Strategies for the prediction of late preeclampsia

Objectives: To evaluate different strategies for the prediction of late preeclampsia.

Methods: A retrospective study was undertaken. A predictive model including maternal parameters (maternal age, maternal BMI, maternal history of preeclampsia or intrauterine growth restriction (PE/IUGR) or maternal chronic disease, and maternal arterial pressure) and mean pulsatility index (PI) of uterine Doppler was created. It was evaluated as an independent model in each trimester, considering 11–13.6 weeks, 20–22.6 weeks and 32–33.6 weeks consequently, and as an integrated model.

Results: In the group of late preeclampsia, patients were more obese and had higher incidence of chronic hypertension. Uterine artery pulsatility index (UtA PI) and mean blood pressure were increased in all three trimesters. When evaluating all three models independently, third trimester model performed better than the other two with a sensitivity of 79% and specificity of 82%. The area under the receiver-operating characteristic (ROC) curve (AUC) was 0.86. The integration of all three determinations did not improve third trimester’s model.

Conclusion: Prediction of late preeclampsia at third trimester seems to be possible if maternal characteristics, blood pressure and UtA Doppler are included.     

Safety of a physical therapy protocol for women with preeclampsia: a randomized controlled feasibility trial

Objective: To assess the feasibility and safety of a physiotherapy protocol applied to pregnant women with preeclampsia. Methods: Randomized, controlled, single-blind feasibility study, with 24 hospitalized pregnant women with preeclampsia. The intervention group received one session of the physiotherapy. The control group remained under the routine care of the hospital. The primary outcomes were Doppler velocimetry, cardiotocography, and maternal–fetal hemodynamics. Secondary outcomes were pain and anxiety assessed before and after the interventions. A mixed effects linear regression model was used, and the data were compared with the level of significance at 5%. Results: The baseline characteristics of the participants were homogeneous between groups. Resistance index of the Middle Cerebral Artery (MAC) and Umbilical Artery (UA) and cardiotocography did not change significantly. The systolic blood pressure (SBP) increased 4.90 mmHg in the control group and 0.22 mmHg in the intervention group. The diastolic blood pressure (DBP) increased 1.34 mmHg in the control group and decreased 0.40 mmHg in the intervention group. The middle bood pressure (MBP) increased 4.66 mmHg in the control group while there was a decrease of 0.09 mmHg in the intervention group, without statistical difference. Heart rate (HR) decreased 0.94 bpm in the control group; whereas, in the intervention group, there was an increase of 6.30 bpm. The pain reduced clinically 2 points after the intervention. The anxiety reduced clinically in both the groups (?1.26 in the intervention group and ?2.17 in the control group). Conclusion: The protocol applied in the intervention group is feasible and safe for both mother and fetus. Both groups showed clinical reduction in the levels of anxiety; whereas, pain was clinically reduced in the intervention group.     

Challenges of studying drugs in pregnancy for off-label indications: Pravastatin for preeclampsia prevention

Statins (3-hydroxy-3 methyl-glutaryl coenzyme-A reductase inhibitors) are the most commonly prescribed cholesterol-lowering medications due to their efficacy in reducing cardiovascular mortality and morbidities, tolerability, and safety profiles. Based on pathophysiologic similarities between cardiovascular disease and preeclampsia, a common and dangerous complication of pregnancy, there is an increasing interest in studying this class of medications during pregnancy to prevent and/or treat preeclampsia. Undergoing such a study, which entails the use of a pregnancy class X medication for an off-label indication in pregnancy, requires intensive multidisciplinary involvement of a group of experts in basic and clinical pharmacology, research methods, pregnancy physiology and maternal–fetal medicine, as well as U.S. Food and Drug Administration (FDA) regulatory guidelines and practice. Issues of potential fetal risk, altered maternal–fetal pharmacokinetics and pharmacodynamics, and regulatory challenges are real, and must be carefully considered in the process of research in this arena.     

Metabolomics and first-trimester prediction of early-onset preeclampsia

Objective: To evaluate the use of metabolomics for the first-trimester detection of maternal metabolic dysfunction and prediction of subsequent development of early-onset preeclampsia (PE). Study design: This was a case-control study of maternal plasma samples collected at 11–13 weeks’ gestation from 30 women who had subsequently developed PE requiring delivery before 34 weeks and 60 unaffected controls. Nuclear magnetic Resonance (NMR) spectroscopy was used to identify and quantify metabolomic changes in cases versus controls. Both genetic computing and standard statistical analyses were performed to predict the development of PE from the metabolite concentrations alone as well as the combination of metabolite concentrations with maternal characteristics and first-trimester uterine artery Doppler pulsatility index (PI). Results: Significant differences between cases and controls were found for 20 metabolites. A combination of four of these metabolites (citrate, glycerol, hydroxyisovalerate, and methionine) appeared highly predictive of PE with an estimated detection rate of 75.9%, at a false-positive rate (FPR) of 4.9%. The predictive performance was improved by the addition of uterine artery Doppler PI and fetal crown-rump length (CRL) and with an estimated detection rate of 82.6%, at a FPR of 1.6%. Conclusion: A profound change in the first-trimester metabolite profile was noted in women who had subsequently developed early-onset PE. Preliminary algorithms appeared highly sensitive for first trimester prediction of early onset PE.     

Etiopathogenesis,prediction, and prevention of preeclampsia

Hypertensive disorders are a major cause of maternal death. Preeclampsia (PE) affects about 5% of pregnancies and is associated to high cardiovascular death risk. Understanding of its origin and cause is difficult and many etiologies have been proposed. So far, little can be done for real prevention and the only treatment is pregnancy interruption, increasing the child’s risk for prematurity complications. Early markers of disease are a promising path for understanding the pathogenesis and developing new strategies for prediction and eventually disease prevention.     

Maternal infection and risk of preeclampsia: systematic review and metaanalysis

There are lingering questions regarding the association between maternal infection and preeclampsia. Systematic review and metaanalysis was conducted of observational studies that examined the relationship between maternal infection and preeclampsia. Forty-nine studies met the inclusion criteria. The risk of preeclampsia was increased in pregnant women with urinary tract infection (pooled odds ratio, 1.57; 95% CI, 1.45-1.70) and periodontal disease (pooled odds ratio, 1.76; 95% CI, 1.43-2.18). There were no associations between preeclampsia and presence of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus, treated and nontreated HIV infection, and malaria. Individual studies did not find a relationship between herpes simplex virus type 2, bacterial vaginosis, and Mycoplasma hominis and preeclampsia. Urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. More studies are required to verify this as well as to explore whether or not such relationships are causal and, if so, the mechanisms involved.     

Combined Doppler ultrasound and platelet indices for prediction of preeclampsia in high-risk pregnancies

Abstract

Objectives: To evaluate Doppler ultrasound and platelet indices for the prediction of preeclampsia (PE).

Design: Prospective observational study.

Methods: The study included 270 normal pregnancy primigravida <20?years at 20–24-week gestation. Doppler ultrasound was done to detect uterine artery diastolic notch and to measure the pulsation index (PI) and the resistance index (RI). The platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW) and platelet large cell ratio (Plcr) was measured by automated blood picture.

Outcome: Validity of combined tests in prediction of PE.

Results: Patients who developed PE had significant higher percentage of diastolic notch, higher mean PI, RI, and significant increase of MPV and PDW than normotensive women (p?<?.001). Patients with abnormal Doppler and abnormal platelet indices had significant higher incidence of severe PE (p?<?.001).

Conclusion: Abnormal platelet indices combined with abnormal Doppler is a predictor of severity rather than the rate of development of PE.     

Identification of patients at risk for preeclampsia with the use of uterine artery Doppler velocimetry and copeptin

Purpose: To investigate the relationship between maternal copeptin levels and uterine artery Doppler examination and progress of preeclampsia.

Materials and methods: A cross-sectional study was designed with women those were screened at 20?+?0 – 24+ 6 weeks’ gestation between May 2014 and August 2014. The obstetric records of all normotensive women were examined. Uterine artery Doppler velocimetry results and serum copeptin levels were measured. The patients were divided into two groups according to normal (n?=?67) and abnormal uterine artery Doppler (n?=?21) findings.

Results: Maternal age was significantly lower in group 1 (n?=?21, 23.9%) than in group 2 (n=?67, 76.1%) (p?p?=?0.002).

Conclusions: Copeptin levels are significantly higher in patients who develop preeclampsia.     

First trimester uterine artery Doppler for the prediction of preeclampsia and foetal growth restriction

Feasibility and reproducibility of uterine artery Doppler (UAD) at 11–14 gestational weeks was recently confirmed. Normal range values were established for resistance and pulsatility indexes. A body of evidence supports that the risk of developing preeclampsia or foetal growth restriction is highest when UAD impedance (evaluated by sus-mentioned indexes or uterine artery notch persistence) remains bilaterally high from first to second trimester, whereas the risk is lowest when UAD impedance is low from 11 to 14 gestational weeks. In unselected women, the sensitivity of 11–14 weeks-UAD is high but the positive predictive value is low, and data do not support its introduction as the sole predictive test. In models using maternal history and 11–14 weeks-UAD, the negative predictive value is high while abnormal UAD may identify a high proportion of women that will develop early-onset preeclampsia. Algorithms combining biochemical markers could still improve this prediction rate at higher cost and complexity.     

Hyperuricemia facilitates the prediction of maternal and perinatal adverse outcome in patients with severe/superimposed preeclampsia

Objective.?Hyperuricemia has received much attention and debate recently with regard to its utility as a marker for preeclampsia and as a predictor of adverse maternal–fetal outcome. This investigation was undertaken in patients with severe/superimposed preeclampsia to determine whether the maternal uric acid (UA) level at initial hospital admission is a useful predictor of subsequent adverse maternal and/or perinatal outcomes.

Methods.?Retrospective analysis of all patients diagnosed with severe preeclampsia, superimposed preeclampsia or HELLP syndrome during 2005 at the University of Mississippi Medical Center (UMMC). Clinical and laboratory data were collected, entered and stored electronically in a password protected, secure system.

Results.?Adverse maternal outcomes occurred in 15.3% of 258 patients in the cohort. Mean UA concentration in the absence of adverse maternal outcomes was 342.6?±?77.3 compared to 396.1?±?117.2?μmol/l in pregnancies with complications (p?<?0.001). The positive likelihood ratio (LR) for adverse maternal outcome was 5.3 with UA?≥?76.3 μmol/l and creatinine ≥1.0 mg/dl. LRs rose in association with other abnormal preeclampsia serum markers. Adverse perinatal outcomes occurred in 45.2% of births. The LRs for adverse perinatal outcomes remained unchanged around 1.0. Mean UA was 363.4?±?91.0 compared to 339.0?±?80.9?μmol/l in pregnancies without adverse outcomes (p?=?0.021).

Conclusions.?Maternal hyperuricemia is a better predictor of maternal than perinatal risk and adverse outcome.     

PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction

Placental growth factor (PlGF) is an angiogenic molecule produced by the placenta and implicated in the pathogenesis of preeclampsia (PE) and intrauterine growth restriction (IUGR). We have evaluated utility and applicability of the PlGF test in a clinical setting of pregnancies at risk of PE or complicated by IUGR in order to assess its relationship with pregnancy outcomes. Seventy-three pregnancies were enrolled between 19 and 35 weeks: 57 pregnancies at risk of PE and 16 at diagnosis of IUGR. Maternal circulating PlGF levels were measured by the Triage PlGF test (Alere, San Diego, CA). Pregnancy outcomes were evaluated in relation to three categories of plasma PlGF levels: very low (<12?pg/ml), low (12–100?pg/ml) and normal (≥100?pg/ml). Uterine artery Doppler velocimetry (UADV) pulsatility index (PI) was measured in the same patients on the day of maternal sampling. Pregnancies at risk with very low plasma PlGF levels had significantly lower gestational age at delivery than patients with low or normal PlGF. The rate of emergency C-section was significantly higher in the group with PlGF?<12?pg/ml. IUGR pregnancies with very low and low PlGF delivered earlier than patients with normal PlGF. All IUGR with very low and low PlGF had UADV PI?>?95th percentile. Our data indicate that PlGF may provide useful information to identify fetuses requiring increased surveillance and possibly urgent delivery in pregnancies at risk of adverse outcomes. Furthermore, in IUGR, PlGF can predict adverse pregnancy outcomes that may be secondary to placental insufficiency.     

孕早中期血清学指标及超声血流监测对子痫前期的预测价值

子痫前期是围产期母儿死亡的重要原因。早期筛选子痫前期发病高危人群,预测疾病进程及不良妊娠结局具有重要的意义。妊娠妇女孕早中期血清学标志物及超声血流等指标在预测子痫前期的发病方面具有重要的应用前景。     

Maternal,fetal and perinatal characteristics of preeclampsia cases with and without abnormalities in uterine artery Doppler indexes

Abstract

Objective: To compare the maternal and fetal characteristics and perinatal outcome in mild and severe preeclampsia cases with and without uterine artery Doppler abnormalities.

Methods: Two hundred and fifty-nine mild and severe preeclampsia cases were evaluated retrospectively. Doppler measurements were done in the section where uterine artery raised from the hypogastric artery. Pulsatility index above the 95th percentile of the corresponding gestational age was accepted as abnormal.

Results: In mild and severe preeclampsia cases with abnormal Doppler (AD), the rate of intrauterine growth restriction, preterm birth and low birth weight was higher than, but the neonatal intensive care unit stay was similar to the cases with normal Doppler. Base excess was higher in the AD group, in mild and severe preeclampsia. The rate of low Apgar score at 5?min and perinatal mortality was higher in the AD group, in the mild preeclampsia. The strongest independent predictor of the perinatal morbidity and mortality was the presence of prematurity and of the prematurity was the presence of abnormal uterine artery Doppler.

Conclusions: Maternal and perinatal morbidity and perinatal mortality increase in mild to severe preeclampsia cases with abnormal uterine artery Doppler. The abnormal uterine artery Doppler increases the morbidity and mortality by increasing the risk of prematurity.     

硝苯地平联合拉贝洛尔治疗对子痫前期患者脐动脉S/D值、胎儿血流动力学的影响#br#

Objective?To analyze the effects of nifedipine combined with labetalol in the treatment of preeclampsia (PE). Methods?110 patients with PE in Ma'anshan Maternal and Child Health Hospital were selected, and randomly divided into control group (54 cases, treated with magnesium sulfate and nifedipine) and observation group (56 cases, treated with labetalol based on the treatment of control group). Clinical effects and fetal hemodynamic parameters were compared between the two groups. Maternal and neonatal outcomes, and adverse reactions were recorded. Results?The total response rate in observation group was higher than that in the control group (P<0.05). After treatment, the 24-hour mean systolic blood pressure, 24-hour mean diastolic blood pressure, 24-hour mean arterial pressure, umbilical artery S/D value, arterial pulsatility index (PI) and arterial blood flow resistance index (RI) of observation group were lower than those of the control group (P<0.05). The incidences of adverse pregnancy outcomes and neonatal outcomes in observation group were lower than those in the control group, and 5 min Apgar score was higher (P<0.05). The incidence rates of adverse reactions were similar in the two groups (P>0.05). Conclusion?Nifedipine combined with labetalol in the treatment of PE can significantly improve the hemodynamic indexes of umbilical artery, which is beneficial to ensure good maternal and infant outcomes.     

Maternal/fetal eNOS-Glu298Asp genotypes and their influence on the severity,prognosis, and lipid profile of preeclampsia

Objectives: To analyze the contribution of maternal eNOS-Glu298Asp genotypes and also the association with fetal genotypes to the development of preeclampsia, prognosis, and maternal dyslipidemia.

Methods: Sixty-nine pairs of preeclamptic mothers/newborns and 94 pairs of normotensive mothers/newborns were genotyped for eNOS-Glu298Asp using PCR-RFLP methods.

Results: Women carriers of at least one Asp298 allele had a 1.53-fold (p?=?NS), 1.88-fold (p?=?NS), and 2.08-fold (p?=?.05), respectively, increased risk to develop PIH, mild, or severe preeclampsia. If both the mother and the newborn were carriers of the Asp298 allele, the risk for preeclampsia was 5.09-fold higher (p?p?=?.02) and LDL (mg/dl, 194.9?±?42.8 versus 144.98?±?54.84, p?=?.04) levels and lower HDL levels (mg/dl, 32.12?±?5.48 versus 57.84?±?20.59, p?=?.02) compared to noncarriers. Also, higher LDL levels (mg/dl, 188.76?±?46.61 versus 136.75?±?41.85, p?=?.03) and lower HDL levels (mg/dl, 32.8?±?5.64 versus 61.06?±?22.45, p?=?.02) were found in preeclamptic women with severe preeclampsia whose newborns were carriers of the Asp298 allele.

Conclusions: The eNOS-Glu298Asp variant (in mothers and newborns) in association with dyslipidemia could affect bioavailability of NO and could represent an increased risk for preeclampsia.     

Serum VEGF and PGF may be significant markers in prediction of severity of preeclampsia

Objective: The aim of this study evaluate the value of vascular endothelial growth factor (VEGF) and placental growth factor (PGF) serum levels in prediction of preeclampsia, severity and onset time of the disease.

Methods: Twenty five placentas of pregnant women diagnosed with preeclampsia (15 severe preeclampsia, 10 mild preeclampsia) and peripheral venous blood samples were collected. The placental and serum levels of VEGF and PGF were measured.

Results: VEGF level was significantly higher in cases and the optimal cut-off point was calculated as 600.5 to differentiate the cases and the controls, with 64% sensitivity and 100% specificity. There was a significant increase in median serum level of VEGF in severe cases compared to the mild cases and the controls. The optimal cut-off point for VEGF was calculated as 673.5 to differentiate mild and severe cases, with 93.3% sensitivity and 90% specificity. Whereas, PGF was significantly lower in severe cases than that in the mild cases and controls. The optimal cut-off point for PGF was calculated as 16.1 to differentiate mild and severe cases, with 66.7% sensitivity and 100% specificity.

Conclusion: VEGF and PGF may be significant markers in prediction of severity of preeclampsia, and VEGF may also be valuable in prediction of preeclampsia.