Hyperhomocysteinaemia: a risk factor for preeclampsia?

Preeclampsia represents one of the most frequent complications of pregnancy, however, little is known about its aetiology. Damage of the endothelial layer lining the blood vessel wall is thought to play an important role in the pathophysiology of preeclampsia, accordingly, mild hyperhomocysteinaemia has been reported to be more prevalent among preeclamptic women. Therefore, we investigated the role of hyperhomocysteinaemia in preeclampsia by measuring plasma levels of homocysteine and studying the prevalence of the 677(C-->T) polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which may lead to reduced MTHFR enzyme activity and subsequently to higher plasma homocysteine levels.Plasma samples of 10 healthy non-pregnant women, 10 normotensive pregnant women, and 20 women with preeclampsia were analysed for total homocysteine levels by high performance liquid chromatography. Furthermore, 167 Dutch non-pregnant women previously hospitalised for preeclampsia and 403 population-based controls were analysed for the 677(C-->T) polymorphism by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR/RFLP).In normotensive pregnancy homocysteine levels were lower compared with levels in healthy non-pregnant controls (8.4 versus 13.7micromol/l, P<0.001). Women with preeclampsia showed higher concentrations than women during normotensive pregnancy (13.3 versus 8.4micromol/l, P<0.02). However, levels of homocysteine in preeclampsia were comparable to those found in healthy non-pregnant women. PCR/RFLP showed no significant difference in the incidence of the 677(C-->T) polymorphism in the MTHFR gene between preeclamptic women with or without HELLP syndrome and controls (13 and 9% homozygous for the less common T-allele, respectively; OR 1.5, 95% CI 0.8-2.6, P=0.17).In contrast with previous reports, we cannot confirm that mild hyperhomocysteinaemia is a risk factor for preeclampsia. Pregnancy induced hyperhomocysteinaemia found in preeclampsia might better be explained by fluctuations in plasma volume than by the presence of the 677(C-->T) polymorphism in the MTHFR gene.     

Is vitamin E a safe prophylaxis for preeclampsia?

The prophylactic use of vitamins E and C for the prevention of preeclampsia is currently being evaluated in multiple clinical trials in Canada, Mexico, the United Kingdom, the United States, and other developing countries. In addition to its antioxidant capacity, exogenous vitamin E may prevent an immunologic switch (Th1 to Th2) that is vital for early-to late transition in normal pregnancies. Moreover, vitamin E could be a potential interferon-gamma (IFN-gamma) mimic facilitating persistent proinflammatory reactions at the fetal-maternal interface. These untoward effects of dietary intake of vitamin E may be more pronounced in those treated cases that fail to develop preeclampsia. A critical test of this hypothesis would be to establish whether, under variable O2 tension, vitamin E is capable of affecting cytokine signaling in placental trophoblasts and maternal immune effector cells, both in early and late human pregnancies.     

Do double-stranded RNA receptors play a role in preeclampsia?

Dysregulation of the maternal immune system during pregnancy has been implicated in the development of preeclampsia (PE), however the pathogenetic signals and mechanisms have not been completely elucidated. Here we provide a hypothesis and evidence that dsRNA is a danger signal leading to maternal immune system activation and an “antiviral” immune response that manifests as PE. dsRNA released from necrotic cells and/or from viruses causes excessive activation of dsRNA receptors and PE-like symptoms in animals. Additionally, high expression levels of dsRNA receptors have been identified in human and animal placental tissue as well as trophoblast cells, and these receptors appear to be excessively activated in PE. These key components of the innate immune system that respond to invading pathogens and dead or necrotic tissue likely play a major role in the development of PE.     

Obesity and oxidative stress: a direct link to preeclampsia?

Overweight is associated with alterations in lipid concentrations and an activation of inflammatory markers and both of these metabolic abnormalities are characteristic of preeclamptic pregnancies before the onset of clinically evident disease. Reactive oxygen species, particularly superoxide anions, evoke endothelial cell activation through many pathways. Markers of lipid peroxidation, including malondialdehyde and 8-epiprostaglandin-F2α, is increased in the plasma of women with preeclampsia, and the low concentrations of water- and lipid-soluble antioxidants in the plasma and the placenta further suggest a state of oxidative stress. This review focuses in the relation between maternal obesity, oxidative stress with development of preeclampsia.     

Change in paternity: a risk factor for preeclampsia in multiparous women?

BACKGROUND: Preeclampsia is often thought of as being a disease of first pregnancies. The incidence of preeclampsia in subsequent pregnancies, after a previous normal pregnancy is lower. However, it has been reported that this beneficial effect of multiparity is lost with a change in paternity. The aim of this study was to assess the impact of change in paternity on the incidence of preeclampsia in Dutch multiparous pregnant women. METHODS: 364 Multiparous patients with hypertension (diastolic blood pressure > or = 100 mmHg) were identified in the obstetric database of the Academic Hospital Vrije Universiteit Amsterdam for the period 1989-1996. The diagnosis in their obstetrical history (Preeclampsia, HELLP-syndrome, chronic hypertension) was defined in a pragmatic way in view of the retrospective nature of the study. The control group consisted of 281 multiparous women from a midwife clinic, with normotensive pregnancies in the same period. Patients and controls were asked, by telephone, if the index pregnancy was from the same partner as the previous pregnancy and what the sex of the newborns had been in each pregnancy. Fisher's Exact test was used for statistical analysis and P < 0.05 was considered significant. RESULTS: The final study group consisted of 333 multiparous patients with hypertension. The control group consisted of 182 multiparous women without hypertension. The prevalence of new paternity was significantly higher (P < 0.0001) both for preeclamptic and HELLP patients in comparison with the controls, with an odds ratio of 8.6 (95%CI: 3.1-23.5) and 10.9 (95%CI: 3.7-32.3), respectively. CONCLUSION: This study confirms that change of partner raises the risk for preeclampsia in subsequent pregnancies. Immune maladaptation on the fetal maternal interface could be an underlying mechanism. Multiparous women with a new partner should be approached as being primigravid women.     

Is oocyte donation a risk factor for preeclampsia? A systematic review and meta-analysis

Purpose

The objective of this meta-analysis is to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared with pregnancies achieved by in vitro fertilization with autologous oocytes (IVF).

Methods

A systematic review was performed to identify relevant studies published from January 1994 until April 2015 with at least an abstract in English using PubMed, ISI Web of Knowledge, and clinicaltrials.gov. The 11 studies included in this systematic review were retrospective and prospective cohort studies of women reporting results on the association between oocyte donation vs. in vitro fertilization (exposure) and preeclampsia (outcome).

Results

Oocyte donation is a risk factor for the development of PE compared to IVF cycles, with a weighted OR of 3.12 under a fixed effects method (FEM: no heterogeneity between the studies). The weighted OR under a random effects model was 2.9 (REM: heterogeneity between the studies). The meta-regression analysis showed that neither multiple pregnancies (estimate?=?0.08; p?=?0.19) nor patient age (estimate?=??2.29; p?=?0.13) significantly explained the variability of the effect of oocyte donation on PE. Q statistic was 12.78 (p?=?0.237), suggesting absence of heterogeneity between the studies.

Conclusions

Pregnancies achieved by oocyte donation confer a threefold increase in the likelihood of developing PE than those achieved by in vitro fertilization with own oocytes. Physicians should be aware of this risk in order to both counsel patients and monitor pregnancies accordingly.

     

Is mid-trimester maternal serum inhibin-A a marker of preeclampsia or intrauterine growth restriction?

BACKGROUND: To evaluate maternal serum Multiple of Median inhibin-A in mid-trimester blood samples of women who subsequently developed preeclampsia, gestational hypertension and intrauterine growth restriction and controls. Also, to verify whether this marker is related to these pathological conditions. METHODS: Retrospective analysis of serum samples from a bank of stored serum, originally taken for Down's syndrome screening over 15-18 weeks, was performed. The sample consisted of 20 patients with gestational hypertension, 20 patients with preeclampsia, 10 patients with intrauterine growth restriction and 40 controls. RESULTS: No statistically significant difference of inhibin-A Multiple of Median values between the control group and the preeclamptic or gestational hypertension groups was found. There was a statistically significant elevation in the intrauterine growth restriction group in comparison with the control group, and the same was true for each subgroup of gestational hypertension and preeclampsia complicated by intrauterine growth restriction. CONCLUSION: Elevated maternal inhibin-A concentrations in the second trimester are strongly associated with intrauterine growth restriction and not with preeclampsia, as previously stated.     

Fatal maternal outcome of a parturient with Eisenmenger’s syndrome and severe preeclampsia

Eisenmenger’s syndrome in pregnancy is associated with a high maternal and fetal morbidity and mortality. When it occurs with severe preeclampsia, the morbidity and mortality are higher. We report the case of a 30 weeks’ pregnant woman with Eisenmenger’s syndrome and severe preeclampsia. Cesarean section was performed due to severe preeclampsia and an unfavorable cervix under general anesthesia. The intraoperative period was uneventful and a healthy 1300 g male infant was delivered, but the patient died on the second postoperative day due to a pulmonary embolism. This case confirms the frequently fatal maternal outcome of Eisenmenger’s syndrome in pregnancy. Early termination of pregnancy is the treatment of choice. Received: 5 October 2001 / Accepted: 3 December 2001 Correspondence to V. Phupong     

How do perinatologists manage preeclampsia?

The members of the Society of Perinatal Obstetricians were surveyed regarding management of preeclampsia, with focus on drug therapy, use of invasive monitors, and both general policies and treatment of hypothetical cases of preterm severe preeclampsia. There was agreement that magnesium sulfate should be given to all patients with preeclampsia during labor and postpartum and that blood pressure should be held to about 160/105 mmHg. The drugs of choice for control of blood pressure were hydralazine, alpha-methyldopamine, and cardioselective beta-blockers. Most perinatologists use invasive monitors only for specific indications, but a substantial minority use either arterial lines or central venous pressure monitors routinely in severe preeclampsia. There was no consensus with respect to management of preterm, severe preeclampsia, but even among the 49% of respondents who volunteered an unequivocal policy of "deliver regardless of gestational age," over three fourths would hospitalize and observe in selected cases meeting American College of Obstetrics and Gynecology criteria for severe preeclampsia.     

Correlation between oral sex and a low incidence of preeclampsia: a role for soluble HLA in seminal fluid?

The involvement of immune mechanisms in the aetiology of preeclampsia is often suggested. Normal pregnancy is thought to be associated with a state of tolerance to the foreign antigens of the fetus, whereas in preeclamptic women this immunological tolerance might be hampered. The present study shows that oral sex and swallowing sperm is correlated with a diminished occurrence of preeclampsia which fits in the existing idea that a paternal factor is involved in the occurrence of preeclampsia. Because pregnancy has many similarities with transplantation, we hypothesize that induction of allogeneic tolerance to the paternal HLA molecules of the fetus may be crucial. Recent data suggest that exposure, and especially oral exposure to soluble HLA (sHLA) or HLA derived peptides can lead to transplantation tolerance. Similarly, sHLA antigens, that are present in the seminal plasma, might cause tolerance in the mother to paternal antigens. In order to test whether this indeed may be the case, we investigated whether sHLA antigens are present in seminal plasma. Using a specific ELISA we detected sHLA class I molecules in seminal plasma. The level varied between individuals and was related to the level in plasma. Further studies showed that these sHLA class I molecules included classical HLA class I alleles, such as sHLA-A2, -B7, -B51, -B35 and sHLA-A9. Preliminary data show lower levels of sHLA in seminal plasma in the preeclampsia group, although not significantly different from the control group. An extension of the present study is necessary to verify this hypothesis.     

Gammapatía monoclonal tipo Kahler asociado a preeclampsia severa,en gestante joven,asociación poco frecuente

Multiple myeloma is a malignant neoplasm derived from clonal plasma cells, resulting in the overproduction of (electrophoretically and immunologically) homogenous monoclonal immunoglobulins. These plasma cells initially grow in the bone marrow and may invade adjacent bone or spread to distant sites; however, the typical presentation consists of bone lesions secondary to tumor cell proliferation and activation of osteoclasts, causing destruction. This disease affects patients in the sixth and seventh decade of life and its presentation in reproductive age is exceptional. We report a case of Kahler's disease in a young pregnant woman, which was complicated by severe preeclampsia. We also provide a review of this entity in the world literature.     

Increased plasma levels of Urotensin-II in preeclampsia–eclampsia: a new mediator in pathogenesis?

OBJECTIVE: To assess the possible role of human Urotensin-II (hU-II), a vasoactive peptide, in the pathophysiology of preeclampsia-eclampsia prospectively. STUDY DESIGN: Sixty subjects, 30 with a diagnosis of preeclampsia-eclampsia (group I) and 30 control subjects (group II), who had been admitted between January, 2002 and December, 2002, were taken into the study. Patients in group I had an increase in blood pressure after 28th week of gestation, without any history of hypertensive disease and/or preeclampsia or eclampsia. hU-II levels were assessed using a radioimmunoassay method. RESULTS: No statistically significant difference in terms of age, gestational age, gravidity, abortion and parity was detected among groups (P > 0.05). Plasma hU-II levels in the preeclampsia-eclampsia and control groups were 10.11 +/- 5.94 pg/mL and 3.93 +/- 1.73 pg/mL, respectively. Difference between plasma hU-II levels of the two groups was found to be statistically significant (P < 0.00001). Also there was correlation between hU-II levels and mean arterial pressures in both groups (r = 0.73, P < 0.0001 and r = 0.72, P < 0.0001 for groups I and II, respectively). CONCLUSION: Results of our study strongly suggest an important role for hU-II in the pathophysiology of preeclampsia-eclampsia. Further studies concerning placenta and cord blood samples will more clearly elucidate the role of Urotensin-II in the pathogenesis of preeclampsia-eclampsia, and its feto-maternal effects.     

Does preeclampsia influence fetal lung maturity?

OBJECTIVE: This retrospective study compared the fetal lung maturity biochemical profile of patients having preeclampsia with that of patients having preterm labor. STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis in 90 patients, 59 patients with preterm labor (PTL) and 31 patients with preeclampsia (PRE). Pregnancies with fetal growth restriction were excluded. Fetal lung maturity was assessed by lecithin/sphingomyelin ratio (L/S) and by a fluorescence polarimetry assay (FLM). Mean values of L/S ratios and FLM were compared between the PTL and the PRE groups, each within two gestational age subgroups (27-32.9 weeks gestation and 33-36 weeks gestation). Student t-test, Chi-square test Fisher's exact test were used for statistical analysis. A p value < 0.05 was considered significant. RESULTS: During the gestational age interval of 33-36 weeks, the mean L/S ratios were significantly lower in pregnancies complicated by PRE than in those complicated by PTL (1.99 +/- 0.26 and 2.4 +/- 0.57, respectively; p = 0.01). Similarly, during this gestational age interval, the FLM values were also lower in PRE than in PTL, although the difference did not reach statistical significance. CONCLUSION: During the gestational age between 33 and 36 weeks of gestation, the biochemical profile of preeclamptic patients without IUGR has a significant lower L/S ratio compared to that of preterm patients.     

Multicenter impact analysis of a model for predicting recurrent early-onset preeclampsia: A before–after study

Objective: This study aims to determine the impact of using a prediction model for recurrent preeclampsia to customize antenatal care in subsequent pregnancies. Methods: We compared care consumption, pregnancy outcomes, and self-reported health state of two risk-based subgroups, and compared these to a reference group receiving standard care. Results: We included a total of 311 women from 12 hospitals. Compared to standard care, recurrence-risk guided care did not lead to different outcomes or self-perceived health. Conclusion: Our study exemplifies that recurrence-risk-based stratification of antenatal care in former preeclampsia patients is feasible; it does not lead to worse pregnancy outcomes.     

Idiopathic facial paralysis (Bell’s palsy) in the immediate puerperium in a patient with mild preeclampsia: a case report

Introduction: Idiopathic peripheral facial palsy is the most common and frequent unilateral cranial neurological disorder characterized by an isolated facial nerve paralysis. Case report: We report a case of an idiopathic facial paralysis (Bells palsy) in the immediate puerperium in a patient with mild preeclampsia and diagnosed fetal IUGR. Additionally, the presence of Bells palsy in the puerperium of the mother of our patient suggests a familiar tendency. Discussion: Every gynaecologist and obstetrician should be aware of this quite uncommon complication during pregnancy and the puerperium. This case report illustrates that Bells palsy can occur in the immediate post-partum after mild preeclamptic symptoms. For these women, a maternal surveillance can be recommended. A fast and accurate diagnosis with a subsequent immediate treatment might be very important in avoiding worsening of the symptoms and therefore improve the recovery prognosis.     

Are there financial savings associated with supplementing current diagnostic practice for preeclampsia with a novel test? Learnings from a modeling analysis from a German payer perspective

Objective: To quantify the financial impact of adding a novel serum test to the current diagnostic toolkit for preeclampsia (PE) detection in Germany. Methods: A decision-analytic model was created to quantify the economic impact of adding a recently developed novel diagnostic test for PE (Roche Diagnostics, Rotkreuz, Switzerland) to current diagnostic practice in Germany. The model simulated a cohort of 1000 pregnant patients receiving obstetric care and quantified the budget impact of adding the novel test to current German PE detection and management practices. Results: The model estimates that the costs associated with managing a typical pregnancy in Germany are €941 when the novel test is used versus €1579 with standard practice. This represents savings of €637 per pregnant woman, even when the test is used as a supplementary diagnostic tool. The savings are attributed to the novel test’s ability to better classify patients relative to current practice, specifically, its ability to reduce false negatives by 67% and false positives by 71%. Conclusion: The novel PE test has the potential to provide substantial cost savings to German healthcare payers, even when used as an addition to standard practice. Better classification of patients at risk for developing PE and declassification of those that are not compared to current practice leads to economic savings for the healthcare system. Furthermore, by reducing the rates of false-positive and false-negative classification relative to current standard of care, the test helps better target healthcare spending and lowers overall costs associated with PE care.