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.
Key words
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Article info
Publication history
Published online: November 14, 2022
Accepted:
November 9,
2022
Received in revised form:
November 8,
2022
Received:
July 5,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
The Acknowledgments show the full listing of the collaborators.
The authors report no conflict of interest.
Research reported in this publication was supported by the Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health (NIH), under award numbers U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319 (Pro-Core), 5U2COD023375-05 (Opportunities and Infrastructure Fund), UG3OD023251, UH3OD023251, UG3OD023272, UH3OD023272, UG3OD023271, UH3OD023271, UG3023305, and UH3OD023305. This work was additionally supported by the Children's Environmental Health and Disease Prevention Research Center (grant numbers ES022848 and RD83543401), T32 NIH Institution Training Grant Predoctoral Traineeships in Endocrine, Developmental, and Reproductive Toxicology (grant number ES007326), US Environmental Protection Agency (grant number RD83543301), National Institute of Environmental Health Sciences (NIEHS; grant numbers P42ES017198, P50ES026049, P01ES022841, R01ES02705, R01ES025169, R01ES016863, P30ES019776, P30ES030284, and P30ES005022), and the Intramural Research Program, NIEHS (grant number ZIAES103313). G.L.M. is supported by the Vanderbilt Diabetes Research Center with funding from the National Institute of Diabetes and Digestive and Kidney Diseases (grant number DK-20593). L.G.K. is supported by an NIH grant R00ES030403.
The sponsors had no role in the study design; the collection, analysis, and interpretation of the data; the writing of the report; or the decision to submit the article for publication.
The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
The datasets for this manuscript are not publicly available because, per the NIH-approved ECHO Data Sharing Policy, ECHO-wide data have not yet been made available to the public for review or analysis. Requests to access the datasets should be directed to the ECHO Data Analysis Center ([email protected]).
Cite this article as: Eick SM, Geiger SD, Alshawabkeh A, et al. Urinary oxidative stress biomarkers are associated with preterm birth: an Environmental Influences on Child Health Outcomes program study. Am J Obstet Gynecol 2022;XX:x.ex–x.ex.
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