Publications

Abstract

Introduction: Preeclampsia, a hypertensive disorder of pregnancy triggered by placental dysfunction, is reproduced in the murine STOX1A model, with hypertension, proteinuria, and abnormalities in umbilical and uterine Dopplers. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an innovative technique that provides insights into tissue perfusion. The present study aims at analyzing placental perfusion using DCE-MRI to further characterize placental defects in the STOX1A model.

Methods: Two study groups were formed: the « TgSTOX13 pregnancy group » from mating TgSTOX13 genotype males with wild-type females, and the « wild-type pregnancy group » from mating wild-type males with wild-type females. Blood pressure, urinary albumin to creatinine ratio, and fetal weights were measured and compared between the groups, while perfusion parameters were analyzed using both conventional compartmental (1C) and free-time point-Hermite (FTPH) models in the DCE analysis.

Results: Seventeen pregnant mice in the « TgSTOX13 pregnancy group » and thirteen in the « wild-type pregnant group » were included in the analysis. During late gestation, the TgSTOX13 pregnancy group exhibited higher blood pressure, elevated albumin/creatinine ratio, and decreased fetal weights compared to the wild-type pregnancy group. In the DCE analysis utilizing the 1C model, blood flow (Fb) was significantly reduced by approximately 31.8 % in the TgSTOX13 pregnancy group compared to the wild-type pregnancy group (p < 0.01), a finding corroborated by the FTPH model with a reduction estimated at 31.5 % (p < 0.01).

Discussion: Our investigation successfully utilized DCE MRI to assess placental perfusion in a mouse model of preeclampsia, revealing a significant reduction of approximately 30 % in the preeclamptic mice, mirroring human pathophysiology.

Abstract

The fitness cost associated with antimicrobial resistance has an important influence on evolutionary dynamics. We compared the genomes of three Klebsiella aerogenes isolates recovered from blood samples or deep abscess cultures from the same patient: the wild-type strain (CT_WT), a piperacillin-tazobactam-resistant strain (CT_PENI), and an extended-spectrum-cephalosporin (ESC)-resistant strain (CT_R). Whole-genome sequencing revealed that CT_PENI had acquired a TEM-1 β-lactamase with a mutated promoter, accounting for overproduction. CT_PENI then acquired an E240G substitution in the TEM-1 β-lactamase (resulting in TEM-207) and lost the porin-encoding ompK36 gene to give CT_R. All three strains showed the same virulence in a mouse model of intraperitoneal infection. The results of recombination and transformation assays indicated that when present separately, the TEM-207 overproduction and the ompK36 gene deletion had only small effects on susceptibility to ESCs. However, the combination of the two changes led to a much lower susceptibility to ESCs. Moreover, the levels of fitness in vitro and in vivo in a murine model of gut colonization were significantly lower after TEM-1 β-lactamase overproduction and lower still after E240G substitution and OmpK36 loss. We hypothesize that the chosen courses of antibiotics led to the stepwise emergence of a clone with resistance to penicillins and ESCs and no loss of virulence. However, acquired resistance may have a fitness cost that limits evolutionary success. Our results might explain why the overproduction of extended-spectrum β-lactamases (which should confer a high level of piperacillin-tazobactam resistance) is not observed in clinical practice and why TEM-207 has rarely been detected in clinical isolates.

Abstract

Background: Maternal exposure to unfavourable social conditions is associated with a higher rate of perinatal complications, such as placental vascular pathologies. A higher risk of preterm birth (PTB) has also been reported, and variations across studies and settings suggest that different patterns may be involved in this association.

Objective: To assess the association between maternal social deprivation and PTB (overall and by phenotype).

Methods: We analysed 9365 patients included in the PreCARE cohort study. Four dimensions (social isolation, insecure housing, no income from work and absence of standard health insurance) defined maternal social deprivation (exposure). They were considered separately and combined into a social deprivation index (SDI). The associations between social deprivation and PTB <37 weeks (primary outcome) were analysed with univariable and multivariable log-binomial models (adjusted for maternal age, parity, education level and birthplace). Then we used multinomial analysis to examine the association with preterm birth phenotypes (secondary outcome): spontaneous labour, preterm prelabour rupture of membranes (PPROM) and placental vascular pathologies.

Results: In all, 66.3%, 17.8%, 8.9% and 7.0% of patients had an SDI of 0, 1, 2 and 3, respectively. Social isolation affected 4.5% of the patients, insecure housing 15.5%, no income from work 15.6% and no standard health insurance 22.4%. Preterm birth complicated 7.0% of pregnancies (39.8% spontaneous labour, 28.3% PPROM, 21.8% placental vascular pathologies and 10.1% other phenotypes). Neither the univariable nor multivariable analyses found any association between social deprivation and the risk of preterm birth overall (SDI 1 versus 0: aRR 1.02, 95% confidence interval [CI] 0.83, 1.26; 2 versus 0: aRR 1.05, 95% CI 0.80, 1.38; 3 versus 0: aRR 0.92, 95% CI 0.66, 1.29) or its different phenotypes.

Conclusions: In the French PreCARE cohort, we observed no association between markers of social deprivation and the risk of preterm birth, regardless of phenotype.

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).