Impact of COVID-19 Pandemic Interventions on Sudden Unexpected Death in Infancy Incidence in France.

OBJECTIVE: To study the impact of non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic on the monthly incidence of sudden unexpected death in infancy (SUDI) cases overall and those with a viral or bacterial identification. STUDY DESIGN: We conducted an interrupted time-series analysis using seasonally adjusted Poisson regression models from the French national prospective and multicenter SUDI registry, that included all SUDI cases under age one year who died from 2016 to 2021 in mainland France. RESULTS: Of 998 SUDI cases analyzed, 750 were recorded during the pre-pandemic period (January 2016 through March 2020) and 248 during the NPI period (April 2020 through December 2021). We found a significant seasonal pattern of overall monthly SUDI incidence, with a peak observed periodically from November to February. The monthly SUDI incidence decreased significantly from the pre-pandemic to NPI periods (adjusted incidence rate ratio 0.83 [95% confidence interval 0·72-0·96]). In particular, the monthly incidence of SUDI cases with a viral or bacterial identification decreased, while no significant difference was found for SUDI cases without a viral or bacterial identification. CONCLUSION: NPIs were associated with a significant change in the incidence of SUDI cases with a viral or bacterial identification. Further investigations are needed to analyze the pathophysiologic role of viruses and bacteria in the SUDI.

Impact of respiratory pathogens detection by a rapid multiplex polymerase chain reaction assay on the management of community-acquired pneumonia for children at the paediatric emergency department. A randomized controlled trial, the Optimization of Pneumonia Acute Care (OPTIPAC) study.

OBJECTIVES: The pathogen of community-acquired pneumonia (CAP) in children is typically uncertain during initial treatment, leading to systematic empiric antibiotic use. This study investigates if having rapid multiplex PCR results in the emergency department (ED) improves empiric treatment. METHODS: OPTIPAC, a French multicentre study (2016-2018), enrolled patients consulting for CAP at the paediatric ED in 11 centres. Patients were randomized to either receive a multiplex PCR test plus usual care or usual care alone and followed for 15 days. The primary outcome was the appropriateness of initial antimicrobial management, determined by a blinded committee. RESULTS: Of the 499 randomized patients, 248 were tested with the multiplex PCR. Appropriateness of the antibiotic treatment was higher in the PCR group (168/245, 68.6% vs. 120/249, 48.2%; Relative risk 1.42 [1.22-1.66]; p < 0.0001), chiefly by reducing unnecessary antibiotics in viral pneumonia (RR 3.29 [2.20-4.90]). No adverse events were identified. DISCUSSION: The multiplex PCR assay result at the ED improves paediatric CAP's antimicrobial stewardship, by both reducing antibiotic prescriptions and enhancing treatment appropriateness.

[Consensus update of the POPI tool]. / Mise à jour par consensus de l'outil POPI.

Medication errors are one of the causes of iatrogenic medication use in children. The POPI tool for detecting inappropriate drug prescriptions and prescription omissions in paediatrics was the first tool to be published in this field in 2014. Our aim was to update the POPI tool for French use based on current recommendations and practice. Criteria were removed, updated or added based on recommendations from learned societies and national bodies. The two-round Delphi method was used to reach a consensus of experts. The level of agreement of the healthcare professionals' proposals was rated on a 9-point Likert scale. In the first round, only proposals with a median agreement of 7 to 9 and an agreement of more than 65% were retained. In the second round, only those with a median agreement of 7 to 9 and over 75% agreement were retained. The POPI tool now includes eight categories (various, infectiology, gastroenterology, pneumonology, dermatology, neurology/pedopsychiatry, haematology and excipients). All the criteria were supported by bibliographical references. They were submitted to 20 French healthcare professionals: 9 pharmacists and 11 doctors (17 hospital-based and 3 self-employed). After two rounds of Delphi testing, 166 criteria were retained and validated (111 inappropriate prescriptions and 55 omissions). In conclusion, this study made it possible to update the POPI tool, which is still available for assessing paediatric prescriptions.

Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study.

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.

Inconsistency Between Pictures on Baby Diaper Packaging in Europe and Safe Infant Sleep Recommendations.

OBJECTIVE: To describe the level of inconsistency between pictures on baby diaper packaging and safe infant sleep recommendations (SISRs) in Europe. STUDY DESIGN: We attempted to identify all packaging of baby diapers sold in 11 European countries for infants weighing less than 5 kg through internet searches from July 2022 through February 2023. For each type of package, we extracted whether there was a picture depicting a baby, whether the baby was sleeping, and whether the picture of the sleeping baby was inconsistent with ≥1 of 3 SISRs: (i) nonsupine sleeping position, (ii) soft objects or loose bedding, or (iii) sharing a sleep surface with another person. Data were aggregated at the country level, and a random-effects meta-analysis of proportions was used to obtain summary estimates. The outcome was the summary estimate of the proportion of pictures that were inconsistent with SISRs. RESULTS: We identified 631 baby diaper packaging types of which 49% (95% CI: 42-57; n = 311) displayed a picture of a sleeping baby. Among those 311 packages, 79% (95% CI 73-84) were inconsistent with ≥1 SISR, including a nonsupine sleeping position, 45% (95% CI 39-51), soft objects or loose bedding such as pillows or blankets, 51% (95% CI 46-57), and sharing a sleep surface with another person, 10% (95% CI 4-18). CONCLUSIONS: Pictures on baby diaper packaging in Europe are often inconsistent with SISRs. The prevention of sudden unexpected death in infancy requires action from manufacturers and legislators to stop parents' exposure to misleading images that may lead to dangerous practices.

Distribution, Consequences, and Determinants of Time to Antibiotics in Children With Community-Onset Severe Bacterial Infection: A Secondary Analysis of a Prospective Population-Based Study.

OBJECTIVES: To describe the distribution, consequences and potential determinants of time to antibiotics administration in children with community-onset severe bacterial infections (COSBIs). DESIGN: Secondary analysis of the available data from a prospective population-based study from 2009 to 2014. SETTING: An administrative area in western France accounting for 13% of the national pediatric population. PATIENTS: All children from 1 month to 16 years old admitted to a PICU or who died before admission and had a COSBI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The time to antibiotics was divided into patient interval (from first signs of COSBI to the first medical consultation) and medical interval (from the first consultation to appropriate antibiotics administration). The association between the medical interval and child outcome was studied by a multinomial logistic regression model and the potential determinants of the patient and medical intervals were by a Cox proportional-hazards model. Of the 227 children included (median age 2.1 yr), 22 died (9.7%), and 21 (9.3%) had severe sequelae at PICU discharge. Median patient and medical intervals were 7.0 hours (interquartile range [IQR], 2.0-16.5 hr) and 3.3 hours (IQR, 1.1-12.2 hr), respectively. The last quartile of medical interval was not associated with death (adjusted odds ratio [aOR], 3.7; 95% CI, 0.8-17.5) or survival with severe sequelae (aOR, 1.3; 95% CI, 0.4-4.0) versus survival without severe sequelae. Patient interval was shorter in younger children (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.92-0.99), and medical interval was reduced when the first consultation was conducted in a hospital (aHR, 1.5; 95% CI, 1.1-2.0) versus outpatient medicine. CONCLUSIONS: For children with COSBI, we found no significant association between medical interval and mortality or severe sequelae. An initial hospital referral could help reduce the time to antibiotics in COSBIs.

Extent of the protection afforded by histo-blood group polymorphism against rotavirus gastroenteritis in metropolitan France and French Guiana.

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.

Suboptimal care was frequent in severe child physical abuse cases and was mainly related to delayed diagnoses and ineffective secondary prevention.

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.

Sudden Unexpected Death in Infancy: Current Practices in Virological Investigations and Documentation in the French Registry.

OBJECTIVE: To describe pre-COVID-19 pandemic current practices in virological investigations, including type, frequency of samplings, and documented viruses, in sudden unexpected death in infancy (SUDI) and to compare results according to the cause of death. STUDY DESIGN: Between May 2015 and December 2019, infants under 2 years of age included in the French SUDI registry were classified in one of 4 groups by causes of death according to the classification by Goldstein et al. : unexplained (SIDS), infectious, explained but noninfectious, and undetermined. Sampling sites and viruses detected were described, and then SIDS and explained deaths (control group) were compared. RESULTS: Among 639 infants, 3.6% died of an established viral infection. From 23 sampling sites and 2238 samples, 19 virus species were detected. Overall, 43.3% of infants carried a virus, with no significant difference between SIDS infants and the control group (P = .06). We found wide variations in frequencies of samples by site (550 for nasopharynx to one for saliva). The highest positivity rate was from the nasopharynx (195/2238; 8.7%). Rhinovirus was the predominant virus detected (135/504; 26.8%), mostly in SIDS (83/254; 32.7%). We found no significant difference between positivity rates and distribution of viruses between the SIDS and control groups. At-autopsy virological analysis never contributed to determining the cause of death. CONCLUSION: Current practices in virological investigations in SUDI are heterogeneous, with wide variability despite published guidelines. Investigations should be limited to the most relevant sites, and systematic at-autopsy sampling should be reconsidered. We found no association between virus detection and SIDS.

Non-immunization associated with increased risk of sudden unexpected death in infancy: A national case-control study.

OBJECTIVE: 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). STUDY DESIGN: 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. RESULTS: 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]). CONCLUSIONS: 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.

Postpartum Depression after Maternal Isolation during the COVID-19 Pandemic: The MUMI-19 Study (Mothers Undergoing Mental Impact of COVID-19 Pandemic).

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.

Prevalence, Characteristics, and Determinants of Suboptimal Care in the Initial Management of Community-Onset Severe Bacterial Infections in Children.

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.

The Ogival Palate: A New Risk Marker of Sudden Unexpected Death in Infancy?

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.

Shift in Clinical Profile of Hospitalized Pneumonia in Children in the Non-pharmaceutical Interventions Period During the COVID-19 Pandemic: A Prospective Multicenter Study.

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.

A very low prevalence of SARS-CoV-2 infection but a high prevalence of other respiratory virus infections in children admitted to paediatric emergency departments.

AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Antibiotic prophylaxis in preterm premature rupture of membranes at 24-31 weeks' gestation: Perinatal and 2-year outcomes in the EPIPAGE-2 cohort.

OBJECTIVE: To compare different antibiotic prophylaxis administered after preterm premature rupture of membranes to determine whether any were associated with differences in obstetric and/or neonatal outcomes and/or neurodevelopmental outcomes at 2 years of corrected age. DESIGN: Prospective, nationwide, population-based EPIPAGE-2 cohort study of preterm infants. SETTING: France, 2011. SAMPLE: We included 492 women with a singleton pregnancy and a diagnosis of preterm premature rupture of membranes at 24-31 weeks. Exclusion criteria were contraindication to expectant management or indication for antibiotic therapy other than preterm premature rupture of membranes. Antibiotic prophylaxis was categorised as amoxicillin (n = 345), macrolide (n = 30), third-generation cephalosporin (n = 45) or any combinations covering Streptococcus agalactiae and >90% of Escherichia coli (n = 72), initiated within 24 hours after preterm premature rupture of membranes. METHODS: Population-averaged robust Poisson models. MAIN OUTCOME MEASURES: Survival at discharge without severe neonatal morbidity, 2-year neurodevelopment. RESULTS: With amoxicillin, macrolide, third-generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third-generation cephalosporin or any E. coli-targeting combinations was associated with improved survival without severe morbidity (adjusted risk ratio 1.25 [95% confidence interval 1.08-1.45] and 1.10 [95 % confidence interval 1.01-1.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen. CONCLUSION: In preterm premature rupture of membranes at 24-31 weeks, antibiotic prophylaxis based on third-generation cephalosporin may be associated with improved survival without severe neonatal morbidity when compared with amoxicillin, with no evidence of increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen. TWEETABLE ABSTRACT: Antibiotic prophylaxis after PPROM at 24-31 weeks: 3rd-generation cephalosporins associated with improved neonatal outcomes.

Variations in Guidelines for Diagnosis of Child Physical Abuse in High-Income Countries: A Systematic Review.

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.

Executive functions and quality of life in children with neurofibromatosis type 1.

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.