The Ohio State University College of Medicine, 395W. 12th Avenue, Room 580, Columbus, OH 43210, USA.
College of Health and Human Services, George Mason University, 4400 University Drive, Fairfax, VA 22030, USA.
Hum Reprod. 2018 Apr 1;33(4):728-735. doi: 10.1093/humrep/dey030.
Are biomarkers of preconception stress associated with pregnancy loss?
Preconception stress, as measured by basal salivary cortisol and alpha-amylase concentrations, is not associated with pregnancy loss.
Many studies, most of which have been retrospective, have identified an association between stressful life events and perceived stress and miscarriage.
STUDY DESIGN, SIZE, DURATION: A prospective pregnancy study with preconception enrollment was conducted between 2005 and 2009. Among the 344 women who became pregnant during the Longitudinal Investigation of Fertility and the Environment (LIFE) study, 337 (98%) had salivary biomarker data for analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples planning pregnancy were followed for up to 12 months as they tried to become pregnant and through pregnancy if it occurred. Participating women collected a basal saliva sample on the morning following enrollment and a second on the morning following their next menses to measure cortisol and alpha-amylase, biomarkers of stress. Women used home pregnancy tests on the day of expected menses. A pregnancy loss was defined as a negative pregnancy test following a positive pregnancy test, the onset of menses, or for pregnancies that survived to clinical recognition, recognition of the loss by a healthcare provider.
Among the 337 couples, the median age of female and male partners was 29 and 31 years, respectively. Most of the women were non-Hispanic white (83%) and highly educated. There were 97 pregnancy losses reported among the 337 pregnancies. The median gestational age at loss was 6 weeks 5 days with only two losses occurring in the second trimester. Using Cox proportional hazards models, we found no clear pattern of association between two preconceptional biomarkers of stress (salivary cortisol and alpha-amylase concentrations) modeled both continuously or in tertiles and incident pregnancy loss after adjustment for confounders.
Our prior work suggests that women enrolled in the LIFE Study had lower stress levels than women in the general population. Owing to concerns regarding participant burden, we were unable to collect serial saliva measurements, which would have allowed us to examine the association between stress in early pregnancy and pregnancy loss. Further, with regard to the measurement of perceived stress, the Cohen's Perceived Stress Scale was only administered at baseline. While every attempt was made to ensure diversity in the cohort, non-Hispanic white women were over-represented, therefore it is possible that the results might not be generalizable to all women.
In one of the largest studies in the USA to prospectively capture data on the incidence of early pregnancy loss, we found no clear association between two biomarkers of preconception stress (measured in saliva) and pregnancy loss.
STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). There are no conflicts of interest to declare.
Not applicable.
孕前应激的生物标志物是否与妊娠丢失有关？
孕前应激，如基础唾液皮质醇和α-淀粉酶浓度所测，与妊娠丢失无关。
许多研究，其中大多数是回顾性的，已经确定了生活压力事件和感知压力与流产之间的关联。
研究设计、大小、持续时间：2005 年至 2009 年进行了一项前瞻性妊娠研究，孕前入组。在生育和环境纵向研究（LIFE）研究中怀孕的 344 名女性中，有 337 名（98%）有唾液生物标志物数据进行分析。
参与者/材料、地点、方法：计划怀孕的夫妇在尝试怀孕的期间以及怀孕后一直被跟踪。参与的女性在入组后的第二天早上收集基础唾液样本，在下一次月经后的第二天早上收集第二次样本，以测量皮质醇和α-淀粉酶，这是应激的生物标志物。女性在预计月经的那天使用家用妊娠测试。妊娠丢失定义为阳性妊娠测试后出现阴性妊娠测试、月经开始或妊娠存活至临床确认，或经医疗保健提供者确认丢失。
在 337 对夫妇中，女性和男性伴侣的中位年龄分别为 29 岁和 31 岁。大多数女性是非西班牙裔白人（83%）和受过高等教育。在 337 次妊娠中报告了 97 次妊娠丢失。中位妊娠丢失的胎龄为 6 周 5 天，只有两次妊娠丢失发生在孕中期。使用 Cox 比例风险模型，我们发现两种孕前应激生物标志物（唾液皮质醇和α-淀粉酶浓度）的连续或三分位模型与调整混杂因素后的妊娠丢失事件之间没有明显的关联模式。
局限性/谨慎的原因：我们之前的工作表明，参加 LIFE 研究的女性的应激水平低于一般人群中的女性。由于担心参与者的负担，我们无法收集连续的唾液测量值，这将使我们能够研究早期妊娠应激与妊娠丢失之间的关系。此外，关于感知压力的测量，Cohen 的感知压力量表仅在基线时进行了测量。虽然尽一切努力确保队列的多样性，但非西班牙裔白人女性的比例过高，因此结果可能不适用于所有女性。
在一项美国最大的前瞻性研究之一中，我们前瞻性地捕获了早期妊娠丢失的发生率数据，我们发现两种孕前应激生物标志物（唾液测量）与妊娠丢失之间没有明显关联。
研究资助/利益冲突：本研究由美国国立儿童健康与人类发展研究所（Eunice Kennedy Shriver National Institute of Child Health and Human Development）内部研究计划资助（合同号 N01-HD-3-3355、N01-HD-3-3356、N01-HD-3358）。没有利益冲突需要声明。
不适用。
