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

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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.