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Objective: Evidence is accumulating that fetal growth is influenced by preexisting maternal disorder(s) hampering endothelial function. We tested the hypothesis that in nonpregnant normotensive, formerly preeclamptic women, vascular function predicts the development of fetal growth restriction., Methods: In 60 formerly preeclamptic women, we measured central hemodynamic and vascular and clotting function mid follicular phase during the menstrual cycle. Inclusion for final analysis required besides normotension, a subsequent singleton pregnancy, established within 1 year after the prepregnant evaluation and ongoing beyond 16 weeks' gestation. In the ongoing pregnancy we determined birth weight and birth weight percentile., Results: Among 60 formerly preeclamptic women, 45 (75%) were normotensive. Thirty-one (69%) participants succeeded in establishing an ongoing pregnancy within 1 year and were included for final analysis. Of the 31 subsequent pregnancies, 8 (26%) were complicated by fetal growth restriction. Prepregnant left and right uterine artery pulsatility index (PI) correlated inversely with carotid artery compliance ( r = 0.57, P = .005, r = 0.62, P = .002) and venous compliance ( r = 0.49, P = .02 and r = 0.45, P = .04, respectively). The latter, in turn, correlates with plasma volume ( r = 0.63, P = .001) and total peripheral vascular resistance index ( r = -0.45, P = .02). Finally, prepregnant left and right uterine artery PI correlated inversely with subsequent achieved fetal growth ( r = -0.68, P < .0001 and r = -0.58, P = .001, respectively)., Conclusion: In nonpregnant normotensive, formerly preeclamptic women, an elevated uterine artery PI predisposes to subsequent restriction in fetal growth.

Background: Both hemodynamic abnormalities and thrombophilia predispose to pregnancy-associated vascular complications such as fetal growth restriction, stillbirth, preeclampsia, and placental abruption. Antithrombotic treatment may reduce the risk for these events. In this study we tested the hypothesis that in normotensive thrombophilic formerly preeclamptic women certain alterations in hemodynamic function as measured under nonpregnant conditions predict the development of hypertensive disorders and/or fetal growth restriction in the subsequent pregnancy., Methods: In 350 nondiabetic formerly preeclamptic women, we measured in the follicular phase of the menstrual cycle at least 5 months postpartum central hemodynamic, metabolic, and hemostatic variables. In the subsequent ongoing pregnancy we determined fetal outcome variables and the incidence of maternal vascular complications. In addition to a normotensive thrombophilic profile, inclusion for final analysis required a subsequent singleton pregnancy, established within 1 year following the pre-pregnant evaluation and ongoing beyond 16 weeks' gestation. As a consequence, 47 normotensive thrombophilic formerly preeclamptic women could be included for final analysis. All formerly preeclamptic participants received aspirin throughout pregnancy. Additionally, those with thrombophilia or hyperhomocysteinemia were treated with low molecular weight heparin and with pyridoxine and folic acid supplementation, respectively., Results: Among 350 formerly preeclamptic women, 266 (76%) were normotensive and 84 (24%) hypertensive. About half (140/266) of normotensive formerly preeclamptic participants were thrombophilic. One hundred eighteen formerly preeclamptic participants succeeded in establishing an ongoing pregnancy within 1 year. From this subset of formerly preeclamptic women, 47 were normotensive thrombophilic; 23 remained normotensive (THROMB), whereas 24 developed at least gestational hypertension (COMPLITHROMB). Participants in the latter subgroup were more obese than those remaining normotensive. In addition, this former subset of women had a higher vascular resistance index, and a lower plasma volume and cardiac index. With respect to fetal outcome, COMPLITHROMB gave birth to an infant with a lower birth weight relative to THROMB. Preeclampsia with or without the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome recurred in 26% of the participants in the whole thrombophilic group, in which a low pre-pregnant plasma volume and a raised vascular resistance predisposed for recurrent hypertensive disorders., Conclusion: Pre-pregnant hemodynamic, metabolic, and clotting variables in formerly preeclamptic women can predict hypertension in the subsequent pregnancy.

Background: In women prone to develop hypertensive complications, vascular reactivity fails to decrease in early pregnancy. Since hypertensive syndromes of pregnancy seem to be superimposed on a preexisting disorder, we tested the hypothesis that in formerly preeclamptic women, as compared to healthy parous controls, circulatory reactivity to angiotensin II is enhanced in the follicular phase of the menstrual cycle., Methods: Sixty formerly preeclamptic women were subdivided into a hypertensive (HYPERT, n = 14), a normotensive thrombophilic (THROMB, n = 26), and a normotensive nonthrombophilic (ASYMPT, n = 20) subgroup. In these women and in 11 healthy parous controls we assessed at least 5 months postpartum at day 5 (+/-2) of the menstrual cycle the following variables: body weight, height, plasma volume, reactivity to infused angiotensin II of arterial blood pressure, heart rate, glomerular filtration rate (GFR), effective renal blood flow, and the hormones of the renin-angiotensin-aldosterone (RAAS) axis., Results: At baseline, THROMB did not differ from controls. In contrast, ASYMPT exhibited slight overweight, reduced plasma volume, and reduced renal blood flow. HYPERT much resembled ASYMPT except for the overweight, renal perfusion, and GFR. Infusion of angiotensin II led to comparable decreases in renal perfusion and filtration, and to increases in blood pressure. However, sensitivity to this substance correlated inversely with relative and absolute sizes of the plasma volume compartment., Conclusion: Circulatory sensitivity to infused angiotensin II is comparable between nonpregnant formerly preeclamptic women and healthy parous controls. However, responsiveness to this agent is enhanced among women with a contracted plasma volume compartment, a condition commonly observed among formerly preeclamptic women.