Placental Maternal Vascular Malperfusion Is Associated with Prepregnancy and Early Pregnancy Maternal Cardiovascular and Thrombotic Profiles

Abstract

Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation potential in healthy young women. Sixty-three healthy young women were recruited and assessed prior to pregnancy on cycle day 9 ± 4, at gestational age 90 ± 6 of early pregnancy, and gestational age 216 ± 5 of late pregnancy. Women were assessed for plasma volume, blood pressure, response to volume loading, cardiac output, and uterine hemodynamics. Platelet-poor plasma was collected to assess thrombin generation on a subset of 33 women at all time points. Following delivery, placentas were collected and analyzed for evidence of MVM. Thrombin generation (TG) was evaluated in the presence of tissue factor (TF) with and without recombinant soluble thrombomodulin (TM). For each, we compared TG lagtime, peak level, and endogenous thrombin potential (ETP). Comparisons were made between dichotomized presence and absence of each individual feature of MVM and cardiovascular and coagulation features. Mean ± standard deviation are presented. Women were 31 ± 4 years of age, body mass index of 24 ± 5 kg/m2, 86% white race, and 80% nulliparous. MVM occurred in 70% of placentas, with infarcts and agglutination (44%), decidual arteriopathy (40%), accelerated villous maturation (32%), placental hypoplasia (29%), and distal villous hypoplasia (17%) documented. Decidual arteriopathy and distal villous hypoplasia were associated with prepregnancy maternal physiology, including decreased plasma volume and subclinical cardiovascular variations. All assessed MVM characteristics had identifiable early pregnancy physiologic characteristics consistent with altered cardiovascular function and decreased uterine response to pregnancy when compared with women who did and did not develop MVM. Accelerated villous maturation was the only MVM feature to differ by thrombin generation parameters in early pregnancy. Thrombin generation potential and blood pressure were elevated in late pregnancy in women who developed decidual arteriopathy. Prepregnancy health status and adaptation to pregnancy play important roles in pregnancy outcomes. Both cardiovascular health and thrombin generation potential may influence early placentation. Longitudinal assessment of subclinical maternal factors may allow for better understanding of the etiologies of MVM lesions, as well as allow for identification of a timeline of the origins of placental pathologies.

Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Preeclampsia and Italian Society of Perinatal Medicine

“…Low TPVR (<1048 dyne s cm -5 ), high CO and eccentric hypertrophy of the LV relate to late complications. 4,97 Pre-conceptional hemodynamic assessment identifies chronic hypertension at risk for complications. The risk of recurrent PE and FGR relates inversely and linearly to preconception plasma volume (8% difference between women who will develop PE and controls).…”

“…Low TPVR (<1,048 dyne•s•cm À5 ), high CO, and eccentric hypertrophy of the LV relate to late complications. 4,97 Preconceptional hemodynamic assessment identifies chronic hypertension at risk for complications.…”

“…Low TPVR (<1,048 dyne·s·cm −5 ), high CO, and eccentric hypertrophy of the LV relate to late complications. 4 97…”

“…Moreover, alongside these widely studied areas, interesting data are emerging regarding other pregnancy diseases such as diabetes and preterm delivery (PTD), as well as a potential role of hemodynamics before pregnancy, in FGR, during tween pregnancy, labor, and delivery with the anesthesiologic implications of hemodynamic profile of the mothers. 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106…”

Thrombin in Pregnancy and Preeclampsia: Expression, Localization, and Vasoactivity in Brain and Microvessels From Rats

“…[19][20][21] We previously showed that pregnancy was protective of ischemic brain injury and associated with high ischemic tolerance, an effect prevented in a model of PE. 22 While it is known that circulating levels of prothrombin and thrombin are elevated in pregnancy and further heightened in PE, which may increase the risk of stroke, 3,12,23,24 it is largely unknown if thrombin levels and PAR expression in the brain and cerebral vasculature are affected, which may impact stroke outcomes. In addition, exogenous thrombin has been shown to have a role in hemodynamic recovery in response to ischemia by promoting both arteriogenesis and angiogenesis in noncerebral vessels.…”