A realistic aneurysm clipping simulation combining 3D-printed and placenta-based models-how I do it.

INTRODUCTION: Neurovascular surgery, particularly aneurysm clipping, is a critical skill for aspiring neurosurgeons. However, hands-on training opportunities are limited, especially with the growing popularity of endovascular techniques. To address this challenge, we present a novel neurovascular surgical training station that combines synthetic 3D-printed models with placental vascular structures to create a semi-realistic surgical field. METHODS: Our model consists of three components: a 3D-printed skull replica with anatomical landmarks, a malleable silicone parenchyma with a Sylvian fissure, and vascular layers (placenta). The placental vascular layer is catheterized and perfused to replicate pulsatile flow, offering a realistic aneurysm simulation. This innovative training station provides a cost-effective solution (approximately 200 USD once) without ethical constraints. Surgeons can practice essential skills such as Sylvian fissure dissection, managing anatomical constraints like bone, and achieving proximal vascular control. The model's realism allows for training in various scenarios, including clipping with different hand orientations and handling ruptures realistically. CONCLUSION: Our neurovascular surgical station bridges the gap between existing training models, offering affordability, ecological considerations, and minimal ethical concerns. It empowers neurosurgery residents to refine their skills in handling both emergencies and elective cases under close-to-real surgical conditions, with the potential for independent practice and senior supervision.

[Preeclampsia: Guidelines for clinical practice from the French College of Obstetricians and Gynecologists]. / La pré-éclampsie : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies to reduce maternal and neonatal morbidity related to preeclampsia. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and recommendations were formulated as a (i) strong, (ii) weak or (iii) no recommendation. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Preeclampsia is defined by the association of gestational hypertension (systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg) and proteinuria≥0.3g/24h or a Proteinuria/Creatininuria ratio≥30mg/mmol occurring after 20 weeks of gestation. Data from the literature do not show any benefit in terms of maternal or perinatal health from implementing a broader definition of preeclampsia. Of the 31 questions, there was agreement between the working group and the external reviewers on 31 (100%). In general population, physical activity during pregnancy should be encouraged to reduce the risk of preeclampsia (Strong recommendation, Quality of the evidence low) but an early screening based on algorithms (Weak recommendation, Quality of the evidence low) or aspirin administration (Weak recommendation, Quality of the evidence very low) is not recommended to reduce maternal and neonatal morbidity related to preeclampsia. In women with preexisting diabetes or hypertension or renal disease, or multiple pregnancy, the level of evidence is insufficient to determine whether aspirin administration during pregnancy is useful to reduce maternal and perinatal morbidity (No recommendation, Quality of the evidence low). In women with a history of vasculo-placental disease, low dose of aspirin (Strong recommendation, Quality of the evidence moderate) at a dosage of 100-160mg per day (Weak recommendation, Quality of the evidence low), ideally before 16 weeks of gestation and not after 20 weeks of gestation (Strong recommendation, Quality of the evidence low) until 36 weeks of gestation (Weak recommendation, Quality of the evidence very low) is recommended. In a high-risk population, additional administration of low molecular weight heparin is not recommended (Weak recommendation, Quality of the evidence moderate). In case of preeclampsia (Weak recommendation, Quality of the evidence low) or suspicion of preeclampsia (Weak recommendation, Quality of the evidence moderate, the assessment of PlGF concentration or sFLT-1/PlGF ratio is not routinely recommended) in the only goal to reduce maternal or perinatal morbidity. In women with non-severe preeclampsia antihypertensive agent should be administered orally when the systolic blood pressure is measured between 140 and 159mmHg or diastolic blood pressure is measured between 90 and 109mmHg (Weak recommendation, Quality of the evidence low). In women with non-severe preeclampsia, delivery between 34 and 36+6 weeks of gestation reduces severe maternal hypertension but increases the incidence of moderate prematurity. Taking into account the benefit/risk balance for the mother and the child, it is recommended not to systematically induce birth in women with non-severe preeclampsia between 34 and 36+6 weeks of gestation (Strong recommendation, Quality of evidence high). In women with non-severe preeclampsia diagnosed between 37+0 and 41 weeks of gestation, it is recommended to induce birth to reduce maternal morbidity (Strong recommendation, Low quality of evidence), and to perform a trial of labor in the absence of contraindication (Strong recommendation, Very low quality of evidence). In women with a history of preeclampsia, screening maternal thrombophilia is not recommended (Strong recommendation, Quality of the evidence moderate). Because women with a history of a preeclampsia have an increased lifelong risk of chronic hypertension and cardiovascular complications, they should be informed of the need for medical follow-up to monitor blood pressure and to manage other possible cardiovascular risk factors (Strong recommendation, Quality of the evidence moderate). CONCLUSION: The purpose of these recommendations was to reassess the definition of preeclampsia, and to determine the strategies to reduce maternal and perinatal morbidity related to preeclampsia, during pregnancy but also after childbirth. They aim to help health professionals in their daily clinical practice to inform or care for patients who have had or have preeclampsia. Synthetic information documents are also offered for professionals and patients.

Interstitial pregnancy management: A multicentric analysis of 98 patients from the FRANCOGENT group comparing surgery and medical treatment.

OBJECTIVE: To evaluate the outcomes associated with each therapeutic option for patients diagnosed with interstitial pregnancy (IP). METHODS: We conducted a multicentric retrospective cohort study within the departments of Gynecology and Obstetrics involved in the Francogent research group. Women treated for an interstitial pregnancy between January 2008 to December 2019 were included. Three therapeutic options were evaluated: surgical treatment (ST); in situ methotrexate combined with systemic methotrexate (IS-MTX); and systemic methotrexate (IM-MTX). Success of first-line treatment was defined by hCG negativation (<5I U/L). Secondary outcomes included the need for secondary surgical procedure, secondary medical treatment, emergency surgery, postoperative complications, duration of hospitalization, and delay before hCG negativation. RESULTS: A total of 98 patients were managed for IP: 42 (42.9%) patients had IM-MTX; 34 (34.7%) had IS-MTX; and 22 (22.4%) had ST. First-line treatment was successful in all patients of the ST group (22/22, 100%), in 31% of patients within the IM-MTX group (13/42) and 70.6% (24/34) in the IS-MTX group. The sole parameter associated with the risk of treatment failure was the mode of methotrexate administration. The size of the gestational sac or the presence of fetal heartbeat was not associated with decreased medical treatment (IS or IM-MTX) efficiency. CONCLUSION: Either ST or IS-MTX are good options for IP treatment associated with high success rates. A single-dose regimen of IM-MTX is less efficient than IS-MTX or ST. Symptomatic patients with severity criteria should always undergo emergency surgery. IP remains a high-risk condition that should be managed, whenever possible, in referral centers to potentialize the chances of favorable outcomes.

Managing pregnancy in patients with sickle cell disease from a transfusion perspective.

Advances in the management of sickle cell disease (SCD) have made it possible for most female patients (whether homozygous or compound heterozygous) to reach childbearing age and become pregnant. However, even in the less symptomatic forms of SCD a high risk of complications during pregnancy and the postpartum period can occur for both the mother (1% to 2% mortality) and the fetus. Coordinated care from the obstetrician and the sickle cell disease expert is essential, together with the active participation of the patient. Vaso-occlusive complications, such as vaso-occlusive crisis and acute chest syndrome, often increase in frequency when hydroxyurea treatment is interrupted. Obstetric complications, such as pre-eclampsia, fetal growth restriction, and preterm delivery, are more common in women with SCD. Recent meta-analysis-based studies support prophylactic transfusion. However, there have been no randomized trials assessing the benefits of prophylactic transfusion. Given the known risk of transfusion complications, including delayed hemolytic transfusion reaction and hyperhemolysis, transfusion is not systematically performed in pregnant women with SCD. We describe here a case-by-case approach to the management of pregnancy in women with SCD based on the medical and transfusion history of each patient.

Management of gynecological cancers in the emergency department: Impact of precariousness and prognostic factors.

OBJECTIVE: The primary objective was to determine the profile of patients consulting in an emergency department and diagnosed with a pelvic cancer. Our secondary objective was to assess the potential impact on this diagnostic trajectory on survival. METHOD: A single-center retrospective study including patients managed for a pelvic cancer between January 2018 and November 2020 in the center Hospitalier Intercommunal de Creteil was conducted. Patients' characteristics were compared based on their diagnostic trajectory (emergency or referred to consultation). Precariousness was assessed using Pascal's tool based on 4 characteristics: being a beneficiary of the former Couverture Maladie Universelle (CMU) or Aide Medicale d'Etat (AME), not having complementary health insurance, being job seeking for more than 6 months and being beneficiary of allowances. A patient was defined as precarious if the Pascal tool was 'TRUE', i.e., at least one positive item. The main socio-demographic and cancer associated factors were analyzed as prognostic factors. RESULTS: Over the inclusion period, among the 283 eligible patients, 37.3 % (87/233) had a diagnosis of cancer following an emergency department visit. There was a significant association between precariousness, rupture of gynecological follow-up, lack of participation in national screening campaigns and the risk of being diagnosed through the emergency pathway for all cancers studied (p = 0.001). There was no difference in terms of stage at diagnostic, management (according to current guidelines), prognostic and overall survival between the two groups. CONCLUSION: Patients in a situation of precariousness are more likely to be diagnosed with cancer in an emergency department. Our study underlines the importance of precariousness as a factor determining the type of diagnostic management of gynecological cancer. Efforts should be made toward improving frail patients to primary care.

Risk factors for hypoxic-ischemic encephalopathy or neonatal death in placental abruption.

OBJECTIVE: To identify risk factors for moderate or severe hypoxic-ischemic encephalopathy (HIE), or neonatal death in clinical placental abruption. MATERIAL AND METHODS: A nested case-control study within a cohort of singleton pregnancies complicated by placental abruption with a live born infant at two academic reference centers in France, from 2006 to 2019. Cases were patients who gave birth to an infant with moderate or severe HIE or death within 28 days (HIE/death group), and controls were patients whose infant did not have any of these outcomes (no-HIE group). Independent risk factors were identified by logistic regression. Binary decision tree discriminant (CART) analysis was performed to define high-risk subgroups of HIE or death. RESULTS: Among 152 patients, the infants of 44 (29%) had HIE or death. Out-of-hospital placental abruption and fetal bradycardia at admission were more frequent in cases than in controls: 39 (89%) vs 61 (56%), p < .01 and 24 (59%) vs 19 (18%), p < .01, respectively. In multivariate analysis, out-of-hospital placental abruption (aOR, 7.05; 95% CI, 1.94-25.66) and bradycardia at admission (aOR, 8.60; 95% CI, 2.51-29.42) were independently associated with an increased risk of HIE or death. The combination of out-of-hospital placental abruption and bradycardia was the highest risk situation associated with HIE or death (67%). The decision-to-delivery interval was 15 [12-20] minutes among cases. CONCLUSION: Out-of-hospital placental abruption combined with bradycardia at admission was associated with a major risk of moderate or severe HIE or death. An optimal decision-to-delivery interval does not guarantee the absence of an adverse neonatal outcome.

Association of fetal heart rate short term variability pattern during term labor with neonatal morbidity and small for gestational age status.

OBJECTIVE: To assess the association of fetal heart rate short-term variability (STV) pattern during term labor with both neonatal composite morbidity (cord blood pH ≤ 7.10 and/or neonatal intensive care unit admission and/or Apgar score at 5 min <7) and small for gestational age (SGA) status. STUDY DESIGN: Retrospective cohort in a single academic institution between January 2016 and December 2018. A total of 1896 women that delivered a singleton during labor in cephalic presentation after 37 weeks of gestation were included (948 women with SGA neonates and 948 women with appropriate weight for gestational age (AGA) neonates that were matched to women with SGA neonates based on maternal age, parity, induction of labor, gestational diabetes, gestational age at delivery and a history of one cesarean section using propensity score matching). STV was compared at labor onset (cervical dilation ≤ 4 cm), in the first stage of labor (cervical dilation = 6 cm) and in the second stage of labor (cervical dilation = 10 cm). A generalized linear mixed model was used to assess the association between SGA status, neonatal composite morbidity and STV. RESULTS: After adjustment for maternal origin, term, gestational diabetes, labor length, SGA status was not associated with any change in STV during labor (mean adjusted STV: -0.20 ms, 95 %CI[-0.58-0.17], p = 0.284 at labor onset, 0.29 ms, 95 %CI[-0.1- 0.68], p = 0.155, in the first stage of labor and 0.36 ms, 95 %CI[-0.02-0.74], p = 0.065 in the second stage of labor). In case of neonatal composite morbidity mean adjusted STV was lower in the first stage of labor (mean adjusted STV: -1.29 ms, 95 %CI[-2.1 - -0.43], p = 0.003) and in the second stage of labor (mean adjusted STV: -1.15 ms, 95 %CI[-1.96 - -0.34], p = 0.005). The results were similar with the addition of delivery mode and meconium-stained amniotic fluid in the model or non-reassuring fetal heart rate and meconium-stained amniotic fluid. CONCLUSIONS: This work suggests that STV decrease during term labor is associated with fetal well-being, independently of fetal weight. This suggests that further prospective studies should consider the evaluation of this parameter in the prediction of neonatal compromise.

Current attitudes and beliefs toward perinatal care orientation before 25 weeks of gestation: The French perspective in 2020.

The survival rate of infants born before 25 weeks of gestational age in France is extremely low compared with that of many other countries: 0%, 1%, and 31% at 22, 23, and 24 weeks' in the last national cohort study. A non-optimal regionalization and variations in practice are prevalent. Some parents in social media and support groups have reported feeling lost and confused with mixed messages leading to lack of trust. These data kindled a major debate in France around perinatal management leading to an investigation exploring neonatologists' perspectives and ways to improve care. The majority (81%) of the responding neonatologists reported more active care and higher survival rates than in 2011, although others continued preferring delivery room comfort care and limited NICU treatment at or before 24 weeks. The desire to improve was an overarching theme in all the respondents' answers to open-ended questions. Barriers to active care included an absence of expertise and of benchmarking to guide optimal care, and limited resources in the NICU and during follow-up - all leading to self-fulfilling prophecies of poor prognosis. Optimization of regionalization, perinatal teamwork and parental involvement, fostering experience by creating specific perinatal centers, stimulating benchmarking, and working with policy makers to allow better long-term outcomes could enable higher survival.

Guidelines for the management of women with severe pre-eclampsia.

OBJECTIVE: To provide national guidelines for the management of women with severe pre-eclampsia. DESIGN: A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The last SFAR and CNGOF guidelines on the management of women with severe pre-eclampsia were published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analysed according to the GRADE® methodology. RESULTS: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1+/-), 9 have a moderate level of evidence (GRADE 2+/-), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. CONCLUSIONS: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe pre-eclampsia.

Impact of pre-eclampsia on renal outcome in sickle cell disease patients.

The long-term consequences of pre-eclampsia (PrE) for renal function have never been determined in patients with sickle cell disease (SCD). Between 2008 and 2015, we screened 306 pregnancies in women with SCD and identified 40 with PrE (13%). The control group consisted of 65 pregnant SCD patients without PrE. In multivariable analysis, PrE events were associated with an increase of 1 log of lactate dehydrogenase level (adjusted odds ratio, aOR = 3·83, P = 0·05), a decrease of 10 g/l of haemoglobin levels (aOR = 2·48, P = 0·006) and one or more vaso-occlusive crisis during pregnancy (aOR = 16·68, P = 0·002). Estimated glomerular filtration rate (eGFR) was similar in the two groups at steady state but was significantly lower in the PrE group after one year of follow-up and at last follow-up (130 vs 148 ml/min/1·73 m2 , P < 0·001 and 120 vs 130 ml/min/1·73 m2 , P < 0·001, respectively). In multivariable analysis, eGFR had returned to steady-state levels one year after pregnancy in patients without PrE but continued to decrease in patients with PrE (ß = -18·15 ml/min/1·73 m2 , P < 0·001). This decline was more marked at the end of follow-up (ß = -31·15 ml/min, P < 0·001). In conclusion, PrE episodes are associated with a significant risk of subsequent renal function decline in SCD patients.

Preeclampsia before 26 weeks of gestation: Obstetrical prognosis for the subsequent pregnancy.

INTRODUCTION: Gestational age at delivery seems to be a risk factor of recurrence of preeclampsia. The objective of this study was to analyze adverse pregnancy outcomes and recurrence of preeclampsia during the subsequent pregnancy in women with a history of pre-eclampsia delivered before 26 weeks of gestation. MATERIAL AND METHOD: We performed a retrospective study in two French tertiary care hospitals between 2000 and 2018. Patients with a history of pre-eclampsia delivered before 26 weeks of gestation were analyzed. Information on the immediate subsequent pregnancy was collected. Adverse composite outcome was defined as recurrent preeclampsia, HELLP syndrome, placental abruption, fetal growth restriction <3rd percentile or <10e percentile with Doppler abnormalities, maternal death and fetal death. RESULTS: Among the 107 patients who met the criteria, 48 were analyzed for a subsequent pregnancy. Seventeen women (35.4 %) developed an adverse composite outcome, occurring for 15 women (31.2 %) before 34 weeks. Ten women (20.8 %) developed a recurrent preeclampsia occurring for 5 women (10.4 %) before 34 weeks. We related 3 HELLP syndromes, 1 placental abruption, 9 fetal growth restrictions, 3 fetal deaths and no maternal death. Compared to baseline normotensive women, chronic hypertension was significantly associated with an increased risk of adverse composite outcome (19.3 vs 58.8 %, p-value 0.014). CONCLUSION: In our population, preeclampsia with delivery before 26 weeks is associated with 35.4 % of adverse composite outcomes and 20.8 % of recurrent preeclampsia during the immediate subsequent pregnancy. These results justify the importance of an ongoing monitoring of these patients during subsequent pregnancy.

Total Versus Free Placental Growth Factor Levels in the Pathogenesis of Preeclampsia.

Elevated circulating sFLT-1 (soluble fms-like tyrosine kinase) and low levels of its ligand, PlGF (placental growth factor), are key characteristics of preeclampsia. However, it is unclear if the low levels of plasma PlGF noted during preeclampsia are due to decreased placental production of PlGF or due to binding of PlGF by increased circulating sFLT-1. Here, we describe a biochemical procedure to dissociate PlGF-sFLT-1 complex ex vivo and when used in conjunction with an immunoassay platform, demonstrate a method to measure total and free PlGF in human blood samples. Using this method, we noted that plasma free PlGF levels were significantly lower in preeclampsia (N=22) than in nonhypertensive controls (N=24; mean, 314 versus 686 pg/mL, P<0.05), but total PlGF levels were not different (mean, 822 versus 800 pg/mL, P=0.49). In contrast, total sFLT-1 levels were significantly higher in preeclampsia than in nonhypertensive controls (mean, 16 957 versus 3029 pg/mL, P<0.01) and sFLT-1 levels correlated with bound PlGF levels (bound PlGF=total PlGF-free PlGF) in these samples (r2=0.68). We confirmed these findings in an independent cohort of subjects (N=49). Furthermore, we did not detect any difference in PlGF mRNA by quantitative polymerase chain reaction or in PlGF protein expression by immunohistochemistry in preeclamptic placentas when compared with nonhypertensive controls. In contrast, sFLT-1 mRNA and protein levels were upregulated in placentas from women with preeclampsia. Taken together with prior studies, our results provide evidence that decrease in circulating PlGF noted during preeclampsia is largely mediated by excess circulating sFLT-1.

A snapshot of the Covid-19 pandemic among pregnant women in France.

OBJECTIVE: To describe the course over time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in French women from the beginning of the pandemic until mid-April, the risk profile of women with respiratory complications, and short-term pregnancy outcomes. METHODS: We collected a case series of pregnant women with COVID-19 in a research network of 33 French maternity units between March 1 and April 14, 2020. All cases of SARS-CoV-2 infection confirmed by a positive result on real-time reverse transcriptase polymerase chain reaction tests of a nasal sample and/or diagnosed by a computed tomography chest scan were included and analyzed. The primary outcome measures were COVID-19 requiring oxygen (oxygen therapy or noninvasive ventilation) and critical COVID-19 (requiring invasive mechanical ventilation or extracorporeal membrane oxygenation, ECMO). Demographic data, baseline comorbidities, and pregnancy outcomes were also collected. RESULTS: Active cases of COVID-19 increased exponentially during March 1-31, 2020; the numbers fell during April 1-14, after lockdown was imposed on March 17. The shape of the curve of active critical COVID-19 mirrored that of all active cases. By April 14, among the 617 pregnant women with COVID-19, 93 women (15.1 %; 95 %CI 12.3-18.1) had required oxygen therapy and 35 others (5.7 %; 95 %CI 4.0-7.8) had had a critical form of COVID-19. The severity of the disease was associated with age older than 35 years and obesity, as well as preexisting diabetes, previous preeclampsia, and gestational hypertension or preeclampsia. One woman with critical COVID-19 died (0.2 %; 95 %CI 0-0.9). Among the women who gave birth, rates of preterm birth in women with non-severe, oxygen-requiring, and critical COVID-19 were 13/123 (10.6 %), 14/29 (48.3 %), and 23/29 (79.3 %) before 37 weeks and 3/123 (2.4 %), 4/29 (13.8 %), and 14/29 (48.3 %) before 32 weeks, respectively. One neonate (0.5 %; 95 %CI 0.01-2.9) in the critical group died from prematurity. CONCLUSION: COVID-19 can be responsible for significant rates of severe acute, potentially deadly, respiratory distress syndromes. The most vulnerable pregnant women, those with comorbidities, may benefit particularly from prevention measures such as a lockdown.

Urinary Placental Growth Factor for Prediction of Placental Adverse Outcomes in High-Risk Pregnancies.

OBJECTIVE: To evaluate whether urinary levels of placental growth factor (PlGF) during pregnancy are associated with the subsequent development of composite adverse outcomes (preeclampsia, fetal growth restriction, placental abruption, perinatal death, maternal death) occurring at less than 34 weeks of gestation. METHODS: This is a preplanned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive either low-molecular-weight (LMW) heparin or aspirin alone. For this substudy we measured urinary levels of PlGF and urinary creatinine at the following gestational windows: 10-13 6/7, 14-17 6/7, 18-21 6/7, 22-25 6/7, 26-29 6/7, 30-33 6/7, and 34-37 6/7 weeks of gestation. RESULTS: Urine samples were available from 187 patients: LMW heparin plus aspirin (n=93) and aspirin alone (n=94). The two groups had comparable baseline characteristics and had similar adverse composite outcomes at less than 34 weeks of gestation (14/93 [15.1%] vs 11/94 [11.7%]; P=.50). There were no significant differences in urine PlGF levels in the patients who received LMW heparin plus aspirin compared with those who received aspirin alone. However, median [interquartile range] urinary PlGF/creatinine concentrations (pg/mg) measured at mid-pregnancy (22-26 weeks of gestation) were significantly lower among women who developed composite adverse outcome at less than 34 weeks of gestation (42.7 [32.4-80.8] vs 255.6 [118.7-391.8] P<.001) and significantly lower among women who developed preeclampsia at less than 34 weeks of gestation (42.7 [27.5-80.7] vs 244.6 [112.9-390.6] P<.001). For a fixed false-positive rate of 10% the sensitivity of urinary PlGF concentrations at mid-pregnancy was 75.2% (area under the curve 0.93) for the subsequent development of composite adverse outcomes. CONCLUSION: Decreased urinary PlGF at mid-gestation (22-26 weeks of gestation) is associated with the subsequent development of preeclampsia-related adverse outcomes at less than 34 weeks of gestation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00986765.

VEGF (Vascular Endothelial Growth Factor) Functionalized Magnetic Beads in a Microfluidic Device to Improve the Angiogenic Balance in Preeclampsia.

Preeclampsia is a hypertensive pregnancy disease associated with a massive increase in sFlt-1 (soluble form of the vascular endothelial growth factor 1) in the maternal circulation, responsible for angiogenic imbalance and endothelial dysfunction. Pilot studies suggest that extracorporeal apheresis may reduce circulating sFlt-1 and prolong pregnancy. Nonspecific apheresis systems have potential adverse effects because of the capture of many other molecules. Our concept is based on a specific and competitive apheresis approach using VEGF (vascular endothelial growth factor) functionalized magnetic beads to capture sFlt-1 while releasing endogenous PlGF (placental growth factor) to restore a physiological angiogenic balance. Magnetic beads were functionalized with VEGF to capture sFlt-1. Experiments were performed using PBS, conditioned media from human trophoblastic cells, and human plasma. The proof of concept was validated in dynamic conditions in a microfluidic device as an approach mimicking real apheresis. Magnetic beads were functionalized with VEGF and characterized to evaluate their surface ligand density and recognition capabilities. VEGF-coated magnetic beads proved to be an efficient support in capturing sFlt-1 and releasing PlGF. In static conditions, sFlt-1 concentration decreased by 33±13%, whereas PlGF concentration increased by 27±10%. In dynamic conditions, the performances were improved, with 40% reduction of sFlt-1 and up to 2-fold increase of free PlGF. The sFlt-1/PlGF ratio was reduced by 63% in the plasma of preeclamptic patients. Apheresis was also associated with VEGF release. A ligand-based approach using VEGF-coated beads is an effective approach to the capture of sFlt-1 and the release of endogenous PlGF. It offers new perspectives for the treatment of preeclampsia.

[Aspirin and preeclampsia]. / Aspirine et prééclampsie.

Indications for aspirin during pregnancy are a matter of debate and there is a recent trend to an extended prescription and an overuse of aspirin in pregnancy. Aspirin is efficient in secondary prevention of preeclampsia essentially in patients with a personal history of preeclampsia. The effect of aspirin on platelet aggregation and on the TXA2/PGI2 balance is dose-dependent. The optimum dosage, from 75mg/day to 150mg/day, needs to be determined. Fetal safety data at 150mg/day are still limited. The efficacy of aspirin seems to be subject to a chronobiological effect. It is recommended to prescribe an evening or bedtime intake. Aspirin, in primary prevention of preeclampsia, given to high-risk patients identified in the first trimester by screening tests, seems to reduce the occurrence of early-onset preeclampsia. Nevertheless, there are insufficient data for the implementation of such screening procedures in practice.

Sildenafil for the treatment of preeclampsia, an update: should we still be enthusiastic?

Preeclampsia is a hypertensive disorder of pregnancy and the clinical manifestation of severe endothelial dysfunction associated with maternal and foetal morbidity and mortality. The primum movens of the disease is the defect of invasion of the uterine arteries by foetal syncytiotrophoblasts, which causes a maladaptive placental response to chronic hypoxia and the secretion of the soluble form of type 1 vascular growth endothelial factor receptor, also called soluble fms-like tyrosine kinase 1 (sFlt-1), the major player in the pathophysiology of the disease. Among its different effects, sFlt-1 induces abnormal sensitivity of the maternal vessels to the vasoconstrictor angiotensin II. This leads to the hypertensive phenotype, recently shown to be abrogated by the administration of sildenafil citrate, which can potentiate the vasodilatory mediator nitrite oxide. This review focuses on the mechanisms of maternal endothelial dysfunction in preeclampsia and discusses the therapeutic window of sildenafil use in the context of preeclampsia, based on the results from preclinical studies and clinical trials. Safety issues recently reported in neonates have considerably narrowed this window.