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In the context of vaccine scepticism, our study aimed to analyse the association between immunization status and the occurrence of sudden unexpected death in infancy (SUDI).A multi-centre case-control study was conducted between May 2015 and June 2017 with data from the French national SUDI registry (OMIN) for 35 French regional SUDI centres. Cases were infants under age 1 year who died from SUDI and who were registered in OMIN. Controls, matched to cases by age and sex at a 2:1 ratio, were infants admitted to Nantes University Hospital. All immunization data for diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), Haemophilus influenzae b (Hib), hepatitis B (HB) and 13-valent pneumococcal conjugate vaccine (PCV13) were collected by a physician. Cases and controls were considered immunized if at least one dose of vaccine was administered.A total of 91 cases and 182 controls were included. The median age was 131 days (interquartile range 98-200.0) and the sex ratio (M/F) was about 1.1. For all vaccines combined (D-T-aP-IPV-Hib and PCV13), 22 % of SUDI cases versus 12 % of controls were non-immunized, which was significantly associated with SUDI after adjustment for potential adjustment factors (adjusted odds ratio 2.01 [95 % confidence interval 1.01-3.98, p = 0,047]).Non-immunization for D-T-aP-IPV-Hib-HB and PCV13 was associated with increased risk of SUDI. This result can be used to inform the general public and health professionals about this risk of SUDI in case of vaccine hesitancy.

To investigate the prevalence of infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses among children admitted to paediatric emergency departments (PEDs).From April to July 2020, a prospective, multicentre cohort study was conducted in the PEDs of eight French university hospitals. Regardless of the reason for admission, a nasopharyngeal swab sample from each child was screened using reverse transcription polymerase chain reaction tests for SARS-CoV-2 and other respiratory viruses. We determined the prevalence of SARS-CoV-2 and other respiratory viruses and identified risk factors associated with a positive test.Of the 924 included children (median [interquartile range] age: 4 years [1-9]; boys: 55%), 908 (98.3%) were tested for SARS-CoV-2. Only three samples were positive (0.3%; 95% confidence interval: 0.1-1) and none of these children had symptoms of coronavirus disease 2019. Of the 836 samples (90%) tested for other viruses, 129 (15.4%) were positive (primarily rhinovirus). Respiratory viruses were significantly more common in young children and in children with respiratory tract symptoms and fever.The prevalence of SARS-CoV-2 among children admitted to emergency departments was low. In contrast, and despite social distancing and other protective measures, the prevalence of other respiratory viruses detection was high.

International audience; Introduction: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED).Methods: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority.Results: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France.Discussion: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.

Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries, but its determinants are poorly understood. Their identification is necessary to design target actions that can improve vaccination uptake. Our aim was to assess the determinants of incomplete vaccination in two-year-old children in France. Among the 18,329 children included in the 2011 ELFE French nationwide population-based birth cohort, we selected those for whom vaccination status was available at age two years. Incomplete vaccination was defined as ≥ 1 missing dose of recommended vaccines. Potential determinants of incomplete vaccination were identified by using logistic regression, taking into account attrition and missing data. Of the 5,740 (31.3%) children analyzed, 46.5% (95% confidence interval [CI] 44.7-48.0) were incompletely vaccinated. Factors independently associated with incomplete vaccination were having older siblings (adjusted odds ratio 1.18, 95% CI [1.03-1.34] and 1.28 [1.06-1.54] for one and ≥ 2 siblings, respectively, vs. 0), residing in an isolated area (1.92 [1.36-2.75] vs. an urban area), parents not following health recommendations or using alternative medicines (1.81 [1.41-2.34] and 1.23 [1.04-1.46], respectively, vs. parents confident in institutions and following heath recommendations), not being visited by a maternal and child protection service nurse during the child's first two months (1.19 [1.03-1.38] vs. ≥ 1 visit), and being followed by a general practitioner (2.87 [2.52-3.26] vs. a pediatrician).Incomplete vaccination was highly prevalent in the studied pediatric population and was associated with several socio-demographic, parental, and healthcare service characteristics. These findings may help in designing targeted corrective actions.• Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries. • The partial understanding of the determinants of incomplete vaccination precludes the design of effective targeted corrective actions.• High prevalence of incomplete vaccination at age two years in France. • Incomplete vaccination was independently associated with several socio-demographic, parental, and healthcare service characteristics.

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.

International audience; BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. METHODS: We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12-17-year-old children between June 15(th), 2021 and January 1(st), 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. FINDINGS: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. INTERPRETATION: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. FUNDING: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.

Objectives To evaluate the impact of implementing a modified Pediatric Emergency Care Applied Research Network (PECARN) rule including the S100B protein assay for managing mild traumatic brain injury (mTBI) in children. Methods A before-and-after study was conducted in a paediatric emergency department of a French University Hospital from 2013 to 2015. We retrospectively included all consecutive children aged 4 months to 15 years who presented mTBI and were at intermediate risk for clinically important traumatic brain injury (ciTBI). We compared the proportions of CT scans performed and of in-hospital observations before (2013–2014) and after (2014–2015) implementation of a modified PECARN rule including the S100B protein assay. Results We included 1,062 children with mTBI (median age 4.5 years, sex ratio [F/M] 0.73) who were at intermediate risk for ciTBI: 494 (46.5%) during 2013–2014 and 568 (53.5%) during 2014–2015. During 2014–2015, S100B protein was measured in 451 (79.4%) children within 6 h after mTBI. The proportion of CT scans and in-hospital observations significantly decreased between the two periods, from 14.4 to 9.5% (p=0.02) and 73.9–40.5% (p Conclusions The implementation of a modified PECARN rule including the S100B protein assay significantly decreased the proportion of CT scans and in-hospital observations for children with mTBI who were at intermediate risk for ciTBI.

Objective(s)To systematically assess the extent to which bone scintigraphy (BS) could improve the detection rate of skeletal injury in children suspected of physical abuse with an initial negative radiological skeletal survey (RSS).Study designWe searched MEDLINE and Web of Science for series of ≥20 children suspected of physical abuse who underwent RSS and add-on BS. We assessed the risk of bias and the heterogeneity and performed random-effects meta-analyses.ResultsAfter screening 1140 unique search results, we reviewed 51 full-text articles, and included 7 studies (783 children, mostly ≤3 years old). All studies were of either high or unclear risk of bias. Substantial heterogeneity was observed in meta-analyses. The summary detection rate of skeletal injury with RSS alone was 52% (95% CI 37 to 68). The summary absolute increase in detection rate with add-on BS was 10 percentage points (95% CI 6 to 15); the summary relative detection rate was 1.19 (95% CI 1.13 to 1.25); the summary number of children with a negative RSS who needed to undergo a BS to detect one additional child with skeletal injury (number needed to test) was 3 (95% CI 2 to 7).ConclusionsFrom the available evidence, add-on BS in young children suspected of physical abuse with a negative RSS might allow for a clinically significant improvement of the detection rate of children with skeletal injury, for a limited number of BS procedures required. The quality of the reviewed evidence was low, pointing to the need for high-quality studies in this field.

Aim We assessed the diagnostic accuracy of serum (1 → 3)-β-D-glucan (BDG) for neonatal invasive candidiasis (NIC) using the recommended cut-off usually used in adults for detecting invasive candidiasis and searched for an optimal cut-off for ruling out NIC. Methods We conducted a prospective cross-sectional study at Nantes University medical centre from January 2017 to July 2018. All consecutive newborn infants of less than 28 days of corrected age, with clinically suspected NIC, who underwent BDG assay, were included. Sensitivity and specificity were calculated by using the recommended cut-off of 80 pg/mL. Receiver operating characteristic curve analysis was used to identify an optimal cut-off value. Results We included 55 newborn infants with 61 episodes of suspected NIC. Their median gestational and chronological ages were 28.0 weeks (interquartile range [IQR] 26.4-34.1) and 10.0 days (IQR 6.0-22.0), respectively. Of 61 episodes, seven revealed NIC. Sensitivity and specificity were 85.7% (95% confidence interval [CI] 42.1%-99.6%) and 51.9% (37.8%-65.7%) with the recommended cut-off, respectively. An optimal cut-off of 174 pg/mL offered the same sensitivity but higher specificity 77.8% (64.4%-88.0%). Conclusion The recommended cut-off of 80 pg/mL was probably too low for ruling out NIC. A higher cut-off might have been more appropriate.

International audience; Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors of early-onset sepsis.Study design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of early-onset sepsis (born after preterm labor or preterm premature rupture of membranes, or from mother who had clinical chorioamnionitis or received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotics started at Day 0 or Day 1 of life, regardless of the duration and type of antibiotics. We compared treated and untreated patients by using inverse probability of treatment weighting based on estimated propensity score. Results: Among 648 very preterm infants at low risk of early-onset sepsis, 173 (26.2%) had early antibiotics treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR=1.04 [95%CI=0.72-1.50]). However, it was associated with higher odds of severe cerebral lesions (OR=2.71 [95%CI=1.25-5.86]) and moderate-to-severe bronchopulmonary dysplasia (OR=2.30 [95%CI=1.21-4.38]). Conclusion: Early empirical antibiotics administrated in very preterm infants at low risk of early-onset sepsis were associated with a higher risk of severe cerebral lesions and moderate-to-severe bronchopulmonary dysplasia.

Key Points Question Are clinical guidelines for the early detection and diagnostic workup of child physical abuse complete, clear, and consistent across high-income countries? Findings In this systematic review that included 20 clinical guidelines issued in 15 countries, guidelines were clear but incomplete and discrepant, particularly in the definition of sentinel injuries and in recommendations for exploratory laboratory testing and advanced imaging. Meaning This systematic review found a lack of standardized guidelines for the identification and management of child physical abuse, which may contribute to practice variation., This systematic review evaluates the completeness, clarity, and consistency of guidelines from high-income countries for the detection and diagnosis of child physical abuse., 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.

International audience

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.To study the prevalence, characteristics, and determinants of suboptimal care in the initial management of COSBIs.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.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.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.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.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.

Summary Introduction Heart failure (HF) in children is a severe condition which diagnosis can be difficult [1] , [2] . Aims We aimed at describing the incidence and outcome of new-onset HF with no know heart disease in the Loire-Atlantique area. Methods We conducted a retrospective monocentric observational study between 2007 and 2016. We included all children under 16 years old with no known heart disease and new-onset HF confirmed by echocardiography. Data collected for the DIACARD study were used. Results One hundred and seventy-four children had a diagnosis of heart disease based on signs of HF during the study period. The incidence of new-onset HF in children was 1.92 per 100,000 including 0.91 per 100,000 due to cardiomyopathies and myocarditis (CM). 120 children had analyzable data including 60 with congenital heart diseases (CHD) and 57 with CM. Median age at diagnosis was 8 days (interquartile range 1–20.3 days) in CHD and 3 months (interquartile range 1–26 months) in CM. Among CHD, coarctation of the aorta was the most frequent diagnosis (21 children, 35%) followed by left-to-right shunts (12 children, 20%). Among CM, dilated cardiomyopathy (DCM) including myocarditis was the most frequent diagnosis (49 children, 86%). Overall one-year mortality rate was 17%, one-year neuro-motor sequel rate was 18%. Conclusion More than half of the children with no known heart disease and new-onset HF are diagnosed with CHD. The incidence of CM in a French area is similar to the reported incidence in other industrialized countries [2] , [3] . Children diagnosed with HF signs have a high mortality rate.

Background Heart failure (HF) in children is a severe condition which diagnosis can be difficult. Time from first symptoms to diagnosis, called time to diagnosis (TTD) is related to prognosis in several diseases. Purpose The aim of this study was to measure TTD in children with new-onset HF and assess its consequences and determinants. The pediatric incidence of new-onset HF was determined. Methods A retrospective population-based observational study was conducted between 2007 and 2016 in a French tertiary care center. All children under 16 years old with no known heart disease and new-onset HF confirmed by echocardiography were included. Two junior doctors assessed TTD independently. With logistic regression used for outcomes and a Cox proportional-hazards model for determinants, analyses were stratified by HF etiology: congenital heart diseases (CHD) and cardiomyopathies/myocarditis (CM). Results A total of 174 children were included. Among them, 117 had CHD or CM with data on TTD (median age [interquartile range (IQR)] 25 days (6–146), 50.4% male, 60 CHD and 57 CM). Overall median (IQR) TTD was 3.3 days (1.0–21.2); it was 2.2 days (0.6–16.5) with CHD and 5.0 days (2.0–28.1) with CM. The frequency of 1-year mortality was 17% and 1-year neuromotor sequel 18%. Death at 1 year was associated with low birth weight for all children (adjusted odds ratio 0.24, 95% confidence interval [CI] 0.08–0.68) and TTD below the median with CM (0.09, 0.01–0.87). Short TTD was associated with clinical severity on the first day of symptoms for all children (adjusted hazard ratio 3.39, 95% CI 2.0–5.72), and young age with CM (0.09, 0.02–0.41). The incidence of new-onset HF in children was 2.07 per 100 000 including 0.98 per 100,000 due to CM. Conclusions In children with new-onset HF presenting in our region, median TTD was short and early serious signs were the main determinant of short TTD. Poor outcome was not associated with long TTD but with low birth weight.

IntroductionFever 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 analysisThis 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.DiscussionIf 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 disseminationThis 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 numberNCT03607162.

Context: The incidence of early-onset neonatal infection has greatly decreased, but a new diagnostic approach is needed to avoid over-diagnosis and -treatment. 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 3080 neonates included, one neonate presented certain infection and 38 neonates 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

Objectives To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution. Design Prospective, observational, population-based study from 2009 to 2014. Setting An administrative area accounting for 13% of the French pediatric population. Patients All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection. Interventions None. Measurements and main results The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period. Conclusions The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.

Background In a context of suboptimal vaccination coverage and increasing vaccine hesitancy, we aimed to study morbidity and mortality in children related to missing or incomplete meningococcal C and pneumococcal conjugate vaccines. Methods We conducted a prospective, observational, population-based study from 2009 to 2014 in a French administrative area that included all children from age 1 month to 16 years who died before admission or were admitted to an intensive care unit for a community-onset bacterial infection. Vaccine-preventable infection was defined as an infection with an identified serotype included in the national vaccine schedule at the time of infection and occurring in a non- or incompletely vaccinated child. Death and severe sequelae were studied at hospital discharge. Frequencies of vaccine-preventable morbidity and mortality caused by meningococcus and pneumococcus were calculated. Results Among the 124 children with serotyped meningococcal (n = 75) or pneumococcal (n = 49) severe infections included (median age 26 months), 20 (16%) died and 12 (10%) had severe sequelae. Vaccine-preventable infections accounted for 18/124 infections (15%, 95% CI 9, 22), 5/20 deaths (25%, 95% CI 9, 49), and 3/12 severe sequelae cases (25%, 95% CI 0, 54). The vaccine schedule for meningococcal C and pneumococcal conjugate vaccinations was incomplete for 71/116 (61%) children targeted by at least one of these two vaccination programs. Conclusions Mortality and morbidity rates related to vaccine-preventable meningococcal or pneumococcal infection could be reduced by one quarter with better implementation of immunisation programs. Such information could help enhance the perception of vaccine benefits and fight vaccine hesitancy.

Aim This study evaluated the epidemiology and performance of biomarkers for identifying bacterial infections in children who presented with fever without source. Methods We conducted a prospective cohort study in the paediatric department at the University Hospital of Nantes, France, in 2016. Children older than six days and younger than five years of age were included. Results A total of 1060 children (52.2% male) with fever without source were admitted, and the median age was 17 months (interquartile range: 6.6-24.3 months). Severe bacterial infections were diagnosed in 127 (11.9%) children and invasive bacterial infections in 11 (1.0%) children: four (0.3%) with bacterial meningitis and seven (0.6%) with bacteraemia. A further 114 (10.7%) had urinary tract infections. We explored the area under the receiver-operating characteristic curves for identifying invasive bacterial infections. The curves for procalcitonin and C-reactive protein assays were better than those for the absolute neutrophil counts and the white blood cell counts. Conclusion This study found that there was a low prevalence of invasive bacterial infections in children who presented with fever without source. It also showed that procalcitonin and C-reactive protein may help to detect invasive bacterial infections in children who have fever without source.

Objectifs Les MIN sont la premiere cause de mortalite en France chez les enfants de moins de 1 an. En 2015, sous l’impulsion de l’association des centres referents de la MIN (Ancremin) et le CHU de Nantes l’Observatoire national des Morts Inattendues du Nourrisson (OMIN) a ete cree. Il regroupe 35 des 37 centres de reference MIN (DROM inclus) francais. Les objectifs de l’OMIN sont de (1) creer une base de donnees standardisee, (2) denombrer de maniere exhaustive les cas de MIN en France et surveiller leur evolution dans le temps (donnees epidemiologiques), (3) d’identifier les mecanismes impliques dans les MIN, (4) d’identifier de nouveaux facteurs de risque et (5) de reunir un groupe d’experts multidisciplinaires pour coordonner et developper la recherche sur les MIN nationalement et internationalement. Pour identifier les causes du deces, la Haute-Autorite de sante (HAS) recommande un examen clinique complet, des examens biologiques, des examens radiologiques, une imagerie cerebrale ainsi que la proposition systematique d’une autopsie. Des resultats toxicologiques positifs peuvent etre evocateurs de maltraitance ainsi qu’etre un facteur participant a la MIN. L’objectif principal de l’etude etaient d’analyser la prevalence des analyses toxicologiques dans les morts inattendues du nourrisson (MIN). Les objectifs secondaires etaient de comparer les caracteristiques des enfants avec des resultats positifs (TOX + ) et negatifs (TOX-) ainsi que l’association de ces resultats avec des facteurs connus des MIN et le niveau socio-economique des parents. Methode Il s’agit d’une etude nationale retrospective observationnelle multicentrique realisee de 2015 a 2018 a partir des donnees de l’OMIN incluant les donnees de tous les enfants de moins de 2 ans pris en charge dans l’un des 35 centres de reference MIN (CRMIN). Les analyses toxicologiques etaient realisees sur le sang, les urines, le liquide gastrique, la bile et les cheveux avec racines (HAS 2007). Resultats Entre mai 2015 et decembre 2018, 624 MIN ont ete enregistrees dans l’OMIN. Des analyses toxicologiques ont ete realisees chez 398 enfants (62 %). Trente-six analyses (9 %) etaient positives pour des toxiques attendus (molecules de reanimation ou traitement habituel) (53 %) et pour des produits inattendus (47 %). Les matrices positives etaient le sang (32 %), le liquide gastrique (27 %), les cheveux (25 %) et les urines (21 %). Les molecules inattendues etaient les opiaces (n = 8), le cannabis (n = 4), la cocaine (n = 3), la cotinine (n = 2), le monoxyde de carbone (n = 2), la cafeine (n = 1), l’alcool (n = 1) et le GHB (n = 1). La distribution des patients TOX+ et TOX- etaient significativement differente. Les conditions socioeconomiques etaient plus souvent precaires dans le groupe TOX+. Ces memes enfants etaient moins souvent seuls dans le lit lors du deces et leur couchage plus souvent constate inadapte. L’examen du corps retrouvait une hygiene plus souvent decrite comme insuffisante. L’anamnese familiale retrouvait plus souvent un antecedent de prise de psychotropes ou de consommation de drogues illicites chez la mere. Conclusion Malgre les recommandations de la HAS, les analyses toxicologiques n’etaient pas realisees dans plus d’1/3 des cas. Pourtant, la prevalence de resultats toxicologiques positifs impose de rappeler le caractere systematique de ce type d’analyse lors d’une MIN. Les enfants TOX+ pour des molecules inattendues sont issus de milieux plus precaires et avec un historique de consommation de molecules sur prescription ou illicites. Les familles identifiees dans ces categories doivent etre mieux reperees en maternite et pourraient beneficier d’un programme de prevention avec un suivi regulier.

Many countries have observed an early and strong impact of implementation of the 13-valent pneumococcal conjugate vaccine (PCV13) on community-acquired pneumonia (CAP). High levels of C-reactive protein (CRP) and procalcitonin (PCT) are considered biomarkers of bacterial infection (particularly infection due to pneumococcus); therefore, PCV13 implementation should have different effectiveness on CAP depending on the levels of these two biomarkers. To demonstrate this assumption, we analyzed the evolution of number of CAP cases seen in pediatric emergency departments in France after PCV13 implementation (in 2010) by levels of these two biomarkers.From June 2009 to May 2015, 8 pediatric emergency units prospectively enrolled all children (1month to 15years) with radiologically confirmed CAP.A cohort of 9586 children with CAP was enrolled (median age 3years). CAP with pleural effusion (PE-CAP) and proven pneumococcal pneumonia (PP-CAP) accounted for 5.5% and 2.0% of cases. During the study period, the number of cases of overall CAP decreased by 25.4%, hospitalized CAP by 30.5%, PE-CAP by 63.4%, CAP with CRP level≥100mg/L by 50.9%, CAP with PCT level≥4ng/L by 60.4% and PP-CAP by 86.4%. We found no change in number of cases of CAP with low levels of CRP (20 or40mg/L) or PCT (0.5ng/mL). The number of cases of CAP overall increased (20.0%) in the last year of the study as compared with the preceeding year but not cases with CRP level≥100mg/L and/or PCT level≥4ng/mL.PCV13 implementation has had a strong impact on number of CAP cases with high levels of CRP and/or PCT in children but no impact on that with low levels of these two biomarkers. Five years after PCV13 implementation, a sustained reduction in CAP cases is observed.

The occurrence of meningitis in children5 years old may be associated with specific predisposing factors that can be anatomic, such as cerebrospinal fluid fistula or breach, or related to genetic susceptibility or N inborn or acquired immunologic defect. This study aimed to assess the anatomical and immunologic risk factors in children5 years old with pneumococcal meningitis and prospectively enrolled in the French national meningitis network.We analyzed all data for children who were 5-15 years old with a diagnosis of pneumococcal meningitis between 2001 and 2013. We describe the frequency and typology of the anatomic or immunologic risk factors, the clinical features and the pneumococcal serotypes.Among the 316 patients with pneumococcal meningitis, the mortality rate was 9.5% and 23.1% of cases presented complications (abscess, coma, hemodynamic failure, thrombophlebitis cerebral or deafness). In total, 108 children (34%) showed risk factors, the most frequent being anatomic: 70 cases (22.8%) were related to a cerebrospinal fluid breach or fistula and 55 (17.9%) to immunodeficiency, primary or acquired. Serotype data were available for 207 pneumococcal isolates (65.5%). The most frequent serotypes were as follows: 3, 18C, 19A and 19F between 2001 and 2009 and 19F, 3, 19A, 12F, 22F, 17F and 24F after 2009.We describe the largest cohort of children5 years old with pneumococcal meningitis. One third of the children had risk factors justifying a complete immunologic and radiologic work-up.

The concept of damage control in pediatrics: everything a physician needs to know in practice. After the terrorist attacks in France and the rest of the world, children may be potential targets and be part of the victims. In order to prepare for these situations of «war medicine» our medical training is inadequate. It seems important to draw attention to the care strategy to adopt in these exceptional situations: the concept of «damage control resuscitation» from military experience in conflict zones aims to reduce preventable deaths, using simple and quick gestures. In practice, the goal is to control bleeding sites and to fight against the lethal triad of hypothermia, acidosis and coagulopathy to bring the patient to a minimalist rescue surgery in one hour. The success of this overall strategy depends on effective communication and coordination between pre-hospital teams on site and hospital teams with the sole objective: patient survival by prioritizing medical care and evacuations. Although the experience of damage control is limited in pediatrics, its principles can be applied to the child taking into account the particularities of its own physiology. It seems essential today for every physician, single witness or real frontline actor, to be familiar with these first aid techniques that could save children's lives.Le concept de « damage control » en pédiatrie : tout ce qu’un médecin doit savoir en pratique. Au vu des attentats terroristes qui ont frappé la France, les enfants peuvent aussi constituer des cibles potentielles et figurer au nombre des victimes. Devant ces situations apparentées à de la « médecine de guerre » face auxquelles nos formations de médecin ne nous ont pas préparés, il nous semble important d’attirer l’attention sur la stratégie à adopter pour la prise en charge des enfants. Le concept de « damage control » issu de l’expérience militaire en zones de conflits a pour objectif de limiter les décès évitables en utilisant des gestes simples et rapides. En pratique, il s’agit de contrôler les sites hémorragiques et de lutter contre la triade létale : hypothermie, acidose, coagulopathie, pour amener le patient à une chirurgie minimaliste de sauvetage dans l’heure. La réussite de cette stratégie globale est conditionnée par une communication et une coordination efficaces entre les équipes préhospitalières sur place et les équipes hospitalières, avec pour seul objectif la survie des patients, en priorisant soins et évacuation. Même si l’expérience du « damage control » est limitée en pédiatrie, ses grands principes peuvent être appliqués à l’enfant en tenant compte des particularités liées à sa physiologie propre. Il semble indispensable aujourd’hui que chaque médecin, simple témoin ou véritable acteur de première ligne, connaissent les gestes de sauvetage des premières minutes susceptibles de sauver la vie d’enfants.

Misuse of antibiotics is largely responsible for the emergence of bacterial resistance. Children represent a subset of the population who frequently receive antibiotics. The objectives were to calculate the frequency of antibiotic prescriptions that do not comply with best practice recommendations in paediatrics primary care and to examine the thoughts and feelings of physicians and parents about antibiotic prescription and recommendations from the national health authorities. We included children admitted at the paediatric emergency room (PER) of the NANTES university hospital between June 2011 and October 2012 and who were under antibiotic drugs. Two independent experts evaluated the compliance with the national recommendations. Parents and general practitioner (GP) who prescribed the antibiotic before admission to PER were called to collect their thoughts and feeling about antibiotic prescription. The median age of the 88 included children was 2.8 years. The upper respiratory tract infection motivated the prescription of antibiotic in 59%. Seventy-six per cent of the prescriptions analysed were inappropriate, 72% of the antibiotics had a too broad spectrum, and one-third was not indicated. Ninety-one per cent of the interviewed parents thought that the antibiotic prescribed to their child was adequate. Among the 77 prescribing GP who were called, 33% agreed that they lacked time during consultation to explain to parents that no antibiotics were required. Antibiotic prescriptions were too often inadequate in this sample of children admitted in a French PER. Efforts have to be made with physicians and general public to optimize the antibiotic drug use.

RESUME L’infection neonatale precoce (INP) reste une preoccupation majeure dans les pays en voie de developpement comme dans les pays industrialises. Parce qu’aucun element clinique ni marqueur biologique n’est assez sensible, ni specifique pour permettre a lui seul d’etablir le diagnostic, la prise en charge repose sur un faisceau d’arguments cliniques et biologiques et expose de nombreux nouveau-nes a des examens complementaires et antibiotherapies neonatales dont les effets deleteres sont aujourd’hui etablis (emergence de bacteries multi resistantes, perturbations du microbiote impliquees dans la survenues de pathologies ulterieures). Alors que la prevalence des infections neonatales precoces a diminue depuis la generalisation de l’antibioprophylaxie per-natale, l’evidence s’impose d’adapter notre strategie medicale a ces modifications epidemiologiques recentes. Une approche basee sur un fort niveau de preuve scientifique, combinant des donnees d’anamnese, cliniques et de biologie comme la procalcitonine semble a ce jour la meilleure strategie pour distinguer la population des nouveau-nes a tres faible risque infectieux de celle a fort risque et limiter ainsi les indications d’antibiotherapie neonatale.

International audience; Objective: To study recent epidemiologic trends of sudden unexpected death in infancy (SUDI) in Western Europe. Study design: Annual national statistics of death causes for 14 Western European countries from 2005 to 2015 were analyzed. SUDI cases were defined as infants younger than 1 year with the underlying cause of death classified as “sudden infant death syndrome,” “unknown/unattended/unspecified cause,” or “accidental threats to breathing.” Poisson regression models were used to study temporal trends of SUDI rates and source of variation. Results: From 2005 to 2015, SUDI accounted for 15 617 deaths, for an SUDI rate of 34.9 per 100 000 live births. SUDI was the second most common cause of death after the neonatal period (22.2%) except in Belgium, Finland, France, and the UK, where it ranked first. The overall SUDI rate significantly decreased from 40.2 to 29.9 per 100 000, with a significant rate reduction experienced for 6 countries, no significant evolution for 7 countries, and a significant increase for Denmark. The sudden infant death syndrome/SUDI ratio was 56.7%, with a significant decrease from 64.9% to 49.7% during the study period, and ranged from 6.1% in Portugal to 97.8% in Ireland. We observed between-country variations in SUDI and sudden infant death syndrome sex ratios. Conclusions: In studied countries, SUDI decreased during the study period but remained a major cause of infant deaths, with marked between-country variations in rates, trends, and components. Standardization is needed to allow for comparing data to improve the implementation of risk-reduction strategies.

Duchenne muscular dystrophy (DMD) has as standard pharmacological therapy with corticoisteroids (CS) that decrease inflammation and immune responses present in patients and animal models. CS have however limited efficacy and important and numerous side effects. Therefore, there is a need for new anti-inflammatory and pro-tolerogenic treatments that could replace or decrease doses of CS. We first assessed the status of immune system of dystrophin-deficient rats (Dmdmdx) that closely reproduce the phenotype of DMD patients. Dmdmdx rats showed increased leukocyte infiltration in skeletal and cardiac muscles, containing mostly macrophages but also T cells, and increased expression of several cytokines. Anti-CD45RC Monoclonal antibody (Mab) treatment induced immune tolerance in models of organ transplantation and GVHD (Graft Versus Host Disease). We observed that muscles and blood of DMD patients contained T CD4+ and CD8+ expressing high levels of CD45RChigh cells. Treatment of young Dmdmdx rats with anti-CD45RC MAb corrected skeletal muscle strength associated to a depletion of effectors CD45RChigh T cells with no obvious side-effects. Prednisolone treatment of Dmdmdx rats similarly increased skeletal muscle strength and was also associated to a depletion of effectors CD45RChigh cells but resulted in severe weight loss.Overall, Dmdmdx rats display important immune inflammatory response and thus represent a useful model to analyze new anti-inflammatory and tolerogenic treatments for DMD. As an example, a new treatment with anti-CD45RC antibodies improved muscle strength in Dmdmdx rats as prednisolone did but without side effects. Anti-CD45RC therapy could complement other therapies in DMD patients.