Cardiopulmonary exercise testing in adolescence following extremely premature birth.

BACKGROUND: Although extremely premature birth disrupts lung development, adolescent survivors of extreme prematurity show good clinical and physiologic outcomes. Cardiopulmonary limitations may not be clinically evident at rest. Data regarding exercise limitation in adolescents following preterm birth in the postsurfactant era are limited. RESEARCH QUESTION: What are the long-term effects of bronchopulmonary dysplasia (BPD) and extreme prematurity (<29 weeks) on ventilatory response during exercise in adolescents in the postsurfactant era? STUDY DESIGN AND METHODS: We followed a longitudinally recruited cohort of children aged 13-19 years who were born at a gestational age of <29 weeks (study group - SG). We compared the cardiopulmonary exercise testing (CPET) results of those with and without BPD, to their own CPET results from elementary school age (mean 9.09 ± 1.05 years). RESULTS: Thirty-seven children aged 15.73 ± 1.31 years, mean gestational age 26 weeks ( ± 1.19), completed the study. CPET parameters in adolescence were within the normal range for age, including mean V̇O2 peak of 91% predicted. The BPD and non-BPD subgroups had similar results. In the longitudinal analysis of the SG, improvement was observed in adolescence, compared with elementary school age, in breathing reserve (36.37 ± 18.99 vs. 26.58 ± 17.92, p = 0.044), tidal volume as a fraction of vital capacity achieved at maximal load (0.51 ± 0.13 vs. 0.37 ± 0.08, p < 0.001), and respiratory exchange ratio at maximal load (1.18 ± 0.13 vs. 1.11 ± 0.10, p = 0.021). INTERPRETATION: In the current cohort, adolescents born extremely premature have essentially normal ventilatory response during exercise, unrelated to BPD diagnosis. CPET results in this population improve over time.

Pulmonary Evaluation in Children with Post-COVID-19 Condition Respiratory Symptoms: A Prospective Cohort Study.

Background: Studies on post-COVID-19 condition (PCC) in adults have shown deterioration in pulmonary function tests (PFTs), mainly a diffusion limitation. Among the pediatric population, data are scarce. Aim: To characterize PFTs in children with PCC, including changes over time. Methods: A prospective longitudinal study of children with defined PCC and respiratory complaints who were referred to a designated multidisciplinary clinic from 11/2020 to 12/2022. Results: Altogether, 184 children with a mean age of 12.4 years (SD 4.06) were included. A mild obstructive pattern was demonstrated in 19/170 (11%) at presentation, as indicated by spirometry and/or positive exercise challenge test and/or reversibility post bronchodilators, only three had a previous diagnosis of asthma. Lung volumes and diffusion were normal in all but one patient (1/134, 0.7%). Exhaled nitric oxide levels were elevated in 32/144 (22%). A total of 33 children who had repeated PFTs had normal or near-normal PFTs on follow-up testing, including seven (21.2%) who had mild obstructive PFTs at presentation. Multivariate analysis identified older age [OR 1.36 (95% CI:1.07-1.75)], specific imaging findings (prominent bronchovascular markings (OR 43.28 (95% CI: 4.50-416.49)), and hyperinflation (OR 28.42, 95% CI: 2.18-370.84)] as significant predictors of an obstructive pattern on PFTs. Conclusions: In children with PCC and respiratory symptoms, the most common impairment was a mild obstructive pattern; most were without a history of asthma. Improvement was witnessed in long-term follow-up. In contrast to the adult population, no diffusion limitation was found. Empirical periodic inhaler therapy may be considered in children with factors associated with PFT abnormalities.

Influenza vaccination in children with pulmonary disease during the COVID-19 pandemic.

INTRODUCTION: Influenza is associated with considerable respiratory morbidity and mortality. Healthcare authorities recommend immunization of all children as vaccinations protect vulnerable populations, minimize influenza triggered asthma attacks, and reduced the burden of respiratory illnesses during the SARS-CoV-2 pandemic. Medical professionals should counsel parents of children with chronic lung disease to receive annual influenza vaccinations as part of supportive care. We aimed to describe adherence to influenza vaccination in respiratory patients and identify potential reasons for non-vaccination. METHODS: This study included questionnaires reviewing personal experience and beliefs regarding influenza vaccination, provided by parents of patients who visited the Pediatric Pulmonary Institute at Schneider Children's Medical Center with their children, during March-August 2021. RESULTS: Of 198 parents who completed our questionnaire, 114 (57.3 %) vaccinated their children against influenza during that year. Average age was 6.9 ± 4.5 years. Demographic data were similar between the vaccinated and unvaccinated groups. Influenza vaccination rates differed significantly between parents who received an explanation from their primary physician and those who did not (65.4 % vs. 43.7 %, respectfully, p = 0.003), and parents who received explanations from a pulmonary specialist and those who did not (77.3 % vs. 48.8 %, respectively, p = 0.004). The combined recommendation of a primary physician and pulmonologist translated to a significantly higher vaccination rate among those who received such recommendations, as compared to those who did not (p < 0.001). Parents who believed in vaccine efficacy and safety were more likely to vaccinate their children (p < 0.001). Factors significantly affecting the decision of the parents to have their child vaccinated were their knowledge, beliefs, and conceptions about the vaccine. CONCLUSIONS: Pediatric respiratory patients' influenza vaccination rate was 57 %. Major factors encouraging vaccination were correct parental knowledge and receiving recommendations from their primary physician\pulmonologist. This emphasizes the need for providing patients with information, by first explaining the vaccine's importance to physicians.

COVID-19 infection in pediatric patients treated for cancer.

BACKGROUND: COVID-19, the novel coronavirus, has caused a global pandemic affecting millions of people around the world. Risk factors for critical disease in adults are advanced age and underlying medical comorbidities, including cancer. Data are sparse on the effect of COVID-19 infection on pediatric patients with cancer during their active antineoplastic therapy. The optimal management of antineoplastic treatment during COVID-19 infection in this unique population is controversial. AIM: To describe the severity and clinical course of COVID-19 infection in pediatric patients with cancer during active antineoplastic treatment and to study their course of treatment. METHODS: Clinical and laboratory data were collected from medical files of patients diagnosed with COVID-19, confirmed by polymerase chain reaction (PCR), who received active antineoplastic treatment between March 2020 and May 2021 in a large tertiary pediatric medical center. RESULTS: Eighteen patients with diverse pediatric cancers are described. They were infected with COVID-19 at different stages of their antineoplastic treatment regimen. Eight had an asymptomatic COVID-19 infection, nine had mild symptoms, and one had severe disease. All of them recovered from COVID-19 infection. Two patients experienced delays in their antineoplastic treatment; none of the other patients had delays or interruptions, including patients who were symptomatic for COVID-19. CONCLUSION: In pediatric patients with cancer who test positive for COVID-19, yet are asymptomatic or have mild symptoms, the continuance of antineoplastic therapy may be considered.

Antibiotic Discontinuation 24 h After Neonatal Late-Onset Sepsis Work-Up-A Validated Decision Tree Model.

Objectives: Neonatal late-onset sepsis work-up is a frequent occurrence in every neonatal department. Blood cultures are the diagnostic gold standard, however, a negative culture prior to 48-72 h is often considered insufficient to exclude sepsis. We aimed to develop a decision tree which would enable exclusion of late-onset sepsis within 24 h using clinical and laboratory variables. Study Design: Infants evaluated for late-onset sepsis during the years 2016-2019, without major malformations, in a tertiary neonatal center were eligible for inclusion. Blood cultures and clinical and laboratory data were extracted at 0 and 24 h after sepsis work-up. Infants with bacteriologically confirmed late-onset sepsis were compared to matched control infants. Univariate logistic regression identified potential risk factors. A decision tree based on Chi-square automatic interaction detection methodology was developed and validated. Results: The study cohort was divided to a development cohort (105 patients) and a validation cohort (60 patients). At 24 h after initial evaluation, the best variables to identify sepsis were C-reactive protein > 0.75 mg/dl, neutrophil-to-lymphocyte ratio > 1.5 and sick-appearance at 24 h. Use of these 3 variables together with blood culture status at 24 h, enabled identification of all infants that eventually developed sepsis through the decision tree model. Our decision tree has an area under the receiver operating characteristic curve of 0.94 (95% CI: 0.90-0.98). Conclusions: In non-sick appearing infants with a negative blood culture at 24 h and normal laboratory values, sepsis is highly unlikely and discontinuing antibiotics after 24 h is a viable option.

Palivizumab Following Extremely Premature Birth Does Not Affect Pulmonary Outcomes in Adolescence.

BACKGROUND: Prematurity is a risk factor for impaired lung function. We sought to assess the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks gestation) on respiratory symptoms and pulmonary function in adolescence. RESEARCH QUESTION: What is the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks) on respiratory symptoms and pulmonary function in adolescence? STUDY DESIGN AND METHODS: We examined survivors of extreme prematurity (<29 weeks gestation) at 13 to 18 years of age (study group). Study group babies who were born immediately before palivizumab immunization (nonpalivizumab group [NPG]) were compared with those babies who were born just after implementation (PG) and with a control group. For study group patients, lung function in adolescence was further compared longitudinally with that at primary school age. RESULTS: Sixty-four adolescents aged 15.76 ± 1.52 years were included: 46 in the study group (17 PG and 29 NPG) and 18 in the control group. For the study group, wheezing episodes, inhaler use, and hospitalizations were uncommon. For the study group compared with the control group, FEV1 percent predicted was 82.60% ± 13.54% vs 105.83% ± 13.12% (P < .001), and the lung clearance index was 7.67 ± 1.02 vs 7.46 ± 0.70 (P = .48), respectively. Study group adolescents with bronchopulmonary dysplasia had a higher lung clearance index than did adolescents with no bronchopulmonary dysplasia (7.94 ± 1.11 vs 7.20 ± 0.60; P = .002). PG and NPG adolescents were not significantly different. Comparing the study group in adolescence with primary school age, we found improvement in mean FEV1 percent predicted bronchodilator response (0.37% ± 9.98% vs 5.67% ± 9.87%; P = .036) and mean provocative concentration causing 20% decline in FEV1 (12.16 ± 4.71 mg/mL vs 4.14 ± 4.51 mg/mL, respectively; P < .001). INTERPRETATION: Palivizumab did not provide any discernable long-term protective effect. Nevertheless, adolescent survivors of extreme prematurity showed good clinical and physiologic outcomes, except for mildly raised lung clearance index in patients with bronchopulmonary dysplasia. Airway hyperreactivity detected at primary school age, decreased by adolescence.

Can we improve early identification of neonatal late-onset sepsis? A validated prediction model.

OBJECTIVE: No single test can accurately identify neonatal late-onset sepsis (LOS). Our aim was to use clinical evaluation with laboratory tests to rapidly assess sepsis risk. STUDY DESIGN: A retrospective case-control study was performed in a tertiary Neonatal Center during the years 2016-2019. Infants with bacteriologically confirmed LOS were compared with control infants. A clinical health evaluation score was assigned to each infant. A prediction model was developed and validated by multivariable analysis. RESULTS: The study included 145 infants, 48 with sepsis, and 97 controls. LOS was independently associated with: sick appearance (OR: 5.7, 95% CI: 1.1-29.1), C-reactive protein > 0.75 (OR: 5.4, 95% CI: 1.1-26.3), and neutrophil-to-lymphocyte ratio > 1.5 (OR: 6.7, 95% CI: 1.2-38.5). Our model had an area under the receiver operating characteristic curve of 0.92 (95% CI: 0.86-0.97). CONCLUSIONS: Clinical evaluation with neutrophil-to-lymphocyte ratio and C-reactive protein can rapidly identify LOS enabling decreased health costs and antibiotic use.

Molecular diagnosis of α-thalassemia in a multiethnic population.

OBJECTIVE: α-Thalassemia, one of the most common genetic diseases, is caused by deletions or point mutations affecting one to four α-globin genes. Molecular diagnosis is important to prevent the most severe forms of the disease. However, the diagnosis of α-thalassemia is complex due to a high variability of the genetic defects involved, with over 250 described mutations. We summarize herein the findings of genetic analyses of DNA samples referred to our laboratory for the molecular diagnosis of α-thalassemia, along with a detailed clinical description. METHODS: We utilized a diagnostic algorithm including Gap-PCR, to detect known deletions, followed by sequencing of the α-globin gene, to identify known and novel point mutations, and multiplex ligation-dependent probe amplification (MLPA) for the diagnosis of rare or novel deletions. RESULTS: α-Thalassemia was diagnosed in 662 of 975 samples referred to our laboratory. Most commonly found were deletions (75.3%, including two novel deletions previously described by us); point mutations comprised 25.4% of the cases, including five novel mutations. Our population included mostly Jews (of Ashkenazi and Sephardic origin) and Muslim Arabs, who presented with a higher rate of point mutations and hemoglobin H disease. Overall, we detected 53 different genotype combinations causing a spectrum of clinical phenotypes, from asymptomatic to severe anemia. CONCLUSION: Our work constitutes the largest group of patients with α-thalassemia originating in the Mediterranean whose clinical characteristics and molecular basis have been determined. We suggest a diagnostic algorithm that leads to an accurate molecular diagnosis in multiethnic populations.

Thyroid Functions in Healthy Infants during the First Year of Life.

OBJECTIVE: To study the pattern of thyroid function testing in healthy newborns during the first year of life. STUDY DESIGN: We used the computerized database of a health management organization. Among the 18,507 infants insured by the Clalit Health Services born in the Sheba Medical Center between 2002 and 2007, 652 full-term healthy newborns with birth weight >2 kg and no significant perinatal morbidity underwent thyrotropin (TSH) determination as outpatients in their first year of life. The Clalit Health Services database provided demographic data, laboratory results, and dispensed medications for the newborns and their mothers. RESULTS: Initial serum TSH levels were within normal range (0.35-5.5 mIU/L) in 91.1%, elevated (> 5.5-≤ 10 mIU/L) in 8.3%, and highly elevated (>10 mIU/L) in 0.6% of the studied cohort. The 97.5 and 2.5 percentile values were 7.4 and 0.74 mIU/L, respectively. TSH measurements were repeated in 34.2%, 72.2%, and 100% of children with normal, elevated, and highly elevated initial levels, respectively; results were normal in 96%, 74%, and 50% of patients with initial normal, elevated, and highly elevated TSH, respectively; repeated TSH levels were > 97.5 percentile in 35% of patients with initial TSH > 97.5 percentile compared with 1% with first results < 97.5 percentile (P = .005). Only 4 (0.6%) of the 652 newborns included in the study received thyroxin treatment. CONCLUSION: The normal TSH levels found in most healthy infants with normal thyroid screening and the spontaneous normalization of TSH values below 7.4 mIU/liter, substantiate the reliability of the screening, reduce unnecessary work-up and unnecessary thyroxin treatment of neonates meeting these criteria.