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Background Although the long-term consequences of the Coronavirus Disease-2019 (COVID-19) pandemic are yet to be fully comprehended, a syndrome symptomatically akin to the COVID-19 disease has been defined, for children and adolescents, in February 2023 by the World Health Organization (WHO) as 'post COVID-19 condition' (PCC). Potential consequences of COVID-19 that affect developmental milestones in children and adolescents should be comprehended in their magnitude and duration. The aim is to investigate the most common symptoms and predictors or risk factors for pediatric PCC. Methods In this umbrella review, the population of interest was defined as children and adolescents from 0 to 19 years old presenting PCC symptoms as defined by the WHO in the International Classification of Diseases. The intervention considered was general follow-up activity to monitor the patients' recovery status. No comparator was chosen, and the outcomes were symptoms of PCC and predictors or risk factors of developing PCC. Methodological quality, risk of bias and the level of overlap between studies were assessed. A random-effects meta-analytic synthesis of respective estimates with inverse variance study weighting was carried out, for the primary studies included by the reviews retrieved, regarding predictors or risk factors reported. Results We identified six eligible systematic reviews, five with meta-analyses, from three databases. The most common symptoms reported were fatigue and respiratory difficulties; female sex and older age were the most reported factors associated with the development of pediatric PCC. Conclusions A deeper understanding of pediatric PCC requires well-designed and clearly defined prospective studies, symptom differentiation, and adequate follow-up. [ABSTRACT FROM AUTHOR]

Background Young adults in Neither in Employment, Education nor Training (NEET) are at risk of adverse labour market outcomes. Earlier studies often measured NEET status at one time point or compared persistent NEETs with non-NEETs, neglecting other patterns of NEET status. Evidence on early life factors associated with NEET patterns is lacking. This study aims to (i) identify patterns of NEET status over time and (ii) examine whether factors in childhood and adolescence are associated with these patterns. Methods Data were used from 1499 participants of the TRacking Adolescents' Individual Lives Survey (TRAILS), a Dutch prospective cohort study with 15-year follow-up. NEET status was assessed at ages 19, 22 and 26. Socioeconomic status of parents (SES), intelligence and negative life events were measured at age 11, educational attainment at age 26 and mental health problems at ages 11, 13.5 and 16. Data were analyzed using multinomial logistic regression analysis. Results Four NEET patterns were identified: (i) non-NEETs (85.2%), (ii) early NEETs (4.5%), (iii) late NEETs (5.7%) and (iv) persistent NEETs (4.5%). Reporting internalizing problems at age 11 was a risk factor for early and late NEETs [odds ratio (OR) 2.77, 95% confidence interval (CI) 1.16–6.62; OR 5.00, 95% CI 2.22–11.3, respectively]. Low parental SES, lower intelligence scores and negative life events (≥3) were risk factors for persistent NEETs (OR 4.45, 95% CI 2.00–9.91; OR 0.96, 95% CI 0.94–0.98; OR 4.42, 95% CI 1.62–12.08, respectively). Conclusions The results highlight the importance of timing and duration of NEET status and emphasize the need for tailored interventions to prevent specific NEET patterns. [ABSTRACT FROM AUTHOR]

Background: Cognitive development in pre-schoolers through healthy eating and socio-demographic support is crucial for their later lives. We investigated healthy eating encouragement, socio-demographic factors and their association with cognitive development in pre-schoolers. Methods: Quantitative data were collected using a multi-stage random sampling between February and April 2021. Pre-schoolers 36 and 71 months and their primary caregivers were recruited from three local government units of Rupandehi district. We compared healthy eating encouragement, socioeconomic and demographic factors with cognitive development using t-test, one-way analysis of variance and multiple linear regression analysis to identify the predictors of the cognitive development among pre-schoolers. Results: Cognitive development in pre-schoolers is significantly positively associated with age 36-48 months (β = 0.153; 95% CI: 0.12, 13.96), living in a nuclear family (β = 0.121; 95% CI: 0.59, 6.88) and following Buddhism (β = 0.148; 95% CI: 0.88, 14.32). Conversely, children from specific caste/ethnic backgrounds, such as Dalit (β = -0.126; 95% CI: -10.79, -0.68), Janajati (β = -0.237; 95% CI: -6.14, -2.09) and non-Dalit Tarai caste or ethnicity (β = -0.133; 95% CI: -3.46, -0.25) and mothers employed (β = -0.134; 95% CI: -10.62, -1.44) show significantly lower levels of cognitive development. Conclusions: The finding shows that socioeconomic factors have an influence on cognitive development and also stimulate the adoption of healthy eating encouragement practices. [ABSTRACT FROM AUTHOR]

Background Fluoride may be a developmental neurotoxicant at elevated exposures. We merged new data from a prospective Odense Child Cohort (OCC) with results from two previous birth cohort studies from Mexico and Canada to characterize the dose–effect relationship in greater detail. Methods The OCC contributed 837 mother–child pairs to the total of >1500. We measured creatinine-adjusted urine-fluoride concentrations in maternal urine samples obtained during late pregnancy. Child IQ was determined at age 7 years using an abbreviated version of the Wechsler Intelligence Scales for Children. Findings from the three cohorts were used to calculate the joint benchmark concentration (BMC) and the lower confidence limit (BMCL) after adjustment for covariables. Results In the OCC, urine-fluoride concentrations varied between 0.08 and 3.04 mg/l (median 0.52 mg/l) but were not significantly associated with full-scale IQ at age 7 years (β = 0.08; 95% confidence interval −1.14 to 1.30 for a doubling in exposure). No difference was apparent between boys and girls. In the OCC, the BMC was 0.92 mg/l, with a BMCL of 0.30 mg/l. The joint analysis of all three cohorts showed a statistically significant association between urine-fluoride and IQ, with a BMC of 0.45 mg/l (BMCL, 0.28 mg/l), slightly higher than the BMC previously reported for the two North American cohorts alone. Conclusions As the BMCL reflects an approximate threshold for developmental neurotoxicity, the results suggest that pregnant women and children may need protection against fluoride toxicity. [ABSTRACT FROM AUTHOR]

Background The obligation to pay for asthma medication in a country with universal healthcare might lead to increased asthma exacerbations and inequitable healthcare access for children from low-income households. Thus, the aim of this study was to examine the association between household income and childhood/preschool asthma regarding hospitalization and medication receipt. Methods In this nationwide register-based cohort study, we encompassed all 3-year-old children residing in Denmark, born between 2000 and 2014, along with their linked parents and followed them until their sixth birthday. Household income was divided into quartiles. Asthma was categorized in two mutually exclusive groups as either the redemption of two prescriptions for asthma medication or receiving a hospital diagnosis. We utilized Poisson regression to estimate the risk ratio (RR). Results The analysis included 834 422 preschool children. The prevalence of asthma dependent on medication alone was 7.3%, while 1.8% of children necessitated asthma-related hospitalization. Income inequality was evident across all income quartiles. Notably, children from the lowest income quartile had a RR of 0.95 (95% CI: 0.92–0.98) of redeeming asthma medication and conversely a RR of 1.18 (95% CI: 1.14–1.23) of asthma-related hospitalization. Conclusions Despite universal healthcare, income inequality has a dual impact on children from low-income households. They face a diminished risk of redeeming asthma medication and a higher susceptibility to asthma-related hospitalizations indicating an unequal access to healthcare. Prioritizing efforts to reduce childhood health inequalities is crucial. However, further research, particularly qualitative studies, is needed to better comprehend the underlying mechanisms to address the complexities of income inequality. [ABSTRACT FROM AUTHOR]

Background Routine childhood vaccination programs have had enormous positive public health impacts worldwide. However, in some areas, these benefits may be impeded by vaccine hesitancy and undervaccination. We estimated the number of reported cases of measles, pertussis, mumps and poliomyelitis averted in Sweden after the introduction of routine childhood vaccination programs. Methods We used annual national data on population size and the number of reported cases of measles (1911–2019), pertussis (1911–2019), mumps (1914–2019) and poliomyelitis (1910–2019) for Sweden. For each disease, we calculated the median and 95% confidence interval of the annual pre-vaccination incidence to estimate the number of counterfactual cases; that is, the estimated number of cases that would have been observed in the post-vaccination period had no vaccine been introduced (median incidence × average annual population). For the post-vaccination periods, we calculated reported cases averted and assumed all decreases were due to vaccines. Results In total, for all four diseases combined, over 2.1 million cases were reported over the respective surveillance periods. Since the introduction of vaccinations, we estimate that over 1.5 million reported cases of these four diseases combined have been averted: measles (633 091), pertussis (608 670), mumps (262 951) and poliomyelitis (58 240). However, due to underreporting, especially during pre-vaccination years, these are likely underestimates. Conclusions Since the introduction of these routine childhood vaccination programs in Sweden, a substantial number of reported cases of vaccine-preventable diseases have been averted. Vigilance against both failure to vaccinate and undervaccination is necessary to prevent future increases of these vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Background Childhood vision impairment (VI) can adversely impact health and social outcomes and limit life chances. We investigated whether its adverse impacts into adult life changed during a period in which legislation, policy and services to address inequalities relating to disability were implemented. Methods Cross-cohort study comprising 14 247 participants from the 1946, 1958 and 1970 British birth cohorts (BC). Participants dichotomized as VI at age 15/16 (distance visual acuity was 6/12 or worse in the better-seeing eye) or normally sighted. Associations of childhood VI with health, well-being, socioeconomic and social participation outcomes in mid-adult life were investigated using regression models adjusted for participants' early life socioeconomic markers and sex. Change in adjusted odds ratios of >10% in the same direction in successive cohorts, or a > 20% difference between 1970BC and one older cohort were considered meaningful. Results Trends over time in impacts of childhood onset VI into mid-adult life were complex. This included worsening of odds of poorer physical health (odds ratio 1.47; 95% confidence interval 1.02–2.14), living in unsatisfactory (1.54; 1.03–2.29) or overcrowded (2.34; 1.26–4.06) households, being unemployed (2.19; 1.19–3.97) and not gaining additional educational qualifications during mid-adult life (1.61; 1.08–2.47). By contrast the odds of not participating in some social activities (e.g. seeing friends) improved over time. Associations with other outcomes were unchanged. Conclusions Many adverse impacts of childhood VI do not appear ameliorated over time by legislation, policies and provision that would have been expected to reduce inequalities. Moreover, some were increased. Childhood VI continues to cast a life-long shadow. [ABSTRACT FROM AUTHOR]

Background Children with major congenital anomalies may be at risk of poor educational outcomes. We aimed to evaluate the educational achievement of children born with major congenital anomalies compared with children without major congenital anomalies in relation to sociodemographic factors. Methods We performed a registry-based study including 401 544 children in Finland, graduates of the compulsory school who applied to secondary education. We used health data from the Finnish Register of Congenital Malformations for children born from 1995 to 2002 linked with education data from the Finnish Ministry of Education and Culture. We used generalized linear regression to compare the mean grade differences of children with specific major congenital anomalies and 'All anomalies' subgroup (major congenital anomalies, chromosomal syndromes, and multiple anomalies) with reference children. Results Children with major congenital anomalies were less likely to apply for further education than reference children (88.0% vs. 96.8%; odds ratio = 4.13; 95% confidence interval, 3.92–4.36). For most non-chromosomal congenital anomalies, children born with congenital anomalies had similar educational achievement to the reference children. For the 'All anomalies' subgroup, children with congenital anomalies had lower educational achievement than reference children. Among children with congenital anomalies, male sex, lower maternal educational levels and younger maternal age were associated with lower educational achievement. Conclusions For children applying to further education, most non-chromosomal congenital anomalies were not associated with lower educational achievement. Nevertheless, efforts are needed to improve educational achievement in children with major congenital anomalies associated with maternal sociodemographic background. [ABSTRACT FROM AUTHOR]

Objectives To identify predictors of a severe clinical course of multisystem inflammatory syndrome in children (MIS-C), as defined by the need for inotropic support. Methods This retrospective study included patients diagnosed with MIS-C (according to the CDC definition) in nine Israeli and one US medical centre between July 2020 and March 2021. Univariate and multivariate regression models assessed odds ratio (OR) of demographic, clinical, laboratory and imaging variables during admission and hospitalization for severe disease. Results Of 100 patients, 61 (61%) were male; mean age 9.65 (4.48) years. Sixty-five patients were hypotensive, 44 required inotropic support. Eleven patients with MIS-C fulfilled Kawasaki disease diagnostic criteria; 87 had gastrointestinal symptoms on admission. Echocardiographic evaluation showed 10 patients with acute coronary ectasia or aneurysm, and 37 with left ventricular dysfunction. In a univariate model, left ventricular dysfunction was associated with severe disease [OR 4.178 (95% CI 1.760, 9.917)], while conjunctivitis [OR 0.403 (95% CI 0.173, 0.938)] and mucosal changes [OR 0.333 (95% CI 0.119, 0.931)] at admission were protective. Laboratory markers for a severe disease course were low values of haemoglobin, platelets, albumin and potassium; and high leukocytes, neutrophils, troponin and brain natriuretic peptide. In multivariate analysis, central nervous system involvement and fever >39.5°C were associated with severe disease. Mucosal involvement showed 6.2-fold lower risk for severe disease. Low haemoglobin and platelet count, and elevated C-reactive protein and troponin levels were identified as risk factors for severe disease. Conclusion Key clinical and laboratory parameters of MIS-C were identified as risk factors for severe disease, predominantly during the disease course and not at the time of admission; and may prompt close monitoring, and earlier, more aggressive treatment decisions. Patients presenting with a Kawasaki-like phenotype were less likely to require inotropic support. [ABSTRACT FROM AUTHOR]

Objectives Acetaminophen has gained interest in the neonatal community for its use in the management of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) comparing the efficacy and safety of acetaminophen with indomethacin for the management of HsPDA in preterm infants. Methods We searched PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library (CDSR and Central), EBSCO CINAHL, and SCOPUS from inception to June 15, 2021. Bibliographies of identified studies were searched for additional references. Data were analyzed with Review Manager (RevMan) Version 5.3. Results Four RCTs were identified, enrolling a total of 380 subjects. There was no difference between the interventions for the outcome of PDA closure after one course (RR 1.04 [95% CIs: 0.84, 1.29], P -value 0.70) or after two courses of treatment (RR 1.01 [95% CIs: 0.92, 1.12], P -value 0.77); and for the outcome of PDA ligation (RR 1.56 [95% CIs: 0.48, 5.12], P -value 0.46). However, patients who received acetaminophen had lower rates of necrotizing enterocolitis (RR 0.37 [95% CIs: 0.14, 0.95], P -value 0.04). There were no significant differences noted in the other clinical outcomes, that is, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, and death. Two studies noted significant post-treatment elevation of serum creatinine and blood urea with indomethacin, as compared to none with acetaminophen use. Conclusions Acetaminophen has comparable efficacy to indomethacin for the outcome of HsPDA closure, with a better safety profile, that is, lesser rates of necrotizing enterocolitis and post-treatment azotemia noted with its use. [ABSTRACT FROM AUTHOR]

Background The potential for cefepime prophylaxis to reduce bloodstream infections (BSIs) in pediatric patients with acute myelogenous leukemia (AML) has been incompletely characterized. Methods A retrospective quasi-experimental study of patients under 21 years of age admitted with AML from 2010 through 2018 at two affiliated pediatric tertiary-care hospitals before and after the adoption of routine cefepime prophylaxis for afebrile AML patients during profound neutropenia. Results The rate of BSIs per 1000 neutropenia days was significantly lower in the prophylaxis group than the baseline group (2.6 vs 15.5, incidence rate ratio [IRR] 0.17, 95% CI 0.09–0.32). Interrupted time-series analysis showed that a sharp reduction in BSIs coincided with the implementation of prophylaxis. Bacteremia with viridans group streptococci was frequent in the baseline group but not observed after adopting prophylaxis. Despite the increased use of cefepime, the rate of cefepime-nonsusceptible BSIs per 1000 neutropenia days decreased (1.6 vs 4.1, IRR 0.40, 95% CI 0.16–0.99). The median number of febrile neutropenia episodes per patient also decreased in the prophylaxis group, as did the proportion of patients admitted to the intensive care unit (ICU) (22/51 (43.1%) vs 26/38 (68.4%); risk difference −25.3%, 95% CI −44.4 to −2.8). A trend was observed toward an increased proportion of patients with Clostridioides difficile infection in the prophylaxis group (10/51 (19.6%) vs 3/38 (7.9%); risk difference 11.7%, 95% CI −3.4 to 29.0). Conclusions Cefepime prophylaxis was associated with a significant reduction in BSIs, febrile neutropenia, and ICU admission among pediatric AML patients. [ABSTRACT FROM AUTHOR]

Background Even though dietary sugars are the most important nutrient for caries development, the disease process is dependent on other dietary practices. The intake of individual nutrient components cannot be evaluated separately from the overall diet which includes other nutrients, foods and habits. Therefore, the aim of this study was to investigate the association between adherence to dietary guidelines and dental caries. Methods This study was embedded in the Generation R Study, conducted in Rotterdam, the Netherlands. In total, 2911 children were included in the present analyses. Dietary intake at the age of 8 years was assessed using food-frequency questionnaires. Diet quality scores were estimated, reflecting adherence to Dutch dietary guidelines. Dental caries was assessed at the age of 13 years using intra-oral photographs. Associations were estimated using multinomial logistic regression analyses, adjusted for sociodemographic characteristics and oral hygiene practices. Results The prevalence of dental caries at the age of 13 years was 33% (n  = 969). Better diet quality was associated with a lower occurrence of severe dental caries after adjustments for sociodemographic factors [e.g. highest vs. lowest quartile of diet quality: odds ratio (OR) 0.62, 95% confidence interval (CI) 0.39–0.98]. After additional adjustments for oral hygiene practices, this association was not statistically significant (OR 0.65, 95% CI 0.41–1.03). Conclusion Adherence to dietary guidelines has the potential to reduce dental caries in children; however, with proper oral hygiene practices, this relationship might be attenuated. To understand the role of dietary patterns and dental caries, the contributing role of daily eating occasions needs to be studied further. [ABSTRACT FROM AUTHOR]

Background Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania. Methods From 2019 to 2021, we enrolled CALHIV aged 1–19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS. Results Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81–0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99–1.34), age 5–9 years (aPR 1.16, 95% CI: 1.07–1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04–1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72–0.92) or two or more (aPR 0.79, 95% CI: 0.66–0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78–0.99) or three or more (aPR 0.77, 95% CI: 0.63–0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively. Conclusions Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed. [ABSTRACT FROM AUTHOR]

Background To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. Methods Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). Results In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1 , VPS37C , TGFB1 , MX2 , and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%–98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%–97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. Conclusions MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C. [ABSTRACT FROM AUTHOR]

Objectives Clinicians concerned about long-term safety of biologics in JIA may consider tapering or stopping treatment once remission is achieved despite uncertainty in maintaining drug-free remission. This analysis aims to (i) calculate how many patients with JIA stop biologics for remission, (ii) calculate how many later re-start therapy and after how long, and (iii) identify factors associated with re-starting biologics. Methods Patients starting biologics between 1 January 2010 and 7 September 2021 in the UK JIA Biologics Register were included. Patients stopping biologics for physician-reported remission, those re-starting biologics and factors associated with re-starting, were identified. Multiple imputation accounted for missing data. Results Of 1451 patients with median follow-up of 2.7 years (IQR 1.4, 4.0), 269 (19%) stopped biologics for remission after a median of 2.2 years (IQR 1.7, 3.0). Of those with follow-up data (N = 220), 118 (54%) later re-started therapy after a median of 4.7 months, with 84% re-starting the same biologic. Patients on any-line tocilizumab (prior to stopping) were less likely to re-start biologics (vs etanercept; odds ratio [OR] 0.3; 95% CI: 0.2, 0.7), while those with a longer disease duration prior to biologics (OR 1.1 per year increase; 95% CI: 1.0, 1.2) or prior uveitis were more likely to re-start biologics (OR 2.5; 95% CI: 1.3, 4.9). Conclusions This analysis identified factors associated with successful cessation of biologics for remission in JIA as absence of uveitis, prior treatment with tocilizumab and starting biologics earlier in the disease course. Further research is needed to guide clinical recommendations. [ABSTRACT FROM AUTHOR]

Background Human bocavirus 1 (HBoV1) is frequently codetected with other viruses, and detected in asymptomatic children. Thus, the burden of HBoV1 respiratory tract infections (RTI) has been unknown. Using HBoV1-mRNA to indicate true HBoV1 RTI, we assessed the burden of HBoV1 in hospitalized children and the impact of viral codetections, compared with respiratory syncytial virus (RSV). Methods Over 11 years, we enrolled 4879 children <16 years old admitted with RTI. Nasopharyngeal aspirates were analyzed with polymerase chain reaction for HBoV1-DNA, HBoV1-mRNA, and 19 other pathogens. Results HBoV1-mRNA was detected in 2.7% (130/4850) samples, modestly peaking in autumn and winter. Forty-three percent with HBoV1 mRNA were 12–17 months old, and only 5% were <6 months old. A total of 73.8% had viral codetections. It was more likely to detect HBoV1-mRNA if HBoV1-DNA was detected alone (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.7–8.9) or with 1 viral codetection (OR: 1.9, 95% CI: 1.1–3.3), compared to ≥2 codetections. Codetection of severe viruses like RSV had lower odds for HBoV1-mRNA (OR: 0.34, 95% CI: 0.19–0.61). The yearly lower RTI hospitalization rate per 1000 children <5 years was 0.7 for HBoV1-mRNA and 8.7 for RSV. Conclusions True HBoV1 RTI is most likely when HBoV1-DNA is detected alone, or with 1 codetected virus. Hospitalization due to HBoV1 LRTI is 10–12 times less common than RSV. [ABSTRACT FROM AUTHOR]

Background Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs). Methods UK-based, multi-center, retrospective, diagnostic accuracy study. Included : any child <16 years presenting to ED with history of fever and travel to a malaria-endemic country, between 01/01/2016 and 31/12/2017. Diagnosis: microscopy for malarial parasites (clinical reference standard) and RDT (index test). UK Health Research Authority approval: 20/HRA/1341. Results There were 47 cases of malaria out of 1,414 eligible cases (prevalence 3.3%) in a cohort of children whose median age was 4 years (IQR 2–9), of whom 43% were female. Cases of Plasmodium falciparum totaled 36 (77%, prevalence 2.5%). The sensitivity of RDT alone to detect malaria infection due to any Plasmodium species was 93.6% (95% CI 82.5–98.7%), specificity 99.4% (95% CI 98.9–99.7%), positive predictive value 84.6% (95% CI 71.9–93.1%) and negative predictive value 99.8% (95% CI 99.4–100.0%). Sensitivity of RDT to detect P. falciparum infection was 100% (90.3–100%), specificity 98.8% (98.1–99.3%), positive predictive value 69.2% (54.9–81.2%, n = 46/52) and negative predictive value 100% (99.7–100%, n = 1,362/1,362). Conclusions RDTs were 100% sensitive in detecting P. falciparum malaria. However, lower sensitivity for other malaria species and the rise of pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions in the P. falciparum parasite mandate the continued use of microscopy for diagnosing malaria. [ABSTRACT FROM AUTHOR]

Background Despite guidelines recommending narrow-spectrum perioperative antibiotics (NSPA) as prophylaxis for most children undergoing congenital heart disease (CHD) surgery, broad-spectrum perioperative antibiotics (BSPA) are variably used, and their impact on postoperative outcomes is poorly understood. Methods We used administrative data from U.S. hospitals participating in the Vizient Clinical Data Base. Admissions from 2011 to 2018 containing a qualifying CHD surgery in children 0–17 years old were evaluated for exposure to BSPA versus NSPA. Propensity score-adjusted models were used to compare postoperative length of hospital stay (PLOS) by exposure group, while adjusting for confounders. Secondary outcomes included subsequent antimicrobial treatment and in-hospital mortality. Results Among 18 088 eligible encounters from 24 U.S. hospitals, BSPA were given in 21.4% of CHD surgeries, with mean BSPA use varying from 1.7% to 96.1% between centers. PLOS was longer for BSPA-exposed cases (adjusted hazard ratio 0.79; 95% confidence interval [CI]: 0.71–0.89, P <.0001). BSPA was associated with higher adjusted odds of subsequent antimicrobial treatment (odds ratio [OR] 1.24; 95% CI: 1.06–1.48), and there was no significant difference in adjusted mortality between exposure groups (OR 2.06; 95% CI: 1.0–4.31; P =.05). Analyses of subgroups with the most BSPA exposure, including high-complexity procedures and delayed sternal closure, also did not find (but could not exclude) a measurable benefit from BSPA on PLOS. Conclusions BSPA use was common in high-risk populations, and varied substantially between centers. Standardizing perioperative antibiotic practices between centers may reduce unnecessary broad-spectrum antibiotic exposure and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

In this ongoing study, substantially increased ancestral SARS-CoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable. (NCT04816643) [ABSTRACT FROM AUTHOR]

Background The severity of SARS-CoV-2-related diseases in children remains unclear. This study aimed to describe the incidence of French pediatric intensive care units (PICUs) admissions with acute COVID-19, incidental positive SARS-CoV-2 test result, and multisystem inflammatory syndrome in children (MIS-C) during the delta and omicron variant periods. Methods This study used the French PICU registry to obtain data on all patients admitted to 41 French PICUs diagnosed with acute COVID-19, incidental positive SARS-CoV-2 test result, or MIS-C between August 30, 2021 and April 20, 2022. Data regarding the total number of positive SARS-CoV-2 polymerase chain reaction results according to the type of variants were obtained from the French National Public Health Agency. Results Of 745 children, 244 (32.8%) were admitted for acute COVID-19, 246 (33.0%) for incidental positive SARS-CoV-2 test results, and 255 (34.2%) for MIS-C. The incidence of each group was higher with delta than with omicron. The incidence rate ratios with the delta variant were 7.47 (95% CI, 4.22–13.26) for acute COVID-19, 4·78 (95% CI, 2.30–9.94) for incidental positive SARS-CoV-2 test results, and 10.46 (95% CI, 5.98–18.31) for MIS-C compared to the omicron variant. The median age was 66 (7.7–126.8) months; 314 (42%) patients had comorbidities. Patients with acute COVID-19 and incidental positive SARS-CoV-2 test results had similar proportions of comorbidities. No patient with MIS-C died, whereas the mortality rates in the acute COVID-19 and incidental positive SARS-CoV-2 test results groups were 6.8% and 3.8%, respectively. Conclusions The incidence of acute COVID-19, incidental positive SARS-CoV-2 test results, and MIS-C admitted to the PICU were significantly higher with the delta variant than with the omicron variant. [ABSTRACT FROM AUTHOR]

Background Covid-19 has had a major negative impact on children's engagement in health-related behaviors. This study examines trends in children's screen time, outdoor play and sports club membership in pre- (2016–19), mid- (2020–21) and post- (2021–22) Covid years. Also, predicting factors (gender, age and active commuting) of these health-related behaviors are examined. Methods Data were collected via yearly self-report questionnaires among pupils in Grades 3–6 (mean age 10.14 ± 1.25 years; total n over the five cohorts = 6351, 50.8% girls). Multilevel path models were constructed in Mplus to examine whether children's screen time, outdoor play and sports club membership differed between pre-, mid- and post-Covid years; and which factors predicted engagement in these health-related behaviors (using data of all cohorts). Results During and after Covid-19, children's screen time was higher, while they engaged less in outdoor play and were less often member of a sports club than before. Although these negative trends peaked during Covid-19, they slowly seem to be returning to pre-Covid levels in recent year. Younger children, girls and active commuters had less minutes screen time per day and played outdoors more days per week; boys and active commuters were more often sports club member. Conclusions Although in the first year post-Covid children seem to be engaging more in health-related behaviors than during Covid-19, we still found lower levels of engagement than in the years before Covid-19, underlining the importance of early intervention to ensure an appropriate amount of engagement in health-related behaviors for all children. [ABSTRACT FROM AUTHOR]

Objective To explore the optimal set of trauma activation criteria predicting paediatric patients' need for acute care following multi-trauma, with particular attention to Glasgow Coma Scale (GCS) cut-off value. Methods A retrospective cohort study of paediatric multi-trauma patients aged 0 to 16 years, performed at a Level 1 paediatric trauma centre. Trauma activation criteria and GCS levels were examined with respect to patients' need for acute care, defined as: direct to operating room disposition, intensive care unit admission, need for acute interventions in the trauma room, or in-hospital death. Results We enrolled 436 patients (median age 8.0 years). The following predicted need for acute care: GCS <14 (adjusted odds ratio [aOR] 23.0, 95% confidence interval [CI]: 11.5 to 45.9, P < 0.001), hemodynamic instability: (aOR 3.7, 95% CI: 1.2-8.1, P = 0.01), open pneumothorax/flail chest (aOR: 20.0, 95% CI: 4.0 to 98.7, P < 0.001), spinal cord injury (aOR 15.4, 95% CI; 2.4 to 97.1, P = 0.003), blood transfusion at the referring hospital (aOR: 7.7, 95% CI: 1.3 to 44.2, P = 0.02) and GSW to the chest, abdomen, neck, or proximal extremities (aOR 11.0, 95% CI; 1.7 to 70.8, P = 0.01). Using these activation criteria would have decreased over- triage by 10.7%, from 49.1% to 37.2% and under-triage by 1.3%, from 4.7% to 3.5%, in our cohort of patients. Conclusions Using GCS<14, hemodynamic instability, open pneumothorax/flail chest, spinal cord injury, blood transfusion at the referring hospital, and GSW to the chest, abdomen, neck of proximal extremities, as T1 activation criteria could decrease over- and under-triage rates. Prospective studies are needed to validate the optimal set of activation criteria in paediatric patients. [ABSTRACT FROM AUTHOR]

Introduction Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning. Methods MEDLINE, EMBASE, PsychINFO, CINAHL, and Clinicaltrials.gov were searched. Observational studies comparing prenatal cannabis use to controls were included. Offspring neuro-behavioural outcomes were grouped in prespecified domains of (1) intelligence and (2) cognitive functioning. Random-effect models were performed for meta-analyses when at least three studies reported the same outcome. All others were summarized qualitatively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework was used to assess evidence certainty. Results Of the 1982 reviewed studies (n = 523,107 patients), 28 were included. Significant heterogeneity and cohort redundancy limited meta-analysis. Very low-quality evidence from pooled analyses showed no significant associations between prenatal cannabis exposure and attention [standardized mean difference = −0.27 (95% CI = −0.60 to 0.07)], global intelligence quotient [−0.16 (−0.42 to 0.10)], reading [−0.05 (−0.29 to 0.20)], written comprehension [−0.09 (−0.40 to 0.22)], spelling [−0.04 (−0.26 to 0.17)], and mathematics [−0.01 (−0.15 to 0.13)]. No significant associations were found between prenatal cannabis exposure for all other outcomes. Individual studies reported significant differences between the heavy use groups and non-exposed, although this did not prove to be significant when outcomes were pooled. Conclusions The current review did not find a clear association between prenatal cannabis use and offspring neuro-behavioural outcomes. However, evidence was low quality and heterogenous. Further prospective investigation is needed to elucidate any potential association between prenatal cannabis use and long-term neuro-developmental outcomes. [ABSTRACT FROM AUTHOR]

Background Penicillin allergy is the most common antibiotic allergy, yet most children labeled as allergic tolerate penicillin. The impact of inaccurate penicillin allergy labels (PALs) on pediatric outpatients is unknown. The objective of this study was to compare outcomes between children with and without a PAL after treatment for outpatient respiratory tract infections (RTI). Methods A retrospective, longitudinal birth cohort study was performed in children who received care in 90 pediatric primary care practices in Philadelphia and Houston metropolitan areas. Prescribing and clinical outcomes of children with a PAL at the time of an RTI were compared to non-allergic children, adjusting for potential confounders. Results Antibiotics were prescribed for 663,473 non-recurrent RTIs among 200,977 children. Children with a PAL (5% of cohort) were more likely than non-allergic children to receive broad-spectrum antibiotics (adjusted relative risk (aRR) 3.24, 95% CI 3.22-3.26) and second-line antibiotics (aRR 4.87, 95% CI 4.83, 4.89). Compared to non-allergic children receiving first-line antibiotics, children with a PAL were more likely to return with adverse drug events (aRR 1.28, 95% CI 1.18–1.39). There was no difference in treatment failure between groups (aRR 0.95, 95% CI 0.90–1.00). Conclusions PALs lead to higher rates of broad-spectrum and second-line antibiotic prescribing in children treated for RTIs in primary care and contribute to unnecessary healthcare utilization through increased adverse events. Given the frequency of PALs, efforts to prevent inappropriate penicillin allergy labeling and promote de-labeling of existing inaccurate allergy labels may improve care of children treated for common bacterial infections. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy of intranasal vaporized lidocaine in reducing pain for children undergoing a nasopharyngeal (NP) swab in the Emergency Department (ED). Study Design A randomized blinded clinical trial was conducted in a paediatric ED. Both participants and the researcher evaluating the primary outcome were blinded. Children aged 6 to 17 years old requiring a NP swab were eligible. Participants were randomly allocated to receive intranasal lidocaine or a sham treatment prior to their NP swab. The primary outcome measure was pain during the swab as assessed by the visual analog scale. Secondary outcome measures were pain using the verbal numeric rating scale, fear using the children fear scale, and adverse effects of the intervention. Results Eighty-eight participants were enrolled—45 in the lidocaine group and 43 controls. The mean visual analog scale scores for pain were 46 mm in the lidocaine group and 53 mm in the control group (mean difference 7 mm; 95% CI: −5 to 19 mm). No serious adverse events were observed. Conclusions Intranasal lidocaine administered prior to NP swabs in the ED failed to show an improvement in pain scores for school-aged children and youth. [ABSTRACT FROM AUTHOR]

We assessed rotavirus vaccine impact using data on acute gastroenteritis (AGE) encounters within an integrated healthcare delivery system during 2000–2018. Following rotavirus vaccine introduction, all-cause AGE rates among children <5 years declined by 36% (95% confidence interval [CI]: 32%–40%) for outpatient and 54% (95% CI: 46%–60%) for inpatient encounters. [ABSTRACT FROM AUTHOR]

Background Antibiotic prescription for uncomplicated upper respiratory tract infection (URTI) in children is not recommended but remains common. The primary objective was to evaluate the relationship between antibiotic prescription for URTI prior to age 2 and antibiotic prescription for URTI after age 2. It was hypothesized that antibiotic prescription for URTI in early childhood may increase the risk of antibiotic use for subsequent URTIs. The secondary objective was to investigate whether this relationship was different for acute otitis media (AOM), for which antibiotics may be indicated. Methods A prospective cohort study was conducted between December 2008 and March 2016 at 9 primary care practices in Toronto, Canada. Healthy children aged 0–5 years that met TARGet Kids! cohort eligibility criteria were included if they had at least one sick visit prior to age 2 and least one sick visit after age 2. Generalized Estimating Equation (GEE) models were used to evaluate this relationship while considering within-subject correlation. Results Of 2380 participants followed for a mean duration of 4.6 years, children who received an antibiotic prescription for URTI prior to age 2 had higher odds of receiving an antibiotic prescription for URTI in later childhood (adjusted odds ratio: 1.39; 95% confidence interval: 1.19 to 1.63; P  < .001). This relationship did not appear to be different for AOM compared to non-AOM URTI. Conclusion Antibiotic prescription for URTI before age 2 was associated with antibiotic prescription for URTI in later childhood. Reducing early life antibiotic prescription for URTI may be associated with reduction in antibiotic prescription for subsequent URTIs. [ABSTRACT FROM AUTHOR]

Background Children of lower-educated parents and children in schools with a relatively high percentage of peers with lower-educated parents (lower parental education schools) are more likely to develop emotional and behavioural problems compared to children in higher-educated households and schools. Universal school-based preventive interventions, such as the Good Behaviour Game (GBG), are generally effective in preventing the development of emotional and behavioural problems, but information about potential moderators is limited. This study examined whether the effectiveness of the GBG in preventing emotional and behavioural problems differs between children in lower- and higher-educated households and schools. Methods Using a longitudinal multi-level randomized controlled trial design, 731 children (M age=6.02 towards the end of kindergarten) from 31 mainstream schools (intervention arm: 21 schools, 484 children; control arm: 10 schools, 247 children) were followed annually from kindergarten to second grade (2004–2006). The GBG was implemented in first and second grades. Results Overall, the GBG prevented the development of emotional and behavioural problems. However, for emotional problems, the GBG-effect was slightly more pronounced in higher parental education schools than in lower parental education schools (B higher parental education schools =−0.281, P  <0.001; B lower parental education schools =−0.140, P   =  0.016). No moderation by household-level parental education was found. Conclusions Studies into universal school-based preventive interventions, and in particular the GBG, should consider and incorporate school-level factors when studying the effectiveness of such interventions. More attention should be directed towards factors that may influence universal prevention effectiveness, particularly in lower parental education schools. [ABSTRACT FROM AUTHOR]

Objective To identify the variables associated with the development of non-criteria manifestations in the presence of antiphospholipid antibodies (aPLs) in a paediatric cohort. Methods Multicentric historical cohort study of children under the age of 18 years to determine thrombotic events (TEs) and non-criteria manifestations in the presence of aPL. Results Eighty-two children were included; 8.5% had at least one TE and 69.5% at least one non-criteria manifestation. Of them, 96.5% did not associate TEs. Haematological manifestations were the most frequent (43.65%), followed by cutaneous (22%), neurological (15.9%) and cardiac (4.9%) events. The most frequent aPLs were: 77.8% LA; 42.7% aCL and 41.5% aβ2GP. The positivity rate was: 64.6% simple, 18.3% double and 17.1% triple. ANA positivity was 68.1%. A bivariate analysis revealed that children with IgM aCL+, IgM aβ2GP+, ANA+, an SLE diagnosis or the absence of TEs had a significantly higher percentage of non-criteria manifestations (P  <0.05). The logistic regression showed family history of autoimmune diseases [odds ratio (OR) 4.26, 95% CI: 0.8, 22.2, P  =0.086] and the absence of TEs (OR 17.18, 95% CI: 1.2, 244.6, P  =0.03) as independent risk factors of developing non-criteria manifestations. An SLE diagnosis, aPL profile and ANA+ were not identified. Conclusion Non-criteria manifestations were more frequent than TEs. A positive family history of autoimmune diseases and the absence of TEs were associated with a higher risk of developing non-criteria manifestations. Therefore, their inclusion as APS classification criteria should be considered in order to get an improved prognosis in the paediatric population. [ABSTRACT FROM AUTHOR]

Background Febrile neutropenia (FN) is an early indicator of infection in oncology patients post-chemotherapy. We aimed to determine clinical predictors of septic shock and/or bacteremia in pediatric cancer patients experiencing FN and to create a model that classifies patients as low-risk for these outcomes. Methods This is a retrospective analysis with clinical data of a cohort of pediatric oncology patients admitted during July 2015 to September 2017 with FN. One FN episode per patient was randomly selected. Statistical analyses include distribution analysis, hypothesis testing, and multivariate logistic regression to determine clinical feature association with outcomes. Results A total of 865 episodes of FN occurred in 429 subjects. In the 404 sampled episodes that were analyzed, 20.8% experienced outcomes of septic shock and/or bacteremia. Gram-negative bacteria count for 70% of bacteremias. Features with statistically significant influence in predicting these outcomes were hematological malignancy (P <.001), cancer relapse (P =.011), platelet count (P =.004), and age (P =.023). The multivariate logistic regression model achieves AUROC = 0.66 (95% CI 0.56–0.76). The optimal classification threshold achieves sensitivity = 0.96, specificity = 0.33, PPV = 0.40, and NPV = 0.95. Conclusions This model, based on simple clinical variables, can be used to identify patients at low-risk of septic shock and/or bacteremia. The model's NPV of 95% satisfies the priority to avoid discharging patients at high-risk for adverse infection outcomes. The model will require further validation on a prospective population. [ABSTRACT FROM AUTHOR]

Objective This study was aimed to assess the incidence of and risk factors for autism spectrum disorder (ASD) among preterm infants born <29 weeks' gestational age (GA). Methods A retrospective cohort study of infants born <29 weeks' GA admitted to two tertiary neonatal intensive care units (2009 to 2017) and followed ≥18 months corrected age (CA) at a neonatal follow-up clinic. The primary outcome was ASD, diagnosed using standardized testing or provisional diagnosis at ≥18 months CA. Patient data and 18-month CA developmental outcomes were obtained from the local Canadian Neonatal Follow Up Network database and chart review. Stepwise logistic regression assessed factors associated with ASD. Results Among 300 eligible infants, 26 (8.7%) were diagnosed with confirmed and 21 (7.0%) with provisional ASD for a combined incidence of 15.7% (95% confidence interval [CI] 11.7 to 20.3). The mean follow-up duration was 3.9 ± 1.4 years and the mean age of diagnosis was 3.7 ± 1.5 years. Male sex (adjusted odds ratio [aOR] 4.63, 95% CI 2.12 to 10.10), small for gestational age status (aOR 3.03, 95% CI 1.02 to 9.01), maternal age ≥35 years at delivery (aOR 2.22, 95% CI 1.08 to 4.57) and smoking during pregnancy (aOR 5.67, 95% CI 1.86 to 17.29) were significantly associated with ASD. Among ASD infants with a complete 18-month CA developmental assessment, 46% (19/41) had no neurodevelopmental impairment (Bayley-III<70, deafness, blindness, or cerebral palsy). Conclusions ASD is common among infants born <29 weeks' GA and possibly associated with identified risk factors. Such findings emphasize the importance of ASD evaluation among infants <29 weeks' GA and for continued reporting of developmental outcomes beyond 18-months of corrected age. [ABSTRACT FROM AUTHOR]

Background Parental education is one of the best predictors of child school achievement. Higher parental education is not only associated with higher child intelligence, but children from highly educated parents also perform better in school due to other family related factors. This study evaluates the relation between parental education, child non-verbal intelligence and parenting practices with child school achievement. Methods Longitudinal data from a large population-based, multi-ethnic cohort of children in the Netherlands (63% Dutch origin) followed from birth to age 13 years (3547 children; 52.3% girls) were analyzed. School achievement was measured at the end of primary school (12 years of age) with a national Dutch academic test score. Parental education was assessed at age 3 years. The non-verbal intelligence of the child was measured at age 6 years and a full intelligence was measured at age 13 years. Maternal and paternal family routines, harsh parenting and corporal punishment were assessed in early and mid-childhood. Mediation analysis was performed with the G-formula and Structural Equation Models. Results Child intelligence partially mediated [B indirect effect =0.54 95% CI (0.46, 0.62) P  < 0.001] the association between parental education and child school achievement. Independent of intelligence, family routines [B indirect effect =0.04 95% CI (0.01, 0.07) P  < 0.01], but not harsh parenting mediated this association. Conclusions Higher parental education was associated with better school achievement through two independent mechanisms, through higher intelligence of the child and parenting practices. [ABSTRACT FROM AUTHOR]

Background Children with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children. Methods A cohort born in 2001–2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100. Results A total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9–97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6–88.9) against all-cause IPD. Conclusion This is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children. [ABSTRACT FROM AUTHOR]

The sensitivity and specificity of SARS-CoV-2 antigen tests have not been widely assessed in children. We evaluated children presenting to outpatient care with Quidel Sofia SARS-CoV-2 antigen test (Sofia-Ag-RDT) compared against Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV reverse transcriptase-polymerase chain reaction test from November 2020 to April 2021. Sofia-Ag-RDT had the highest sensitivity in symptomatic (82%; 95% confidence interval, 68%-91%) children. [ABSTRACT FROM AUTHOR]

Objective Early aggressive therapy using biologicals is increasingly being used in JIA for early disease remission. Pulse steroids are used in induction regimes for rheumatic disorders such as SLE and systemic JIA; however, no controlled studies have demonstrated their use in non-systemic JIA. The objective of the present study was to evaluate the efficacy and safety of pulse dexamethasone therapy in children with treatment-naïve non-systemic JIA as early aggressive therapy in resource-limited settings. Methods Sixty treatment-naïve children with non-systemic JIA with an active joint count of ≥5 and/or involvement of hip or cervical joints were randomized to receive either pulse dexamethasone (3 mg/kg/day, max 100 mg/day) or placebo (normal saline) for three consecutive days during each visit at 0, 6 (±2) and 12 (±2) weeks; along with standard therapy (MTX and NSAIDs). The use of oral bridge steroids was permissible for persistent severe disease as per predefined criteria. The primary outcome was ACR-Pedi 70 response at 16 (±2) weeks after enrolment in the two groups. Results The proportion of children achieving ACR-Pedi 70 in the two groups at last follow-up was 11/30 (36.7%) in pulse dexamethasone arm vs 11/28 (39.3%) in the placebo arm (P -value 0.837, relative risk 0.93, 95% CI 0.48, 1.80). We did not observe any significant difference in the proportion of children requiring bridge steroids. Adverse events were comparable in the two groups. Conclusion The addition of pulse dexamethasone to standard treatment may not add any advantage in improving ACR-Pedi 70 scores at medium-term follow-up. Trial registration Clinical Trial Registry-India; www.ctri.nic.in CTRI/2018/08/015151. [ABSTRACT FROM AUTHOR]

Background Data are limited on the resolution of symptoms and signs in children treated for pulmonary tuberculosis (PTB) and whether this resolution differs from children with other lower respiratory tract infections (LRTIs). Methods A prospective study of children ≤ 15 years presenting with features suggestive of PTB was performed. Clinical, microbiological, and radiological investigations were done at enrollment. Symptoms and clinical features were measured 1, 3, and 6 months after enrollment. Participants were categorized into 3 groups based on National Institutes of Health consensus definitions: confirmed PTB, unconfirmed PTB, and unlikely PTB (children with other LRTIs). Univariable and multivariable logistic regression modeling was used to investigate predictors of persistence of symptoms or signs. Results Among 2019 participants, there were 427 (21%) confirmed, 810 (40%) unconfirmed, and 782 (39%) with unlikely PTB. Of 1693/2008 (84%) with cough and 1157/1997 (58%) with loss of appetite at baseline, persistence at 3 months was reported in 24/1222 (2%) and 23/886 (3%), respectively. Of 934/1884 (50%) with tachypnoea and 947/1999 (47%) with abnormal auscultatory findings at baseline, persistence at 3 months occurred in 410/723 (57%) and 216/778 (28%), respectively. HIV infection and abnormal baseline chest radiography were associated with persistence of symptoms or signs at month 3 (adjusted odds ration [aOR] 1.6; 95% confidence interval [CI]: [1.1, 2.3] and aOR 2.3; 95% CI: [1.5, 3.3], respectively]. The resolution of symptoms and signs was similar across categories. Conclusions Symptoms resolved rapidly in most children with PTB, but signs resolved more slowly. The pattern and resolution of symptoms or signs did not distinguish children with PTB from those with other LRTIs. [ABSTRACT FROM AUTHOR]

Background C-reactive protein (CRP) has shown promise as a triage tool for pulmonary tuberculosis (TB) in adults living with the human immunodeficiency virus. We performed the first assessment of CRP for TB triage in children. Methods Symptomatic children less than 15 years old were prospectively enrolled in Kampala, Uganda. We completed a standard TB evaluation and measured CRP using a point-of-care assay. We determined the sensitivity and specificity of CRP to identify pulmonary TB in children using 10 mg/L and 5 mg/L cut-off points and generated a receiver operating characteristic (ROC) curve to determine alternative cut-offs that could approach the target accuracy for a triage test (≥90% sensitivity and ≥70% specificity). Results We included 332 children (median age 3 years old, interquartile range [IQR]: 1–6). The median CRP level was low at 3.0 mg/L (IQR: 2.5–26.6) but was higher in children with Confirmed TB than in children with Unlikely TB (9.5 mg/L vs. 2.9 mg/L, P -value =.03). At a 10 mg/L cut-off, CRP sensitivity was 50.0% (95% confidence interval [CI], 37.0–63.0) among Confirmed TB cases and specificity was 63.3% (95% CI, 54.7–71.3) among children with Unlikely TB. Sensitivity increased to 56.5% (95% CI, 43.3–69.0) at the 5 mg/L cut-off, but specificity decreased to 54.0% (95% CI, 45.3–62.4). The area under the ROC curve was 0.59 (95% CI, 0.51–0.67), and the highest sensitivity achieved was 66.1% at a specificity of 46.8%. Conclusions CRP levels were low in children with pulmonary TB, and CRP was unable to achieve the accuracy targets for a TB triage test. [ABSTRACT FROM AUTHOR]

Objectives Mandatory audiological testing before autism spectrum disorder (ASD) assessment is common practice. Hearing impairment (HI) in the general paediatric population is estimated at 3%; however, hearing impairment prevalence among children with ASD is poorly established. Our objective was to determine which children referred for ASD assessment require preliminary audiological assessment. Methods Retrospective chart review of children (n=4,173; 0 to 19 years) referred to British Columbia's Autism Assessment Network (2010 to 2014). We analyzed HI rate, risk factors, and timing of HI diagnosis relative to ASD referral. Results ASD was diagnosed in 53.4%. HI rates among ASD referrals was 3.3% and not significantly higher in children with ASD (ASD+; 3.5%) versus No-ASD (3.0%). No significant differences in HI severity or type were found, but more ASD+ females (5.5%) than ASD+ males (3.1%) had HI (P<0.05). Six HI risk factors were significant (problems with intellect, language, vision/eye, ear, genetic abnormalities, and prematurity) and HI was associated with more risk factors (P<0.01). Only 12 children (8.9%) were diagnosed with HI after ASD referral; all males 6 years or younger and only one had no risk factors. ASD+ children with HI were older at ASD referral than No-ASD (P<0.05). Conclusions Children with ASD have similar hearing impairment rates to those without ASD. HI may delay referral for ASD assessment. As most children were diagnosed with HI before ASD referral or had at least one risk factor, we suggest that routine testing for HI among ASD referrals should only be required for children with risk factors. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to identify nephrology topics of lowest perceived competency and importance for general paediatricians. Methods Surveys were distributed to general paediatricians, paediatric residents, paediatric residency program directors, and paediatric nephrologists. Perceived importance and competence were rated on a 5-point Likert scale. Means and 95% confidence intervals were calculated. Results Mean perceived competency from general paediatricians across all nephrology domains was 3.0, 95%CI (2.9 to 3.1) and mean importance was 3.2, 95%CI (3.1 to 3.3). Domains scoring below the means for competence and importance, respectively were kidney stones (2.5, 95%CI [2.2 to 2.7]) and 2.6, 95%CI [2.3 to 2.8]), acute kidney injury (2.5, 95%CI [2.2 to 2.8] and 2.4, 95%CI [2.1 to 2.8]), chronic kidney disease (1.9, 95%CI [1.7 to 2.2] and 2.1, 95%CI [1.8 to 2.4]), tubular disorders (1.8, 95%CI [1.6 to 2.0] and 2.0, 95%CI [1.8 to 2.3]), and kidney transplant (1.6, 95%CI [1.4 to 1.8] and 1.7, 95%CI [1.4 to 1.9]). Residents, program directors, and paediatric nephrologists agreed that stones, chronic kidney disease, tubular disorders, and transplant were of lower importance. However, acute kidney injury was the domain with the largest discrepancy in perceived importance between residents (4.4, 95%CI [4.2 to 4.6]), nephrologists (4.2, 95%CI [3.8 to 4.6]), and program directors (4.2, 95%CI [3.7 to 4.7]) compared to general paediatricians ([2.4, 95%CI [2.1 to 2.8]; P<0.05). Conclusion Paediatricians did not believe acute kidney injury was important to their practice, despite expert opinion and evidence of long-term consequences. Educational interventions must address deficits in crucial domains of renal health in paediatrics. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seroprevalence studies largely focus on adults, but little is known about spread in children. We determined SARS-CoV-2 seroprevalence in children and adolescents from Arkansas over the first year of the coronavirus disease of 2019 (COVID-19) pandemic. Methods We tested remnant serum samples from children ages 1-18 years who visited Arkansas hospitals or clinics for non-COVID-19-related reasons from April 2020 through April 2021 for SARS-CoV-2 antibodies. We used univariable and multivariable regression models to determine the association between seropositivity and participant characteristics. Results Among 2357 participants, seroprevalence rose from 7.9% in April/May 2020 (95% CI, 4.9-10.9) to 25.0% in April 2021 (95% CI, 21.5-28.5). Hispanic and black children had a higher association with antibody positivity than non-Hispanic and white children, respectively, in multiple sampling periods. Conclusions By spring 2021, most children in Arkansas were not infected with SARS-CoV-2. With the emergence of SARS-CoV-2 variants, recognition of long-term effects of COVID-19, and the lack of an authorized pediatric SARS-CoV-2 vaccine at the time, these results highlight the importance of including children in SARS-CoV-2 public health, clinical care, and research strategies. [ABSTRACT FROM AUTHOR]

Background In developing evidence-based physical activity (PA) guidelines for youth, a knowledge gap exists regarding the health effects of sedentary time (SED). The aim of this study was to determine the joint associations of moderate- and vigorous-intensity PA (MVPA) and SED with adiposity during adolescence. Methods The study sample was 2619 non-obese participants (56.7% female) from the UK Avon Longitudinal Study of Parents and Children. Accelerometer-measured MVPA and SED at age 11, 13, 15 years and self-reported TV viewing at age 13 and 16 years were used to create two exposure variables: six MVPA&SED combinations based on two MVPA patterns [≥60 (active) and <60 min/day (inactive)] and three SED patterns [≈25 (low), ≈30 (middle) and ≈35 min/h (high)] and six MVPA&TV combinations based on two MVPA patterns and three TV viewing patterns [<1–2 (low), 1–2 (middle) and >1–2 h/day (high)]. Adiposity was evaluated using fat mass index (FMI) at age 17 years. Results SED was not significantly associated with FMI in either active or inactive adolescents. However, higher TV viewing was associated with higher FMI in both active [adjusted FMI = 4.53 vs. 5.09 (95% CI = 4.87, 5.33) for low TV vs. high TV] and inactive adolescents [adjusted FMI = 4.91 vs. 5.21 (95% CI = 5.02, 5.39) for low TV vs. high TV]. Conclusions Higher TV viewing time, but not total SED, was prospectively associated with higher adiposity among both active and inactive adolescents, suggesting a specific sedentary behavior target for public health. [ABSTRACT FROM AUTHOR]

Objectives Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. Methods We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n  = 3753) were matched to 5 non-KD controls from the general population (n  = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. Results There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. Conclusion Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD. [ABSTRACT FROM AUTHOR]

Objective To describe risk factors for IBD development in a cohort of children with JIA. Methods JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different DMARDs were calculated, and differences between therapies were expressed as relative risks (RR). Results Out of 8942 patients, 48 (0.54%) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were enthesitis-related arthritis [odds ratio (OR): 3.68, 95% CI: 1.41, 9.40] and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12, 4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99, 29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42, 22.77) and infliximab (RR: 7.61, 95% CI: 1.27, 45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15, 13.89). Conclusion IBD in JIA was associated with enthesitis-related arthritis and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use. [ABSTRACT FROM AUTHOR]

Objectives Screening for hypertension in children is recommended by pediatric consensus guidelines. However, current practice is unknown. We evaluated rates of blood pressure assessment and hypertension recognition in primary care. Methods This retrospective cohort study evaluated electronic medical record data from the Canadian Primary Care Sentinel Surveillance Network between 2011 and 2017. Children aged 3 to <18 years with at least one clinical encounter were included. Screening, follow-up, and hypertension recognition rates were evaluated. Descriptive statistics and multivariate logistical regression were used to determine patient and provider characteristics associated with increased screening and recognition of pediatric hypertension. Results Among 378,002 children, blood pressure was documented in 33.3% of all encounters, increasing from 26.7% in 2011 to 36.2% in 2017; P=0.007. Blood pressure was documented in 76.0% of well child visits. Follow-up visits occurred within 6 months for 26.4% of children with elevated blood pressure, 57.1% of children with hypertension, and within 1 month for 7.2% of children with hypertension. Patient factors associated with increased blood pressure screening include being overweight (OR 2.15, CI 2.09 to 2.22), having diabetes (OR 1.69, CI 1.37 to 2.08), chronic kidney disease (OR 7.51, CI 6.54 to 8.62), increased social deprivation (OR 1.10, CI 1.09 to 1.11), and urban residence (OR 1.27, CI 1.15 to 1.4). Overall prevalence of hypertension was 1.9% (n=715) and of those, 5.6% (n=40) had recognized hypertension. Factors associated with increased recognition include male sex, overweight, and hyperlipidemia. Conclusions Rates of hypertension screening and recognition are low in primary care settings in Canada, suggesting pediatric hypertension should be a priority for implementation and dissemination of interventions. [ABSTRACT FROM AUTHOR]

We examined whether secondhand smoke exposure during childhood was associated with cancer mortality in adulthood among never smokers. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we analyzed data from 45,722 Japanese lifetime nonsmokers aged 40–79 years with no history of cancer at baseline (1988–1990) who had completed a lifestyle questionnaire, including information on the number of family members who had smoked at home during their childhood (0, 1, 2, or ≥3 family members). A Cox proportional hazards model and competing-risks regression were used to calculate multivariable hazard ratios and subdistribution hazard ratios with 95% confidence intervals for overall and site-specific cancer mortality according to the number of family members who smoked during the participant's childhood, after adjusting for potentially confounding factors. During a median follow-up period of 19.2 years, a total of 2,356 cancer deaths were documented. Secondhand smoke exposure was positively associated with the risk of mortality from pancreatic cancer in adulthood; the multivariable hazard ratio for having 3 or more family members who smoked (as compared with none) was 2.32 (95% confidence interval: 1.14, 4.72). Associations were not evident for total cancer risk or risk of other types of smoking-related cancer. In this study, secondhand smoke exposure during childhood was associated with an increased risk of pancreatic cancer mortality in adulthood. [ABSTRACT FROM AUTHOR]

Objective Axonal/neuronal damage has been shown to be a pathological finding that precedes neuropsychiatric manifestations in SLE. The objective of this study was to determine the presence of axonal dysfunction in childhood-onset SLE patients (cSLE) and to determine clinical, immunological and treatment features associated with its occurrence. Methods We included 86 consecutive cSLE patients [median age 17 (range 5–28) years] and 71 controls [median age 18 (5–28) years]. We performed proton magnetic resonance spectroscopic imaging using point resolved spectroscopy sequence over the superior–posterior region of the corpus callosum and signals from N -acetylaspartate (NAA), choline-based (CHO), creatine-containing (Cr), myo -inositol (mI), glutamate, glutamine and lactate were measured and metabolites/Cr ratios were determined. Complete clinical, laboratory and neurological evaluations were performed in all subjects. Serum IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, TNF-α and INF-γ cytokine levels, antiribosomal P protein antibodies (anti-P) and S100β were measured by ELISA using commercial kits. Data were compared by non-parametric tests. Results NAA/Cr ratios (P  = 0.035) and lactate/Cr ratios (P  = 0.019) were significantly decreased in cSLE patients when compared with controls. In multivariate analysis, IFN-γ levels [odds ratio (OR) = 4.1; 95% CI: 2.01, 7.9] and depressive symptoms (OR = 1.9; 95% CI: 1.1, 3.2) were associated with NAA/Cr ratio. Increased CHO/Cr was associated with the presence of cognitive impairment (OR = 3.4; 95% CI: 2.034, 5.078; P  < 0.001). mI/Cr ratio correlated with cumulative glucocorticoids dosage (r  = 0.361, P  = 0.014). Conclusion NAA and CHO ratios may be useful as biomarkers in neuropsychiatric cSLE. Longitudinal studies are necessary to determine whether they predict structural damage. [ABSTRACT FROM AUTHOR]

Toxic stress caused by child maltreatment can lead to adverse mental health outcomes in later life, yet unmeasured confounding has been a major issue in many previous studies. To examine the association between child maltreatment and resilience and behavior problems among early elementary school-age children, we used data from a population-based longitudinal survey targeting all first-grade children in 2015 in Adachi City, a ward in Tokyo, Japan. Children whose caregivers provided valid responses during the 2015 (first grade; ages 6–7 years), 2016 (second grade; ages 7–8 years), and 2018 (fourth grade; ages 9–10 years) waves of the study were included in the analysis (n  = 2,920). Fixed-effects regression models revealed that child maltreatment was inversely associated with resilience (β = −0.89, 95% confidence interval (CI): −1.05, −0.72) and prosocial behavior (β = −0.03, 95% CI: −0.05, −0.003) and positively associated with behavior problems (β = 0.32, 95% CI: 0.27, 0.37) over 4 years of follow-up (2015–2018), after controlling for all time-invariant confounders and measured time-varying confounders and survey year. These associations were consistent across sex. Child maltreatment may hamper the development of resilience and prosocial behavior and induce behavior problems in early elementary school children over time. Future researchers should identify modifiable protective factors for better mental health among maltreated children. [ABSTRACT FROM AUTHOR]

Background There is no gold standard for tuberculosis diagnosis in children. Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children were proposed by international experts in 2012 and updated in 2015. We aimed to compare the 2012 and 2015 Clinical Case Definitions in HIV-infected children with suspected tuberculosis. Methods We enrolled HIV-infected children with suspected tuberculosis in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS [Agence Nationale de Recherches sur le SIDA et les hépatites virales] 12229 PAANTHER [Pediatric Asian African Network for Tuberculosis and HIV Research] 01 Study). We classified children using the 2012 and 2015 Case Definitions considering as tuberculosis cases those with confirmed tuberculosis and those with probable and unconfirmed tuberculosis in the 2012 and the 2015 classifications, respectively. We assessed agreement between both classifications. Results Of 438 children enrolled, 197 (45.0%) children were classified as tuberculosis (45 confirmed, 152 probable) using the 2012 Case Definition and 251 (57.3%) were classified as tuberculosis (55 confirmed, 196 unconfirmed) using the 2015 classification. Inter-classification agreement for tuberculosis diagnosis was 364/438, 83.1%, with a kappa statistic of 0.667 (95% confidence interval 0.598-0.736). Of 152 children with probable tuberculosis (2012), 142 (93.4%) were considered as tuberculosis by the 2015 version and 10 (6.6%) as unlikely tuberculosis including 9 with spontaneous clinical improvement. Of 132 possible tuberculosis (2012), 58 (43.9%) were reclassified as tuberculosis (2015). Conclusions Agreement between the 2 versions of the Case Definition was substantial but more children were considered as tuberculosis using the 2015 version. Spontaneous symptom resolution reinforces both confidence in the "unlikely" category as being children without tuberculosis and the importance of the clinician's treatment decision in the study. [ABSTRACT FROM AUTHOR]

Using hospital surveillance data, we estimated Human metapneumovirus (hMPV) hospitalization incidence by age and HIV-exposure status. hMPV-associated hospitalization incidence was highest in <1-year children. Incidence rate ratios of HIV-exposed over unexposed children were 1.5 (95%CI 0.9–2.4) for <6-month children, 1.4 (95%CI 0.7–2.4) for 6- to 11-month children and 0.9 (95%CI 0.4–1.9) for 12- to 59-month children. [ABSTRACT FROM AUTHOR]