraction of 8-iso-PGF2α derived from inflammation was associated with PTB (OR = 1.73, 95% CI = 1.09, 2.93), while the fraction of 8-iso-PGF2α derived from oxidative stress was not associated with PTB (OR = 1.17, 95% CI = 0.90, 1.54). CONCLUSIONS: Our results suggest that oxidative stress and inflammation, as measured by these biomarkers, may be important contributors to PTB. Further research is needed to improve our understanding of the role these biomarkers may play in the causal pathway between environmental factors and PTB.
BACKGROUND: Preterm birth (PTB; gestational age <37 weeks), the leading cause of infant morbidity and mortality worldwide, is of particular concern in Puerto Rico. Rates of PTB in Puerto Rico peaked at 20% in 2006, which are historically some of the highest in the world. Oxidative stress and inflammation have been implicated as contributors to adverse birth outcomes, including PTB, and these associations have not been explored in Puerto Rico. Our objective was to examine associations between urinary oxidative stress biomarkers and PTB in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort (N = 469). METHODS: 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite, and prostaglandin F2α (PGF2α) were included as biomarkers of oxidative stress or inflammation. Biomarkers were measured in urine samples collected at up to 3 timepoints across pregnancy (mean 18, 24, 28 weeks gestation). We quantified the proportion of 8-iso-PGF2α originating from oxidative stress and inflammation pathways with a formula based on the ratio of 8-iso-PGF2α to PGF2α. Logistic regression models were used to calculate adjusted odds ratios (OR) for associations between average biomarker concentrations from each woman (visits 1-3) and PTB. Associations between biomarker concentrations at each study visit and PTB were analyzed in separate models. RESULTS: Averaged levels of 8-iso-PGF2α, its primary metabolite, and PGF2α were associated with increased odds of PTB (OR = 1.64, 95% confidence interval [CI] = 1.07-2.54; OR = 1.79, 95% CI = 1.14-2.84; OR = 1.98, 95% CI = 1.32-3.02, respectively). Odds ratios for PTB were greater in magnitude in association with oxidative stress biomarkers measured later in pregnancy. The fraction of 8-iso-PGF2α derived from inflammation was associated with PTB (OR = 1.73, 95% CI = 1.09, 2.93), while the fraction of 8-iso-PGF2α derived from oxidative stress was not associated with PTB (OR = 1.17, 95% CI = 0.90, 1.54). CONCLUSIONS: Our results suggest that oxidative stress and inflammation, as measured by these biomarkers, may be important contributors to PTB. Further research is needed to improve our understanding of the role these biomarkers may play in the causal pathway between environmental factors and PTB.
Authors: Stephanie M Eick; John D Meeker; Phil Brown; Andrea Swartzendruber; Rafael Rios-McConnell; Ye Shen; Ginger L Milne; Carmen Vélez Vega; Zaira Rosario; Akram Alshawabkeh; José F Cordero; Kelly K Ferguson Journal: Free Radic Biol Med Date: 2019-07-29 Impact factor: 7.376
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Authors: Stephanie M Eick; John D Meeker; Andrea Swartzendruber; Rafael Rios-McConnell; Phil Brown; Carmen Vélez-Vega; Ye Shen; Akram N Alshawabkeh; José F Cordero; Kelly K Ferguson Journal: PLoS One Date: 2020-01-29 Impact factor: 3.240
Authors: Pahriya Ashrap; Deborah J Watkins; Ginger L Milne; Kelly K Ferguson; Rita Loch-Caruso; Jennifer Fernandez; Zaira Rosario; Carmen M Vélez-Vega; Akram Alshawabkeh; José F Cordero; John D Meeker Journal: Antioxidants (Basel) Date: 2021-01-15
Authors: Stephanie M Eick; Elizabeth K Hom Thepaksorn; Monika A Izano; Lara J Cushing; Yunzhu Wang; Sabrina Crispo Smith; Songmei Gao; June-Soo Park; Amy M Padula; Erin DeMicco; Linda Valeri; Tracey J Woodruff; Rachel Morello-Frosch Journal: Environ Health Date: 2020-09-16 Impact factor: 5.984