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OBJECTIVE: To identify strategies to reduce maternal and neonatal morbidity related to preeclampsia.
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).
CONCLUSIONS: 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.

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The aim of the study was to evaluate if fetal cell-free DNA (cfDNA) fraction circulating in maternal blood at the beginning of the second trimester is associated with obstetrical complications.
This is a retrospective unicentric study conducted at the hospital of Poissy Saint Germain between the 1st January 2015, and the 31st. December 2016, Each woman who had a genetic counseling in order to realize a non-invasive prenatal test (NIPT) was included. Only singleton pregnancies with a documented-issue were analysed. The primary criteria was a composite criteria, defined as the occurrence of preeclampsia, in utero fetal growth, or a spontaneous preterm delivery. A descriptive analyse was first conducted, secondly completed by a sub-group one: \"high fetal fraction\" (>90th percentile) group, \"low fetal-fraction\" group (<10th percentile) and \"medium fetal-fraction\" (control group) group.
A total of 417 women had a cfDNA test, which was performed at a mean gestational age of 17.1 weeks of gestation. A total of 17% of pregnancies met the primary criteria. Among them, there were 8 (1.9%) pre-eclampsia, 49 (11.8%) intra-uterine growth restriction and 14 (3.4%) preterm births. There was no significant difference for the occurrence of the primary criteria (P>0.99) and of each obstetrical complication between each group.
Fetal cf-DNA fraction measured at the beginning of the second trimester is not associated with common obstetrical complications.

Ascites in severe pre-eclampsia may impact foetal and maternal outcomes. The objective was to determine the prevalence of ascites in women with severe pre-eclampsia by point of care (POC) ultrasound and to determine whether it correlates with higher perinatal risks.
Prospective cohort study of patients admitted with severe pre-eclampsia at 2 teaching hospitals in Kigali, Rwanda. Serial POC ultrasound was performed to document ascites. Patients were stratified by the presence of ascites in perinatal period. Maternal demographics and complications were recorded and compared between groups.
There were 112 patients with severe pre-eclampsia, and ascites was found in 53.5% (76.7% antepartum, and 23.3% postpartum). Antepartum ascites correlated with an earlier delivery (32.2 ± 0.51 vs. 33.8 ± 0.47 weeks, P = 0.022) as well as lower birthweight (1587.3 ± 77.03 vs. 2011.6 ± 103.5 g, P = 0.002). Antepartum ascites was associated with higher stillbirth rates (P = 0.034) and NICU admission (87.2% vs. 68%, P = 0.034). Maternal hospital stay was increased in the ascites group (P < 0.0001).
Ascites is common in severe pre-eclampsia in Rwanda and maybe a prognosticator for poor outcomes. A larger sample is necessary to determine whether ascites is independently associated with maternal morbidity and mortality and whether documenting its presence aids in the management of the foetus and mother.
L\'ascite dans la pré-éclampsie sévère peut avoir un impact sur les résultats pour le fœtus et la mère. L\'objectif était de déterminer la prévalence de l\'ascite chez les femmes présentant une échographie de pré-éclampsie sévère au point des soins et de déterminer si elle corrélait avec des risques périnataux plus élevés. MÉTHODES: Etude de cohorte prospective de patientes admises avec une pré-éclampsie sévère dans deux hôpitaux universitaires de Kigali, au Rwanda. Une échographie au point des soins a été réalisée en série pour documenter l\'ascite. Les patientes ont été stratifiées en fonction de la présence d\'ascite en période périnatale. Les données démographiques maternelles et les complications ont été enregistrées et comparées entre les groupes. RÉSULTATS: Il y avait 112 patientes atteintes de pré-éclampsie sévère et l\'ascite a été trouvé chez 53,5% (76,7% antépartum et 23,3% postpartum). L\'ascite antépartum corrélait avec un accouchement antérieur (32,2 ± 0,51 vs 33,8 ± 0,47 semaines, p = 0,022) ainsi qu\'avec un poids à la naissance plus faible (1587,3 ± 77,03 vs 2011,6 ± 103,5 g, p = 0,002). L\'ascite antépartum était associée à des taux de mortinatalité plus élevés (p = 0,034) et à une admission en USIN-US (87,2% contre 68%, p = 0,034). Le séjour à l\'hôpital de la mère était augmenté dans le groupe ascite (p <0,0001).
L\'ascite est fréquente dans la pré-éclampsie sévère au Rwanda et peut être un pronostic pour des résultats médiocres. Un échantillon plus important est nécessaire pour déterminer si l\'ascite est associée de manière indépendante à la morbidité et à la mortalité maternelles et si la documentation de sa présence facilite la prise en charge du fœtus et de la mère.

The role of angiogenic factors in the onset of clinical manifestations of preeclampsia was demonstrated in 2003 by the implication of sFlt-1, PlGF and VEGF, and in 2006 by the implication of soluble endoglin. Placental ischemia and inflammation observed in preeclampsia alter both the production and progression of angiogenic factors during pregnancy. During the first trimester, the combination of PlGF with clinical, biophysical and biological factors results in a better test than the conventional one. However, the clinical value of this method remains to be confirmed. During the second and third trimesters, the sFlt-1/PlGF ratio may be used, with or without pre-existing renal disease, for short-term prediction, diagnosis, and prognosis, and to evaluate the effectiveness of preeclampsia treatment. While a sFlt-1/PlGF ratio<38 and≤33, respectively, rules out the short-term onset and diagnosis of preeclampsia, a sFlt-1/PlGF ratio≥85 between 20 and 34 weeks of pregnancy and≥110 beyond 34 weeks of pregnancy confirms a diagnosis of preeclampsia. Angiogenic and non-angiogenic preeclampsia are identified by a sFlt-1PlGF≥85 and<85, respectively, with the risk of maternal and fetal complications at two weeks differing between the two. Similarly, a sFlt-1/PlGF ratio>665 and>205, respectively, is a good short-term predictor of adverse outcomes of early and late-onset preeclampsia. These values could be incorporated into future guidelines for better clinical management of preeclampsia.

Preeclampsia: New Classifications Abstract. Preeclampsia is a multisystem disease leading to systemic impairment of the maternal endothelial function. A dysbalance of pro- and antiangiogenic factors appears to be significantly involved. The vascular disease leads to the manifestation of symptoms such as arterial hypertension and involvement of end organs such as kidney, liver and brain. The classical diagnostic criterion for arterial hypertension, \'proteinuria\' has been downgraded and is no longer obligatory for diagnosis, if other criteria, as maternal organ dysfunction or intrauterine growth retardation, are present. In addition, white-coat hypertension has been included in the classification of hypertension in pregnancy. To classify preeclampsia as \'mild\' is being discouraged in the clinical setting to account for the possibility of rapid worsening with significant danger for mother and foetus.
Zusammenfassung. Die Präeklampsie ist eine Multisystemerkrankung, die vorwiegend zu einer systemischen Beeinträchtigung der mütterlichen Endothelfunktion führt. Eine Dysbalance von proangiogenen und antiangiogenen Faktoren ist dabei massgeblich beteiligt. Die vaskuläre Erkrankung führt zur klinischen Manifestation der Symptome wie arterieller Hypertonie und zur Beteiligung der Endorgane, v.a. Niere, Leber und Gehirn. Das klassische Diagnosekriterium «Proteinurie» ist gemäss internationaler Empfehlungen nicht mehr obligat zur Diagnosestellung erforderlich, sondern nur noch ein mögliches Kriterium und kann durch die Kriterien mütterliche Organbeteiligung oder fetale Wachstumsretardierung ersetzt werden. Die Weisskittelhypertonie wird in die Klassifikation der hypertensiven Erkrankungen zusätzlich aufgenommen. Die Begrifflichkeit «leichte» Präeklampsie wird im klinischen Setting wegen der potenziell raschen Verschlechterung und damit einhergehenden mütterlichen und fetalen Gefährdung nicht empfohlen.

Preeclampsia is an inflammatory disease and has connection with increased pro-inflammatory cytokines. Aspirin reduces the incidence of preeclampsia complications. However, the effects of aspirin on lipopolysaccharide-induced preeclampsia-like symptoms in rats have not been reported and the underlying molecular mechanism has not been illuminated. Hence, we investigated the anti-inflammatory effects of aspirin on lipopolysaccharide-induced preeclampsia-like phenotypes in pregnant rats and elucidated the potential molecular mechanism. Preeclampsia-like phenotypes were induced by tail vein injection of lipopolysaccharide (1 μg/kg) on gestational day 14. Aspirin (2 mg/kg per day) were administered from gestational day 14 to 19. Clinical phenotypes were recorded. Placenta tissues and serum were obtained to measure inflammatory cytokines levels using ELISA kit on gestational day 20. The mRNA expressions of IL-6, IL-1β, and MCP-1 were measured by real-time PCR. Protein expressions including TLR4, MyD88, NF-κBp65, and TLR2 were determined by Western blot analysis in the rat placentas of each group. Aspirin obviously assuaged lipopolysaccharide-induced preeclampsia-like phenotypes in pregnant rats. Aspirin treatment significantly decreased the levels of pro-inflammatory cytokines in serum and placenta tissues of preeclampsia rats. Aspirin also obviously downregulated the mRNA expressions of IL-6, IL-1β, and MCP-1 and assuaged the activation of TLR4, MyD88, NF-κBp65, and TLR2 in the placental tissue. Our results indicated that aspirin could assuage preeclampsia-like phenotypes, and this improvement effect is possibly the result of the suppression of pro-inflammatory cytokines via the TLR4, MyD88, NF-κBp65, and TLR2 signaling pathway.

Pre-eclampsia prevention represents a major public health issue, as this vasculo-placental disorder generates a great burden of foeto-maternal morbi-mortality. Aspirin has proved its efficacy in primary and secondary pre-eclampsia prevention, especially when it is given at 150mg per day bedtime before 15 weeks of gestation to high-risk women. In the English trial ASPRE, high-risk women were identified by an algorithm taking into account angiogenic biomarkers ascertained at the end of first trimester of pregnancy. This article focuses on physiopathological mechanisms and risk factors of pre-eclampsia and on the interest of early angiogenic biomarkers dosing during pregnancy, for the assessment of pre-eclampsia risk. Unlike Great Britain or Israel, cost-effectiveness of this algorithm in general population has not been assessed in France. Finally, systemic lupus erythematous is at high risk of vasculo-placental disorders. Although few studies of angiogenic biomarkers dosing during lupus pregnancies identified a correlation between high sFlt1 levels at the end of first trimester and subsequent onset of severe vasculo-placental disorders, with a very good negative predictive value of sFtl1. Angiogenic biomarkers ascertainment for screening of vasculo-placental disorders in pregnant women with systemic lupus erythematous could allow targeting at best women needing an aspirin treatment and a closer monitoring.