UBC Theses and Dissertations
Angiogenic factors in placentally-mediated pregnancy complications Benton, Samantha Jayne
Placentally-mediated pregnancy complications include pre-eclampsia, intrauterine growth restriction (IUGR), placental abruption and some causes of stillbirth. These complications are believed to arise from abnormal placental development in early gestation that leads to compromised placental function in later pregnancy which can adversely affect both mother and fetus. It is a priority in obstetrics to identify these pregnancies early and accurately so that appropriate monitoring and intervention can optimise outcomes for these mothers and babies. Novel biomarkers such as angiogenic factors in the maternal circulation may improve the prediction and/or diagnosis of these complications by adding to the information gained from tools already used in clinical practice. In this thesis, I investigated angiogenic factors in 1) the diagnosis of pre-eclampsia using new clinical immunoassays, 2) the prediction of placentally-mediated complications in a high-risk pregnancy cohort and 3) the diagnosis of placental IUGR in pregnancies with small for gestational age (SGA) fetuses. Additionally, I investigated the association between levels of circulating angiogenic factors and the presence of histopathological lesions of dysfunction in the placenta after delivery. I found that angiogenic factors, particularly low circulating placental growth factor (PlGF), had high sensitivity and specificity in the diagnosis of pre-eclampsia but all markers had poor performance as predictive markers for placentally-mediated complications. In pregnancies with SGA fetuses, low maternal PlGF discriminated between fetuses with placental IUGR (defined by the presence of histological lesions of placental dysfunction) from constitutionally small fetuses (no pathological lesions present) with high sensitivity and high negative predictive value. Additionally, low maternal PlGF in the second trimester was associated with the presence of lesions of placental dysfunction in pregnancies at high-risk for placentally-mediated complications. Low maternal PlGF was also associated with lesions of placental dysfunction as well as altered placental morphology in pregnancies with SGA fetuses. Taken together, these findings suggest that PlGF may be an antenatal marker of placental dysfunction and may provide a novel clinical tool to identify pregnancies with placental dysfunction. This work improves our understanding of angiogenic factors in placentally-mediated complications and contributes to the growing body of evidence supporting their integration in clinical practice.
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Attribution-NonCommercial-NoDerivs 2.5 Canada