Recurrence of hypertensive disorders of pregnancy: results from a nationwide prospective cohort study (CONCEPTION).

OBJECTIVE: To assess the risk of gestational hypertension (GH) and pre-eclampsia (PE) during a second pregnancy after occurrence during a first pregnancy. DESIGN: Prospective cohort study. SETTING: CONCEPTION is a French nationwide cohort study that used data from the National Health Data System (SNDS) database. METHODS: We included all women who gave birth for the first time in France in 2010-2018 and who subsequently gave birth. We identified GH and PE through hospital diagnoses and the dispensing of anti-hypertensive drugs. The incidence rate ratios (IRR) of all hypertensive disorder of pregnancy (HDP) during the second pregnancy were estimated using Poisson models adjusted for confounding. MAIN OUTCOME MEASURES: Incidence rate ratios of HDP during the second pregnancy. RESULTS: Of the 2 829 274 women included, 238 506 (8.4%) were diagnosed with HDP during their first pregnancy. In women with GH during their first pregnancy, 11.3% (IRR 4.5, 95% confidence interval [CI] 4.4-4.7) and 3.4% (IRR 5.0, 95% CI 4.8-5.3) developed GH and PE during their second pregnancy, respectively. In women with PE during their first pregnancy, 7.4% (IRR 2.6, 95% CI 2.5-2.7) and 14.7% (IRR 14.3, 95% CI 13.6-15.0) developed GH and PE during their second pregnancy, respectively. The more severe and earlier the PE during the first pregnancy, the stronger the likelihood of having PE during the second pregnancy. Maternal age, social deprivation, obesity, diabetes and chronic hypertension were all associated with PE recurrence. CONCLUSION: These results can guide policymaking that focuses on improving counselling for women who wish to become pregnant more than once, by identifying those who would benefit more from tailored management of modifiable risk factors, and heightened surveillance during post-first pregnancies.

Non-invasive cell-free DNA prenatal screening for trisomy 21 as part of primary screening strategy in twin pregnancies.

OBJECTIVES: The performance of non-invasive prenatal screening using cell-free DNA testing in maternal blood in twin pregnancies is still under-evaluated, while serum marker-based strategies yield poor results. This study aims at assessing the performance of non-invasive prenatal screening for trisomy 21 in twin pregnancies as a first-tier test. The secondary objectives were to assess the failure rate and associated factors. METHODS: This retrospective cohort study included twin pregnancies for which non-invasive prenatal screening using cell-free DNA was performed as the primary screening strategy between May 2017 and October 2019. We used the NIPT VeriSeq® test for in vitro diagnosis and set a fetal fraction cut-off of 4% for monochorionic pregnancies and 8% for dichorionic ones. Clinical data and pregnancy outcome was collected from either physicians or midwives through a questionnaire or were retrieved directly on site. We calculated the performance of non-invasive cell free DNA screening for trisomy 21 and analyzed failure rate and factors. RESULTS: We included 2577 multiple pregnancies among which 1885 (84.8%) were retained after excluding vanishing twins and pregnancies without follow-up. Overall, there were six confirmed trisomy 21 cases (0.32%). For trisomy 21, sensitivity was 100% (95% CI, 61-100%) and the false-positive rate 0.2% (95% CI, 0.07-0.6%). The primary failure rate was 4.6% with 4% due to insufficient fetal fraction. After a new blood draw (59.8% of failed cases), failure rate was only 1.5%. Body mass index and chorionicity were significantly correlated with the risk of failure. CONCLUSION: This study adds further evidence on the high performance of NIPS in twins, as part of the primary screening strategy for trisomy 21, at an extremely low false-positive rate. This article is protected by copyright. All rights reserved.

Performance of semiconductor sequencing platform for non-invasive prenatal genetic screening for fetal aneuploidy: results from a multicenter prospective cohort study in a clinical setting.

OBJECTIVE: To validate and evaluate the performance metrics of the high-throughput semiconductor sequencing platform, Ion Proton®, in non-invasive prenatal genetic screening (NIPS) for common fetal aneuploidies in a clinical setting. METHODS: This prospective cohort study included 2505 pregnant women from eight academic genetics laboratories (695 high risk for trisomy 21 (risk ≥ 1/250) pregnancies in a validation study, and 1810 such pregnancies, without ultrasound anomalies, in a real-life NIPS clinical setting). Outcome was available for all cases in the validation cohort and for 521 in the clinical cohort. Cell-free DNA from plasma samples was sequenced using the Ion Proton sequencer, and sequencing data were analyzed using the open-access software, WISECONDOR. Performance metrics for detection of trisomies 21, 18 and 13 were calculated based on either fetal karyotype result or clinical data collected at birth. We also evaluated the failure rate and compared three methods of fetal fraction quantification (RASSF1A assay, and DEFRAG and SANEFALCON software). RESULTS: Results from both cohorts were consistent and their gestational age was not significantly different so their data were combined to increase the sample size for analysis. Sensitivities and specificities, respectively, were as follows: for trisomy 21, 98.3% (95% CI, 93.5-99.7%) and 99.9% (95% CI, 99.4-100%); for trisomy 18, 96.7% (95% CI, 80.9-99.8%) and 100% (95% CI, 99.6-100%); and for trisomy 13, 94.1% (95% CI, 69.2-99.7%) and 100% (95% CI, 99.6-100%). Our failure rate was 1.2% initially and as low as 0.6% after retesting some of the failed samples. Fetal fraction estimation by the RASSF1A assay was consistent with DEFRAG results, and both were adequate for routine diagnosis. CONCLUSIONS: We describe one of the largest studies evaluating Ion Proton-based NIPS and the first clinical study reporting pregnancy outcome in a large series of patients. This platform is highly efficient in detecting the three most common trisomies. Our protocol is robust and can be implemented easily in any medical genetics laboratory. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Magnetic resonance imaging for abnormally invasive placenta: the added value of intravenous gadolinium injection.

OBJECTIVES: To assess the added value of intravenous gadolinium injection to magnetic resonance imaging (MRI) -based diagnosis of abnormally invasive placenta (AIP) and to examine this in relation to the radiologist's experience. DESIGN: Retrospective study. SETTING: Between March 2009 and October 2012, 31 pregnant women who had previous caesarean delivery together with a placenta praevia and suspected placenta accreta on ultrasound in the third trimester of pregnancy. POPULATION: All were offered MRI examination, and made aware of the limited (but so far reassuring) data regarding fetal safety of gadolinium. Twenty pregnant women agreed to undergo prenatal MRI (1.5 T), with and without gadolinium injection. METHODS: Two sets of MRI examinations without and with gadolinium were reviewed independently 2 months apart by two senior and two junior radiologists; all were blinded to the outcome (known in all cases). Histopathological findings and clinical signs of AIP were considered as the defining criteria of diagnosis. MAIN OUTCOME MEASURE: accuracy of MRI with and without gadolinium was assessed. RESULTS: Eight of the 20 women had confirmed abnormal placental invasion. The overall performance of both sets of readers in detecting AIP increased with gadolinium-sensitivity and specificity of 75.0% (42.0-100%) and 47.9% (19.9-75.9%) increasing to 87.5% (57.1-100%) and 60.4% (33.9-86.9%), respectively (P = 0.04). The added value of gadolinium remained irrespective of radiologist's experience, although senior radiologists performed better overall (sensitivity and specificity of 87.5% and 62.5% versus 62.5% and 33.3%, respectively, increasing with injection to 93.8% and 70.8% versus 81.3% and 50%, respectively; P < 10-4 ). CONCLUSION: There was an association between gadolinium use and improvement in MRI-based diagnostic accuracy for the diagnosis of AIP, for both junior and senior radiologists. TWEETABLE ABSTRACT: Gadolinium injection improves MRI performance of radiologists for the diagnosis of placenta accreta.

[Simulation training for French obstetrics and gynecology residents: A national survey in 2022]. / Formation initiale par la simulation pour les internes français de gynécologie et obstétrique : état des lieux en 2022.

OBJECTIVES: To evaluate the use of simulation among French Obstetrics and Gynecology residency programs. METHODS: A survey was conducted with all 28 French residency program directors. The questionnaire covered equipment and human resources, training programs, types of simulation tools and time spent. RESULTS: Of the cities hosting a residency program, 93% (26/28) responded regarding equipment and human resources, and 75% (21/28) responded regarding training program details. All respondents declared having at least one structure dedicated to simulation. A formal training program was reported by 81% (21/26) of cities. This training program was mandatory in 73% of the cases. There was a median number of seven senior trainers involved, three of whom had received a specific training in medical education. Most of declared simulation activities concerned technical skills in obstetrics and surgery. Simulations to practice breaking bad news were offered by 62% (13/21) of cities. The median number of half-days spent annually on simulation training was 55 (IQR: 38-83). CONCLUSION: Simulation training is now widely available among French residency programs. There remains heterogeneity between centers regarding equipment, time spent and content of simulation curricula. The French College of Teachers of Gynecology and Obstetrics has proposed a roadmap for the content of simulation-based training based on the results of this survey. An inventory of all existing "train the trainers" simulation programs in France is also provided.

Association between oocyte donation and maternal and perinatal outcomes in women aged 43 years or older.

BACKGROUND: Although older maternal age is a risk factor for pregnancy complications, an increasing number of women delay conception until the age of 40, and some must resort to IVF with oocyte donation. Our objective was to study the association between IVF, both with and without oocyte donation, and maternal and perinatal outcomes in a population of older women. METHODS: This retrospective study covered all women, aged 43 or more, who gave birth between 2008 and 2010. Univariate and multivariate analyses with logistic regression models were used to compare maternal and perinatal outcomes as a function of mode of conception: without IVF, with IVF using own oocytes or with IVF and oocyte donation. RESULTS: The study included 380 women, including 40 who had IVF without oocyte donation (10.5%) and 104 who had both (27.4%). There were 326 singleton and 54 multiple pregnancies. Overall, the complication rate was high: 8.7% pre-eclampsia, 6.1% gestational diabetes, 20.2% preterm delivery and 8.2% very preterm delivery (before 33 weeks), 44.8% Cesarean sections and 7.4% severe post-partum hemorrhage (PPH). The pre-eclampsia rate differed significantly between the groups (3.8% after no IVF, 10.0% after IVF only and 19.2% after IVF with oocyte donation, P< 0.001). After adjustment, the risk of pre-eclampsia was significantly higher in women with donated oocytes compared with pregnant women without IVF [adjusted OR = 3.3 (1.2-8.9)]. The rate of twin pregnancy was significantly higher in women with IVF and oocyte donation (39.4 versus 15.0% with IVF only and 2.5% without IVF, P< 0.001). Twin pregnancy was significantly associated with the risk of preterm delivery [adjusted OR = 8.9 (4.0-19.9)] and PPH [adjusted OR = 3.5 (1.3-9.5)]. CONCLUSION: In women aged 43 years or older, pregnancies obtained by IVF with oocyte donation are associated with higher rates of pre-eclampsia and twin pregnancies than those obtained without IVF or with IVF using their own oocytes.

Comparison of perinatal outcome after pre-viable preterm prelabour rupture of membranes in two centres with different rates of termination of pregnancy.

OBJECTIVE: To assess perinatal outcomes after expectant management in the case of preterm prelabour rupture of membranes (PPROM) before 25 weeks of gestation, according to the rate of termination of pregnancy (TOP). DESIGN: Retrospective comparative cohort study. POPULATION: Singleton pregnancies complicated by PPROM between 15(0/7) and 24(6/7) weeks of gestation, from January 2003 to January 2007. METHODS: Comparison of perinatal outcomes in two French tertiary care referral centres presumed to have different rates of TOP. MAIN OUTCOME MEASURE: Rates of TOP, survival and survival without major morbidity. RESULTS: A total of 113 women experienced PPROM (49 in centre A and 64 in centre B). A lower proportion of patients opted for TOP in centre A (40.8%) than in centre B (56.3%). The baseline characteristics of patients and pregnancies, and gestational age at PPROM, were not different between the two centres. Mean gestational age at delivery (28.1 versus 25.4 weeks of gestation; P < 0.01), mean latency period (45.5 versus 16.1 days; P < 0.01), mean birthweight (1295 versus 929 g; P = 0.04) and survival (46.9 versus 20.3%; P < 0.01) were significantly higher in centre A than in centre B. The percentage of neonates alive without major morbidity was also higher in centre A than in centre B (42.9 versus 20.3%; P = 0.01). CONCLUSIONS: Perinatal outcomes of pregnancies managed expectantly were not better in the centre where the TOP rate was higher. The perinatal risk of pregnancies complicated by pre-viable PPROM remains high.

Semi-automated adjusted measurement of nuchal translucency: feasibility and reproducibility.

OBJECTIVE: The variability of nuchal translucency thickness (NT) measurements in the first trimester appears to be associated in part with caliper placement. Methods for obtaining semi-automated adjusted measurements (SAAMs) can provide several NT values (maximum, minimum, mean and median) automatically within a manually set frame in the zone of interest. This study sought to assess the feasibility and reproducibility of these SAAM-NTs. METHODS: Three readers, two experts and one less experienced, examined archive images of 160 patients and obtained SAAM-NTs from them, on two separate occasions. The intra- and interobserver reproducibility were assessed by calculating the intraclass correlation coefficients (ICCs) for maximum, mean and median SAAM-NTs, and Bland-Altman plots were constructed. RESULTS: SAAM-NTs were technically feasible for all 160 images. The range of ICCs for intraobserver reproducibility was 0.76-0.93 for mean SAAM-NT, 0.76-0.95 for median SAAM-NT and 0.74-0.95 for maximum SAAM-NT. Interobserver ICCs were 0.85, 0.85 and 0.84 for mean SAAM-NT, median SAAM-NT and maximum SAAM-NT, respectively. There were no significant differences for intra- and interobserver reproducibility of median, mean and maximum SAAM-NTs. CONCLUSIONS: SAAM-NT is feasible with a high level of intra- and interobserver reproducibility. This easy-to-use method has the potential to simplify screening during the first trimester. It should be evaluated further and compared with the manual measurement method.

Fetal tumors of the choroid plexus: is differential diagnosis between papilloma and carcinoma possible?

Fetal choroid plexus tumors are uncommon. The prognosis is widely variable and depends on the histological findings: papilloma or carcinoma. We report a case of prenatal diagnosis of choroid plexus mass detected by ultrasound at 33 weeks of gestation. Prenatal (T1, T2, T2* and diffusion weighted sequences) magnetic resonance imaging (MRI) was used to rule out a hematoma. Follow-up examination by ultrasound and MRI revealed a significant increase in the volume of the mass, suggesting a diagnosis of malignant tumor. A healthy neonate was delivered by Cesarean section at 38 weeks of gestation. Full surgical excision of the tumor was performed at 20 days after delivery and histological analysis revealed a papilloma.

Correlation between uteroplacental three-dimensional power Doppler indices and true uterine blood flow: evaluation in a pregnant sheep model.

OBJECTIVES: Three-dimensional (3D) Doppler quantification within the uteroplacental unit could be of great help in understanding and screening for pre-eclampsia and intrauterine growth restriction. Yet the correlation between 3D Doppler indices and true blood flow has not been confirmed in vivo. The aim of this study was to evaluate this correlation in a pregnant sheep model. METHODS: A blood flow quantitative sensor and a controllable vascular occlusion system were placed around the common uterine artery in seven sheep in late pregnancy, while all the other arterial supplies were ligated. Several occlusion levels were applied, from 0 to 100%, simultaneously with 3D Doppler acquisitions of several placentomes, using standardized settings. Each placentome was analyzed using VOCAL™ (Virtual Organ Computer-aided AnaLysis) software. The correlation between true blood flow and Doppler indices (vascularization index (VI), flow index (FI) and vascularization flow index (VFI)) was evaluated, together with measurement reproducibility. RESULTS: Forty-eight acquisitions were analyzed. All 3D Doppler indices were significantly correlated with true blood flow. Higher correlations were observed for VI and VFI (r = 0.81 (0.74-0.87), P < 0.0001 and r = 0.75 (0.67-0.82), P < 0.0001) compared with FI (r = 0.53 (0.38-0.64) P < 0.0001). Both intra- and interobserver reproducibility were high, with intraclass correlation coefficients of at least 0.799. CONCLUSION: This is the first in-vivo experimental study confirming a significant correlation between true blood perfusion and quantitative 3D Doppler indices measured within the uteroplacental unit. These results confirm the potential usefulness of 3D Doppler ultrasound for the assessment of placental vascular insufficiency both in clinical cases and in a research setting.

Inter-observer agreement in clinical decision-making for abnormal cardiotocogram (CTG) during labour: a comparison between CTG and CTG plus STAN.

OBJECTIVE: To compare inter-observer agreement for clinical decision-making with cardiotocography (CTG) and combined CTG with ST-segment analysis (STAN). DESIGN: Experimental study. SETTING: Three hospital obstetrics departments in France. POPULATION: Thirty randomly selected nonreassuring CTG recordings during labour of women with singleton term pregnancies in cephalic position. METHODS: Seven obstetricians independently assessed the tracings, displayed in a random order on their computers, on two separate sessions, the first without and the second with STAN information. The observers received clinical information about the labour as the tracings continued and were asked whether they would intervene. For analysis, we considered that intervention was justified for the neonates with pH < 7.05 and that nonintervention was justified for those with a pH > 7.10 after spontaneous delivery. MAIN OUTCOME MEASURES: Kappa values and rates of inter-observer agreement for intervention and for nonintervention. RESULTS: Kappa for inter-observer agreement was 0.50 (0.29-0.69) with CTG, and 0.67 (0.48-0.81) with CTG + STAN. The rate of inter-observer agreement for the decision to intervene was 73% (68-77%) with CTG and 70% (66-75%) with CTG + STAN (P = 0.4), and for the nonintervention decision it was 48% (42-54%) and 69% (64-74%), respectively (P < 0.0001). The rate of agreement for justified intervention was 94% (91-97%) with CTG and 85% (80-90%) with CTG + STAN (P < 0.001) and for justified nonintervention, 56% (48-63%) with CTG and 84% (79-89%) with CTG + STAN (P < 0.0001). CONCLUSIONS: In cases with abnormal CTG, ST analysis may improve consistency in clinical decision-making and decrease unnecessary interventions, but may also lead on rare occasions to unjustified decisions not to intervene.

Radiofrequency ablation of retained placenta accreta after conservative management: preliminary evaluation in the pregnant ewe and in normal human placenta in vitro.

OBJECTIVE: To evaluate radiofrequency (RF) efficiency and safety for the ablation of retained placenta in humans, using a pregnant sheep model. DESIGN: Experimental study. SETTING: Laboratory of Surgery School, Nancy, France. POPULATION/SAMPLE: Three pregnant ewes/ten human placentas. METHODS: Various RF procedures were tested in pregnant ewes on 50 placentomes (individual placental units). Reproducibility of the best procedure was then evaluated in a further 20 placentomes and on ten human term placentas in vitro after delivery. MAIN OUTCOME MEASURES: Placental tissues destruction, lesions' size, myometrial lesions. RESULTS: Low power (100 W) and low target temperatures (60 degrees C) lead to homogenous tissue destruction, without myometrial lesion. No significant difference was observed in terms of lesion size and procedure duration for in the placentomes of pregnant ewe in vivo and in human placentas in vitro. The diameter of the ablation could be correlated with the tines deployment. CONCLUSION: The placental tissue structure is very permissive to RF energy, which suggests that RF could be used for the ablation of retained placenta, providing optimal control of tissue destruction. These results call for further experimental evaluations.

Is rapid aneuploidy screening used alone acceptable in prenatal diagnosis? An evaluation of the possible role of ultrasound examination.

OBJECTIVE: The objectives of this study were to use a factual basis to: (1) determine the number, nature, and probable phenotypic consequences of karyotype anomalies that would probably be missed (structural anomalies, uncommon aneuploidies and mosaic aneuploidies) by rapid aneuploidy screening (RAS), and (2) appraise whether RAS can replace traditional karyotyping when amniocenteses are performed for increased risk of Down's syndrome by maternal serum screening or advanced maternal age in the absence of ultrasound abnormality. METHODS: This retrospective cohort study analysed the indications, results and outcomes of 5,713 consecutive amniocenteses over a 5-year period at a single prenatal diagnosis centre in Paris. RESULTS: Advanced maternal age and increased Down's risk with maternal serum marker were the most common indications. Chromosome abnormalities were detected in 3.64% of the pregnancies tested, and unexpected structural anomalies in 0.63% (n = 36). Translocations were more likely to be reciprocal, balanced and of parental origin. There were 6 mosaic gonosomal aneuploidies. Overall, 4 mosaic autosomal aneuploidies and 36 structural aberrations would not have been recognised by RAS alone. Of the 4 mosaic autosomal aneuploidies, all were terminated, one had major malformations and the others had discrete signs that a good quality ultrasound examination would probably not detect. Of the 36 structural aberrations, 24 would be undetected by ultrasound scan, from which 6 would be associated with a significant risk of an abnormal phenotype outcome. CONCLUSION: In conclusion, our data do not provide evidence that RAS can replace the traditional karyotype. It is probably impossible to arrive in a universal conclusion of which approach (karyotype or RAS) is definitely better than the other. Each prenatal centre could have its own approach depending on the local data analysis, including quality control of ultrasounds.

[Assessment of thyroid hormones and androgens in amniotic fluid: clinical interest]. / Dosage des hormones thyroïdiennes et surrénaliennes dans le liquide amniotique: aide au diagnostic.

Ultrasound scanning is able to detect foetal goiter due either to an hypothyroidy either to an hyperthyroidy, or clitoris hypertrophia resulting from adrenal hyperplasia in female, during the second half of pregnancy. The diagnosis of these rare diseases is of interest because the treatment can be started during pregnancy. An amniotic fluid punction can be discussed and its biochemical analysis may be of interest even though very few commercial assays have been tested on amniotic fluid. Our aim was two investigate the practicability and the value of free thyroxin (FT4), thyrotropin (TSH), 17alpha hydroxyprogesterone (17-OHP) and delta 4 androstenedione (Delta4A) measurement on amniotic fluid using commercially available assays for serum. FT4 and TSH are detectable at low levels in amniotic fluid. FT4 significantly increases from 2.1 pmol/L to 4.2 pmol/L while TSH significantly decreases from 0.27 mU/L to 0.12 mU/L during the second half of pregnancy. An increase in amniotic fluid TSH concentration contributes to the diagnosis of foetal hypothyroidy while the measurement of amniotic fluid FT4 is not informative in case of foetal goiter. 17-OHP and Delta4A are present in amniotic fluid at the same level as in serum. 17-OHP significantly decreases from 1.9 ng/mL to 1 ng/mL during the second half of pregnancy while Delta4A significantly increases from 0.5 ng/mL to 0.8 ng/mL. Absence of increase in their concentrations excludes any severe adrenal hyperplasia.

[Decision making on breech delivery: information as a way to reconcile maternal autonomy and medical responsibility]. / Peut-on concilier autonomie maternelle et responsabilité médicale dans les décisions de voies d'accouchement des foetus en siège? Rôle de l'information.

As far as breech vaginal delivery remains an acceptable option, each case has to be evaluated in order to determine whether in that particular situation it is medically relevant. When vaginal delivery is to be envisaged, maternal consent is needed. This implies seeking medical information that allows women to express their autonomy and to be part of the decision regarding their delivery. This article concerns a physicians reflection on medical information and on connections between the obstetrician's responsibility, that of the future mother, and autonomy. Understanding information as necessarily arising from an exchange between the care giver and the future mother is the condition that allows the coexistence of maternal autonomy and medical responsibility.

Management of threatened preterm delivery in France: a national practice survey (the EVAPRIMA study).

OBJECTIVES: To describe the management of threatened preterm delivery (TPD) in France 3 years after publication of the French guidelines and to analyse the factors of variation of the practices observed. DESIGN: Population-based study. SETTING: Representative sample of French maternity units. The study included 107 hospitals, accounting for 20% of all French maternity units. POPULATION: Women hospitalised for TPD during May 2005. METHODS: Cross-sectional national practice survey. RESULTS: Of the 734 admissions for TPD, 12.1% involved premature rupture of membranes and 12.9% were in utero transfers. Women admitted for TPD accounted for roughly 6% of all annual deliveries, regardless of the unit's level of care, and 42.4% of these women delivered preterm: none delivered before 32 weeks in level 1 maternity units, 11.6% in level 2 and 88.4% in level 3. Transvaginal cervical ultrasound was performed for 54.5% of the women with intact membranes. Tocolysis was administered in 87.1% of women with intact membranes, with 45.6% of such women receiving this intervention for longer than 48 hours. First-line tocolytics used were calcium channel blockers (53.7%), beta-agonists (34.7%) or atosiban (8.8%), but their distribution differed substantially according to level of care. Maintenance tocolysis was administered to 385 women (59.8%) with intact membranes. Of the women admitted before 34 weeks, 21.1% did not receive corticosteroids. CONCLUSIONS: Practices for the management of TPD vary widely and appear to depend on the level of care. Some practices appear less than optimal, especially those related to duration of tocolysis, maintenance tocolysis, antenatal corticosteroid and use of cervical ultrasound.

[Pathophysiology of preeclampsia]. / Physiopathologie de la prééclampsie.

Preeclampsia is a human disease, usually occurring during the third trimester of pregnancy. The underlying pathogenetic mechanisms of preeclampsia are much debated. Current hypotheses include placental dysfunction, inflammatory disease, genetic predisposition and immune maladaptation. Recent studies highlight the role of vascular-mediated factors in the pathophysiology of preeclampsia and allow new hopes for screening and therapeutic approaches. This article describes pathophysiological mechanisms involved in the defective uteroplacental vascularization leading to placental and endothelial dysfunction.

Cost-effectiveness of vaccination against cytomegalovirus (CMV) in adolescent girls to prevent infections in pregnant women living in France.

BACKGROUND: CMV infections are the most frequent congenital infections worldwide. AIM: Assess the cost-effectiveness of vaccination strategies of adolescent girls vs. current practice (hygiene counseling) to prevent CMV seroconversions during pregnancy in France. METHOD: A Markov decision-tree model simulated overtime the trajectory of a single fictive cohort of 390,000 adolescent women aged 14 years old, living in France. Impact of vaccination was explored until the end of their reproductive live 40 years later. STRATEGIES COMPARED: "S1: No vaccination" (current practice); "S2: Routine vaccination"; "S3: Screening and vaccination of the seronegative". MODEL PARAMETERS: Seroconversion rate without vaccination (0.035%/pregnant woman-week); fetal transmission risk (41%). Vaccine vs. no vaccination: a 50% decrease in maternal seroconversions. OUTCOMES: Quality-Adjusted Life-Years (QALYs) of the cohort-born babies; discounted costs; Incremental Cost-Effectiveness Ratio (ICER). RESULTS: S2 was the most effective strategy (with 35,000 QALYs gained) and the most expensive (€211,533,000); S1 was the least effective and least costly (€75,423,000). ICERs of strategy S3 vs. S1, and S2 vs. S3 were 6,000€/QALY gained (95% uncertainty range [2700-13,300]) and 16,000€/QALY [negative ICER (S3 dominated by S2) - 94,000] gained, respectively; highly cost-effective because ICER < 1∗France's GPD/capita = €30,000. SENSITIVITY ANALYSIS: If the seroprevalence was >62% (vs. 20% in the base case), S3 would become the most efficient strategy. CONCLUSION: In France, systematic vaccination of adolescent girls was the most efficient strategy to prevent maternal seroconversions. If the population was less than 62% immune, systematic screening and vaccination of susceptibles would become the most cost-effective approach.

Involvement of PPARgamma in human trophoblast invasion.

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily that controls the expression of a large array of genes in a ligand-dependent manner. In the human placenta, PPARgamma is specifically expressed in the villous cytotrophoblast and syncytiotrophoblast as well as in the extravillous cytotrophoblastic cells (EVCT) along their invasive pathway. The present study used two cellular models, primary cultures of trophoblastic cells differentiated in vitro in extravillous trophoblastic cells and a cell line (HIPEC65), which was established from a primary culture of EVCT transformed by T-SV40. We observed that natural (15d-PGJ2) or synthetic ligands of PPARgamma (rosiglitazone) inhibit cell invasion in a concentration-dependent manner, with no effect on cell proliferation. This is associated with a modulation of the expression of trophoblastic genes described to be directly involved in the control of EVCT invasiveness, such as GH-V (-20%), TGFbeta2 (-30%), PAPP-A (-60%) and IL1beta (+300%.). In order to identify PPARgamma potential ligands at the fetomaternal interface, we purified LDL (low density lipoprotein) from human sera and oxidized them in vitro in the presence of copper. OxLDL inhibit in vitro extravillous trophoblast cell invasion, whereas native LDL have no effect. In situ OxLDL and their LOX-1 receptor, as well as PPARgamma are immunodetected in trophoblasts at the maternofetal interface.

PPARs and the placenta.

The discovery of the peroxisome proliferator-activated receptors (PPARs) in 1990s provided new insights in understanding the mechanisms involved in the control of energy homeostasis and in cell differentiation, proliferation, apoptosis and the inflammatory process. The PPARs became thus an exciting therapeutic target for diabetes, metabolic syndrome, atherosclerosis, and cancer. Unexpectedly, genetic studies performed in mice established that PPARgamma are essential for placental development. After a brief description of structural and functional features of PPARs, we will summarize in this review the most recent results concerning expression and the role of PPARs in placenta and of PPARgamma in human trophoblastic cells in particular.