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.

OBJECTIVE: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality. Early treatment by aspirin has been shown to significantly reduce PE risk before 37weeks supporting the implementation of first-trimester screening.
METHODS: A targeted screening was recently implemented at Toulouse University Hospital for women in their first pregnancy or those with personal or familial history of PE. It uses Fetal Medicine Foundation (FMF) algorithm that combines maternal characteristics, clinical, biophysical and biochemical (PAPP-A, Pregnancy Associated Plasma Protein-A, and PlGF, Placental Growth Factor) data. We describe this first population of pregnant women and compare our results with those of a mini-test that excludes PlGF and biophysical data.
RESULTS: Between October 2016 and September 2017, 500women have benefited from this screening. In such targeted population, we identified 3,6 % (n=18) of women at high risk to develop PE before 34weeks and 9,6 % (n=48) of women at high risk to develop PE between 34 and 37weeks. When we recalculated the risk using the mini-test, only 10women (56 %) were identified at high risk of early PE.
CONCLUSIONS: For the first time in France, we report the result of a targeted screening of PE during the first trimester using the FMF algorithm. We describe the screened population and show that it is more efficient than the mini-test.

Aspirin (acetylsalicylic acid) has been used ever since the Antiquity for its painkilling and anti-inflammatory effects. Its antiplatelet properties have then extended its indications to the field of coronaropathy and vascular cerebral disease, and finally to vascular placental disease. Aspirin has been widely prescribed since the 1980\'s to prevent pre-eclampsia, intra-uterine growth retardation and fetal death of vascular origin. It has also been proposed to prevent unexplained recurrent miscarriages. Its use during pregnancy is considered as safe, provided the daily doses do not exceed 100mg. Aspirin has been proven efficient to prevent pre-eclampsia and fetal growth restriction in high-risk patients. The benefits of prescribing aspirin have been demonstrated neither for vascular placental disease prevention in low risk patients, nor in cases of unexplained recurrent miscarriages.

The use of low-dose aspirin in pregnancy should remain a highly targeted indication since its long-term safety has not been established and should be restricted to women at high risk of vascular complications. Indications for which the benefit of aspirin has been shown are women with a history of preeclampsia responsible for a premature birth before 34 weeks, those having at least two history of preeclampsia, those with an antiphospholipid syndrome and those with lupus associated with positive antiphospholipid antibodies or renal failure. In all other cases, the level of evidence of the benefit of aspirin is insufficient to recommend its routine prescription.

In normal pregnancies, the earliest stages of development take place in a low oxygen (O2) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O2free radicals. Oxidative stress is manifested at the maternal-fetal interface from early pregnancy onwards. In early pregnancy, a well-controlled oxidative stress plays a role in modulating placental development, functions and remodelling. Focal trophoblastic oxidative damage and progressive villous degeneration trigger the formation of the fetal membranes, which is an essential developmental step enabling vaginal delivery. Our data have demonstrated that the first trimester placenta in humans is histiotrophic and not haemochorial. The development and maintenance of a physiological O2 gradient between the uterine and fetal circulations is also essential for placental functions, such as transport and hormonal synthesis. Pathological oxidative stress arises when the production of reactive O2 species overwhelms the intrinsic anti-oxidant defences causing indiscriminate damage to biological molecules, leading to loss of function and cell death. We here review the role of oxidative stress in the pathophysiology of miscarriage, pre-eclampsia and fetal growth restriction.