Early-Pregnancy Circulating Antioxidant Capacity and Hemodynamic Adaptation in Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIMS: Placental syndromes (PS) refer to pregnancy complications that include gestational hypertension, (pre)eclampsia, HELLP syndrome, and/or placental insufficiency-induced fetal growth restriction. These disorders are characterized by increased oxidative stress. This study aims to test the hypothesis that the abnormal hemodynamic adaptation to pregnancy, typical for early PS pregnancy, is accompanied by abnormal maternal levels of antioxidants relative to those in normal pregnancy. METHODS: Before, and at 12, 16, and 20 weeks pregnancy, we measured trolox equivalent antioxidant capacity (TEAC), uric acid (UA), and TEACC (TEAC corrected for UA) in maternal serum of former PS patients, who either developed recurrent PS (rPS; n = 16) or had a normal next pregnancy (non-rPS; n = 23). Concomitantly, we also measured various hemodynamic variables. RESULTS: rPS differed from non-rPS by higher TEACC levels before pregnancy (178 vs. 152 µM; p = 0.02) and at 20 weeks pregnancy (180 vs. 160 µM; p = 0.04). Only non-rPS responded to pregnancy by significant rises in hemodynamic measures. CONCLUSION: These data indicate that rPS pregnancies are preceded by an increase in antioxidant capacity, presumably induced by subclinical vascular injury and low-grade chronic inflammation.

Circulating Fibronectin and Plasminogen Activator Inhibitor-2 Levels as Possible Predictors of Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIM: Placental syndromes (PS) are characterized by endothelial dysfunction complicating placental dysfunction. Possible markers for endothelial dysfunction and amount of trophoblast are fibronectin and plasminogen activator inhibitor-2 (PAI-2), respectively. We aimed (1) to determine whether in women with recurrent PS (rPS), this complication is preceded by deviating fibronectin- and PAI-2-levels, and (2) whether this is dependent on pre-pregnant plasma volume (PV). METHODS: In 36 former patients, we determined fibronectin- and PAI-2-levels in blood-samples collected preconceptionally and at 12-16 weeks in their next pregnancy. Differences were analyzed between pregnancies with rPS (n = 12) and without rPS (non-rPS, n = 24) using linear mixed models, with subanalyses based on pre-pregnant normal or subnormal PV. RESULTS: We observed higher fibronectin-levels at 12-16 weeks (p < 0.05 and p < 0.01, respectively) and lower PAI-2-levels at 16 weeks (p < 0.01) in the rPS subgroup, the intergroup differences being larger in women with subnormal PV. CONCLUSION: We showed that former PS patients who developed rPS have raised fibronectin- and reduced PAI-2-levels already in early/mid pregnancy. These deviations are even more prominent in women with subnormal pre-pregnant PV, supporting development of a 2-step screening program for former patients to identify the high-risk subgroup of women who may benefit from closer surveillance.

Renal function after preeclampsia: a longitudinal pilot study.

BACKGROUND: Women with a history of preeclampsia are at increased risk to develop end-stage renal disease. In this longitudinal study, we evaluated renal function in women with a history of severe preeclampsia and parous controls over a period of 14 years. METHODS: Renal function was measured 1 and then 14 years postpartum by para-aminohippurate and inulin clearances in 20 women with a history of severe preeclampsia and 8 parous controls. RESULTS: The difference in glomerular filtration rate 1 year postpartum between women with a history of preeclampsia and parous controls (112 ± 10 and 125 ± 8 ml/min/1.73 m(2), p < 0.01) had disappeared 14 years postpartum (104 ± 10 and 109 ± 13 ml/min/1.73 m(2), p = 0.37). There was a consistent trend for a lower effective renal plasma flow both 1 and 14 years postpartum (477 ± 90 and 543 ± 92, p = 0.09 and 473 ± 85 and 543 ± 98 ml/min/1.73 m(2), p = 0.07). CONCLUSIONS: This explorative study suggests no accelerated renal function loss in the first decade after preeclampsia.

Platelet monitoring follow-up in a pregnant patient with HELLP syndrome.

Monitoring the course of platelet function in HELLP (haemolysis, elevated liver-enzymes and low platelets) syndrome is important for clinical decision-making. We present a primigravid woman developing HELLP syndrome at 29 weeks and 6 days. Platelet function was monitored by multiple electrode aggregometry (MEA), platelet function analyzer (PFA-100®), platelet count and mean platelet volume (MPV) over an 11-day period. MPV and PFA-100® seem better predictors for platelet function than platelet levels.

Insulin resistance relates to microvascular reactivity 23 years after preeclampsia.

Preeclampsia, an endothelial disorder of pregnancy, is associated with an increased risk on cardiovascular diseases. Cardiovascular risk factors may mediate vascular dysfunction both during pregnancy but also later in life. This study aims to investigate microvascular reactivity, and its relationship with several cardiovascular risk factors, in women with a history of preeclampsia and controls. In this cross-sectional study we compared women with a history of preeclampsia (PE, n=22) with women with uneventful pregnancies only (CON, n=29) 23 years after their first delivery. Participants were matched for BMI, age and date of delivery. We assessed blood concentrations of fasting glucose, HbA1c, insulin, (total, HDL-, LDL-) cholesterol, triglycerides and CRP. Endothelial function was assessed by measurement of skin microcirculatory blood flow by Laser Doppler flowmetry at the dorsal and ventral site of the finger during post-occlusive reactive hyperemia (PORH). PE had higher fasting insulin levels and HOMA-IR compared with CON. The PORH response was similar in both groups. The area under the curve of PORH correlated with insulin and HOMA-IR at both sites, with BMI, triglycerides at the dorsal site and with CRP at the ventral site of the finger in PE and not in CON. In conclusion, 23 years after pregnancy we did not observe a difference in the microvascular hyperemic response between women with a history of preeclampsia and controls. Meanwhile, the results of our study suggest that insulin resistance and other cardiovascular risk factors are related to microvascular reactivity in middle-aged women with a history of preeclampsia.

Reduced renal function after preeclampsia does not result from accelerated age-dependent renal function loss.

Preeclampsia is associated with later kidney disease. This study tested the hypothesis that the normal decline in renal function with age is more rapid in formerly preeclamptic women than in controls. Four groups were compared cross-sectionally: young women with a history of preeclampsia (n = 34), young controls (n = 12), middle-aged women with a history of preeclampsia (n = 22) and middle-aged controls (n = 29). We measured blood pressure (semi-automatic device), effective renal plasma flow (ERPF, para-aminohippurate clearance), glomerular filtration rate (GFR, creatinine clearance) and cardiac output (Doppler echocardiography). ERPF was lower in both young and middle-aged women with a history of preeclampsia relative to controls. The decrease in both GFR and ERPF with age was comparable in both groups. In conclusion, the lower renal function in middle-aged formerly preeclamptic women does not result from accelerated age-dependent renal function loss, but from an already reduced renal function relative to parous controls at young age.

Remote hemodynamics and renal function in formerly preeclamptic women.

OBJECTIVE: Women with a history of preeclampsia have an increased risk of developing chronic hypertension and cardiovascular disease. However, little is known about the mechanism responsible for vascular disease in formerly preeclamptic women. The aim of our study was to test whether preeclampsia predisposes to central hemodynamic and renal impairments 20 years after pregnancy. METHODS: In this cross-sectional study, 22 formerly preeclamptic women and 29 parous controls participated, matched for body mass index, age, and date of birth. All women delivered in the period of 1979-1987. Measures included automated blood pressure, Doppler echocardiography, microalbuminuria, paraaminohippurate, and creatinine clearances. Hypertension was defined as blood pressure at or above 140/90 mm Hg, using antihypertensive drugs, or both. RESULTS: Hypertension was present in 55% of the formerly preeclamptic women and 7% of the women in the control group (P<.01). Mean arterial pressure was higher in the formerly preeclamptic women compared with those in the control group (100 and 88 mm Hg, respectively, P<.01). Peripheral vascular resistance was about 20% higher, renal vascular resistance about 30% higher, and renal blood flow about 15% lower in the formerly preeclamptic women compared with those in the control group (P<.05). Similar results were observed after stratification for hypertension in both groups. CONCLUSION: Both normotensive and hypertensive middle-aged, formerly preeclamptic women showed impaired central hemodynamic and renal function compared with parous controls. LEVEL OF EVIDENCE: II.

First trimester placental vascularization and angiogenetic factors are associated with adverse pregnancy outcome.

BACKGROUND: Hypertensive disorders, fetal growth restriction and preterm birth are major obstetrical complications and are related to impaired placentation. Early identification of impaired placentation can advance clinical care by preventing or postpone adverse pregnancy outcome. OBJECTIVES: Determine whether sonographic assessed placental vascular development and concomitant changes in inflammation- and/or angiogenesis-related serumproteins differ in the first trimester between uncomplicated pregnancies and pregnancies with adverse outcome. STUDY DESIGN: This prospective longitudinal study defines adverse pregnancy outcome as conditions associated with impaired placentation; fetal growth restriction, hypertensive disorder, preterm birth and placental abruption. The vascularization index, flow index, vascularization flow index and placental volume were determined at 8, 10 and 12 weeks pregnancy from 64 women using 3D power Doppler. Serum levels were analyzed for Angiopoetin-1 and -2, Leptin, VEGF-R, VEGF, and EGF. RESULTS: The vascularization index and vascular flow index increased in uneventful pregnancies with almost 50% between 8 and 12 weeks, resulting in a ∼50% higher vascularization index at 12 weeks compared to women with an adverse pregnancy outcome. Women with an adverse pregnancy outcome (n = 13) had significantly lower indices and placental volumes at all time points measured and these indices did not increase between 8 and 12 weeks. Reduced vascular development was associated with increased Angiopoietin-1 levels at 8 and 12 weeks and increased Leptin levels at 8 weeks. CONCLUSIONS: Pregnancies with an adverse outcome caused by conditions associated with impaired placentation differ from uneventful pregnancies in having reduced placental vascularization accompanied by elevated circulating levels of Angiopoietin-1 and Leptin already in the first trimester.

Configuration of the microcirculation in pre-eclampsia: possible role of the venular system.

OBJECTIVE: To test the hypothesis that during pre-eclampsia microvascular function and structure are disturbed, which contributes to raised venular resistance. METHODS: The microcirculation of the skin and bulbar conjunctiva was studied in 11 women with preeclampsia and nine parous controls, both in the third trimester and 3 months postpartum. Using intravital videomicroscopy, arteriolar and venular diameters were determined in the conjunctiva. In addition, skin capillary densities and morphology were determined. RESULTS: Conjunctival venular diameters were 30% smaller in pre-eclampsia compared with controls, both during pregnancy (P < 0.01) and postpartum (P = 0.045). Arteriolar diameters also tended to be smaller; however, this difference was not statistically significant. In women with pre-eclampsia we found a higher percentage of tortuous/dilated skin capillaries (5%) compared with controls (0%; P < 0.05). Three months postpartum, this difference had disappeared. Skin capillary densities did not differ between the groups. CONCLUSION: Women with severe pre-eclampsia have narrow venules, both during manifest disease and postpartum. Possibly, these narrow venules raise venular resistance and with it, hydrostatic pressure in the capillary bed. The latter, in turn, may explain the higher number of tortuous/dilated capillaries in women with preeclampsia. These findings support an important role of the venous system in the pathogenesis of pre-eclampsia.

Subclinical signs of vascular damage relate to enhanced platelet responsiveness among nonpregnant formerly preeclamptic women.

OBJECTIVE: In nonpregnant formerly preeclamptic women, the prevalence of occult cardiovascular abnormalities is increased. These high-risk women mildly benefit from low-dose aspirin in the prevention of recurrent disease. How this effect is mediated, either by affecting platelet or vascular function, is still unsettled. In this study, we tested the hypothesis that in these nonpregnant women, enhanced platelet responsiveness is common and related to microvascular damage. STUDY DESIGN: At least 6 months' postpartum we evaluated in 66 formerly preeclamptic women platelet count, volume, and in vitro response to low-dose ADP (0.5 microg/mL). Peripheral levels of fibronectin (microg/mL), von Willebrand factor antigen (%), C-reactive protein (high-sensitive CRP, mg/L), urinary albumin, and protein (24-hour collection, g/mol creatinine) served as markers of vascular damage. Hemodynamic function was determined by plasma volume (iodine I 125 HSA indicator dilution method, mL/kg lean body mass), cardiac index (Doppler, mL/min/m2), blood pressure and heart rate (Dinamap [Critikon, Tampa, FL], mm Hg and beats/min, respectively). Thereafter, we subdivided these 66 women into 2 subgroups either with (n = 10, 15%) or without increased platelet responsiveness (n = 56, 85%). Both groups were compared nonparametrically. RESULTS: Groups were comparable with respect to age, blood pressure, body mass index, parity, plasma volume, and cardiac index. Women with enhanced platelet responsiveness had higher levels of circulation fibronectin and CRP, and displayed more often albuminuria and proteinuria. In addition, even though platelet count was comparable between groups, the mean platelet volume was higher among women with enhanced platelet responsiveness. CONCLUSION: Fifteen percent of formerly preeclamptic women had enhanced platelet responsiveness, which was associated with elevated levels of various markers for (micro) vascular damage. We speculate that in these women platelets are presensitized on a relatively dysfunctional endothelium. Although this association does not prove causality, these results may indicate a subgroup of women who benefit from low-dose aspirin in the prevention of recurrent disease in a next pregnancy.

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

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.

Vascular expression of adrenomedullin is increased in Wistar rats during early pregnancy.

OBJECTIVE: Circulating levels of adrenomedullin (ADM)--a vasodilator peptide with long-lasting effects--increase in the course of pregnancy. Neither the site nor the concomitant rate of ADM synthesis in pregnancy is known. The aim of this study was to test the hypothesis that the rise in plasma levels of ADM during pregnancy is paralleled by increased gene expression and protein levels in the vascular bed. STUDY DESIGN: We determined in cardiovascular and reproductive tissues of non-pregnant (n=10) and 10-days pregnant (n=10) Wistar rats ADM gene expression by semi-quantitative RT-PCR (normalized to GAPDH). As a support for the mRNA data, protein concentrations were measured by both ELISA and Western blot analysis. Finally, ADM in these tissues was localized by immunohistochemical staining. Statistical analysis was carried out by applying Mann-Whitney U-test. RESULTS: ADM mRNA levels in the abdominal aorta, renal artery and the kidney were increased during pregnancy. In addition, immunohistochemical staining in the kidney, uterus, abdominal aorta, renal, uterine and superior mesenteric artery was more intense as compared to non-pregnant rats. However, we observed lower concentrations of tissue ADM protein in pregnant rats, indicating an increased release of the hormone by the producing cells. CONCLUSION: Vascular ADM gene expression is increased in the first half of rat pregnancy. This coincides and may be functionally related to the institution of a high flow/low resistance circulation in pregnancy.

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

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.

Aging blunts remodeling of the uterine artery during murine pregnancy.

OBJECTIVE: The progressive increase in uterine blood flow (UBF) during pregnancy is accommodated by morphologic changes in the uterine artery (UA) in a process defined as arterial remodeling. This process is accompanied by changes in cytoskeletal architecture of the arterial smooth muscle cells (SMCs) and surrounding extracellular matrix (ECM). Aging reduces flow-induced arterial remodeling. We studied changes in the murine UA during pregnancy and on the effects of aging on the capacity of the UA to remodel in response to pregnancy. METHODS: We determined morphologic and cytologic changes in UA from nonpregnant and pregnant mice aged 12 weeks (young) and 40 weeks (old) and correlated them with their reproductive performance. RESULTS: In young mice, pregnancy induced an early increase in UA wall mass, which preceded lumen widening. These changes were not accompanied by altered densities of elastin and collagen in the ECM of the medial layer. Smooth muscle cell proliferation increased in midpregnancy and was paralleled by a transient decrease in smoothelin and smooth muscle alpha-actin expression. In old mice, these pregnancy-dependent changes in the UA wall were either absent or markedly reduced. Although by day 11 of pregnancy litter size did not differ between both age groups, the number of viable pups in old mice by day 17 of pregnancy and at birth was 25% and 60% less than in young mice. CONCLUSION: Outward hypertrophic remodeling of the UA during pregnancy in young mice is characterized by transient phenotypic modulation and proliferation of SMCs and alterations in the composition of the ECM. In contrast, in older mice, UA remodeling is markedly reduced and accompanied with a loss of viable fetuses near term pregnancy.

Posttraumatic stress disorder after pre-eclampsia: an exploratory study.

Information about the psychological sequelae of pre-eclampsia (PE) is scarce. Post-traumatic stress disorder (PTSD) may develop after exposure to a stress condition. This study explored whether PE predisposes to PTSD in patients and their partners. Primiparas with a recent history of preterm PE (n=18), preterm birth (PT; n=29), term PE (n=23), or uneventful term birth (C; n=43), and most of their partners completed questionnaires measuring PTSD, depression and related psychological factors. About one-fourth of patients developed PTSD after preterm PE as well as after PT. It occurred in 17% after term PE and in none of the control subjects. A substantial minority of partners was also affected. PTSD symptoms were strongly related to individual psychological characteristics (peritraumatic dissociation, negative interpretations of symptoms, and thought suppression) rather than to objective indicators of condition-severity. The data suggest that PE predisposes to PTSD, primarily but not exclusively resulting from concomitant preterm birth.

Age-related alterations in cardiac geometry in formerly preeclamptic women and healthy parous controls: an explorative study.

INTRODUCTION: Preeclamptic pregnancies induce concentric left ventricular hypertrophy instead of eccentric left ventricular hypertrophy as seen in healthy pregnancies. Although these differences persist for at least several months postpartum, the long-term fate of these changes is unknown. OBJECTIVE: To explore the age-related changes in cardiovascular structure and function in formerly preeclamptic women relative to parous controls. METHODS: A total of 20 formerly preeclamptic women and 8 parous controls underwent 2 echocardiograms at 1 and 14 years of postpartum. With the nonparametric Mann-Whitney U test and the Wilcoxon Signed Ranks test, we analyzed the between-group differences in cardiac structure and function at both time points and the time-related changes in these indices. RESULTS: Left ventricular geometry and dimensions and systolic function were comparable in the 2 study groups at both time points. The age-related decline in E/A ratio and increase in intraventricular septum thickness were noted in both groups over time, without appreciable differences between groups. CONCLUSION: A history of preeclampsia does not affect the age-related cardiac remodeling over a period of 14 years.

Metabolic syndrome as a risk factor for hypertension after preeclampsia.

OBJECTIVE: To identify metabolic and obstetric risk factors associated with hypertension after preeclampsia. METHODS: We analyzed demographic and clinical data from a postpartum screening (blood pressure, microalbuminuria and fasting plasma levels of glucose, insulin, and lipid profile) from 683 primiparous women with a history of preeclampsia. We excluded women with pre-existing hypertension, kidney disease, or diabetes mellitus. In the group of women who were normotensive at postpartum screening, we evaluated the risk of developing chronic hypertension in the years after screening using questionnaires. RESULTS: Hypertension at postpartum screening (n=107, 17% of all cases) was related to obesity (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.2), elevated fasting levels of insulin (OR 1.7, 95% CI 1.0-2.9), low-density lipoprotein (OR 1.6, 95% CI 1.1-2.6), microalbuminuria (OR 2.3, 95%-CI 1.3-4.0), family history of hypertension (OR 1.8, 95% CI 1.1-2.8), and delivery before 34 weeks of gestation (OR 2.5, 95% CI 1.6-4.0). We identified 27 cases of hypertension within 2,095 person-years during a median 6-year follow-up in the group of women normotensive at postpartum screening. The hazard rate for the development of hypertension was 2.9 (95% CI 1.2-7.5) and 8.1 (95% CI 2.8-22.9), respectively, when two and three or more components of the metabolic syndrome were present; 3.7 (95% CI 1.4-10.0) for family history of hypertension; and 4.3 (95% CI 1.6-11.5) for recurrence of a hypertensive disorder in pregnancy. CONCLUSION: Several metabolic and obstetric risk factors related to hypertension postpartum in the short term and predisposed to the subsequent development of chronic hypertension after preeclampsia in initially normotensive women. LEVEL OF EVIDENCE: III.

Early-onset preeclampsia and the prevalence of postpartum metabolic syndrome.

OBJECTIVE: To determine the prevalence of the metabolic syndrome postpartum in women with a history of pregnancy complicated by early-onset vascular disorders compared with women with late-onset disorders. METHODS: In this retrospective cohort study 849 women with a history of pregnancy complicated by vascular disorders (preeclampsia; gestational hypertension; hemolysis, elevated liver enzymes, low platelets syndrome; eclampsia; placental abruption; fetal growth restriction; and stillbirth as a result of placental insufficiency) were divided into early-onset (delivery before 32 weeks of gestation, n=376) and late-onset (delivery at or beyond 32 weeks, n=473). By use of four internationally accepted criteria to diagnose metabolic syndrome, we compared its prevalence in both groups using odds ratios (ORs), adjusted for maternal age, smoking, alcohol and coffee consumption, birth weight centile, stillbirth, and interval between delivery and measurements. RESULTS: The metabolic syndrome was present in 15-25% of women after early-onset vascular-complicated pregnancy and in 10-14% of women after late-onset disease, depending on the criteria set used; adjusted OR 2.51 (95% confidence interval [CI] 1.66-3.80) using World Health Organization criteria; adjusted OR 2.01 (95% CI 1.37-2.96) using International Diabetes Federation criteria; adjusted OR 2.16 (95% CI 1.31-3.55) using Third Adult Treatment Panel (ATPIII) criteria; and adjusted OR 2.02 (95% CI 1.28-3.17) using Third Adult Treatment Panel updated criteria. CONCLUSION: The prevalence of the metabolic syndrome postpartum is twice as high in women with a history of early-onset (delivery before 32 weeks) compared to late-onset vascular-complicated pregnancy (delivery at or beyond 32 weeks). LEVEL OF EVIDENCE: II.

Simple prepregnant prediction rule for recurrent early-onset hypertensive disease in pregnancy.

OBJECTIVE: We aimed to develop a simple clinically useful prediction rule for early-onset recurrent preeclampsia and/or HELLP syndrome. METHODS: Women with previous early-onset preeclampsia and/or HELLP, enrolled between 1996 and 2007, and a subsequent ongoing pregnancy were included. Prepregnant cardiovascular, metabolic, renal, and clotting parameters were evaluated as potential predictors for recurrent disease by logistic regression analysis. RESULTS: Early-onset preeclampsia and/or HELLP recurred in 16 (9%) of 186 next pregnancies. The prediction model included high-density lipoprotein (mmol/L) and 24-hour urinary total protein excretion (mg/mmol creatinine). The receiver operating characteristic area was 0.77 (95% confidence interval: 0.68-0.87). Predictive sensitivity and specificity were 94% (69%-99%) and 53% (45%-60%), respectively. Nearly 50% of the women could be classified as having <1% risk of recurrent early-onset disease. CONCLUSIONS: The prediction rule identified, with clinically relevant predictive capacity, those women at very low risk for recurrent early-onset disease.