In many neonatal intensive care units, newborns are exposed to many sounds, including alarms and human activity. Noise consistently exceeds recommendations, having a potential negative impact on newborns’ development. This study aimed to evaluate the impact of multimodal interventions on noise reduction in a level 3 neonatal intensive care unit. This was a quality-improvement monocentric study, conducted from February 2022 to May 2023. Interventions included a multiprofessional reflection on ways to reduce noise, a staff training, and a modification of the alarms’ thresholds. Noise was evaluated before and after intervention using the number of noise peaks ≥ 45 dB/day, and the number of alarms/patient/day. Peaks ≥ 45 dB/day significantly decreased by 48

Malgré les indications grandissantes de la ventilation non-invasive en néonatalogie, le recours à l’intubation trachéale reste une des pierres angulaires de la réanimation néonatale. Ce geste est rendu techniquement difficile par la taille des patients, les spécificités anatomiques de leurs voies aériennes, leurs faibles réserves respiratoires, la diversité des équipements existants et le risque élevé d’évènements indésirables liés à la procédure. Au-delà de l’apprentissage technique, la bonne connaissance et l’anticipation des difficultés les plus fréquentes sont à connaître pour tout clinicien devant intuber un nouveau-né. Cet article évoque les principales notions à connaître et les pratiques actuellement recommandées pour faciliter la réalisation de cette procédure pour des opérateurs expérimentés ou non.

OBJECTIVE:To explore the impact of intensity of perinatal ('survival-focused') care on outcomes at 5½ years for two groups of survivors: those born at 24-26 and at 27-28 weeks of gestation. DESIGN:Prospective, population-based national cohort. SETTING:France, 2011. PATIENTS:Children surviving to 5½ years who were born at <29 weeks gestation. INTERVENTIONS:Intensity of perinatal care, defined at the hospital level, categorised into three based on the ratio of babies of 24-25 weeks of gestation admitted into neonatal intensive care to the number of fetuses alive at maternal admission to hospital subsequently delivered at 24-25 weeks gestation. MAIN OUTCOME MEASURES:Neurodevelopmental disability (NDD-none, mild, moderate or severe) comprising cognitive, behavioural, sensory and motor abilities. RESULTS:Among 3217 births, 472 children born at 24-26 weeks and 633 born at 27-28 weeks survived. At 24-26 weeks, compared with children born in low-intensity hospitals, children born in high-intensity hospitals had the lowest levels of mild (33.9%) and moderate-severe (21.9%) NDD (ORs 0.42, 0.20-0.88 and 0.47, 0.20-1.12, respectively); no difference was found between hospitals of low and medium intensity. At 27-28 weeks of gestation, no differences were seen between hospitals of any intensity level (p=0.75). CONCLUSIONS:No evidence was found to support concerns that survival-focused perinatal care is associated with increased long-term NDDs in children born extremely preterm or at a higher gestational age.

Necrotizing enterocolitis (NEC) is probably the most painful intestinal disease affecting infants born preterm. NEC is known to cause highly severe and prolonged pain that has been associated with adverse short- and long-term effects. However, research on pain management in infants with NEC is scarce. This is likely due to its low incidence and very acute occurrence. As a result, the optimal pain management for these vulnerable infants remains unknown, and analgesic therapy practices are highly variable. Therefore, we aimed to establish expert-based consensus recommendations on pain management for NEC. Experts of the European Society for Paediatric Research (ESPR) Special Interest Groups on Neonatal pain and NEC were invited to participate in two consensus meetings. Prior to the first hybrid consensus meeting, an online survey provided input for potential recommendations. During the consensus meetings, experts shared clinical expertise and voted on recommendations. An expert consensus statement, comprising nine recommendations on optimal pain assessment and pain treatment in infants with NEC, was developed. Expert recommendations included regular pain assessments with a neonatal pain scale with additional assessments on indication and pre-emptive administration of analgesic therapy (e.g., paracetamol and an opioid) in infants with NEC stage ≥ II. Conclusion: This expert consensus statement provides clinical recommendations essential for any healthcare professional caring for premature infants with NEC. The recommended guidance this statement provides on pain management strategies is key to preventing and reducing pain in this vulnerable population.

Premature neonates often require mechanical ventilation during intensive care. However, there is a lack of clinical consensus on the provision, type, and dosage of analgosedatives. The purpose of this scoping review is to assess the risks and benefits of providing analgesic and sedative drugs to ventilated premature infants. We sourced primary empirical research reporting outcomes related to the use of pharmacological analgesics and sedatives in ventilated premature infants. We included articles published in any language in peer-reviewed journals before February 2024 from MEDLINE, Embase, Web of Science, Cochrane Library, and Google Scholar databases. We present the overall study characteristics, and the reported risks and benefits of analgosedatives within drug sub-groups. 80 studies were included in the scoping review. Morphine was the most studied drug (39 studies), followed by fentanyl (19 studies). Midazolam (8 studies) and dexmedetomidine (3 studies) were the most frequently studied sedatives. Analgesic efficacy was more consistently reported for fentanyl than morphine. The sedative effect of opioids was rarely assessed. Respiratory, cardiovascular, gastrointestinal, neurological and neurodevelopmental risks were unclear for all opioids. Alternative synthetic opioids and midazolam appear to be associated with significant risks in the absence of clear benefits. Dexmedetomidine shows encouraging but limited results and merits further investigation as an opioid-sparing adjunct. At present, fentanyl appears to have the best efficacy and safety profile for analgosedation in this patient population. This scoping review will support clinicians in their analgosedative management of ventilated premature infants and identifies research gaps and priorities.

The purpose of this study was to compare two initial surgical strategies for spontaneous intestinal perforation (SIP) in a bi-centric cohort of extremely preterm and/or extremely low birthweight infants. Observational, retrospective study including infants born before 28 weeks of gestation and/or with birthweight < 1000 g, born between 2010 and 2020, operated for SIP in two type 3 centers. Infants were attributed to groups according to the surgical technique of the first intervention: primary anastomosis or suturing (PAS) or enterostomy (ES). The primary endpoint was the duration of parenteral nutrition (PN) analyzed using multivariate Cox model. Secondary endpoints included total number of surgeries under general anesthesia, morbidity and mortality at discharge, and outcomes at 2 years. Among 65 included patients, those in the PAS group (n = 46) had a higher median [IQR] CRIB II score than those from the ES group (n = 19) (11.5 [10–13] vs 8 [4–10], p = 0.01) and were more frequently operated in Robert Debré (78

OBJECTIVE:To determine whether pulmonary hypertension (PH) is associated with higher risk of adverse neurodevelopmental outcome at age 5 in a population-based cohort of 22-31+6 preterm children. STUDY DESIGN:In the EPIPAGE-2 French prospective population-based cohort of preterm children born in 2011, the neurodevelopmental outcome of children with PH was collected at 5 years. The primary outcome was a composite measure with four levels of neurodevelopmental disabilities: severe, moderate, mild, no disability, based on cerebral palsy, visual, hearing or cognitive deficiencies, behavioral difficulties and developmental coordination disorders. Secondary outcomes were autism spectrum disorders and school attendance. Missing data were multiply imputed. Developmental measures were compared using generalized estimating equations models. RESULTS:Of the 3007 eligible children, 1825 were analyzed, of whom 79 (4.3 %) were PH+. At age 5, 36.9 % (95 % CI, 26.0-47.8) of PH + children had moderate to severe overall neurodevelopmental disabilities compared with 17.9 % (95 % CI, 16.1-19.8) of PH-children, P < 0.001. Significant differences at 5 years between the PH+ and PH- groups were observed for cerebral palsy (CP) (6 % versus 2.3 % for severe CP, P = 0.003), cognitive deficiency (31.7 % versus 15.0 %, P < 0.001) and developmental coordination disorders (27.1 % versus 11.7 %, P < 0.001). There were no significant differences in behavioral difficulties and autism spectrum disorders. Normal school was attended by 69.2 % of PH + children versus 88.3 % of PH- children. CONCLUSION:In this nationwide population-based cohort of extremely preterm and very preterm infants, moderate to severe overall neurodevelopmental disability at age 5 was significantly associated with neonatal PH.

Background:Data on preschool neurodevelopment of preterm infants according to the duration of their neonatal exposure to opioids with/without midazolam is limited. We aimed to assess neurodevelopment outcome in children aged five years, born very preterm (24-31 weeks), according to exposure to these drugs. Methods:Secondary analysis from the French prospective cohort study EPIPAGE-2 (Etude Epidémiologique sur les Petits Ages Gestationnels, 2011). Exposure to opioids with/without midazolam was classified as none, ≤7 or >7 days. Percentages were weighted to account for the study design. The primary outcome was moderate/severe neurodevelopmental disabilities (NDD). Analyses were conducted using logistic regression and adjusted for perinatal confounders. Findings:Among 3117 survivors, 1165 (35.9%) were exposed (762/1165 (68.0%) ≤7 days, 403/1165 (32.0%) >7 days). Of these 49.5% received opioids only, 41.4% opioids and midazolam, and 9.1% midazolam only. Moderate/severe NDD occurred in 17.8%, 18.9%, and 31.7% in the unexposed, exposed ≤7 days, and exposed >7 days groups, respectively. After adjustment for baseline confounders, only exposure >7 days was associated with increased rates of moderate/severe NDD (adjusted odds ratio 2.07; 95% CI 1.32-3.26). After additional adjustment for severe neonatal morbidities no significant association was found between any duration of exposure and NDD. Interpretation:Exposure to opioids with/without midazolam >7 days might be associated with a higher prevalence of moderate/severe NDD at five years in very preterm born children but severe neonatal morbidities are a major modulator of this association. Funding:French Institute of Public Health Research, National Institute of Health and Medical Research, National Institute of Cancer, National Solidarity Fund for Autonomy, PremUp, APICIL Foundations.

OBJECTIVE:To evaluate the implementation of the 2023 French Society of Neonatology (SFN) guidelines for premedication before laryngoscopy in neonates without life-threatening emergencies. STUDY DESIGN:A prospective, observational cohort study was conducted across 141 French and Belgian neonatal units. Laryngoscopy data from intubation or less invasive surfactant administration in neonates <45 weeks postmenstrual age were collected. The primary outcome was the proportion of premedication consistent with SFN guidelines. Factors associated with guideline compliance were analyzed using multivariable mixed-effects logistic regression adjusted for neonatal and procedural characteristics. RESULTS:Six hundred seventy-three laryngoscopies were included. The mean (SD) gestational age was 30.1 (4.8) weeks. Of 506 intubations, 110 (21.7%) were immediate life-threatening emergencies. Among 396 non-life-threatening intubations, 357 (90.1%) were preceded by premedication with 169 (42.7%) consistent with SFN guidelines (propofol alone [n = 149, 37.6%]; a fast-acting opioid + muscle blocker [n = 20, 5.1%]). Independent factors associated with SFN guidelines compliance were non-emergent intubation (adjusted odds ratio 3.1 [95% CI 1.4-7.0]) and absence of hemodynamic compromise (adjusted odds ratio 31.0 [95% CI 6.4-150.3). Propofol and ketamine were the most frequent premedications before intubation, followed by opioids and/or anesthetics. Of the 167 less invasive surfactant administration procedures, 151 (90.4%) were preceded by a specific premedication including propofol (n = 84, 50.3%), consistent with SFN guidelines. CONCLUSIONS:Ninety percent of non-life-threatening laryngoscopies were preceded by a premedication but fewer than half complied with SFN guidelines. Further studies on efficacy and tolerance of neonatal anesthetics and drugs associations are needed.

BackgroundMachine-learning methods are gaining in popularity to predict medical events but their added value to other methods is still to be determined. We compared performances of clinical prediction models for bronchopulmonary dysplasia (BPD) or death in very preterm infants using logistic regression and random forests methods.MethodsTwo population-based cohorts of very preterm infants were used: EPIPAGE-2 (France, 2011) for development and internal validation and EPICE (Europe, 2011) for external validation. Eligible infants were born before 30 weeks' gestation and admitted in neonatal units. BPD was defined as any respiratory support at 36 weeks postmenstrual age. Candidate predictors were available shortly after birth or at day 3. Logistic regression and random forest models performance was assessed in terms of discrimination (c-statistic) and calibration plots.ResultsPrevalence of BPD/death was 32.1% (668/1923) in EPIPAGE-2 and 41.0% (1368/3335) in EPICE. At both time points, logistic regression and random forest models showed similar performance during internal validation. At birth, external validation in EPICE showed good discrimination (logistic regression model: c-statistics 0.81, 95% CI 0.80-0.83; random forest: 0.80, 95% CI 0.79-0.81) but both models underestimated the probability of BPD/death. Model performances were heterogeneous throughout European regions.ConclusionsBoth modelling methods performed similarly to predict BPD/death shortly after birth in very preterm children.ImpactWhether machine-learning methods predict better short-term respiratory outcomes in very preterm infants than logistic regression models is debated.Random forest-based prediction models did not perform better than logistic regression to predict bronchopulmonary dysplasia or death shortly after birth in very preterm infants.Calibration performances varied among European countries.While offering the same performance, regression models are easier to understand, to disseminate and to apply to different populations.

This study aimed to describe the early assessment of lung function and respiratory morbidity in children born extremely preterm with or without bronchopulmonary dysplasia (BPD). METHODS:This was a prospective study including all the children born at gestational age ≤28 weeks who received treatment in the NICU of the Centre Intercommunal de Créteil in France, from January 2006 to March 2012. Lung function, using the impulse oscillometry system, respiratory morbidity and growth were assessed at age 4 years. Lung function and clinical course of children were compared in children with and without BPD. RESULTS:We included 136 extremely premature children; 26 (19 %) had BPD. Children with and without BPD did not significantly differ in resistance measurements at 5 Hz (R5) and 20 Hz (R20) and reactance (X5) measurements at age 4 years. A total of 104 (76 %) pre-term children had respiratory resistance R5 above the 95th percentile for the reference population (z-score >1.64), regardless of BPD status. The mean (SD) R5 z-score for all children was 2.1 (±0.7), whereas the mean (SD) R20 was in the normal range (z-score = 1.1 [±0.3]). After treatment with bronchodilators, all children showed no significant change in resistance. The prevalence of asthma symptoms at age 4 years was common and estimated at 30 % regardless of BPD status. CONCLUSION:Early assessment of lung function by the impulse oscillometry system revealed that most preschool children who were born extremely preterm had abnormal total airway resistance regardless of BPD status. The system is an essential tool for the early assessment of children born prematurely.

Background Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear.Methods We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed.Results The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%]).Conclusions In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.) Respiratory syncytial virus is a leading cause of bronchiolitis. In a prospective, multicenter, matched case-control study involving infants in France, nirsevimab decreased RSV-associated hospitalization by 83%.