Current and new frontiers in hereditary cancer surveillance: Opportunities for liquid biopsy.

At least 5% of cancer diagnoses are attributed to a causal pathogenic or likely pathogenic germline genetic variant (hereditary cancer syndrome-HCS). These individuals are burdened with lifelong surveillance monitoring organs for a wide spectrum of cancers. This is associated with substantial uncertainty and anxiety in the time between screening tests and while the individuals are awaiting results. Cell-free DNA (cfDNA) sequencing has recently shown potential as a non-invasive strategy for monitoring cancer. There is an opportunity for high-yield cancer early detection in HCS. To assess clinical validity of cfDNA in individuals with HCS, representatives from eight genetics centers from across Canada founded the CHARM (cfDNA in Hereditary and High-Risk Malignancies) Consortium in 2017. In this perspective, we discuss operationalization of this consortium and early data emerging from the most common and well-characterized HCSs: hereditary breast and ovarian cancer, Lynch syndrome, Li-Fraumeni syndrome, and Neurofibromatosis type 1. We identify opportunities for the incorporation of cfDNA sequencing into surveillance protocols; these opportunities are backed by examples of earlier cancer detection efficacy in HCSs from the CHARM Consortium. We seek to establish a paradigm shift in early cancer surveillance in individuals with HCSs, away from highly centralized, regimented medical screening visits and toward more accessible, frequent, and proactive care for these high-risk individuals.

Association Between Family Income and Positive Developmental Screening Using the Infant Toddler Checklist at the 18-Month Health Supervision Visit.

OBJECTIVE: To examine the associations between several potential predictors (child biologic, social, and family factors) and a positive screen for developmental delay using the Infant Toddler Checklist (ITC) at the 18-month health supervision visit in primary care. METHODS: This was a cross-sectional study of healthy children attending an 18-month health supervision visit in primary care. Parents completed a standardized questionnaire, addressing child, social, and family characteristics, and the ITC. Logistic regression analyses were used to assess the associations between predictors and a positive ITC. RESULTS: Among 2188 participants (45.5% female; mean age, 18.2 months), 285 (13%) had a positive ITC and 1903 (87%) had a negative ITC. The aOR for a positive ITC for male compared with female sex was 2.15 (95% CI, 1.63-2.83; P < .001). The aOR for birthweight was 0.65 per 1 kg increase (95% CI, 0.53-0.80; P < .001). The aOR for a family income of <$40,000 compared with ≥$150,000 was 3.50 (95% CI, 2.22-5.53; P < .001), and the aOR for family income between $40,000-$79,999 compared with ≥$150,000 was 1.88 (95% CI, 1.26-2.80; P = .002). CONCLUSIONS: Screening positive on the ITC may identify children at risk for the double jeopardy of developmental delay and social disadvantage and allow clinicians to intervene through monitoring, referral, and resource navigation for both child development and social needs. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01869530).

Hemoglobin Threshold for Blood Transfusion in Young Children Hospitalized with Iron Deficiency Anemia.

Current recommendations advise against blood transfusion in hemodynamically stable children with iron deficiency anemia. In an observational study of 125 children aged 6 through 36 months, hospitalized with iron deficiency anemia, we found that hemoglobin level predicted red blood cell transfusion (area under the curve 0.8862). A hemoglobin of 39 g/L had sensitivity 92% and specificity 72% for transfusion.

Connecting families: a qualitative study examining the experiences of parenting young children under financial strain in Ontario, Canada.

BACKGROUND: There is little research investigating the subjective experiences of parenting young children while living in poverty and experiencing financial strain using qualitative methodologies. Therefore, the objective of this study was to employ a qualitative approach to provide a nuanced and balanced view on the topic of parenting young children under financial strain in the Canadian context. METHODS: We conducted a qualitative study using semi-structured interviews between July and August 2021 in Kingston, Ontario, Canada. Sixteen participants aged 20-39 self-identified as living under financial strain while parenting a child aged 2-5 years. A qualitative inductive thematic analysis was undertaken with a focus on describing the contents of the data. RESULTS: Four major themes emerged from the data: experience of being a parent, impact of financial strain on the family unit, impact of financial strain on the children, and impact of financial strain on the parent. Numerous deleterious physical, mental, and material impacts on the family unit and parent were identified, however parent-perceived impacts of financial strain on their children were minimal. Parents described striking levels of resourcefulness and resiliency in providing the necessities for their families, absorbing the most significant impacts of financial strain through the phenomenon of self-sacrifice. CONCLUSION: The impacts of financial strain on families with young children are far reaching. Further research into the impacts of self-sacrifice on parents experiencing financial strain are needed to better understand this issue, and to inform social programming and resources that could help alleviate the deleterious impacts of poverty on parent mental, social, and physical health.

Cost-Effectiveness of a Quality Improvement Initiative for the Clinical Management of Children with Newly Diagnosed Immune Thrombocytopenia.

OBJECTIVE: To assess the cost-effectiveness of an evidence-informed institutional protocol for physicians that encouraged management of children with newly diagnosed immune thrombocytopenia (ITP) 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 1 year time horizon. Patient-level data were 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 quality improvement initiative preparation and staff physician training. Incremental costs, incremental effects, and CIs were calculated from 10 000 model iterations. RESULTS: Forty-eight patients were followed for 1 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) Canadian Dollars 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 toward 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.

Determinants of Anishinabeck infant and early childhood growth trajectories in Northwestern Ontario, Canada: a cohort study.

BACKGROUND: The Developmental Origins of Health and Disease (DOHaD) paradigm emphasizes the significance of early life factors for the prevention of chronic health conditions, like type 2 diabetes (T2DM) and obesity, which disproportionately affect First Nations communities in Canada. Despite increasing DOHaD research related to maternal health during pregnancy, early childhood growth patterns, and infant feeding practices with many populations, data from First Nations communities in Canada are limited. In partnership with Sandy Lake First Nation, the aims of this project were to characterize birthweights and growth patterns of First Nations infants/children over the first 6 years of life and to study the impact of maternal and infant social and behavioral factors on birthweight and growth trajectories. METHODS: We recruited 194 families through community announcements and clinic visits. Infant/child length/height and weight were measured at 1 and 2 weeks; 1, 2, 6, 12, and 18 months; and 2, 3, 4, 5 and 6 years. Maternal and infant/child questionnaires captured data about health, nutrition, and social support. Weight-for-Age z-score (WAZ), Height-for-Age z-score (HAZ), and BMI-for-Age z-score (BAZ) were calculated using WHO reference standards and trajectories were analyzed using generalized additive models. Generalized estimating equations and logistic regression were used to determine associations between exposures and outcomes. RESULTS: WAZ and BAZ were above the WHO mean and increased with age until age 6 years. Generalized estimating equations indicated that WAZ was positively associated with age (0.152; 95% CI 0.014, 0.29), HAZ was positively associated with birthweight (0.155; 95% CI 0.035, 0.275), and BAZ was positively associated with caregiver's BMI (0.049; 95% CI 0.004, 0.090). There was an increased odds of rapid weight gain (RWG) with exposure to gestational diabetes (OR: 7.47, 95% CI 1.68, 46.22). Almost 70% of parents initiated breastfeeding, and breastfeeding initiation was modestly associated with lower WAZ (-0.18; 95% CI -0.64, 0.28) and BAZ (-0.23; 95% CI -0.79, 0.34). CONCLUSIONS: This work highlights early life factors that may contribute to T2DM etiology and can be used to support community and Indigenous-led prevention strategies.

Factors Associated with Surgery and Imaging Characteristics in Severe Orbital Infections.

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.

Selumetinib for symptomatic, inoperable plexiform neurofibromas in children with neurofibromatosis type 1: A national real-world case series.

Neurofibromatosis type 1-associated plexiform neurofibromas can cause debilitating symptoms and be life threatening. Treatment options are limited, given their tendency to regrow following surgery and their propensity to transform into malignant tumours following radiation. Selumetinib is an oral selective inhibitor of RAS-mitogen-activated protein kinase (MAPK) 1 and 2, which has shown efficacy for tumour shrinkage/stabilisation and symptom improvement. We report a national case series of 19 children treated with selumetinib. All patients experienced symptom improvement or stabilisation with an acceptable toxicity profile, including those patients previously treated with trametinib. This real-world experience confirms previous trials showing significant clinical benefit for this patient population.

Children's screen use and school readiness at 4-6 years: prospective cohort study.

BACKGROUND: The primary aim of this study was to determine if screen use in early childhood is associated with overall vulnerability in school readiness at ages 4 to 6 years, as measured by the Early Development Instrument (EDI). Secondary aims were to: (1) determine if screen use was associated with individual EDI domains scores, and (2) examine the association between screen use and EDI domains scores among a subgroup of high screen users. METHODS: This prospective cohort study was carried out using data from young children participating in a large primary care practice-based research network in Canada. Logistic regression analyses were run to investigate the association between screen use and overall vulnerability in school readiness. Separate linear regression models examined the relationships between children's daily screen use and each separate continuous EDI domain. RESULTS: A total of 876 Canadian participants participated in this study. Adjusted logistic regression revealed an association between increased screen use and increased vulnerability in school readiness (p = 0.05). Results from adjusted linear regression demonstrated an association between higher screen use and reduced language and cognitive development domain scores (p = 0.004). Among high screen users, adjusted linear regression models revealed associations between increased screen use and reduced language and cognitive development (p = 0.004) and communication skills and general knowledge domain scores (p = 0.042). CONCLUSIONS: Screen use in early childhood is associated with increased vulnerability in developmental readiness for school, with increased risk for poorer language and cognitive development in kindergarten, especially among high users.

Randomized Trial of Oral Iron and Diet Advice versus Diet Advice Alone in Young Children with Nonanemic Iron Deficiency.

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.

Nutritional Risk in Early Childhood and School Readiness.

BACKGROUND: Nutrition in early childhood is important for healthy growth and development. Achieving school readiness is considered one of the most important developmental milestones for young children. OBJECTIVES: The purpose of this study is to determine if nutritional risk in early childhood is associated with school readiness in kindergarten. METHODS: A prospective cohort study was conducted through The Applied Research Group for Kids (TARGet Kids!) primary care research network in Toronto, Canada, 2015-2020. Nutritional risk was measured (18 mo to 5 y) using validated parent-completed questionnaires called Nutrition Screening for Toddlers and Preschoolers (NutriSTEP). High nutritional risk was categorized as scores ≥21. School readiness was measured using the validated teacher-completed Early Developmental Instrument (EDI), which measures 5 developmental domains in kindergarten (2 y of schooling, ages 4-6 y, before they enter grade 1). Vulnerability indicates scores lower than a population-based cutoff at the 10th percentile on at least 1 domain. Multiple logistic and linear regression models were conducted adjusting for relevant confounders. RESULTS: The study included 896 children: 53% were male, 9% had high nutritional risk, and 17% were vulnerable on the EDI. A 1-SD increase in NutriSTEP total score was associated with 1.54 times increased odds of being vulnerable on the EDI among children in year 2 of kindergarten (P = 0.001). High nutritional risk cutoff was associated with 4.28 times increased odds of being vulnerable on the EDI among children in year 2 of kindergarten (P < 0.001). NutriSTEP total score and high nutritional risk were associated with lower scores on all 5 EDI domains, with the strongest association observed for the domains of language and cognitive development and communication skills and general knowledge. CONCLUSIONS: Higher nutritional risk in early childhood is associated with lower school readiness in year 2 of kindergarten. Nutritional interventions early in life may offer opportunities to enhance school readiness. This trial was registered www.clinicaltrials.gov as NCT01869530.

Parenteral versus enteral fluid therapy for children hospitalised with bronchiolitis.

BACKGROUND: The main focus of treatment for children hospitalised with bronchiolitis is supportive, including oxygen supplementation, respiratory support, and fluid therapy. Up to half of infants hospitalised with bronchiolitis require non-oral fluid therapy due to dehydration or concerns related to the safety of oral feeding. The two main modalities used for non-oral fluid therapy are parenteral (intravenous (IV)) and enteral tube (nasogastric (NG) or orogastric (OG)). However, it is not known which mode is optimal in young children. OBJECTIVES: To systematically review randomised clinical trials (RCTs) of the effectiveness and safety of parenteral and enteral tube fluid therapy for children under two years of age hospitalised with bronchiolitis. SEARCH METHODS: We conducted a search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 8 March 2021. We handsearched conference proceedings, conducted forward and backward searching of citation lists of relevant articles, and contacted experts. SELECTION CRITERIA: We included RCTs and quasi-RCTs of children aged up to two years admitted to hospital with a clinical diagnosis of bronchiolitis who required fluid therapy. The trials compared enteral tube fluid therapy with parenteral fluid therapy. The primary outcome was difference in length of hospital stay in hours after each non-oral fluid therapy modality. As actual time of discharge can be impacted by various factors, we also assessed theoretical length of stay (i.e. time when a patient is safe for discharge). We assessed several secondary outcomes. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  MAIN RESULTS: The searches yielded 615 unique records, of which four articles underwent full-text screening. We included two trials (810 children). Oakley 2013 was an open, non-blinded RCT of infants aged two to 12 months admitted to hospitals in Australia and New Zealand with a clinical diagnosis of bronchiolitis during three bronchiolitis seasons. The trial enrolled 759 children, of which 381 were randomised to NG tube therapy and 378 to IV therapy. Risk of bias was low in most domains. Kugelman 2013 was an open, non-blinded RCT that enrolled infants aged less than six months with a clinical diagnosis of "moderate bronchiolitis" at a single hospital in Israel. The study enrolled 51 infants, of which 31 were assigned to NG or OG tube therapy and 20 to IV therapy. Risk of bias was unclear in most domains. The application of enteral tube fluid therapy compared to IV fluid therapy probably makes little to no difference for actual length of hospital stay (mean difference (MD) 6.8 hours, 95% confidence interval (CI) -4.7 to 18.4 hours; 2 studies, 810 children, moderate certainty evidence). There was also little to no difference for theoretical length of stay (MD 4.4 hours, 95% CI -3.6 to 12.4 hours; 2 studies, 810 children, moderate certainty evidence). For the secondary outcomes, enteral tube fluid therapy probably makes little to no difference for time to resume full oral feeding compared to IV fluid therapy (MD 2.8 hours, 95% CI -3.6 to 9.2 hours; 2 studies, 810 children, moderate certainty evidence). The use of enteral tube for fluid therapy probably results in a large increase in the success of insertion of fluid modality at first attempt (risk ratio (RR) 1.52, 95% CI 1.36 to 1.69; 1 study, 617 children, moderate certainty evidence), and probably largely reduces the chances of change in fluid therapy modality (RR 0.52, 95% CI 0.38 to 0.71; 1 study, 759 children, moderate certainty evidence) compared to IV fluid.  Oakley 2013 reported 47 local complication events after discharge in the IV fluid group compared to 30 events in the NG tube group. They also evaluated parental satisfaction, which was high with both modalities. Enteral tube fluid therapy makes little to no difference to the duration of oxygen supplementation (MD 2.2 hours, 95% CI -5.0 to 9.5 hours; 2 studies, 810 children, moderate certainty evidence). Compared with the IV fluid therapy group, there was a 17% relative reduction in the number of intensive care unit admissions (RR 0.83, 95% CI 0.47 to 1.46; 1 study, 759 children, moderate certainty evidence) and a 19% relative reduction in number of readmissions to hospital (RR 0.81, 95% CI 0.33 to 2.04; 1 study, 678 children, moderate certainty evidence) in the enteral tube fluid therapy group. Adverse events were uncommon in both trials, with likely little to no differences between groups. AUTHORS' CONCLUSIONS: Based on two RCTs, enteral tube feeding likely results in little to no difference in length of hospital stay compared with the IV fluid group. However, enteral tube fluid therapy likely results in a large increase in the success of insertion of fluid modality at first attempt, and a large reduction in change in modality of fluid therapy. It also probably reduces local complications compared to the IV fluid group. Despite bronchiolitis being one of the most prevalent childhood conditions, we identified only two studies with under 1000 participants in total, which highlights the need for multicentre trials. Future studies should explore type of fluid administered, parent-reported outcomes and preferences, and the role of shared decision-making.

Corticosteroids for periorbital and orbital cellulitis.

BACKGROUND: Periorbital and orbital cellulitis are infections of the tissue anterior and posterior to the orbital septum, respectively, and can be difficult to differentiate clinically. Periorbital cellulitis can also progress to become orbital cellulitis. Orbital cellulitis has a relatively high incidence in children and adults, and potentially serious consequences including vision loss, meningitis, and death. Complications occur in part due to inflammatory swelling from the infection creating a compartment syndrome within the bony orbit, leading to elevated ocular pressure and compression of vasculature and the optic nerve. Corticosteroids are used in other infections to reduce this inflammation and edema, but they can lead to immune suppression and worsening infection. OBJECTIVES: To assess the effectiveness and safety of adjunctive corticosteroids for periorbital and orbital cellulitis, and to assess their effectiveness and safety in children and in adults separately. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 3); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 2 March 2020. SELECTION CRITERIA: We included studies of participants diagnosed with periorbital or orbital cellulitis. We excluded studies that focused exclusively on participants who were undergoing elective endoscopic surgery, including management of infections postsurgery as well as studies conducted solely on trauma patients. Randomized and quasi-randomized controlled trials were eligible for inclusion. Any study that administered corticosteroids was eligible regardless of type of steroid, route of administration, length of therapy, or timing of treatment. Comparators could include placebo, another corticosteroid, no treatment control, or another intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. MAIN RESULTS: The search yielded 7998 records, of which 13 were selected for full-text screening. We identified one trial for inclusion. No other eligible ongoing or completed trials were identified. The included study compared the use of corticosteroids in addition to antibiotics to the use of antibiotics alone for the treatment of orbital cellulitis. The study included a total of 21 participants aged 10 years and older, of which 14 participants were randomized to corticosteroids and antibiotics and 7 participants to antibiotics alone. Participants randomized to corticosteroids and antibiotics received adjunctive corticosteroids after initial antibiotic response (mean 5.13 days), at an initial dose of 1.5 mg/kg for three days followed by 1 mg/kg for another three days before being tapered over a one- to two-week period. We assessed the included study as having an unclear risk of bias for allocation concealment, masking (blinding), selective outcome reporting, and other sources of bias. Risk of bias from sequence generation and incomplete outcome data were low. The certainty of evidence for all outcomes was very low, downgraded for risk of bias (-1) and imprecision (-2). Length of hospital stay was compared between the group receiving antibiotics alone compared to the group receiving antibiotics and corticosteroids (mean difference (MD) 4.30, 95% confidence interval (CI) -0.48 to 9.08; 21 participants). There was no observed difference in duration of antibiotics between treatment groups (MD 3.00, 95% CI -0.48 to 6.48; 21 participants). Likewise, preservation of visual acuity at 12 weeks of follow-up between group was also assessed (RR 1.00, 95% CI 0.82 to 1.22; 21 participants). Pain scores were compared between groups on day 3 (MD -0.20, 95% CI -1.02 to 0.62; 22 eyes) along with the need for surgical intervention (RR 1.00, 95% CI 0.11 to 9.23; 21 participants). Exposure keratopathy was reported in five participants who received corticosteroids and antibiotics and three participants who received antibiotic alone (RR 1.20, 95% CI 0.40 to 3.63; 21 participants). No major complications of orbital cellulitis were seen in either the intervention or the control group. No side effects of corticosteroids were reported, although it is unclear which side effects were assessed. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw conclusions about the use of corticosteroids in the treatment of periorbital and orbital cellulitis. Since there is significant variation in how corticosteroids are used in clinical practice, additional high-quality evidence from randomized controlled trials is needed to inform decision making. Future studies should explore the effects of corticosteroids in children and adults separately, and evaluate different dosing and timing of corticosteroid therapy.

Nutritional risk in early childhood and parent-reported school concerns.

OBJECTIVE: To determine if nutritional risk in early childhood is associated with parent-reported school concerns. DESIGN: A prospective cohort study conducted through the TARGet Kids! primary care research network (2011-2018). Nutritional risk was measured between 18 months and 5 years of age using validated parent-completed NutriSTEP® questionnaires with eating behaviour and dietary intake subscores (0 = lowest and 68 = highest total nutritional risk score). Parent-reported school concerns were measured at school age (4-10 years of age) and included: speech and language; learning; attention; behaviour; social relationships; physical coordination; fine motor coordination and self-help skills and independence. The primary outcome was any parent-reported school concerns, and individual school concerns were used as secondary outcomes. Multiple logistic regression models were conducted adjusting for clinically relevant confounders to assess the relationship between nutritional risk and school concerns. SETTING: Toronto, Canada. PARTICIPANTS: Children aged 18 months to 10 years. RESULTS: The study included 3655 children, 52 % were male, mean NutriSTEP® score was 14·4 (sd 6·4). Each 1 sd increase in NutriSTEP® total score was associated with a 1·18 times increased odds of school concerns (adj OR: 1·18, 95 % CI 1·07, 1·28, P = 0·0004), and high nutritional risk was associated with a 1·42 times increased odds of school concerns (adj OR: 1·42, 95 % CI 1·13, 1·78, P = 0·002). CONCLUSIONS: Nutritional risk in early childhood was associated with school concerns. Nutritional interventions in early childhood may reveal opportunities to enhance school outcomes.

Reference intervals for hemoglobin and mean corpuscular volume in an ethnically diverse community sample of Canadian children 2 to 36 months.

OBJECTIVE: To establish reference intervals for hemoglobin and mean corpuscular volume (MCV) in an ethnically diverse community sample of Canadian children 36 months and younger. METHODS: We collected blood samples from young children at scheduled primary care health supervision visits at 2 weeks, 2, 4, 6, 9, 12, 15, 18, 24, and 36 months of age. Samples were analyzed on the Sysmex XN-9000 Hematology Analyzer. We followed the Clinical and Laboratory Standards Institute guidelines in our analysis. Data were partitioned by sex and also combined. We considered large age partitions (3 and 6 months) as well as monthly partitions. Reference intervals (lower and upper limits) and 90% confidence intervals were calculated. RESULTS: Data from 2106 children were included. The age range was 2 weeks to 36 months, 46% were female, 48% were European and 23% were of mixed ethnicity. For hemoglobin, from 2 to 36 months of age, we found a wide reference interval and the 90% confidence intervals indicated little difference across age groups or according to sex. For MCV, from 2 to 7 months of age there was considerable decrease in the reference interval, which was lowest during the second year of life, followed by a slight increase in the last months of the third year of life. CONCLUSION: These findings suggest adoption of a single hemoglobin reference interval for children 2-36 months of age. Further studies in children under 4 months of age are needed. TRIAL REGISTRATION: TARGet Kids! cohort is registered at ClinicalTrials.gov. www.clinicaltrials.gov . Identifier: NCT01869530 .

Screening for marginal food security in young children in primary care.

BACKGROUND: Household food insecurity (FI), even at marginal levels, is associated with poor child health outcomes. The Nutrition Screening Tool for Every Preschooler (NutriSTEP®) is a valid and reliable 17-item parent-completed measure of nutrition risk and includes a single item addressing FI which may be a useful child-specific screening tool. We evaluated the diagnostic test properties of the single NutriSTEP® FI question using the 2-item Hunger Vital Sign™ as the criterion measure in a primary care population of healthy children ages 18 months to 5 years. RESULTS: The sample included 1174 families, 53 (4.5%) of which were marginally food secure. An affirmative response to the single NutriSTEP® question "I have difficulty buying food I want to feed my child because food is expensive" had a sensitivity of 85% and specificity of 91% and demonstrated good construct validity when compared with the Hunger Vital Sign™. CONCLUSION: The single NutriSTEP® question may be an effective screening tool in clinical practice to identify marginal food security in families with young children and to link families with community-based services or financial assistance programs including tax benefits. TRIAL REGISTRATION: TARGet Kids! practice-based research network (Registered June 5, 2013 at www.clinicaltrials.gov ; NCT01869530); www.targetkids.ca.

Associations Between Meeting the 24-Hour Movement Guidelines and Cardiometabolic Risk in Young Children.

INTRODUCTION: The authors aimed to examine the association between meeting the integrative movement behavior guidelines (physical activity, screen viewing, and sleep) and cardiometabolic risk (CMR) factors in young children. METHODS: In this cross-sectional study, physical activity, screen viewing, and sleep were assessed using parent-reported data. The 24-Hour Movement Guidelines for the Early Years (0-4 y) were defined as 180 minutes of physical activity/day (of which ≥60 min should be moderate-to-vigorous intensity), ≤1 hour of screen viewing/day, and 10 to 13 hours of sleep/night. Waist circumference, glucose, high-density lipoprotein cholesterol, triglycerides, and systolic blood pressure were measured in a clinical setting by trained staff. A total CMR score and individual CMR factors served as primary and secondary outcomes, respectively. RESULTS: Of the 767 participants (3-4 y), 26.4% met none of the guideline's recommendations, whereas 41.3%, 33.1%, and 10.6% of the sample met 1, 2, or all 3 recommendations, respectively. The number of recommendations met was not associated with the total CMR score or individual CMR factors (P > .05), with the exceptions of high-density lipoprotein (odds ratio = 1.61; 95% confidence interval, 1.11 to 2.33; P = .01). CONCLUSION: Meeting the 24-Hour Movement Guidelines in early childhood was not associated with overall CMR, but was associated with favorable cholesterol outcomes.

Association between Serum Ferritin and Cognitive Function in Early Childhood.

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.

The association between screen time and cardiometabolic risk in young children.

OBJECTIVES: While studies exist on the association between screen time and cardiometabolic risk among adolescents, research examining the effect of screen time on cardiometabolic risk in young children is lacking. The primary objective of this study was to examine the association between daily screen time and cardiometabolic risk (CMR) [sum of age- and sex-standardized z-scores of systolic blood pressure (SBP), glucose, log-triglycerides, waist circumference (WC), and negative high-density lipoprotein (HDL) cholesterol divided by the square root of five] in young children. Secondary objectives included examining individual CMR risk factors, including waist-to-height ratio and non high-density lipoprotein (non-HDL) cholesterol, as well as the individual cut-offs of these risk factors. Additional analyses include examining the association between screen time and CMR by handheld/non-handheld devices. METHODS: A study was conducted among young children 3 to 6 years from the TARGet Kids! practice-based research network in Toronto and Montreal, Canada. Children with one or more measures of screen time and CMR were included in this study. Generalized estimating equation (GEE) multivariable linear regressions and multivariable logistic regressions, using published cut-offs, were conducted to evaluate these associations. RESULTS: Data from 1317 children [mean age 52 months (SD = 13.36), 44.34% female] were included for analyses. There was no evidence of associations between screen time and total CMR score or individual risk factors (p > 0.05) after adjusting for confounders. A statistically significant, but small association between daily screen time and non-HDL cholesterol was found (B = 0.046; CI = [0.017 to 0.075]; p = 0.002. CONCLUSIONS: Though no relationship was reported between daily screen time and the majority of CMR factors in early childhood, there was an association between daily screen time and non-HDL cholesterol. As the relationship between daily screen time and CMR factors may not be apparent in early childhood, studies to evaluate longer-term cardiometabolic effects of screen time are needed. Although there is an evidence-based rationale to reduce screen time in early childhood, prevention of cardiometabolic risk may not be the primary driver.

Overweight and obesity in preschool aged children and risk of mental health service utilization.

OBJECTIVE: To determine if overweight or obesity in preschool-age children is associated with mental health service utilization in later childhood. SUBJECTS: Overall, 10,522 children 2 to <5 years, with no previous history of mental health service utilization, were identified from primary care electronic medical records (EMRs) across Ontario, Canada. METHODS: This was a retrospective longitudinal cohort study. Height and weight data were extracted and body mass index z-scores (zBMI) were calculated using the World Health Organization Growth Standards. Mental health service utilization, between ages 5 and <19, was defined using administrative billing codes for mental health outpatient visits, emergency department visits, and hospitalizations. A multivariable Cox proportional hazards model was performed. RESULTS: In total, 74.9% of children were healthy weight (zBMI between -2 and ≤1), 18.8% of children were at risk of overweight (zBMI between 1 and ≤2), 4.9% were overweight (zBMI > 2 and ≤3), and 1.5% had obesity (zBMI > 3). The median follow-up time was 2.2 years (IQR 1.0-4.2). The overall incidence rate of mental health service use was 44.5 events per 1000 person-years. The hazard ratio for girls with obesity was 2.73 (95% CI 1.62-4.60; p < 0.001) compared to girls with healthy weight. Compared to boys with healthy weight, boys 'at risk of overweight' and overweight were 1.22 (95% CI 1.03-1.44; p = 0.02) and 1.43 (95% CI 1.09-1.87; p = 0.01) times at higher risk of an incident mental health visit. CONCLUSION: Our study shows an association between weight status in preschool school aged children and higher incidence of mental health service use in later childhood. This relationship was strongest in girls. Future research is needed to understand this relationship by mental health diagnosis, sex, and age.