Preterm Birth (PTB) affects approximately 1 out of every 9 infants born in the United States and is the leading cause of infant mortality. Despite advances in risk factor identification and obstetrical care, racial disparities persist in the occurrence of PTB, with particularly high rates among African American (AA) women. An exaggerated inflammatory response is one of four discrete mechanisms for the pathogenesis of PTB. There is a significant racial disparity in inflammation-associated PTB, with African-Americans disproportionately affected. Exaggerated inflammation can be triggered by infectious processes and behavioral risk factors that promote pathogenic vaginal microbial colonization or inflammation. Identification of novel biobehavioral risk factors may provide additional insight int mechanisms and potential targets for intervention to eliminate this stubbornly persistent racial disparity in PTB. A key mediator of the inflammatory response, and also associated with PTB, is the complement pathway (complement). Complement is an innate defense mechanism composed of more than 30 blood proteins that are critically involved in the elimination of pathogenic microbes. Complement also is activated to assist in embryo implantation and the vascular remodeling and removal of cellular debris resulting from implantation that is essential to a healthy pregnancy. Dysregulation of the complement fragment C3a during early pregnancy has recently been identified as a biological risk factor for PTB and preterm premature rupture of membranes (PPROM). Exploring factors associated with C3a activation during early pregnancy among AA women may prove beneficial in the identification of biobehavioral mechanisms contributing to the later development of PTB. The purpose of this revised F31 proposal is to investigate the relationship between the vaginal microbiome, complement activation, PTB associated clinical measures, and modifiable biobehavioral risk factors linked to PTB and AA race. The proposed study is nested within a larger parent study (1R01NR014800) that is prospectively exploring the biobehavioral determinants of the microbiome and the risk of PTB in AA women. This F31 proposed study will enroll 100 of the AA women in the parent study from whom biological samples and questionnaire data will be collected at prenatal care visits occurring at time point 1 (8-14 wks) and clinical measures and outcomes collected from the medical record at time point 2 (delivery). In this prospective study we will:(1) Determine the relationship between vaginal microflora (vaginal microbiome and presence/absence of genital tract infection) and C3a levels in AA women during early pregnancy; and (2) Investigate the relationship between C3a levels in AA women during early pregnancy and PTB associated clinical measures (20 wk cervical length, gestational age at delivery). We will also explore the influence of biobehavioral risk factors (e.g., vaginal hygiene practices, sexual practices, substance use) on identified study variables.
Preterm Birth (PTB) affects approximately 1 out of every 9 infants born in the United States and despite advances in risk factor identification and obstetrica care, racial disparities persist in the occurrence of PTB, with particularly high rates among African American (AA) women. There is a significant racial disparity in inflammation-associated PTB among AA women suggesting a need to explore biobehavioral mechanisms of inflammation within this high risk group. The purpose of this revised F31 proposal is to investigate the relationship between the vaginal microbiome, complement activation, PTB associated clinical measures, and modifiable biobehavioral risk factors linked to PTB and AA race.
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|Dunn, Alexis B; Dunlop, Anne L; Hogue, Carol J et al. (2017) The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth. Biol Res Nurs 19:295-307|
|Jordan, Sheila; Baker, Brenda; Dunn, Alexis et al. (2017) Maternal-Child Microbiome: Specimen Collection, Storage, and Implications for Research and Practice. Nurs Res 66:175-183|