[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.

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.

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.

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.

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.

Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: A randomized trial.

OBJECTIVE: To assess whether antibiotics used for treatment in asymptomatic second-trimester women positive for Mycoplasma or Ureaplasma spp. detected by amniotic-fluid PCR prevents preterm delivery. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: 10 maternal fetal medicine centers in France. POPULATION: Women with a singleton pregnancy who underwent amniocentesis between 16 and 20 weeks' gestation (weeks) for Down syndrome screening. A sample of 238 women with PCR-positive findings per treatment group was needed to show a 50% reduction in the preterm delivery rate. METHODS: Amniotic fluid was tested. Women with positive findings on real-time PCR of amniotic fluid for Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum and Ureaplasma parvum were randomized to receive josamycin or placebo. Amniotic fluid was also tested for 16S PCR. MAIN OUTCOME MEASURES: The primary outcome was delivery before 37 weeks. RESULTS: In total, 1043 women underwent amniotic-fluid screening with specific PCR detection between July 2008 and July 2011: PCR detection failed in 27 (2.6%), and 20 (1.9%) underwent termination of pregnancy. Among the 1016 women with PCR results, 980 had available data for the primary outcome (delivery before 37 weeks) and 29 (3.0%) were positive for Ureaplasma and/or Mycoplasma spp. Because of the low rate of women with PCR-positive findings, the trial was stopped prematurely. In total, 19 women were randomized to receive placebo (n = 8) or josamycin (n = 11) and their characteristics were comparable, as was the rate of preterm delivery and secondary outcomes. In comparing all PCR-positive and -negative women regardless of treatment, PCR positivity for Ureaplasma and/or Mycoplasma spp. was not associated with any adverse pregnancy or neonatal outcome. Amniotic-fluid screening by 16S PCR showed no other bacterial colonization associated with preterm birth. CONCLUSIONS: Because of a low amniotic fluid colonization rate, the trial was interrupted. Maternal amniotic-fluid colonization by Mycoplasma and/or Ureaplasma spp. at 16-20 weeks in asymptomatic women is rare and not associated with adverse pregnancy outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00718705.

In utero ultrasound diagnosis of corpus callosum agenesis leading to the identification of orofaciodigital type 1 syndrome in female fetuses.

BACKGROUND: OFD1 syndrome is a rare ciliopathy inherited on a dominant X-linked mode, typically lethal in males in the first or second trimester of pregnancy. It is characterized by oral cavity and digital anomalies possibly associated with cerebral and renal signs. Its prevalence is between 1/250,000 and 1/50,000 births. It is due to heterozygous mutations of OFD1 and mutations are often de novo (75%). Familial forms show highly variable phenotypic expression. OFD1 encodes a protein involved in centriole growth, distal appendix formation, and ciliogenesis. CASES: We report the investigation of three female fetuses in which corpus callosum agenesis was detected by ultrasound during the second trimester of pregnancy. In all three fetuses, fetopathological examination allowed the diagnosis of OFD1 syndrome, which was confirmed by molecular analysis. CONCLUSIONS: To our knowledge, these are the first case reports of antenatal diagnosis of OFD1 syndrome in the absence of familial history, revealed following detection of agenesis of the corpus callosum. They highlight the impact of fetal examination following termination of pregnancy for brain malformations. They also highlight the contribution of ciliary genes to corpus callosum development.

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.

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.

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.

In utero treatment of severe fetal anemia resulting from fetomaternal red blood cell incompatibility: a comparison of simple transfusion and exchange transfusion.

OBJECTIVE: To compare in utero exchange transfusions (IUET) and in utero simple transfusions (IUST) for the treatment of fetal anemia resulting from red blood cell fetomaternal incompatibility. STUDY DESIGN: Retrospective comparative study from January 2006 through December 2011. The two techniques were compared for effectiveness, complications, and neonatal outcomes. RESULTS: 36 patients had 87 IUETs and 85 patients 241 IUSTs. Gestational age at the first transfusion was similar in both groups (IUET: 27±3.8 weeks; IUST: 27±4.7 weeks; NS) as was the initial fetal hemoglobin level (IUET: 6.4±2.8g/dL; IUST: 6.0±2.5g/dL; NS). No significant differences were noted for postprocedure complications or efficacy. The daily drop in hemoglobin level was similar in both groups (IUET: 0.41±0.23g/dL/day; IUST: 0.44±0.17g/dL/day; NS) as were the time intervals between two procedures. Gestational age at birth was earlier in the IUET group (34.4±1.3 weeks vs 35.5±1.8 weeks; p<0.001), but the postnatal transfusions or exchange transfusions rates and the duration of intensive phototherapy did not differ. No significant differences were noted for the overall survival rates (IUET: 100%; IUST: 96.4%; p>0.99). CONCLUSION: IUET does not appear to provide any benefits compared with IUST, neither to be associated with a higher complication rate. The choice of the technique depends on availability of packed blood cells with high hematocrit (70-80%).

Assessment of an e-learning training program for cardiotocography analysis: a multicentre randomized study.

OBJECTIVE: To assess the improvement of knowledge in cardiotocography (CTG) analysis, with the use of a dedicated e-learning program. STUDY DESIGN: Multicentre randomized controlled trial conducted in 5 maternity departments of Eastern-Paris Perinatal network. Midwives and obstetricians were recruited on a voluntary basis. At first log-in, they were tested on CTG interpretation and on labor management. They were then randomly allocated to a "training" group (n=57) with the e-learning program, or to a "no-training" group (n=56). After three months, a second test was performed. Mean scores at first and second tests, rate of participants in the bottom quartile, and mean scores between doctors and midwives were compared between "training" and "no-training" groups. RESULTS: Seventy-five midwives and 38 obstetricians participated in the study. The mean scores at first test were similar in both groups (32.4 ± 5.2 out of 50 and 32.5 ± 4.6, p=0.989). After e-learning, the results were significantly higher in the "training" group than in the "no-training" group (mean 37.1 ± 5.5 vs. 32.6 ± 5.7, respectively; p=0.0026). The number of participants in the bottom quartile reached 36.0% in the "no-training" group, while it decreased to 12.6% in the "training" group (p=0.032). Doctors had higher results than midwives in the first test (34.9 ± 5.9 vs. 32.4 ± 4.3; p=0.0048), but not in the second test in the group with training (37.7 ± 6.7 vs. 36.8 ± 4.8; p=0.64). CONCLUSION: Training in CTG interpretation using an e-learning program improves the performance of obstetric staff. The possibility of logging-in from any place at any time may favor the use of an e-learning program in maternity staff.

Foetal scalp blood sampling during labour for pH and lactate measurements.

Second-line methods of foetal monitoring have been developed in an attempt to reduce unnecessary interventions due to continuous cardiotocography (CTG), and to better identify foetuses that are at risk of intrapartum asphyxia. Very few studies directly compared CTG with foetal scalp blood (FBS) and CTG only. Only one randomised controlled trial (RCT) was published in the 1970s and had limited power to assess neonatal outcome. Direct and indirect comparisons conclude that FBS could reduce the number of caesarean deliveries associated with the use of continuous CTG. The main drawbacks of FBS are its invasive and discontinuous nature and the need for a sufficient volume of foetal blood for analysis, especially for pH measurement, resulting in failure rates reaching 10%. FBS for lactate measurement became popular with the design of test-strip devices, requiring <0.5 mL of foetal blood. RCTs showed similar outcomes with the use of FBS for lactates compared with pH in terms of obstetrical interventions and neonatal outcomes. In conclusion, there is some evidence that FBS reduces the need for operative deliveries. However, the evidence is limited with regard to actual standards, and large RCTs, directly comparing CTG only with CTG with FBS, are still needed.

Cause of Preterm Birth as a Prognostic Factor for Mortality.

OBJECTIVE: To investigate the association of the cause of preterm birth on in-hospital mortality of preterm neonates born from 24 to 34 weeks of gestation. METHODS: L'Etude épidémiologique sur les petits âges gestationnels (EPIPAGE)-2 is a prospective, nationwide, population-based cohort of very preterm births. After dividing causes of preterm birth into six mutually exclusive groups, we analyzed the association of each cause with in-hospital deaths of preterm neonates born alive with adjustment for organizational, maternal, and obstetric factors. RESULTS: The analysis included 3,138 singleton live births from 24 to 34 weeks of gestation with a newborn in-hospital mortality rate of 5.0% (95% confidence interval 4.5-5.7). Preterm labor was the most frequent cause of preterm birth (n=1,293 [43.5%]) followed by preterm premature rupture of membranes (n=765 [23.9%]), hypertensive disorders without suspected fetal growth restriction (n=397 [12.7%]), hypertensive disorders with suspected fetal growth restriction (n=408 [10.9%]), placental abruption after an uncomplicated pregnancy (n=92 [3.0%]), and suspected fetal growth restriction without hypertensive disorders (n=183 [5.9%]). Neonates born because of suspected fetal growth restriction with or without hypertensive disorders (adjusted odds ratio [OR] 3.0 [1.9-4.7] and adjusted OR 2.3 [1.1-4.6], respectively) had higher adjusted risks of in-hospital death than those born after preterm labor. Risks of in-hospital mortality for preterm births caused by preterm premature rupture of membranes (adjusted OR 1.3 [0.9-1.9]), hypertensive disorders without fetal growth restriction (adjusted OR 0.7 [0.4-1.4]), or placental abruption (adjusted OR 1.6 [0.7-3.7]) were similar to those born after preterm labor. CONCLUSION: Among neonates born alive before 34 weeks of gestation, only those born because of suspected fetal growth restriction have a higher mortality risk than those born after preterm labor.

Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome?

The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary.

Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.

OBJECTIVE: To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix. METHODS: We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-ß=0.8, α=0.05, two-sided). RESULTS: The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups. CONCLUSION: Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.