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Objective: Placental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin. Study Design: Secondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60mg/d (n=102) or placebo (n=72), with PlGF collected at 13w 0d-16w 6d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders. Results: ROC analysis indicated 87.71pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p=0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p=0.445). Conclusions: Unlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated. Condensation: High-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) impacts 8 million mother-infant pairs worldwide each year. This human pregnancy-specific disease characterized by hypertension and proteinuria accounts for significant maternal and neonatal morbidity and mortality. The current theory of the pathogenesis of PE as reviewed by Drs. Christopher Redman and Ian Sargent is thought to occur as a 2-stage process with poor placentation in the first half of pregnancy resulting in the maternal response in the second half of pregnancy. Our studies have focused on understanding the placental contribution to this serious disease by examining the gene expression profile of the deciduas basalis or basal plate, the region of the placenta involved in the "poor placentation". In this review we present summaries of our microarray datasets both of normal placentation and those gene expression changes resulting in the context of PE. Additionally, we have taken this opportunity to combine the data sets to provide a more comprehensive view of this region of the placenta. As defects in the basal plate are, in part, at the root of the disease process, we believe that understanding the pathobiology that occurs in this region will increase our ability to alter the development and/or course of PE. [ABSTRACT FROM AUTHOR]

Introduction Assisted reproduction is associated with an increased risk for hypertensive disease in pregnancy. The underlying pathophysiology is still debated. Endothelial dysfunction is a central component of hypertensive disease and can be determined non-invasively by Pulse-Amplitude-Tonometry (PAT). Objectives We hypothesized that a non-physiologic maternal environment in early pregnancy, specifically the absence of a corpus luteum (CL), negatively impacts maternal endothelial health. Patients and methods For this ongoing study women with spontaneous conceptions and conceptions after assisted reproduction were recruited at an academic infertility clinic after confirmation of a viable intrauterine pregnancy between 7 and 10 weeks gestation. Exclusion criteria were multiples, chronic hypertension, chronic kidney disease, diabetes mellitus, autoimmune disease, age >50 years or BMI >30. Endothelial function was determined using the Endo-PAT2000 system by calculating the reactive hyperemia index (RHI) at 11–14 weeks gestation. RHI ⩽1.67 is associated with a higher cardiovascular risk. A fasting lipid panel was obtained for each participant. Statistical analysis was performed using Kruskal–Wallis-test with post hoc analysis. Results are shown as means and standard errors. Results 47 women participated in the research visit. We found a significant difference in endothelial function with lower RHI in pregnant women with no CL ( N = 10, RHI = 1.65 ± 0.08; p = 0.04) compared to women with 1 CL ( N = 21; RHI = 1.99 ± 0.11). This difference was also evident between frozen-thawed ET in programmed ( N = 10; RHI = 1.65 ± 0.03, p = 0.03) compared to natural cycles ( N = 9; RHI = 1.95 ± 0.08). There was no difference when comparing the data to the group of women with fresh ET and supraphysiologic numbers of CL. Age, blood pressure and lipid levels were not different between groups. Conclusions A non-physiologic maternal environment, which is generated by suppression of CL in programmed cycles, negatively impacts maternal endothelial health in early pregnancy. The cause could be the absence of CL products. Specifically, relaxin, a potent vasodilator, might play a crucial role. A deficiency in relaxin could therefore contribute to an increased risk of hypertensive disease in pregnancy after assisted reproduction. [ABSTRACT FROM AUTHOR]