Publications

Abstract

Aims: To evaluate the impact of onset time, duration, and severity of various types of hypertensive disorders of pregnancy (HDP) on the risk of incident DM.

Methods: We used data from the ongoing French nationwide prospective cohort study CONCEPTION. We included all primiparous women in CONCEPTION who delivered between 2010 and 2018 (n = 2,816,793 women). Follow-up spanned from childbirth to 31 December 2021. HDP and incident DM onset during follow-up were identified using algorithms combining ICD-10 coded diagnoses during hospitalization and/or medication dispensing. We used Cox models to assess the associations between incident DM and preexisting chronic hypertension, gestational hypertension (GH), and various phenotypes of pre-eclampsia.

Results: Pre-eclampsia and GH alone occurred in 2.6 % and 4.6 % of the population, respectively. During follow-up (mean = 4.5 years), 16,670 women had incident DM. The cumulative incidences of DM were 15.8 % and 1.8 % in women who had pre-eclampsia during pregnancy with and without concomitant gestational diabetes, respectively. The risk of DM was higher after HDP (all types) irrespective of gestational diabetes status during pregnancy. In women without gestational diabetes, compared with those who had no HDP, the risk of incident DM was higher in women who had GH (adjusted hazard ratio, aHR = 1.97 [1.81-2.16]), pre-eclampsia (aHR = 2.42 [2.21-2.65]), and preexisting chronic hypertension prior to pregnancy (aHR = 3.35 [3.03-3.70]). Pre-eclampsia duration was significantly associated with a higher risk of DM.

Conclusion: Women who experienced an HDP had twice the risk of developing DM. Early blood glucose assessment and blood pressure monitoring should be more widely recommended after HDP diagnosis.

Abstract

Objective : Cervical ripening for induction of labor is often associated with negative patient experience. The debate over the most effective cervical ripening method persist, with a significant gap in research specifically addressing patient satisfaction. Our study aims to compare patient experience with two induction methods, slow-release intravaginal dinoprostone device and orally administered misoprostol.

Method : We conducted a before-and-after comparative study at a university tertiary hospital, including all patients undergoing cervical ripening with a Bishop score of 3 or lower. Our study compared two separate two-month periods, where the methods for cervical ripening differed. The first period employed an intravaginal dinoprostone slow-release device, while the second period used oral misoprostol. The primary outcome was patient experience, assessed using the EXIT questionnaire, a standardized and validated self-reported measure. Secondary outcomes were efficacy and safety outcomes.

Results : A total of 165 patients were included, 81 induced with dinoprostone and 84 induced with misoprostol. The EXIT questionnaire completion rate was 67.9 % (n = 55) in the dinoprostone group and 76.1 % (n = 64) in the misoprostol group (p = 0.23). Patients induced with misoprostol reported higher levels of satisfaction compared to those induced with dinoprostone, which can be attributed to reduced discomfort associated with the induction process (mean satisfaction score 2.26 ± 0.98 versus 2.80 ± 0.85 on a 1 to 5 likert-scale, p-value < 0.01). Adverse effects were reported less frequently with misoprostol compared to dinoprostone (20.2 % vs 48.1 %, p-value < 0.01). Time between cervical ripening and delivery was shorter in the misoprostol group (27.0 ± 10.2 h vs 32.5 ± 10.0, p < 0.01). There were no difference in mode of delivery or other obstetrical and neonatal outcomes.

Conclusion : For women undergoing cervical ripening, oral misoprostol appears to be a less invasive method for labor induction, associated with higher levels of satisfaction and reduced discomfort compared to the intravaginal dinoprostone slow-release device.

Abstract

Background: Fontaine progeroid syndrome (FPS, OMIM 612289) is a recently identified genetic disorder stemming from pathogenic variants in the SLC25A24 gene, encoding a mitochondrial carrier protein. It encompasses Gorlin-Chaudry-Moss syndrome and Fontaine-Farriaux syndrome, primarily manifesting as craniosynostosis with brachycephaly, distinctive dysmorphic facial features, hypertrichosis, severe prenatal and postnatal growth restriction, limb shortening, and early aging with characteristic skin changes, phalangeal anomalies, and genital malformations.

Cases: All known occurrences of FPS have been postnatally observed until now. Here, we present the first two prenatal cases identified during the second trimester of pregnancy. While affirming the presence of most postnatal abnormalities in prenatal cases, we note the absence of a progeroid appearance in young fetuses. Notably, our reports introduce new phenotypic features like encephalocele and nephromegaly, which were previously unseen postnatally. Moreover, paternal SLC25A24 mosaicism was detected in one case.

Conclusions: We present the initial two fetal instances of FPS, complemented by thorough phenotypic and genetic assessments. Our findings expand the phenotypical spectrum of FPS, unveiling new fetal phenotypic characteristics. Furthermore, one case underscores a potential novel inheritance pattern in this disorder. Lastly, our observations emphasize the efficacy of exome/genome sequencing in both prenatal and postmortem diagnosis of rare polymalformative syndromes with a normal karyotype and array-based comparative genomic hybridization (CGH).

Abstract

Introduction: Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases.

Patients and methods: We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients.

Results: For three patients, intravenous immunoglobulins were initiated at the βHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG.

Conclusion: This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.

Abstract

Purpose: The primary objective was to evaluate the impact of necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) on mortality and neurodevelopmental outcomes at 2 years’ corrected age (CA) in infants born before 32 weeks’ gestation (WG).

Methods: We studied neurodevelopment at 2 years’ CA of infants with NEC or SIP who were born before 32 WG from the EPIPAGE-2 cohort study. The primary outcome was death or the presence of moderate-to-severe motor or sensory disability defined by moderate-to-severe cerebral palsy or hearing or visual disability. The secondary outcome was developmental delay defined by a score < 2 SDs below the mean for any of the five domains of the Ages and Stages Questionnaire.

Results: At 2 years’ CA, 46% of infants with SIP, 34% of infants with NEC, and 14% of control infants died or had a moderate-to-severe sensorimotor disability (p < 0.01). This difference was mainly due to an increase in in-hospital mortality in the infants with SIP or NEC. Developmental delay at 2 years’ CA was more frequent for infants with SIP than controls (70.8% vs 44.0%, p = 0.02) but was similar for infants with NEC and controls (49.3% vs 44.0%, p = 0.5). On multivariate analysis, the likelihood of developmental delay was associated with SIP (adjusted odds ratio = 3.0, 95% CI 1.0-9.1) but not NEC as compared with controls.

Conclusion: NEC and SIP significantly increased the risk of death or sensorimotor disability at 2 years’ CA. SIP was also associated with risk of developmental delay at 2 years’ CA.

Abstract

Objectives: Prolonging the passive second stage of labor could increase vaginal birth rate, but the data concerning maternal and fetal morbidity are contradictory. The French guidelines did not specify a maximum duration of the passive second stage. Our objective was to assess if allowing a 4th hour after full dilatation before pushing increased maternal morbidity, compared to 3 h after full dilatation.

Study design: This single-center, retrospective, observational cohort study took place from January 1-December 31, 2020, in a tertiary maternity unit. All consecutive term nulliparous women who delivered under epidural anesthesia and without pathological fetal heart rate and reaching a second-stage passive phase of labor lasting at least 3 h were included. We compared 2 groups according to the duration of the passive second stage: « 3-hour group » and « 4-hour group ». In the « 3-hour group, » featuring a second-stage passive phase of up to 3 h, pushing is initiated for favorable conditions, while a cesarean section is performed if conditions are deemed unfavorable. In the « 4-hour group », obstetric conditions not justifying immediate pushing after three hours, and the obstetric team believed that an additional hour of expectant management could lead to a successful vaginal delivery. The principal endpoint was a composite criterion of maternal morbidity including obstetric anal sphincter injuries, postpartum hemorrhage, transfusion and intrauterine infection.

Results: We included 111 patients in the « 4-hour group » and 349 in the « 3-hour group ». Composite maternal morbidity did not increase in the « 4-hour group » compared to the « 3-hour group » (21 (18.9 %) versus 61 (17.5 %); p = 0.73). Neonatal morbidity was similar between the two groups. In the « 4-hour group, 91 (82 %) patients had vaginal deliveries », 62 (55,9 %) by spontaneous vaginal delivery and 29 (26,1 %) with instrumental assistance.

Conclusion: For selected patients, waiting for 4 h at full dilation can be beneficial due to the high rate of vaginal delivery and low incidence of maternal and fetal complications.

Abstract

Objective: To assess the long-term neurodevelopmental impact of doxapram for treating apnoea of prematurity.

Design: Secondary analysis of the French national cohort study EPIPAGE-2. Recruitment took place in 2011. A standardised neurodevelopmental assessment was performed at age 5-6 years. A 2:1 propensity score matching was used to control for the non-randomised assignment of doxapram treatment.

Setting: Population-based cohort study.

Patients: All children born before 32 weeks’ gestation alive at age 5-6 years.

Interventions: Blind and standardised assessment by trained neuropsychologists and paediatricians at age 5-6 years.

Main outcome measures: Neurodevelopmental outcomes at age 5-6 years assessed by trained paediatricians and neuropsychologists: cerebral palsy, developmental coordination disorders, IQ and behavioural difficulties. A composite criterion for overall neurodevelopmental disabilities was built.

Results: The population consisted of 2950 children; 275 (8.6%) received doxapram. Median (IQR) gestational age was 29.4 (27.6-30.9) weeks. At age 5-6 years, complete neurodevelopmental assessment was available for 60.3% (1780 of 2950) of children and partial assessment for 10.6% (314 of 2950). In the initial sample, children receiving doxapram had evidence of greater clinical severity than those not treated. Doxapram treatment was associated with overall neurodevelopmental disabilities of any severity (OR 1.43, 95% CI 1.07 to 1.92, p=0.02). Eight hundred and twenty-one children were included in the 2:1 matched sample. In this sample, perinatal characteristics of both groups were similar and doxapram treatment was not associated with overall neurodevelopmental disabilities (OR 1.09, 95% CI 0.76 to 1.57, p=0.63).

Conclusions: In children born before 32 weeks’ gestation, doxapram treatment for apnoea of prematurity was not associated with neurodevelopmental disabilities.

Abstract

Background: The aim of this study was to assess temporal trends in incidence and underlying causes of maternal deaths from obstetric hemorrhage in France and to describe clinical care before and after implementation of the first national guidelines published in 2004 and updated in 2014.

Methods: Data from all hemorrhage-related maternal deaths between 2001 and 2015 were extracted from the French Confidential Enquiry into Maternal Deaths. We compared the maternal mortality ratio (MMR), cause of obstetric hemorrhage, and death preventability by triennium. Critical care, transfusion, and obstetric management among women who died were described for 2001 to 2003 and 2013 to 2015.

Results: The MMR from obstetric hemorrhage significantly decreased over time from 2.3 of 100,000 livebirths (54 of 2,391,551) in 2001 to 2003 to 0.8 of 100,000 livebirths (19 of 2,412,720) in 2013 to 2015. In 2001 to 2003, uterine atony accounted for 50% (27 of 54) of maternal deaths vs 21% (4 of 19) in 2013 to 2015. As compared to 2001 to 2003, an increased proportion of women had hemodynamic continuous monitoring in 2013 to 2015 (30%, 9 of 30, vs 47%, 8 of 18) and received vasopressor infusion therapy (57%, 17 of 30, vs 72%, 13 of 18), and a smaller proportion was extubated during active hemorrhage (17%, 5 of 30, vs 0 of 18). Transfusion therapy was initiated more frequently and earlier in 2013 to 2015 (71 vs 58 minutes). In 2013 to 2015, 88% of maternal deaths due to hemorrhage remained preventable. The main identified improvable care factors were related to delays in diagnosis and surgical management, particularly after cesarean delivery.

Conclusions: Maternal mortality by obstetric hemorrhage decreased dramatically in France between 2001 and 2015, particularly mortality due to uterine atony. Among women who died, we detected fewer instances of substandard transfusion management or critical care. Nevertheless, opportunities for improvement were observed in most of the recent cases.

Abstract

Objectives: To assess the role of CT venography (CTV) in the diagnosis of venous thromboembolism (VTE) during the postpartum period.

Materials and methods: This multicenter prospective cohort study was conducted between April 2016 and April 2020 in 14 university hospitals. All women referred for CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE) within the first 6 weeks postpartum were eligible. All CTPAs were performed on multidetector CT machines with the usual parameters and followed by CTV of the abdomen, pelvis, and proximal lower limbs. On-site reports were compared to expert consensus reading, and the added value of CTV was assessed for both.

Results: The final study population consisted of 123 women. On-site CTPA reports mentioned PE in seven women (7/123, 5.7%), all confirmed following expert consensus reading, three involving proximal pulmonary arteries and four limited to distal arteries. Positive CTV was reported on-site in nine women, five of whom had negative and two indeterminate CTPAs, bringing the VTE detection rate to 11.4% (14/123) (95%CI: 6.4-18.4, p = 0.03). Expert consensus reading confirmed all positive on-site CTV results, but detected a periuterine vein thrombosis in an additional woman who had a negative CTPA, increasing the VTE detection rate to 12.2% (15/123) (95%CI: 7.0-19.3, p = 0.008). Follow-up at 3 months revealed no adverse events in this woman, who was left untreated. Median Dose-Length-Product was 117 mGy.cm for CTPA and 675 mGy.cm for CTPA + CTV.

Conclusion: Performing CTV in women suspected of postpartum PE doubles the detection of venous thromboembolism, at the cost of increased radiation exposure.

Abstract

Background: Among hypertensive disorders of pregnancy (HDP), eclampsia is a rare but serious event, often considered avoidable. Detailed assessment of the adequacy of care for the women who have eclampsia can help identify opportunities for improvement and for prevention of the associated adverse maternal and neonatal outcomes.

Objective: 1/ To estimate the incidence and describe the characteristics of women with eclampsia and to compare them with those of women with non-eclamptic hypertensive disorders of pregnancy (HDP)-related severe maternal morbidity (SMM) and of control women without SMM 2/ To analyse the quality of management in women who had eclampsia, at various stages of their care pathway.

Methods: It was a planned ancillary analysis of the EPIMOMS population-based study, conducted in six French regions in 2012-2013. Among the 182,309 maternities of the source population, all women with eclampsia (n = 51), with non-eclamptic HDP-related SMM (n = 351) and a 2% representative sample of women without SMM (n = 3,651) were included. Main outcome was the quality of care for eclampsia assessed by an independent expert panel at three different stages of management: antenatal care, care for pre-eclampsia and care for eclampsia.

Results: The eclampsia incidence was 2.8 per 10,000 (95%CI 2.0-4.0). Antenatal care was considered completely inadequate or substandard in 39% of women, as was pre-eclampsia care in 76%. Care for eclampsia was judged completely inadequate or substandard in 50% (21/42), mainly due to inadequate use of magnesium sulphate.

Conclusion: The high proportion of inadequate quality of care underlines the need for an evidence-based standardisation of care for HDP.