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Updated: Aug 20, 2025
Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay
Published on: May 12, 2020
Urinary oxidative stress biomarkers are associated with preterm birth: an Environmental Influences on Child Health
Stephanie M Eick1, Sarah D Geiger2, Akram Alshawabkeh3
1Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA.
Insights
Elevated oxidative stress biomarkers in urine are linked to a higher risk of preterm birth, especially spontaneous preterm birth. This finding emerged from a large, diverse study of US birth cohorts.
Area of Science:
- Environmental Health
- Reproductive Health
- Biomarkers
Background:
- Preterm birth is a major global health concern, contributing significantly to infant mortality and morbidity.
- Elevated oxidative stress is a suspected risk factor for preterm birth, but prior research often lacked demographic diversity.
- This study addresses this gap by examining diverse US populations.
Approach:
- A pooled analysis and meta-analysis of four large birth cohorts (N=1916) from the Environmental Influences on Child Health Outcomes Program.
- Measured urinary concentrations of 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α during pregnancy.
- Utilized logistic regression to assess associations between oxidative stress biomarkers and preterm birth outcomes.
Key Points:
- Increased urinary levels of F2-IsoP-M were associated with higher odds of all preterm births (OR, 1.29) and spontaneous preterm births (OR, 1.47).
- Elevated 8-iso-prostaglandin-F2α also showed an association with increased odds of all preterm births (OR, 1.19).
- Findings were consistent across pooled analysis and meta-analysis, reinforcing the link between oxidative stress and preterm birth.
Conclusions:
- Urinary oxidative stress markers, including 8-iso-prostaglandin-F2α and F2-IsoP-M, are associated with an increased likelihood of preterm birth.
- The association was particularly notable for spontaneous preterm birth and early deliveries (before 34 weeks).
- These findings highlight the role of oxidative stress in adverse pregnancy outcomes across diverse populations.
Background:
Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States.
Objective:
We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin.
Study Design:
This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models.
Results:
Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis.
Conclusion:
Here, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.
