Overt Preeclampsia Research Articles

Association of C-reactive Protein in Preeclampsia

Introduction: Preeclampsia is a multisystemic disorder that complicate about 7-10 percent of human pregnancies.Worldwide this syndrome contributes high maternal and perinatal mortality and morbidity. C-reactive protein, a marker of tissue damage and inflammation, is elevated in seurm in overt preeclampsia. It is used as an objective and sensitive index of overall inflammatory activities in the body. Aims and Objectives: To explore the association of C-reactive protein level with the preeclampsia patients. Materials and Methods: The present study was a Case–Control study, conducted in the Department of Obstetrics and Gynaecology in collaboration with the Department of clinical pathology of Sir Salimullah Medical College Hospital, Mitford, Dhaka during the period of January 2013 to December 2013.The study population was pregnant women with preeclampsia and normal term pregnant patients admitted during study period. A total of 66 patients were included in the study. Among them 33 were clinically diagnosed preeclampsia women grouped as Cases and another 33 were age, parity and BMI matched term pregnant women as Controls. Eastmation of serum C-reactive protein was done by Nyco Card Reader-II method (Appendix-11). Statisticians analysis was perform by using SPSS. Results: C-reactive protein concentration (mg/L) was found significantly higher (p<0.001) in case group (17.93±10.5) than control group (7.45±1.80). Creactive protein was _ 6mg/L in 29(87.9%) in case group and 9 (27.3%) in control group and C-reactive protein values showed significant positive correlation with systolic and diastolic blood pressure (p<0.001) in case group. C-reactive protein concentration was found significantly higher (p<0.001) in severe preeclampsia group than mild preeclampsia group. Conclusion: Therefore, it can apparently be concluded from this study that increased maternal serum C-reactive protein level might be a strong risk factor for preeclampsia, although the precise role of C-reactive protein in this regard whether causal or consequential, is yet to be determined. Finding of this study might be helpful for formulating a guideline for management of pregnant women with preeclampsia. Medicine Today 2024, Vol.36 (2): 67-71

Early increase in circulating carbonic anhydrase IX: A potential new predictive biomarker of preeclampsia.

Preeclampsia (PE) is a severe complication of pregnancy. The identification of a reliable predictive biomarker could help in setting up a specific preventive strategy. To this aim, we studied carbonic anhydrase IX (CAIX) as a marker of hypoxia (a pathway involved in PE pathogenesis) and compared the diagnostic accuracy of CAIX to that of the validated biomarker sFlt1/PlGF ratio. Fifteen women with overt PE and 38 women at a risk of developing PE, sampled at different time intervals during gestation (a total of 82 plasma samples collected), were enrolled and underwent the CAIX measurement. CAIX levels significantly increased (p < .001) before the onset of the disease in women (25% of the total number) who later on developed PE when compared to women who did not, starting from 28th gestational week. The best CAIX cut-off of 68.268pg/mL yielded a sensitivity of 100%, a specificity of 81.82%, and an AUC value of .9221. In our pilot study, when compared to the sFlt1/PlGF ratio, CAIX performed better in predicting PE before the clinical onset. Furthermore when implemented as CAIX/PlGF ratio, showed up to be comparable in the identification of women with overt early PE. In conclusion, CAIX could represent an effective predictive biomarker of PE, and larger studies are mandatory to validate this finding.

Association between platelet indices and risk of preeclampsia in pregnant women

We aimed to examine the association between the platelet indices and the risk of preeclampsia (PE) at different gestational weeks (GW) to explore the feasibility of early prediction of PE with these indices. About 7314 normotensive pregnant women and 396 PE patients were included and platelet indices, including platelet count (PC), plateletcrit (PCT), platelet distribution width (PDW), mean platelet volume (MPV) at different gestational weeks (1–12, 13–28, 29–32, 33–36 and 37–41 GW) were compared in two statistical methods. Patients with PE tended to have higher means of PC, PCT, PDW and MPV than normal pregnant women at early stage of pregnancy. The odds of PE were significantly increased with the increase of PC, PCT, PDW and MPV both at 13–28 GW and 29–32 GW, which indicated that increased values of PC, PCT, PDW and MPV at 13-32 GW were associated with greater subsequent risk of preeclampsia. Increased PC, PCT, PDW and MPV may have potential to predict preeclampsia before the disease onset. Impact Statement What is already known on this subject? Previous studies indicated that preeclampsia patients may have decreased platelet count (PC), plateletcrit (PCT) and increased platelet distribution width (PDW) and mean platelet volume (MPV). Increased PDW and MPV or decreased PC/MPV may have predictive values for PE. What do the results of this study add? The discrepancy with previous studies lay in the increased values of PC and PCT in PE patients at early stage of pregnancy. The study indicated that increased PC, PCT, PDW and MPV may have potential to predict preeclampsia far ahead of the disease onset. The results may reflect the abnormal turnover of platelets in PE patients. What are the implications of these findings for clinical practice and/or further research? These findings may help to guide early interventions before progress to overt preeclampsia by predicting onset of preeclampsia via easily available platelet indices in early weeks of gestation, which is especially valuable in areas lacking medical resources. The inconsistency with previous studies can facilitate researchers to further explore the coagulation mechanism beneath preeclampsia and pay more attention to the dynamic changes of platelet indices and other coagulation indices during pregnancy.

Association between Serum C-reactive Protein and Pre-eclampsia

Among the common disorders of pregnancy, Pre-eclampsia is important one which causes significant maternal and perinatal morbidity and mortality. Its incidence is still high in the developing countries. The triad of high blood pressure, edema and albuminuria is neither specific nor sensitive enough; therefore, a reliable biochemical marker is needed to solve the problem. C-reactive protein(CRP), a marker of tissue damage and inflammation, is elevated in serum in overt preeclampsia. The present study is aimed to explore the association of high maternal serum C-reactive protein (CRP) level with preeclampsia and correlation with the severity of pre-eclamptic process. A total of 60 pregnant women constituting 30 pre-eclamptic (case) and 30 normal (control) pregnant women in the third trimester were enrolled in this study. Both the groups were matched for their age, parity and other baseline characteristics. More than three quarters (76.70%) of the case group exhibited raised serum CRP, which was 20% in control group (p=0.001). CRP was elevated about 13 fold higher than that in the normal pregnant women. The mean systolic and diastolic blood pressure were significantly higher in case group (154±12 mm of Hg) vs (107±7 mm of Hg) in control group (p&lt;_0.001) and serum level of CRP bears linear relationship with both systolic and diastolic blood pressures. Preeclamptic women with higher serum CRP level were at a significantly (p&lt;0.001) lower gestational age than control. Twenty two (73.30%) cases had gestational age &lt;37 weeks (p=0.302) and 66.70% control group had gestational age &gt; 37 weeks. The hypothesis of the study was supported by the study findings that maternal CRP concentration was higher in women with preeclampsia and was correlated with disease progression as evidenced by the investigative analysis. Faridpur Med. Coll. J. Jan 2020;15(2): 58-61

The importance of pathological insulin resistance and hyperinsulinemia in the pathogenesis of preeclampsia

Aim : to assess dynamic changes in insulin resistance (IR), hyperinsulinemia (HI) and related parameters of carbohydrate and lipid metabolism, endothelial dysfunction, pro-inflammatory and prothrombotic states in pregnancy complicated with preeclampsia (PE). Materials and Methods . A prospective observational study was conducted consisting of laboratory monitoring 148 high-PE-risk pregnant women comprising Group I - 72 women with overt PE; 36 healthy women with physiological course of pregnancy were included into Group II. All women were assessed level of venous blood glucose, insulin, total cholesterol, high-density lipoproteins (HDL), triglycerides (TG), leptin, placental lactogen, uric acid, tumor necrosis factor-a, C-reactive protein, circulating endothelial cells, fibronectin, nitric oxide metabolites, platelet aggregation at gestational periods 11-14 weeks, 18-21 weeks and 30-34 weeks. We also calculated insulin resistance index, atherogenic coefficient, and TG/HDL ratio, estimating accumulation and distribution of adipose tissue. Results . There were found physiological changes in IR and HI, lipid, endothelial-hemostasis axis, pro-inflammatory, placental parameters supposed to provide proper fetal energy supply during normal pregnancy. During PE, these parameters were aberrantly elevated starting from early pregnancy stage due to failure of gestational adaptation mechanisms, which acquire important pathogenetic significance therein. Conclusion . A holistic view at the mechanisms of forming atherogenic transformation of the lipid profile, endothelial dysfunction, pro-inflammatory and prothrombotic status, oxidative stress, hyperuricemia, visceral type of abdominal wall fat deposition as well as correlation analysis data indicate that all such changes were associated with unified pathogenetic arm consisting of pathological IR and HI serving as early baseline mechanisms in PE development.

Meta-Analysis and Systematic Review to Assess the Role of Soluble FMS-Like Tyrosine Kinase-1 and Placenta Growth Factor Ratio in Prediction of Preeclampsia: The SaPPPhirE Study.

Preeclampsia is a major cause of morbidity and mortality worldwide. Numerous candidate biomarkers have been proposed for diagnosis and prediction of preeclampsia. Measurement of maternal circulating angiogenesis biomarker as the ratio of sFlt-1 (soluble FMS-like tyrosine kinase-1; an antiangiogenic factor)/PlGF (placental growth factor; an angiogenic factor) reflects the antiangiogenic balance that characterizes incipient or overt preeclampsia. The ratio increases before the onset of the disease and thus may help in predicting preeclampsia. We conducted a meta-analysis to explore the predictive accuracy of sFlt-1/PlGF ratio in preeclampsia. We included 15 studies with 534 cases with preeclampsia and 19 587 controls. The ratio has a pooled sensitivity of 80% (95% confidence interval, 0.68-0.88), specificity of 92% (95% confidence interval, 0.87-0.96), positive likelihood ratio of 10.5 (95% confidence interval, 6.2-18.0), and a negative likelihood ratio of 0.22 (95% confidence interval, 0.13-0.35) in predicting preeclampsia in both high- and low-risk patients. Most of the studies have not made a distinction between early- and late-onset disease, and therefore, the analysis for it could not be done. It can prove to be a valuable screening tool for preeclampsia and may also help in decision-making, treatment stratification, and better resource allocation.

БИОМАРКЕРЫ ПРОГНОЗИРОВАНИЯ И ДИАГНОСТИКИ ПРЕЭКЛАМПСИИ

Preeclampsia (PE) is a life-threatening complication of pregnancy associated with a high rate of maternal and perinatal morbidity and/or mortality. This study was aimed at evaluation of total and fetal cell-free DNA (cftDNA and cffDNA) in maternal plasma to assess whether this could represent a reliable predictive marker of early, late PE and whether intrauterine growth restriction (IUGR) as seen in PE is associated with levels of cell-free DNA. Diagnostic criteria for fetal growth retardation are calculated from the results of blood test results obtained in 26-36 weeks of gestation. We performed a PCR assay to compare the cftDNA and cffDNA concentration in maternal plasma among 3 groups of pregnant women. These included 119 women with overt PE (47 - early PE, 72 - late PE), 24 women at risk for the disease who developed PE (8 -early PE, 16 - late PE), and 30 controls. CffDNA quantification is a promising marker for early preeclampsia prediction. Cut-off value of 0,87 ng/ml for cffDNA (87.5 % sensitivity and 66,67 % specificity). Since the increase in cftDNA and cffDNA seems to be related to the presence IUGR in pregnancies which are complicated with early PE. Thus, it suggests that cftDNA and cffDNA could represent a potential biomarker of IUGR among individuals with early PE.

Using critical flicker frequency in the evaluation of visual impairment in preeclamptic women

ObjectiveTo assess critical flicker frequency (CFF) in normal uneventful pregnancy and preeclampsia. Study-designCase-control observational study at the University Hospital Jena and Outpatient Institute for Prenatal Diagnosis and Preventive Medicine. 25 non-pregnant women, 75 uncomplicated pregnant women in first, second and third trimester, and 15 women with overt preeclampsia. For comparison with preeclamptic patients we matched 15 normal pregnant women (mNP) for age, parity, body mass index, current smoking and family history of cardiovascular disease (CVD). We measured CFF using the portable HEPAtonorm Analyzer (nevoLAB GmbH, Germany). This device generates a flickering red light, starting with a frequency of 60Hz, giving the subjective an impression of a steady light. The participant signifies once the impression of a flickering light is recognized, and this CFF is recorded. Mean CFF and standard deviation is automatically calculated. Statistical analysis was performed using SPSS Version 22 for Windows. Following assessment of normal distribution with Kolmogorov-Smirnow test, comparisons were made with univariate and multivariate ANOVA and with unpaired and paired t test for continuous data and with χ2 test for categorical data. ResultsCritical flicker frequency in healthy pregnant women does not differ from nonpregnant women. No significant differences in CFF measurements exist in first, second, and third trimester. In preeclampsia, CFF is significantly decreased compared to normal pregnant women (PE 38.80±2.16 vs. mNP 46.23±3.37; p=0.000). This alteration persists even some weeks postpartum (PE 41.17±1.13 vs. mNP 46.45±3.44; p=0.003). ConclusionIn preeclamptic women, CFF is decreased indicating an altered endothelial situation. The finding that CFF remains reduced postpartum may be explained by either the effect of preeclampsia on maternal endothelium causing longer lasting damage or indicate a preexisting endothelial disorder. Up to this point, precise responsible mechanisms for altered CFF in preeclampsia are currently unclear and further studies are needed.

Circulating levels of natural killer T cells and EPC cells in pre-eclamptic pregnant women

Natural killer T cells are bone marrow origin, they represent about 70% of decidua leukocytes and play an important role in the remodeling of spiral arteries [1]. Endothelial progenitor cells (EPC) are bone-marrow derived cells able to differentiate into endothelial cells [2]. During stress conditions (burns, wounds, coronary artery bypass) a mobilization of these cells from bone-marrow in repairing wounds and during pregnancy occurs [3]. The aim of our study was to evaluate the circulating levels of NK lymphocytes and circulating EPC cells in women with overt preeclampsia. Our study population consists of 39 women in the third trimester of gestation. The patients were divided into two groups: group A with 13 women affected by pre-eclampsia diagnosed according to the criteria established by AIPE 2013 guidelines, and a group B composed of 26 patients with normal pregnancy. Of these women, EPC cells (CD34+) and NK lymphocytes (CD+) circulating were assayed by flow cytometry [4]. A significant difference between groups was observed, either in EPC values (group A: 1.61±0:29 vs group B: 2.42±0.45 cells per μL, p p

Prospective evaluation of RASSF1A cell-free DNA as a biomarker of pre-eclampsia.

This study aims to quantify total and fetal cell-free DNA (cfDNA) in maternal plasma at different gestational ages and to assess whether this could represent a reliable predictive marker of pre-eclampsia (PE) before clinical onset. We performed a qPCR assay to compare the cfDNA concentration of hypermethylated and unmethylated RASSF1A promoter gene sequences in maternal plasma among 3 groups of pregnant women. These included 17 women with overt PE, 33 women at risk for the disease subsequently differentiated into 9 who developed PE and 24 who did not, and 73 controls. All women at risk were consecutively sampled throughout the whole gestation. Both total and fetal cfDNA had a good diagnostic performance in distinguishing patients with overt PE from healthy controls. When comparing women at risk who developed PE to women at risk who did not, the predictive capability was satisfactory at a gestational age ranging from 17 to 30 weeks. This allowed establishing within this time interval a cut-off value of 735GE/ml for total cfDNA (87.5% sensitivity and 70.0% specificity), and a cut-off value of 7.49GE/ml for fetal cfDNA (100% sensitivity and 50% specificity). cfDNA levels turned positive several weeks before the onset of the disease: from 2 to 18 weeks for total cfDNA and from 8 to 17 weeks for fetal cfDNA. The simultaneous use of total and fetal cfDNA would allow an accurate monitoring and prevention of PE development thus suggesting that RASSF1A could represent a potential biomarker of PE.

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Objectives Evidence indicates involvement of endoglin (ENG) and soluble ENG (sENG) in preeclampsia. Circulating sENG concentrations are elevated in women with preeclampsia, even prior to overt clinical manifestations. We previously demonstrated that ENG genetic variation is associated with susceptibility to/protection from preeclampsia in Caucasians. In this study, we investigated if maternal endoglin genotypes contribute to circulating sENG concentrations in women with/without preeclampsia. Methods Genotype data on five ENG tagging single nucleotide polymorphisms (rs10987746, rs10819309, rs10760505, rs11792480, rs10121110) were collected with iPLEX® in women with/without preeclampsia in our previous study. Available maternal plasma samples obtained from n = 102 Caucasian women during clinically evident preeclampsia (cases) were 1:1 frequency matched by gestational age (±3 weeks) to samples from n = 102 healthy Caucasian controls. We used linear regression models, stratified by preeclampsia status, to test the relationship between ENG genotypes and logarithmically transformed sENG concentrations (outcome), while adjusting for gestational age at sampling. Bonferroni correction was used to adjust for multiple comparisons in cases and controls separately (threshold for significance: α Results Median sENG concentrations were significantly higher in women with overt preeclampsia compared to healthy controls (30.4 vs. 8.0 ng/mL, P Conclusions During overt preeclampsia, we were unable to demonstrate that maternal ENG genotypes significantly influence circulating sENG concentrations, suggesting that other pathways may drive late pregnancy sENG elevations. Maternal ENG genetic variation may influence susceptibility to/protection from preeclampsia via other mechanisms in early pregnancy, such as trophoblast invasion/spiral artery remodeling. It is also possible that the effects of ENG genotypes on sENG concentration in overt preeclampsia may be masked by the high concentrations of sENG secondary to other pathophysiological features of the disorder. Disclosures M.J. Schmella: None. J.M. Roberts: None. A.D. Althouse: None. C.A. Hubel: None.

Evaluation of a panel of circulating DNA, RNA and protein potential markers for pathologies of pregnancy

Among markers of pregnancy complications, corticotropin-releasing hormone (CRH) mRNA, long pentraxin 3 (PTX3) protein and fetal and total DNA had been reported to be increased in the plasma of women with overt preeclampsia (PE). We developed an optimized protocol to evaluate whether concentrations of CRH mRNA, PTX3 mRNA and protein, fetal and/or total DNA are increased in fetal growth restriction (FGR), and whether they predict complications of pregnancy. The protocol included a preamplification step to enrich rare mRNA species. CRH and PTX3 mRNA, DNA and PTX3 protein were measured in the plasma of women with PE or FGR, in women at risk of developing these pathologies and in healthy women matched for gestational age. CRH mRNA, fetal and/or total DNA and PTX3 protein were significantly increased in women with overt PE when compared to controls. Pregnant women who later developed PE or FGR during pregnancy showed total DNA levels that were significantly increased before the onset of both pathologies, while RNA markers were increased only in women who later developed PE. Our protocol for plasma RNA quantification may allow for the extension of a panel of predictive markers to be investigated in larger patient cohorts.

Maternal plasma concentrations of the soluble tumor necrosis factor receptor 2 are increased prior to the diagnosis of preeclampsia

Soluble receptor levels of tumor necrosis factor (sTNF-R)-1 and -2 are increased during preeclampsia. We postulated the increase preceded overt disease. Archived plasma from the Eunice Kennedy Shriver National Institute of Child Health and Human Development aspirin to prevent preeclampsia in high risk women trial were used to measure serial sTNF-R1 and sTNF-R2 (enrollment, 24-28 week's gestation) in 986 women (577 also sampled at 34-38 weeks). Preeclampsia incidence was 21.2%. sTNF-R2 levels were higher at enrollment (P = .02) and weeks 24-28 (P = .01) in women who eventually developed preeclampsia. The magnitude of increase from baseline of both receptors was significantly greater in women who developed preeclampsia in the future. Women with week 24-28 sTNF-R2 levels in the highest quartile had significantly increased odds to develop preeclampsia (P = .03 vs quartile 1). This association was observed in the placebo but not the aspirin arm (P <or= .002). Sensitivities and positive predictive values were low. sTNF-R2 levels are elevated prior to overt preeclampsia, suggesting a pathogenetic role for these proinflammatory cytokines.

Murine Pre-Eclampsia Induced by Unspecific Activation of the Immune System Correlates with Alterations in the eNOS and AT1 Receptor Expression in the Kidneys and Placenta

It remains arguable if an animal model can be of use in pre-eclampsia (PE) studies, as it is clearly a human disease not observed spontaneously in other species. The aim of this study was to investigate whether PE-like signs in mice inoculated with activated Th1 cells were accompanied by abnormal expression of molecules related to the regulation of blood pressure, viz. nitric oxide synthase enzymes (eNOS and iNOS) and angiotensin (Ang) II receptors (AT1R and AT2R), in order to analyse the relevance of this model for human disease. In this model, C57/BL6-mated BALB/c females received lymphocytes crosslined with anti-CD3 and cultured with interleukin (IL)-2 and IL-12 to mimic PE pathology. Control mice received PBS. eNOS, iNOS and AT1R but not AT2R expression was augmented in the kidneys of PE-mice compared with control pregnant mice. The expression of eNOS but not of iNOS was augmented at the fetal–maternal interface of PE-mice as compared with the controls. NOSs regulate the synthesis of NO, a blood pressure and parturition mediator. As its expression is increased in PE patients, our data suggest that the Th1 cells-induced signs in this model are due to similar mechanisms as in humans. AT1R and AT2R mediate the effect of Ang II, and particularly the AT1R appears to be involved in the pathogenesis of human PE. The increased AT1R expression in the kidneys of PE-mice reinforces the theory that Th1 cells elicit a pathological situation closely resembling the human PE. All together, our data support the use of this animal model to study mechanisms underlying clinically overt PE.

Blood pressure reduction in pregnancy by sodium chloride

Volume expansion in the presence of elevated aldosterone availability is a hallmark of normal pregnancy. Intravascular volume depletion characterizes severe pregnancy-associated disease conditions such as intra-uterine growth retardation, chronic hypertension or pre-eclampsia [1]. Two hypotheses have been forwarded to explain volume depletion in pregnancy: the first hypothesis charges inappropriate sensing of vascular ‘overfilling’, resulting in an increased transendothelial loss of fluid to the extravascular compartment. In contrast, the second hypothesis focuses on vascular ‘underfilling’ due to inappropriately low aldosterone levels. The second hypothesis is based on the assumption that a compensatory increase in the circulating fluid volume is required in normal pregnancy to support fetal substrate delivery. According to the second concept, maternal blood pressure increases due to counter-regulatory mechanisms when placental blood supply is reduced [2]. In support of the ‘underfilling’ hypothesis are observations that a compromised volume status before pregnancy or a reduced ability to retain sodium by pregnant women predicts a complicated pregnancy outcome. The relevance of intravascular volume expansion during normal pregnancy is also supported by the clinical observation that further reduction of fluids by prescribing either diuretics or salt restriction does not prevent or improve the course of the disease [3]. On the contrary, acute volume expansion in overt pre-eclampsia has been observed to transiently decrease blood pressure [4]. Assuming low aldosterone availability to be the cause rather than the consequence of pre-eclampsia [5], we recently observed an association between a reduced 18-methyl oxidase, the rate limiting enzymatic step of aldosterone synthase (CYP11B2), an increased frequency of polymorphisms in the gene of the same enzyme and pre-eclampsia [6]. Likewise, patients with inborn corticosterone methyl oxidase deficiency are known to decompensate at times of sodium deprivation. Here, we demonstrate for the first time the utility of prescribing supplemental NaCl for a woman with neither the increase in aldosterone production nor the blood pressure drop expected during pregnancy.

Cerebrovascular Hemodynamics in Chronic Hypertensive Pregnant Women Who Later Develop Superimposed Preeclampsia

We have previously shown that normotensive pregnant women who later develop preeclampsia demonstrate lower baseline pulsatility index (PI) and resistance index (RI) but normal vasodilatory responses to stimulation tests. In the current study, we tested the hypothesis that women with chronic hypertension who later developed superimposed preeclampsia behave similarly. Transcranial Doppler ultrasound was performed on 17 women with chronic hypertension during the second trimester of pregnancy to measure middle cerebral artery (MCA) velocities. Superimposed preeclampsia developed in seven patients (SUPER group) while the rest did not develop preeclampsia (CHT group). Measurements were performed in the left lateral position at baseline on room air, during 5% CO2 inhalation, and during a 2-minute isometric handgrip test. Blood pressure, heart rate, O2 saturation, and end-tidal PCO2 were recorded with each Doppler measurement. Mean PI, RI, and cerebral perfusion pressure (CPP) at each time were compared using two-way repeated measures analysis of variance. Statistical significance was set at P < .05. The women who developed superimposed preeclampsia did this an average of 8.7 +/- 1.3 weeks after the study. MCA PI and RI were lower, and CPP higher, in the SUPER group compared to the CHT group (0.64, 0.46, and 80.7 vs 0.74, 0.51, and 63.6, respectively; P < .05). Both maneuvers caused reduction in MCA PI and RI in both groups, whereas CPP increased only in the SUPER group. These findings suggest that women destined to develop preeclampsia have cerebral hemodynamic changes that predate the development of overt preeclampsia.

Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction

Elevated circulating homocysteine is an independent risk factor for cardiovascular disease. Increased homocysteine plasma levels have been reported to occur in approximately 20-30% of women with preeclampsia and it has been suggested that they may predict the subsequent development of preeclampsia. In a cohort of 1874 pregnant women followed longitudinally, who participated in the Down screening program, 27 developed preeclampsia and 36 intrauterine growth restriction (IUGR). A control group of 63 uneventful pregnancies was selected. Plasma homocysteine was assayed in the early second trimester and at delivery in all groups. Data were compared with Wilcoxon's matched-pair test. No statistically significant difference of plasma homocysteine between controls and preeclamptic or IUGR pregnancies in the early second trimester were found. There was a significant difference, only at delivery, between the preeclamptic subjects and the controls. We failed to demonstrate a plasma homocysteine predictive value in pregnancies subsequently complicated by preeclampsia and IUGR. As previously stated, we found that an elevated homocysteine plasma level is associated with overt preeclampsia.

Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction

Background. Elevated circulating homocysteine is an independent risk factor for cardiovascular disease. Increased homocysteine plasma levels have been reported to occur in approximately 20–30% of women with preeclampsia and it has been suggested that they may predict the subsequent development of preeclampsia. Methods. In a cohort of 1874 pregnant women followed longitudinally, who participated in the Down screening program, 27 developed preeclampsia and 36 intrauterine growth restriction (IUGR). A control group of 63 uneventful pregnancies was selected. Plasma homocysteine was assayed in the early second trimester and at delivery in all groups. Data were compared with Wilcoxon's matched-pair test. Results. No statistically significant difference of plasma homocysteine between controls and preeclamptic or IUGR pregnancies in the early second trimester were found. There was a significant difference, only at delivery, between the preeclamptic subjects and the controls. Conclusions. We failed to demonstrate a plasma homocysteine predictive value in pregnancies subsequently complicated by preeclampsia and IUGR. As previously stated, we found that an elevated homocysteine plasma level is associated with overt preeclampsia.

Elevated C-reactive protein levels during first trimester of pregnancy are indicative of preeclampsia and intrauterine growth restriction

C-reactive protein (CRP) is a marker of tissue damage and inflammation. Maternal levels of CRP are elevated in overt preeclampsia, but there is still debate about its use as a predictive marker for preeclampsia during the first and second trimesters of pregnancy. In this study, we measured CRP levels during the first trimester of pregnancy in women who later developed preeclampsia or gave birth to a growth-restricted baby. In total, 107 women from a low-risk population participated in the study, six women developed preeclampsia and nine gave birth to a growth-restricted baby. Although there is a large overlap in measured CRP levels between the three groups, mean CRP levels were significantly elevated in women who later developed preeclampsia ( P=0.031) or delivered a growth-restricted baby ( P=0.041) when compared with women from the control group, matched for maternal and gestational age, parity, and gravidity. This study shows that in a low-risk population, CRP levels are already elevated between weeks 10 and 14 in pregnant women who develop preeclampsia or deliver a growth-restricted baby.

Transcranial doppler measurement of cerebral velocity indices as a predictor of preeclampsia

Objective: We have previously shown that women with preeclampsia demonstrate cerebral hyperperfusion and abnormal cerebrovascular autoregulation. In the current study, we tested the hypothesis that abnormal cerebrovascular function can be detected before the clinical onset of preeclampsia. Study Design: Transcranial Doppler ultrasonography was performed for 166 women in the second trimester of pregnancy to measure peak, end-diastolic, and mean velocities in the middle cerebral arteries. Preeclampsia developed in 10 patients who were initially normotensive. In a nested case-controlled design, each patient with preeclampsia who was initially normotensive was matched for gestational age at the time of initial examination, maternal age, and parity with two pregnant women who remained normotensive and who were delivered at term. All measurements were performed with the subject in the left lateral position at baseline, during 5% carbon dioxide inhalation, and during a 2-minute isometric handgrip test. Blood pressure, heart rate, oxygen saturation, and end-tidal PCO2 were recorded with each Doppler measurement. The mean pulsatility index, resistance index, and cerebral perfusion pressure at each time were calculated and compared. Statistical significance was set at a probability value of <.05. Results: The studies were performed at 19 to 28 weeks of gestation. Preeclampsia developed an average of 13.6 ± 1.0 weeks after the study. Baseline mean blood pressure and heart rate were similar, but middle cerebral arteries pulsatility and resistance indices were lower in the women with preeclampsia who were initially normotensive compared with the pregnant women who were normotensive (0.83 and 0.54 vs 0.73 and 0.50, respectively; P <.05). Both maneuvers caused a significant reduction in the pulsatility and resistance indices. With the use of baseline values as covariates, no significant differences were noted in the response to either carbon dioxide inhalation or handgrip between the group of women who remained normotensive and the group of women with preeclampsia who were initially normotensive. Conclusion: Normotensive pregnant women who later have preeclampsia demonstrate lower baseline pulsatility and resistance indices but normal vasodilatory responses to challenge tests. These findings suggest that women who are destined to have preeclampsia experience cerebral hemodynamic changes that predate the development of overt preeclampsia symptoms. (Am J Obstet Gynecol 2002;187:1667-72.)