Project Summary:
Pregnancy complications represents a significant concern in women’s health. Every year, at least 25 Wisconsin women die during pregnancy or within a year of giving birth. In Wisconsin, the infant death rate is approximately 6.3 per 1,000 live births, which is higher than the overall rate of 5.8 per 1,000 live births in the United States. In 2017, 7.7% of Wisconsin babies were born with low birthweight; this percentage has been slowly increasing since 2011. Addressing pregnancy in women’s health is particularly crucial, as complications during pregnancy can have long-term health implications on both mothers and babies. Focusing health issues during pregnancy can improve outcomes for both mothers and babies, leading to healthier families and communities.
Leading causes of pregnancy complications include infection, hemorrhage, abnormal placental attachment, and coagulation disorders. Physiological changes during pregnancy create a hypercoagulable state which is designed to protect the mother from the hemostatic challenges of childbirth. Coagulation disorders, such as thrombophilia (which increases the tendency of making blood clots), can further exaggerate this hypercoagulable state and increase the risk of pregnancy complications such as recurrent pregnancy loss, poor fetal growth, stillbirth, preeclampsia and placental abruption. Indeed, epidemiological studies show an association between thrombophilia and pregnancy complications. This project will specifically focus on understanding how thrombophilia modifies maternal uterine response to pregnancy by utilizing an established murine model of human factor V Leiden (FVL) polymorphism. FVL polymorphism (G1619A) is one of the most common forms of inherited thrombophilia and is characterized by poor anticoagulant response to activated protein C (a natural anticoagulant that regulates the physiologic function of coagulation). It is associated with two- to three-fold increased risk of obstetric complications such as recurrent pregnancy loss, preeclampsia, placental abruption and small for gestational age fetus.