Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise.

Contains fulltext : 47812.pdf (publisher's version ) (Open Access)INTRODUCTION: In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise. PATIENTS AND METHODS: We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC). RESULTS: The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups. CONCLUSION: The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise

Blunted autonomic response to volume expansion in formerly preeclamptic women with low plasma volume.

Contains fulltext : 80636.pdf (publisher's version ) (Closed access)OBJECTIVE: We hypothesize that low plasma volume in normotensive formerly preeclamptic women reflects reduced venous storage capacity. To test this hypothesis, we compared circulatory and autonomic responses to acute volume loading between women with low and those with normal plasma volume. METHODS: In 24 normotensive formerly preeclamptic women at least 6 months postpartum, we administered 500 mL of iso-oncotic fluid by constant intravenous infusion in 30 minutes, while recording changes in heart rate, blood pressure, cardiac output, and measuring active plasma renin and alpha-atrial natriuretic peptide concentrations. We estimated arterial sympathetic control, cardiac autonomic regulatory balance, and baroreflex sensitivity using spectral analysis. Intergroup and intragroup changes were analyzed nonparametrically. RESULTS: 17 women (71%) had low plasma volume and 7 (29%) had normal plasma volume. Plasma volume expansion induced comparable changes in blood pressure, heart rate, baroreflex sensitivity, and active plasma renin concentration in low plasma volume and normal plasma volume. Cardiac output and alpha-atrial natriuretic peptide increased in low plasma volume but not in normal plasma volume. Volume expansion reduced sympathetic activity ( from 2.41 to 1.76 mm Hg(2), P = .03) in normal plasma volume but not in low plasma volume ( from 2.72 to 2.48 mm Hg(2), P > .05). CONCLUSION: The sympathoinhibitory response to volume expansion is diminished in low plasma volume, which suggests that cardiovascular reflex function is impaired. We speculate that this defect contributes to circulatory maladaptation to pregnancy, sympathetic dominance, and the development of gestational hypertensive disease

Is it useful to measure C-reactive protein and leukocytes in patients with prelabor rupture of membranes?

Neonatal infection is the main complication of prelabor rupture of membranes (PROM). We studied the accuracy of measuring C-reactive protein (CRP) and leukocytes in maternal serum to predict neonatal infection. We performed a retrospective cohort study in two hospitals in the Netherlands between 2003 and 2006. We included consecutive women hospitalized for PROM. In both hospitals, CRP and leukocytes were measured routinely in maternal serum every 2 days until delivery. End points considered were clinical neonatal infection and proven neonatal sepsis. The accuracy of CRP and leukocytes was assessed using receiver operating characteristic (ROC) analysis. We included 299 women with PROM, 12 of whom had a twin pregnancy. Gestational age at inclusion varied between 26 weeks and 0 days and 41 weeks and 5 days with a median of 37 weeks and 3 days. In 47 women (16%), the neonate developed a clinical infection. The areas under the ROC curve of CRP and leukocytes in the prediction of clinical neonatal infection were 0.61 and 0.62, respectively. Of the 47 infected neonates, six neonates (2%) had a proven neonatal sepsis. In the mothers of these septic neonates, maternal CRP did not rise above 50 mg/L and leukocyte values varied between 9.8 and 25.8 × 109/L. In women with PROM, CRP and leukocytes should not be measured routinely.Jantien L. van der Heyden, Stijn S.P van Teeffelen, Anne C.G Coolen, Feico J. Halbertsma, Robert Aardenburg, Helena J.M.M Mertens, Ben Willem J Mo

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

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

Maternal nonpregnant vascular function correlates with subsequent fetal growth.

Contains fulltext : 48774.pdf (publisher's version ) (Closed access)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

A subnormal plasma volume in formerly preeclamptic women is associated with a low venous capacitance.

Contains fulltext : 48810.pdf (publisher's version ) (Open Access)OBJECTIVE: Pregnancy induces a smaller rise in plasma volume in formerly preeclamptic women with a pre-existent subnormal plasma volume than in their counterparts with a normal plasma volume. These women also have a three times higher recurrence rate of pregnancy-induced hypertensive disorders. In this study we tested the hypothesis that a subnormal plasma volume in these women is related to a lower capacitance of their venous compartment. METHODS: In 31 nonpregnant formerly preeclamptic women with a subnormal plasma volume and eight parous controls, we infused intravenously 500 mL of a modified gelatin solution over 30 minutes. Before and after infusion we measured the circulating levels of alpha-atrial natriuretic peptide (alpha-ANP) and active plasma renin concentration (APRC). During volume loading, we recorded the change in heart rate, stroke volume, and cardiac output using pulse contour analysis. We measured the ratio of percent change in blood volume and percent change in cardiac output during volume loading as a marker for venous capacitance. RESULTS: During volume loading, patients differed from controls by a larger rise in alpha-ANP, pulse rate, and cardiac output, and by a lower estimated venous capacitance. The concomitant response of stroke volume and APRC did not differ appreciably between groups. CONCLUSION: Formerly preeclamptic women with a subnormal plasma volume differ from controls with a normal plasma volume by a reduced venous capacitance. These results support our hypothesis that, in these women, a subnormal plasma volume indicates the presence of a subnormal venous capacitance

Pregnancy enhances the prejunctional vasodilator response to adrenomedullin in selective regions of the arterial bed of Wistar rats.

Contains fulltext : 52225.pdf (publisher's version ) (Closed access)The objective of this study is to determine whether the vascular response to adrenomedullin is modulated by pregnancy. To this end, the authors study the effect of adrenomedullin on different contractile responses of mesenteric, uterine, renal, and saphenous arteries of 10-day pregnant and nonpregnant rats in myographs. Adrenomedullin inhibited contractile responses induced by electrical field stimulation in only the mesenteric and uterine arteries. This effect was more pronounced during pregnancy than in the nonpregnant state. Adrenomedullin did not modify concentration response curves to noradrenaline. The reduction of contractile responses to 40 mmol/L K(+) by adrenomedullin was similar in arteries of pregnant and nonpregnant rats. However, after incubation with capsaicin, this effect was significantly increased in mesenteric arteries of the pregnant group. The authors conclude that pregnancy is associated with a rise in the prejunctional inhibitory effect of adrenomedullin in some regions of the arterial system

External validation and clinical usefulness of first-trimester prediction models for small- and large-for-gestational-age infants:a prospective cohort study

ObjectiveTo assess the external validity of all published first-trimester prediction models based on routinely collected maternal predictors for the risk of small- and large-for-gestational-age (SGA and LGA) infants. Furthermore, the clinical potential of the best-performing models was evaluated. DesignMulticentre prospective cohort. SettingThirty-six midwifery practices and six hospitals (in the Netherlands). PopulationPregnant women were recruited at MethodsPrediction models were systematically selected from the literature. Information on predictors was obtained by a web-based questionnaire. Birthweight centiles were corrected for gestational age, parity, fetal sex, and ethnicity. Main outcome measuresPredictive performance was assessed by means of discrimination (C-statistic) and calibration. ResultsThe validation cohort consisted of 2582 pregnant women. The outcomes of SGA 90th percentile occurred in 203 and 224 women, respectively. The C-statistics of the included models ranged from 0.52 to 0.64 for SGA (n=6), and from 0.60 to 0.69 for LGA (n=6). All models yielded higher C-statistics for more severe cases of SGA (95th percentile). Initial calibration showed poor-to-moderate agreement between the predicted probabilities and the observed outcomes, but this improved substantially after recalibration. ConclusionThe clinical relevance of the models is limited because of their moderate predictive performance, and because the definitions of SGA and LGA do not exclude constitutionally small or large infants. As most clinically relevant fetal growth deviations are related to vascular' or metabolic' factors, models predicting hypertensive disorders and gestational diabetes are likely to be more specific