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Neonatal herpes simplex virus (HSV) infection (HSV infection in infants less than 6 weeks of age) is rare but mortality and morbidity rates are high after disseminated disease and encephalitis. In France, the epidemiology is poorly described, and two decades ago, incidence was estimated to be 3 per 100,000 live births a year. We describe determinants, epidemiologic and clinical characteristics of neonatal HSV infection in a managed-care population attending in two major obstetric and paediatric centres, Paris, France, over a 10-year period. This retrospective case series study was conducted from 2013 to 2023, in infants less than 42 days of age who had virologically confirmed HSV infection. We report an overall rate of neonatal herpes of 5.5 per 100,000 live births a year and an incidence of symptomatic cases of 1.2 per 100,000 live births a year. HSV-1 was the major serotype involved (84.2%) and post-natal acquisition through the orolabial route reached 63.2%. All neonates who had neonatal HSV PCR screening (owing to clinical signs in parents) and who received prompt acyclovir treatment remained asymptomatic. Symptomatic forms accounted for 21.1% cases of the total and mortality was high (62.5% of symptomatic forms).   Conclusion: This case series confirms that neonates at risk for HSV disease and poor outcome are those born to HSV-seronegative mothers, preterm infants, and those who received acyclovir after onset of symptoms (mainly because mothers did not present evidence of acute HSV infection). Our study confirms the major role of HSV-1 and the frequency of its early post-natal acquisition. What is known: • Neonatal herpes simplex virus infection is rare but motality and morbidity rates are high after disseminted disease and encephalitis. National recommendations exist worldwide but mangement of this disease is not always easy. What is new: • As in France epidemiology of neonatal herpes is poorly described, our report is potentially an important addition to the existing literature. Moreover, we describe local practice that may be useful to physicians., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Health care-associated primary bloodstream infections (BSIs), defined as not secondary to an infection at another body site, including central line-associated BSI, are a leading cause of morbidity and mortality in patients in neonatal intensive care units (NICUs). Our objective was to identify factors associated with severe morbidity and mortality after these infections in neonates in NICUs., Methods: This ancillary study of the SEPREVEN trial included neonates hospitalized ≥2 days in one of 12 French NICUs and with ≥ 1 BSI during the 20-month study period. BSIs (all primary and health care-associated) were diagnosed in infants with symptoms suggestive of infection and classified prospectively as possible (one coagulase-negative staphylococci (CoNS)-growing blood culture) or proven (two same CoNS, or ≥1 recognized pathogen-growing blood culture). BSI consequences were collected prospectively as moderate morbidity (antibiotic treatment alone) or severe morbidity/mortality (life-saving procedure, permanent damage, prolonged hospitalization, and/or death)., Results: Of 557 BSIs identified in 494 patients, CoNS accounted for 378/557 (67.8%) and recognized bacterial or fungal pathogens for 179/557 (32.1%). Severe morbidity/mortality was reported in 148/557 (26.6%) BSIs. Independent factors associated with severe morbidity/mortality were corrected gestational age <28 weeks (CGA) at infection ( P  < .01), fetal growth restriction (FGR) ( P  = .04), and proven pathogen-related BSI vs. CoNS-related BSI ( P  < .01). There were no differences in severe morbidity and mortality between proven and possible CoNS BSIs. In possible BSI, S. epidermidis was associated with a lower risk of severe morbidity than other CoNS ( P  < .01), notably S. capitis and S. haemolyticus ., Conclusions: In BSIs in the NICU, severe morbidity/mortality was associated with low CGA at infection, FGR, and proven pathogen-related BSIs. When only one blood culture was positive, severe morbidity/mortality were less frequent if it grew with S. epidermidis compared to other CoNS. Further studies to help distinguish real CoNS BSIs from contaminations are needed., Study Registration: ClinicalTrials.gov (NCT02598609)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jaloustre, Cohen, Biran, Decobert, Layese, Audureau, Le Saché, Chevallier, Boukhris, Bolot, Caeymaex, Tauzin and with SEPREVEN study Group.)

Background: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome., Methods: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076., Findings: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia., Interpretation: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction., Funding: French Ministry of Health., Competing Interests: Declaration of interests TS reports receiving consulting fees from Dilafor. LS reports receiving consulting fees from Dilafor; lecture fees from Bayer, GlaxoSmithKline, and Sigvaris; and lecture and consulting fees from Ferring Pharmaceuticals. AJV reprts receiving consulting fees from Norgine. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Patients in neonatal intensive care units (NICUs) are at high risk of adverse events. The effects of medical and paramedical education programmes to reduce these have not yet been assessed., Methods: In this multicentre, stepped-wedge, cluster-randomised controlled trial done in France, we randomly assigned 12 NICUs to three clusters of four units. Eligible neonates were inpatients in a participating unit for at least 2 days, with a postmenstrual age of 42 weeks or less on admission. Each cluster followed a 4-month multifaceted programme including education about root-cause analysis and care bundles. The primary outcome was the rate of adverse events per 1000 patient-days, measured with a retrospective trigger-tool based chart review masked to allocation of randomly selected files. Analyses used mixed-effects Poisson modelling that adjusted for time. This trial is registered with ClinicalTrials.gov, NCT02598609., Findings: Between Nov 23, 2015, and Nov 2, 2017, event rates were analysed for 3454 patients of these 12 NICUs for 65 830 patient-days. The event rate per 1000 patient-days reduced significantly from the control to the intervention period (33·9 vs 22·6; incidence rate ratio 0·67; 95% CI 0·50-0·88; p=0·0048)., Interpretation: A multiprofessional safety-promoting programme in NICUs reduced the rate of adverse events and severe and preventable adverse events in highly vulnerable patients. This programme could significantly improve care offered to critically ill neonates., Funding: Solidarity and Health Ministry, France., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The correct choice of intra vascular access in critically ill neonates should be individualized depending on the type and duration of therapy, gestational and chronological age, weight and/or size, diagnosis, clinical status, and venous system patency. Accordingly, there is an ongoing demand for optimization of catheterization. Recently, the use of ultrasound (US)-guided cannulation of the subclavian vein (SCV) has been described in children and neonates. This article gives an overview of the current use of US for achieving central venous catheter placement in the SCV or the brachiocephalic vein (BCV) in neonates. More than 1,250 catheters have been reported inserted in children and neonates for a cumulated success rate of 98.4% and the complication rate is reported to be low. The technical aspects of various approaches are discussed, and we offer our recommendation of an US-guided technique for SCV and BCV cannulation based on our experience in a large NICU setting. Although the cannulation the SCV or BCV does not substitute the use of peripherally inserted central catheters or umbilical venous central catheters in neonates, it is a feasible route in very small children who are in need of a large caliber central venous access.

Objectives: Central venous access in critically ill, small infants remains technically challenging even in experienced hands. Several vascular accesses exist, but the subclavian vein is often preferred for central venous catheter insertion in infants where abdominal malformation and/or closure of the vein preclude the use of umbilical venous catheters, as catheterization of the subclavian vein is easier in very short necks than the internal jugular vein for age-related anatomical reasons. The subclavian vein approach is yet relatively undescribed in low birth weight infants (i.e., < 2,500 g), and this study aims to explore the feasibility of this technique in very small infants., Design: Retrospective data collection of prospectively registered data on central venous catheter insertion in infants., Setting: Neonatal ICU and PICU at a university hospital., Patients: One hundred and five newborn children hospitalized in at the ICU., Interventions: An ultrasound-guided supraclavicular approach was applied on all infants who had an subclavian vein catheterization during a 30-month period from January 2013 to July 2015., Measurements and Main Results: One hundred seven supraclavicular subclavian vein catheters were placed in 105 children weighing less than 5,000 g. Among those, 40 patients weighed less than 2,500 g and 10 patients weighed less than 1,500 g. Successful central venous catheter insertion, defined as the correct placement of a functional double-lumen catheter (3F or 4F), was obtained in 97.3%. All three registered failed attempts were due to hematomas from venous bleeding and occurred in infants weighing greater than 2,500 g. No case of accidental arterial puncture or pleural puncture was registered., Conclusions: This large series of subclavian vein catheterizations in small infants demonstrates the feasibility of subclavian vein catheterizations even in very small neonates weighing less than 1,500 g.

Single-lumen cannula venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a special extracorporeal life support (ECLS) technique used for neonatal and pediatric refractory hypoxemia. This is an alternative flow rate ECLS that consists of successive clamping on the drainage and the injection lines. Currently, the Armand-Trousseau's pediatric intensive care unit remains the only pediatric ECMO center proposing this partial assistance. This article details a technical note and a retrospective analysis of our experience in refractory hypoxemia. The retrospective study, from 2007 to 2011, included all pediatric and neonatal patients treated by single-lumen cannula VV ECMO. The study was focused on pre-ECMO patient characteristics and complications during ECMO course. During the last 5 years, 67 pediatric patients were assisted by this single-lumen cannula VV ECMO. Sixty-one patients (91%) were newborns. Thirty-nine patients presented with meconium aspiration syndrome (58%), which was the most frequent etiology. Before cannulation, mean oxygenation index (OI) was 32 ± 11, alveolar-arterial oxygen difference was 604 ± 47 mm Hg, and partial pressure arterial oxygen/fraction inspired oxygen ratio was 59.2 ± 35.8. Forty-eight patients (72%) presented pulmonary hypertension, and 66 patients were treated by nitric oxide (98%). Fifty patients (75%) were treated by vasopressors or inotropic drugs. Average duration of ECMO was 13.2 ± 7.8 days. There were forty-six survivors (69%). The worst prognosis was for respiratory syncytial virus pneumonia. Complications like acute renal injury and hematologic and transfusion acts were not so different than those observed in classical ECMO techniques. Nevertheless, 19 patients presented a stroke (28% of the overall population), but this high rate did not seem to be due to the ECLS technique used. Single-lumen cannula VV ECMO is a partial and efficient ECMO support. Our experience shows that this technique is as efficient and less invasive than two cannulas ECMO. The single-lumen cannula VV ECMO is a simple and safe ECLS support used for neonatal or pediatric refractory hypoxemia. Because this is a partial assistance, it is a promising ECLS support., (© 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Relative to the cefotaxime-gentamicin combination, the moxifloxacin-cefotaxime combination significantly reduced microglial activation and immature oligodendrocyte cell death and delayed myelination in the developing white matter of neonatal rats with experimental Escherichia coli sepsis. These neuroprotective effects were not due to differences in in vivo bactericidal activities or in the systemic inflammatory responses and could be related to the intrinsic immunomodulatory properties of moxifloxacin. Molecular mechanisms underlying the neuroprotective effect of moxifloxacin remain to be elucidated.

Objective: Perinatal infections and the systemic inflammatory response to them are critical contributors to white matter disease (WMD) in the developing brain despite the use of highly active antibiotics. Fluoroquinolones including ciprofloxacin (CIP) have intrinsic anti-inflammatory effects. We hypothesized that CIP, in addition to its antibacterial activity, could exert a neuroprotective effect by modulating white matter inflammation in response to sepsis., Methods: We adapted an Escherichia coli sepsis model to 5-day-old rat pups (P5), to induce white matter inflammation without bacterial meningitis. We then compared the ability of CIP to modulate inflammatory-induced brain damage compared with cefotaxime (CTX) (treatment of reference)., Results: Compared with CTX, CIP was associated with reduced microglial activation and inducible nitric oxide synthase (iNOS) expression in the developing white matter in rat pups subjected to E. coli sepsis. In addition to reducing microglial activation, CIP was able to prevent myelination delay induced by E. coli sepsis and to promote oligodendroglial survival and maturation. We found that E. coli sepsis altered the transcription of the guidance molecules semaphorin 3A and 3F; CIP treatment was capable of reducing semaphorin 3A and 3F transcription levels to those seen in uninfected controls. Finally, in a noninfectious white matter inflammation model, CIP was associated with significantly reduced microglial activation and prevented WMD when compared to CTX., Interpretation: These data strongly suggest that CIP exerts a beneficial effect in a model of E. coli sepsis-induced WMD in rat pups that is independent of its antibacterial activity but likely related to iNOS expression modulation., (Copyright © 2010 American Neurological Association.)

Skin abnormalities in the spinal lumbosacral region of infants are not infrequent. Physicians should look for underlying spinal malformations. We report 2 cases of dermal sinus in infants revealed by severe, acute meningitis. The dermal sinus is an abnormal tract between the skin and underlying neural structures, most often located in the lumbosacral region. It may end blindly in the subcutaneous tissues, or it may extend into the medullary space. The diagnosis should be suspected in patients with other skin findings: localized hypertrichosis, subcutaneous lipomas, hyperpigmented lesions, etc. It must be distinguished from the very frequent coccygeal pits (4% of newborns), which require no treatment. Magnetic resonance imaging should be done every time the diagnosis is suspected. Recurrent bacterial meningitis or meningitis caused by unusual bacteria is frequently associated with dermal sinus. A variety of neurologic abnormalities have been described: sensory changes, motor weakness, reflex changes, abnormal bowel and bladder function, etc. Infants generally have few neurologic symptoms, such as delayed walking or sphincter control. Orthopaedic abnormalities are rare. The dermal sinus tract needs to be detected at an early stage in order to avoid these complications, which can be prevented by early surgery.