Publications

Abstract

Background: Necrotizing enterocolitis (NEC) is still one of the leading causes of neonatal death. The present study reports the data from a French case-control prospective multicenter study.

Methods: A total of 146 preterm neonates (PNs) with or without NEC were included. Bacterial 16S rRNA gene sequencing was performed on stool samples (n = 103). Specific culture media were used to isolate Escherichia coli, Clostridium butyricum, and Clostridium neonatale, and strains were phenotypically characterized.

Results: The gut microbiota of PNs was dominated by Firmicutes and Proteobacteria, and five enterotypes were identified. The microbiota composition was similar between NEC cases and PN controls. However, differences were observed in the relative abundance of Lactobacillus genus, which was significantly lower in the NEC group, whereas that of the Clostridium cluster III was significantly higher (p < 0.05). Within enterotypes, several phylotypes were significantly more abundant in NEC cases (p < 0.05). Regarding perinatal factors, a statistical association was found between the gut microbiota and cesarean delivery and antifungal therapy. In NEC cases and PN controls, the carriage rates and virulence genes of uropathogenic E. coli were equivalent based on culture. No correlation was found between E. coli, C. butyricum, and C. neonatale carriages, beta-lactam resistance, and antibiotic treatment.

Conclusions: At disease onset, our data support a microbiota dysbiosis between NEC and control infants at the genus level. In addition, it provides valuable information on bacterial antimicrobial susceptibility.

Abstract

To determine the early factors associated with continuous positive airway pressure (CPAP) failure in moderate-to-late preterm infants (32 + 0/7 to 36 + 6/7 weeks’ gestation) from the NEOBS cohort study. The NEOBS study was a multi-center, prospective, observational study in 46 neonatal intensive care units in France, which included preterm and late preterm infants with early neonatal respiratory distress. This analysis included a subset of the NEOBS population who had respiratory distress and required ventilatory support with CPAP within the first 24 h of life. CPAP failure was defined as the need for tracheal intubation within 72 h of CPAP initiation. Maternal and neonatal clinical parameters in the delivery room and clinical data at 3 h of life were analyzed. CPAP failure occurred in 45/375 infants (12%), and compared with infants with CPAP success, they were mostly singletons (82.2% vs. 62.1%; p < 0.01), had a lower Apgar score at 10 min of life (9.1 ± 1.3 vs. 9.6 ± 0.8; p = 0.02), and required a higher fraction of inspired oxygen (FiO₂; 34.4 ± 15.9% vs. 22.8 ± 4.1%; p < 0.0001) and a higher FiO₂*positive end-expiratory pressure (PEEP) (1.8 ± 0.9 vs. 1.1 ± 0.3; p < 0.0001) at 3 h. FiO₂ value of 0.23 (R² = 0.73) and FiO₂*PEEP of 1.50 (R² = 0.75) best predicted CPAP failure. The risk of respiratory distress and early CPAP failure decreased 0.7 times per 1-week increase in gestational age and increased 1.7 times with every one-point decrease in Apgar score at 10 min and 19 times with FiO₂*PEEP > 1.50 (vs. ≤ 1.50) at 3 h (R² of the overall model = 0.83). Conclusion: In moderate-to-late preterm infants, the combination of singleton pregnancy, lower Apgar score at 10 min, and FiO₂*PEEP > 1.50 at 3 h can predict early CPAP failure with increased accuracy. What is Known: •Respiratory distress syndrome (RSD) represents an unmet medical need in moderate-to-late preterm births and is commonly treated with continuous positive airway pressure (CPAP) to reduce mortality and the need for additional ventilatory support. • Optimal management of RSD is yet to be established, with several studies suggesting that identification of predictive factors for CPAP failure can aid in the prompt treatment of infants likely to experience this failure. What is New: •Secondary analysis of the observational NEOBS study indicated that oxygen requirements during CPAP therapy, especially the product of fraction of inspired oxygen (FiO2) and positive end-expiratory pressure (PEEP), are important factors associated with early CPAP failure in moderate-to-late term preterm infants. •The combination of a singleton pregnancy, low Apgar score at 10 minutes, and high FiO2*PEEP at 3 hours can predict early CPAP failure with increased accuracy, highlighting important areas for future research into the prevention of CPAP failure.

No abstract available.

Abstract

The increase in emerging drug resistant Gram-negative bacterial infections is a global concern. In addition, there is growing recognition that compromising the microbiota through the use of broad-spectrum antibiotics can impact long term patient outcomes. Therefore, there is the need to develop new bactericidal strategies to combat Gram-negative infections that would address these specific issues. In this study, we report and characterize one such approach, an antibody-drug conjugate (ADC) that combines (i) targeting the surface of a specific pathogenic organism through a monoclonal antibody with (ii) the high killing activity of an antimicrobial peptide. We focused on a major pathogenic Gram-negative bacterium associated with antibacterial resistance: Pseudomonas aeruginosa. To target this organism, we designed an ADC by fusing an antimicrobial peptide to the C-terminal end of the VH and/or VL-chain of a monoclonal antibody, VSX, that targets the core of P. aeruginosa lipopolysaccharide. This ADC demonstrates appropriately minimal levels of toxicity against mammalian cells, rapidly kills P. aeruginosa strains, and protects mice from P. aeruginosa lung infection when administered therapeutically. Furthermore, we found that the ADC was synergistic with several classes of antibiotics. This approach described in this study might result in a broadly useful strategy for targeting specific pathogenic microorganisms without further augmenting antibiotic resistance.

Abstract

Background: The skin is the largest organ in the human body. It provides multiple barrier functions, tactile or defensive, and acts as a mediator allowing for the attachment of vital monitoring devices with medical adhesives. Adhesives consist of several layers with varying compositions and properties. We aimed to provide recommendations for their use in the care of hospitalized neonates on the basis of a systematic literature review.

Methods: We searched PubMed for English or French articles published before May 29, 2020, using the keywords « adhesive, » « tape, », « skin, » and « neonat*. » Recommendations were developed after review by a multidisciplinary group including 15 professionals and parent representatives.

Results: We identified 295 studies, and from 30 eligible studies we developed six recommendations according to four perspectives: assessment of the skin condition to improve the methods of application of the different adhesives and their removal; use of adhesives as a platform; and discouraging the regular use of semi-permeable dressings to compensate for the immaturity of the skin barrier.

Conclusion: Skin lesions are common for hospitalized neonates. Use of adhesives may increase the occurrence of such lesions. Adhesives should be subject to good clinical practice guidelines. Health professionals caring for newborns should know the tools for screening and preventing skin lesions.

Abstract

Objective: To develop and validate a clinical prediction model for outcomes at 5 years of age for children born extremely preterm and receiving active perinatal management.

Design: The EPIPAGE-2 national prospective cohort.

Setting: France, 2011.

Population: Live-born neonates between 24⁺⁰ and 26⁺⁶ weeks of gestation who received active perinatal management (i.e. birth in a tertiary-level hospital, with antenatal steroids and resuscitation at birth).

Methods: A prediction model using logistic modelling, including gestational age, small-for gestational-age (SGA) status and sex, was developed. Model performance was assessed through calibration and discrimination, with bootstrap internal validation.

Main outcome measures: Survival without moderate or severe neurodevelopmental disability (NDD) at 5 years.

Results: Among the 557 neonates included, 401 (72%) survived to 5 years, of which 59% survived without NDD (95% CI 54% to 63%). Predicted rates of survival without NDD ranged from 45% (95% CI 33% to 57%), to 56% (95% CI 49% to 64%) to 64% (95% CI 57% to 70%) for neonates born at 24, 25 and 26 weeks of gestation, respectively. Predicted rates of survival without NDD were 47% (95% CI 18% to 76%) and 62% (95% CI 49% to 76%) for SGA and non-SGA children, respectively. The model showed good calibration (calibration slope 0.85, 95% CI 0.54 to 1.16; calibration-in-the-large -0.0123, 95% CI -0.25 to 0.23) and modest discrimination (C-index 0.59, 95% CI 0.53 to 0.65).

Conclusions: A simple prediction model using three factors easily known antenatally may help doctors and families in their decision-making for extremely preterm neonates receiving active perinatal management.

No abstract available

Abstract

Objective

To determine the prevalence, short-term prognosis and pharmacologic management of pulmonary hypertension (PH) among very preterm infants born before 32 weeks gestation (WG).

Study design

In the EPIPAGE-2 French national prospective population-based cohort of preterm infants born in 2011, those presenting with PH were identified and prevalence was estimated using multiple imputation. The primary outcome was survival without severe morbidity at discharge and was compared between infants with or without PH after adjusting for confounders, using generalized estimating equations models. Subgroup analysis was performed according to gestational age (GA) groups.

Results

Among 3383 eligible infants, 3222 were analyzed. The prevalence of PH was 6.0 % (95 % CI, 5.2–6.9), 14.5 % in infants born at 22–27⁺⁶ WG vs 2.7 % in infants born at 28–31⁺⁶ WG (P < .001). The primary outcome (survival without severe morbidity at discharge) occurred in 30.2 % of infants with PH vs 80.2 % of infants without PH (P < .001). Adjusted incidence rate ratios for survival without severe morbidity among infants with PH were 0.42 (0.32–0.57) and 0.52 (0.39–0.69) in infants born at 22–27⁺⁶ weeks gestation and those born at 28–31⁺⁶ weeks, respectively. Among infants with PH, 92.2 % (95 % CI, 87.7–95.2) received sedation and/or analgesia, 63.5 % (95 % CI, 56.6–69.9) received inhaled NO and 57.6 % (95 % CI, 50.9–64.0) received hemodynamic treatments.

Conclusion

In this population-based cohort of very preterm infants, the prevalence of PH was 6 %. PH was associated with a significant decrease of survival without severe morbidity in this population.

Abstract

The vaginal microbiota refers to the microorganisms that reside in the vagina. These microorganisms contribute significantly to a woman’s reproductive and general health. A healthy vaginal microbiota is typically a low-diversity environment with a predominance of lactic acid-producing Lactobacillus species. Factors such as antibiotic use, sexual activity, and hormonal changes can disrupt the balance of the vaginal microbiota, leading to conditions such as bacterial vaginosis. The composition of the vaginal microbiota changes and takes on added importance during pregnancy, serving as a barrier against infection for both mother and fetus. Despite the importance of the microorganisms that colonize the vagina, details of how changes in composition and diversity can impact pregnancy outcomes is poorly understood. This is especially true for woman with a high prevalence of Gardnerella vaginalis. Here we report on a diverse cohort of 749 women, enrolled in the InSPIRe cohort, during their final trimester of pregnancy. We show that Lactobacilli, including L. crispatus are important in maintaining low diversity, and that depletion in this critical community is linked with preterm delivery. We further demonstrate that it is overall diversity of the vaginal microbiota, not specific species, which provides the best indicator of risk.

No abstract available