Neonatal sepsis-induced cardiovascular dysfunction includes impaired myocardial function (which may be systolic and/or diastolic) and vasoregulatory failure (which may lead to vasodilation or vasoconstriction). The haemodynamic response in neonatal sepsis may therefore be hyperdynamic or hypodynamic, and the underlying pathophysiological mechanisms are heterogenous. The assessment of the neonate with sepsis and cardiovascular dysfunction is critical for targeted pathophysiology-based management. However, this assessment is challenging; it may include clinical features, echocardiography, electrocardiography and heart rate variability monitoring, non-invasive cardiac output monitoring (NICOM), near-infrared spectroscopy (NIRS) and biomarkers. Neonatologist performed echocardiography (NPE), in particular, can aid in the evaluation of the pathophysiological mechanism of cardiovascular dysfunction specific to each patient and further guide individualised management. IMPACT: WHAT DOES THIS ARTICLE ADD TO THE EXISTING LITERATURE?: This review provides an integrative overview of current methods for assessing cardiovascular dysfunction in neonatal sepsis, combining clinical evaluation with echocardiographic, electrocardiographic, non-invasive hemodynamic (NICOM, NIRS), and biomarker-based approaches to support early recognition and management.

La recherche conjointe sur des questions importantes possède une longue tradition dans la néonatologie suisse. Déjà dans les années 1990 s’est créé, sous la direction de Hans Ulrich Bucher, président de la Société suisse de néonatologie pendant plusieurs années, un réseau national des centres de soins intensifs pour nouveau-nés avec pour objectif d’améliorer, par la récolte régulière de données et leur analyse, la qualité de la prise en charge des enfants prématurés en Suisse.

Die gemeinsame Erforschung klinisch relevanter Fragestellungen blickt in der schweizerischen Neonatologie auf eine langjährige Tradition zurück. Bereits Mitte der 90er Jahre bildete sich unter der Leitung von Hans Ulrich Bucher, dem langjährigen Präsidenten der Schweizerischen Gesellschaft für Neonatologie, ein landesweites Netzwerk aus Neugeborenen-Intensivstationen mit dem Ziel, über regelmässige Datenerhebungen und deren Beforschung die Versorgungsqualität von Frühgeborenen in der Schweiz zu verbessern.

BACKGROUND:Sepsis is defined as a dysregulated host response to infection leading to organ dysfunction. It represents a major global health concern, particularly in childhood. The underlying pathophysiological and genetic mechanisms remain insufficiently understood. METHODS:Using samples and clinical data from 650 children enrolled in the Swiss Pediatric Sepsis Study, a national multicentre cohort for culture-proven bacterial sepsis, we conducted within-cohort analyses and a separate case-control analysis in 510 cases and 994 controls, testing genome-wide polymorphisms for association with sepsis susceptibility and, in cases only, with disease characteristics. FINDINGS:In the within-cohort analysis, no significant genome-wide associations were found when assessing host, microbiological, and outcome features. In the case-control analysis, we identified one locus significantly associated with sepsis susceptibility, encompassing the CTNNAL1 and ELP1 genes. INTERPRETATION:Our results suggest contribution of genetic modulators to susceptibility for sepsis in children. FUNDING:The Swiss Pediatric Sepsis Study received funding from the Swiss National Science Foundation (342730_153158/1 and 320030_201060/1), the Swiss Society of Intensive Care, the Bangerter Foundation, the Vinetum and Borer Foundation, the Foundation for the Health of Children and Adolescents, and the Sanofi-Aventis Suisse. LJS was supported by the NOMIS and the Thomas and Doris Ammann Foundation.

OBJECTIVE:To evaluate enteral feeding practices in preterm infants in neonatal intensive care units (NICUs) in high-income countries across three continents, and compare results with a similar survey 13 years earlier. METHODS:Web-based survey distributed to neonatologists at 258 NICUs across 15 countries in Europe, Australia, New Zealand and Canada, October 2023 and February 2024. Survey domains focused on availability of human milk, onset of enteral feeding, breast milk fortification (BMF), cytomegalovirus (CMV) screening and enteral supplements including probiotics. Results were compared with a similar survey performed in 2010. RESULTS:Replies were received from 185 (72%) NICUs. Access to donor human milk (DHM) was high (91%). Across all NICUs, feeds were started on day 1 in 64%, 73% and 85% among infants born <25, 25-27 and 28-31 weeks' gestation, respectively. Bovine milk-based BMF was routinely used in 88% of NICUs, with large variation in when it was commenced and discontinued. Routine use of human milk-based BMF was uncommon (4%). Maternal CMV status was routinely determined in 33% of all NICUs who then pasteurised or froze milk if the mother was CMV-seropositive. Probiotics were provided in 66% of the NICUs, with large variations in products and birth weight/gestational age criteria. CONCLUSIONS:Compared with our survey from 2010, more NICUs now start feeding preterm infants on day 1, and DHM availability has increased in some countries. Substantial variation remains in the use of BMF, probiotics and CMV screening. A stronger evidence base is needed to update guidelines, aiming ultimately to improve growth and long-term neurodevelopment.

BACKGROUND:Although COVID-19 is usually mild in children, antibiotics are frequently prescribed during hospitalisation, often without evidence of bacterial infection. OBJECTIVE:To assess the frequency and predictors of antibiotic use in children hospitalised with SARS-CoV-2 infection in Switzerland. METHODS:In this nationwide prospective study, children aged 0-18 years hospitalised with confirmed SARS-CoV-2 infection or symptoms compatible with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) between January 2022 and March 2023 were included. Univariable and multivariable logistic regression analyses were used to identify risk and protective factors for antibiotic use. A sensitivity analysis was conducted excluding high-risk patients. RESULTS:Among 1944 hospitalised children, 586 (30%) received antibiotics. Of these, 71 (12%) had a clinically suspected bacterial infection without microbiological confirmation and 41 (7%) had microbiologically confirmed infection. Predictors of antibiotic use were microbiologically confirmed bacterial infection (aOR 138.08), clinically suspected bacterial infection (aOR 114.48), haematologic/oncologic disease (aOR 6.77), PIMS-TS (aOR 5.36), fever (aOR 2.98), neonatal age (aOR 2.80) and treatment in tertiary centres (aOR 1.65). After excluding high-risk patients, however, treatment in tertiary centres and PIMS-TS were no longer significant predictors in the sensitivity analysis. Respiratory distress/tachypnoea (aOR 0.72) and admission with confirmed SARS-CoV-2 as the primary diagnosis (aOR 0.42) were associated with lower antibiotic use in the primary analysis. After excluding high-risk patients, this association was no longer observed and nasal symptoms (aOR 0.68) and seizures (aOR 0.34) emerged as protective factors. CONCLUSION:Antibiotics were frequently prescribed to children hospitalised with SARS-CoV-2 despite limited evidence of bacterial infection. Our findings underscore the need to strengthen antimicrobial stewardship in paediatric COVID-19 care.

INTRODUCTION:Ophthalmia Neonatorum (ON) is a serious neonatal eye infection, primarily caused by Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (NG). Although the World Health Organization (WHO) recommends universal antibiotic prophylaxis at birth, many high-resource countries have suspended this procedure. European data on incidence of ON and prophylaxis use are limited. AIMS:To evaluate the routine implementation of prophylaxis across a selected sample of European birth centres, to assess adherence to WHO recommendations, and estimate the incidence of conjunctivitis caused by CT and NG among newborns, comparing centres with and without prophylaxis. METHODS:An electronic questionnaire was distributed to 94 birth centres in 21 European countries, focusing on those with significant birth volumes and university or referral hospital status. Data collection occurred over two days, 20-21 November 2024, with cases of CT/NG conjunctivitis reported for 2023. RESULTS:Among 94 responding centres, 54 (57.5%) routinely implemented prophylaxis, but 74% of them did not adhere to WHO guidelines. Of 1,636 newborns observed, 598 (36.6%) received prophylaxis at birth. Seventeen cases of CT/NG conjunctivitis were reported in 2023, with similar incidence rates in centres with and without prophylaxis (6.2 vs. 5.8 per 100,000 live births; p = 0.89). CONCLUSIONS:Variations in ocular prophylaxis across involved centres, coupled with low rates of NG and CT conjunctivitis and no significant differences between centres using or not using prophylaxis, suggest that this practice could inform antibiotic stewardship in newborns. A unified, evidence-based European protocol is essential to enhance safety and reduce early antibiotic use.

Therapeutic drug monitoring (TDM) of vancomycin, ideally based on the ratio of the daily area under the curve to the minimal inhibitory concentration at steady state (AUC24,SS/MIC), is hindered by sampling limitations in neonates, so trough concentration (Ctrough) is often used as a surrogate. This virtual TDM study aimed to evaluate the performance of Bayesian model-informed precision dosing (MIPD) for vancomycin in neonates. Reference pharmacokinetic (PK) parameters and drug concentrations were simulated in NONMEM for 1000 virtual neonates using a published population PK model. Four TDM strategies were compared based on the percentage of patients achieving an AUC24,SS/MIC between 360 and 540 h. Strategy 1 maintained the initial regimen unchanged; strategy 2 adjusted doses using a standard rule of three to target a Ctrough of 10–15 mg/L; strategies 3 and 4 used the MIPD software Tucuxi with a steady-state Ctrough and two concentrations after the first dose, respectively, for Bayesian dosage optimization. Individual dosages were adjusted following each strategy, recalculating AUC24,SS to determine the percentage of target attainment. Iterative adjustments were performed by resampling Ctrough. A sub-study evaluated optimal sampling time by comparing Tucuxi-estimated AUC24,SS with the reference value. Less than 49

The 2024 Phoenix sepsis criteria define sepsis and septic shock in children as life-threatening organ dysfunction, operationalized by a Phoenix Sepsis Score of 2 or more, in presence of suspected or confirmed infection. The Phoenix sepsis criteria have not been validated in children with proven bacterial infection. To determine the diagnostic performance of Phoenix sepsis criteria in predicting mortality, and mortality or prolonged intensive care unit (ICU) stay in a population-based cohort of children with blood culture-proven bacterial infection. We assessed the discriminative power of the scores for the primary outcome, 30-day in-hospital mortality, and the secondary outcome, 30-day in-hospital mortality or ICU length of stay of 3 days or longer, after blood culture sampling, using area under the curve of receiver operating characteristic curves (AUROC) and the area under the precision recall curve (AUPRC). Logistic mixed-effects models were adjusted for age, sex, and presence of chronic medical conditions. 877 bacteremia episodes in 807 children were analyzed. Mortality was 1

Sepsis is a life-threatening syndrome defined by organ dysfunctions caused by a dysregulated host response to an infection. Prompt recognition and management are key to improving outcomes. Artificial intelligence (AI) is well positioned to support clinicians in the early identification and management of sepsis. This article presents a critical appraisal of AI algorithms for the early recognition of sepsis.

OBJECTIVES:Group B Streptococcus (GBS) is a leading cause of invasive infection in newborns and infants. Yet the genomic basis of invasiveness and disease severity remains incompletely defined. We aimed to identify bacterial genomic features associated with invasive GBS disease and to explore associations between bacterial genomics and severe clinical outcomes. METHODS:We performed PacBio long-read whole-genome sequencing of 381 GBS isolates, including 127 invasive isolates obtained from blood cultures of infants with GBS disease and 254 serotype-matched colonizing isolates obtained from recto-vaginal swabs of pregnant women. Gene presence/absence and allele-level variation were analysed for virulence, adhesion, haemolysis, regulatory, and antimicrobial resistance genes. Associations with invasive disease, life-threatening organ dysfunction (LTOD), and meningitis were assessed using univariable logistic regression with false discovery rate correction. Correlation matrices were constructed to identify lineage-associated genomic profiles. RESULTS:Invasive disease was strongly associated with clonal complex 17 (CC17), which accounted for 83 of 127 (65%) invasive isolates compared with 72 of 254 (28%) colonizing isolates. After correction for multiple testing, the presence of hylB, hvgA, and ermB was significantly associated with invasive disease, whereas pilus island 1 was negatively associated. Invasive isolates also carried CC17-associated allelic variants in genes involved in antimicrobial resistance, transcriptional regulation, virulence, and haemolysis, forming a tightly correlated genomic constellation. Among infants with invasive disease, 28 of 127 (22%) developed LTOD. Prematurity (17/28 vs. 24/99), early-onset disease (14/28 vs. 23/99), and lower birthweight were associated with LTOD, whereas no bacterial gene or allelic variant remained associated with severity after correction for multiple testing. No meningitis-specific genomic signatures were identified. CONCLUSIONS:Neonatal GBS invasiveness is primarily associated with a CC17-linked genomic profile comprising both specific virulence genes and lineage-associated allelic variants. In contrast, progression to LTOD appears to be driven predominantly by clinical factors rather than bacterial genomic variation.

Background:Antibiotics save lives but also carry significant risks, including increased antimicrobial resistance, higher healthcare costs, and disruption of the microbiome. However, the association between antibiotic exposure and short-term adverse outcomes remains uncertain. Our study aimed to evaluate whether early unnecessary antibiotic exposure in the first 7 days of life of very preterm infants is linked to short-term adverse outcomes. Methods:This retrospective study included infants born below 32 weeks of gestation and hospitalized at the University Hospital of Lausanne between January 1, 2007 and December 31, 2022. Antibiotic exposure was quantified during the first seven postnatal days by the median number of days of antibiotics. Multilinear regressions and mixed effect models analyzed the association between the number of days of antibiotics and death, late-onset sepsis, necrotizing enterocolitis, severe bronchopulmonary dysplasia, severe retinopathy of prematurity and cystic periventricular leukomalacia. The primary outcome was a composite of at least one of the listed adverse outcomes, while the secondary outcomes consisted of each adverse outcome individually. Adjusted odds ratio (aOR) and p-value were calculated. Results:We included 1,398 preterm infants. The median gestational age was 29 weeks (IQR: 27-30) and the median birthweight was 1,144 grams (895-1,420). The median number of days of antibiotics declined by 53%, from 4 days in 2007 to 1.9 days in 2022 (p < 0.0001). The number of days of antibiotics was not associated with the composite outcome [aOR: 0.97 (0.82-1.17), p = 0.80, adjusted p = 0.80] or any of the following adverse outcomes: mortality [aOR: 1.10 (0.78-1.55), p = 0.58, adjusted p = 0.69], late-onset sepsis [aOR: 0.74 (0.59-0.93), p = 0.01, adjusted p = 0.07], necrotizing enterocolitis [aOR: 1.22 (0.86-1.74), p = 0.26, adjusted p = 0.65], severe bronchopulmonary dysplasia [aOR: 1.12 (0.88-1.42), p = 0.36, adjusted p = 0.65], severe retinopathy of prematurity [aOR: 1.34 (0.65-2.78), p = 0.43, adjusted p = 0.65], and cystic periventricular leukomalacia [aOR: 1.02 (0.69-1.99), p = 0.91, adjusted p = 0.91]. Conclusion:We found no association between early antibiotic exposure and short-term adverse outcomes.

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.

Importance:Sepsis is one of the leading causes of neonatal mortality. There is heterogeneity in the outcomes measured and reported in studies of neonatal sepsis. To address this challenge, a core outcome set (COS) for research on neonatal sepsis was needed. Objective:The Neonatal Sepsis Core Outcome Set (NESCOS) project aims to develop a COS for research evaluating the effectiveness of neonatal sepsis treatments. Evidence Review:For this consensus statement, the research team obtained ethics approval and used a 4-stage process: (1) a systematic review of qualitative studies, (2) a real-time Delphi (RTD) survey to identify important outcomes for consensus meetings, (3) consensus meetings to finalize the COS, and (4) dissemination of the findings. The study was conducted from May 2, 2022, to October 27, 2023. The steering group and project participants consisted of health care workers, researchers, academics, parents, and parent representatives from low-, middle-, and high-income countries. An RTD survey and consensus meetings were conducted, with measures including a 9-point Likert scale rating (where 1 indicated not at all important and 9 indicated critically important) for outcome importance and a minimum 80% agreement threshold among stakeholders for final COS inclusion. The systematic review identified 19 outcomes, which were combined with outcomes from previous systematic reviews of clinical trials. Findings:The RTD survey included 306 participants, leading to the identification of 55 outcomes for further discussion in consensus meetings. The finalized COS comprises 9 outcomes: all-cause mortality, need for mechanical ventilation, brain injury on imaging, neurologic status at discharge, escalation of antimicrobial therapy, central nervous system infections, multiorgan dysfunction, neurodevelopmental impairment, and quality of life of parents. Conclusions and Relevance:This consensus-based COS for research on neonatal sepsis treatments will help standardize the outcomes measured and reported, enhancing the comparability of research findings. Future efforts should focus on establishing standardized and reliable methods for measuring these outcomes.

ImportanceSepsis is one of the leading causes of neonatal mortality. There is heterogeneity in the outcomes measured and reported in studies of neonatal sepsis. To address this challenge, a core outcome set (COS) for research on neonatal sepsis was needed.ObjectiveThe Neonatal Sepsis Core Outcome Set (NESCOS) project aims to develop a COS for research evaluating the effectiveness of neonatal sepsis treatments.Evidence ReviewFor this consensus statement, the research team obtained ethics approval and used a 4-stage process: (1) a systematic review of qualitative studies, (2) a real-time Delphi (RTD) survey to identify important outcomes for consensus meetings, (3) consensus meetings to finalize the COS, and (4) dissemination of the findings. The study was conducted from May 2, 2022, to October 27, 2023. The steering group and project participants consisted of health care workers, researchers, academics, parents, and parent representatives from low-, middle-, and high-income countries. An RTD survey and consensus meetings were conducted, with measures including a 9-point Likert scale rating (where 1 indicated not at all important and 9 indicated critically important) for outcome importance and a minimum 80% agreement threshold among stakeholders for final COS inclusion. The systematic review identified 19 outcomes, which were combined with outcomes from previous systematic reviews of clinical trials.FindingsThe RTD survey included 306 participants, leading to the identification of 55 outcomes for further discussion in consensus meetings. The finalized COS comprises 9 outcomes: all-cause mortality, need for mechanical ventilation, brain injury on imaging, neurologic status at discharge, escalation of antimicrobial therapy, central nervous system infections, multiorgan dysfunction, neurodevelopmental impairment, and quality of life of parents.Conclusions and RelevanceThis consensus-based COS for research on neonatal sepsis treatments will help standardize the outcomes measured and reported, enhancing the comparability of research findings. Future efforts should focus on establishing standardized and reliable methods for measuring these outcomes.