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Introduction: In light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their use while minimising the risk of delayed diagnosis of intracranial lesions (ICLs). Identifying children at higher risk of poor outcomes would enable them to be better monitored. The use of the blood-based brain biomarkers glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) could help clinicians in this decision. The overall aim of this study is to provide new knowledge regarding GFAP and UCH-L1 in order to improve TBI management in the paediatric population., Methods and Analysis: We will conduct a European, prospective, multicentre study, the BRAINI-2 paediatric study, in 20 centres in France, Spain and Switzerland with an inclusion period of 30 months for a total of 2880 children and adolescents included. To assess the performance of GFAP and UCH-L1 used separately and in combination to predict ICLs on CT scans (primary objective), 630 children less than 18 years of age with mild TBI, defined by a Glasgow Coma Scale score of 13-15 and with a CT scan will be recruited. To evaluate the potential of GFAP and UCH-L1 in predicting the prognosis after TBI (secondary objective), a further 1720 children with mild TBI but no CT scan as well as 130 children with moderate or severe TBI will be recruited. Finally, to establish age-specific reference values for GFAP and UCH-L1 (secondary objective), we will include 400 children and adolescents with no history of TBI., Ethics and Dissemination: This study has received ethics approval in all participating countries. Results from our study will be disseminated in international peer-reviewed journals. All procedures were developed in order to assure data protection and confidentiality., Trial Registration Number: NCT05413499., Competing Interests: Competing interests: OM and VP are employees of bioMérieux. The other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Our aim was to assess suboptimal care before a diagnosis of severe child physical abuse in western France., Methods: A confidential inquiry was carried out, based on children under 6 years of age who were hospitalised in the Nantes regional university hospital from 2016 to 2018. Two researchers retrospectively reviewed the medical records of all the children who were reported to the authorities for suspected severe child physical abuse. Two experts determined the optimality of care and identified the main categories of suboptimal care., Results: The median age of the 94 children included in the study was 8 months. A fifth of them had intra-cranial injuries and a quarter had fractures. One child died and a third had severe sequelae at hospital discharge. Included children frequently (37%) received suboptimal care before the diagnosis of severe CPA and this fell into two categories: delayed diagnosis was experienced by 17% and ineffective secondary prevention by 22%., Conclusion: Suboptimal care for severe child physical abuse was frequent and fell into two categories: delayed diagnosis and ineffective secondary prevention. These results can help us to design corrective actions., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Human rotaviruses attach to histo-blood group antigens glycans and null alleles of the ABO , FUT2 and FUT3 genes seem to confer diminished risk of gastroenteritis. Yet, the true extent of this protection remains poorly quantified. Here, we conducted a prospective study to evaluate the risk of consulting at the hospital in non-vaccinated pediatric patients according to the ABO, FUT2 (secretor) and FUT3 (Lewis) polymorphisms, in Metropolitan France and French Guiana. At both locations, P genotypes were largely dominated by P [8]-3, with P [6] cases exclusively found in French Guiana. The FUT2 null (nonsecretor) and FUT3 null (Lewis negative) phenotypes conferred near full protection against severe gastroenteritis due to P [8]-3 strains (OR 0.03, 95% CI [0.00-0.21] and 0.1, 95% CI [0.01-0.43], respectively in Metropolitan France; OR 0.08, 95% CI [0.01-0.52] and 0.14, 95%CI [0.01-0.99], respectively in French Guiana). Blood group O also appeared protective in Metropolitan France (OR 0.38, 95% CI [0.23-0.62]), but not in French Guiana. The discrepancy between the two locations was explained by a recruitment at the hospital of less severe cases in French Guiana than in Metropolitan France. Considering the frequencies of the null ABO, Secretor and Lewis phenotypes, the data indicate that in a Western European population, 34% (95% CI [29%; 39%]) of infants are genetically protected against rotavirus gastroenteritis of sufficient severity to lead to hospital visit., 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., (Copyright © 2023 Masson, Barbé, Henaff, Ahmed, Le Moullac-Vaidye, Peltier, Marchand, Scherdel, Vibet, Ruvoën-Clouet, Elenga, Imbert-Marcille, Gras-Le Guen and Le Pendu.)

Background: The COVID-19 pandemic has shaken the world by imposing unprecedented health measures, including in the postpartum period. Objectives: We aim to assess the impact of maternal isolation in the immediate postpartum period on the rate of postpartum depression (PPD) in a tertiary center. Study Design: We conducted a prospective cohort study, between 22 April and 29 October 2020, using anonymous questionnaires on 265 participants (129 during lockdown and 135 outside). The Edinburgh Postnatal Depression Scale (EPDS) was used as screening for PPD. We used a univariate logistic regression model to analyze the association between risk factors and PPD. Results: There was no difference between the two groups for PPD assessed by an EPDS score >10.5 on day 30 and/or day 60 (23.1% vs. 29.3%, p = 0.661) but on day 3 it was higher (31% vs. 17.8%, p = 0.015) during the lockdown period and partners were more impacted psychologically (48.3% vs. 10.5%, p < 0.001). Parity ≥1 was a protective factor for PPD (OR = 0.2, 95% CI [0.1−0.6], p = 0.003). Risk factors of PPD were: history of psychological abuses (OR = 6.4, CI 95% [1.1−37.6], p = 0.04), stressful life event (OR = 4.5, CI 95% [1.6−12.6], p = 0.004), and bad birth experience (OR = 5.1, CI 95% [1.4−17.8], p = 0.012). Conclusion: Maternal isolation in the immediate postpartum period is associated with an increased rate of moderate to severe symptoms of postpartum blues. The well-known long-term consequences of PPD must be balanced against the expected benefits of partner’s restrictive access to maternity ward.

Importance: Assessment of the quality of initial care is necessary to target priority actions that can reduce the still high morbidity and mortality due to community-onset severe bacterial infections (COSBIs) among children., Objective: To study the prevalence, characteristics, and determinants of suboptimal care in the initial management of COSBIs., Design, Setting, and Participants: This prospective, population-based, cohort study and confidential enquiry was conducted between August 2009 and January 2014 in western France, a region accounting for 15% of the French pediatric population (1 968 474 children aged 1 month to 16 years) and including 6 pediatric intensive care units (PICUs) and 35 emergency departments. Participants included all children aged 1 month to 16 years who died before PICU admission or were admitted to a PICU with a COSBI (ie, bacterial sepsis, including meningitis, purpura fulminans, and pulmonary, osteoarticular, intra-abdominal, cardiac, and soft-tissue severe infections). Data were analyzed from March to June 2020., Exposures: Suboptimal care determined according to evaluation of 8 types of care: (1) the delay in seeking care by family, (2) the physician's evaluation of severity, (3) the patient's referral at the first consultation with signs of severity, (4) the timing and (5) dosage of antibiotic treatment, (6) the timing and (7) volume of fluid bolus administration, and (8) the clinical reassessment after fluid bolus., Main Outcomes and Measures: Two experts assessed the quality of care before death or PICU admission as optimal, possibly suboptimal, or certainly suboptimal. The consequences and determinants of certainly suboptimal care were identified with multinomial logistic regression and generalized linear mixed models., Results: Of the 259 children included (median [IQR] age, 24 [6-66] months; 143 boys [55.2%]), 27 (10.4%) died, and 25 (9.6%) had severe sequelae at PICU discharge. The quality of care was certainly suboptimal in 89 cases (34.4%). Suboptimal care was more frequent in children with sequelae (adjusted odds ratio [aOR], 5.61; 95% CI, 1.19-26.36) and less frequent in children who died (aOR, 0.16; 95% CI, 0.04-0.65) vs those surviving without sequelae. Factors independently associated with suboptimal care were age younger than 5 years (aOR, 3.15; 95% CI, 1.25-7.90), diagnosis of sepsis with no source (aOR, 5.77; 95% CI, 1.64-20.30) or meningitis (aOR, 3.39; 95% CI, 1.15-9.96) vs other severe infections, and care by a primary care physician (aOR, 3.22; 95% CI, 1.17-8.88) vs a pediatric hospital service., Conclusions and Relevance: This study found that suboptimal care is frequent in the initial management of COSBI and is associated with severe sequelae. The paradoxical association with reduced risk of death may be explained by an insufficient adjustment on bacterial or host intrinsic factors. Management could be optimized by improving the quality of primary care, especially for young children.

Objective: Ogival palate (i.e., a narrow and high-arched palate) is usually described in obstructive breath disorder but has been found in infants unexpectedly deceased. We studied the association between ogival palate and sudden unexpected death in infancy (SUDI) on the basis of a computed tomography (CT) evaluation., Methods: We conducted a monocentric case-control study of children under 2 years of age who died of SUDI, for which a head CT scan and an autopsy were performed between 2011 and 2018. Each case was matched by sex and age (± 30 days) to two controls selected among living children in the same center who benefited from a cranio-encephalic CT scan. Four parameters of the hard palate were measured by CT: height, width, length, and sagittal angle; the height/width ratio was calculated. The presence of an ogival palate was also subjectively evaluated by the radiologists, independently from the measurements. Standardized odds ratios (OR) were calculated using conditional logistic regression models, all expressed for +1 standard deviation (SD)., Results: Thirty-two deceased children were matched to 64 living control children. Mean ages were 5.0 and 5.3 months, respectively. Twenty-eight cases were considered to have died as a result of SIDS. The mean heights of the hard palate were significantly higher in the deceased children [4.1 (± 0.7) millimeters (mm)] than in the living children [3.2 (± 0.6) mm], with OR (+1SD) = 4.30 (95% confidence interval [CI], 2.04-9.06, P = 0.0001). The mean widths of the hard palate were 21.0 (± 1.9) mm and 23.2 (± 2.1) mm, respectively, with OR = 0.15 (95% CI, 0.06-0.40, P = 0.0001). The mean sagittal angles were significantly more acute in deceased children [134.5° (± 9.3)] than in living children [142.9° (± 8.1)], with OR = 0.28 (95% CI, 0.14-0.56, P = 0.0003). The mean height/width ratios were 19.8 (± 3.7) and 14.1 (± 3.3), respectively, with OR = 6.10 (95% CI, 2.50-14.9, P = 0.0001). The hard palate was subjectively considered as ogival in 59.4% (19/32) of the cases versus 12.5% (8/64) of the controls., Conclusion: Radiological features of the ogival palate were strongly associated with SUDI. This observation still needs to be confirmed and the corresponding clinical features must be identified., 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., (Copyright © 2022 Ducloyer, Wargny, Medo, Gourraud, Clement, Levieux, Gras-Le Guen, Corre and Rambaud.)

Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 were implemented in March 2020. These measures were followed by a major impact on viral and non-viral diseases. We aimed to assess the impact of NPI implementation in France on hospitalized community-acquired pneumonia (hCAP) frequency and the clinical and biological characteristics of the remaining cases in children. We performed a quasi-experimental interrupted time-series analysis. Between June 2014 and December 2020, eight pediatric emergency departments throughout France reported prospectively all cases of hCAP in children from age 1 month to 15 years. We estimated the impact on the monthly number of hCAP using segmented linear regression with autoregressive error model. We included 2,972 hCAP cases; 115 occurred during the NPI implementation period. We observed a sharp decrease in the monthly number of hCAP after NPI implementation [-63.0% (95 confidence interval, -86.8 to -39.2%); p < 0.001]. Children with hCAP were significantly older during than before the NPI period (median age, 3.9 vs. 2.3 years; p < 0.0001), and we observed a higher proportion of low inflammatory marker status (43.5 vs. 33.1%; p = 0.02). Furthermore, we observed a trend with a decrease in the proportion of cases with pleural effusion (5.3% during the NPI period vs. 10.9% before the NPI; p = 0.06). NPI implementation during the COVID-19 (coronavirus disease 2019) pandemic led not only to a strong decrease in the number of hCAP cases but also a modification in the clinical profile of children affected, which may reflect a change in pathogens involved., 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., (Copyright © 2022 Rybak, Ouldali, Angoulvant, Minodier, Biscardi, Madhi, Hau, Santos, Bouvy, Dubos, Martinot, Dommergues, Gras-Le Guen, Launay, Levieux, Zenkhri, Craiu, Lorrot, Gillet, Mezgueldi, Faye, Béchet, Varon, Cohen and Levy.)

Importance: The highly variable practices observed regarding the early detection and diagnostic workup of suspected child physical abuse contribute to suboptimal care and could be partially related to discrepancies in clinical guidelines., Objective: To systematically evaluate the completeness, clarity, and consistency of guidelines for child physical abuse in high-income countries., Evidence Review: For this systematic review, national or regional guidelines that were disseminated from 2010 to 2020 related to the early detection and diagnostic workup of child physical abuse in infants aged 2 years or younger by academic societies or health agencies in high-income countries were retrieved. The definitions of sentinel injuries and the recommended diagnostic workup (imaging and laboratory tests) for child physical abuse were compared. Data were analyzed from July 2020 to February 2021., Findings: Within the 20 included guidelines issued in 15 countries, 168 of 408 expected statements (41%) were missing and 10 statements (4%) were unclear. Among 16 guidelines characterizing sentinel injuries, all of them included skin injuries, such as bruises, hematoma, or burns, but only 8 guidelines (50%) included intraoral injuries and fractures. All 20 guidelines agreed on the indication for radiological skeletal survey, head computed tomography, and head magnetic resonance imaging but differed for those of bone scintigraphy, follow-up skeletal survey, spinal magnetic resonance imaging, cranial ultrasonography, chest computed tomography, and abdominal ultrasonography and computed tomography. Additionally, 16 guidelines agreed on exploring primary hemostasis and coagulation but not on the tests to perform, and 8 guidelines (50%) mentioned the need to investigate bone metabolism., Conclusions and Relevance: These findings suggest that guidelines for the diagnosis of child physical abuse in infants were often clear but lacked completeness and were discrepant on major issues. These results may help identify priorities for well-designed original diagnostic accuracy studies, systematic reviews, or an international consensus process to produce clear and standardized guidelines to optimize practices and infant outcomes.

Background: To examine the impact of executive function disorders on health-related quality of life (QoL) in children with neurofibromatosis type 1 (NF1), we conducted a prospective single-center study among 40 children with NF1 aged 8-12 years (mean = 9.7, SD = 1.4) and their parents, comparing them with 56 healthy control children matched for age, sex, parental education level, and handedness. We collected children's self-reports and parents' proxy reports of QoL with the Kidscreen-52 questionnaire, and measured executive functions by combining seven performance-based tests and a daily life questionnaire completed by parents and teachers., Results: Several QoL domains were significantly impaired in the children with NF1, compared with healthy controls, mainly according to their parents' reports (3 out of 9 scales; Cohen's d: 0.57-0.76), with particularly low scores in the social support and peers and school environment domains. Executive function difficulties (Cohen's d: 0.64-1.72) significantly predicted the impairment of QoL domains as perceived by the children or their parents, regardless of the indirect indicators of learning disabilities., Conclusions: Both performance-based executive function scores and behavioral ratings of executive functions in daily life by parents and teachers were associated with low QoL levels in the children with NF1. The school environment and social integration appear to be particularly affected and should therefore be targeted in the management of the disease., (© 2021. The Author(s).)

Background: Timely diagnosis of child physical abuse is of paramount importance. The added value of bone scintigraphy (BS) after a negative radiological skeletal survey (RSS) in children with suspected physical abuse has never been evaluated. Objective: The objective of this study was to assess the extent to which BS could improve the detection rate of skeletal injury in children with suspected physical abuse with an initial negative RSS. Methods: We used discharge codes to retrospectively identify children evaluated for suspected physical abuse in a university hospital (Nantes, France). We included all consecutive children younger than 3 years old who underwent both RSS and BS, with an interval of ≤96 h between tests, from 2013 to 2019. BS and RSS results were interpreted independently during the study period. We specifically analyzed BS results for children with a negative RSS to assess the value of BS as an add-on test. Results: Among the 268 children ≤3 years old with suspected physical abuse who underwent RSS, 140 (52%) also underwent BS within 96 h and were included in the analysis. The median age was 6 months old (interquartile range: 3-8). The detection rate of ≥1 skeletal injury with RSS alone was 49% ( n = 69/140, 95% CI: 41-58%) vs. 58% ( n = 81/140, 50-66%) with RSS followed by add-on BS, for an absolute increase in the detection rate of 9% points (95% CI: 4-14%). The number of children with a negative RSS who would need to undergo BS to detect one additional child with ≥1 skeletal injury was 6 (95% CI: 4-11). Conclusion: In young children with suspected physical abuse with a negative RSS, add-on BS would allow for a clinically significant improvement in the detection rate of skeletal injuries for a limited number of BS procedures required. Prospective multicenter studies are needed to confirm these findings., (Copyright © 2020 Blangis, Poullaouec, Launay, Vabres, Sadones, Eugène, Cohen, Chalumeau and Gras-Le Guen.)

Introduction: Fever is one of the most common reasons for consultation in the paediatric emergency department (ED). Because of fear of bacterial infection in parents and caregivers, clinicians often overprescribe laboratory tests and empirical antibiotic treatment. The aims of this study are to demonstrate that using a procalcitonin (PCT) rapid test-based prediction rule (1) would not be inferior to usual practice in terms of morbidity and mortality (non-inferiority objective) and (2) would result in a significant reduction in antibiotic use (superiority objective)., Methods and Analysis: This prospective multicentric cluster-randomised study aims to include 7245 febrile children aged 6 days to 3 years with a diagnosis of fever without source in 26 participating EDs in France and Switzerland during a 24-month period. During first period, all children will receive usual care. In a second period, a point-of-care PCT-based algorithm will be used in half of the clusters. The primary endpoints collected on day 15 after ED consultation will be a composite outcome of death or intensive care unit admission for any reason, disease-specific complications, diagnosis of bacterial infection after discharge from the ED for the non-inferiority objective and proportion of children with antibiotic treatment administered for the superiority objective. The endpoints will be compared between the two groups (experimental and control) by using a mixed logistic regression model adjusted on clustering of participants within centres and period within centres., Discussion: If the algorithm is validated, a new strategy will be discussed with medical societies to safely manage fever in young children without the need for invasive procedures for microbiological testing or empirical antibiotics., Ethics and Dissemination: This study was submitted to an independent ethics committee on 17 May 2018 (no. 2018-A00252-53). Results will be submitted to international peer-reviewed journals and presented at international conferences., Trial Registration Number: NCT03607162; Pre-results., Competing Interests: Competing interests: The DIAFEVERCHILD study received a French national grant from the French Ministry of Health. ThermoFisher will provide instruments and tests for the micromethod PCT assay, the B.R.A.H.M.S PCT-direct system., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: The incidence of early-onset neonatal infection has greatly decreased, but a new diagnostic approach is needed to avoid overdiagnosis and overtreatment. The aim of this study was to assess the potential impact of an algorithm incorporating umbilical-cord-blood procalcitonin (PCT) level on neonatal antibiotics prescription rate as compared with current practice. Material and methods: We conducted a prospective study in three maternity wards in France. All term and preterm neonates with the usual risk factors for neonatal group B Streptococcus infection were eligible for umbilical-cord-blood PCT testing. We compared the proportion of neonates who were exposed early to antibiotics (before 6 days of life) to that of neonates for whom antibiotics prescription would be indicated according to the PCT-based algorithm. Results: Among the 3,080 neonates included, 1 neonate presented with certain infection and 38 neonates with probable infection. The global antibiotics prescription rate was 4.6% [95% confidence interval (CI), 4.1-5]. With the PCT-based algorithm, the potential decrease in prescription rate would be 1.8% (95% CI, 1.3-2.3), corresponding to a 39% (95% CI, 37.3-40.7) relative reduction in antibiotics exposure ( p < 0.05). Conclusion: These results suggest that the umbilical-cord-blood PCT-based algorithm could significantly help the clinicians in their antibiotic prescription decision to decrease neonatal antibiotics exposure as compared with current practice. If validated in a larger interventional randomized study, this approach could help clinicians stratify the risk of early-onset neonatal infection and initiate early antibiotics treatment in newborns at high risk of infection while limiting the deleterious effects of useless prescriptions in non-infected newborns., (Copyright © 2020 Huetz, Launay, Gascoin, Leboucher, Savagner, Muller, Denizot, Boscher, Caillon, Masson and Gras Le Guen.)

Corticosteroids (CS) are standard therapy for the treatment of Duchenne's muscular dystrophy (DMD). Even though they decrease inflammation, they have limited efficacy and are associated with significant side effects. There is therefore the need for new protolerogenic treatments to replace CS. Dystrophin-deficient rats ( Dmd mdx ) closely resemble the pathological phenotype of DMD patients. We performed the first Immunophenotyping of Dmd mdx rats and showed leukocyte infiltration in skeletal and cardiac muscles, which consisted mostly of macrophages and T cells including CD45RC high T cells. Muscles of DMD patients also contain elevated CD45RC high T cells. We treated Dmd mdx rats with an anti-CD45RC MAb used in previous studies to deplete CD45RC high T cells and induce immune tolerance in models of organ transplantation. Treatment of young Dmd mdx rats with anti-CD45RC MAb corrected skeletal muscle strength and was associated with depletion of CD45RC high T cells with no side effects. Treatment of young Dmd mdx rats with prednisolone resulted in increase in skeletal muscle strength but also severe growth retardation. In conclusion, anti-CD45RC MAb treatment has potential in the treatment of DMD and might eventually result in reduction or elimination of CS use.

Introduction: Even after 'back-to-sleep' campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area., Methods and Analysis: This observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths., Ethics and Dissemination: The French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l'Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais d'Ethique dans le Domaine de la Santé: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: As the most recent French bronchiolitis guidelines were published in 2000, there is a current overinvestigation and an overtreatment of infants hospitalised with bronchiolitis in France. In 2012, the Group of Pediatric University Hospitals in Western France ('HUGO') proposed new evidence-based clinical practice guidelines in keeping with the latest international guidelines. We hypothesise that the implementation of these guidelines contributed to the quality improvement of the management of bronchiolitis in our hospital. The aim of this study was to determine the impact of these guidelines on the management of bronchiolitis inpatients., Methods: This retrospective before/after study design was conducted in the general paediatric unit of a tertiary care French hospital, looking at 1 year before (ie, the winter of 2011-2012) and 1 year after (ie, the winter of 2013-2014) the implementation of the guidelines. Two hundred and eighty bronchiolitis inpatients, all less than 1 year of age, 115 in 2011-2012 and 165 in 2013-2014, were included. The primary outcome we sought to evaluate was the proportion of children administered a diagnostic test associated with a treatment not routinely recommended by the guidelines. As balancing measures, we evaluated the length of stay, the intensive care unit transfer and the readmission rates., Results: Following implementation of the guidelines, use of any given treatment associated with a diagnostic test was reduced by 66% (p<0.001). There were major decreases in the use of chest X-ray (86%vs26%, p<0.001), antibiotics (38%vs13%, p<0.001) and corticosteroids (10%vs3%, p=0.011). Balancing measures were not significantly different., Conclusions: HUGO guidelines were effective at reducing the administration of unnecessary diagnostic tests and medications. This study was the first step in convincing French paediatricians to streamline their practices until updated national guidelines are published., Competing Interests: Competing interests: None declared.

Objectives: To assess the health-related quality of life (HRQOL) of children with specific language impairment (SLI)., Study Design: In a prospective sample at a Learning Disabilities Reference Center, proxy-rated HRQOL (KIDSCREEN-27) was assessed for children with SLI and unaffected children from January 1, 2014 to March 31, 2015. Quality of life predictors for children with SLI were evaluated by recording the length and number of speech therapy and psychotherapy sessions and the specific school organization that the children had participated in. The KIDSCREEN scores of the two groups were compared using nonparametric statistics., Results: The questionnaires were completed by the parents of 67 children with SLI and 67 unaffected children. For children with SLI, the mean HRQOL scores were significantly lower for physical and psychological well-being, autonomy and parent relation, social support, and school environment compared to the reference group, controlling for age and parental education (β = -6.7 (-12.7;-.7) P = 0.03, β = -4.9 (-9.5;-.3) P = 0.04, β = -8.4 (-14.2;-2.6) P = 0.005, β = -11.6 (-19.5;-3.7) P = 0.004, β = -7.1(-12.4;-1.7) P = 0.010, respectively). Multivariate analyses in the group of children with SLI found that children who had undergone psychotherapy sessions or who had been enrolled in specific schooling programs had reduced HRQOL scores in social support and school environment and that children who were in a special class had higher scores in physical well-being., Conclusion: Children with SLI had significantly lower HRQOL scores as compared to unaffected children. Measurement of HRQOL could serve as one of the strategies employed throughout the follow-up of these individuals to provide them with the most appropriate and comprehensive care possible., Competing Interests: The authors have declared that no competing interests exist.

Background: Lower respiratory tract infection is a common cause of consultation and antibiotic prescription in paediatric practice. The misuse of antibiotics is a major cause of the emergence of multidrug-resistant bacteria. The aim of this study was to evaluate the frequency, changes over time, and determinants of non-compliance with antibiotic prescription recommendations for children admitted in paediatric emergency department (PED) with community-acquired pneumonia (CAP)., Methods: We conducted a prospective two-period study using data from the French pneumonia network that included all children with CAP, aged one month to 15 years old, admitted to one of the ten participating paediatric emergency departments. In the first period, data from children included in all ten centres were analysed. In the second period, we analysed children in three centers for which we collected additional data. Two experts assessed compliance with the current French recommendations. Independent determinants of non-compliance were evaluated using a logistic regression model. The frequency of non-compliance was compared between the two periods for the same centres in univariate analysis, after adjustment for confounding factors., Results: A total of 3034 children were included during the first period (from May 2009 to May 2011) and 293 in the second period (from January to July 2012). Median ages were 3.0 years [1.4-5] in the first period and 3.6 years in the second period. The main reasons for non-compliance were the improper use of broad-spectrum antibiotics or combinations of antibiotics. Factors that were independently associated with non-compliance with recommendations were younger age, presence of risk factors for pneumococcal infection, and hospitalization. We also observed significant differences in compliance between the treatment centres during the first period. The frequency of non-compliance significantly decreased from 48 to 18.8 % between 2009 and 2012. The association between period and non-compliance remained statistically significant after adjustment for confounding factors. Amoxicillin was prescribed as the sole therapy significantly more frequently in the second period (71 % vs. 54.2 %, p < 0.001)., Conclusions: We observed a significant increase in the compliance with recommendations, with a reduction in the prescription of broad-spectrum antibiotics, efforts to improve antibiotic prescriptions must continue.

Background: To date, the Pediatric Emergency Care Applied Research Network (PECARN) rule for identifying children who are at very low risk of clinically-important traumatic brain injuries after minor head trauma has not been validated prospectively in an independent population. Our goal was to evaluate the diagnostic performance of the PECARN clinical decision rule in a French pediatric population in multiple clinical settings., Methods: We conducted a multicenter, prospective, non-interventional cohort study of patients with minor head trauma who presented to three emergency departments in France. We enrolled patients younger than 16 years of age seeking a consultation within 24 h of head trauma with Glasgow Coma Scale scores of 14-15., Results: During the study period, we included 1499 children of which 421 (28 %) were under 2 years of age, and 955 (64 %) were male. A cranial computed tomography (CT) scan was performed on 76 patients (5.1 %). Of the 1499 included patients, 9 children (0.6 %) had a clinically-important traumatic brain injury, and none were classified as very low risk by the PECARN rule. In our study, the sensitivity of this clinical decision rule was 100 % (95 % CI 66.4 to 100 %), the specificity was 69.9 % (95 % CI 67.5 to 72.2 %) and the negative predictive value was 100 % (95 % CI 99.7 to 100 %)., Discussion: Our study confirmed the good predictive performances of the PECARN clinical decision rule for minor head trauma in children. The PECARN rule performed similarly to our study and to its internal validation study., Conclusions: We conducted an external validation study of the PECARN clinical decision rule for the detection of clinically-important traumatic brain injuries in children with minor head trauma, according to the methodological standards. The PECARN rule successfully identified all patients with clinically-important traumatic brain injuries, with a limited use of CT scans. Conducting a broad validation study with a large cohort is a prerequisite to provide sufficient statistical power before authorizing its implementation and generalization., Trial Registration: This study has been registered in ClinicalTrials.gov with identifier number: NCT02752711 on April 27, 2016.

Objectives: The Sudoscan™ system (Impeto Medical, Paris, France) has been recently proposed as a standardized, easy, painless tool for sudomotor function assessment. It is now used as an additional diagnostic tool in small fibre neuropathy. So far, no work has been published in children. The aim of this study was to measure electrochemical skin conductance (ESC) using the Sudoscan™ system in children in order to assess its feasibility and to provide normative values., Methods: 100 children were included in the study: 55 girls and 45 boys, age rank 2-17, mean 10.5 y. They were accompanying their brother or sister who came as outclinic patients in the Department of Paediatrics or the Department of Paediatric surgery of the University Hospital., Results: All subjects underwent the test. It was performed without any difficulty, except for some of the youngest who sometimes had some trouble in keeping calm for 3 min over the plates. 4 subjects who took the test were excluded from the analysis (2 diabetic patients and 2 having had previous chemotherapy). ESC was quite stable along childhood with an overall 80.1 μS value for hands and 81.9 μS for feet, very similar to what is observed in adults., Conclusion: Maturation process seems to occur early in life, in accordance to sudomotor control when assessed by sympathetic skin response, which is also recorded early in infancy., Significance: ESC measurement is a simple and easy-to-perform test that can be performed in the clinical setting in children in 5 min.

Diagnostic of early neonatal infection remains a serious challenge. Since clinical symptoms and biological markers are neither sensitive nor specific, a lot of newborns suspected of infection, undergo biological analysis and empirical antibiotic treatment awaiting bacteriological results. However the prevalence of the disease has dramatically decreased since the last twenty years, subsequently to the generalization of the per partum antibioprophylaxis strategy. Because the possible deleterious effects of neonatal antibiotic treatment are well described now, it appears very urgent to restrict their use to the infected newborns only. Recent studies underline the benefit of using procalcitonin (PCT) to diferentiate virai infections of bacterial infections. PCT in blood cord could become a new and efficient marker to help neonatologists taking care of infection-suspected newborns. An evidence based approach is necessary, combining anamnestic, clinical and biological data as PCT to identify the very low risk newborns population and to limit the neonatal antibiotic prescriptions.

Introduction: Suboptimal care is frequent in the management of severe bacterial infection. We aimed to evaluate the consequences of suboptimal care in the early management of severe bacterial infection in children and study the determinants., Methods: A previously reported population-based confidential enquiry included all children (3 months- 16 years) who died of severe bacterial infection in a French area during a 7-year period. Here, we compared the optimality of the management of these cases to that of pediatric patients who survived a severe bacterial infection during the same period for 6 types of care: seeking medical care by parents, evaluation of sepsis signs and detection of severe disease by a physician, timing and dosage of antibiotic therapy, and timing and dosage of saline bolus. Two independent experts blinded to outcome and final diagnosis evaluated the optimality of these care types. The effect of suboptimal care on survival was analyzed by a logistic regression adjusted on confounding factors identified by a causal diagram. Determinants of suboptimal care were analyzed by multivariate multilevel logistic regression., Results: Suboptimal care was significantly more frequent during early management of the 21 children who died as compared with the 93 survivors: 24% vs 13% (p = 0.003). The most frequent suboptimal care types were delay to seek medical care (20%), under-evaluation of severity by the physician (20%) and delayed antibiotic therapy (24%). Young age (under 1 year) was independently associated with higher risk of suboptimal care, whereas being under the care of a paediatric emergency specialist or a mobile medical unit as compared with a general practitioner was associated with reduced risk., Conclusions: Suboptimal care in the early management of severe bacterial infection had a global independent negative effect on survival. Suboptimal care may be avoided by better training of primary care physicians in the specifics of pediatric medicine.

The interplay between the colonic microbiota and gut epithelial and immune cells during the neonatal period, which establishes the structure of the microbiota and programs mucosal immunity, is affected by the diet. We hypothesized that protein-enriched milk formula would disturb this interplay through greater flux of protein entering the colon, with consequences later in life. Piglets were fed from postnatal day (PND) 2 to 28 either a normal-protein formula (NP; 51 g protein/L) or high-protein formula (HP; 77 g protein/L) and weaned at PND28, when they received standard diets until PND160. HP feeding transiently increased the quantity of protein entering the colon (PND7) but did not change the microbiota composition at PND28, except for a higher production of branched-chain fatty acids (BCFAs) in an in vitro fermentation test (P < 0.05). HP piglets had greater colonic mucosa densities of cluster of differentiation (CD) 3(+) and CD172(+) cells and lower Il-1β and Tnfα mRNA levels at PND28 (P < 0.05). Later in life (PND160), HP females, but not males, had a higher increase in colonic permeability after ex vivo oxidative stress and higher cytokine secretion in response to lipopolysaccharide in colonic explant cultures than NP females (P < 0.05). HP females also had lower colonic amounts of F. prausnitzii and BCFAs (P < 0.05). BCFAs displayed a dose-dependent protection against inflammation-induced alteration of barrier function in Caco-2 cells (P < 0.05). In conclusion, protein-enriched formula had little impact on colonic microbiota, but it modified colonic immune cell development and had a long-term effect on adult colonic mucosa sensitivity to inflammatory insults, probably through microbiotal and hormonal factors.

Background: Milk formulas have higher protein contents than human milk. This high protein level could modify the development of intestinal microbiota, epithelial barrier and immune functions and have long-term consequences., Methodology/principal Findings: We investigated the effect of a high protein formula on ileal microbiota and physiology during the neonatal period and later in life. Piglets were fed from 2 to 28 days of age either a normoprotein (NP, equivalent to sow milk) or a high protein formula (HP, +40% protein). Then, they received the same solid diet until 160 days. During the formula feeding period ileal microbiota implantation was accelerated in HP piglets with greater concentrations of ileal bacteria at d7 in HP than NP piglets. Epithelial barrier function was altered with a higher permeability to small and large probes in Ussing chambers in HP compared to NP piglets without difference in bacterial translocation. Infiltration of T cells was increased in HP piglets at d28. IL-1β and NF-κB sub-units mRNA levels were reduced in HP piglets at d7 and d28 respectively; plasma haptoglobin also tended to be reduced at d7. Later in life, pro-inflammatory cytokines secretion in response to high doses of LPS in explants culture was reduced in HP compared to NP piglets. Levels of mRNA coding the NF-κB pathway sub-units were increased by the challenge with LPS in NP piglets, but not HP ones., Conclusions/significance: A high protein level in formula affects the postnatal development of ileal microbiota, epithelial barrier and immune function in piglets and alters ileal response to inflammatory mediators later in life.

Neonates with intrauterine growth restriction (IUGR) are prone to suffer from digestive diseases. Using neonatal pigs with IUGR, we tested the hypothesis that IUGR may induce alterations in the developmental pattern of intestinal barrier and thereby may be responsible for IUGR-associated increased morbidity. Piglets with a birth weight near the mean birth weight (+/-0.5 SD) were identified as normal birth weight (control) and piglets with a mean -2 SD lower birth weight (-30%) were defined as piglets with IUGR. The developmental pattern of intestinal structure, transcriptomic profile, and bacterial colonization was investigated from birth to d 5 postnatal. At birth, intestinal weight and length, ileal and colonic weight per unit of length, and villous sizes were lower (P < 0.05) in piglets with IUGR than in same-age control piglets. These IUGR-induced intestinal alterations further persisted, although they were less marked at d 5. Counts of adherent bacteria to ileal and colonic mucosa were greater (P < 0.05) in 2-d-old piglets with IUGR than in same-age control piglets. Dynamic analyses of the transcriptomic profile of the intestine revealed molecular evidence of IUGR-induced intestinal growth impairment that may result from a change in the cell proliferation-apoptosis balance during the first days of life, while a protective process would occur later on. In addition, changes in the expression of several genes suggest a pivotal role of both glucocorticoids and microbiota in driving IUGR intestinal development during the neonatal period.