[Fetal death: Expert consensus from the College of French Gynecologists and Obstetricians]. / Mort fœtale : consensus formalisé d'experts du Collège national des gynécologues-obstétriciens français.

Fetal death is defined as the spontaneous cessation of cardiac activity after fourteen weeks of amenorrhea. In France, the prevalence of fetal death after 22 weeks is between 3.2 and 4.4/1000 births. Regarding the prevention of fetal death in the general population, it is not recommended to counsel for rest and not to prescribe vitamin A, vitamin D nor micronutrient supplementation for the sole purpose of reducing the risk of fetal death (Weak recommendations; Low quality of evidence). It is not recommended to prescribe aspirin (Weak recommendation; Very low quality of evidence). It is recommended to offer vaccination against influenza in epidemic periods and against SARS-CoV-2 (Strong recommendations; Low quality of evidence). It is not recommended to systematically look for nuchal cord encirclements during prenatal screening ultrasounds (Strong Recommendation; Low Quality of Evidence) and not to perform systematic antepartum monitoring by cardiotocography (Weak Recommendation; Very Low Quality of Evidence). It is not recommended to ask women to perform an active fetal movement count to reduce the risk of fetal death (Strong Recommendation; High Quality of Evidence). Regarding evaluation in the event of fetal death, it is suggested that an external fetal examination be systematically offered (Expert opinion). It is recommended that a fetopathological and anatomopathological examination of the placenta be carried out to participate in cause identification (Strong Recommendation. Moderate quality of evidence). It is recommended that chromosomal analysis by microarray testing be performed rather than conventional karyotype, in order to be able to identify a potentially causal anomaly more frequently (Strong Recommendation, moderate quality of evidence); to this end, it is suggested that postnatal sampling of the placental fetal surface for genetic purposes be preferred (Expert Opinion). It is suggested to test for antiphospholipid antibodies and systematically perform a Kleihauer test and a test for irregular agglutinins (Expert opinion). It is suggested to offer a summary consultation, with the aim of assessing the physical and psychological status of the parents, reporting the results, discussing the cause and providing information on monitoring for a subsequent pregnancy (Expert opinion). Regarding announcement and support, it is suggested to announce fetal death without ambiguity, using simple words and adapting to each situation, and then to support couples with empathy in the various stages of their care (Expert opinion). Regarding management, it is suggested that, in the absence of a situation at risk of disseminated intravascular coagulation or maternal vitality, the patient's wishes should be taken into account when determining the time between the diagnosis of fetal death and induction of birth. Returning home is possible if it's the patient wish (Expert opinion). In all situations excluding maternal life-threatening emergencies, the preferred mode of delivery is vaginal delivery, regardless the history of cesarean section(s) history (Expert opinion). In the event of fetal death, it is recommended that mifepristone 200mg be prescribed at least 24hours before induction, to reduce the delay between induction and delivery (Low recommendation. Low quality of evidence). There are insufficient data in the literature to make a recommendation regarding the route of administration (vaginal or oral) of misoprostol, neither the type of prostaglandin to reduce induction-delivery time or maternal morbidity. It is suggested that perimedullary analgesia be introduced at the start of induction if the patient asks, regardless of gestational age. It is suggested to prescribe cabergoline immediately in the postpartum period in order to avoid lactation, whatever the gestational age, after discussing the side effects of the treatment with the patient (Expert opinion). The risk of recurrence of fetal death after unexplained fetal death does not appear to be increased in subsequent pregnancies, and data from the literature are insufficient to make a recommendation on the prescription of aspirin. In the event of a history of fetal death due to vascular issues, low-dose aspirin is recommended to reduce perinatal morbidity, and should not be combined with heparin therapy (Low recommendation, very low quality of evidence). It is suggested not to recommend an optimal delay before initiating another pregnancy just because of the history of fetal death. It is suggested that the woman and co-parent be informed of the possibility of psychological support. Fetal heart rate monitoring is not indicated solely because of a history of fetal death. It is suggested that delivery not be systematically induced. However, induction can be considered depending on the context and parental request. The gestational age will be discussed, taking into account the benefits and risks, especially before 39 weeks. If a cause of fetal death is identified, management will be adapted on a case-by-case basis (expert opinion). In the event of fetal death occurring in a twin pregnancy, it is suggested that the surviving twin be evaluated as soon as the diagnosis of fetal death is made. In the case of dichorionic pregnancy, it is suggested to offer ultrasound monitoring on a monthly basis. It is suggested not to deliver prematurely following fetal death of a twin. If fetal death occurs in a monochorionic twin pregnancy, it is suggested to contact the referral competence center, in order to urgently look for signs of acute fetal anemia on ultrasound in the surviving twin, and to carry out weekly ultrasound monitoring for the first month. It is suggested not to induce birth immediately.

X-linked transient antenatal Bartter syndrome related to MAGED2 gene: enriching the phenotypic description and pathophysiologic investigation.

PURPOSE: Transient Bartter syndrome related to pathogenic variants of MAGED2 is the most recently described antenatal Bartter syndrome. Despite its transient nature, it is the most severe form of Bartter syndrome in the perinatal period. Our aim was to describe 14 new cases and to try to explain the incomplete penetrance in women. METHODS: We report on 14 new cases, including 3 females, and review the 40 cases described to date. We tested the hypothesis that MAGED2 is transcriptionally regulated by differential methylation of its CpG-rich promotor by pyrosequencing of DNA samples extracted from fetal and adult leukocytes and kidney samples. RESULTS: Analysis of the data from 54 symptomatic patients showed spontaneous resolution of symptoms in 27% of cases, persistent complications in 41% of cases and fatality in 32% of cases. Clinical anomalies were reported in 76% of patients, mostly renal anomalies (52%), cardiovascular anomalies (29%) and dysmorphic features (13%). A developmental delay was reported in 24% of patients. Variants were found in all regions of the gene. Methylation analysis of the MAGED2 CpG-rich promotor showed a correlation with gender, independent of age, tissue or presence of symptoms, excluding a role for this mechanism in the incomplete penetrance in women. CONCLUSION: This work enriches the phenotypic and genetic description of this recently described disease, and deepens our understanding of the pathophysiological role and regulation of MAGED2. Finally, by describing the wide range of outcomes in patients, this work opens the discussion on genetic counseling offered to families.

The clinical value of optical genome mapping in the rapid characterization of RB1 duplication and 15q23q24.2 triplication, for more appropriate prenatal genetic counselling.

BACKGROUND: Despite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy-number-variant duplications and defining the mechanisms underlying the formation of certain chromosomal rearrangements. Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations. METHODS: Here, we report on the use of OGM in a prenatal diagnosis setting. Detailed breakpoint mapping was used to determine the relative orientations of triplicated and duplicated segments in two unrelated foetuses harbouring chromosomal aberrations: a de novo 15q23q24.2 triplication and a paternally inherited 13q14.2 duplication that overlapped partially with the RB1 gene. RESULTS: OGM enabled us to suggest a plausible mechanism for the triplication and confirmed that the RB1 duplication was direct oriented and in tandem. This enabled us to predict the pathogenic consequences, refine the prognosis and adapt the follow-up and familial screening appropriately. CONCLUSION: Along with an increase in diagnostic rates, OGM can rapidly highlight genotype-phenotype correlations, improve genetic counselling and significantly influence prenatal management.

Risk of congenital malformation after first trimester mRNA COVID-19 vaccine exposure in pregnancy: the COVI-PREG prospective cohort.

OBJECTIVES: This study aimed to evaluate the risk of congenital malformation among pregnant women exposed to the mRNA COVID-19 vaccines during the first trimester of pregnancy, which is a developmental period where the foetus is at risk of teratogenicity. METHODS: Pregnant women were prospectively enrolled from March 2021 to March 2022, at the time of COVID-19 vaccination. Pregnant women exposed to at least one dose of mRNA COVID-19 vaccine from conception to 11 weeks of gestations and 6 days were compared with pregnant women exposed to the vaccine from 12 weeks to the end of pregnancy. The primary outcome was a confirmed congenital malformation at birth. RESULTS: A total of 1450 pregnant women were enrolled including 124 in the first trimester and 1326 in the second and third trimester. The overall proportion of congenital malformation was 0.81% (n = 1/124; 95% CI: 0.02-4.41) and 0.83% (n = 11/1326; 95% CI: 0.41-1.48) among pregnant exposed to the COVID-19 vaccine during the first and second/third trimester, respectively. First trimester exposure was not associated with a higher risk of congenital malformation with a relative risk of 0.89 (95% CI: 0.12-6.80) with no significant changes after adjustment through exploratory analysis. CONCLUSIONS: Pregnant women exposed to mRNA COVID-19 vaccine before 12 weeks of gestation did not have an increased risk of congenital malformation compared with women exposed outside the teratogenic window. Because vaccination is safe and effective, emphasis must be placed on promoting vaccination during pregnancy.

Maternal and perinatal outcomes following pre-Delta, Delta, and Omicron SARS-CoV-2 variants infection among unvaccinated pregnant women in France and Switzerland: a prospective cohort study using the COVI-PREG registry.

Background: SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. Methods: This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. Findings: Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. Interpretation: The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. Funding: Swiss Federal Office of Public Health, Fondation CHUV.

Is gestational age at term a risk factor for ongoing pregnancies in nulliparous women: A prospective cohort study.

BACKGROUND: The results of American observational studies and 1 large, randomized trial show that elective induction of labor among nulliparous women can reduce cesarean delivery rates and suggest that gestational age at delivery may be a risk factor for cesarean delivery in pregnancies managed expectantly. However, data on the risk of cesarean delivery at term in ongoing pregnancies are sparse, especially in high-income countries, and further information is needed to explore the external validity of these previous studies. OBJECTIVE: This study aimed to evaluate the risk of cesarean delivery for each gestational week of ongoing pregnancy in nulliparous women with a singleton fetus in the cephalic presentation at term in a French population. STUDY DESIGN: This retrospective study was conducted in a perinatal network of 10 maternity units from January 1, 2016, to December 31, 2017, and included all nulliparous women with a singleton fetus in the cephalic presentation who gave birth at term (≥37 0/7 weeks of gestation). From the start of term (37 completed weeks) and at the start of each subsequent week of completed gestation (each week + 0 days), ongoing pregnancy was defined as that of a woman who was still pregnant and who gave birth at any time after that date. For each week of gestation for these ongoing pregnancies, the cesarean delivery rate was defined as the number of cesarean deliveries performed in each ongoing pregnancy group divided by the number of women in this group. Separate models for each week of gestation, adjusted by maternal characteristics and hospital status, were used to compare the cesarean delivery risk between ongoing pregnancies and those delivered the preceding week. The same methods were applied to subgroups defined according to the mode of labor onset. Odds ratios were calculated after adjusting for maternal age and educational level, presence of severe preeclampsia, and maternity unit status. RESULTS: The study included 11,308 nulliparous women, 2544 (22.5%) of whom had a cesarean delivery. These rates remained stable for ongoing pregnancies at 37 0/7, 38 0/7, and 39 0/7 weeks of gestation; the rates were 22.5% (95% confidence interval, 21.7-23.2), 22.6% (95% confidence interval, 21.8-23.3); and 22.7% (95% confidence interval, 21.9-23.6), respectively. The risk of cesarean delivery started to increase in ongoing pregnancies at 40 0/7 weeks of gestation (24.3%; 95% confidence interval, 23.1-25.4) and especially at 41 0/7 weeks of gestation (30.7%; 95% confidence interval, 28.9-32.5). Similar trends were also shown for all modes of labor onset and in every maternity unit. In univariate and multivariate analyses, ongoing pregnancy at or beyond 40 0/7 weeks of gestation was associated with a higher risk of cesarean delivery than pregnancy delivered the previous week: 24.3% of ongoing pregnancies at 40 0/7 weeks of gestation vs 19.9% of deliveries between 39 0/7 weeks of gestation and 39 6/7 weeks of gestation. The odds ratios were 1.28 (95% confidence interval, 1.15-1.44) or 30.4% of ongoing pregnancies at 41 0/7 weeks of gestation vs 1.73 (95% confidence interval, 1.51-1.96) or 19.6% of deliveries between 40 0/7 weeks of gestation and 40 6/7 weeks of gestation. CONCLUSION: Cesarean delivery rates increased starting at 40 0/7 weeks of gestation in ongoing pregnancies regardless of the mode of labor onset.

Risk of preterm delivery after medically indicated termination of pregnancy with induced vaginal delivery: a case-control study.

We investigated whether nonsurgical termination of pregnancy after 14 weeks of gestation increases the risk of preterm delivery in a subsequent pregnancy. We conducted a two-centre retrospective case-control study. Patients who underwent non-surgical termination of pregnancy after 14 weeks of gestation between 2012 and 2015 and who gave birth after 14 weeks of gestation to a live-born singleton infant were included. Control patients were those who gave birth after 37 weeks of gestation (the same month as a case patient) and had a second delivery of a singleton foetus after 14 weeks of gestation. The primary outcome was preterm delivery during the second pregnancy period. We included 151 cases and 302 controls and observed 13 (8.6%) preterm births during the second pregnancy in the case group versus 8 (2.6%) (odds ratio: 3.62; 95% confidence interval: 1.40-8.65, p < .001) in the control group. This result remained significant after multivariate analysis. Impact statementWhat is already known about this topic? Many studies have evaluated the association between first-trimester surgical or non-surgical termination of pregnancy and the risk of preterm birth in the subsequent pregnancy. However, no study has evaluated the association between second- or third-trimester non-surgical termination of pregnancy due to foetal disease and the risk of preterm birth in the subsequent pregnancy. A small number of studies have included a small proportion of patients who previously underwent non-surgical termination of pregnancy after 14 weeks of gestation and later experienced first-trimester termination during their second pregnancy. These studies focussed on the impact of the interpregnancy interval or pharmacological induction of labour on the risk of preterm delivery in the subsequent pregnancy.What did the results of this study add? This is the first study to specifically evaluate the association between second- and third-trimester non-surgical terminations of pregnancy and the risk of preterm birth in the subsequent pregnancy. When compared with term birth, nonsurgical termination of pregnancy was associated with the risk of spontaneous preterm birth and hospitalisation in the neonatal intensive care unit in the subsequent pregnancy.What are the implications of these findings for clinical practice and further research? Further studies are required to confirm our results, but information delivered to patients with a late termination of pregnancy and during their pregnancy follow-up for the subsequent pregnancy could be modified to provide this information.

Cesarean section rate changes after audit and feedback with the Ten Group Classification System in a French perinatal network: A retrospective pre-post study.

INTRODUCTION: The rise in the number of cesarean sections (CS) is a major health public problem which concerns nearly all countries. It is suggested that the Ten Group Classification System be adapted to a procedure of audit/feedback cycles, which could have an effect on CS practice. Therefore, we aimed to study changes in CS rates between maternity wards in a perinatal network after implementation of the Ten Group Classification System in an audit with feedback. MATERIAL AND METHODS: This was a retrospective pre-post study of all births from 1 January 2012 to 31 December 2018, in a French perinatal network of 10 maternity wards in the Yvelines district of France. All live births occurring at a gestational age ≥24 weeks in the network were included. During the pre-period (1 January 2012 to 31 December 2014), the audit and feedback provided only overall CS rates. During the post-period (1 January 2015 to 31 December 2018), CS rates for each Robson Ten Group Classification System group were provided. Regression models, adjusted for maternal characteristics and maternity ward, were used to compare CS rates globally and for each group of the system. Variability of CS rates between maternity wards was analyzed using the coefficients of variation. RESULTS: There were 51 082 women who delivered during the pre-period and 63 964 during the post-period. The overall CS rate did not decrease (24.5% during the pre-period vs 25.1% during the post-period). There were no significant differences in CS rates for any group of the Ten Group Classification System after adjustment for maternity, maternal age and sociodemographic characteristics, nor did audit implementation decrease CS rate variability between maternity wards or within groups of the system. CONCLUSIONS: Implementation of an audit-and-feedback cycle using the Ten Group Classification System did not decrease either CS rates or variability between maternity wards.

Impact of COVID-19-Related Lockdown on Delivery and Perinatal Outcomes: A Retrospective Cohort Study.

OBJECTIVE: The magnitude and direction of effects on pregnancy outcomes of the lockdown imposed during COVID-19 have been uncertain and debated. Therefore, we aimed to quantify delivery and perinatal outcomes during the first nationwide lockdown due to the COVID-19 pandemic compared with the same durations of time for the pre- and post-lockdown periods. STUDY DESIGN: This was a retrospective cohort study of six university hospital maternity units distributed across France, each of which serves as the obstetric care referral unit within its respective perinatal network. Maternal and perinatal outcomes were compared between the lockdown period and same-duration (i.e., 55-day) periods before and after the 2020 lockdown (pre-lockdown: 22 January-16 March; lockdown: 17 March-10 May; post-lockdown: 11 May-4 July). We compared the overall rates of Caesarean delivery (CD), pre-labor CD, labor induction, operative vaginal delivery, severe postpartum hemorrhage (≥1 L), severe perineal tear, maternal transfusion, and neonatal mortality and morbidity (1- and 5-min Apgar scores < 7), hypoxia and anoxia (umbilical arterial pH < 7.20 or <7.10, respectively), and admission to a neonatal intensive care unit before discharge. Adjusted odds ratios were estimated using logistic regression, controlling for region of birth, maternal age category, multiparity, multiple pregnancies, diabetes, and hypertensive disorders. RESULTS: The study sample consisted of 11,929 women who delivered consecutively at one of the six maternity units studied (4093 pre-lockdown, 3829 during lockdown, and 4007 post-lockdown) and their 12,179 neonates (4169 pre-lockdown, 3905 during lockdown, and 4105 post-lockdown). The maternal and obstetric characteristics of the women delivering during the lockdown period were alike those delivering pre- and post-lockdown on maternal age, parity, body mass index, rate of complication by hypertensive disorders or insulin-treated diabetes, and gestational age at delivery. Overall CD rates were similar during the three periods (23.6%, 24.8%, and 24.3% pre-lockdown, lockdown, and post-lockdown, respectively) and no outcome differed significantly during lockdown compared to pre- and post-lockdown. These findings were consistent across maternity units. CONCLUSION: The maternal and perinatal outcomes are reassuring regarding the performance of the health-care system during the COVID-19 lockdown studied. Such information is crucial, because additional COVID-19-related lockdowns might still be needed. They are also instructive regarding potential future pandemics.

Impact of COVID-19 Lockdown on Preterm Births, Low Birthweights and Stillbirths: A Retrospective Cohort Study.

OBJECTIVE: The effect of lockdowns during the coronavirus (COVID-19) pandemic on pregnancy outcomes remains uncertain. We aimed to evaluate the association between the COVID-19-related lockdown and pregnancy outcomes in maternity hospitals in France. STUDY DESIGN: This was a retrospective cohort study from six tertiary referral hospitals in different regions of France. Three 55-day periods were compared: pre-lockdown from 22 January 2020, lockdown from 17 March 2020, and post-lockdown from 11 May 2020 to 4 July 2020. We included all women who delivered singleton or multiple pregnancies, who delivered at ≥24 weeks of gestation and with birthweights ≥500 g. We documented gestational ages at the delivery of liveborn and stillborn infants ('stillbirths'). These were categorized as having a very low birthweight (VLBW, <1500 g), or a low birthweight (LBW, <2500 g). Adjustments were made for place of birth, maternal age, parity and diabetes, and hypertensive disorders, as well as for multiple pregnancies. RESULTS: In total, 11,929 women delivered in the six selected centers. This figure is constituted of 4093, 3829, and 4007 deliveries in the pre-lockdown (1), peri-lockdown (2), and post-lockdown (3) periods, respectively. There were no differences in pregnancy outcomes between these three periods. Overall, birth rates <27+6 weeks, between weeks 28+0 and 31+6, and between 32+0 and weeks 36+6 were 1.0%, 1.9%, and 4.4%, respectively. After adjustment, these rates were stable between periods 1 and 2 (adjusted odds ratio, aOR 0.90; 95% confidence interval, CI 0.69-1.19) and between periods 2 and 3 (aOR 1.04; 95% CI 0.80-1.36). Although more VLBW neonates were born during lockdown (3.5% vs. 2.6%, p = 0.03), this difference did not persist after adjustment (aOR 0.84, CI 95% 0.64-1.10). The LBW rates were similar during the three periods at 12.5% overall. The stillbirth rate was unaffected by the lockdown. CONCLUSION: The pregnancy outcomes (preterm birth, LBW, VLBW, and stillbirth rates) were not modified by the COVID-19 lockdown in our cohort study in France. Considering the discrepancies in results and methodological issues in previous published studies, there is not sufficient evidence to conclude that such lockdowns have any impact on perinatal outcomes.

Effects of the implementation of second-line prenatal cell-free DNA testing on termination of pregnancy in a French perinatal network.

OBJECTIVE: To evaluate the impact of implementing cell-free DNA (cfDNA) testing on gestational age (GA) at termination of pregnancy in a French perinatal network. METHODS: We conducted a retrospective study. All women having undergone a termination of pregnancy between 1 January 2012 and 31 December 2017 were included. We compared the periods before and after the introduction of second-line cfDNA testing, which started on 1 January 2015. Throughout the study period, the invasive procedures were foetal karyotyping and chromosomal microarray analysis. The primary study outcome was GA at termination. The secondary outcomes were GA at termination for trisomy 21 and the frequency and GA at the time of invasive procedures. RESULTS: During the 6-year study period, 840 women underwent termination. The median GA at termination before and after the implementation of cfDNA testing was 19.4 and 19.0 weeks, respectively (p = 0.38). Although the frequency of termination for trisomy 21 increased significantly from 23% to 32% (p < 0.01), the median GA at termination did not change significantly (p = 0.80). The implementation of cfDNA testing was associated with a decrease in the frequency of invasive procedures in general and chorionic villus sampling in particular (p = 0.04). CONCLUSION: The introduction of cfDNA testing does not increase the GA at termination for trisomy21.

Variation between hospital caesarean delivery rates when Robson's classification is considered: An observational study from a French perinatal network.

INTRODUCTION: WHO has recommended using Robson's Ten Group Classification System (TGCS) to monitor and analyze CD rates. Its failure to take some maternal and organizational factors into account, however, could limit the interpretation of CD rate comparisons, because it may contribute to variations in hospital CD rates. OBJECTIVE: To study the contribution of maternal socioeconomic and clinical characteristics and hospital organizational factors to the variation in CD rates when using Robson's ten-group classification system for CD rate comparisons. METHODS: This prospective, observational, population-based study included all deliveries at a gestational age > 24 weeks at the 10 hospitals of the French MYPA perinatal network in the Paris area. CD rates were calculated for each TGCS group in each hospital. Interhospital variations in these rates were investigated with hierarchical logistic regression models to quantify the variation explained by differences in patient and hospital characteristics when the TGCS is considered. Variations in CD rates between hospitals were estimated with median odds ratios (MOR) to express interhospital variance on the standard odds ratio scale. The percentage of variation explained by TGCS and maternal and hospital characteristics was also calculated. RESULTS: The global CD rate was 24.0% (interhospital range: 17-32%). CD rates within each TGCS group differed significantly between hospitals (P<0.001). CD was significantly associated with maternal age (>40 years), severe preeclampsia, and two organizational factors: hospital status (private maternities) and the deliveries per staff member per 24 hours. The MOR in the empty model was 1.27 and did not change after taking the TGCS into account. Adding maternal characteristics and hospital organizational factors lowered the MOR to 1.14 and reduced the variation between hospital CD rates by 70%. CONCLUSION: Maternal characteristics and hospital factors are needed to address variation in CD rates among the TGCS groups. Therefore, comparisons of these rates that do not consider these factors should be interpreted carefully.

Paternal and maternal long-term psychological outcomes after uterine artery embolization for severe post-partum hemorrhage.

This study intend to compare the long-term psychological impact (depression, post-traumatic stress disorder) on both partners between patients that underwent uterine artery embolization (UAE) for post-partum hemorrhage (PPH) and uneventful deliveries. Women who experienced severe PPH treated by UAE in our institution between 2003 and 2013 were identified in our obstetrical database. These cases were matched to controls with uneventful deliveries. Matching criteria were maternal age, parity, ethnicity, year of delivery, birthweight, gestational age and mode of delivery. Patients and their partners completed validated questionnaires measuring post-traumatic stress (TSQ), as well as depression symptoms (MINI). A total of 63 cases of PPH and 189 matched controls (1:3) participated in a study exploring gynecological and obstetrical outcomes. With a mean of 8 years post-index delivery, patients after PPH showed increased risk of depression (p = 0.015) and post-traumatic stress disorder (22.2% versus 4.8%, p < 0.005) compared to controls. PPH remains strongly associated with post-traumatic stress disorder, even after adjustment for depression (adjusted odds ratio 5.1; 95% confidence intervals 1.5-17.5). Similarly, partners of patients with PPH showed a propensity to depression (p = 0.029) and post-traumatic stress disorder (11.5% versus 1.5%, p = 0.019). In conclusion, both women and their partners are at increased risk of long-term psychological adverse outcomes after PPH. Couples may benefit from psychological support.

Gynecological, reproductive and sexual outcomes after uterine artery embolization for post-partum haemorrage.

In this case control study, long-term gynecological, reproductive and sexual outcomes after uterine artery embolization (UAE) for postpartum hemorrhage (PPH) were evaluated. The study was performed in a single referral hospital for PPH in Lausanne from 2003 to 2013. Each woman whose delivery was complicated by PPH and treated by UAE was included, and compared to a control group of women whose delivery was uncomplicated. Cases were matched by maternal age, parity, ethnicity, year and mode of delivery, birth weight and gestational age in a 1-3 ratio. A total of 77 patients treated by UAE for PPH were identified in our obstetrical database. Among them, 63 were included and compared to 189 matched patients (no PPH). The mean interval time between UAE and this study was 8.1 years. Time to menstrual cycle recovery after delivery (3.9 vs 5.6 months, p = 0.66), spotting (7.9% vs 7.2%, p = 0.49), dysmenorrhea (25.4% vs 22.2%, p = 0.60) and amenorrhea (14.3% vs 12.2%, p = 0.66) were similar between the two groups. There was no difference in the FSFI score between the groups (23.2 ± 0.6 vs 23.8 ± 0.4; p = 0.41). However, the interval time to subsequent pregnancy was longer for patients after UAE than the control group (35 vs 18 months, p = 0.002). In case of pregnancy desire, the success rate was lower after UAE compared to controls (55% vs 93.5%, p < 0.001). The rate of PPH was higher in those with previous PPH (6.6% vs 36.4%, p = 0.010). Patients treated by UAE for PPH did not report higher rates of gynecological symptoms or sexual dysfunction compared to patients with uneventful deliveries. The inter-pregnancy interval was increased and the success rate was reduced. In subsequent pregnancies, a higher rate of PPH was observed in those that underwent UAE.

Prenatal diagnosis of 2q13 duplications: The crucial role of the family survey in genetic counseling on novel copy number variations.

In recent years, the introduction of novel genome analysis technologies (such as array comparative genomic hybridization) has enabled the prenatal diagnosis of various recurrent copy number variations (CNVs). Some of these CNVs have been linked to a greater susceptibility of developmental and neuropsychiatric disorders; for example, recurrent duplication at the 2q13 locus is associated with developmental delay, dysmorphism and intellectual disability. However, this CNV has low penetrance and variable clinical expressivity. It also can be observed in healthy controls and can be transmitted by unaffected parents, making genetic counseling especially challenging. Here, we report on the inheritance of a 2q13 duplication in an asymptomatic family; the case highlights the role of the family survey in genetic counseling with regard to novel CNVs diagnosed before birth.

Non-invasive assessment of placental perfusion in vivo using arterial spin labeling (ASL) MRI: A preclinical study in rats.

INTRODUCTION: Non-invasive assessment of placental perfusion is of great interest to characterize placental function in clinical practice. This article proposes a strictly non-invasive MRI technique using ASL to quantify placental blood flow in vivo. The aim of this study was to develop a fMRI tool to quantify placental blood flow (PBF) in rat, by using arterial spin labeling (ASL) MRI at 4.7 T. MATERIALS AND METHODS: MRI was performed with a dedicated magnet for small animals, in pregnant rats on day 20 of the 22-day gestation period. A Look-Locker flow-sensitive alternating inversion recovery gradient echo sequence was developed as ASL technique (TE: 1.55 ms; TR: 3.5 ms, TI: 56 ms, deltaTI: 56 ms, FA: 20°, Matrix: 128 × 128, 8 segments, 4 Nex). Labeling was performed with global and slice-selective inversions, and T1 map was obtained for each mode of inversion. PBF was then derived from a compartmental model of the variation of T1 between global and slice-selective inversions. RESULTS: The full protocol was completed and ASL image post-processing was successful in 18 rats. Forty-seven placentas were analyzed, with a mean PBF of 147 ±â€¯70 ml/min/100 g of placenta, consistent with published values of placental perfusion using invasive techniques. CONCLUSION: ASL MRI is feasible for the quantification of PBF in rats at 4.7 T. This technique, which requires no administration of contrast media, could have implications for non-invasive longitudinal and in vivo animal studies and may be useful for the management of human pregnancies.

Fetal diagnosis of right cardiac ventricular aneurysms: A report of three cases.

Congenital ventricular aneurysms and diverticula are rare congenital heart diseases, currently accessible to prenatal diagnosis. Information on the natural course of ventricular aneurysm or diverticulum detected during fetal life is limited as there are only few case reports and case series enumerating the defect. We aimed to describe through three cases, the prenatal features and clinical outcomes of fetal cardiac aneurysms. The first one was diagnosed during the second trimester and spontaneous evolution was favorable. The two others were diagnosed in the first trimester with a large and early pericardial effusion. For one, the parents opted for termination of pregnancy at 15 weeks of gestation and the other showed a spontaneous regression of the effusion and no hemodynamic compromise.

Impact of recommended changes in labor management for prevention of the primary cesarean delivery.

BACKGROUND: The dramatic rise in cesarean delivery rates worldwide in recent decades, without evidence of a concomitant decrease in cerebral palsy rates, has raised concerns about its potential negative consequences for maternal and infant health. In 2014, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine jointly published an Obstetric Care Consensus for safe prevention of the primary cesarean delivery. OBJECTIVE: We sought to assess whether modification of our protocol to implement these recommendations helped to decrease our primary cesarean delivery rate safely. STUDY DESIGN: This is a before-and-after retrospective cohort study at a university referral hospital. In March 2014, the threshold for defining active labor changed from 4 to >6 cm and arrest of first-stage labor from lack of cervical change despite regular contractions after 3 hours of oxytocin administration with amniotomy and epidural anesthesia to no change after 4 hours of adequate or 6 hours of inadequate contractions in women with an epidural. The definition of second-stage arrest of labor changed simultaneously from lack of progress for 3 hours with adequate contractions in women with epidural anesthesia to no progress for ≥4 hours in nulliparas or 3 hours in multiparas with an epidural. We compared maternal and neonatal outcomes over two 1 year periods: from March 2013 to February 2014 (before, preguideline) and from June 2014 to May 2015 (after, postguideline). We included all women with singleton pregnancies at ≥37 weeks' gestation, in vertex presentation, in spontaneous or induced labor, and with epidural anesthesia. We excluded women with an elective or previous cesarean delivery and those with obstetric or fetal complications. RESULTS: This study included 3283 and 3068 women in the before and after periods, respectively. The groups had similar general and obstetric characteristics. The global cesarean delivery rate decreased significantly from 9.4% in the preguideline to 6.9% in the postguideline period (odds ratio, 0.71; 95% confidence interval, 0.59-0.85; P < .01). The cesarean delivery rate for arrest of first-stage labor fell by half, from 1.8% to 0.9% (odds ratio, 0.51; 95% confidence interval, 0.31-0.81; P < .01) but was significant only among nulliparous women. The cesarean delivery rate for second-stage arrest of labor decreased but not significantly between periods (1.3% vs 1.0%; odds ratio, 0.73; 95% confidence interval, 0.44-1.22; P = .2), and the cesarean delivery rate for failure of induction remained similar (3.7% vs 3.5%; odds ratio, 1.06; 95% confidence interval, 0.06-13.24; P = .88). The median duration of labor before cesarean delivery also became significantly longer among nulliparous women during the later period. Maternal and neonatal outcomes did not differ between the 2 periods, except that the rate of 1 minute Apgar score <7 fell significantly in the later period (8.4% vs 6.9%; odds ratio, 0.80; 95% confidence interval, 0.66-0.97; P = .02). CONCLUSION: The modification of our protocol by implementing the new consensus recommendations was associated with a reduction of the rate of primary cesarean delivery performed for arrest of labor with no apparent increase in immediate adverse neonatal outcomes in nulliparous women at term with singleton pregnancies in vertex presentation and with epidural anesthesia. Further studies are needed to assess the long-term maternal and neonatal safety of these policies.

Uterine contractility and elastography as prognostic factors for pregnancy after intrauterine insemination.

OBJECTIVE: To determine the impact of the frequency and intensity of uterine contractions (UCs) at the time of IUI on subsequent fertility. DESIGN: Observational pilot study. SETTING: University hospital. PATIENT(S): One hundred volunteer women scheduled for IUI between April 2011 and July 2013, in whom UCs were assessed during the ultrasound before IUI. INTERVENTION(S): A two-dimensional sagittal uterus elastography was recorded for 5 minutes. The elasticity index, defined as the mean ratio of elastographic measurements between the subendometrial area (of interest) and the endometrial area (control), was computed. UC frequency, endometrial thickness and volume, and subendometrial vascularisztion were also measured. MAIN OUTCOME MEASURE(S): These parameters, along with characteristics of the IUI cycle, were entered into a logistic regression model for predicting ongoing pregnancy. RESULT(S): The elasticity index was significantly higher (2.4 ± 1.3 vs. 1.5 ± 0.7, i.e., with stiffer myometrium), and the endometrium was significantly less echogenic in future pregnant women. Factors closely reaching significance were age, previous fertility, day 3 hormonal assessments, number of inseminated spermatozoa, endometrial thickness, and UC count. In multivariate analysis, low UC frequency (<2.8/minute; odds ratio [OR] = 0.039), high elasticity index (>1.7; OR = 63.26), high endometrial thickness on the ovulation triggering day (>8 mm; OR = 28.21), and low patient age (<32 years; OR = 0.001) were predictive of pregnancy after IUI. CONCLUSION(S): A low frequency and high intensity of UCs at the day of IUI appears associated with a higher pregnancy rate. Elastography provides a promising innovative tool for IUI monitoring.

Active Management of the Third Stage of Labor With a Combination of Oxytocin and Misoprostol to Prevent Postpartum Hemorrhage: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of misoprostol administered simultaneously with oxytocin as part of the active management of the third stage of labor. METHODS: This multicenter, double-blind, randomized, placebo-controlled trial recruited women in the first stage of labor with expected vaginal deliveries at 36-42 weeks of gestation. Exclusion criteria were multiple pregnancies, hypersensitivity to misoprostol, and cesarean delivery. Participants received routine intravenous oxytocin and were randomly allocated to receive 400 micrograms misoprostol or placebo orally immediately after delivery of the newborn. The primary outcome was postpartum hemorrhage (500 mL or greater within 2 hours of birth). Secondary outcomes included severe postpartum hemorrhage (1,000 mL or greater) and adverse maternal events such as fever, shivering, and nausea. Two groups of 1,550 women were required to demonstrate a 33% decrease of postpartum hemorrhage according to a two-tailed α at 0.05 with 80% power. An interim analysis was planned after 50% enrollment. RESULTS: Participant enrollment occurred from April 2010 to September 2013. Baseline characteristics were similar in the two groups. The study was discontinued after the planned interim analysis including 1,721 patients showed that misoprostol was not effective and was associated with significantly more adverse effects. The rate of postpartum hemorrhage was 8.4% (68/806) in the misoprostol and 8.3% (66/797) in the placebo group (P=.98), and rates of severe postpartum hemorrhage were 1.8% and 2.4%, respectively (P=.57). Maternal adverse events occurred significantly more frequently in the misoprostol group (for fever 30.4% in the misoprostol group compared with 6.3% in the placebo group, P<.001; for shivering 10.8% in the misoprostol group compared with 0.6% in the placebo group, P<.001). CONCLUSION: Misoprostol administered with prophylactic routine oxytocin did not reduce the rate of postpartum hemorrhage risk and increased the rate of adverse events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01113229.