Effect of pregnancy prolongation in early-onset pre-eclampsia on postpartum maternal cardiovascular, renal and metabolic function in primiparous women: an observational study.

OBJECTIVE: To evaluate the association between deferred delivery in early-onset pre-eclampsia and offspring outcome and maternal cardiovascular, renal and metabolic function in the postpartum period. DESIGN: Observational study. SETTING: Tertiary referral hospital. POPULATION: Nulliparous women diagnosed with pre-eclampsia before 34 weeks' gestation who participated in a routine postpartum cardiovascular risk assessment programme. Women with hypertension, diabetes mellitus or renal disease prior to pregnancy were excluded. METHODS: Regression analyses were performed to assess the association between pregnancy prolongation and outcome measures. MAIN OUTCOME MEASURES: Offspring outcome and prevalence of deviant maternal cardiovascular, renal and metabolic function. RESULTS: The study population included 564 women with a median pregnancy prolongation of 10 days (interquartile range [IQR] 4-18) who were assessed at on average 8 months (IQR 6-12) postpartum. Pregnancy prolongation after diagnosis resulted in a decrease in infant mortality (adjusted odd ratio [aOR] 0.907, 95% CI 0.852-0.965 per day prolongation). This improvement in offspring outcome was associated with an elevated risk of moderately increased albuminuria (aOR 1.025, 95% CI 1.006-1.045 per day prolongation), but not with aberrant cardiac geometry, cardiac systolic or diastolic dysfunction, persistent hypertension or metabolic syndrome. CONCLUSION: Pregnancy prolongation in early-onset pre-eclampsia is associated with improved offspring outcome and survival. These effects do not appear to be deleterious to short-term maternal cardiovascular and metabolic function but are associated with a modest increase in risk of residual albuminuria. TWEETABLE ABSTRACT: Pregnancy prolongation in pre-eclampsia has only a limited effect on postpartum maternal cardiovascular function

Low plasma volume coincides with sympathetic hyperactivity and reduced baroreflex sensitivity in formerly preeclamptic patients.

Contains fulltext : 50660.pdf (publisher's version ) (Open Access)BACKGROUND: Preeclampsia is associated with enhanced sympathetic activity as well as subnormal plasma volume. Meanwhile, in over 50% of these complicated pregnancies, the subnormal plasma volume has been found to persist for a prolonged period after pregnancy. The objective of this study is to test the hypothesis that in normotensive formerly-preeclamptic women, persistence of a subnormal plasma volume coincides with enhanced sympathetic activity and with it, an altered autonomic control of blood pressure. METHODS: Forty-eight formerly-preeclamptic women participated in this study. After measurement of their plasma volume by iodine 125-albumin indicator dilution, they were subdivided into a group with a normal plasma volume (plasma volume > 48 ml/kg lean body mass) and a group with a subnormal plasma volume (< or = 48 ml/kg lean body mass). We performed spectral analysis on their beat-to-beat blood pressure and heart rate recordings and compared both groups using non-parametric tests. RESULTS: Formerly-preeclamptic women with a subnormal plasma volume had a higher sympathetic activity (P = .001) and a lower baroreflex sensitivity (P = .04) than their counterparts with a normal plasma volume. CONCLUSION: In normotensive formerly-preeclamptic women, a subnormal plasma volume coincides with a higher sympathetic activity in the blood pressure regulation and lower baroreflex sensitivity. Whether these alterations in the autonomic control mechanisms are a cause or effect of the subnormal plasma volume remains to be elucidated

Angiotensin II sensitivity in nonpregnant formerly preeclamptic women and healthy parous controls.

Contains fulltext : 58141.pdf (publisher's version ) (Closed access)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

Pre-pregnant prediction of recurrent preeclampsia in normotensive thrombophilic formerly preeclamptic women receiving prophylactic antithrombotic medication.

Contains fulltext : 49207.pdf (publisher's version ) (Open Access)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

Fetal fibronectin status and cervical length in women with threatened preterm labor and the effectiveness of maintenance tocolysis

Item does not contain fulltextOBJECTIVE: To assess the effect of maintenance tocolysis in women who are at high or low risk for preterm delivery according to fetal fibronectin (fFN) status and cervical length (CL). STUDY DESIGN: We compared the risk of preterm delivery in fFN pos and fFN neg women and in women with a CL /=15 mm, by using the Cox regression. Differences between the effectiveness of maintenance tocolysis in high- and low-risk women were assessed by using an interaction term. RESULTS: 122 fFN tests were taken, of which 50 were fFN pos. CL was measured in 236 women, of whom 52 women had a CL <15 mm. The median gestational age at delivery was lower in fFN pos women; fFN pos women had a higher hazard for preterm delivery at any point of time (HR 4.7; 95% CI 2.9 to 7.6). Comparable results were seen for CL. Neither fFN status nor CL did alter the effect of maintenance tocolysis, which was ineffective in the total randomized group, on the risk of preterm delivery (p for interaction = 0.87 for fFN and 0.18 for CL). CONCLUSION: Maintenance tocolytic therapy with nifedipine is ineffective and not dependent on fFN or CL status

Mechanisms leading to increased vasodilator responses to calcitonin-gene-related peptide in mesenteric resistance arteries of early pregnant rats.

Contains fulltext : 69189.pdf (publisher's version ) (Closed access)The objective of this study was to explore the mechanism responsible for the higher relaxing responses of mesenteric arteries to calcitonin-gene-related peptide (CGRP) in pregnancy. We performed myograph and ligand binding studies to determine the role of matrix metalloproteinase-2 (MMP-2) and CGRP receptor density. MMP activity was manipulated in isolated arteries by exposing them to the blocking effects of doxycycline. Vascular activity of MMP-2 was studied by gelatin zymography, and CGRP receptor density was determined by ligand binding analysis. Compared to nonpregnant rats, CGRP elicited stronger arterial relaxation in pregnant rats. The latter effect was neither accompanied by a change in relaxing responses to direct activation of adenylyl cyclase by forskolin nor by a change in the response to stimulation of G-protein-coupled adrenergic receptors by isoproterenol. Doxycycline did not affect the stronger arterial relaxation in pregnancy in spite of the observed more than threefold higher arterial MMP-2 activity. Density of binding sites for [(125)I]CGRP in arteries from pregnant rats (64 +/- 14 fmol/mg protein) and from virgin rats (54 +/- 5 fmol/mg protein) were comparable. The results of this study provide evidence for increased coupling of CGRP receptors to adenylyl cyclase in early pregnancy