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Whole-genome sequencing-based typing methods for Clostridium butyricum strains from clinical, animal, plant, and environmental sources

Abstract

Clostridium butyricum exhibits a dual role, acting not only as a probiotic but also as an opportunistic pathogen associated with neonatal necrotizing enterocolitis (NEC) and infant botulism. We aimed to establish high-resolution genotyping frameworks to improve molecular surveillance and outbreak investigations. We analyzed 297 C. butyricum genomes, including 200 isolates from preterm neonates across 13 French neonatal intensive care units over a 20-year period and 97 publicly available genomes. A core-genome multilocus sequence typing (cgMLST) scheme was developed using chewBBACA, defining 2,621 loci, and applied to genomes with ≥95% locus presence. Core-genome single-nucleotide polymorphism (cgSNP) analysis was performed for complementary resolution. Phylogenetic cgMLST classified isolates into nine major clades. Some clinical strains displayed clonal relationships, whereas others were geographically and temporally unrelated. All botulinum neurotoxin type E-producing strains were grouped within a single clade. NEC-associated isolates showed geographic and temporal clustering, but no clade was uniquely linked to NEC. cgSNP analysis identified 11 clusters with overall discriminatory power similar to cgMLST while providing finer resolution for NEC-related strains. We propose robust cgMLST and cgSNP schemes for C. butyricum, enabling high-resolution genotyping and supporting epidemiological surveillance and outbreak investigation of this emerging opportunistic pathogen in neonatal settings.

Importance: Clostridium butyricum has been identified in fecal samples from both asymptomatic neonates and cases of necrotizing enterocolitis (NEC). Using a large collection of strains from different origins and spatiotemporal contexts, we developed and established a cgMLST scheme for the molecular typing of C. butyricum. Our results show that most C. butyricum strains cluster independently of origin and spatiotemporal context factors. However, specific cgMLST clades of C. butyricum were found for plant and botulinum neurotoxin type E strains. Clonal strains were also identified. No specific cgMLST clade was found to be genetically associated with NEC. cgSNP showed higher discriminatory power compared to cgMLST. Importantly, cgSNP provided better discriminatory power for strain relatedness with respect to strains isolated from NEC patients.

Factors influencing unit-level differences in prevalence of prematurity associated bronchopulmonary dysplasia in a European cohort: an observational study

Abstract

Background: Bronchopulmonary dysplasia (BPD) is the most common morbidity of very preterm (VPT) infants born <32 weeks’ gestation with life-long consequences. Studies document wide variation between regions and units in BPD prevalence.

Research question: Which unit-level factors contribute to the variation in BPD prevalence among very preterm infants between European neonatal units?

Study design and methods: Analyses were conducted using the prospective population-based EPICE cohort in 19 regions in 11 European countries. We compared prevalence of moderate/severe BPD among VPT infants without severe congenital anomalies in neonatal units with ≥40 annual VPT admissions (83 units, 5,285 infants). Unit prevalence was adjusted for individual risk factors using standardised morbidity rates. Spearman correlation and multilevel logistic regression were used to assess associations of BPD with unit-level variables: unit mortality rates, first week oxygen saturation targets, proportion of infants ventilated within the first 24 hours, unit practice of postnatal corticosteroid use for hypotension or BPD prevention and unit volume.

Results: Unadjusted BPD prevalence ranged from 2%-47% (median:13%) between units and was 8%-42% (median:17%) after adjustment and standardisation. Oxygen saturation targets, proportion of initial mechanical ventilation and postnatal corticosteroid use partly explained the between-unit variability (proportional change of variance: 25%, 5%, 17% respectively), leaving 53% unexplained. Risk-adjusted in-hospital mortality (range 8%-21%) and patient volume were not correlated with BPD prevalence.

Interpretation: Large variability in BPD prevalence exists between European units, which was only partially explained by patient characteristics. Our findings suggest that improving respiratory management for VPT infants could be beneficial for reducing BPD prevalence. The association of unit postnatal corticosteroid use practice with BPD requires further investigation.

High Risk of Anxiety and Depression in Women With Different Types of Pregnancy Complications in France: A Cross-Sectional Study

Abstract

Background: Pregnancy complications are known to be risk factors for the onset of depression and anxiety symptoms. This study assessed associations between pregnancy complications, including concurrent complications, and symptoms of anxiety and depression among pregnant women living in France.

Methods: A cross-sectional study was carried out among 492 pregnant women. Sociodemographic and obstetric characteristics were collected using an online questionnaire. Depression and anxiety symptoms were evaluated using the Edinburgh Postnatal Depression Scale and the Spielberger State-Trait Anxiety Inventory, respectively. Multivariate logistic regressions were employed to identify associations between mental health outcomes and pregnancy complications.

Results: While 37% of women declared no pregnancy complications, 9.76% declared two or more complications, and 63% of participants had at least one complication. Among these latter, 68.9% had a high risk of depression, 83.9% elevated state anxiety, and 77.4% elevated trait anxiety. State anxiety scores were significantly higher in women who felt they did not receive adequate social support from their partner, family, and friends and who reported dissatisfaction with medical care. Adjusting for confounders, we identified that women with complications had higher odds of experiencing higher state anxiety scores (adjusted OR: 2.94; 95% CI: 1.40-6.10). Positive associations were also observed between gestational diabetes mellitus and increased likelihood of reporting depressive symptoms (adjusted OR: 1.99; CI:1. 20-3.29) and high state anxiety scores (OR: 3.31; CI: 1.22-9.01).

Conclusion: We found a high prevalence of depression and anxiety among pregnant women with complications. Gestational diabetes mellitus was positively associated with antenatal depression and high state anxiety levels. These findings suggest that women with complications have a higher risk of developing depressive and anxious symptoms. Screening for and treating physical and mental health problems in women experiencing pregnancy complications and poor mental health symptoms are crucial to safeguard the well-being of the mother and the fetus.

In Reply:

We thank Chen et al for their thoughtful comments regarding our recent study on pregnancy-related complications in osteogenesis imperfecta. We appreciate the opportunity to clarify several points and to discuss future research directions.We thank Chen et al1 for their thoughtful comments regarding our recent study on pregnancy-related complications in osteogenesis imperfecta.2 We appreciate the opportunity to clarify several points and to discuss future research directions.

Reassessing Cognitive Trends in Very Preterm Children-Reply

No abstract available

Extracorporeal membrane oxygenation (ECMO) in neonates with severe uropathies: A single-center experience

Abstract

Introduction: Extracorporeal membrane oxygenation (ECMO) is an advanced extracorporeal life support rarely used in neonates with severe uropathies. This study describes our experience with ECMO support in five neonates presenting with life-threatening respiratory failure associated with congenital uropathy.

Materials and methods: We conducted a retrospective review on five neonates treated with ECMO between 2015 and 2024. All had severe uropathies (four with posterior urethral valves, one with a solitary dysplastic cystic kidney) and required ECMO for refractory hypoxia. Veno-arterial jugular-carotid cannulation was used in all cases. Data collected included procedural details, renal and neurological outcomes, and follow-up.

Results: Median gestational age was 36 weeks. ECMO was initiated at a median of 1 day of life for a median duration of 6 days. No procedural mortality occurred. One circuit failure and one jugular thrombosis occurred. Three patients survived. Two had stable renal function; one developed chronic kidney disease stage 5 (CKD-5). Neurological outcomes were encouraging. At follow-up, two children had normal development, one had psychomotor delay.

Conclusion: ECMO is a reliable rescue strategy in selected neonates even with uropathies experiencing respiratory failure. Complication rates remained within reasonable limits for such critical interventions, and long-term outcomes varied, underscoring the need for individualized multidisciplinary care

sFlt-1/PlGF ratio use does not reduce hospitalisation duration in suspected preeclampsia: the PRECOG study, a multicentre randomised trial

Abstract

The aim of the PRECOG study was to evaluate if the use of the sFlt-1/PlGF ratio in patients hospitalized for suspected preeclampsia before 35 weeks could improve patient management and reduce the length of hospitalization. A prospective randomized multicenter interventional open-label study in a hospital population with 2 parallel groups with or without taking into account the sFlt-1/PlGF ratio for the management of patients admitted for suspected pre-eclampsia. 80 patients were included in the study. Characteristics of patients were equally distributed among randomization groups. There was no difference in the primary outcome between the two groups. Hospitalization for more than 24 h was 75% in the group reveal versus 80% in the group conceal (Relative Risk p = 0.59). Groups did not differ in hospitalization duration for different cut-off values such. When stratifying by ratio value, among those with a ratio < 38, 37% were discharged home < 24 h in the conceal group and 47% in the reveal group. There was no difference in the secondary outcomes between the two groups. In this randomized controlled trial in women hospitalized for suspected of preeclampsia, the use of the sFlt-1/PlGF ratio at was not associated with a benefit in terms of duration of hospitalization or in maternal and neonatal outcomes.

Adherence to the nirsevimab immunization campaign: analysis of sociodemographic and medico-economic influences-single-centre prospective cohort study in France

Abstract

Respiratory syncytial virus (RSV) is a common and highly contagious viral pathogen responsible for acute lower respiratory tract infection in infants. It represents an important public health and economic concern. This study, performed in a level 3 perinatal center, evaluated adherence to the first French national RSV immunization campaign with nirsevimab. This retrospective single-center study included 1361 newborns born at 34 weeks of gestation or after, from October 1, 2023, to January 10, 2024 in France. Data collected included sociodemographic and medico-economic characteristics of families (parents and newborns), and nirsevimab administration. Multivariable logistic regression was performed to determine factors associated with immunization acceptance. Overall, 87.7% of newborns received nirsevimab. The median postnatal age at administration was 2.8 days. Among parents initially refusing the administration, 17.7% of their infants (12/68) finally received the product, and among those initially reluctant to its administration, 57.4% (101/176) of their infants received it. On multivariable analysis, maternal birth in France, mother’s occupation, and adherence to recommended vaccination during pregnancy were positively associated with passive immunization acceptance; delivery in January was negatively associated.

Conlusion: The study observed a high adherence rate to the 2023-2024 RSV immunization campaign. The administration of nirsevimab free of charge and before maternity unit discharge may have contributed to these results. Socio-demographic and medico-economic factors appeared to influence immunization adherence, suggesting that the period before maternity hospital discharge could represent a key time to carry out preventive actions and reduce social and territorial health inequalities.

What is known: • Respiratory syncytial virus (RSV) is among the leading causes of acute lower respiratory-tract infection in young children with substantial economic impacts. • The first national passive immunization campaign against RSV was launched during the 2023-2024 RSV epidemics in France.

What is new: • Medical, social, and territorial factors associated with parental adherence to passive immunization for their newborns are unknown. • Despite high adherence rates, disparities in passive immunization with nirsevimab uptake underscore the need for targeted interventions to ensure equitable access to healthcare: differences in uptake, despite free access, highlight the need for targeted communication and support strategies to overcome non-financial barriers and ensure equitable preventive care.

Year 116 of the plastic age: a Pandora’s box as a time bomb for pregnancy? Review of clinical and fundamental data on prenatal exposure to plastics

Abstract

Plastics constitute an area of interest within the context of the placental exposome. A growing body of evidence now indicates that various micro- and nanoplastics – including notably polystyrene, polypropylene, polyethylene, and polyvinylchloride – are present in the human placenta, from the basal plate to the fetal membranes. Results from in vitro and ex vivo studies have shown that these environmental pollutants can enter the maternal bloodstream and reach the placenta, where they concentrate in the syncytiotrophoblast. These so-called « plasticenta » have been observed even in uncomplicated pregnancies, and to date, no longitudinal study has confirmed harmful long-term consequences for the newborn. However, plastics appear to alter placental functions and may therefore be associated with adverse outcomes such as miscarriage, intrauterine growth restriction and preterm birth. Findings from ex vivo human studies, in vivo murine models, and in vitro experiments with micro- and nanoplastics indicate that factors such as particle type, size, concentration, surface functionalization, route of exposure, and environmental conditions play key roles in cellular uptake and subsequent alterations in cell function and phenotype. Consequently, various impairments in placental metabolic and immune functions may contribute to abnormal development of the placenta and the fetus. Maternal exposure to these ubiquitous environmental pollutants may induce prenatal and neonatal disease states. In this review, we examine the current clinical, in vivo and in vitro data on the occurrence, distribution and impact of micro- and nanoplastics in the placenta.

[« My First Days Booklet »: a tool to support parental presence in neonatal medicine]

Abstract

Parental presence in neonatal medicine is essential for the development of premature newborns and the parent-child relationship. Through collaborative work with the neonatal medicine teams at Louis-Mourier Hospital, a tool to support parental presence called « Mon livret des premiers jours » has been designed and developed. This booklet is made available to parents with the aim of encouraging them to be present and enabling caregivers to more easily identify their needs and vulnerabilities. Parents can fill out the booklet daily, writing or using stickers to express what they are doing or feeling. The booklet is the subject of action research that will assess its contribution to parenting support. At the end of their hospital stay, parents can take the booklet home with them as a record of their experience that they can share with their child later on.