Child Functional Impairment Research Articles

Mental disorder diagnoses and symptoms and functional impairment in school-age children in the care of child protective services

BackgroundAbout 50 % of children in the care of child protective services present at least one mental disorder, but few studies have looked at whether there are differences in mental disorders or symptoms between children placed in out-of-home care (foster care and residential care) and their community peers. ObjectiveThis study documents the mental disorder diagnoses and symptoms among children in out-of-home care and their associations with children functional impairment. It also compares out-of-home care children with those from the community. Participants and settingThe sample was composed of children aged 5 to 12 years in foster care (n = 154), in residential care (n = 111), and from the community (n = 92). MethodsCaregivers reported the children's diagnoses and completed questionnaires on the children's symptoms. Results1) Proportionally more children in out-of-home care presented a mental disorder than did children from the community. Proportions were similar for those in foster care and those in residential care; 2) Children in out-of-home care presented more symptoms than those from the community for all the mental disorders considered and the children in residential care presented more symptoms than did those in foster care for about half of the disorders considered; 3) symptoms were strongly associated with functional impairment; and 4) the symptoms of RAD, ADHD, OCD, CD, and ODD proved significant predictors of functional impairment. ConclusionsThis study provides a picture of the mental disorders and symptoms among samples of school-age children in the care of child protective services and raises questions about the proportions of some of the diagnosis that children receive.

Pulmonary function and bronchopulmonary dysplasia classification: insights from the Spanish Registry.

In 2016, the Spanish Research Group on Bronchopulmonary Dysplasia (BPD) (GEIDIS) established a national registry with participation of 66 hospitals to collect information on clinical characteristics and long-term outcomes of BPD infants into adulthood. The aim of this observational study is to examine forced spirometry data in early childhood and to assess their correlation with the respiratory support required at 36weeks postmenstrual age (PMA). The study analyzed data from preterm infants with BPD born between January 2016 and December 2017 who underwent forced spirometry at 5-7years of age. Statistical analyses were conducted to investigate the relationships between spirometry results, perinatal factors, and the required respiratory support at 36weeks PMA. The study involved 143 patients with a median gestational age (GA) of 27.3weeks (range 25.7-28.7) and a median weight of 880g (range 740-1135). Abnormal spirometry results were observed in 39.2% (56) of the patients. Among patients diagnosed with BPD type 3, those requiring over 30% oxygen at 36weeks PMA exhibited an increased risk of abnormal spirometry results (OR 4.48; 95% CI 1.11-18.13) compared to those requiring positive pressure with less than 30% oxygen. In addition, this subgroup had a higher risk of developing a restrictive-mixed pattern compared to those with BPD type 1 (OR 10.65; 95% CI 2.06-54.98) and BPD type 2 (OR 6.76; 95% CI 1.09-42.06). No significant differences were found in the incidence of an obstructive pattern between BPD types. Conclusion:The requirement of more than 30% oxygen at 36weeks PMA serves as a risk indicator for pulmonary function impairment in school-aged children with BPD. These findings suggest persistent airway and parenchymal injury in this specific patient population, and highlight the importance of careful monitoring to evaluate their long-term effects on lung function. What is Known: • Premature patients with bronchopulmonary dysplasia (BPD) may present abnormalities in pulmonary function tests during school age. However, the predictive accuracy of consensus BPD severity classification remains uncertain. What is New: • The requirement of more than 30% oxygen at 36weeks postmenstrual age (PMA) indicates a potential risk of pulmonary function impairment in school-aged children with BPD. Additionally, a significant correlation has been observed between a restrictive-mixed pattern with exposure to mechanical ventilation and the development of severe forms of BPD.

#896 Long-term renal outcome in childhood-onset lupus nephritis

Abstract Background and Aims Lupus nephritis (LN) is a common and severe complication of childhood-onset SLE. Little is known about the long-term renal outcome of childhood-onset LN. We investigated predictive factors of end-stage kidney disease (ESKD) and chronic kidney disease (CKD) in a paediatric cohort of patients with LN. Method This is a retrospective multicentre study including patients with childhood-onset (<18 years) biopsy-proven LN. Clinical features were analysed at disease onset, time of kidney biopsy, 12 and 24 months after biopsy, and last follow-up. We investigated the prognostic significance of clinical, laboratory and histologic characteristics on the incidence of ESKD and CKD stage 3-5. Results We included 73 patients with a median age of 14 years (IQR 11.5-17) . At the time of kidney biopsy, most subjects displayed an aggressive disease: 2 (3%) children required haemodialysis, 27 (38%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The overall median eGFR was 70 mL/min/1.73 m2 (IQR 43-96) . Moreover, the median proteinuria was 4 g/24 h (IQR 1.35-7.41) , with 41 (59%) children displaying a nephrotic range proteinuria (i.e., >3 g/24 h) . The median follow-up was 13.3 years (IQR 4.7-25.4) . A total of 10 patients (13.7%) reached ESKD, the majority of whom (12%) within 10 years from kidney biopsy; during the subsequent follow-up the incidence of ESKD stabilised (Fig. 1). At last follow-up, around 50% of patients displayed an eGFR <90 mL/min/1.73 m2. A younger age at LN onset, a lower eGFR and central nervous system involvement at the time of kidney biopsy were identified as predictors of ESKD by a univariable Cox regression model (Table 1). The same features were significantly associated with the occurrence of CKD stage 3-5 at last follow-up at a univariable logistic regression analysis. Conclusion LN often presents with severe kidney function impairment and aggressive systemic involvement in children. In our cohort, whose follow-up was among the longest reported in the literature, 12% of patients reached ESKD within 10 years from kidney biopsy. Significant predictors of poor kidney outcome in the long term were a younger age at LN onset, a lower eGFR and the presence of neurological manifestations at the time of kidney biopsy.

Elevated plasma solMER concentrations link ambient PM2.5 and PAHs to myocardial injury and reduced left ventricular systolic function in children

Exposure to fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) is known to be associated with the polarization of pro-inflammatory macrophages and the development of various cardiovascular diseases. The pro-inflammatory polarization of resident cardiac macrophages (cMacs) enhances the cleavage of membrane-bound myeloid-epithelial-reproductive receptor tyrosine kinase (MerTK) and promotes the formation of soluble MerTK (solMER). This process influences the involvement of cMacs in cardiac repair, thus leading to an imbalance in cardiac homeostasis, myocardial injury, and reduced cardiac function. However, the relative impacts of PM2.5 and PAHs on human cMacs have yet to be elucidated. In this study, we aimed to investigate the effects of PM2.5 and PAH exposure on solMER in terms of myocardial injury and left ventricular (LV) systolic function in healthy children. A total of 258 children (aged three to six years) were recruited from Guiyu (an area exposed to e-waste) and Haojiang (a reference area). Mean daily PM2.5 concentration data were collected to calculate the individual chronic daily intake (CDI) of PM2.5. We determined concentrations of solMER and creatine kinase MB (CKMB) in plasma, and hydroxylated PAHs (OH-PAHs) in urine. LV systolic function was evaluated by stroke volume (SV). Higher CDI values and OH-PAH concentrations were detected in the exposed group. Plasma solMER and CKMB were higher in the exposed group and were associated with a reduced SV. Elevated CDI and 1-hydroxynaphthalene (1-OHNa) were associated with a higher solMER. Furthermore, increased solMER concentrations were associated with a lower SV and higher CKMB. CDI and 1-OHNa were positively associated with CKMB and mediated by solMER. In conclusion, exposure to PM2.5 and PAHs may lead to the pro-inflammatory polarization of cMacs and increase the risk of myocardial injury and systolic function impairment in children. Furthermore, the pro-inflammatory polarization of cMacs may mediate cardiotoxicity caused by PM2.5 and PAHs.

Erythrocyte Glutathione S-Transferase Activity as a Sensitive Marker of Kidney Function Impairment in Children with IgA Vasculitis.

IgA vasculitis (IgAV) is the most common childhood vasculitis. The main cause of morbidity and mortality in children with IgAV is nephritis (IgAVN), but the risk of its development, severity, and chronicity remain unclear. Erythrocyte glutathione S-transferase (e-GST) activity has been previously detected as a sensitive marker of kidney function impairment in several diseases. We spectrophotometrically assessed and correlated e-GST activity between 55 IgAV patients without nephritis (IgAVwN), 42 IgAVN patients, and 52 healthy controls. At disease onset, e-GST activity was significantly higher in IgAVN patients (median (interquartile range)) (5.7 U/gHb (4.4-7.5)) than in IgAVwN patients (3.1 U/gHb (2.2-4.2); p < 0.001), and controls (3.1 U/gHb (1.9-4.2); p < 0.001). Therewithal, there were no differences between the IgAVwN patients and controls (p = 0.837). e-GST activity was also significantly higher in the IgAVN patients than in the IgAVwN patients after 3 months (5.0 U/gHb (4.2-6.2) vs. 3.3 U/gHb (2.3-4.1); p < 0.001) and 6 months (4.2 U/gHb (3.2-5.8) vs. 3.3 U/gHb (2.1-4.1); p < 0.001) since the disease onset. Consistent correlations between e-GST activity and serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria levels were not detected. In conclusion, increased e-GST activity can serve as a subtle indicator of kidney function impairment in children with IgAV.

Nitrogen dioxide exposure, attentional function, and working memory in children from 4 to 8 years: Periods of susceptibility from pregnancy to childhood

BackgroundAir pollution exposure during pregnancy and childhood has been linked to executive function impairment in children, however, very few studies have assessed these two exposure periods jointly to identify susceptible periods of exposure. We sought to identify potential periods of susceptibility of nitrogen dioxide (NO2) exposure from conception to childhood on attentional function and working memory in school-aged children. MethodsWithin the Spanish INMA Project, we estimated residential daily NO2 exposures during pregnancy and up to 6 years of childhood using land use regression models (n = 1,703). We assessed attentional function at 4–6 years and 6–8 years, using the Conners Kiddie Continuous Performance Test and the Attention Network Test, respectively, and working memory at 6–8 years, using the N-back task. We used distributed lag non-linear models to assess the periods of susceptibility of each outcome, adjusting for potential confounders and correcting for multiple testing. We also stratified all models by sex. ResultsHigher exposure to NO2 between 1.3 and 1.6 years of age was associated with higher hit reaction time standard error (HRT-SE) (0.14 ms (95 % CI 0.05; 0.22) per 10 μg/m3 increase in NO2) and between 1.5 and 2.2 years of age with more omission errors (1.02 (95 % CI 1.01; 1.03) of the attentional function test at 4–6 years. Higher exposure to NO2 between 0.3 and 2.2 years was associated with higher HRT-SE (10.61 ms (95 % CI 3.46; 17.75) at 6–8 years only in boys. We found no associations between exposure to NO2 and working memory at 6–8 years. ConclusionOur findings suggest that NO2 exposure during the first two years of life is associated with poorer attentional function in children from 4 to 8 years of age, especially in boys. These findings highlight the importance of exploring long-term effects of traffic-related air pollution exposure in older age groups.

Abdominal fat and risk of impaired lung function and asthma in children: A population‐based prospective cohort study

AbstractBackgroundObesity, specifically abdominal adiposity, is associated with increased risks of lung function impairment and asthma in children, but potential adverse effects among adolescents are unknown. We hypothesized that elevated amounts of specific abdominal fat depots during childhood and adolescence may lead to adverse respiratory outcomes in adolescents.MethodsIn a population‐based prospective cohort study among 2877 children at 13 years, we measured specific abdominal fat depots including subcutaneous fat mass and visceral fat mass by magnetic resonance imaging. Lung function was measured by spirometry, and current asthma by a questionnaire. Conditional regression analyses were used to examine the associations of abdominal fat depots with respiratory outcomes in adolescence.ResultsAfter adjustment for confounders and child's body mass index, higher subcutaneous and visceral fat mass index at age 13 years, independent of these measures at earlier age, were associated with lower FEV1, FEV1/FVC, and FEF75 (range Z‐score difference (95% CI): −0.10 (−0.15, −0.06) to −0.06 (−0.11, −0.01)). Also, an increase in subcutaneous and visceral fat between ages 10 and 13 years was associated with a decrease in FEV1, FEV1/FVC, and FEF75 during the same period. No associations of abdominal fat depots with asthma were observed.ConclusionAdolescents with higher amounts of subcutaneous and visceral fat, independent of that at an earlier age and body mass index, have an increased risk of lung function impairment.

Prevalence and Characteristics of Dental Fluorosis in a Group of Brazilian Children

Background: Dental fluorosis (DF) is characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation. DF phenotype presents different severities, ranging from very mild to severe phenotypes according to the enamel alteration. This dental development alteration is a common disorder worldwide. It is important to understand the prevalence in certain populations as a preventive strategy for the child's aesthetic, functional and psychological impairment. Purpose: to evaluate a prevalence and characteristics of DF in a group of children from Brazil. Methods: Three hundred and fifty-three children, aged 8-11 years, were clinically evaluated according to the DF phenotype. Only erupted permanent teeth were assessed. Results: DF prevalence was 7.6 %. Boys showed a higher prevalence of DF than girls. Very mild DF phenotypes were more common than more severe phenotypes of DF. Conclusion: the prevalence of DF in this Brazilian population of children was low.

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.

The role of family accommodation in child posttraumatic stress symptoms and functional impairment in the context of cognitive behavioral therapy

BackgroundCaregiver behaviors such as family accommodation (FA) are negatively reinforced by reduced distress in the short term, but ultimately maintain symptoms. It is important to explore the role of FA on symptoms and impairment. The current study examined the relationship among FA, posttraumatic stress symptoms (PTSS), and functional impairment in a sample of children and their caregivers who completed trauma treatment. MethodParticipants included 183 children and their caregivers (M age = 7.89; 55.19 % female; 73.22 % non-Hispanic; 51.37 % White). Data consisted of parent-reported measures collected at baseline, post-treatment, and 12-month follow-up from a randomized control trial (RCT) comparing Stepped Care CBT for Children after Trauma and Trauma-Focused Cognitive Behavior Therapy (TF-CBT). Correlational, mediation, and hierarchical linear regression analyses were conducted to test the interrelationships among FA, child PTSS, and child functional impairment. ResultsFA was significantly, positively associated with total PTSS and functional impairment at baseline. Baseline FA partially mediated the relationship between baseline total PTSS and baseline functional impairment. Lastly, greater pre- to post-treatment changes in FA were mostly associated with relevant outcome variables at post-treatment and 12-month follow-up. LimitationsStudy limitations include use of a single informant, cross-sectional data analysis, lack of differentiation among trauma types, concerns regarding generalizability. ConclusionAssessing FA may be a helpful tool in better understanding how child PTSS relates to functional impairment following exposure to trauma. This study is clinically relevant it offers insight on the relationship among FA, PTSS, and functional impairment for families involved in trauma treatment.

Executive and motor function in children with autism spectrum disorder.

The purpose of this study was to investigate the relationship between executive function, mainly attention and impulse control, and motor function impairment in children with ASD. Fifteen children with ASD (ages 8-14years) were examined on their executive function using the Conners continuous performance test-3 and motor function using the movement assessment battery for children-2 (MABC-2). It was found that children with ASD were delayed on executive and motor function. This means that those effects were also observed in male children with Autism Spectrum Disorder (ASD) who had similar characteristics as the participants in the study. This study may have practical implications in the relationship between executive function and motor performance in children with ASD and for clinicians and educators working with children with ASD. Furthermore, the findings suggest that variability in reaction time may be a useful predictor of motor skill performance in children with ASD and may reflect underlying difficulties in executive function and future research is suggested.

A scoping review of lung function in children and adolescents living with HIV in the era of antiretroviral treatment.

Human immunodeficiency virus (HIV) in children and adolescents remains an important health challenge in many countries and is commonly associated with lung disease. The introduction of antiretroviral therapy (ART) has greatly improved survival but chronic lung disease is a common ongoing challenge. We conducted a scoping review of studies that have reported lung function in school-aged children and adolescents living with HIV. A systematic literature search was performed by searching Medline, Embase, and PubMed databases, limited to articles published between 2011 and 2021 in English language. Inclusion criteria were studies involving participants living with HIV aged 5-18 years and having spirometry data. The primary outcome was lung function as measured by spirometry. Twenty-one studies were included in the review. Most study participants were living in the sub-Saharan African region. The prevalence of reduced forced expiratory volume in 1 s(FEV1 ) ranged from 25.3% to 73% across studies, reduced forced vital capacity (FVC) ranged from 10% to 42% and reduced FEV1 /FVC ranged from 3% to 26%. The mean z-score of FEV1 ranged from -2.19 to -0.73, mean zFEV1 /FVC ranged from -0.74 to 0.2, and mean FVC ranged from -1.86 to -0.63. There is a high prevalence of lung function impairment in children and adolescents living with HIV, which persists in the ART era. Further studies are needed of interventions that might improve lung function in these vulnerable populations.

Validation of the Asthma Severity Scoring System (ASSESS) in the ALLIANCE Cohort

The Asthma Severity Scoring System (ASSESS) quantifies asthma severity in adolescents and adults. Scale performance in children younger than 12 years is unknown. To validate the ASSESS score in the All Age AsthmaCohort and explore its use in children younger than 12 years. Scale properties, responsiveness, and known-group validity were assessed in 247 children (median age, 11 years; interquartile range, 8-13 years) and 206 adults (median age, 52 years; interquartile range, 43-63 years). Overall, measures of internal test consistency and test-retest reliability were similar to the original data of the Severe Asthma Research Program. Cronbach α was 0.59 in children aged 12 to 18 years and 0.73 in adults, reflecting the inclusion of multiple and not-always congruent dimensions to the ASSESS score, especially in children. Analysis of known-group validity confirmed the discriminatory power, because the ASSESS score was significantly worse in patients with poor asthma control, exacerbations, and increased salbutamol use. In children aged 6 to 11 years, test-retest reliability was inferior compared with that in adults and adolescents (Cronbach α, 0.27) mostly because of a less lung function impairment in children with asthma of this age group. Known-group validity, however, confirmed good discriminative power regarding severity-associated variables similar to adolescents and adults. Test-retest reliability and validity of the ASSESS score was confirmed in the All Age Asthma Cohort. In children aged 6 to 11 years, internal consistency was inferior compared with that in older patients with asthma; however, test validity was good and thus encourages age-spanning usage of the ASSESS score in all patients 6 years or older.

Australian children living with rare diseases: health service use and barriers to accessing care.

Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare. We aimed to determine health service utilization by Australian children with rare diseases and barriers to accessing healthcare. Parents completed an online survey on health professional and emergency department (ED) presentations, hospitalization, and barriers to accessing services. Potential barriers to service access included residential location (city, regional, remote) and child health-related functioning, determined using a validated, parent-completed measure-of-function tool. Parents of 462 children with over 240 rare diseases completed the survey. Compared with the general population, these children were more likely to be hospitalized [odds ratio (OR)= 17.25, 95% confidence interval (CI)= 15.50-19.20] and present to the ED (OR= 4.15, 95% CI= 3.68-4.68) or a family physician (OR= 4.14, 95% CI= 3.72-4.60). Child functional impairment was nil/mild (31%), moderate (48%) or severe (22%). Compared to children with nil/mild impairment, those with severe impairment were more likely to be hospitalized (OR= 13.39, 95% CI= 7.65-23.44) and present to the ED (OR= 11.16, 95% CI= 6.46-19.27). Most children (75%) lived in major cities, but children from regional (OR= 2.78, 95% CI= 1.72-4.55) and remote areas (OR= 9.09, 95% CI= 3.03-25.00) experienced significantly more barriers to healthcare access than children from major cities. Barriers included distance to travel, out-of-pocket costs, and lack of specialist medical and other health services. Children with rare diseases, especially those with severe functional impairment have an enormous impact on health services, and better integrated multidisciplinary services with patient-centered care are needed. Access must be improved for children living in rural and remote settings.

Environmental and Behavioral Factors in Association with Lung Function Impairment in Children Living in Wuhan, China.

Children’s lung function is a significant predictor of health status throughout their lifetime. This study aims to identify the prevalence of impaired lung function in children and the potential influencing factors in elementary school children of Wuhan, China. Children of 6−12 years old were enrolled from elementary schools in Wuhan, China, in 2018, on the basis of a cross-sectional study design. Information on personal behavior patterns and household characteristics, as well as parental factors, was collected based on a questionnaire survey. Spirometry was used to measure fifteen lung function indicators. Logistic regression models were used to estimate odds ratios of prevalence of impaired lung function with regard to socioeconomic, personal behavior patterns, household, and parental factors, respectively. Four lung function indicators such as FET and EVC in urban children had higher values than in the suburban children after adjusting for confounders (p < 0.05). A higher prevalence of impaired lung function (FEV6, FEV3, EVC, and VC) was found in the children from the rural area than in those from the urban area. A sex difference in FET impairment was observed, however, no significant difference in impairment in other lung function indicators were found between girls and boys. The elevated height and weight of the children was significantly associated with an increased and decreased prevalence of impaired lung function, respectively, particularly both for FEV6, FEV3, FIVC, and FIV1. Opening windows for a longer time in summer was significantly associated with a lower prevalence of impaired FEF25 and MVV, and an extended time of opening windows in winter was significantly associated with a lower prevalence of impaired FEV6. While, opening windows for a longer time in autumn was significantly associated with higher prevalence of impaired FEV6 and FEV1/VC. Home renovations, doing physical exercise for more than 30 min per day, air pollution exposure during commuting, sleeping in own rooms, height stunting, and preterm birth were significantly associated with an increased risk of impaired lung function. Breastfeeding, having a father with a white-collar profession and with a higher education level were positively associated with the lower prevalence of impaired lung function. Impaired lung function is commonly found in school children in Wuhan, nowadays. Breastfeeding, opening windows long-term in summer and winter, higher socioeconomics, and an urban living environment were protective factors for impaired lung function. However, opening windows long-term and using air conditioning short-term in autumn, as well as home renovations, doing physical exercise for more than 30 min per day, preterm birth, height stunting, and air pollution exposure during commuting were regarded as significant risk factors for impaired lung function. Promoting breastfeeding, lengthening window opening times in winter and summer, and controlling household renovation and air pollution exposure during commuting are recommended to reduce the risk of impaired lung function in children in Wuhan.

Clinical Characteristics of Kawasaki Disease Combined with Liver Function Impairment in Children

Clinical Characteristics of Kawasaki Disease Combined with Liver Function Impairment in Children

Relationship between methylenetetrahydrofolate reductase gene polymorphisms and methotrexate drug metabolism and toxicity.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, and methotrexate (MTX) is the key drug for ALL. Studies on the relationship between High-Dose methotrexate (HD-MTX) toxicity and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genes have drawn different conclusions. This study aimed to investigate the relationship between the polymorphism of MTHFR C677T and A1298C genes and the toxicity responses of MTX. The MTHFR C677T and A1298C genotypes of 271 children with ALL who received HD-MTX chemotherapy in southern China from September 2017 to June 2021 were analyzed, and the toxicity of HD-MTX was evaluated and analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The MTHFR C677T and A1298C gene polymorphisms were not correlated with the 48-hour MTX blood concentrations (P>0.05). Unconditional logistic regression model analysis also revealed that the risk of liver function impairment [odds ratio (OR) =1.656, 95% confidence interval (CI): 1.179-2.324, P<0.05] and mucosal damage (OR =1.508, 95% CI: 1.042-2.183, P<0.05) were 1.656 and 1.508 times higher for the heterozygous mutant (CT), and homozygous mutant (TT) mutant type than for the wild-type (CC), wild-type, respectively. The risk of neutropenia and liver function impairment were 0.498 (OR =0.498, 95% CI: 0.251-0.989, P<0.05) and 6.067 (OR =6.067, 95% CI: 1.183-31.102, P<0.05) times higher in low-risk children with CT+TT mutant genotypes than in those with CC wild genotypes, respectively. Furthermore, the risk of mucosal damage was 1.906 times higher in high-risk children with the CT+TT genotype than in those with the CC genotype (OR =1.906, 95% CI: 1.033-3.518, P<0.05). The MTHFR A1298C genotypes differed in the incidence of liver function damage and gastrointestinal toxic reactions in children with ALL. Nonetheless, no increased risk of liver function impairment nor gastrointestinal reactions in children with the heterozygous mutant (AC)+CC mutation was observed. Advancements in MTHFR genotype testing in children with ALL and the introduction of personalised treatments based on genotype results during HD-MTX chemotherapy will help to predict, prevent, and reduce the occurrence of adverse MTX-related toxic reactions.

Effect of diagnosis delay on pulmonary function in children with asthma

BackgroundThe effects of a delayed diagnosis of asthma on lung function in children have not been well investigated. Therefore, a retrospective cohort study was conducted in a children’s hospital to analyse the effect of delayed diagnosis time on lung function in children with asthma.MethodsWe conducted a retrospective cohort study in Jinan Children's Hospital from January 1, 2010, to December 31, 2020. All children were divided into different groups according to the presence or absence of rhinitis, age at first onset (first coughing and wheezing attack) and delayed diagnosis duration (≤ 3 months, 3–12 months, 1–3 years, 3–5 years and > 5 years).ResultsA total of 1,014 children with asthma were included in this study. The median (quartile) delay in asthma diagnosis among all participants was 11 (2, 26) months. The shortest delay in diagnosis time was on the same day of onset, and the longest delay in diagnosis time was 10 years. The median (quartile) duration of delayed diagnosis was 10 (2, 26) months in 307 asthmatic children without rhinitis and 11 (2, 26) months in 707 children with asthma and rhinitis (P < 0.05). The delayed diagnosis time was shorter among female children than among male children (P < 0.05), and the first %predicted forced volume capacity (FVC%pred) results for females were higher than those for males (P = 0.036). The children whose age at first asthma onset was ≤ 3 years had a longer delayed diagnosis duration than those whose age at first onset was > 3 years (P < 0.05). The FVC%pred and %predicted forced expiratory volume in 1 s (FEV1%pred) in the first and second pulmonary function tests were significantly lower in the five delayed diagnosis groups (all P < 0.05). After standardised treatment for 3–6 months, FVC%pred showed a significant difference in the third test among the 5 groups (P < 0.05), but the other pulmonary function indices showed no significant difference. Logistic regression analysis showed that longer delay and young age of onset were associated with lower lung function (P < 0.05), whereas sex, rhinitis and eczema had no significant effects (all P > 0.05) on FVC%pred and FEV1%pred.ConclusionAlthough delayed asthma diagnosis can lead to lung function impairment in children with asthma, lung function can be improved quickly after standardised treatment. Therefore, early asthma diagnosis and standardised treatment are very important.

Pulmonary function in children with persistent tachypnea of infancy.

Data on the prevalence and type of lung function impairment in preschool and school-aged children previously diagnosed with persistent tachypnea of infancy (PTI) are scarce. Therefore, this study aims to assess pulmonary function in this age group. Children diagnosed with PTI over 3 years old were admitted for follow-up visits and healthy controls were enrolled. The study group included children who were able to complete pulmonary function tests (PFTs). Medical history, physical examination, and pulmonary function (spirometry, body plethysmography, impulse oscillometry, nitrogen multiple breath washout test, diffusing capacity for carbon monoxide [DLCO ]) were assessed. Thirty-seven children (26 boys, 11 girls; median age: 5.6 years) diagnosed with PTI and 37 healthy controls were recruited. Forced expiratory volume in 1 sand forced vital capacity were significantly lower (-1.12 vs. 0.48, p = 0.002 and -0.83 vs. 0.31, p = 0.009, respectively); respiratory resistance at 5 Hz (0.06 vs. -0.62, p = 0.003), resonant frequency (1.86 vs. 1.36, p = 0.04), residual volume(RV) (2.34 vs. -1.2, p < 0.0001), RV%TLC (total lung capacity) (2.63 vs. -0.72, p < 0.0001), and specific airway resistance (5.4 vs. 2.59, p = 0.04) were significantly higher in PTI patients as compared with controls (data were presented as median z-score). Air trapping was found in 60.0%, and abnormally high lung clearance index and DLCO were found in 73.3% and 90.9% of PTI patients, respectively. This study demonstrated that lung function is affected in most children with PTI. PFTs showed that peripheral airways are the major zone of functional impairment.

Quercetin alleviates kainic acid-induced seizure by inhibiting the Nrf2-mediated ferroptosis pathway.

Epilepsy is one of the most common neurological disorders in childhood. However, classical antiepileptic drugs are linked with drug toxicity and cognitive function impairment in children. Hence, it is essential to develop a novel therapy to solve this problem. Currently, studies indicate regulating the nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated ferroptosis pathway represents a potential advanced therapy for seizures. Hence, the present study aimed to explore whether quercetin, a natural polyphenol, could alleviate seizure-induced neuron death and preserve cognitive function by inhibiting Nrf2-mediated ferroptosis. Kainic acid-induced epileptic mice model, morris water maze (MWM) test, cell counting kit-8 (CCK-8) assays, western blotting analysis, enzyme-linked immunosorbent assay, flow cytometry, quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence staining, and RNA sequencing analysis were employed to explore the potential mechanisms by which quercetin exerts protective effects on seizure-induced neuron death in kainic acid-induced epileptic mice model and glutamate-induced HT22 neuronal cell death. Our findings suggested the association between the Nrf2-mediated ferroptosis pathway and seizures in a clinical setting. Quercetin pretreatment alleviates seizure-like behaviors and cognitive impairment in KA-induced epileptic mice. Additionally, in vitro, co-treatment with quercetin effectively exerts neuroprotective effects in glutamate-induced HT22 neuronal cell death. These protective effects were also closely linked to regulating the Nrf2-mediated ferroptosis pathway. Furthermore, bioinformatic profiling revealed that the SIRT1/Nrf2/SLC7A11/GPX4 pathway plays a crucial role in the Glu-induced HT22cell death pretreated with quercetin. These findings indicated that quercetin effectively protects against seizure-induced neuron death in vivo and in vitro and alleviates cognitive function impairment via the SIRT1/Nrf2/SLC7A11/GPX4 pathway.