Impact of prenatal estimation of the risk of respiratory distress in neonates with congenital pulmonary malformations on the choice of delivery site.

BACKGROUND: The vast majority of prenatally diagnosed congenital pulmonary malformations (CPM) remain asymptomatic at birth. The maximal value of the CPM volume ratio (CVRmax) predicts the risk of neonatal respiratory distress (NRD), and should allow for better assessment of the level of expertise needed at the delivery site. AIM: This study evaluated the level of maternity units currently chosen for the delivery of CPMs, and determined the impact of the choice of delivery site based on the CVRmax, with a threshold of 0.4 cm2. METHODS: Data were extracted from the French prospective MALFPULM cohort, with inclusion between March 2015 and June 2018. RESULTS: The final study population consisted of 383 women. Deliveries in level 1 or 2 maternity units (n = 98, 25%) involved CPMs with lower CVRmax (p<0.001), causing fewer signs of prenatal compression (p = 0.025). Among the 62 children (16%) who presented with NRD, only seven (11%) were born in level 1 or 2 units (p = 0.0078). Choosing the maternity level according to the CVRmax would have increased the number of births in level 1 or 2 maternity hospitals by 70%. In these maternity units, the percentage of children with NRD would have increased from 8% in the actual distribution to 10% in the new strategy. CONCLUSION: Our results showed an overuse of level 3 maternity hospitals for the delivery of newborns with a prenatal diagnosis of CPM. The use of CVRmax should enable a reduction in the use of expertise centers without an adverse impact on newborns.

Pediatric hospital care organization: Cross-sectional enquiry in four regions in France.

OBJECTIVE: The aim of this study was to characterize conventional pediatric care capacities in French public hospitals and identify the main difficulties in guiding upcoming health policies. The secondary objective was to assess the quality of care by the implementation of the European Charter of the Rights of Children in Hospital. METHOD: Multicenter cross-sectional study using a questionnaire survey sent by e-mail to the heads of conventional pediatric departments in four French regions identified on the French Hospital Federation's website. The survey was conducted between 25 September and 25 October 2018. RESULTS: Fifty-six of 113 heads of departments participated in the survey. The mean annual number of admissions per unit in 2017 was 2066 (SD, 1433), with a median length of stay of 2.7 days (range, 1-10). Children were admitted up to age 18 years in 76% of the departments, and 83% of the departments had an individualized pediatric emergency department. The nurse care load was very high, specifically during the night shift (9.5 patients/nurse). Inpatient education and academic teaching were unavailable in 38% of the departments. Overall, 89% of department heads declared knowing the European Charter of the Rights of Children in Hospital, and a copy of it was posted in all units in 57% (95% confidence interval, 44-70) of the services/departments. At all times and in all departments, parents were allowed to be with their children, and for 34% (95% CI, 21-47) of the departments, an accommodation for parents was available close to the hospital. CONCLUSION: Public hospital pediatric departments lack sufficient medical and nonmedical caregivers. Department heads were well aware of the European Charter, and it was well disseminated but should be updated to address today's challenges in pediatrics. An area of improvement would be to include parents in their child's care more effectively.

Respiratory morbidity in children with congenital heart disease.

OBJECTIVE: To evaluate the respiratory outcome in children with congenital heart disease (CHD), considering recent management procedures and the CHD pathophysiology. DESIGN AND SETTING: Clinical and functional respiratory outcome were evaluated in 8-year-old children with isolated CHD followed up from birth in the prospective population-based EPICARD cohort. PATIENTS: Children were assigned to two groups, based on the pathophysiology of the CHD: CHDs with left-to-right shunt (n = 212) and CHDs with right outflow tract obstruction (n = 113). RESULTS: Current wheezing episodes were observed in 15% of the children with isolated CHD and left-to-right shunt, and 11% of the children with isolated CHD and right outflow tract obstruction (not significant). Total lung capacity (TLC) was the only respiratory function parameter that significantly differed between the two groups. It was lower in children with left-to-right shunt (88.72 ± 0.65% predicted) than in those with right outflow tract obstruction (91.84 ± 0.96, p = 0.006). In multivariate analysis, CHD with left-to-right shunt (coeff. [95% CI]: -3.17 [-5.45; -0.89]) and surgery before the age of 2 months (-6.52 [-10.90; -2.15]) were identified as independent factors associated with significantly lower TLC values. CONCLUSION: Lower TLC remains a long-term complication in CHD, particularly in cases with left-to-right shunt and in patients requiring early repair. These findings suggest that an increase in pulmonary blood flow may directly impair lung development.

French pediatricians' views on industry-sponsored clinical trials: Toward stronger research on ethics?

INTRODUCTION: There is a crucial need to perform clinical trials in pediatrics due to an increased prescription rate of unapproved drugs. Since pediatricians are the gatekeepers of clinical trials, the primary objective of the current study was to evaluate, for the first time in France, pediatricians' views on performing clinical trials. The second objective was to identify the factors that influence their perceptions. MATERIAL AND METHODS: In 2017, pediatricians who were members of the French Pediatric Society completed an online survey comprising 27 questions. Fisher's exact test was performed to evaluate possible correlations between pediatrician characteristics (age, sex, parenthood, professional experience, status, type of practice, previous participation in clinical trials, ethics education) and personal views on clinical trials. A value of P≤0.001 was considered statistically significant. RESULTS: Overall, 207 pediatricians completed the questionnaire. Almost all participants (96.6%) were in favor of performing clinical trials. Pediatricians with teaching experience at university hospitals were more reluctant to propose children's participation in clinical trials for fear of increasing parental stress (P<0.001), or the occurrence of serious adverse reactions (P<0.001). Pediatricians with coordinator or investigator experience considered that one of the ethical drifts in pediatric clinical trials is the risk of child exploitation (P<0.001). CONCLUSION: Our findings suggest a favorable position of pediatricians concerning clinical trials, despite numerous concerns. Another outcome is the need to create an educational system of research in ethics in France dedicated to pediatricians in order to guarantee good clinical practice in research.

Reopening schools in the context of increasing COVID-19 community transmission: The French experience.

BACKGROUND AND OBJECTIVES: The role of schools in the spread of SARS-CoV-2 infections in the community is still controversial. The objective of our study was to describe the epidemiology of SARS-CoV-2 infections in different pediatric age groups during the first 2 months of the fall back-to-school period, in the context of increasing viral transmission in France. METHODS: Weekly epidemiological data provided by Santé Publique France and the Ministry of National Education were analyzed according to the age groups defined by the different school levels. Weeks (W) 34-42 were considered for analysis. RESULTS: The PCR positivity rate and incidence rate increased in all age groups during the study period, in an age-dependent manner. At W42, with adults being considered as reference, the risk ratio for a positive PCR test was 0.46 [95% CI: 0.44-0.49] and 0.69 [0.68-0.70] for children aged 0-5 years and 6-17 years, respectively. Similarly, the incidence rate ratio was 0.09 [0.08-0.09], 0.31 [0.30-0.32], 0.64 [0.63-0.66], and 1.07 [1.05-1.10] for children aged 0-5 years, 6-10 years, 11-14 years, and 15-17 years, respectively. Children and adolescents accounted for 1.9% of the newly hospitalized patients between W34 and W42, and for 1.3% of new intensive care admissions. No death was observed. Among infected children and adolescents, the percentage of asymptomatic individuals was 57% at W34 and 48% at W42. The number of schools closed remained low, less than 1% throughout the study period. The number of confirmed cases among school staff was consistent with the data measured in the general population. CONCLUSION: In the context of increasing viral transmission in the population, the spread among children and adolescents remained lower than that observed among adults, despite keeping schools open. However, the impact was age-dependent, with data in high schools close to those observed in adults.

COVID-19 and schools. Guidelines of the French Pediatric Society.

The educational and social benefits provided by school far outweigh the risks of a possible COVID-19 contamination of children in school environments or in daycare centers. Following summer break, the back-to-school period in France is taking place in the context of an increasing viral spread and requires strict adherence to health measures to limit the risk of outbreaks in communities. Based on a critical update of the role of children in the transmission of the infection, and of children's susceptibility to infection, the French Pediatric Society published practical guidelines for school re-entry and the management of COVID-19 infections in schools.

Tuberculosis contact investigation and short-course preventive therapy among young children in Africa.

SETTING: The largest cities in Benin, Burkina Faso, Cameroon and Central African Republic.OBJECTIVE: To demonstrate the feasibility and document the effectiveness of household contact investigation and preventive therapy in resource-limited settings.DESIGN: Children under 5 years living at home with adults with bacteriologically confirmed pulmonary tuberculosis (TB) were screened using questionnaire, clinical examination, tuberculin skin test and chest X-ray. Children free of active TB were offered preventive treatment with a 3-month rifampicin-isoniazid (3RH) or 6-month isoniazid (6H) regimen in Benin. Children were followed-up monthly during treatment, then quarterly over 1 year. Costs of transportation, phone contacts and chest X-rays were covered.RESULTS: A total of 1965 children were enrolled, of whom 56 (2.8%) had prevalent TB at inclusion. Among the 1909 children free of TB, 1745 (91%) started preventive therapy, 1642 (94%) of whom completed treatment. Mild adverse reactions, mostly gastrointestinal, were reported in 2% of children. One case of incident TB, possibly due to a late TB infection, was reported after completing the 3RH regimen.CONCLUSION: Contact investigation and preventive therapy were successfully implemented in these resource-limited urban settings in programmatic conditions with few additional resources. The 3RH regimen is a valuable alternative to 6H for preventing TB.

New insights on congenital pulmonary airways malformations revealed by proteomic analyses.

BACKGROUND: Congenital Pulmonary Airway Malformation (CPAM) has an estimated prevalence between 0.87 and 1.02/10,000 live births and little is know about their pathogenesis. To improve our knowledge on these rare malformations, we analyzed the cellular origin of the two most frequent CPAM, CPAM types 1 and 2, and compared these malformations with adjacent healthy lung and human fetal lungs. METHODS: We prospectively enrolled 21 infants undergoing surgical resection for CPAM. Human fetal lung samples were collected after termination of pregnancy. Immunohistochemistry and proteomic analysis were performed on laser microdissected samples. RESULTS: CPAM 1 and 2 express mostly bronchial markers, such as cytokeratin 17 (Krt17) or α-smooth muscle actin (ACTA 2). CPAM 1 also expresses alveolar type II epithelial cell markers (SPC). Proteomic analysis on microlaser dissected epithelium confirmed these results and showed distinct protein profiles, CPAM 1 being more heterogeneous and displaying some similarities with fetal bronchi. CONCLUSION: This study provides new insights in CPAM etiology, showing clear distinction between CPAM types 1 and 2, by immunohistochemistry and proteomics. This suggests that CPAM 1 and CPAM 2 might occur at different stages of lung branching. Finally, the comparison between fetal lung structures and CPAMs shows clearly different protein profiles, thereby arguing against a developmental arrest in a localized part of the lung.

Prenatal natural history of congenital pulmonary malformations: MALFPULM population-based cohort study.

OBJECTIVES: To assess prenatal changes in the volume of congenital pulmonary malformations (CPM) and examine whether these changes differ in lesions that appear cystic on ultrasound compared with hyperechoic lesions, and to study the relationship between CPM volume and risk of fetal compression. METHODS: We conducted a nationally representative, multicenter, prospective cohort study, which included 579 ultrasound examinations in 176 pregnant women with a diagnosis of fetal CPM, between March 2015 and November 2016. Several ultrasound examinations were performed between diagnosis and delivery, including measurement of CPM volume. We modeled changes in CPM volume ratio (CVR) as a function of gestational age, overall and for cystic/mixed vs hyperechoic malformations, and examined the association between CVR and signs of compression during pregnancy. RESULTS: When modeling CVR changes over time, there was a statistically significant decrease in CVR with increasing gestational age (P < 0.001), but the pattern of change differed according to CPM phenotype at first ultrasound examination: cystic/mixed CPM were characterized by a monotonic decrease in CVR with increasing gestational age (P = 0.002), whereas hyperechoic CPM showed an initial increase in CVR up to 27 weeks of gestation, followed by a decrease thereafter (P < 0.001). Peak CVR values were predicted as early as 21-22 weeks for cystic/mixed CPMs compared with 25-26 weeks for hyperechoic malformations. Regardless of CPM phenotype, fetuses that showed no sign of compression at any point had substantially lower CVR at first CVR measurement, and the CVR remained relatively constant thereafter. Among the subpopulation of fetuses with no sign of compression at first CVR measurement, the odds of a subsequent compression was 7-fold higher (adjusted odds ratio, 7.0; 95% CI, 1.6-29.9) if initial CVR was > 0.4 vs CVR ≤ 0.4 cm2 . CONCLUSIONS: Predicted changes in CVR during pregnancy differ between cystic and hyperechoic malformations. This may be the result of different pathophysiological mechanisms or differences in the timing of occurrence of these different types of CPM. CVR measured at the initial diagnostic ultrasound examination was strongly associated with the odds of subsequent compression. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Potentially preventable tuberculosis cases in children exposed to a contaminant case.

Early screening is recommended in children exposed to a contagious case of tuberculosis (TB), to prevent rapid progression to active TB. The aim of this study was to evaluate the percentage of potentially preventable cases of pediatric TB stemming from inadequate screening. The data gathered on children aged 0 to 10 years, who were evaluated by the Paris Center for TB Control (CLAT75) between January 2009 and December 2013, were extracted and retrospectively analyzed. French National Guidelines for screening were used as reference. During the study period, 1232 children 0-10 years were screened, because of a known exposure to an index case, including 124 (10%) with criteria for latent tuberculosis infection (LTBI) and 26 (2%) with active TB. Twelve additional cases of TB were reported, diagnosed based on symptoms or systematic exams. As a whole, 68% of pediatric TB cases were diagnosed at screening around an adult index case, highlighting the quality of the screening network. Among the 38 TB cases, 19 (50%) had a missed opportunity for potential prevention, due to the absence of screening despite a known contaminant (n=2) or to screening not in compliance with current recommendations (n=17). Delayed first evaluation was the most frequent error of the screening procedures. In conclusion, despite the quality of the screening network set up in Paris, half of the pediatric TB cases in this study did not undergo the recommended screening procedures. A significant reduction in the number of pediatric TB cases can be expected through the optimization of screening networks.

Value of chest X-ray in TB diagnosis in HIV-infected children living in resource-limited countries: the ANRS 12229-PAANTHER 01 study.

OBJECTIVE: To evaluate inter-reader agreement and diagnostic accuracy of chest radiography (CXR) in the diagnosis of tuberculosis (TB) in children with human immunodeficiency virus (HIV) infection. DESIGN: HIV-infected children with clinically suspected TB were enrolled in a prospective study conducted in Burkina Faso, Cambodia, Cameroon and Viet Nam from April 2010 to December 2014. Three readers-a local radiologist, a paediatric pulmonologist and a paediatric radiologist-independently reviewed the CXRs. Inter-reader agreement was then assessed using the κ coefficient. Diagnostic accuracy of CXR was assessed in culture-confirmed cases and controls. RESULTS: A total of 403 children (median age 7.3 years, interquartile range 3.5-9.7; 49.6% males) were enrolled. Inter-reader agreement was as follows: between local radiologist and paediatric pulmonologist, κ = 0.36 (95%CI 0.27-0.45); local radiologist and paediatric radiologist, κ = 0.16 (95%CI 0.08-0.24); and paediatric pulmonologist and paediatric radiologist, κ = 0.30 (95%CI 0.21-0.40). Among 51 cases and 151 controls, after a consensus, CXR had a sensitivity of 71.4% (95%CI 58.8-84.1) and a specificity of 50.0% (95%CI 41.9-58.1). Alveolar opacities and enlarged lymph nodes on CXR had limited specificity for TB (64.7% and 70.2%, respectively). Miliary and/or nodular opacities patterns on CXR were more specific to TB (specificity 94.3%). CONCLUSION: CXR showed poor-to-fair inter-reader agreement and limited diagnostic accuracy for TB in HIV-infected children, likely due to comorbidities. Radiological criteria for this specific population require further investigation.

[Hot tub lung: A case report]. / Poumon de jacuzzi : à propos d'un cas.

Hot tub lung is a type of hypersensitivity pneumonitis caused by inhalational exposure to the Mycobacterium avium complex. We report the case of a 14-year-old boy presenting dyspnea with hypoxemia, whose medical history and clinical course helped make the diagnosis. Infectious causes were considered first, and antibiotics were initiated without success. Further questioning and explorations led to discussing a hypersensitivity pneumonitis diagnosis. Relapse after exposure to a hot tub enabled us to confirm hot tub lung. Hypersensitivity pneumonitis is a rare cause of pulmonary disorder, especially in children. It should be discussed with unusually severe and progressive cough or dyspnea. Further explorations should therefore be undertaken (CT, fibroscopy). Taking a precise medical history allows early diagnosis, leading to a quick withdrawal from the allergenic source and appropriate treatments.

[Recommendations for the use of diagnostic testing in low respiratory infections in children older than three months]. / Recommandations sur l'utilisation des nouveaux outils diagnostiques étiologiques des infections respiratoires basses de l'enfant de plus de trois mois.

Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP(2)A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP(2)A website.

[Antibiotic prophylaxis in pediatric pulmonology (excluding cystic fibrosis): which indications for rotating (or alternating) antibiotics and prolonged antibiotic therapy?]. / Antibioprophylaxie en pneumologie pédiatrique (hors mucoviscidose) : quelles indications pour l'antibiothérapie rotative ou alternée et pour l'antibiothérapie prolongée ?

Some children with chronic lung disease associated with mucociliary clearance impairment and chronic bronchial congestion develop, during their evolution, bronchial bacterial colonization and recurrent infections. Therefore, antibioprophylaxis (ABP) is proposed by pediatric pulmonology specialists. Although some children seem improved by this strategy, it is worthy to note that no pediatric study supports its effectiveness, and no guidelines from society currently recommend its prescription. Demonstrated clinical benefits of ABP involve rare and highly targeted diseases. These children require a specialized assessment before any decision of ABP. Cystic fibrosis is definitely a situation where the interest of ABP is well established. By extension of the data obtained in adults, children with bronchiectasis (DDB) could potentially benefit from prolonged antibiotic therapy. In recurrent bacterial infections of the airways without DDB, ABP should be limited and restricted to most severe cases. In the absence of data on the benefit of alternate antibiotic treatment, we propose to focus on a single-molecule antibiotic prescribed for long periods. It may be amoxicillin, macrolides or cotrimoxazole. Furthermore, there is currently no data justifying the prescription of long-term macrolides in childhood asthma.