Novel growth reference ImaGrow differed from existing charts for preterm children aged 0-2 years.

AIM: This study aimed to address the critical need for more accurate growth reference charts for preterm infants, with a particular focus on low- and very low-birth-weight infants. METHODS: The subjects were recruited at a single tertiary centre. The cohort comprised singleton and twin infants born before 37 weeks of gestation, with data collected from 2000 to 2016. Standardised measurements of body parameters were recorded in this mixed longitudinal survey. LMS method was utilised for data analysis. Statistical analysis was performed using SPSS Statistics Version 21. The validation with another new cohort was executed. RESULTS: A total of 1781 infants (52.5% boys) met the inclusion criteria. The median gestational age at birth was 30 weeks, with a median birth weight of 1350 grams. The main findings included the construction of ImaGrow charts for low- and very low-birth-weight infants and significant differences in growth trajectories compared to Fenton+WHO charts. CONCLUSION: Our comprehensive growth references, ImaGrow, are based on a long-term auxological assessment of preterm infants and differ from charts derived from size-at-birth standards or charts for term babies. These charts have significant implications for clinical practice in monitoring and assessing the growth of preterm infants.

Symptomatic preterm infants suffer from lung function deficits, regardless of bronchopulmonary dysplasia.

BACKGROUND: The long-term respiratory consequences for children with bronchopulmonary dysplasia (BPD) are well known. However, there is little emphasis on monitoring preterm infants without BPD. Few studies have explored the lung function status of infants with the symptoms of chronic lung disease of prematurity (CLD). OBJECTIVE: To evaluate functional lung deficits in preterm infants with CLD, and to assess the perinatal determinants of diminished lung function. METHODS: In our cross-sectional study, 132 preterm infants with symptomatic CLD underwent infant pulmonary function testing (iPFT) at a median post-term age of 0.9 years. The iPFT included bodypletysmography, compliance measurement, tidal breath analysis, and rapid thoracoabdominal compression. The relationships between the respective z scores of the iPFT parameters and perinatal characteristics, postnatal treatment, and BPD status were investigated. RESULTS: Seventy-three patients (55.3%) were born before the 28th week of gestation, and 92 (69.7%) met the BPD criteria. Functional deficits were detected in 85.8%. The obstructive ventilatory pattern was more prevalent than restrictive (36.3 vs. 12.4%, p < 0.001). Infants with restriction had lower birth weight (BW) and required a longer duration of oxygenotherapy. In a univariate model, the lung function correlated with the duration of invasive mechanical ventilation, gestational week, and BW. In a general linear model, BPD status was not an additional determinant of the iPFT results. CONCLUSION: IPFT may reveal significant functional deficits in preterm infants with CLD even without BPD. The current symptoms and perinatal factors may be more important determinants of functional deficits than the BPD status itself.

The respiratory consequences of COVID-19 lasted for a median of 4 months in a cohort of children aged 2-18 years of age.

AIM: We focused on the clinical picture, severity and prognosis of children who experienced long-term respiratory issues after COVID-19. METHODS: This was a national Czech multicentre study of paediatric post-COVID syndrome, which used a standard protocol to evaluate structural and functional anomalies and exclude alternative diagnoses. From 6 January to 30 June 2021, 11 paediatric pulmonologists enrolled all paediatric referrals aged 2-18 years with persistent respiratory symptoms more than 12 weeks after COVID-19, namely cough, dyspnoea and chest pain. Medical histories were taken, and physical examinations, lung function testing, chest X-ray and blood tests were performed. RESULTS: The dominant symptoms in the 39 children (56.4% girls) were exertional dyspnoea (76.9%) and a chronic cough (48.7%), while dyspnoea at rest (30.8%) and chest pain (17.9%) were less prevalent. More than half (53.8%) reported more than 1 symptom, and 38.5% had abnormal results for 1 of the following tests: lung function, chest X-ray or D-dimers. The median age of the children was 13.5 years (interquartile range ±4.8 years), and the median recovery time was 4 months (range 1.5-8 months). CONCLUSION: Our initial data suggest that the long-term respiratory impact of COVID-19 was relatively mild in our cohort, with a favourable prognosis.

Early inhaled budesonide in extremely preterm infants decreases long-term respiratory morbidity.

BACKGROUND: There is no strict correlation between early bronchopulmonary dysplasia and long-term respiratory disease. Early inhaled corticosteroids seem to reduce the incidence of bronchopulmonary dysplasia, but the long-term outcome remains unknown. RESEARCH QUESTION: The aim of this study was to evaluate the effect of early inhaled corticosteroids on chronic respiratory morbidity. METHODS: Fifty-nine survivors from the Prague cohort included in Neonatal European Study of Inhaled Steroids underwent further follow-up comprising of respiratory morbidity monitoring during the first 2 years of life followed by objective lung function testing performed at the age of 5.9 years (range 5-7 years). Both outcomes were pursued and finalized before the unblinding of budesonide subgroups. RESULTS: Fifty randomized (budesonide vs placebo group, 56% vs 44%) survivors were included in the study. Spirometry was successfully performed in 48 children. No statistically significant differences were found in the lung function test (forced expiratory flow [FEF] - FEF75 , FEF50, FEF25 , and FEF25-75; FEV1 , forced vital capacity [FVC], FEV1 /FVC) although mild trend to the improvement of expiratory flow pattern was observed in the budesonide group (median z-score of FEV1 /FVC -0.376 vs -0.983, P = .13; median z-score of FEF25-75 -1.004 vs -1.458, P = .13; median z-score of FEF75 -0.527 vs -0.996, P = .17). Children assigned to budesonide had a significantly lower rate of symptoms of chronic lung disease (34.6% vs 68.2%; P = .04) than children assigned to placebo. INTERPRETATION: Our study suggests that early inhaled budesonide was associated with the trend to the improvement of functional lung parameters and with a lower rate of symptoms of chronic lung disease within the first 2 years of life.

677TT genotype is associated with elevated risk of methotrexate (MTX) toxicity in juvenile idiopathic arthritis: treatment outcome, erythrocyte concentrations of MTX and folates, and MTHFR polymorphisms.

OBJECTIVE: To investigate whether methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and erythrocyte concentration of methotrexate (EMTX) could serve as predictors of methotrexate (MTX) efficacy and toxicity in patients with juvenile idiopathic arthritis (JIA). METHODS: Genetic analyses and EMTX and folate assessment were performed in 69 patients with JIA aged 2.5-19.6 years (30 male) treated with MTX using a dose-escalation protocol and classified as full responders (disease inactivity; n = 51) or nonresponders (< 30% improvement in pediatric American College of Rheumatology-30 criteria while receiving ≥ 15 mg/m(2)/week parenteral MTX for at least 3 months; n = 18). RESULTS: Nonresponders were treated with the higher median MTX dose (17.2 vs 12.6 mg/m(2)/week; p < 0.0001) and accumulated more EMTX (217 vs 106 nmol/l; p < 0.02) and erythrocyte folates (763 vs 592 nmol/l; p = 0.052) than responders. Analysis of MTHFR allele and genotype frequencies in relation to response failed to detect association. The frequency of any adverse effect was 29.4% in responders and 33.3% in nonresponders (p = 0.77). The frequency of 677T allele was elevated in patients with adverse effects (52.4% vs 20.9%; OR 3.88, 95% CI 1.8-8.6, p < 0.002). The probability of any adverse effect was significantly higher in patients with 677TT compared to the 677CC genotype (OR 55.5, 95% CI 2.9-1080, p < 0.001). CONCLUSION: MTHFR genotyping may have a predictive value for the risk of MTX-associated toxicity in patients with JIA. Despite the lack of therapeutic effect, nonresponders accumulated adequate concentrations of EMTX.

An improved high-performance liquid chromatography method for quantification of methotrexate polyglutamates in red blood cells of children with juvenile idiopathic arthritis.

Methotrexate is used widely in the pharmacotherapy of juvenile idiopathic arthritis. Polyglutamates of methotrexate are active metabolites which accumulate in cells including erythrocytes. Their intracellular concentration may reflect methotrexate bioavailability and, at the same time, may serve as a bioindicator for optimization of methotrexate therapy and drug monitoring. Therefore, a simple and selective isocratic reversed phase chromatographic method with fluorescence detection (excitation/emission wavelengths of 370/463 nm) was developed which quantifies the sum of all methotrexate polyglutamates in erythrocytes as methotrexate after their enzymatic conversion with gamma-glutamylhydrolase. Separation was carried out on a Phenomenex GEMINI C18 column using a mobile phase flowing at a rate of 0.6 ml/min and consisting of a mixture (110:890:0.25 v/v) of acetonitrile, ammonium acetate buffer (0.05 M, pH=5.5) and hydrogen peroxide 30% (w/w). The method was found linear over the concentration range of 25-400 nmol/l. Its intra- and inter-day precision and accuracy were characterized by coefficients of variation and relative errors less than 20%. The limits of detection and quantification achieved 10.9 and 32.9 nmol/l, respectively. The method was proved suitable for monitoring the concentration of methotrexate polyglutamates in erythrocytes of patients with juvenile idiopathic arthritis.