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Oxytocin Sensitivity and Postpartum Hemorrhage: Testing Genetic and Epigenetic Biomarkers for Improving Maternal Morbidity

Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development

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$612.1K Funding
3 People
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Abstract

Project SummaryPostpartum hemorrhage is a complication of childbirth that affects 3-8% of births in the United States eachyear this represents a minimum of 120000 births. Postpartum hemorrhage is also a primary cause of maternalmortality worldwide. Rates of severe postpartum hemorrhage and hemorrhage requiring invasive treatments orblood transfusions are on the rise particularly for labors that are induced. Severe hemorrhage is also morecommon among women of color contributing to disparities in maternal health. Oxytocin is a naturally occurringhormone as well as a medication used to stimulate labor prevent or treat postpartum hemorrhage. Oxytocinbinds available oxytocin receptors in uterine muscle stimulating contraction. While oxytocin is the first-linehemorrhage treatment people who have been given oxytocin to stimulate contractions during labor are morelikely to have a less effective uterine contraction response to oxytocin administered postpartum leading tomore bleeding and the need for other medical treatments or procedures. Currently 4 of 10 people whohemorrhaged did so despite not having been identified as high risk by current clinical prediction tools. Thisinaccuracy and the rising rates of hemorrhage indicate that more research is needed to help identify possiblerisks for this potentially life-threatening complication. Because people with ineffective labor contractions or apersonal/family history (of hemorrhage) are more likely to have postpartum hemorrhage the role of innateoxytocin function/ sensitivity is the primary focus of this investigation. As such our lab has been researchingbiomarkers that can help identify people at risk for hemorrhage by testing how genetic and epigenetic variationof the oxytocin receptor gene is associated with oxytocin response and hemorrhage. In this proposal we use abiosocial framework to test the central hypothesis that maternal variation in the oxytocin receptor gene can beuseful for predicting pharmacologic oxytocin needs and hemorrhage. First we will examine DNA methylation(epigenetic differences) from blood samples using banked data as well as prospectively collected non-invasivesalivary samples in association with oxytocin needs in labor and postpartum hemorrhage. Social determinantsof health will be examined in association with DNA methylation differences; evaluating the role of adverseenvironments in shaping the oxytocin receptor epigenotype. Furthermore we will test how DNA methylationaffects gene expression and the oxytocin receptor availability in uterine tissues. Second we will examinegenetic variants of the oxytocin receptor gene in association with the clinical endpoints with the aforementionedspecimens and test pharmacologic response by measuring contractility of uterine muscle specimens. Giventhat clinicians have no method of predicting how well oxytocin will work in the emergency of postpartumhemorrhage we aim to develop a clinically useful biomarker measuring intrinsic oxytocin sensitivity beforelabor or birth occurs. The long-range goal of this project is to use biomarker data to improve clinical decision-making test personalized interventions and lower maternal morbidity.

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