The Role of Hypothalamic Pituitary - Adrenal Axis Dysregulation in Preterm Birth

项目摘要/摘要 早产(PTB)仍然是婴儿死亡、儿科发病率和 重大的公共卫生问题。肺结核现在被认为是一种全球性的产科综合征，发生于一种复杂的 一系列具有重叠风险因素和影响的问题，包括暴露在创伤性事件中。 在过去对创伤经历和肺结核的研究中，一个主要的挑战是缺乏可靠的生物标志物 个人面临心理压力，特别是慢性压力。几项关于男性和非女性的研究 患有老年痴呆症的孕妇表现出下丘脑-垂体-肾上腺(HPA)轴的改变。 有精神创伤史。新出现的数据，包括我们自己的数据，提供了令人信服的证据来证明 母体创伤经历和不良妊娠结局，如肺结核。然而，到目前为止， 有创伤病史和与肺结核潜在联系的孕妇HPA轴调节失调 系统评估。我们将对2700个队列中的数据和样本进行二次分析 秘鲁利马的孕妇。拟议中的项目将是评估假设的第一次调查 皮质醇分泌的时间积分测量(使用头皮皮质醇浓度)之间的相关性 [肝细胞癌])和肺结核在一大群孕妇中发生。值得注意的是，这项拟议的研究利用了为数不多的 秘鲁利马低收入拉美裔女性头发样本前瞻性采集的队列-a 高度暴露于创伤和精神健康障碍的人群(R01 HD059835)。如果是我们的成本造成的- 有效的研究表明了HPA失调的作用，其结果将有助于机械设计 研究，以及旨在减少早期生活逆境的影响和干预研究的设计 易感人群围产期不良结局的其他危险因素。我们的研究结果将 阐明HPA轴失调在妊娠中的作用，这对于理解 妊娠并发症的病因，如肺结核。

PROJECT SUMMARY/ABSTRACT Preterm birth (PTB) continues to be one of the leading causes of infant mortality, pediatric morbidity, and a major public health problem. PTB, now recognized as a global obstetrical syndrome, occurs due to a complex cluster of problems with a set of overlapping risk factors and influences including exposure to traumatic events. A major challenge in past studies of trauma experiences and PTB has been a lack of reliable biomarkers for individuals’ exposure to psychological stress, particularly chronic stress. Several studies in men and non- pregnant women have shown alterations in the hypothalamic–pituitary–adrenal (HPA) axis in individuals with a history of trauma. Emerging data, including our own, provides compelling evidence on the relationship between maternal trauma experiences and adverse pregnancy outcomes such as PTB. However, to date, the role of HPA axis dysregulation in pregnant women with a history of trauma and potential links to PTB has not been systematically evaluated. We will conduct this secondary analysis of data and samples from a cohort of 2,700 pregnant women in Lima, Peru. The proposed project will be the first investigation to assess the hypothesized association between time-integrated measures of cortisol secretion (using scalp hair cortisol concentrations [HCC]) and PTB in a large cohort of pregnant women. Of note, the proposed study leverages one of the few cohorts with prospectively collected hair samples among low-income Hispanic women in Lima, Peru – a population highly exposed to trauma and mental health disorders (R01 HD059835). If results from our cost- effective study indicate a role of HPA dysregulation, the results will contribute to the design of mechanistic studies, as well as the design of intervention studies aimed at reducing the impact of early life adversities and other risk factors of adverse perinatal outcomes in vulnerable populations. Findings from our study will illuminate the role of HPA axis dysregulation in pregnancy which is important to understanding the etiopathogenesis of pregnancy complications such as PTB.