From the Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA.
Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY.
Epidemiology. 2023 Sep 1;34(5):759-766. doi: 10.1097/EDE.0000000000001631. Epub 2023 Jul 31.
Although redox stress likely plays an important role in reproductive health, the utility of peripheral biomarkers of oxidative stress, such as isoprostanes, during the periconception period remains underexplored. We evaluated the relationship between isoprostanes during preconception and gestational week 4 and women's reproductive health outcomes.
The Effects of Aspirin in Gestation and Reproduction trial (2007-2011) enrolled 1228 women attempting pregnancy and followed them for up to 6 menstrual cycles and throughout pregnancy if they became pregnant. We measured creatinine-adjusted, log-transformed isoprostanes 8-iso-prostaglandin F 2α (8-iso-PGF2α), its metabolite 2,3-dinor-iPF2α-III, and stereoisomers 5-iso-PGF2α-VI and 8,12-iso-iPF2α-VI in urine during preconception and 4 weeks gestation. We evaluated pregnancy among participants in each menstrual cycle using human chorionic gonadotropin (hCG) and defined pregnancy loss as observed loss following positive hCG. We calculated fecundability odds ratios (FOR) and 95% confidence intervals (CI) using discrete-time Cox proportional hazards models and relative risk of pregnancy loss using adjusted log-binomial models.
Higher preconception isoprostane levels were associated with lower fecundability [e.g., FOR = 0.89; 95% CI = 0.81, 0.97 per interquartile range (IQR) increase in 8-iso-PGF2α]. Among 797 pregnancies, isoprostane levels increased from preconception to 4 weeks gestation (e.g., mean difference = 0.12; 95% CI = 0.10, 0.14 ng/mL for 8-iso-PGF2α) and higher isoprostanes at 4 weeks gestation were associated with lower risk of pregnancy loss (e.g., RR = 0.79; 95% CI = 0.62, 1.00 per IQR increase in 8-iso-PGF2α).
Preconception urinary isoprostanes may identify redox stress pathways associated with lower fecundability. However, the increase in isoprostanes into gestational week 4 and the associated lower risk of pregnancy loss may suggest confounding by latent factors in early pregnancy.
尽管氧化应激可能在生殖健康中起着重要作用，但外周氧化应激生物标志物（如异前列烷）在受孕前期间的应用仍未得到充分探索。我们评估了受孕前和妊娠第 4 周时异前列烷与女性生殖健康结局之间的关系。
妊娠和生殖中的阿司匹林影响试验（2007-2011 年）招募了 1228 名试图怀孕的女性，并在多达 6 个月经周期内对她们进行随访，如果她们怀孕则在整个孕期进行随访。我们在受孕前和妊娠第 4 周时测量了尿液中肌酐调整后、对数转换的异前列烷 8-异前列腺素 F2α（8-iso-PGF2α）、其代谢物 2,3-二去甲-iPF2α-III 以及立体异构体 5-异前列腺素 F2α-VI 和 8,12-异 iPF2α-VI。我们使用人绒毛膜促性腺激素（hCG）评估每个月经周期中参与者的妊娠情况，并将观察到的 hCG 阳性后流产定义为妊娠丢失。我们使用离散时间 Cox 比例风险模型计算了受孕可能性比值比（FOR）和 95%置信区间（CI），并使用调整后的对数二项式模型计算了妊娠丢失的相对风险。
较高的受孕前异前列烷水平与较低的受孕可能性相关[例如，每增加一个四分位距（IQR），8-iso-PGF2α 的 FOR = 0.89；95%CI = 0.81，0.97]。在 797 例妊娠中，异前列烷水平从受孕前到妊娠第 4 周升高（例如，8-iso-PGF2α 的平均差值= 0.12；95%CI = 0.10，0.14ng/mL），而妊娠第 4 周较高的异前列烷水平与较低的妊娠丢失风险相关（例如，RR = 0.79；95%CI = 0.62，1.00，每增加一个 IQR 的 8-iso-PGF2α）。
受孕前尿液中的异前列烷可能识别出与较低受孕可能性相关的氧化应激途径。然而，妊娠第 4 周时异前列烷的增加以及与之相关的妊娠丢失风险降低可能表明早孕期间存在潜在因素的混杂。
