Non-pregnant circulatory volume status predicts subsequent pregnancy outcome in normotensive thrombophilic formerly preeclamptic women.

BACKGROUND: Preeclampsia seems to be superimposed upon a preexisting hemodynamic, hemostatic, autoimmune or metabolic disorder. We tested the hypothesis that in normotensive thrombophilic formerly preeclamptic subjects, the non-pregnant circulatory volume status predicts the development of subsequent hypertensive pregnancy and/or fetal growth restriction. METHODS: In 250 non-diabetic formerly preeclamptic women and 15 normal parous controls, we measured and calculated the following variables at least 5 months postpartum at day 5 (+/-2) of the menstrual cycle: mean arterial pressure, body mass index, plasma volume and the clotting function. In the subsequent pregnancy we determined, birth weight, birth-weight centile and the incidence of preterm birth, fetal growth restriction, pregnancy-induced hypertension, preeclampsia and HELLP-syndrome. We only included in the final analysis normotensive subjects with a thrombophilic phenotype at the time of the pre-pregnant screening, who had a subsequent singleton pregnancy, ongoing beyond 16 weeks gestation within 1 year after pre-pregnant evaluation. As a consequence, 23 formerly preeclamptic women and 12 controls were eligible for final analysis. The thrombophilic formerly preeclamptic participants received aspirin in combination with low-molecular-weight heparin throughout pregnancy. If thrombophilia was diagnosed on the basis of hyperhomocysteinemia, the treatment consisted of aspirin, pyridoxine and folic acid, instead. RESULTS: Among 250 formerly preeclamptic 131/250 (52%) had a normotensive thrombophilic phenotype. Only 23 (18%) of these 131 participants had an ongoing pregnancy within 1 year. They were allocated to subgroup THROMB. None of the controls had hypertension or thrombophilia. In contrast, 12/15 (80%) controls had an ongoing pregnancy within a year. The observations in the THROMB subgroup were compared with those in the control group. None of the baseline demographic and blood pressure variables differed between THROMB and controls. With respect to pregnancy outcome, the incidence of the following pregnancy complications were observed in THROMB subjects: preterm birth: 9%, pregnancy-induced hypertension: 44%, preeclampsia: 13%, HELLP-syndrome: 13%, and fetal growth restriction: 30%. A low non-pregnant plasma volume was found to predispose for hypertensive complications in a subsequent pregnancy. CONCLUSION: Pre-pregnant plasma volume in normotensive thrombophilic formerly preeclamptic women have predictive value with respect to hypertensive complications in the subsequent pregnancy.

The effect of pregnancy on the compliance of large arteries and veins in healthy parous control subjects and women with a history of preeclampsia.

OBJECTIVE: Early pregnancy is characterized by a fall in total peripheral vascular resistance. In this study we tested the hypothesis that this phenomenon is accompanied by rising compliances of the large arteries and veins. STUDY DESIGN: In 42 women with a history of preeclampsia and 10 healthy parous control subjects we measured the following variables in the midfollicular phase and the midluteal phase during the menstrual cycle and again at 5 and at 7 weeks of amenorrhea: cardiac output, mean arterial pressure, carotid and femoral artery compliances, and venous compliance. The total peripheral vascular resistance was determined as the ratio of mean arterial pressure and cardiac output. After screening for thrombophilia and hypertension, women with a history of preeclampsia were divided into subgroups with hypertension, thrombophilic disorders, and no underlying abnormalities. RESULTS: In parallel with the fall in total peripheral vascular resistance during early pregnancy, femoral artery compliance and venous compliance increased in the control group. Except for venous compliance, these changes were also observed in the women with thrombophilia and a history of preeclampsia. In the subgroups of the women with a history of preeclampsia with hypertension and with no underlying disorder both arterial and venous compliance failed to increase despite a drop in total peripheral vascular resistance. CONCLUSION: These data support the concept that during normal pregnancy the fall in total peripheral vascular resistance is paralleled by improved macrovascular compliance. The latter adaptive change did not occur in women with a history of preeclampsia with hypertension or without an underlying disorder.

Changes in hemodynamic parameters and volume homeostasis with the menstrual cycle among women with a history of preeclampsia.

OBJECTIVE: Among women with a history of preeclampsia the prevalence of hemodynamic and clotting disorders is elevated. In this study we tested the hypothesis that the normal cyclic variation in hemodynamic and renal function parameters with the menstrual cycle that is seen among healthy women would be preserved in women with a history of preeclampsia irrespective of whether they had an underlying hemodynamic or clotting disorder. STUDY DESIGN: We compared the hemodynamic and volume cyclic variations during the menstrual cycle among women with a history of preeclampsia (n = 39) with those among healthy parous control women (control group, n = 10). The participants with a history of preeclampsia were subdivided into groups of women with hypertension with or without thrombophilia (hypertension group, n = 10), women with a normotension and a thrombophilic disorder (thrombophilia group, n = 17), and women without either of these abnormalities (symptom-free group, n = 12). We measured > or =5 months post partum, once during the follicular phase of the menstrual cycle (day 5 +/- 2) and once during the luteal phase (day 22 +/- 2), the following variables: body weight and length, mean arterial pressure, heart rate, cardiac output, plasma volume, glomerular filtration rate, effective renal plasma flow, and concentrations of renal volume homeostatic hormones, reproductive hormones, and catecholamines. From the measured data we calculated body mass index, cardiac index, left ventricular work, total peripheral and renal vascular resistances, effective renal blood flow, and renal filtration fraction. RESULTS: The hypertension group differed from the control group in having higher baseline (follicular phase) values for cardiac output, cardiac output, left ventricular work, renal vascular resistance, and atrial natriuretic peptide and norepinephrine levels. The symptom-free group differed from the control group in having a lower baseline plasma volume and higher baseline cardiac output and left ventricular work values. Women in the thrombophilia group were comparable to those in the control group with respect to baseline hemodynamic and renal function variables except for a higher renal vascular work value. In the control group heart rate, plasma volume, effective renal plasma volume, effective renal blood flow, and concentrations of renin-angiotensin-aldosterone system hormones and norepinephrine were increased during the luteal phase with respect to values during the follicular phase, whereas the renal vascular resistance and atrial natriuretic peptide values were decreased. In the three subgroups of women with a history of preeclampsia this cyclic pattern with the menstrual cycle was preserved for most of these parameters. CONCLUSION: Although baseline hemodynamic and volume status among women with a history of preeclampsia differed from that among healthy parous control subjects, the cyclic variation with the menstrual cycle was largely preserved.

Cardiac output increases independently of basal metabolic rate in early human pregnancy.

Early pregnancy is characterized by the institution of a high-flow low-resistance circulation. In this study, we tested the hypothesis that these hemodynamic changes develop independently of changes in basal metabolic rate. In 12 healthy women, we determined and calculated once during the follicular phase (day 5 +/- 2) and at 6, 8, 10, and 12 wk of pregnancy the following variables: body weight and length, body mass index, fat-free mass (FFM), mean arterial pressure (MAP), heart rate (HR), stroke volume, cardiac output (CO), total peripheral vascular resistance (TPVR), resting energy expenditure (REE), FFM REE (REE(FFM)), and respiratory quotient (RQ). At 6 wk of gestational age, HR and CO had increased, whereas MAP and TPVR had decreased. These changes persisted throughout the study period. Meanwhile, REE, REE(FFM), RQ, FFM, and body weight did not change consistently. The changes with pregnancy in hemodynamics did not correlate with those in basal metabolic rate. In early pregnancy, the institution of a high-flow low-resistance circulation develops without a concomitant rise in basal metabolic rate. These findings support the concept that the hemodynamic changes in early pregnancy develop independently of concomitant changes in basal metabolic rate.

Latent hemodynamic abnormalities in symptom-free women with a history of preeclampsia.

OBJECTIVE: Most women with a pregnancy complicated by preeclampsia have either hypertension or a disorder with a thrombophilic phenotype or both of these. In this study we evaluated whether hemodynamic variables and volume homeostasis in a subgroup of normotensive women with a history of preeclampsia with normal clotting function (defined as the symptom-free subgroup) were comparable with those in a healthy parous control group. STUDY DESIGN: In a group of 58 subjects with a history of preeclampsia and a group of 11 healthy parous control subjects we measured the following variables > or = 5 months post partum at day 5 +/- 2 of the menstrual cycle: body weight and length, mean arterial pressure, heart rate, cardiac output, plasma volume, glomerular filtration rate, effective renal plasma flow, and plasma concentrations of volume regulatory hormones, clotting factors, antiphospholipid antibodies, and homocysteine before and after a methionine load. From the measured data we calculated body mass index, body surface area, cardiac index, left ventricular work, total peripheral and renal vascular resistances, effective renal blood flow, and renal filtration fraction. RESULTS: Among women with a history of preeclampsia 26 were normotensive with thrombophilia (45%), 14 had hypertension (24%), and 18 were normotensive without thrombophilia (31%). These last symptom-free subjects with a history of preeclampsia were more obese than were control subjects. They also had higher cardiac output and left ventricular work and a lower plasma volume than the healthy parous control subjects. Thus they resemble the second subgroup of subjects (subjects with hypertension and a history of preeclampsia) rather than the control subjects. The hemodynamic and renal functions in the subgroup of subjects with a history of preeclampsia with normotension and thrombophilia were similar to those in healthy parous control subjects. CONCLUSION: On the basis of this study we conclude that hemodynamic parameters and volume homeostasis in the symptom-free subgroup of women with a history of preeclampsia are different from those in healthy parous control subjects. Hemodynamic parameters and volume homeostasis in this subgroup resemble those of women with hypertension and a history of preeclampsia. We therefore propose the classification of these symptom-free subjects with a history of preeclampsia as having "latent" hypertension.

Persistent abnormalities in plasma volume and renal hemodynamics in patients with a history of preeclampsia.

OBJECTIVE: The objective was to test the hypothesis that women with a recent history of preeclampsia have abnormalities in renal hemodynamics and volume status. STUDY DESIGN: We studied a group of 26 primiparous women with history of preeclampsia and a group of 12 parous women with a history of uneventful pregnancies (control group). At least 4 months post partum we compared the following variables between these groups: effective renal plasma flow, glomerular filtration rate, plasma volume, plasma concentration of active renin, plasma concentration of angiotensin II, plasma concentration of aldosterone, and plasma concentration of atrial natriuretic peptide. RESULTS: Both plasma volume and plasma concentration of atrial natriuretic peptide were lower in the formerly preeclamptic group. Compared with the control subjects, the formerly preeclamptic group also had a lower effective renal plasma flow, a higher filtration fraction, and a higher renal vascular resistance. Intergroup differences in plasma concentration of active renin, plasma concentration of angiotensin II and plasma concentration of aldosterone were small and inconsistent. CONCLUSIONS: Women with history of preeclampsia are relatively hypovolemic and tend to have lower effective renal plasma flow and higher renal vascular resistance and filtration fraction than do control subjects. These findings support the hypothesis that otherwise healthy women with a history of preeclampsia show abnormalities in their volume status and renal hemodynamics, irrespective of their blood pressure.