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Objective Familial aggregation of systemic autoimmune diseases is frequently reported, but little is known about how fathers and mothers differentially contribute to the development of autoimmune diseases in their offspring. This study aimed to investigate the impact of maternal and paternal autoimmunity on the risk of offspring rheumatic diseases. Methods We constructed a nationwide population-based cohort using data from the Maternal and Child Health Database and the Taiwan National Health Insurance Research Data (NHIRD) from 2004 to 2019. The outcome was presence of an autoimmune disease in the offspring. Inverse probability of treatment–weighted Cox models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs for autoimmune diseases. Results Babies born to a father or mother with an autoimmune disease had, respectively, 1.22 times and 1.38 times the risk of developing an autoimmune disease compared with their counterparts with no parental autoimmune diseases. Maternal autoimmunity substantially contributed to the risk of SLE (aHR = 5.46, 95% CI: 5.28–5.66), and paternal autoimmunity contributed to the risk of JIA (aHR = 1.76, 95% CI: 1.71–1.81) and of type 1 diabetes mellitus (aHR = 1.59, 95% CI: 1.39–1.81) in their offspring. The contributions of mothers to the risk of development of SLE (aHR = 8.55, 95% CI: 8.10–9.02) and inflammatory myopathy (aHR = 2.08, 95% CI: 1.72–2.51) in their offspring were exacerbated in boys. Babies of two parents with an autoimmune disease showed a 1.39-fold risk of developing an autoimmune disease. The maternal contribution effect was stronger for preterm births than for full-term births. Conclusion This study demonstrated broadly how autoimmune diseases pass from parents to infants of both genders and separately quantified the maternal and paternal contributions to disease. [ABSTRACT FROM AUTHOR]

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P  <.001). HRs were higher for girls (HR = 4.17; 95% CI, 3.60-4.82) than for boys (HR = 1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology. [ABSTRACT FROM AUTHOR]

Background Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH and children not living with HIV treated for nonsevere TB in the SHINE trial. Methods SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CWH. Results Of 1204 children enrolled, 127 (11%) were CWH, of similar age (median, 3.6 years; interquartile range, 1.2, 10.3 versus 3.5 years; 1.5, 6.9; P =.07) but more underweight (weight-for-age z score, −2.3; (3.3, −0.8 versus −1.0; −1.8, −0.2; P <.01) and anemic (hemoglobin, 9.5 g/dL; 8.7, 10.9 versus 11.5 g/dL; 10.4, 12.3; P <.01) compared with children without HIV. A total of 68 (54%) CWH were ART-naive; baseline median CD4 count was 719 cells/mm3 (241–1134), and CD4% was 16% (10–26). CWH were more likely to be hospitalized (adjusted odds ratio, 2.4; 1.3–4.6) and to die (adjusted hazard ratio [aHR], 2.6; 95% confidence interval [CI], 1.2 to 5.8). HIV status, age <3 years (aHR, 6.3; 1.5, 27.3), malnutrition (aHR, 6.2; 2.4, 15.9), and hemoglobin <7 g/dL (aHR, 3.8; 1.3,11.5) independently predicted mortality. Among children with available viral load (VL), 45% and 61% CWH had VL <1000 copies/mL at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 versus 6 months) on TB treatment outcomes by HIV status (P for interaction = 0.42). Conclusions We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CWH treated for nonsevere TB. Irrespective of TB treatment duration, CWH had higher rates of mortality and hospitalization than their counterparts without HIV. Clinical Trials Registration.  ISRCTN63579542. [ABSTRACT FROM AUTHOR]

Background In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. Methods Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000–2020. Results A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P =.013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P <.001; odds ratio [95% confidence interval], 2.073 [1.37–3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P <.001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P <.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P =.083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P =.004). Conclusions Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies. [ABSTRACT FROM AUTHOR]

Background Intussusception is the primary cause of acute bowel obstruction in infants. The majority of cases <2 years of age are classed as idiopathic, with viral infection implicated as one of the causes. Coronavirus disease 2019 (COVID-19) public health measures led to significant decreases in communicable disease prevalence. During these times, reductions in intussusception frequency were greater than would be expected with our previous understanding of its infectious etiology. Methods We conducted a retrospective, multistate, ecological study over a 12-year period. Monthly case numbers of "intussusception"-coded admissions (code K56.1; International Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification) were acquired from state-wide admissions data sets from New South Wales, Victoria, and Queensland, representing 77.62% of the eligible Australian population. These counts within differing jurisdictional lockdowns were compared with non-lockdown periods in order to investigate a correlation between intussusception frequency and lockdown periods. Results We found a negative association between intussusception frequency and lockdown periods in both eligible states. The largest reductions were seen in the <2-year age groups, with Victoria experiencing a 62.7% reduction (rate ratio, 0.37; P <.001) and New South Wales a 40.1% reduction (0.599; P =.006) during lockdown times. Controls for variations in lockdown restrictions between both regional and metropolitan areas also showed expected decreases. Conclusions Our ecological study demonstrates significant decreases in the frequency of pediatric intussusception admissions during the COVID-19 lockdown periods. The unexpected magnitude of the reductions suggests that the true proportion of infectious disease-caused idiopathic intussusception is greatly underestimated. [ABSTRACT FROM AUTHOR]

Objectives Access to early phase trials for children with relapsed, refractory or progressive (RRPD) cancer is limited in Canada. Patients and families face barriers to access trials, which are poorly understood. The aims of this study were to assess availability of early phase trials and examine the impact of distance from home to study centre on trial enrolment among paediatric oncology patients with RRPD. Methods Oncology patients ≤18 years at diagnosis who later had RRPD were identified retrospectively via registry at the only quaternary paediatric oncology centre in British Columbia (BC). We determined if distance to home, as calculated using geocoding software, was predictive of trial offer or enrolment. Results Between January 2015 and July 2021, 266 patients experienced 396 RRPD events. Seventy-five patients (28.2%) were eligible for an early phase trial at least once. At first eligible event, 61 patients (22.9%) were offered trial (median age 11.8 years; 69.0% male; 46.0% with CNS tumour) and thirty patients (11.3%) enrolled. Distance was not associated with odds of offer (OR 1.01, CI 0.98 to 1.05) or enrolment (OR 0.99, CI 0.95 to 1.03) on univariate or multivariable analysis adjusted for sex and disease (OR 0.93, CI 0.86 to 1.00). For offered patients, 2-year event-free survival (EFS) and overall survival (OS) were 39.1% (CI 28.0% to 54.8%) and 51.8% (CI 39.9% to 67.2%), respectively. EFS/OS did not differ with distance or enrolment, but varied by disease (EFS P = 0.002, OS P < 0.0001). Conclusions Children in BC with cancer and RRPD have limited access to early phase trials. Distance was not predictive of enrolment, suggesting that families travel to access therapy. [ABSTRACT FROM AUTHOR]

Background Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. Methods In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post–COVID-19 condition (PCC) was assessed in SARS-CoV-2–positive participating children after 90 days' follow-up. Results A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2–positive and –negative index children was 10.6% (19/179; 95% CI: 6.5%–16.1%) and 2.0% (13/663; 95% CI: 1.0%–3.3%), respectively (relative risk = 5.4; 95% CI: 2.7–10.7). In households with a SARS-CoV-2–positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2–infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%–16.2%) reported PCC. Conclusions Asymptomatic SARS-CoV-2–infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2–infected children may develop PCC. [ABSTRACT FROM AUTHOR]

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]

Context Although the nutritional composition of organic food has been thoroughly researched, there is a dearth of published data relating to its impact on human health. Objective This systematic review aimed to examine the association between organic food intake and health effects, including changes in in vivo biomarkers, disease prevalence, and functional changes. Data Sources PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception through Nov 13, 2022. Data Extraction Both observational and interventional studies conducted in human populations were included, and association between level of organic food intake and each outcome was quantified as "no association," "inconsistent," "beneficial correlation/harmful correlation," or "insufficient". For outcomes with sufficient data reported by at least 3 studies, meta-analyses were conducted, using random-effects models to calculate standardized mean differences. Data Analysis Based on the included 23 observational and 27 interventional studies, the association between levels of organic food intake and (i) pesticide exposure biomarker was assessed as "beneficial correlation," (ii) toxic metals and carotenoids in the plasma was assessed as "no association," (iii) fatty acids in human milk was assessed as "insufficient," (iv) phenolics was assessed as "beneficial", and serum parameters and antioxidant status was assessed as "inconsistent". For diseases and functional changes, there was an overall "beneficial" association with organic food intake, and there were similar findings for obesity and body mass index. However, evidence for association of organic food intake with other single diseases was assessed as "insufficient" due to the limited number and extent of studies. Conclusion Organic food intake was found to have a beneficial impact in terms of reducing pesticide exposure, and the general effect on disease and functional changes (body mass index, male sperm quality) was appreciable. More long-term studies are required, especially for single diseases. Systematic Review Registration PROSPERO registration no. CRD42022350175. [ABSTRACT FROM AUTHOR]

Objectives Juvenile PsA (JPsA) has varied clinical features that are distinctive from other JIA categories. This study investigates whether such features impact patient-reported and clinical outcomes. Methods Children and young people (CYP) were selected if recruited to the Childhood Arthritis Prospective Study, a UK multicentre JIA inception cohort, between January 2001 and March 2018. At diagnosis, patient/parent-reported outcomes (as age-appropriate) included the parental global assessment (10 cm visual analogue scale), functional ability (Childhood Health Assessment Questionnaire (CHAQ)), pain (10 cm visual analogue scale), health-related quality of life (Child Health Questionnaire PF50 psychosocial score), mood/depressive symptoms (Moods and Feelings Questionnaire) and parent psychosocial health (General Health Questionnaire 30). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA and PaGA, respectively). Patient-reported outcomes and outcome trajectories were compared in (i) CYP with JPsA vs other JIA categories and (ii) CYP within JPsA, with and without psoriasis via multivariable linear regression. Results There were no significant differences in patient-reported outcomes at diagnosis between CYP with JPsA and non-JPsA. Within JPsA, those with psoriasis had more depressive symptoms (coefficient = 9.8; 95% CI: 0.5, 19.0) than those without psoriasis at diagnosis. CYP with JPsA had 2.3 times the odds of persistent high PaGA than other ILAR categories, despite improving joint counts and PGA (95% CI: 1.2, 4.6). Conclusion CYP with psoriasis at JPsA diagnosis report worse mood, supporting a greater disease impact in those with both skin and joint involvement. Multidisciplinary care with added focus to support wellbeing in children with JPsA plus psoriasis may help improve these outcomes. [ABSTRACT FROM AUTHOR]

International sharing of cohort data for research is important and challenging. We explored the feasibility of multicohort federated analyses by examining associations between 3 pregnancy exposures (maternal education, exposure to green vegetation, and gestational diabetes) and offspring body mass index (BMI) from infancy to age 17 years. We used data from 18 cohorts (n  = 206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0–1, 2–3, 4–7, 8–13, and 14–17 years. Associations were estimated using linear regression via 1-stage individual participant data meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z score comparing low with high education, at age 2–3 years = 0.03 (95% confidence interval (CI): 0.00, 0.05), at 4–7 years = 0.16 (95% CI: 0.14, 0.17), and at 8–13 years = 0.24 (95% CI: 0.22, 0.26)). Gestational diabetes was positively associated with BMI from age 8 years (BMI z score difference = 0.18, 95% CI: 0.12, 0.25) but not at younger ages; however, associations attenuated towards the null when restricted to cohorts that measured gestational diabetes via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age 1 year but not at older ages. Opportunities of cross-cohort federated analyses are discussed. [ABSTRACT FROM AUTHOR]

Context Vitamin D plays an important role in immune function, and the deficiency thereof has been associated with several infections, most notably respiratory tract infections. However, data from intervention studies investigating the effect of high-dose vitamin D supplementation on infections have been inconclusive. Objective The aim of this study was to evaluate the level of evidence regarding the efficacy of vitamin D supplementation above the standard dose (400 IU) in preventing infections in apparently healthy children < 5 years of age. Data Sources PubMed, Scopus, Science Direct, Web of Science, Google Scholar, CINAHL, and MEDLINE electronic databases were searched between August 2022 and November 2022. Seven studies met the inclusion criteria. Data Extraction Meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. Randomized controlled trials in which vitamin D was supplemented at > 400 IU compared with placebo, no treatment, or standard dose were included. Data Analysis Seven trials that enrolled a total of 5748 children were included. Odds ratios (ORs) with 95%CIs were calculated using random- and fixed-effects models. There was no significant effect of high-dose vitamin D supplementation on the incidence of upper respiratory tract infection (OR, 0.83; 95%CI, 0.62–1.10). There was a 57% (95%CI, 0.30–0.61), 56% (95%CI, 0.27–0.07), and 59% (95%CI, 0.26–0.65) reduction in the odds of influenza/cold, cough, and fever incidence, respectively, with daily supplementation of vitamin D > 1000 IU. No effect was found on bronchitis, otitis media, diarrhea/gastroenteritis, primary care visits for infections, hospitalizations, or mortality. Conclusion High-dose vitamin D supplementation provided no benefit in preventing upper respiratory tract infections (moderate certainty of evidence) but reduced the incidence influenza/cold (moderate certainty of evidence), cough, and fever (low certainty of evidence). These findings are based on a limited number of trials and should be interpreted with caution. Further research is needed. Systematic Review Registration PROSPERO registration number CRD42022355206. [ABSTRACT FROM AUTHOR]

Objective Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients. Methods A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis. Results Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation. Conclusion The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies. [ABSTRACT FROM AUTHOR]

Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage. [ABSTRACT FROM AUTHOR]

Background The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older. Methods The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1–17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR. Results In total, 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2. Conclusions A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18). [ABSTRACT FROM AUTHOR]

Objective The purposes of this pilot study were to compare short-term outcomes of the Perception-Action Approach (P-AA) and standard care based on 5 components of first-choice interventions listed in the congenital muscular torticollis (CMT) clinical practice guideline. Changes in postural alignment, symmetrical use of both sides of the body during movement and play, gross motor development, and behavior observed during therapy were considered. Methods Thirty-two participants were enrolled in a 2-group (P-AA and standard care) randomized, single-blind trial with pre–posttest measures. Participants were infants with CMT, age range 5 to 35 weeks at enrollment. Outcome measures administered at initial and final evaluations included still photography, arthrodial goniometry, Muscle Function Scale, Alberta Infant Motor Scale, and Functional Symmetry Observation Scale. Participants in both groups attended 3 intervention sessions. Their behavior exhibited during therapy was compared using the Therapy Behavior Scale Version 2.2. Results Data collection was interrupted by the COVID-19 pandemic lockdown. Twenty-four infants completed the study (10 in P-AA and 14 in the standard care group). There were no significant differences between the groups in performance at initial and final evaluations. Both groups improved on most outcome measures. The P-AA group made greater gains on the Functional Symmetry Observation Scale, and the Therapy Behavior Scale Version 2.2 scores were higher in the P-AA group; however, these results did not reach significance. Conclusion Results suggest that similar short-term outcomes may be obtained in infants with CMT undergoing P-AA and standard care interventions. Definitive conclusions regarding the efficacy of the P-AA in infants with CMT cannot be made at this time. Nevertheless, the pilot findings provide valuable preliminary data for a future efficacy trial, which will require funding. Impact This was the first randomized controlled trial to provide evidence for use of P-AA intervention in infants with CMT. Lay Summary Compared to standard treatment, the Perception-Action Approach (P-AA) provided similar short-term benefits to infants with congenital muscular torticollis. The P-AA group participants demonstrated higher symmetry and behavior scores, which needs to be confirmed in a larger future study. [ABSTRACT FROM AUTHOR]

Objectives There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse. Methods We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001–2021 to investigate the incidence and outcomes related to renal relapse. Results Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [ n  = 36 (38%)] or MMF [ n  = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [ n  = 53 (54%)] or AZA [ n  = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s. d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P  = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P  = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P  = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P  = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3–5) and end-stage kidney disease (17.9% vs 1.8%, P  < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P  = 0.02), osteopenia (38.5% vs 17.9%, P  = 0.04) and hypertension (30.8% vs 7.1%, P  < 0.01). Conclusion Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse. [ABSTRACT FROM AUTHOR]

Childhood obesity is a major public health challenge. Previous research has identified the impact of school-based interventions for preventing and treating obesity; we hypothesized that when curricular changes are integrated, results could be exponentiated. This study aimed to systematically review and conduct a meta-analysis of the published literature analyzing information about school-based interventions inserted in the curriculum. The Cochrane Handbook methodology was followed. An electronic search was conducted in five databases, with a specific design strategy per database. Randomized controlled trials or quasi-experimental studies of children with nutrition and physical activity (PA) interventions inserted into the school curricula were included. The risk of bias was assessed with the Risk of Bias tool. The mean differences were pooled using a fixed-effects model for the meta-analysis. The certainty of the evidence was evaluated according to the guidelines of the Grading of the Recommendations, Assessment, Development, and Evaluations working group (Protocol ID: CRD42021270557). After the screening and selection process, 12 studies were included. The interventions identified, based on the school curricula, include classroom activities and homework, among others. A meta-analysis with five intervention groups presented an overall mean difference of −0.14 body mass index (BMI) Z -score (95% CI: −0.25, −0.03) after this intervention with high certainty of the evidence. This systematic review and meta-analysis suggest that nutrition and PA lessons inserted into the curricula and supported with additional activities (i.e. homework, workshops, etc.) could increase nutrition knowledge and improve attitudes toward fruit, vegetables, and water consumption, and BMI Z -score reduction. [ABSTRACT FROM AUTHOR]

Observational studies in adults suggest nasal methicillin-resistant Staphylococcus aureus (MRSA) swabs have a high negative predictive value (NPV) for ruling out MRSA pneumonia, however, pediatric data are limited. This retrospective study of 505 pediatric patients found a 99.8% NPV among children with suspected respiratory infections. [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 Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. Methods We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7–10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion. During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. Results Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval,.70–.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P =.22). Conclusions Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285. [ABSTRACT FROM AUTHOR]

Background During the 2022–2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010–2011. Influenza A/H3N2 infections were predominant. Methods We analyzed acute respiratory illness (ARI)–associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months–17 years who had influenza molecular testing during October 2022–March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A–positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models. Results Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A–positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44–52%) overall, 53% (95% CI, 47–58%) among children aged 6 months–4 years, and 38% (95% CI, 30–45%) among those aged 9–17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6–61%) overall, 56% (95% CI, 23–75%) among children ages 6 months–4 years, and 46% (95% CI, 2–70%) among those 5–17 years. Conclusions During the 2022–2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40–48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents. [ABSTRACT FROM AUTHOR]

Background We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. Methods Infants with HIV aged 1–12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. Results Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1–9.9), weight was 6.3 kg (5.6–7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)0–24h 0.91 (95% confidence interval,.59–1.42), Ctrough 0.95 (0.57–1.59), Cmax 0.87 (0.57–1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir Ctrough <0.32 mg/L, and none had Ctrough <0.064 mg/L. The dolutegravir metabolic ratio (dolutegravir-glucuronide AUC/dolutegravir AUC) was 2.3-fold higher in combination with rifampicin versus without rifampicin. Five of 82 reported AEs were possibly related to rifampicin or dolutegravir and resolved without treatment discontinuation. Upon TB treatment completion, HIV viral load was <1000 copies/mL in 76% and 100% of infants and undetectable in 35% and 20% of infants with and without rifampicin, respectively. Conclusions Dolutegravir BID in infants receiving rifampicin resulted in adequate dolutegravir exposure, supporting this treatment approach for infants with HIV–TB coinfection. [ABSTRACT FROM AUTHOR]

Background Nearly half of all pediatric musculoskeletal infections (MSKIs) are culture negative. Plasma microbial cell-free DNA (mcfDNA) sequencing is noninvasive and not prone to the barriers of culture. We evaluated the performance of plasma mcfDNA sequencing in identifying a pathogen, and examined the duration of pathogen detection in children with MSKIs. Methods We conducted a prospective study of children, aged 6 months to 18 years, hospitalized from July 2019 to May 2022 with MSKIs, in whom we obtained serial plasma mcfDNA sequencing samples and compared the results with cultures. Results A pathogen was recovered by culture in 23 of 34 (68%) participants, and by initial mcfDNA sequencing in 25 of 31 (81%) participants. Multiple pathogens were detected in the majority (56%) of positive initial samples. Complete concordance with culture (all organisms accounted for by both methods) was 32%, partial concordance (at least one of the same organism(s) identified by both methods) was 36%, and discordance was 32%. mcfDNA sequencing was more likely to show concordance (complete or partial) if obtained prior to a surgical procedure (82%), compared with after (20%), (RR 4.12 [95% CI 1.25, 22.93], p = .02). There was no difference in concordance based on timing of antibiotics (presample antibiotics 60% vs no antibiotics 75%, RR 0.8 [95% CI 0.40, 1.46], p = .65]). mcfDNA sequencing was positive in 67% of culture-negative infections and detected a pathogen for a longer interval than blood culture (median 2 days [IQR 1, 6 days] vs 1 day [1, 1 day], p < .01). Conclusions Plasma mcfDNA sequencing may be useful in culture-negative pediatric MSKIs if the sample is obtained prior to surgery. However, results must be interpreted in the appropriate clinical context as multiple pathogens are frequently detected supporting the need for diagnostic stewardship. [ABSTRACT FROM AUTHOR]

Objective Acute bronchiolitis (AB) is one of the most common respiratory diseases in early childhood and is still an important health problem worldwide. The systemic immune-inflammatory index (SII) is thought to have potential to be a new-generation inflammatory biomarker. We sought to investigate the value of SII for severity assessment in children with AB. Methods A total of 74 AB patients were included in a prospective observational study. Patients were classified into 3 AB groups according to this classification: mild (1-5 points), moderate (6-10 points), and severe (11-12 points). Complete blood count, C-reactive protein, and procalcitonin tests were carried out. Modified Tal score was evaluated to determine severity. The performance of parameters to predict the severity of AB was assessed using the receiver operating characteristic (ROC). Results Whereas neutrophil count (P =.037), neutrophil-to-lymphocyte ratio (P =.030), and SII (P =.030) values increased significantly with disease severity, red cell distribution width (P =.048) values were higher in the moderate AB group. The SII was found to have the highest area under the curve in the comparison of the mild-moderate groups combination and the high group on ROC analysis (P =.009). Conclusion The SII values of pediatric patients hospitalized with the diagnosis of AB were significantly higher in the high-severity group. The SII may offer additional severity stratification in children with AB. [ABSTRACT FROM AUTHOR]

Background Tetanus, a life-threatening infection, has become rare in the United States since introduction of tetanus toxoid-containing vaccines (TTCVs), recommended as a childhood series followed by decennial boosters beginning at age 11–12 years; vaccination uptake is high in children but suboptimal in adults. The objective of this study was to estimate the prevalence of sero-immunity to tetanus among persons aged ≥6 years in the United States and to identify factors associated with tetanus sero-immunity. Understanding population protection against tetanus informs current and future vaccine recommendations. Methods Anti-tetanus toxoid antibody concentrations were measured for participants of the 2015–2016 National Health and Nutrition Examination Survey (NHANES) aged ≥6 years for whom surplus serum samples were available using a microsphere-based multiplex antibody capture assay. Prevalence of sero-immunity, defined as ≥0.10 IU/mL, was estimated overall and by demographic characteristics. Factors associated with tetanus sero-immunity were examined using multivariable regression. Results Overall, 93.8% of the US population aged ≥6 years had sero-protection against tetanus. Prevalence of sero-immunity was above 90% across racial/ethnic categories, sex, and poverty levels. By age, ≥ 90% had protective sero-immunity through age 69 years, but prevalence of sero-immunity declined thereafter, with 75.8% of those aged ≥80 years having protective sero-immunity. Older age (adjusted prevalence ratio [aPR]: 0.89, 95% confidence interval [CI]:.85–.92) and being born outside the United States (aPR: 0.96, 95% CI:.93–.98) were significantly associated with lower prevalence of sero-immunity. Conclusions The majority of the US population has vaccine-induced sero-immunity to tetanus, demonstrating the success of the vaccination program. [ABSTRACT FROM AUTHOR]

Objective The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra. Methods This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up. Results Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P  = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4–1.0). Conclusion We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome. [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 Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. Methods This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3–17 years old who were 3–35 months post-allogeneic HCT, with each formulation administered twice, 28–42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28–42 days following each dose, and 138–222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3–5 and 6–35 months post-HCT, respectively. Results During 3 influenza seasons (2016–2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14–4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60–6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01–3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59–1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68–2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56–2.03]). Conclusions Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. Clinical Trials Registration NCT02860039. [ABSTRACT FROM AUTHOR]

Background A low-level risk of intussusception following rotavirus vaccination has been observed in some settings and may vary by vaccine type. We examined the association between RotaTeq vaccination and intussusception in low-income settings in a pooled analysis from 5 African countries that introduced RotaTeq into their national immunization program. Methods Active surveillance was conducted at 20 hospitals to identify intussusception cases. A standard case report form was completed for each enrolled child, and vaccination status was determined by review of the child's vaccination card. The pseudo-likelihood adaptation of self-controlled case-series method was used to assess the association between RotaTeq administration and intussusception in the 1–7, 8–21, and 1–21 day periods after each vaccine dose in infants aged 28–245 days. Results Data from 318 infants with confirmed rotavirus vaccination status were analyzed. No clustering of cases occurred in any of the risk windows after any of the vaccine doses. Compared with the background risk of naturally occurring intussusception, no increased risk was observed after dose 1 in the 1–7 day (relative incidence = 2.71; 95% confidence interval [CI] = 0.47–8.03) or the 8–21 day window (relative incidence = 0.77; 95%CI = 0.0–2.69). Similarly, no increased risk of intussusception was observed in any risk window after dose 2 or 3. Conclusions RotaTeq vaccination was not associated with increased risk of intussusception in this analysis from 5 African countries. This finding mirrors results from similar analyses with other rotavirus vaccines in low-income settings and highlights the need for vaccine-specific and setting-specific risk monitoring. [ABSTRACT FROM AUTHOR]

In a cross-sectional analysis of 354 Ugandan children (age 12–48 months) infected with Schistosoma mansoni , we assessed relationships between infection intensity and nutritional morbidities. Higher intensity was associated with an increased risk for anemia (RR = 1.05, 95% confidence interval [CI] 1.01–1.10) yet not associated with risk for underweight, stunting, or wasting. [ABSTRACT FROM AUTHOR]

Context Early adverse experience can have a long-term effect on growth and development and negative repercussions into adulthood. Among the various consequences of undernutrition is depression. Objective The present work aimed to evaluate the relationship between early-life undernutrition and depression in adult life. Data Sources Data were obtained from the PubMed, SCOPUS, and Web of Science databases in November 2021 and were selected using the systematic bibliographic review manager program State of the Art Through Systematic Review. Data Extraction Data were extracted using the State of the Art Through Systematic Review program. Data Analysis Of the 559 articles that were identified, 114 were duplicates, and 426 were excluded after inclusion and exclusion criteria were applied to the title and abstract. One other relevant study was included. From the 20 remaining articles, 8 were excluded after the full-text screening. Finally, 12 articles remained for review in the present work. The studies described in these articles investigated humans, rats, or mice, and correlated early-life malnutrition and depression in adulthood as the principal outcome. Conclusions Undernutrition in early life and later depression are linked. Furthermore, the knowledge that the risk factors for depression start at the beginning of life points to public health policies starting in intrauterine life and extending throughout childhood and adolescence. [ABSTRACT FROM AUTHOR]

Background Critically ill pediatric patients are frequently initiated methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics during infection evaluation even though MRSA infections are rare in many patient populations. The MRSA nasal swab polymerase chain reaction assay (MRSA-NS-PCR) is a test that has been shown to have a high negative predictive value (NPV) for MRSA infection in adults. This study evaluated the diagnostic test characteristics of the MRSA-NS-PCR in predicting the presence of MRSA infection in critically ill pediatric patients. Study Design A retrospective cohort study was performed in a 44-bed pediatric intensive care unit (PICU) between 2013 and 2017. 3860 pediatric patients (54% male, median age 4 years [IQR 1–11 years]) admitted to the PICU who met pediatric systemic inflammatory response syndrome (pSIRS) criteria, were screened with a MRSA-NS-PCR, and had cultures obtained within seven days of MRSA-NS-PCR collection were included. Predictive values and post-test probabilities of the MRSA-NS-PCR for MRSA infection were calculated. Results MRSA-NS-PCR was positive in 8.6% of patients. MRSA infection was identified in 40 patients, equaling an incidence rate of 2 per 1000 patient days. The MRSA-NS-PCR demonstrated a positive predictive value (PPV) of 9.7%, a NPV of 99.8%, and a post-test probability for a negative test of 0.2% for MRSA infection. Conclusions The MRSA-NS-PCR has a poor PPV but a high NPV for MRSA infection in PICU patients when the incidence of MRSA infection is low. Creation of protocols to guide antimicrobial selection based on MRSA-NS-PCR results may lead to improved antimicrobial stewardship and significant risk reduction. [ABSTRACT FROM AUTHOR]

Background Widespread school closures and health care avoidance during the COVID-19 pandemic led to disruptions in access to pediatric mental health care. Methods We conducted a retrospective study of emergency and inpatient administrative claims from privately insured children aged 6–20 years in North Carolina between January 2019 and December 2020. We compared rates of emergency department (ED) visits (per 100 000 person-days) and risks of hospitalizations (per 100 000 persons) with diagnosis codes in each category (mental/behavioral health; suicidal ideation, suicide attempt, and intentional self-harm [SI/SA/ISH]; and social issues) across 3 time periods (pre-pandemic, lockdown, and reopening). We calculated the proportion and 95% confidence intervals (CI) of total ED visits and total hospitalizations attributable to mental/behavioral health and SI/SA/ISH across the 3 time periods. Results Rates of all categories of ED visits decreased from pre-pandemic to the lockdown period; from pre-pandemic to the reopening period, mental/behavioral health visits decreased but rates of SI/SA/ISH visits were unchanged. The proportion of ED visits attributable to mental/behavioral health increased from 3.5% (95% CI 3.2%–3.7%) pre-pandemic to 4.0% (95% CI 3.7%–4.3%) during reopening, and the proportion of SI/SA/ISH diagnoses increased from 1.6% (95% CI 1.4%–1.8%) pre-pandemic to 2.4% (95% CI 2.1%–2.7%) during the reopening period. Emergency care use for social issues and hospital admissions for mental/behavioral health and SI/SA/ISH diagnoses were unchanged across the study periods. Conclusions In the early pandemic, pediatric mental health care and acute suicidal crises accounted for increased proportions of emergency care. During pandemic recovery, understanding the populations most impacted and increasing access to preventative mental health care is critical. [ABSTRACT FROM AUTHOR]

Background To evaluate the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU). Methods We identified a cohort of infants discharged from a Pediatrix NICU between 1997 and 2020 who did not have an immunodeficiency, had at least 1 CSF culture collected within the first 120 days of life, and at least 1 CSF laboratory specimen obtained on the day of culture collection. We only included an infant's first CSF culture and excluded cultures from CSF reservoirs and those growing contaminants or nonbacterial organisms. We examined the utility of CSF WBC components to diagnose or predict bacterial meningitis by calculating sensitivity, specificity, positive and negative predictive values, likelihood ratios, and area under the receiver operating curve (AUC) at different cutoff values for each parameter. We performed subgroup analysis excluding infants treated with antibiotics the day before CSF culture collection. Results Of the 20 756 infants that met the study inclusion criteria, 320 (2%) were diagnosed with bacterial meningitis. We found (AUC [95% CI]) CSF WBC count (0.76 [0.73–0.79]), CSF neutrophil count (0.74 [0.70–0.78]), and CSF neutrophil percent (0.71 [0.67–0.75]) had the highest predictive values for bacterial meningitis, even when excluding infants with early antibiotic administration. Conclusions No single clinical prediction rule had the optimal discriminatory power for predicting culture-proven bacterial meningitis, and clinicians should be cautious when interpreting CSF WBC parameters in infants with suspected meningitis. [ABSTRACT FROM AUTHOR]

Background We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). Methods We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies. We performed subgroup analysis in EOS episodes caused by Gram-negative and Gram-positive organisms. Results Of the 62,178 infants and 64,559 cultures that met study inclusion criteria, 739 (1%) cultures were positive. The median (25th, 75th percentile) glucose value was 75 mg/dL (50, 106) on the day of or day prior to a positive culture versus 70 mg/dL (50, 95) on the day of or day prior to a negative culture. We found that hypoglycemia was not associated with the occurrence of EOS for all organisms and Gram-positive organisms, whereas there was a small but significant association between the lower AAP glucose cutoff value and EOS due to Gram-negative organisms (logistic regression: risk difference [RD] 0.24% [95% CI, 0.01-0.47]; IPW: RD 0.22% [95% CI, 0.00-0.43]). Conclusions Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia. [ABSTRACT FROM AUTHOR]

Objectives This study explored if parents are accurate in their reading concerns, with implications for paediatric practice. Methods Parents of school-aged children in 34 schools in Ontario, Canada responded to a questionnaire about their children's academic development (27% response), and their children participated in standardized, norm-referenced tests of word reading and an oral sentence recall task. Parental concern status was retrospectively cross-referenced with reading difficulty status (<25th percentile on the word reading tests) for grade 2 children with complete data (n = 294); diagnostic accuracy was evaluated. Demographic and reading-related characteristics of children whose parents' concern did not match their reading difficulty status were explored. Results Approximately 22% of parents endorsed concern, while 18.5% of children had word reading difficulty. Parental concern status accurately corresponded with reading difficulty status in 81% of cases (95% CI: 76% to 85%). Specificity was 85% (95% CI: 80% to 90%), while sensitivity was 59% (95% CI: 44% to 73%). Children of unconcerned parents rarely had word reading problems (NPV 91%; 95% CI: 88% to 94%), while children with concerned parents had word reading difficulty in 45% of cases (PPV; 95% CI: 36% to 54%). Apparent inaccuracy (i.e. mismatch between parental concern and reading difficulty status) was related to children's word reading, oral sentence recall skills, and English language learner (ELL) status, but not child age, sex, or parent education. Conclusions Many parents of grade 2 children endorse reading concerns. Parental concern is an overall accurate screener for word reading difficulty, although some children will be missed. Evidence-informed recommendations for responding to parental concern are provided. [ABSTRACT FROM AUTHOR]

Background The role of SARS-CoV-2 viral load in predicting contagiousness, disease severity, transmissibility, and clinical decision-making continues to be an area of great interest. However, most studies have been in adults and have evaluated SARS-CoV-2 loads using cycle thresholds (Ct) values, which are not standardized preventing consistent interpretation critical to understanding clinical impact and utility. Here, a quantitative SARS-CoV-2 reverse-transcription digital PCR (RT-dPCR) assay normalized to WHO International Units was applied to children at risk of severe disease diagnosed with COVID-19 at St. Jude Children's Research Hospital between March 28, 2020, and January 31, 2022. Methods Demographic and clinical information from children, adolescents, and young adults treated at St. Jude Children's Research Hospital were abstracted from medical records. Respiratory samples underwent SARS-CoV-2 RNA quantitation by RT-dPCR targeting N1 and N2 genes, with sequencing to determine the genetic lineage of infecting virus. Results Four hundred and sixty-two patients aged 0–24 years (median 11 years old) were included during the study period. Most patients were infected by the omicron variant (43.72%), followed by ancestral strain (22.29%), delta (13.20%), and alpha (2.16%). Viral load at presentation ranged from 2.49 to 9.14 log10 IU/mL, and higher viral RNA loads were associated with symptoms (OR 1.32; CI 95% 1.16–1.49) and respiratory disease (OR 1.23; CI 95% 1.07–1.41). Viral load did not differ by SARS-CoV-2 variant, vaccination status, age, or baseline diagnosis. Conclusions SARS-CoV-2 RNA loads predict the presence of symptomatic and respiratory diseases. The use of standardized, quantitative methods is feasible, allows for replication, and comparisons across institutions, and has the potential to facilitate consensus quantitative thresholds for risk stratification and treatment. [ABSTRACT FROM AUTHOR]

Data are limited on the incidence of coronavirus disease 2019 (COVID-19) reinfection in children. This population-based cohort study in Niigata, Japan from January to November 2022 demonstrated the incidence of reinfection was 1337/48 099 (2.8%), and the hazard ratio for reinfection in vaccinated children was 0.29 (95% confidence interval, 0.20–0.40). [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 Current guidelines by the Canadian Paediatric Society on treating urinary tract infections (UTIs) exclude infants ≤ 60 days old. There is considerable practice variability in this age group, especially around the optimal duration of parenteral antibiotics. The study aimed to assess local practice patterns, and the safety of a short course (≤3 days) of parenteral antibiotics in young infants. Methods In this retrospective cohort study, 95 infants (≤60 days) with confirmed UTIs were identified at British Columbia Children's Hospital. Patients receiving short (≤3 days) and long (>3 days) duration of parenteral antibiotics were compared. Outcomes of interest included urinary tract infection recurrence within 30 days, hospital length of stay (LOS), representation, and readmission. Results Twenty infants (21%) received a short course of parenteral antibiotics. These infants were older (median 47 days versus 28 days) and non-bacteremic. Urinary tract infection recurrence was identified in 8 patients (8%), of which 7 were treated with a long duration (P = 1.0). Patients treated with a short duration had a significantly shorter LOS, with a mean difference of 4.21 days [95% CI: 3.37 to 5.05] (P < 0.001). All five (5%) bacteremic patients were treated exclusively with parenteral antibiotics. Conclusions In a Canadian setting, a short course of parenteral antibiotics is safe in young, non-bacteremic infants with UTIs. Despite substantial evidence, local practice patterns suggest a tendency towards prescription of long courses, providing an opportunity for quality improvement. [ABSTRACT FROM AUTHOR]

In March–June 2023, we conducted a test-negative study in 1671 children who were hospitalized with acute respiratory illness in Hong Kong. Two hundred and eighty-six children (17.2%) were tested positive for influenza virus including 188 with A(H1N1). We estimated influenza vaccine effectiveness against influenza-associated hospitalization as 69.6% (95% confidence interval: 49.3%, 81.7%). [ABSTRACT FROM AUTHOR]

Background Trimethoprim–sulfamethoxazole (TMP–SMX) is active against most Staphylococcus aureus isolates but is not widely used for the treatment of pediatric osteoarticular infections. Methods This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP–SMX vs. other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at 3 hospitals using inverse probability of treatment weighted propensity score analysis. The primary outcome was treatment failure, a composite of unanticipated emergency department (ED) or outpatient visits, hospital readmissions, extension, or change of antibiotic therapy due to inadequate clinical response, or death, all within 6 months after completing antibiotics. The secondary outcome was antibiotic-associated adverse events (AEs) within 6 months. The exposed group for the treatment failure analysis included children who received ≥7 days of TMP–SMX and did not experience treatment failure while on another antibiotic. Children receiving at least 1 dose of TMP–SMX were the exposed group for the AE analysis. Results One-hundred and sixteen patients met eligibility criteria; 26 (22.4%) patients were classified into the TMP–SMX cohort and 90 (77.6%) into the other antibiotics cohort (most commonly clindamycin, vancomycin, and cefazolin). There was no significant difference in treatment failure between TMP–SMX and other antibiotics (43% vs. 19%; 95% CI.9–10.4). More patients in the TMP–SMX cohort experienced an unplanned ED or outpatient visit (OR 4.8, 95% CI 1.3–17.8). There was no difference in hospital readmission, antibiotic change, or duration extension. Exposure to TMP–SMX was associated with more AEs (41% vs. 19%, P  = .012). Conclusions Treatment with TMP–SMX was not associated with greater clinical failure but was associated with more AEs compared to alternative agents for the treatment of pediatric acute osteoarticular infections. [ABSTRACT FROM AUTHOR]