Publications

Abstract

The patent ductus arteriosus is a very common condition in preterm infants, and a hemodynamically significant patent ductus arteriosus increases morbidity and mortality in these vulnerable patients. However, despite numerous randomized controlled trials, there is no consensus regarding management. Medical therapy is typically offered as first-line treatment, although it yields limited success and carries the potential for severe adverse events. In recent years, there has been rapid development in transcatheter patent ductus arteriosus closure primary with the use of the Amplatzer Piccolo Occluder, and this has gained widespread acceptance as a safe and effective alternative to surgical ligation in extremely low-birth-weight infants weighing over 700 g. This article aims to provide an appraisal of the patient selection process, a step-by-step procedural guide, and a comprehensive review of the outcomes associated with this approach.

Abstract

Objective: To report neurodevelopment at age 5.5 years according to developmental delay screening with the Ages & Stages Questionnaire (ASQ) in late infancy in preterm-born children.

Design: Population-based cohort study, EPIPAGE-2.

Setting: France, 2011-2017.

Participants: 2504 children born at 24-26, 27-31 and 32-34 weeks, free of cerebral palsy, deafness or blindness at 2 years’ corrected age.

Main outcome measures: Moderate/severe, mild or no disability at age 5.5 years using gross and fine motor, sensory, cognitive and behavioural evaluations. Results of the ASQ completed between 22 and 26 months’ corrected age described as positive screening or not.

Results: Among 2504 participants, 38.3% had ASQ positive screening. The probability of having moderate/severe or mild disability was higher for children with ASQ positive versus negative screening: 14.2% vs 7.0%, adjusted OR 2.5 (95% CI 1.8 to 3.4), and 37.6% vs 29.7%, adjusted OR 1.5 (1.2 to 1.9). For children with ASQ positive screening, the probability of having neurodevelopmental disabilities at age 5.5 years was associated with the number of domain scores below threshold, very low gestational age and severe neonatal morbidities. For children with ASQ negative screening, this probability was increased for boys and children born small-for-gestational age. For both groups, maternal level of education was strongly associated with outcomes.

Conclusion: In preterm-born children, ASQ screening at 2 years’ corrected age was associated with neurodevelopmental disabilities at age 5.5 years. However, other factors should be considered when interpreting the ASQ data to draw further follow-up.

Abstract

Thrombocytopenia is common in preterm neonates and can be associated with hemorrhage. Most platelet transfusions are prophylactic. Previously, higher platelet-count thresholds were recommended for neonates, but this recommendation has been questioned in recent studies. In the PlaNeT2 trial, mortality and serious bleeding were more frequent in neonates with the highest platelet-count threshold than in others. Following this trial, we changed our platelet transfusion practice by lowering the platelet-count threshold for prophylactic transfusion from 50,000 to 25,000/mm³. We conducted a before-after retrospective cohort study to quantify the frequency of platelet transfusions and assess the new protocol by analyzing death and serious hemorrhage events. This retrospective monocentric study included neonates born before 37 weeks of gestation with platelet count < 150,000/mm³ during the 2 years preceding the new platelet transfusion protocol (high prophylactic transfusion threshold, 50,000/mm³) and during the 2 years after the new platelet transfusion protocol (low prophylactic transfusion threshold, 25,000/mm³). The primary outcome was the proportion of neonates receiving at least one platelet transfusion in both groups. We also compared the proportion of deaths and severe hemorrhage events. A total of 707 neonates with thrombocytopenia were identified. In the high-threshold group, 99/360 (27.5%) received at least one platelet transfusion as compared with 56/347 (16.1%) in the low-threshold group (p < 0.001). The groups did not differ in proportion of deaths or severe hemorrhage events.

Conclusions: A reduced platelet-count threshold for transfusion allowed for a significant reduction in the number of platelet transfusions without increasing severe hemorrhage events.

No abstract available

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.