[Skin and pregnancy]. / Peau et grossesse.

Pregnancy has a substantial impact on the hormonal status of the organism, consequently influencing the physiology of the skin. This results in dermatoses that only occur during pregnancy, which can also improve or exacerbate pre-existing dermatoses. In this article, we explain the management of pregnancy-specific dermatoses : atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis, impetigo herpetiformis, and intrahepatic cholestasis of pregnancy. It is essential to clearly distinguish these different dermatoses as some of them, such as pemphigoid gestationis, impetigo herpetiformis and intrahepatic cholestasis of pregnancy, can have fetal consequences and as result, need to be closely monitored by the obstetricians.

La grossesse a un impact considérable sur le statut hormonal de l'organisme, influençant ainsi la physiologie cutanée. Cela se traduit par des dermatoses qui ne se manifestent que pendant la grossesse. Cette dernière peut également améliorer ou exacerber des dermatoses préexistantes. Dans cet article, nous précisons la prise en charge des dermatoses spécifiques de la grossesse : l'eczéma atopique de la grossesse, l'éruption polymorphe gravidique, la pemphigoïde gestationnelle, l'impétigo herpétiforme et la cholestase intrahépatique gravidique. Il est important de distinguer ces dermatoses, puisque la pemphigoïde gestationnelle, l'impétigo herpétiforme et la cholestase intrahépatique gravidique présentent un risque fœtal et par conséquence nécessitent un suivi obstétrical rapproché.

Methods of induction of labor and women's experience: a population-based cohort study with mediation analyses.

BACKGROUND: Negative childbirth experience may affect mother wellbeing and health. However, it is rarely evaluated in studies comparing methods of induction of labor (IoL). AIM: To compare women's experience of IoL according to the method, considering the mediating role of interventions and complications of delivery. METHODS: We used data from the MEDIP prospective population-based cohort, including all women with IoL during one month in seven French perinatal networks. The experience of IoL, assessed at 2 months postpartum, was first compared between cervical ripening and oxytocin, and secondarily between different cervical ripening methods. Mediation analyses were used to measure the direct and indirect effects of cervical ripening on maternal experience, through delivery with interventions or complications. FINDINGS: The response rate was 47.8% (n = 1453/3042). Compared with oxytocin (n = 541), cervical ripening (n = 910) was associated less often with feelings that labor went 'as expected' (adjusted risk ratio for the direct effect 0.78, 95%CI [0.70-0.88]), length of labor was 'acceptable' (0.76[0.71-0.82]), 'vaginal discomfort' was absent (0.77[0.69-0.85]) and with lower global satisfaction (0.90[0.84-0.96]). Interventions and complications mediated between 6 and 35% of the total effect of cervical ripening on maternal experience. Compared to the dinoprostone insert, maternal experience was not significantly different with the other prostaglandins. The balloon catheter was associated with less pain. DISCUSSION: Cervical ripening was associated with a less positive experience of childbirth, whatever the method, only partly explained by interventions and complications of delivery. CONCLUSION: Counselling and support of women requiring cervical ripening might be enhanced to improve the experience of IoL.

Comparison of effectiveness and safety of cervical ripening methods for induction of labour: A population-based study using coarsened exact matching.

BACKGROUND: There is no consensus about the ideal cervical ripening method to use for induction of labour. OBJECTIVE: To compare in current practice the effectiveness and safety of four cervical ripening methods. METHODS: We performed a matched comparative study using data from the MEDIP prospective population-based cohort conducted during one month in 2015 in all maternity units of seven French perinatal networks (3042 consecutive women with a live fetus and induction of labour). We analysed 1671 women with singleton cephalic fetus, unscarred uterus, and bishop score <7. Dinoprostone vaginal pessary (reference) was compared to dinoprostone vaginal gel, misoprostol vaginal tablet, and balloon catheter. Effectiveness outcomes were the need for more than one induction agent, oxytocin use, failure to achieve vaginal delivery within 24 hours (VD < 24 hours), and caesarean delivery. Safety outcomes were meconium-stained amniotic fluid, uterine hyperstimulation, NICU admission, and post-partum haemorrhage. Coarsened exact matching was used to balance confounders among the groups. Outcomes were compared using multivariable logistic regression models. RESULTS: Compared to the dinoprostone pessary (N = 1142, 68.3%), dinoprostone gel (N = 335, 20.1%) was associated with less failure to achieve VD < 24 hours (adjusted OR 0.66, 95% CI 0.47, 0.91). Misoprostol (N = 103, 6.2%) was associated with less need of more than one induction agent (aOR 0.56, 95% CI 0.34, 0.92) and less oxytocin use (aOR 0.60, 95% CI 0.37, 0.99). The balloon catheter (N = 91, 5.4%) was associated with more failure to achieve VD < 24 hours (aOR 2.62, 95% CI 1.37, 5.01), more caesarean delivery (aOR 1.84, 95% CI 1.09, 3.08), and less meconium-stained amniotic fluid (aOR 0.12, 95% CI 0.02, 0.70). Uterine hyperstimulation rates seemed lower with the balloon catheter (1.2% vs 4.2% for the pessary). CONCLUSIONS: In current practice, no cervical ripening method appears clearly superior to the others considering all effectiveness and safety outcomes.

Fetal Brain Injury Associated with Parvovirus B19 Congenital Infection Requiring Intrauterine Transfusion.

BACKGROUND: Infection with parvovirus B19 (B19V) during pregnancy may cause severe fetal anemia, hydrops, and fe tal death. Furthermore, neurodevelopmental impairment among survivors may occur despite appropriate prenatal management, including intrauterine transfusion (IUT). OBJECTIVES: Our primary objective was to describe cerebral lesions on MRI in fetuses with severe anemia requiring IUT for B19V infection. Our secondary objective was to search for clinical and biological characteristics associated with the occurrence of such lesions. STUDY DESIGN: We performed a retrospective review of data on fetuses infected with B19V and requiring at least one IUT between 2005 and 2016. Fetuses with abnormal cerebral MRI results in the 3rd trimester were compared to those with normal MRI results. RESULTS: Of 34 transfused fetuses, 26 children were born at full term. Five intrauterine fetal deaths, 1 neonatal death, and 2 terminations of pregnancy occurred. Cerebral anomalies were observed in 7/27 fetuses on MRI, including cerebellar hemorrhage or a small cerebellum. Only viral load in fetal blood appeared to be associated with brain lesions (11.5 log10 copies/mL [10.5-12.5] in case of abnormal MRI results vs. 9.5 log10 copies/mL [7.8-10.0]; p = 0.05). CONCLUSIONS: Among the fetuses transfused for B19V infection, 26% presented with prenatal abnormal cerebral imaging results. In our study, viral load in fetal blood appeared to be the only factor associated with fetal brain lesions.

Clinical input of anti-D quantitation by continuous-flow analysis on autoanalyzer in the management of high-titer anti-D maternal alloimmunization.

BACKGROUND: In addition to titration by indirect antiglobulin test most widely used, anti-D quantitation by continuous-flow analysis (CFA) may be performed to assess severity of maternal immunization. Only five studies have reported its added value in the management of pregnancies complicated by anti-D immunization. STUDY DESIGN AND METHODS: A retrospective study of 74 severe anti-D-immunized pregnancies was conducted from January 1, 2013, to December 31, 2014, in the Trousseau Hospital in Paris (France). Concentration of maternal anti-D was measured by titration and by CFA two-stages method (2SM; total amount of anti-D) and one-stage method (1SM; high-affinity IgG1 anti-D). These biologic data were analyzed according to the severity of the hemolytic disease of the fetus and the newborn. RESULTS: The value of 5 IU anti-D/mL in maternal serum is validated as a threshold to trigger ultrasonographic and Doppler fetal close follow-up. A high 1SM/2SM ratio was associated with a higher risk of intrauterine transfusion (IUT). For pregnancies requiring IUT and without increasing titer, maternal 1SM anti-D concentration tends to correlate with the precocity of fetal anemia. In the "without-IUT" group 1SM and 2SM anti-D concentrations correlate significantly with cord bilirubin levels of the newborn at birth. CONCLUSION: Altogether our results underline the importance of anti-D quantitation by CFA to optimize the management of anti-D-alloimmunized pregnancies.

Effectiveness and costs of non-invasive foetal RHD genotyping in rhesus-D negative mothers: a French multicentric two-arm study of 850 women.

BACKGROUND: The determination of foetal Rhesus D (RHD) status allows appropriate use of IgRh prophylaxis by restricting its use to cases of RHD feto-maternal incompatibilities. There is a degree of uncertainty about the cost-effectiveness of foetal RHD determination, yet screening programs are being introduced into clinical practice in many countries. This paper evaluates the impact of non-invasive foetal Rhesus D (RHD) status determination on the costs of managing RHD-negative pregnant women and on the appropriate use of anti-D prophylaxis in a large sample of RHD-negative pregnant women using individual prospectively collected clinical and economic data. METHODS: A prospective two-armed trial of RHD negative pregnant women was performed in 11 French Obstetric Departments. Non-invasive foetal RHD genotyping was performed before 26 weeks' gestation in the experimental arm whereas the control arm participants received usual care. The costs associated with patient management in relation to their RHD negative status (biological tests, anti-D prophylaxis and visits) were calculated from inclusion to the end of the postpartum period. The costs of hospital admissions during pregnancy and delivery were also determined. RESULTS: A total of 949 patients were included by 11 centres between 2009 and 2012, and 850 completed follow-up, including medical and biological monitoring. Patients were separated into two groups: the genotyping group (n=515) and the control group (n=335). The cost of the genotyping was estimated at 140 euros per test. The total mean cost per patient was estimated at €3,259 (SD ± 1,120) and €3,004 (SD ± 1,004) in the genotyping and control groups respectively. The cost of delivery represented three quarters of the total cost in both groups. The performance of managing appropriately RHD negative anti-D prophylaxis was 88% in the genotyping group, versus 65% in the control group. Using the costs related to RHD status (biological tests, anti-D immunoglobulin injections and visits) the incremental cost-effectiveness ratio (ICER) was calculated to be €578 for each percentage gain in women receiving appropriate management. CONCLUSION: Early knowledge of the RHD status of the foetus using non-invasive foetal RHD genotyping significantly improved the management of RHD negative pregnancies with a small increase in cost. TRIAL REGISTRATION: Clinical trials registry- NCT00832962 -13 January 2009 - retrospectively registered.

Impact of Latency Duration on the Prognosis of Preterm Infants after Preterm Premature Rupture of Membranes at 24 to 32 Weeks' Gestation: A National Population-Based Cohort Study.

OBJECTIVE: To assess the impact of latency duration on survival, survival without severe morbidity, and early-onset sepsis in infants born after preterm premature rupture of membranes (PPROM) at 24-32 weeks' gestation. STUDY DESIGN: This study was based on the prospective national population-based Etude Épidémiologique sur les Petits Ȃges Gestationnels 2 cohort of preterm births and included 702 singletons delivered in France after PPROM at 24-32 weeks' gestation. Latency duration was defined as the time from spontaneous rupture of membranes to delivery, divided into 4 periods (12 hours to 2 days [reference], 3-7 days, 8-14 days, and >14 days). Multivariable logistic regression was used to assess the relationship between latency duration and survival, survival without severe morbidity at discharge, or early-onset sepsis. RESULTS: Latency duration ranged from 12 hours to 2 days (18%), 3-7 days (38%), 8-14 days (24%), and >14 days (20%). Rates of survival, survival without severe morbidity, and early-onset sepsis were 93.5% (95% CI 91.8-94.8), 85.4% (82.4-87.9), and 3.4% (2.0-5.7), respectively. A crude association found between prolonged latency duration and improved survival disappeared on adjusting for gestational age at birth (aOR 1.0 [reference], 1.6 [95% CI 0.8-3.2], 1.2 [0.5-2.9], and 1.0 [0.3-3.2] for latency durations from 12 hours to 2 days, 3-7 days, 8-14 days, and >14 days, respectively). Prolonged latency duration was not associated with survival without severe morbidity or early-onset sepsis. CONCLUSION: For a given gestational age at birth, prolonged latency duration after PPROM does not worsen neonatal prognosis.

Accuracy of Middle Cerebral Artery Doppler Assessment between 34 and 37 Weeks in Fetuses with Red Cell Alloimmunization.

BACKGROUND: The Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) is considered the gold standard for the noninvasive detection of moderate to severe anemia. However, the accuracy of this test has not been evaluated so far, specifically beyond 34 weeks. OBJECTIVES: To assess the accuracy of MCA-PSV to detect moderate to severe fetal anemia and to identify risk factors associated with false-positive and false-negative MCA-PSV values after 34 weeks. STUDY DESIGN: We studied a retrospective cohort of 150 pregnant women with severe alloimmunization who delivered between 2010 and 2014 and correlated MCA-PSV and fetal or neonatal hemoglobin levels. RESULTS: Sensitivity to predict severe anemia was 69%, with a false-negative rate of 3.6%. When MCA Doppler assessment was normal, the identification of serosal effusions increased the detection rate of severe fetal anemia to 94%, with a false-negative rate of 0.8%. False-positive MCA-PSV measurements were more frequent in fetuses with 1 previous intrauterine transfusion (p = 0.0002), but were not associated with MCA resistance index, intrauterine growth restriction and fetal heart rate. CONCLUSIONS: Between 34 and 37 weeks, sensitivity of MCA-PSV Doppler assessment alone is 69% and increases to 94% when also considering signs of hydrops. False-positive MCA-PSV measurements are more frequent in case of former fetal transfusion.

Genetic and epigenetic mechanisms collaborate to control SERPINA3 expression and its association with placental diseases.

SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a serine protease inhibitor involved in a wide range of biological processes. Recently, it has been shown to be up-regulated in human placental diseases in association with a hypomethylation of the 5' region of the gene. In the present study, we show that the promoter of SERPINA3 is transcriptionally activated by three transcription factors (TFs) (SP1, MZF1 and ZBTB7B), the level of induction being dependent on the rs1884082 single nucleotide polymorphism (SNP) located inside the promoter, the T allele being consistently induced to a higher level than the G, with or without added TFs. When the promoter was methylated, the response to ZBTB7B was allele specific (the G allele was strongly induced, while the T allele was strongly down-regulated). We propose an adaptive model to explain the interest of such a regulation for placental function and homeostasis. Overexpression of SERPINA3 in JEG-3 cells, a trophoblast cell model, decreased cell adhesion to the extracellular matrix and to neighboring cells, but protects them from apoptosis, suggesting a way by which this factor could be deleterious at high doses. In addition, we show in different human populations that the T allele appears to predispose to Intra Uterine Growth Restriction (IUGR), while a G allele at a second SNP located in the second exon (rs4634) increases the risk of preeclampsia. Our results provide mechanistic views inside the involvement of SERPINA3 in placental diseases, through its regulation by a combination of epigenetic, genetic and TF-mediated regulations.

Clinical presentation and outcome of 20 fetuses with parvovirus B19 infection complicated by severe anemia and/or fetal hydrops.

AIM: The aim of this study was to assess the prognosis of parvovirus B19 infection with severely anemic and/or hydropic fetuses according to initial ultrasound and biological criteria. MATERIAL AND METHODS: Retrospective study of 20 cases of congenital parvovirus B19-proven infection (positive PCR) complicated by fetal anemia and/or hydrops was examined. Anemia was suspected on an elevated peak systolic velocity of the middle cerebral artery and was confirmed by fetal blood sampling. RESULTS: Survival rate was 70% (14/20) overall and 76% (13/17) for fetuses with one or more transfusions. When fetal effusion regressed after the transfusion, all 11 fetuses survived, and neonatal condition was favorable for all. Among the 14 live-born children, there was one neonatal death and one admission to the neonatal care unit with no major complications. CONCLUSION: Despite active management by transfusion in fetuses with parvovirus B19 infection, mortality remained substantial during the acute phase of anemia and fetal hydrops. Regression of effusion appears to be an important variable for prognosis. Non-anemic forms exist with isolated refractory ascites or pleural effusion. Maternal mirror syndrome appears to reflect the intensity and persistence of the fetal anemia.

Calcium channel blockers for inhibiting preterm labour and birth.

BACKGROUND: Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low- and middle-income countries. Tocolytics are drugs used to suppress uterine contractions for women in preterm labour. The most widely used tocolytic are the betamimetics, however, these are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs) (e.g. atosiban) also have a low side-effect profile. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of CCBs, administered as a tocolytic agent, to women in preterm labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013). SELECTION CRITERIA: All published and unpublished randomised trials in which CCBs were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, undertook quality assessment and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with the 95% confidence interval (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) were calculated for categorical outcomes that were statistically significantly different. MAIN RESULTS: This update includes 26 additional trials involving 2511 women, giving a total of 38 included trials (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used nicardipine. Blinding of intervention and outcome assessment was undertaken in only one of the trials (a placebo controlled trial). However, objective outcomes defined according to timing of birth and perinatal mortality were considered to have low risk of detection bias.Two small trials comparing CCBs with placebo or no treatment showed a significant reduction in birth less than 48 hours after trial entry (RR 0.30, 95% CI 0.21 to 0.43) and an increase in maternal adverse effects (RR 49.89, 95% CI 3.13 to 795.02, one trial of 89 women). Due to substantial heterogeneity, outcome data for preterm birth (less than 37 weeks) were not combined; one placebo controlled trial showed no difference (RR 0.96, 95% CI 0.89 to 1.03) while the other (non-placebo controlled trial) reported a reduction (RR 0.44, 95% CI 0.31 to 0.62). No other outcomes were reported.Comparing CCBs (mainly nifedipine) with other tocolytics by type (including betamimetics, glyceryl trinitrate (GTN) patch, non-steriodal anti inflammatories (NSAID), magnesium sulphate and ORAs), no significant reductions were shown in primary outcome measures of birth within 48 hours of treatment or perinatal mortality.Comparing CCBs with betamimetics, there were fewer maternal adverse effects (average RR 0.36, 95% CI 0.24 to 0.53) and fewer maternal adverse effects requiring discontinuation of therapy (average RR 0.22, 95% CI 0.10 to 0.48). Calcium channel blockers resulted in an increase in the interval between trial entry and birth (average MD 4.38 days, 95% CI 0.25 to 8.52) and gestational age (MD 0.71 weeks, 95% CI 0.34 to 1.09), while decreasing preterm and very preterm birth (RR 0.89, 95% CI 0.80 to 0.98 and RR 0.78, 95% CI 0.66 to 0.93); respiratory distress syndrome (RR 0.64, 95% CI 0.48 to 0.86); necrotising enterocolitis (RR 0.21, 95% CI 0.05 to 0.96); intraventricular haemorrhage (RR 0.53, 95% CI 0.34 to 0.84); neonatal jaundice (RR 0.72, 95% CI 0.57 to 0.92); and admissions to neonatal intensive care unit (NICU) (average RR 0.74, 95% CI 0.63 to 0.87). No difference was shown in one trial of outcomes at nine to twelve years of age.Comparing CCBs with ORA, data from one study (which did blind the intervention) showed an increase in gestational age at birth (MD 1.20 completed weeks, 95% CI 0.25 to 2.15) and reductions in preterm birth (RR 0.64, 95% CI 0.47 to 0.89); admissions to the NICU (RR 0.59, 95% CI 0.41 to 0.85); and duration of stay in the NICU (MD -5.40 days,95% CI -10.84 to 0.04). Maternal adverse effects were increased in the CCB group (average RR 2.61, 95% CI 1.43 to 4.74).Comparing CCBs with magnesium sulphate, maternal adverse effects were reduced (average RR 0.52, 95% CI 0.40 to 0.68), as was duration of stay in the NICU (days) (MD -4.55, 95% CI -8.17 to -0.92). No differences were shown in the comparisons with GTN patch or NSAID, although numbers were small.No differences in outcomes were shown in trials comparing nicardipine with other tocolytics, although with limited data no strong conclusions can be drawn. No differences were evident in a small trial that compared higher- versus lower-dose nifedipine, though findings tended to favour a high dose on some measures of neonatal morbidity. AUTHORS' CONCLUSIONS: Calcium channel blockers (mainly nifedipine) for women in preterm labour have benefits over placebo or no treatment in terms of postponement of birth thus, theoretically, allowing time for administration of antenatal corticosteroids and transfer to higher level care. Calcium channel blockers were shown to have benefits over betamimetics with respect to prolongation of pregnancy, serious neonatal morbidity, and maternal adverse effects. Calcium channel blockers may also have some benefits over ORAs and magnesium sulphate, although ORAs results in fewer maternal adverse effects. However, it must be noted that no difference was shown in perinatal mortality, and data on longer-term outcomes were limited. Further, the lack of blinding of the intervention diminishes the strength of this body of evidence. Further well-designed tocolytic trials are required to determine short- and longer-term infant benefit of CCBs over placebo or no treatment and other tocolytics, particularly ORAs. Another important focus for future trials is identifying optimal dosage regimens of different types of CCBs (high versus low, particularly addressing speed of onset of uterine quiescence) and formulation (capsules versus tablets). All future trials on tocolytics for women in preterm labour should employ blinding of the intervention and outcome assessment, include measurement of longer-term effects into early childhood, and also costs.

Catastrophic antiphospholipid syndrome and pregnancy: an experience of 13 cases.

OBJECTIVE: Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening disease caused by the onset of rapidly progressive and widespread small-vessel thromboses in the presence of aPLs. The aim of this study was to examine pregnancy-related CAPS. METHODS: Retrospective series of 13 patients with pregnancy-related CAPS with special focus on the follow-up. RESULTS; Eleven patients had known APS and had been treated with low-molecular-weight heparin (n = 10), aspirin (n = 8), oral anticoagulants (n = 1), HCQ (n = 3) and/or steroids (n = 1) during pregnancy. The most frequent manifestations of CAPS were cutaneous (n = 11), hepatic (n = 11), renal (n = 10), cardiac (n = 8) and neurological (n = 5). CAPS usually followed haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome (n = 12), which was associated with pre-eclampsia (n = 6) or with eclampsia (n = 3). No maternal death was observed. The perinatal mortality of 54% was related to prematurity with a mean gestational age of 26.6 weeks at onset of CAPS or HELLP syndrome. During a mean follow-up of 4.8 years (range 2-8 years), seven new pregnancies occurred in five patients and led to one miscarriage, four successful pregnancies and two HELLP syndrome with pre-eclampsia or eclampsia that occurred at 28 weeks gestation in both cases despite optimal treatment. No relapse of CAPS was observed. Two mothers suddenly died 2.5 and 6 years after CAPS. CONCLUSION: The occurrence of HELLP syndrome in a patient with APS should raise the suspicion of CAPS in the following days, and anticoagulation should be maintained post-partum or post-abortum. Subsequent pregnancies are at very high risk.

Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors.

TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is frequently mutated in myeloid malignancies, including myeloproliferative neoplasms. Here we show that the level of 5-hmC is decreased in granulocyte DNA from myeloproliferative neoplasm patients with TET2 mutations compared with granulocyte DNA from healthy patients. Inhibition of TET2 by RNA interference decreases 5-hmC levels in both human leukemia cell lines and cord blood CD34(+) cells. These results confirm the enzymatic function of TET2 in human hematopoietic cells. Knockdown of TET2 in cord blood CD34(+) cells skews progenitor differentiation toward the granulomonocytic lineage at the expense of lymphoid and erythroid lineages. In addition, by monitoring in vitro granulomonocytic development we found a decreased granulocytic differentiation and an increase in monocytic cells. Our results indicate that TET2 disruption affects 5-hmC levels in human myeloid cells and participates in the pathogenesis of myeloid malignancies through the disturbance of myeloid differentiation.

Ultrasound markers for the detection of women at risk of developing pre-eclampsia.

Pre-eclampsia (PE) is a consequence of an abnormal placental invasion. Uterine artery Doppler (Ut-AD) is directly related to trophoblastic invasion of the spiral arteries, which occurs before 18 weeks' gestation. A correct interpretation of Ut-AD indices and waveform patterns requires a rigorous and standardized methodology, in particular for the definition of notches. To date, aspirin is the only treatment associated with a decreased incidence of PE, and early identification of women at risk is crucial to optimize its use. The diagnostic performance of Ut-AD as a screening test should take into account the characteristics of the population studied. In women at high-risk of PE (i.e., women with a previous history of PE), results vary from a detection rate of 63%, with 25% false-positive results for all forms of PE, to 91% detection with 5% false-positive for early PE if repeated measurements, combined with maternal characteristics, are performed. Multicenter randomized clinical trials failed to demonstrate a benefit from administering aspirin in low-risk women with abnormal Ut-AD. In unselected populations, the use of Ut-AD, alone or integrated into algorithms including maternal characteristics, cannot be recommended for clinical practice at any gestational age. Combination with biological markers is a new field of research that could improve the performance of Ut-AD.

Effect of intravenous immunoglobulins to postpone the gestational age of first intrauterine transfusion in very severe red blood cell alloimmunization: A case-control study.

BACKGROUND: Early intrauterine transfusion (IUT) is associated with a higher risk of fetal loss. Our objective was to evaluate the efficiciency of intravenous immunoglobulins (IVIG) to postpone the gestational age at first IUT beyond 20 weeks of gestation (WG) compared to the previous pregnancy in case of very severe red blood cell (RBC) alloimmunization. STUDY DESIGN AND METHODS: Very severe RBC alloimmunization was defined by a high titer of antibodies and a previous pregnancy complicated by a first IUT before 24 WG and/or perinatal death directly related to alloimmunization. We performed a single-center case-control study. Cases and controls were patients respectively treated with weekly IVIG infusions started before 13 WG, and without. RESULTS: Twenty cases and 21 controls were included. Gestational age (GA) at first IUT was postponed after 20 WG in 18/20 (90 %) of patients treated with IVIG and in 15/21 (71 %) in the control group (p = 0.24). Compared to the previous pregnancy, the GA at first IUT was postponed by a median of 22 [+11; +49] days in the IVIG group and occurred in average 2 days earlier [-17 ; +12] in the non-treated group (p = 0.02). There was no difference between number of IUT and need for exchange-transfusion. IVIG treatment was associated with a significant decrease of antibodies' quantitation. CONCLUSION: In our series, IVIG tends to differ first IUT beyond 20 WG and have a significant effect in postponing the gestational age of the first IUT in patients with very severe RBC alloimmunization.

Fertility-sparing approach in a teenager with uterine tumor diagnosed as a sarcoma on imaging.

BACKGROUND: Uterine tumors are extremely rare in teenage patients. Although magnetic resonance imaging (MRI) can help distinguish between leiomyoma and sarcoma, it may also seriously mislead the diagnosis. CASE REPORT: An 18-year-old female patient presented with marked anemia, and a rapidly growing uterine tumor that strongly suggested uterine sarcoma on MRI. In order to avoid dispensable radical surgery, explorative laparotomy with tumor biopsy was performed after balancing risk/benefit ratio. Extemporaneous pathologic examination revealed a benign leiomyoma, and the patient subsequently underwent complete conservative myomectomy. CONCLUSION: Preserving fertility is an important issue in young patients with uterine tumors, and tumor biopsy may overcome MRI false positive results, as illustrated in this case. Conservative approach deserves further evaluation in this specific setting.

[Pregnancy after gynecologic or breast cancer]. / Grossesse après cancer gynécologique ou mammaire.

Breast cancer often occurs in women of childbearing age, many of whom go on to have children. Several studies suggest that pregnancy does not worsen the outcome of breast cancer, and that a history of breast cancer does not affect the outcome of pregnancy. The timing of pregnancy after breast cancer should take into account the risk of recurrence and metastasis. Conservative surgical treatment for cervical cancer may increase the risk of late fetal loss or preterm birth. Candidates for conservative treatment of ovarian and endometrial cancer must be carefully selected, as recurrence during or after pregnancy is not uncommon.

Dissatisfaction of women with induction of labour according to parity: Results of a population-based cohort study.

OBJECTIVE: To determine the factors associated with dissatisfaction in women whose labour was induced, according to parity. DESIGN: Prospective population-based cohort study. SETTING: Seven French perinatal health networks including 94 maternity units PARTICIPANTS: Among 3042 consecutive women who underwent induction of labour (IoL) with a live foetus from November 17 to December 20, 2015, in participating maternity units, this study included the 1453 who answered the self-administered questionnaire about their experience of IoL at two months post-delivery. MEASUREMENTS: The associations between women's dissatisfaction at two months post-delivery and the characteristics of their pregnancy, labour, and delivery were assessed with multivariable logistic regression models. Analyses were stratified for nulliparous and parous women. Multivariable mixed models were used to take a random effect for the maternity unit into account. FINDINGS: The response rate was 47.8% (n = 1453/3042). Overall, 30% of the nulliparous women were dissatisfied (n = 231/770) and 19.7% (n = 130/659) of the parous women. The specific independent determinants of dissatisfaction for nulliparous women were antenatal birth classes that failed to include discussion of IoL (OR: 2.68, 95% CI [1.37; 5.23]) and lack of involvement in the decision-making process (OR: 1.92, 95% CI [1.23; 3.02]). For the parous women, a specific determinant was a delivery that lasted more than 24 h (OR: 4.04, 95% CI [1.78; 9.14]). Determinants of maternal dissatisfaction common to both groups were unbearable vaginal discomfort (respectively, OR: 1.98, 95% CI [1.16; 3.37] and OR: 4.23, 95% CI [2.04; 8.77]), inadequate pain relief (respectively, OR: 5.55, 95% CI [3.48; 8.86] and OR: 9.17, 95% CI [5.24; 16.02]), lack of attention to requests (respectively OR: 3.81, 95% CI [2.35; 6.19] and OR: 5.01, 95% CI [2.38; 10.52]), caesarean delivery (respectively, OR: 5.55, 95% CI [3.41; 9.03] and OR: 4.61, 95% CI [2.02; 10.53]) and severe maternal complications (respectively, OR: 2.45, 95% CI [1.02; 5.88] and OR: 5.29, 95% CI [1.32; 21.21]). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: To reduce dissatisfaction in nulliparous women, IoL should be discussed during antenatal birth classes and women should be made to feel that they shared in the medical decision to perform IoL. For parous women, care providers should inform them that the duration of delivery may exceed 24 h. Continuous support for all women during IoL should pay closer attention to vaginal discomfort, pain and women's requests. Postpartum discussions with mothers should be arranged to enable conversation about the experience of unexpected events.

Effect of a speculum blade on dynamic MRI evaluation of pelvic organ prolapse.

We aimed to evaluate whether the use of a speculum blade modifies the evaluation of pelvic organ prolapse (POP) as assessed by dynamic magnetic resonance imaging (MRI). Twenty-seven women with POP Quantification (POPQ) stage II or greater, scheduled for POP surgery, were evaluated using MRI. The procedure was repeated using the posterior blade of a standard plastic Grave's speculum to successively retract the anterior and posterior vaginal walls. Standard POPQ was 15% stage II (n =4), 59% stage III (n =16) and 26% stage IV (n =7). The use of a blade evidenced hidden pelvic prolapsed compartments in 59% (n =16) of cases. For 48% of patients (n =13), the variation of the leading edge of at least one additional prolapsed compartment was diagnosed as more than 20 mm. In this series, the use of a speculum blade during dynamic MRI modified the POP evaluation in a large proportion of patients with POP stage > or =II.