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Objectives: To examine patterns of non-high-density lipoprotein (HDL) cholesterol in early childhood and identify factors associated with persistent high non-HDL cholesterol in healthy urban children.Study Design: We identified all children enrolled in a primary care practice-based research network called TARGet Kids! (The Applied Research Group for Kids) with ≥3 laboratory measurements of non-HDL cholesterol. Latent class growth model analysis was performed to identify distinct trajectory groups for non-HDL cholesterol. Trajectory groups were then categorized into "normal" vs "persistent-high" non-HDL cholesterol based on guideline cut-off values and logistic regression was completed to examine the association between trajectory group and the presence of anthropometric and cardiometabolic risk factors.Results: A total of 608 children met inclusion criteria for the trajectory analysis (median age at enrolment = 18.3, IQR = 27.9 months). Four trajectory groups were identified with 2 groups (n = 451) categorized as normal non-HDL cholesterol and 2 groups (n = 157) as persistent high non-HDL cholesterol. Family history of high cholesterol (OR 2.04, 95% CI 1.27-3.28) was associated significantly with persistent high non-HDL cholesterol, whereas East/Southeast Asian vs European ethnicity (OR 0.33, 95% CI 0.14-0.78), longer breastfeeding duration (OR 0.96, 95% CI 0.93-1.00), and greater birth weight (OR 0.69, 95% CI 0.48-1.00) were associated with lower odds of persistent high non-HDL cholesterol.Conclusions: Patterns of non-HDL cholesterol are identified during early childhood, and family history of high cholesterol was associated most strongly with persistent high non-HDL cholesterol. Future research should inform the development of a clinical prediction tool for lipids in early childhood to identify children who may benefit from interventions to promote cardiovascular health. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost-effectiveness of an evidence-informed institutional protocol for physicians that encouraged management of children with newly diagnosed immune thrombocytopenia with observation over active therapy, where appropriate.Study Design: We conducted a probabilistic cost-effectiveness analysis from an institutional perspective using a decision tree with a one year time horizon. Patient-level data was retrospectively ascertained for children diagnosed in pre-protocol (2007-2009) and post-protocol (2013-2018) time periods. ITP resolution was defined as achieving a sustained platelet count of >100×103/μL at 9-12 months after diagnosis. Outpatient care and inpatient costs were obtained from the institution and provincial sources. Intervention costs accounted for QI initiative preparation and staff physician training. Incremental costs, incremental effects, and confidence intervals were calculated from 10 000 model iterations.Results: Forty-eight patients were followed for one year in the pre-protocol period and 84 in the post-protocol period. After protocol implementation, an average cost savings per child managed of $2055 (95% CI: $656, $3890) CAD was observed, as was a higher proportion of resolved ITP cases. The implementation strategy remained less costly and more effective in 99.7% of model iterations.Conclusions: Implementation of an evidence-informed institutional protocol to guide physicians towards increased uptake of observation over active therapy when managing children with newly diagnosed ITP resulted in significant cost savings on a per case basis, even after accounting for training-related costs. Though the long-term cost implications regarding the sustainability of the intervention are not yet known, it is anticipated that continued institutional savings could occur. [ABSTRACT FROM AUTHOR]

An ongoing challenge has been determining clinically relevant serum ferritin cut-offs in the diagnosis of iron deficiency in children aged 1-3 years. We identified 2 potential clinically relevant serum ferritin cut-off values through their association with clinically important cut-off of hemoglobin as the indicator of anemia. [ABSTRACT FROM AUTHOR]

Objectives: To examine the relationship between family immigrant status and unscheduled 7-day revisits to the emergency department (ED) and to test this relationship within subgroups of immigrants by visa class (family, economic, refugee), native tongue on landing in Canada, and region of origin.Study Design: Population-based cohort study that used multiple linked health administrative and demographic datasets of landed immigrant and nonimmigrant children (<18 years) in urban Ontario who visited an ED and were discharged between April 2003 and March 2010. Logistic regression was used to model the odds of 7-day ED revisits with family immigrant status, with adjustment for patient and ED characteristics.Results: Of 3,322,901 initial visits to the ED, 249,648 (7.5%) resulted in a 7-day revisit. There was no significant association of immigrant status with either ED revisits or poor revisit outcomes (greater acuity visit or need for admission) in the adjusted models. Within immigrants, the odds of revisit were not associated with immigrant classes or region of origin; however, immigrants whose native tongue was not English or French had a slightly greater odds of revisiting the ED (aOR 1.05; 95% CI 1.01, 1.09). Significant predictors of revisits included younger age, greater triage acuity score, greater predilection for using an ED, daytime shifts, and greater deprivation index.Conclusions: Immigrant children are not more likely to have short-term revisits to the ED, but there may be barriers to care related to language fluency that need to be addressed. These findings may be relevant for improving translation services in EDs. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of corticosteroids with intravenous immune globulin (IVIG) for the initial treatment of children with acute immune thrombocytopenic purpura (ITP). Study design: A systematic review and meta-analysis of randomized controlled trials comparing corticosteroids with IVIG. Studies were identified from eight electronic databases, meeting abstracts, expert consultation, and hand-searched reference lists. Two authors independently reviewed potentially eligible studies and extracted data. The number of patients with a platelet count >20,000/mm3, 48 hours after treatment initiation, was the primary outcome. Relative risks (RR) and risk differences were pooled using a random effects model, and numbers needed to treat (NNT) were calculated. Results: A total of 1248 abstracts were reviewed, 55 articles were retrieved, and 10 studies were included. The RR (steroids vs IVIG) of achieving a platelet count >20,000/mm3 at 48 hours was 0.74 (95% CI: 0.65, 0.85), and the NNT was 4.55 (95% CI: 3.23, 7.69). Conclusion: Children treated with corticosteroids for acute ITP are 26% less likely to have a platelet count >20,000/mm3 after 48 hours of therapy, when compared with children treated with IVIG. Given the importance of low platelets in the pathogenesis of intracranial hemorrhage (ICH), this difference may hold important clinical implications. [Copyright &y& Elsevier]

Objective: To compare the effects of 2 treatment options on neurodevelopmental and laboratory outcomes in young children with nonanemic iron deficiency.Study Design: A blinded, placebo-controlled, randomized trial of children 1-3 years with nonanemic iron deficiency (hemoglobin ≥110 g/L, serum ferritin <14 μg/L) was conducted in 8 primary care practices in Toronto, Canada. Interventions included ferrous sulfate or placebo for 4 months; all parents received diet advice. The primary outcome was the Early Learning Composite (ELC) using the Mullen Scales of Early Learning (mean 100, SD 15). Secondary outcomes included serum ferritin. Measurements were obtained at baseline and 4 and 12 months. Sample size was calculated to detect a between-group difference of 6-7 points in ELC.Results: At enrollment (n = 60), mean age was 24.2 (SD 7.4) months and mean serum ferritin was 10.0 (SD 2.4) μg/L. For ELC, the mean between-group difference at 4 months was 1.1 (95% CI -4.2 to 6.5) and at 12 months was 4.1 (95% CI -1.9 to 10.1). For serum ferritin, at 4 months, the mean between-group difference was 16.9 μg/L (95% CI 6.5 to 27.2), and no child randomized to ferrous sulfate had a serum ferritin <14 μg/L (0% vs 31%, P = .003).Conclusions: For young children with nonanemic iron deficiency, treatment options include oral iron and/or diet advice. We remain uncertain about which option is superior with respect to cognitive outcomes; however, adding ferrous sulfate to diet advice resulted in superior serum ferritin outcomes after 4 months. Shared decision-making between practitioners and parents may be considered when selecting either option.Trial Registration: Clinicaltrials.gov: NCT01481766. [ABSTRACT FROM AUTHOR]

In infants 1-3 years of age, we found higher serum ferritin values associated with higher cognitive function, as measured by the Mullen Scales of Early Learning (P =.02 for the nonlinear relationship). A serum ferritin of 17 μg/L corresponded to the maximum level of cognition, beyond which there was no meaningful improvement. Clinicaltrials.gov NCT01481766 and NCT01869530. [ABSTRACT FROM AUTHOR]

In infants 1-3 years of age, we found higher serum ferritin values associated with higher cognitive function, as measured by the Mullen Scales of Early Learning (P = .02 for the nonlinear relationship). A serum ferritin of 17 μg/L corresponded to the maximum level of cognition, beyond which there was no meaningful improvement. TRIAL REGISTRATION: Clinicaltrials.gov NCT01481766 and NCT01869530. [ABSTRACT FROM AUTHOR]

Objectives: To determine the association between cow's milk-fat and non-high-density lipoprotein (non-HDL) cholesterol, a marker of cardiovascular disease (CVD) risk in young children, and whether this association is mediated by the typical volume of cow's milk consumed.Study Design: A longitudinal study in 2- to 8-year-old children (n = 2890) was conducted through The Applied Research Group for Kids (TARGet Kids!), a practice-based research network in Toronto, Canada. Generalized estimating equations were used to examine the relationship between parent-reported cow's milk-fat percentage intake and serum non-HDL cholesterol concentrations as well as having high non-HDL cholesterol (≥3.75 mmol/L [145 mg/dL]), adjusting for covariates including age, sex, body mass index z score, breastfeeding duration, mother's ethnicity, and parental history of CVD. Bootstrap resampling (10 000 repetitions) was used to assess whether typical volume consumed mediated the association between cow's milk-fat percentage and non-HDL cholesterol.Results: In total, 156 (5.4%) had high non-HDL cholesterol. Each percent increase in cow's milk-fat was associated with a 0.035 mmol/L (1.35 mg/dL) (P < .001) and 0.024 mmol/L (0.92 mg/dL) (P = .01) increase in non-HDL cholesterol, unadjusted and adjusted for covariates respectively. Cow's milk-fat percentage was not associated with greater odds of having high non-HDL cholesterol. Volume of cow's milk partially mediated the association between cow's milk-fat percentage and non-HDL cholesterol, accounting for 28% of the relationship (P < .001).Conclusions: Consumption of higher-fat cow's milk was associated with a small increase in non-HDL cholesterol but not greater odds of having high non-HDL cholesterol. Further research is needed to assess this relationship with other CVD risk factors in young children.Trial Registration: ClinicalTrials.gov: NCT01869530. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between body mass index (BMI) and iron deficiency in early childhood, while considering the influence of low-grade systemic inflammation.Study Design: Healthy children ages 1-3 years were included in a cross-sectional analysis. Age- and sex-standardized World Health Organization BMI z score (zBMI) was calculated using height/length and weight measurements; iron status was assessed by serum ferritin; inflammation was assessed by C-reactive protein (CRP). Children with CRP ≥10 mg/L were excluded because this may indicate acute systemic inflammation. Adjusted multivariable regression analyses were used to investigate the association between zBMI and both serum ferritin (µg/L), and iron deficiency (serum ferritin <12 µg/L). We performed prespecified subgroup analyses according to CRP level (normal [≤1.0 mg/L] and low-grade inflammation [>1.0 mg/L to <10.0 mg/L]).Results: Of 1607 children included, 20% were categorized as with zBMI >1, 13% had iron deficiency, and 18% had low-grade inflammation. Higher zBMI was associated with lower serum ferritin (-1.51 µg/L, 95% CI -2.23, -0.76, P < .0001) and increased odds of iron deficiency (OR 1.28, 95% CI 1.10, 1.50, P = .002). Though there was no interaction between zBMI and CRP for the adjusted linear regression model (P = .79) or logistic regression model (P = .43), children with low-grade inflammation had a higher serum ferritin (P < .0001).Conclusions: Higher zBMI is associated with increased risk for iron deficiency in children between 1 and 3 years, and should be considered as a risk factor in targeted screening. Further research is needed to better understand the relationship between serum ferritin and CRP for children in all weight categories.Trial Registration: ClinicalTrials.gov: NCT01869530. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between breastfeeding duration and early childhood cardiometabolic risk.Study Design: A cross-sectional study of 1539 healthy children, 3-6 years of age, recruited through The Applied Research Group for Kids! practice-based research network between October 2009 and August 2015. Adjusted multivariable linear regression was used to examine the association between breastfeeding duration and cardiometabolic risk z score and individual cardiometabolic risk factors of waist circumference, systolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides.Results: The mean breastfeeding duration was 12.5 months (SD = 8.4). Breastfeeding duration was associated with lower cardiometabolic risk z score (beta = -0.03; 95% CI -0.05, -0.01). In analysis of cardiometabolic risk factors, each additional 3 months of breastfeeding was associated with a 0.13 cm (95% CI -0.20, -0.05) lower waist circumference and 0.16 mm Hg (95% CI -0.30, -0.02) lower systolic blood pressure. Compared with children who breastfed for 6-12 months, those who breastfed for 12-24 months had a lower systolic blood pressure of 1.07 mm Hg (95% CI -2.04, -0.10). There was no association between breastfeeding duration and cardiometabolic risk for those who breastfed beyond 24 months.Conclusions: Breastfeeding duration is associated with lower cardiometabolic risk, although the magnitude of association is small. Causation cannot be inferred. Breastfeeding beyond 24 months may not have an added benefit for cardiometabolic health. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association between fasting duration and lipid and metabolic test results.Study Design: A cross-sectional study was conducted in healthy children aged 0-6 years from The Applied Research Group for Kids! (TARGet Kids!) primary care practice network, Toronto, Canada, 2008-2013. The associations between duration of fasting at blood collection and serum lipid tests and metabolic tests were evaluated using linear regression.Results: Among 2713 young children with blood tests the fasting time ranged from 0 to 5 hours (1st and 99th percentiles). Fasting duration was not significantly associated with total cholesterol (β = 0.006; P = .629), high-density lipoprotein (HDL) (β = 0.002; P = .708), low-density lipoprotein (β = 0.0013; P = .240), non-HDL (β = 0.004; P = .744), or triglycerides (β = -0.016; P = .084) adjusted for age, sex, body mass index, maternal ethnicity, and time of blood draw. Glucose, insulin, and homeostasis model assessment of insulin resistance were significantly associated with fasting duration, and the average percent change between 0 and 5 hours was -7.2%, -67.1%, and -69.9%, respectively. The effect of fasting on lipid or metabolic test results did not differ by age or sex; HDL and triglycerides may differ by weight status.Conclusions: In this cohort of healthy young children, we found little evidence to support the need for fasting prior to measurement of lipids. The effect of fasting on glucose was small and may not be clinically important. When measuring serum lipid tests in early childhood, fasting makes a very small difference.Trial Registration: ClinicalTrials.gov: NCT0186953. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate risk factors associated with surgical intervention and subperiosteal/orbital abscess in hospitalized children with severe orbital infections., Study Design: We conducted a multicenter cohort study of children 2 months to 18 years hospitalized with periorbital or orbital cellulitis from 2009 to 2018 at 10 hospitals in Canada. Clinical details were extracted, and patients were categorized as undergoing surgical or medical-only management. Primary outcome was surgical intervention and the main secondary outcome was clinically important imaging. Logistic regression was used to identify predictors., Results: Of 1579 patients entered, median age was 5.4 years, 409 (25.9%) had an orbital/subperiosteal abscess, and 189 (12.0%) underwent surgery. In the adjusted analysis, the risk of surgical intervention was associated with older age (age 9 to <14: aOR 3.9, 95% CI 2.3-6.6; and age 14 to ≤18 years: aOR 7.0, 95% CI 3.4-14.1), elevated C-reactive protein >120 mg/L (aOR 2.8, 95% CI 1.3-5.9), elevated white blood cell count of 12-20 000/μL (aOR 1.7, 95% CI 1.1-2.6), proptosis (aOR 2.6, 95% CI 1.7-4.0), and subperiosteal/orbital abscess (aOR 5.3, 95% CI 3.6-7.9). There was no association with antibiotic use before hospital admission, sex, presence of a chronic disease, temperature greater than 38.0°C, and eye swollen shut. Complications were identified in 4.7% of patients, including vision loss (0.6%), intracranial extension (1.6%), and meningitis (0.8%)., Conclusions: In children hospitalized with severe orbital infections, older age, elevated C-reactive protein, elevated white blood cell count, proptosis, and subperiosteal/orbital abscess were predictors of surgical intervention., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To examine if the initial oxygen saturation (SaO2) in the Emergency Department is a useful predictor of prolonged frequent bronchodilator therapy (FBT) in children with acute asthma., Study Design: Prospective cohort study of 273 children, 1 to 17 years of age, requiring systemic corticosteroids. Patients were categorized as needing FBT for >4 hours (n=166) versus >4 hours (n=107) and >12 hours (n=79) versus >12 hours (n=194). Multiple logistic regression determined the association between SaO2 and these outcomes., Results: Baseline SaO2 remains a significant independent predictor of FBT for >4 hours (OR=0.81) and >12 hours (OR=0.84); 91% of patients with SaO2 of 90% to 91% had FBT >4 hours and 80% of patients with SaO2 of < or =89% had FBT >12 hours. Children with SaO2 of < or =91% are 14.7 and 12.0 times more likely to require FBT for >4 hours and >12 hours, respectively, than those with SaO2 of 98% to 100%. The interval likelihood ratios for FBT >4 hours were 12.3 for SaO2 of < or =89%, 6.5 for 90% to 91%, but only 1.8 for 92% to 93%. The likelihood ratios for FBT >12 hours decreased from 9.8 for SaO2 of < or =89% to 3.5 for SaO2 of 90% to 91%., Conclusions: SaO2 is a useful predictor of FBT >4 hours if it is < or =91% and of FBT >12 hours if it is < or =89%.

Objective: To develop a clinical dehydration scale for use in children <3 years of age., Study Design: Prospective cohort study of children between 1 and 36 months of age who presented to a tertiary pediatric emergency department (ED) with gastroenteritis. Children were weighed and scored for 12 clinical signs, were rehydrated, and then were reweighed and rescored when rehydration was completed. Weight change from pre- to post-rehydration was used to assess criterion validity with independent global assessments of dehydration severity by attending physicians and nurses as measures of construct validity. Formal approaches to item selection and reduction, reliability, discriminatory power, validity, and responsiveness were used., Results: 137 children (median age: 18 months) with gastroenteritis were studied. The final dehydration scale consisted of four clinical characteristics: general appearance, eyes, mucous membranes, and tears. The measurement properties were as follows: validity as assessed by Pearson's correlation coefficient was 0.36 to 0.57; reliability as assessed by the intra-class correlation coefficient was 0.77; discriminatory power as assessed by Ferguson's delta was 0.83; and responsiveness to change as assessed by Wilcoxon signed rank test was significant at P <.01., Conclusion: Clinicians and researchers may consider this four-item, 8-point rating scale, developed using formal measurement methodology, as an alternative to scales developed ad hoc.