Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Services, University of California San Francisco, San Francisco, CA, United States.
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.
Free Radic Biol Med. 2020 Jan;146:299-305. doi: 10.1016/j.freeradbiomed.2019.11.003. Epub 2019 Nov 5.
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).
8-iso-prostaglandin F (8-iso-PGF), its primary metabolite, and prostaglandin F (PGF) 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 originating from oxidative stress and inflammation pathways with a formula based on the ratio of 8-iso-PGF to PGF. 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.
Averaged levels of 8-iso-PGF, its primary metabolite, and PGF 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 derived from inflammation was associated with PTB (OR = 1.73, 95% CI = 1.09, 2.93), while the fraction of 8-iso-PGF derived from oxidative stress was not associated with PTB (OR = 1.17, 95% CI = 0.90, 1.54).
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.
早产（PTB；胎龄<37 周）是全球婴儿发病率和死亡率的主要原因，在波多黎各尤其令人关注。波多黎各的 PTB 发生率在 2006 年达到 20%的峰值，这在历史上是世界上最高的之一。氧化应激和炎症已被认为是导致不良分娩结局（包括 PTB）的因素，但这些关联尚未在波多黎各得到探讨。我们的目的是在波多黎各探索污染威胁试验场（PROTECT）妊娠队列（N=469）中研究尿氧化应激生物标志物与 PTB 之间的关联。
8-异前列腺素 F（8-iso-PGF）及其主要代谢物前列腺素 F（PGF）被作为氧化应激或炎症的生物标志物。在妊娠期间（平均 18、24、28 周）最多采集 3 次尿液样本测量生物标志物。我们使用基于 8-iso-PGF 与 PGF 比值的公式，量化了 8-iso-PGF 来源于氧化应激和炎症途径的比例。使用逻辑回归模型计算每个女性（访问 1-3）平均生物标志物浓度与 PTB 之间的调整比值比（OR）。分别在单独的模型中分析每个研究访问时生物标志物浓度与 PTB 之间的关联。
8-iso-PGF、其主要代谢物和 PGF 的平均水平与 PTB 的发生几率增加有关（OR=1.64，95%置信区间 [CI]=1.07-2.54；OR=1.79，95%CI=1.14-2.84；OR=1.98，95%CI=1.32-3.02）。与妊娠后期测量的氧化应激生物标志物相比，PTB 关联的 OR 值更大。8-iso-PGF 来源于炎症的部分与 PTB 相关（OR=1.73，95%CI=1.09，2.93），而 8-iso-PGF 来源于氧化应激的部分与 PTB 无关（OR=1.17，95%CI=0.90，1.54）。
我们的结果表明，这些生物标志物所测量的氧化应激和炎症可能是 PTB 的重要原因。需要进一步研究以提高我们对这些生物标志物在环境因素与 PTB 之间的因果途径中可能发挥的作用的认识。
