Background: Maternal blood Pressure (BP) is closely monitored in pregnancy to identify the development of hypertensive disorders of pregnancy (HDPs), i.e. gestational hypertension (GH) and preeclampsia (PE). In addition to their association with increased risk for adverse perinatal outcomes, these hypertensive disorders in pregnancy are also been associated with increased risk of developing hypertension later in life. In 2017, the American Association of Cardiology/American Heart Association (ACC-AHA) introduced new BP criteria for non-pregnant populations, lowering the level at which elevated BP and hypertension are diagnosed, yet the previous cut off of 140/90 is still used during pregnancy. Imbalances of angiogenic biomarkers (elevated levels of soluble endoglin (sEng) and soluble Fms-like tyrosine kinase-1(sFlt-1) and lower levels of placental growth factor (Plgf)) in maternal blood are associated with PE. Less is known about associations between angiogenic biomarkers during pregnancy in pregnant individuals with elevated BP lower than 140/90. If angiogenic and anti-angiogenic biomarkers are correlated with BP in these ranges, they could provide clues to pregnancy health and to maternal vessel health later in life for these groups as well.℗ Aims: This dissertation first explores associations between angiogenic biomarkers (Plgf, sFlt-1 and endoglin) and MAP (mean arterial pressure: the average pressure throughout one cardiac cycle) during pregnancy (Aim 1). It then examines whether the combination of MAP and angiogenic biomarkers are associated with adverse pregnancy outcomes, such as preterm or small for gestational age birth (Aim 2). The final aim of the dissertation explores associations between angiogenic biomarkers during pregnancy and the development of later life hypertension among women with normal BP, moderately elevated BP and hypertensive℗ disorders during pregnancy (Aim 3).℗ Methods: Secondary analysis of data from the POUCH (Pregnancy Outcomes and Community Health) Study which enrolled pregnant people at 16-27 weeks gestation followed them throughout pregnancy, and from the POUCHmoms follow up study 7-15 years later. First, multivariable logistic regression models are used to estimate the association between each angiogenic biomarker having MAP in the top quartile close to 20 weeks gestation, and at the time of the highest BP in pregnancy (both for the whole sample, and only those who do not have PE, GH or cHtn). Then associations between combinations of MAP and angiogenic biomarker levels and size for gestational age, as well as length of gestation are assessed. Finally associations between angiogenic biomarker levels in pregnancy and stage of hypertension 7-15 years later are estimated, and then associations between groups based on blood pressure category in pregnancy combined with biomarker level are used in polytomous regression models.Findings: Lower levels of Plgf at mid-pregnancy in this study are associated with having higher (MAP), even among participants without pre-eclampsia or other hypertensive disorders. Of the three biomarkers, 'low' Plgf levels associated with SGA and 'high' endoglin levels were associated with shorter length of gestation. Pregnancies with MAP 'high' and Plgf 'low' had greater than twice the odds of delivering an SGA infant. Given the lack of any association between sFlt-1 and pregnancy BP in the first two studies, we only examined Plgf and endoglin and found in our study they do not help determine which individuals with moderately elevated BP during pregnancy are at greatest risk of hypertension 7-15 years later.℗
Read
