The Impact of Hydroxychloroquine on Primary Feto-Placental Endothelial Cells from Healthy and Early-Onset Preeclamptic Placentas.

Hydroxychloroquine (HCQ), an anti-malarial drug, is suggested as a promising candidate for the treatment of pregnancy-related disorders associated with endothelial activation, among which there is preeclampsia (PE). Arterial feto-placental endothelial cells (fpECAs) were isolated from control (CTR) and early-onset preeclamptic (EO-PE) placentas. The aim of this study was to test potential protective effects of HCQ in an in vitro model of endothelial activation as well as in cells isolated from EO-PE placentas. To mimic PE conditions, CTR fpECAs were exposed to a pro-inflammatory environment consisting of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1ß (furtherly referred as MIX) with or without varying concentrations of HCQ (1 µg/mL and 10 µg/mL). Their effect on wound healing and endothelial barrier integrity was analyzed. Variations in the expression of IL-8 and leukocyte adhesion molecules (LAM) on both mRNA and protein levels were determined between CTR and PE fpECAs in the presence or absence of HCQ. MIX decreased wound healing and stability of the endothelial barrier, but HCQ did not affect it. Significant differences between CTR and EO-PE fpECAs were observed in IL-8 mRNA, protein secretion, and vascular cell adhesion protein 1 (VCAM-1) mRNA expression levels. After challenging CTR fpECAs with MIX, upregulation of both mRNA and protein levels was observed in all molecules. Combined treatment of HCQ and MIX slightly lowered VCAM-1 total protein amount. In CTR fpECAs, treatment with low concentrations of HCQ alone (1 µg/mL) reduced basal levels of IL-8 and VCAM-1 mRNA and secretion of IL-8, while in EO-PE fpECAs, a higher (10µg/mL) HCQ concentration slightly reduced the gene expression of IL-8. Conclusion: These results provide additional support for the safety of HCQ, as it did not adversely affect endothelial functionality in control fpECAs at the tested concentration. Furthermore, the observed limited effects on IL-8 secretion in EO-PE fpECAs warrant further investigation, highlighting the need for clinical trials to assess the potential therapeutic effects of HCQ in preeclampsia. Conducting clinical trials would offer a more comprehensive understanding of HCQ's efficacy and safety, allowing us to explore its potential benefits and limitations in a real-world clinical setting.

A core outcome set for studies of gestational diabetes mellitus prevention and treatment.

AIMS/HYPOTHESIS: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM). METHODS: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised. RESULTS: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth). CONCLUSIONS/INTERPRETATION: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies. TRIAL REGISTRATION: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/.

Disturbed Cardiorespiratory Adaptation in Preeclampsia: Return to Normal Stress Regulation Shortly after Delivery?

Women with pregnancies complicated by preeclampsia appear to be at increased risk of metabolic and vascular diseases in later life. Previous research has also indicated disturbed cardiorespiratory adaptation during pregnancy. The aim of this study was to follow up on the physiological stress response in preeclampsia several weeks postpartum. A standardized laboratory test was used to illustrate potential deviations in the physiological stress responding to mildly stressful events of the kind and intensity in which they regularly occur in further everyday life after pregnancy. Fifteen to seventeen weeks postpartum, 35 women previously affected by preeclampsia (19 mild, 16 severe preeclampsia), 38 women after uncomplicated pregnancies, and 51 age-matched healthy controls were exposed to a self-relevant stressor in a standardized stress-reactivity protocol. Reactivity of blood pressure, heart rate, stroke index, and systemic vascular resistance index as well as baroreceptor sensitivity were analyzed. In addition, the mutual adjustment of blood pressure, heart rate, and respiration, partitioned for influences of the sympathetic and the parasympathetic branches of the autonomic nervous system, were quantified by determining their phase synchronization. Findings indicated moderately elevated blood pressure levels in the nonpathological range, reduced stroke volume, and elevated systemic vascular resistance in women previously affected by preeclampsia. Despite these moderate abnormalities, at the time of testing, women with previous preeclampsia did not differ from the other groups in their physiological response patterns to acute stress. Furthermore, no differences between early, preterm, and term preeclampsia or mild and severe preeclampsia were observed at the time of testing. The findings suggest that the overall cardiovascular responses to moderate stressors return to normal in women who experience a pregnancy with preeclampsia a few weeks after delivery, while the operating point of the arterial baroreflex is readjusted to a higher pressure. Yet, their regulation mechanisms may remain different.

Activated protein C resistance assay and factor V Leiden.

The authors suggest that functional testing for activated protein C resistance is cheaper and more clinically relevant than genetic testing to detect a factor V Leiden mutation in identifying persons who are at risk for thromboembolism.

Placental fractalkine is up-regulated in severe early-onset preeclampsia.

The pathogenesis of preeclampsia (PE) includes the release of placental factors into the maternal circulation, inducing an inflammatory environment in the mother. One of the factors may be the proinflammatory chemokine fractalkine, which is expressed in the syncytiotrophoblast of human placenta, from where it is released into the maternal circulation by constitutive shedding. We examined whether placental fractalkine is up-regulated in severe early-onset PE and whether the proinflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 are able to increase the expression of fractalkine. Gene expression analysis, enzyme-linked immunosorbent assay, and immunohistochemistry consistently showed increased fractalkine expression in placentas from severe early-onset PE, compared to gestational age-matched controls. Expression of a disintegrin and metalloproteinases (ADAMs) 10 and 17, which convert transmembrane fractalkine into the soluble form, was significantly increased in these cases. Incubation of first-trimester placental explants with TNF-α provoked a significant increase in fractalkine expression and release of the soluble form, whereas IL-6 had no effect. TNF-α-mediated up-regulation of placental fractalkine was reversed in the presence of the aspirin-derivative salicylate, which impaired activation of NF-κB p65 in TNF-α-treated explants. On the basis of data from placental explants, we suggest that increased maternal TNF-α may up-regulate the expression and release of placental fractalkine, which, in turn, may contribute to an exaggerated systemic inflammatory response in PE.

The impact of severe preeclampsia on maternal quality of life.

PURPOSE: Preeclampsia (PE) is a serious life event that can change women's psychological profile. The aim of this study was to evaluate the physical and mental health-related quality of life (HR-QoL) in women after PE and the impact of contributing factors. METHODS: Ninety-five women who had suffered from PE answered the Short-Form-12 Health Survey on general state of health. Comparison was made with the reference values and among the study cohorts, namely mild (14.7 %), severe (74.7 %) and superimposed PE (10.5 %). Medical parameters were evaluated as additional factors, and age served as covariate. RESULTS: Quality of mental life was significantly worse in all patients (p < 0.01), especially in those after severe PE (p < 0.01) compared to the reference range. These women demonstrated significantly worse results than those affected by the mild form (p = 0.03). Women who had had superimposed PE were neither physically nor mentally impaired compared to the standard population values (p = 0.94 and p = 0.90, respectively). After controlling for medical parameters and age, differences remained statistically significant. Multiparous women scored significantly worse on the mental scale than primiparous (p = 0.02), and pregnant women scored significantly worse than non-pregnant women on the physical level (p = 0.04). CONCLUSIONS: This study shows that women who have suffered from severe PE are substantially reduced in their mental quality of life. An extensive medical care including HR-QoL parameters might improve pregnancy outcome.

The impact of resilience on psychological outcomes in women after preeclampsia: an observational cohort study.

BACKGROUND: Preeclampsia is a frequent obstetric complication which affects the mother`s and the fetus's health and can be life threatening. It also has an impact on psychological outcomes. There may be protective variables such as resilience shielding against psychosocial distress in women experiencing these pregnancy complications. The aim of this study was to examine differences in resilience in terms of quality of life, depression and post-traumatic stress symptoms in women after preeclampsia. METHODS: Four international validated questionnaires were used to measure the psychological outcomes (Medical Outcome Study Short-Form SF12, Edinburgh Postnatal Depression Scale EPDS, Resilience Scale RS13, Impact of Event Scale IES-R). Statistical analyses were performed using independent-samples t-test and chi-square test. RESULTS: 67 women with previous preeclampsia returned the questionnaires. Women with high resilience showed significantly less depression (p = 0.001) and better mental quality of life (p = 0.002) compared to women with low resilience. No group differences were found on the medical and socio-demographic characteristics. CONCLUSIONS: Resilience has an important impact on the psychological outcomes in women after preeclampsia. A screening for resilience, depression and quality of life may be appropriate to identify these women.

Preeclampsia and the Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPLs). Preeclampsia complicates about 10-17% of pregnancies with APS. However, only early onset preeclampsia (<34 weeks of gestation) belongs to the clinical criteria of APS. The similarities in the pathophysiology of early onset preeclampsia and APS emphasize an association of these two syndromes. Overall, both are the result of a defective trophoblast invasion and decidual transformation at early gestation. Women with APS are at increased risk for prematurity; the reasons are mostly iatrogenic due to placental dysfunction, such as preeclampsia or FGR. Interestingly, women with APS have also an increased risk for preterm delivery, even in the absence of FGR and preeclampsia, and therefore it is not indicated but spontaneous. The basic treatment of APS in pregnancy is low-dose aspirin and low-molecular-weight heparin. Nevertheless, up to 20-30% of women develop complications at early and late gestation, despite basic treatment. Several additional treatment options have been proposed, with hydroxychloroquine (HCQ) being one of the most efficient. Additionally, nutritional interventions, such as intake of vitamin D, have shown promising beneficial effects. Curcumin, due to its antioxidant and anti-inflammatory properties, might be considered as an additional intervention as well.

Comparison of mean platelet volume (MPV) and sFlt-1/PlGF ratio as predictive markers for preeclampsia.

INTRODUCTION: Preeclampsia is characterised by an increased platelet consumption with consecutive reduction of overall platelet count and a consecutive rise in mean platelet volume (MPV). MPV has therefore been suggested as a predictive marker for preeclampsia. We aimed to investigate MPV longitudinally in women with preeclampsia compared to healthy controls during pregnancy for potential early detection of preeclampsia and to compare potential MPV changes against the sFlt-1/PlGF ratio. STUDY DESIGN: This longitudinal study included 38 women with preeclampsia and 84 women with normal pregnancies, where MPV and sFlt-1 and PLGF levels were determined every 4 weeks, starting in early pregnancy. RESULTS: MPV was significantly higher in women who developed preeclampsia compared to women with normal pregnancies at 12, (p = .029), 24 (p = .011), 28 (p = .037), 32 (p = .002), and 36 weeks of gestation, respectively (p = .015). Further analysis revealed a cut-off point of 10.85 fl (sensitivity 65.6%, specificity 26.2%) for the prediction of preeclampsia. The sFlt-1/PlGF ratio was significantly higher in women who developed preeclampsia compared to women with normal pregnancies at the same time points (p = .001). The cut-off point for predicting preeclampsia was 10.3 (sensitivity 87.5%, specificity 11.9%). ROC curve analysis showed that MPV has a high predictive value for early-onset preeclampsia (p < .05) but not for late-onset preeclampsia. CONCLUSION: MPV is significantly elevated even in early pregnancy in women who develop preeclampsia and seems, therefore, a valuable predictor for preeclampsia even at early gestation. However, according to our results, MPV seems reliable in predicting early onset preeclampsia.

Diabetes Mellitus, Obesity, and the Placenta.

The placenta is exposed to metabolic derangements in the maternal and fetal circulation. The effects of the early placental "exposome" determine further trajectories. Overstimulation of the fetal pancreas in early gestation results in fetal hyperinsulinemia, augmenting glucose transfer with adverse effects on the fetus. The manifold placental changes at the end of pregnancy can be regarded as adaptive responses to protect the fetus from diabetes and obesity. The causal role of the placenta, if any, in mediating long-term effects on offspring development is an important area of current and future research.

Preeclampsia before fetal viability in women with primary antiphospholipid syndrome- materno-fetal outcomes in a series of 7 cases.

INTRODUCTION: Preeclampsia complicates about 10-17 % of pregnancies with antiphospholipid syndrome (APS). It is often severe and might occur sometimes at early gestation. The development of preeclampsia before fetal viability is a huge challenge for obstetricians and demands an intensive discussion regarding the therapeutical options. PATIENTS AND METHODS: We retrospectively reviewed the data of 7 women with primary APS who developed preeclampsia before 24 weeks of gestation. Plasma exchange had been performed in four of the cases and two women received corticosteroids. One of the women had received 20 mg of pravastatin daily, starting at 18 weeks of gestation. Neonatal outcome was: live birth in four cases and IUFD in three cases. The main pediatric complications were noted in a 28-week-old premature born boy, who developed severe IRDS and thrombocytopenia. At the present time, the boy continues to have a retarded status. DISCUSSION: This retrospective analysis revealed that women with APS can develop severe preeclampsia even before 20 weeks of gestation. Several management options for prolongation of pregnancy such as plasma exchange, pravastatin, LMHW, hydroxychloroquine/HCQ, or TNF-alpha blocker should be discussed with the patients. Optimal management of preeclampsia before 24 weeks of gestation usually depends on weighing the maternal and fetal complications from expectant management with prolongation of pregnancy versus the predominant fetal and neonatal risks of extreme prematurity from "aggressive" management with immediate delivery.

Changes of platelet count throughout pregnancy in women with antiphospholipid syndrome.

OBJECTIVE: Antiphospholipid antibodies (aPL) activate several cell types, such as endothelial cells, monocytes, neutrophils, fibroblasts, trophoblasts and platelets, thus leading to thrombosis and obstetric complications in patients with antiphospholipid syndrome (APS). The aim of the present study was the longitudinal investigation of platelet count in women with APS. Additionally, platelet count in women with APS who developed preeclampsia during pregnancy were compared to women with APS and uncomplicated pregnancy for potential early detection of preeclampsia. MATERIAL AND METHODS: This longitudinal study included 65 women with APS, 38 women with preeclampsia and 84 women with normal pregnancies, where platelet count was determined every four weeks, starting in early pregnancy. RESULTS: Platelet count was significantly lower in women with APS compared to women who developed preeclampsia and normal pregnancies starting at 12 weeks of gestation. The areas under the curve (AUC) for platelet count were 0.765 at 12 weeks of gestation (95% of CI of 0.634-0.896), 0.747 at 20 weeks (95% of CI of 0.600-0.894), 0.719 at 24 weeks (95% of CI of 0.555-0.882), respectively. The cut off points for platelets were 216 at 12-14 weeks of gestation, 226.5 at 20 weeks of gestation, and 163.5 at 24 weeks of gestation, respectively. DISCUSSION: We demonstrated a significant lower platelet count in women with APS throughout gestation. Additionally, platelet count is significantly decreased in women with APS who developed preeclampsia. According to our results, platelet count seems to have a predictive value for the development of preeclampsia in these women.

Effect of Low-Dose Aspirin on Soluble FMS-Like Tyrosine Kinase 1/Placental Growth Factor (sFlt-1/PlGF Ratio) in Pregnancies at High Risk for the Development of Preeclampsia.

BACKGROUND: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1) and placental growth factor (PlGF) have been reported to be highly predictive several weeks before the onset of preeclampsia. OBJECTIVE: To investigate longitudinal changes of serum levels sFlt-1 and PlGF in pregnant women at high risk for the development of preeclampsia and to reveal an impact of aspirin on maternal serum concentrations of sFlt-1 and PlGF. METHODS: This was a prospective longitudinal study in 394 women with various risk factors for the development of preeclampsia (chronic hypertension, antiphospholipid syndrome/APS or systemic lupus erythematosus/SLE, thrombophilia, women with a history of preeclampsia, pathologic first trimester screening for preeclampsia) and 68 healthy women. Serum levels of sFlt-1 and PlGF were measured prospectively at 4-week intervals (from gestational weeks 12 until postpartum). RESULTS: The sFlt-1/PlGF ratio was significantly higher in women with an adverse obstetric outcome compared to women with a normal pregnancy, starting between 20 and 24 weeks of gestation. There was no effect of aspirin on sFlt-1/PlGF ratio in women with chronic hypertension, APS/SLE, thrombophilia and controls. The use of aspirin showed a trend towards an improvement of the sFlt-1/PlGF ratio in women with preeclampsia in a previous pregnancy and a significant effect on the sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia. CONCLUSIONS: Our findings reveal an impact of aspirin on sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia, strongly supporting its prophylactic use.

Angiogenic factors in pregnancies of women with antiphospholipid syndrome and systemic lupus erythematosus.

OBJECTIVES: An imbalance of angiogenic placental factors such as endoglin, soluble fms-like tyrosine kinase 1(sFlt-1) and placental growth factor (PlGF) has been implicated in the pathophysiology of preeclampsia. This study aimed to evaluate serum levels of sFlt-1, PlGF and endoglin in women with primary and secondary antiphospholipid Syndrome (APS) and systemic lupus erythematosus (SLE) longitudinally through pregnancy. MATERIAL AND METHODS: Serum levels of sFlt-1, PlGF and endoglin were measured prospectively at 4-week intervals (from gestational weeks 12-36) in 17 women with primary APS (PAPS), 18 women with secondary APS (SAPS), and 23 women with SLE. RESULTS: 6/17 (35%) of women with PAPS, 3/18 (17%) of women with SAPS, and 2/23 (9%) of women with SLE developed early-onset preeclampsia. Women who developed preeclampsia had significantly higher mean sFlt-1 and endoglin levels, higher sFlt-1/PlGF ratios, and lower mean PlGF-levels than women who did not. These changes became statistically significant at 12 weeks for sFlt-1, PlGF and endoglin. DISCUSSION: Endoglin, sFlt-1 and PlGF are potential early screening parameters for the development of preeclampsia in pregnant women with autoimmune diseases like APS and SLE.

Risk assessment for preterm preeclampsia in first trimester: Comparison of three calculation algorithms.

OBJECTIVE: To better adjust the risk for preeclampsia, multifactorial models in first trimester of pregnancy have found the way in clinical practice. This study compares the available test algorithms. STUDY DESIGN: In a cross-sectional study between November 2013 and April 2016 we compared the tests results of three first trimester testing algorithms for preeclampsia in 413 women. Risk for preterm preeclampsia was calculated with three different algorithms: Preeclampsia Predictor™ Software by PerkinElmer (PERK), ViewPoint® Software by GE Healthcare (VP) and the online calculator of the Fetal Medicine Foundation (FMF).We analyzed the data descriptively and determined Cohen's Kappa to assess the agreement among the algorithms. RESULTS: VP classified 89(21.5%) women, PERK 43(10.4%) women and FMF 90 (21.8%) women as having high risk for preterm preeclampsia (<34 weeks of gestation for VP and PERK and <37 weeks of gestation for FMF). Agreement between tests ranged from moderate to substantial (PERK/VP: κ = 0.56, PERK/ FMF: κ = 0.50, and VP/ FMF: κ = 0.72). CONCLUSION: The three algorithms are similar but not equal. This may depend on chosen cut off, but also on test properties. This study cannot decide which algorithm is the best, but differences in results and cut offs should be taken into account.

Maternal cardiovascular and endothelial function from first trimester to postpartum.

OBJECTIVE: To explore noninvasively the complex interactions of the maternal hemodynamic system throughout pregnancy and the resulting after-effect six weeks postpartum. METHODS: Eighteen women were tested beginning at the 12th week of gestation at six time-points throughout pregnancy and six weeks postpartum. Heart rate, heart rate variability, blood pressure, pulse transit time (PTT), respiration, and baroreceptor sensitivity were analyzed in resting conditions. Additionally, hemoglobin, asymmetric and symmetric dimethylarginine and Endothelin (ET-1) were obtained. RESULTS: Heart rate and sympathovagal balance favoring sympathetic drive increased, the vagal tone and the baroreflex sensitivity decreased during pregnancy. Relative sympathetic drive (sympathovagal balance) reached a maximum at 6 weeks postpartum whereas the other variables did not differ compared to first trimester levels. Postpartum diastolic blood pressure was higher compared to first and second trimester. Pulse transit time and endothelial markers showed no difference throughout gestation. However, opposing variables PTT and asymmetric dimethylarginine (ADMA) were both higher six weeks postpartum. CONCLUSIONS: The sympathetic up regulation throughout pregnancy goes hand in hand with a decreased baroreflex sensitivity. In the postpartum period, the autonomic nervous system, biochemical endothelial reactions and PTT show significant and opposing changes compared to pregnancy findings, indicating the complex aftermath of the increase of blood volume, the changes in perfusion strategies and blood pressure regulation that occur in pregnancy.

Comparison of two-risk assessment algorithms for preeclampsia in first trimester with consecutive intake of low-dose aspirin in the high-risk group - an observational study.

We analyzed outcome of women screened for preeclampsia with two different multifactorial risk algorithms (Predictor®Software by PerkinElmer, PerkinElmer, Waltham, MA; PERK-group: n = 214 and Viewpoint® by GE Healthcare, Dornstadt, Germany; VIEW-group: n = 209) in first trimester. Women at high risk for developing preeclampsia were advised to take low-dose acetylsalicylic acid (LDA). Screening positive rates for early onset preeclampsia differed significantly between the two groups (7.9% versus 26.3%; p = 0.000). According the clinical use of screening test criteria, LDA was prescribed in 63 (29.4%) women in the PE-group and 55 (26.3%) in the VP-group (p = 0.516). There were no differences in onset of preeclampsia [4 (1.9%) versus 6 (2.9%); p = 0.540]. No early or severe preeclampsia occurred in the whole population.

Endothelial indoleamine 2,3-dioxygenase-1 regulates the placental vascular tone and is deficient in intrauterine growth restriction and pre-eclampsia.

Indoleamine 2,3-dioxygenase-1 (IDO1) mediates the degradation of L-tryptophan (L-Trp) and is constitutively expressed in the chorionic vascular endothelium of the human placenta with highest levels in the microvasculature. Given that endothelial expression of IDO1 has been shown to regulate vascular tone and blood pressure in mice under the condition of systemic inflammation, we asked whether IDO1 is also involved in the regulation of placental blood flow and if yes, whether this function is potentially impaired in intrauterine growth restriction (IUGR) and pre-eclampsia (PE). In the large arteries of the chorionic plate L-Trp induced relaxation only after upregulation of IDO1 using interferon gamma and tumor necrosis factor alpha. However, ex vivo placental perfusion of pre-constricted cotyledonic vasculature with L-Trp decreases the vessel back pressure without prior IDO1 induction. Further to this finding, IDO1 protein expression and activity is reduced in IUGR and PE when compared to gestational age-matched control tissue. These data suggest that L-Trp catabolism plays a role in the regulation of placental vascular tone, a finding which is potentially linked to placental and fetal growth. In this context our data suggest that IDO1 deficiency is related to the pathogenesis of IUGR and PE.

Pregnancy Outcome in Women with Obstetric and Thrombotic Antiphospholipid Syndrome-A Retrospective Analysis and a Review of Additional Treatment in Pregnancy.

Antiphospholipid syndrome (APS) is associated with pregnancy complications such as recurrent early fetal loss (RFL), fetal death, preeclampsia (PE), and intrauterine growth restriction (obstetric APS/OAPS). Other clinical manifestations are venous and/or arterial thromboses (thrombotic APS/TAPS). The data of 37 pregnancies with OAPS and 37 pregnancies with TAPS were analyzed and compared. Overall, the most frequent APS antibodies (aPl) were LA as well as "triple-positivity"; LA antibodies were significantly more frequent in women with TAPS (67.6 % TAPS vs. 29.7 % OAPS, p < 0.010), whereas "triple-positivity" was significantly more seen in women with OAPS (40.5 % OAPS vs. 13.5 % TAPS, p < 0.010). Adequate therapy has been administered in nearly all pregnancies with TAPS, whereas in 18.9 % of pregnancies with OPS, no therapy has been given at all. One woman in OAPS and four women in TAPS were treated with plasmapheresis and immunoadsorption. There was no significant association between adverse obstetric outcome and therapy. The most frequent pregnancy complications were RFL in the OAPS group (32.4 vs. 13.5 % in TAPS) and PE in the TAPS group (18.9 % in OAPS and TAPS, respectively). The data of our study showed that pregnancies with OAPS and TAPS have a similar rate of pregnancy complications. However, pregnancies with OAPS tend to have rather RFL. Although we were not able to reveal a significant association with adverse obstetric outcome, it seems that the current adequate therapy for APS in pregnancy, consisting of LDA and LMWH, might rather prevent the development of RFL. Additionally, it might be considered to divide the obstetric APS into obstetric APS with early pregnancy complications and obstetric APS with late pregnancy complications. The division into two groups of obstetric APS might facilitate the choice of additional therapy in these women.

Response to Plasmapheresis Measured by Angiogenic Factors in a Woman with Antiphospholipid Syndrome in Pregnancy.

An imbalance of angiogenic and antiangiogenic placental factors such as endoglin and soluble fms-like tyrosine kinase 1 has been implicated in the pathophysiology of preeclampsia. Extraction of these substances by plasmapheresis might be a therapeutical approach in cases of severe early-onset preeclampsia. Case Report. A 21-year-old primigravida with antiphospholipid syndrome developed early-onset preeclampsia at 18 weeks' gestation. She was treated successfully with plasmapheresis in order to prolong pregnancy. Endoglin and sflt-1-levels were measured by ELISA before and after treatment. Endoglin levels decreased significantly after treatment (p < 0.05) and showed a significant decrease throughout pregnancy. A rerise of endoglin and sflt-1 preceded placental abruption 4 weeks before onset of incident. Conclusion. Due to the limited long-term therapeutical possibilities for pregnancies complicated by PE, plasmapheresis seems to be a therapeutical option. This consideration refers especially to pregnancies with early-onset preeclampsia, in which, after first conventional treatment of PE, prolongation of pregnancy should be above all.