Repeated measures of urinary oxidative stress biomarkers and preterm birth in Puerto Rico

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 F_2α (8-iso-PGF_2α), its primary metabolite, and prostaglandin F_2α (PGF_2α) 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-PGF_2α originating from oxidative stress and inflammation pathways with a formula based on the ratio of 8-iso-PGF_2α to PGF_2α. 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-PGF_2α, its primary metabolite, and PGF_2α 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-PGF_2α derived from inflammation was associated with PTB (OR = 1.73, 95% CI = 1.09, 2.93), while the fraction of 8-iso-PGF_2α 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.

Keywords: Epidemiology; Isoprostanes; Oxidative stress; Preterm birth; Puerto Rico; Repeated measures.