Risk factors for placenta accreta spectrum disorders in women with any prior cesarean and a placenta previa or low lying: a prospective population-based study.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

Maternal occupational exposure to carbonaceous nanoscale particles and neurodevelopmental outcomes in early childhood: Analysis of the French Longitudinal Study of Children - Elfe study.

OBJECTIVE: To investigate the association between occupational exposures to carbonaceous unintentionally emitted nanoscale particles (UNPs) during pregnancy and the child's language development and behaviour at two years old. METHODS: Using data from the French Longitudinal Study of Childhood - ELFE, we selected mothers who worked during pregnancy and their children. Exposure to carbonaceous UNPs was assessed by the MatPUF (job-exposure matrix for ultrafine particles). Children's lexical development was analysed using 'the Mac Arthur - Bates communicative development inventories-words and sentences-short form' (MB-CDI) in a multivariate binary logistic regression. Their risk for autism spectrum disorders was studied using 'the Modified-CHecklist for Autism in Toddler' (M-CHAT) according to the recommended thresholds (low risk = 0-2; intermediate risk = 3-6 and high risk = 7-23) in unordered multinomial logistic regression models. RESULTS: Maternal occupational exposure to carbonaceous UNPs was associated with delayed child language development (ORadj: 1.34; 95 % CI: 1.00, 1.80) but not with behavioural disorders (autism spectrum disorders) at two years old. CONCLUSION: This is the first epidemiological study to show a significant association between maternal occupational exposure to carbonaceous nanoscale particles and child language development at 2 years old.

Survival without severe neonatal morbidity after antenatal betamethasone dose reduction: a post hoc analysis of a randomized non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated. OBJECTIVE: This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes. STUDY DESIGN: We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia. RESULTS: After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial. CONCLUSION: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings.

Oxytocin versus prostaglandins for labour Induction of women with an unfavourable cervix after 24 hours of cervical ripening (OPIC): protocol for an open multicentre randomised non-inferiority trial.

INTRODUCTION: It remains uncertain whether the most appropriate management for women with an unfavourable cervix after 24 hours of cervical ripening is repeating the ripening procedure or proceeding directly to induction by oxytocin. No adequately powered trial has compared these strategies. We hypothesise that induction of labour with oxytocin among women who have just undergone an ineffective first ripening procedure is not associated with a higher risk of caesarean delivery than a repeated cervical ripening with prostaglandins. METHODS AND ANALYSIS: We will conduct a multicentre, non-inferiority, open-label, randomised controlled trial aimed at comparing labour induction by oxytocin with a second cervical ripening that uses prostaglandins (slow-release vaginal dinoprostone; oral misoprostol 25 µg; dinoprostone vaginal gel 2 mg). Women (n=1494) randomised in a 1:1 ratio in 10 French maternity units must be ≥18 years with a singleton fetus in vertex presentation, at a term from ≥37+0 weeks of gestation, and have just completed a 24-hour cervical ripening procedure by any method (pharmacological or mechanical) with a Bishop score ≤6. Exclusion criteria comprise being in labour, having more than 3 contractions per 10 min, or a prior caesarean delivery or a history of uterine surgery, or a fetus with antenatally suspected severe congenital abnormalities or a non-reassuring fetal heart rate. The primary endpoint will be the caesarean delivery rate, regardless of indication. Secondary outcomes concern delivery, perinatal morbidity, maternal satisfaction and health economic evaluations. The nature of the assessed procedures prevents masking the study investigators and patients to group assignment. ETHICS AND DISSEMINATION: All participants will provide written informed consent. The ethics committee 'Comité de Protection des Personnes Ile de France VII' approved this study on 2 April 2021 (No 2021-000989-15). Study findings will be submitted for publication and presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT04949633.

Association Between Surgeon Gender and Maternal Morbidity After Cesarean Delivery.

Importance: The stereotype that men perform surgery better than women is ancient. Surgeons have long been mainly men, but in recent decades an inversion has begun; the number of women surgeons is increasing, especially in obstetrics and gynecology. Studies outside obstetrics suggest that postoperative morbidity and mortality may be lower after surgery by women. Objective: To evaluate the association between surgeons' gender and the risks of maternal morbidity and postpartum hemorrhage (PPH) after cesarean deliveries. Design, Setting, and Participants: This prospective cohort study was based on data from the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial, a multicenter, randomized, placebo-controlled trial that took place from March 2018 through January 2020 (23 months). It aimed to investigate whether the administration of tranexamic acid plus a prophylactic uterotonic agent decreased PPH incidence after cesarean delivery compared with a uterotonic agent alone. Women having a cesarean delivery before or during labor at or after 34 weeks' gestation were recruited from 27 French maternity hospitals. Exposures: Self-reported gender (man or woman), assessed by a questionnaire immediately after delivery. Main Outcomes and Measures: The primary end point was the incidence of a composite maternal morbidity variable, and the secondary end point was the incidence of PPH (the primary outcome of the TRAAP2 trial), defined by a calculated estimated blood loss exceeding 1000 mL or transfusion by day 2. Results: Among 4244 women included, men surgeons performed 943 cesarean deliveries (22.2%) and women surgeons performed 3301 (77.8%). The rate of attending obstetricians was higher among men (441 of 929 [47.5%]) than women (687 of 3239 [21.2%]). The risk of maternal morbidity did not differ for men and women surgeons: 119 of 837 (14.2%) vs 476 of 2928 (16.3%) (adjusted risk ratio, 0.92 [95% CI, 0.77-1.13]). Interaction between surgeon gender and level of experience on the risk of maternal morbidity was not statistically significant. Similarly, the groups did not differ for PPH risk (adjusted risk ratio, 0.98 [95% CI, 0.85-1.13]). Conclusions and Relevance: Risks of postoperative maternal morbidity and of PPH exceeding 1000 mL or requiring transfusion by day 2 did not differ by the surgeon's gender.

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. METHODS: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. FINDINGS: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. INTERPRETATION: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. FUNDING: French Ministry of Health.

Tranexamic acid for the prevention of blood loss after cesarean among women with twins: a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery randomized clinical trial.

BACKGROUND: Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of >1000 mL or red cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies. OBJECTIVE: This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies. STUDY DESIGN: This was a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial data, a double-blind, randomized controlled trial from March 2018 to January 2020 in 27 French maternity hospitals, that included 319 women with multiple pregnancies. Women with a cesarean delivery before or during labor at ≥34 weeks of gestation were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss of >1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements. RESULTS: Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, and 298 (93.4%) had primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% confidence interval, 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons). CONCLUSION: Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.

Arabin pessary to prevent adverse perinatal outcomes in twin pregnancies with a short cervix: a multicenter randomized controlled trial (PESSARONE).

BACKGROUND: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial. OBJECTIVE: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix. STUDY DESIGN: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of <35 mm compared pessary placement at 16+0 to 24+0 weeks' gestation with standard care alone. The primary endpoint was a composite of adverse neonatal outcomes, namely peripartum or neonatal death or significant neonatal morbidity before hospital discharge, defined as at least 1 of the following complications: bronchopulmonary dysplasia, intraventricular hemorrhage grade III to IV, periventricular leukomalacia, necrotizing enterocolitis grade II or higher, culture-proven sepsis, and retinopathy requiring treatment. A sample size of 308 pregnancies was planned to ensure 80% power to compare the proportions of women with at least 1 infant with an adverse neonatal outcome. The intention-to-treat analysis after multiple imputation of missing data, was supplemented with a secondary analysis that controlled for gestational age and cervical length, both at inclusion. The primary endpoint was also compared between randomization groups in the per-protocol population, which excluded patients with prespecified major protocol violations (mostly cervical cerclage and/or progesterone after inclusion). Secondary endpoints included preterm birth, spontaneous preterm birth, and pessary side effects. RESULTS: In total, 315 women were randomized to either receive a pessary (n=157) or standard management (n=158). Overall, 10.8% (34 women) of participants had a missing value for the primary endpoint, mostly (79%) because of the lack of paternal consent for neonatal data collection. In the intention-to-treat analysis, the adverse neonatal outcome occurred in 16.8% of the pessary group vs in 22.5% of the control group (risk ratio, 0.69; 95% confidence interval, 0.39-1.23; P=.210). The per-protocol analysis did not show any significant difference between groups (risk ratio, 0.78; 95% confidence interval, 0.47-1.28; P=.320). The occurrence of preterm birth or spontaneous preterm birth did not differ significantly between groups. No serious side effects were associated with pessary use. CONCLUSION: Pessary use in our study did not significantly reduce adverse neonatal outcomes in twin pregnancies with a short cervix.

Survival Without Severe Neonatal Morbidity in Very Preterm Twins According to Planned Mode of Delivery.

OBJECTIVE: To assess survival to discharge without severe neonatal morbidity by planned mode of delivery for twins born before 32 weeks of gestation. METHODS: The JUMODA (JUmeaux MODe d'Accouchement) study was a French national prospective, population-based, cohort study of twin deliveries conducted from February 2014 to March 2015. This planned secondary analysis included diamniotic twin pregnancies from 26 0/7 through 31 6/7 weeks of gestation. Exclusion criteria included contraindications to vaginal delivery and situations for which planned cesarean delivery is favored, and neonatal prognosis depends largely on the underlying pathology rather than the planned mode of delivery. The primary outcome was survival to discharge without severe neonatal morbidity (bronchopulmonary dysplasia, grade 3 or grade 4 intraventricular hemorrhage, periventricular leukomalacia, stage 2 or stage 3 necrotizing enterocolitis). The association between planned mode of delivery and primary outcome was assessed by multivariate Poisson regression model. A propensity-score approach with inverse probability of treatment weighting also was performed to control for indication bias. Subgroup analyses according to birth order and sensitivity analyses limited to spontaneous preterm births only were performed. RESULTS: Among 424 very preterm twin pregnancies, 192 (45.3%) had a planned cesarean delivery and 232 (54.7%) had a planned vaginal delivery. Survival to discharge without severe morbidity did not differ in the two groups: 308 of 384 (80.2%) after planned cesarean and 375 of 464 (80.8%) after planned vaginal delivery (crude relative risk 0.99; 95% CI 0.91-1.15; adjusted relative risk 1.02; 95% CI 0.93-1.11). After applying inverse probability of treatment weighting, planned cesarean delivery still was not associated with higher survival to discharge without severe neonatal morbidity than planned vaginal birth (relative risk 1.11; 95% CI 0.84-1.46). Subgroup and sensitivity analyses showed similar results. CONCLUSION: Planned cesarean delivery for very preterm twins is not associated with higher survival to discharge without severe neonatal morbidity than planned vaginal delivery. These results suggest that very preterm delivery should not be considered a per se indication for planned cesarean in twin pregnancies.

Who needs prenatal counselling with a pediatric surgeon? Experience from a large tertiary care university hospital.

OBJECTIVES: To describe our experience with prenatal counselling for surgical anomalies in a large volume center. The secondary aim is to suggest a list of prenatal abnormalities warranting counselling by a pediatric surgeon. METHODS: We reviewed all prenatal counselling consultations performed by the pediatric surgery team between January 1st, 2015 and December 31st, 2016. RESULTS: A total of 169 patients or couples had a prenatal consultation with a pediatric surgeon. Prenatal work-up included a fetal MRI in 26% of cases, mainly for digestive and thoracic pathologies (56.1% of cases). Consultation with the pediatric surgeon led mainly to recommendations concerning the place of delivery. Induction for reasons related to the fetal anomaly occurred in 22.2% of cases. Most children were surgically treated within the first year of life (63.5%). Correlation between predicted prognosis and actual status at four years of life was 96.9%. Correlation between prenatal and postnatal diagnosis was 87.4%. CONCLUSIONS: Prenatal counselling by a pediatric surgeon allows couples to obtain clear information on the pathology of their unborn child, giving them greater autonomy in their decision to continue the pregnancy.

Uterine-sparing surgical procedures to control postpartum hemorrhage.

Postpartum hemorrhage remains one of the principal causes of maternal mortality in the United States and throughout the world. Its management, which must be multidisciplinary (obstetrics, midwifery, anesthesiology, interventional radiology, and nursing), depends on the speed of both diagnosis and implementation of medical and surgical treatment to control the hemorrhage. The aim of this work is to describe the various techniques of vessel ligation and of uterine compression for controlling and treating severe hemorrhage, and to present the advantages and disadvantages of each. It is not difficult to perform vessel ligation of the uterine arteries: O'Leary's bilateral ligation of the uterine artery, Tsirulnikov's triple ligation, and AbdRabbo's stepwise uterine devascularization (that is, stepwise triple ligation). These procedures are associated with a high success rate (approximately 90%) and a low complication rate. Bilateral ligation of the internal iliac (hypogastric) arteries is more difficult to perform and potentially less effective (approximately 70% effectiveness) than the previously mentioned procedures. Its complication rate is low, but the complications are most often serious. There is no evidence that future fertility or subsequent obstetrical outcomes are impaired by ligation of either the uterine or internal iliac arteries. There are many techniques used for uterine compression sutures, and none has shown clear superiority to another. Uterine compression suture has an effectiveness rate of approximately 75% after failure of medical treatment and approximately 80% as a second-line procedure after unsuccessful vessel ligation. The risk of synechiae after uterine compression suture has not yet been adequately evaluated, but is probably around 5%. The risk of synechiae after uterine compression suture has not yet been adequately evaluated, but probably ranges between 5% and 10%. The methodologic quality of the studies assessing uterine-sparing surgical procedures remains limited, with no comparative studies. Accordingly, no evidence suggests that any one of these methods is better than any other. Accordingly, the choice of surgical technique to control hemorrhage must be guided firstly by the operator's experience. If the hemorrhage continues after a first-line uterine-sparing surgical procedure and the patient remains hemodynamically stable, a second-line procedure can be chosen. Nonetheless, the application of these procedures must not delay the performance of a peripartum hysterectomy in cases of hemodynamic instability.

Greater Risk of Pregnancy Complications for Female Surgeons: A Cross-Sectional Electronic Survey.

BACKGROUND: Female surgeons are exposed to physical and mental stressors that differ from those of other specialties. We aimed to assess whether female surgeons are more at risk of pregnancy complications than women in other medical specialties. METHODS: We used a cross-sectional electronic survey of female physicians working in the French Region Nouvelle-Aquitaine who were pregnant between 2013 and 2018. A pregnancy complication was defined as the occurrence of miscarriage, ectopic pregnancy, fetal growth restriction, prematurity, fetal congenital malformation, stillbirth, or medical termination of the pregnancy. Multivariate logistic regression models were used to evaluate the risk of pregnancy complications for female surgeons relative to women practicing in other medical specialties. RESULTS: Among the 270 women included, 52 (19.3%) experienced pregnancy complications and 28 (10.4%) were surgeons. In the multivariate analysis, female surgeons had a higher risk of pregnancy complications: adjusted odds ratio = 3.53, 95% confidence interval [1.27-9.84]. CONCLUSION: Further research is necessary to identify the hazards specifically involved in the practice of surgery to be able to propose preventive actions targeted to female surgeons during their pregnancy.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome. METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396. FINDINGS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030). INTERPRETATION: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies. FUNDING: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.

Occupational Exposure to Ultrafine Particles and Placental Histopathological Lesions: A Retrospective Study about 130 Cases.

Ultrafine particles (UFPs) are particles smaller than 100 nanometers that are produced unintentionally during human activities or natural phenomena. They have a higher biological reactivity than bigger particles and can reach the placenta after maternal exposure. One study has shown an association between maternal occupational exposure to UFPs and fetal growth restriction. Yet few studies have focused on the effects of UFP exposure on placental histopathological lesions. The aim of this study was to investigate the association between maternal occupational exposure to UFPs and histopathological lesions of their placenta. The analyses were based on data from the ARTEMIS Center. A job-exposure matrix was used to assess occupational exposure to UFPs. The histopathological placental exam was performed by two pathologists who were blinded to the exposure of each subject. The examination was conducted in accordance with the recommendations of the Amsterdam consensus. The study sample included 130 placentas (30 exposed, 100 unexposed). Maternal occupational exposure to UFPs during pregnancy is significantly associated with placental hypoplasia (the phenomenon affected 61% of the exposed patients and 34% of the unexposed ones, p < 0.01). Further research is needed to explain its pathophysiological mechanisms.

A multicenter observational survey of management strategies in 442 pregnancies with suspected placenta accreta spectrum.

INTRODUCTION: Management options for women with placenta accreta spectrum (PAS) comprise termination of pregnancy before the viable gestational age, leaving the placenta in situ for subsequent reabsorption of the placenta or delayed hysterectomy, manual removal of placenta after vaginal delivery or during cesarean section, focal resection of the affected uterine wall, and peripartum hysterectomy. The aim of this observational study was to describe actual clinical management and outcomes in PAS in a large international cohort. MATERIAL AND METHODS: Data from women in 15 referral centers of the International Society of PAS (IS-PAS) were analyzed and correlated with the clinical classification of the IS-PAS: From Grade 1 (no PAS) to Grade 6 (invasion into pelvic organs other than the bladder). PAS was usually diagnosed antenatally and the operators performing ultrasound rated the likelihood of PAS on a Likert scale of 1 to 10. RESULTS: In total, 442 women were registered in the database. No maternal deaths occurred. Mean blood loss was 2600 mL (range 150-20 000 mL). Placenta previa was present in 375 (84.8%) women and there was a history of a previous cesarean in 329 (74.4%) women. The PAS likelihood score was strongly correlated with the PAS grade (P < .001). The mode of delivery in the majority of women (n = 252, 57.0%) was cesarean hysterectomy, with a repeat laparotomy in 20 (7.9%) due to complications. In 48 women (10.8%), the placenta was intentionally left in situ, of those, 20 (41.7%) had a delayed hysterectomy. In 26 women (5.9%), focal resection was performed. Termination of pregnancy was performed in 9 (2.0%), of whom 5 had fetal abnormalities. The placenta could be removed in 90 women (20.4%) at cesarean, and in 17 (3.9%) after vaginal delivery indicating mild or no PAS. In 34 women (7.7%) with an antenatal diagnosis of PAS, the placenta spontaneously separated (false positives). We found lower blood loss (P < .002) in 2018-2019 compared with 2009-2017, suggesting a positive learning curve. CONCLUSIONS: In referral centers, the most common management for severe PAS was cesarean hysterectomy, followed by leaving the placenta in situ and focal resection. Prenatal diagnosis correlated with clinical PAS grade. No maternal deaths occurred.

Assessment of fresh and preserved amniotic membrane for guided bone regeneration in mice.

Thanks to its biological properties, the human amniotic membrane (HAM) can be used as a barrier membrane for guided bone regeneration (GBR). However, no study has assessed the influence of the preservation method of HAM for this application. This study aimed to establish the most suitable preservation method of HAM for GBR. Fresh (F), cryopreserved (C) lyophilized (L), and decellularized and lyophilized (DL) HAM were compared. The impact of preservation methods on collagen and glycosaminoglycans (GAG) content was evaluated using Masson's trichrome and alcian blue staining. Their suture retention strengths were assessed. In vitro, the osteogenic potential of human bone marrow mesenchymal stromal cells (hBMSCs) cultured on the four HAMs was evaluated using alkaline phosphatase staining and alizarin red quantification assay. In vivo, the effectiveness of fresh and preserved HAMs for GBR was assessed in a mice diaphyseal bone defect after 1 week or 1 month healing. Micro-CT and histomorphometric analysis were performed. The major structural components of HAM (collagen and GAG) were preserved whatever the preservation method used. The tearing strength of DL-HAM was significantly higher. In vitro, hBMSCs seeded on DL-HAM displayed a stronger ALP staining, and alizarin red staining quantification was significantly higher at Day 14. In vivo, L-HAM and DL-HAM significantly enhanced early bone regeneration. One month after the surgery, only DL-HAM slightly promoted bone regeneration. Several preserving methods of HAM have been studied for bone regeneration. Here, we have demonstrated that DL-HAM achieved the most promising results for GBR.

Maternal occupational exposure to carbonaceous nanoscale particles and small for gestational age and the evolution of head circumference in the French Longitudinal Study of Children - Elfe study.

OBJECTIVES: To investigate the association between exposure to unintentionally emitted carbonaceous nanoscale particles (NPs) and small for gestational age (SGA), as well as head circumference (HC) at birth and at two years of age. METHODS: Mothers from the French Longitudinal Study of Children (Elfe cohort) who worked during pregnancy were selected for our study. Data collected at birth and during follow-up (up to two years) were used. The probability and frequency of maternal occupational exposure to unintentionally emitted carbonaceous NPs was estimated using a job exposure matrix (MatPUF). Multivariate logistic regression, linear regression, and mixed models were applied to estimate any associations. Analyses were carried out depending on whether mothers stopped working during the first, second, or third trimester of pregnancy. RESULTS: Maternal occupational exposure to unintentionally emitted carbonaceous NPs was associated with SGA in the overall study population by multivariate analysis (ORa = 1.80, 95% CI: 1.29, 2.46), as well as in sub-groups of mothers who stopped working during the second (ORa = 1.84, 95% CI: 1.13, 3.02) or third (ORa = 1.80, 95% CI: 1.10, 2.95) trimesters. There were no significant associations with HC at birth or two years of age. CONCLUSIONS: We found a significant association between occupational exposure to carbonaceous NPs and SGA, with the effect depending on the period of exposure during pregnancy. These results should encourage further studies concerning the adverse effects of exposure to carbonaceous NPs on the development of offspring.

Management and outcomes of 27 pregnancies in women with myeloproliferative neoplasms.

Introduction: Philadelphia-negative myeloproliferative neoplasms (MPNs) greatly increase the risk of maternal and fetal complications during pregnancy. Currently, international agreements regarding the management of these women are lacking.Patients and methods: Our study aimed to assess the current management and outcomes of MPN pregnancies in a French cohort. We retrospectively analyzed 27 pregnancies in women with MPNs that were associated with a specific mutation. Nineteen pregnancies in nine women with essential thrombocythemia and eight pregnancies in five women with polycythemia vera were identified.Results: Our study showed 70% live births, but only 30% uneventful pregnancies. Fetal complications were mainly early spontaneous abortions (22%), fetal growth restriction (15%), and premature delivery (15%). Maternal issues were divided between thrombosis (15%) and hemorrhages (11%). High rates of preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome (15%) were reported. Uterine artery Doppler was performed in 70% pregnancies. Abnormal Doppler results were found in 43% pregnancies. Pregnancies with high platelet counts and packed cell volume remaining static or increasing ended with fetal death and utero-placental dysfunction. According to expert consensus, most of the pregnancies (67%) could be stratified in the high risk group and had a bad obstetrical outcome, with 50% standard-risk pregnancies versus 22% high-risk pregnancies that were uneventful. Higher risk pregnancies were prescribed heparin and/or interferon α in 72%.Conclusions: The prognosis of these pregnancies remains very bad and may be improved by a more effective collaboration between specialists as well as a therapeutic intensification including heparin and interferon α.