Jonathon L. Maguire

Association Between Iron-Deficiency Anemia and Stroke in Young Children

OBJECTIVE. Iron-deficiency anemia occurs with a peak prevalence of 4% to 8% in children between 1 and 3 years of age. Case reports have suggested an association between iron-deficiency anemia in healthy children and ischemic stroke. Our objective was to investigate whether iron-deficiency anemia is associated with stroke in young children. METHODS. A case-control study was conducted of case patients who were selected from the stroke registry at the Hospital for Sick Children (Toronto, Ontario, Canada) and control subjects selected from a database of healthy children who were prospectively enrolled in an outpatient setting. Children were aged 12 to 38 months and were previously healthy with no identifiable risk factors for stroke. Age, gender, mean corpuscular volume, platelet count, and hemoglobin and ferritin levels were collected. Iron-deficiency anemia was defined as a hemoglobin level of <110 g/L, mean corpuscular volume <73 fL, and serum ferritin level <12 μg/L. Stroke was defined according to clinical and radiologic criteria. RESULTS. Case (n = 15) and control (n = 143) subjects were similar with respect to median age and percentage of boys. Case patients had a lower median hemoglobin level and mean corpuscular volume and a higher median platelet count. Iron-deficiency anemia was significantly more common among case patients (8 [53%] of 15) than control subjects (13 [9%] of 143). CONCLUSIONS. Previously healthy children with stroke were 10 times more likely to have iron-deficiency anemia than healthy children without stroke. Furthermore, children with iron-deficiency anemia accounted for more than half of all stroke cases in children without an underlying medical illness, which suggests that iron-deficiency anemia is a significant risk factor for stroke in otherwise healthy young children. Primary prevention and early identification of iron-deficiency anemia must remain a priority.

Should a Head-Injured Child Receive a Head CT Scan? A Systematic Review of Clinical Prediction Rules

CONTEXT: Given radiation- and sedation-associated risks, there is uncertainty about which children with head trauma should receive cranial computed tomography (CT) scanning. A high-quality and high-performing clinical prediction rule may reduce this uncertainty. OBJECTIVE: To systematically review the quality and performance of published clinical prediction rules for intracranial injury in children with head injury. METHODS: Medline and Embase were searched in December 2008. Studies were selected if they included clinical prediction rules involving children aged 0 to 18 years with a history of head injury. Prediction-rule quality was assessed by using 14 previously published items. Prediction-rule performance was evaluated by rule sensitivity and the predicted frequency of CT scanning if the rule was used. RESULTS: A total of 3357 titles and abstracts were assessed, and 8 clinical prediction rules were identified. For all studies, the rule derivations were reported; no study validated a rule in a separate population or assessed its impact in actual practice. The rules differed considerably in population, predictors, outcomes, methodologic quality, and performance. Five of the rules were applicable to children of all ages and severities of trauma. Two of these were high quality (≥11 of 14 quality items) and had high performance (lower confidence limits for sensitivity >0.95 and required ≤56% to undergo CT). Four of the 8 rules were applicable to children with minor head injury (Glasgow coma score ≥13). One of these had high quality (11 of 14 quality items) and high performance (lower confidence limit for sensitivity = 0.94 and required 13% to undergo CT). Four of the 8 rules were applicable to young children, but none exhibited adequate quality or performance. CONCLUSIONS: Eight clinical prediction-rule derivation studies were identified. They varied considerably in population, methodologic quality, and performance. Future efforts should be directed toward validating rules with high quality and performance in other populations and deriving a high-quality, high-performance rule for young children.

Does this child have appendicitis? A systematic review of clinical prediction rules for children with acute abdominal pain.

OBJECTIVES To systematically identify clinical prediction rules (CPRs) for children with suspected appendicitis and compare their methodological quality and performance. STUDY DESIGN AND SETTING Included studies involved children aged 0-18 years with suspected appendicitis identified through MEDLINE and EMBASE from 1950 to 2012. The quality was assessed using 17 previously published items. The performance was evaluated using the sensitivity, negative likelihood ratio, and predicted frequency of appendicitis diagnosis that would result if the rule was used. RESULTS Twelve studies fulfilled the inclusion criteria describing the derivation or validation of six unique CPRs involving 4,201 children with suspected appendicitis. Migratory pain, nausea or vomiting, and right lower quadrant tenderness were common predictors to all rules. Methodological quality varied widely. The most poorly addressed quality items were the predictor and outcome assessor blinding, predictor description, and reproducibility of predictor assessment. The most well-validated CPRs were the Pediatric Appendicitis Score (PAS) and MANTRELS (Migration, Anorexia, Nausea/vomiting, Tenderness in the right lower quadrant, Rebound pain, Elevation in temperature, Leukocytosis, Shift to the left)/Alvarado Score. Overall, the PAS validation studies outperformed the Alvarado validation studies. CONCLUSION The PAS and Alvarado scores were the most well validated but neither met the current performance benchmarks. A high quality, well validated, and consistently high-performing CPR was not identified. Further research is needed before a CPR for children with suspected appendicitis can be used in routine practice.

Low Serum 25-Hydroxyvitamin D Level and Risk of Upper Respiratory Tract Infection in Children and Adolescents

Respiratory tract infections (RTIs) are very common worldwide. We prospectively demonstrate an association between low serum 25-hydroxyvitamin D level and increased risk of laboratory-confirmed viral upper RTI in children. Future studies should evaluate the role of supplementation to reduce RTIs.

Cohort Profile: The Applied Research Group for Kids (TARGet Kids!)

The Applied Research Group for Kids (TARGet Kids!) is an ongoing open longitudinal cohort study enrolling healthy children (from birth to 5 years of age) and following them into adolescence. The aim of the TARGet Kids! cohort is to link early life exposures to health problems including obesity, micronutrient deficiencies and developmental problems. The overarching goal is to improve the health of Canadians by optimizing growth and developmental trajectories through preventive interventions in early childhood. TARGet Kids!, the only child health research network embedded in primary care practices in Canada, leverages the unique relationship between children and families and their trusted primary care practitioners, with whom they have at least seven health supervision visits in the first 5 years of life. Children are enrolled during regularly scheduled well-child visits. To date, we have enrolled 5062 children. In addition to demographic information, we collect physical measurements (e.g. height, weight), lifestyle factors (nutrition, screen time and physical activity), child behaviour and developmental screening and a blood sample (providing measures of cardiometabolic, iron and vitamin D status, and trace metals). All data are collected at each well-child visit: twice a year until age 2 and every year until age 10. Information can be found at: http://www.targetkids.ca/contact-us/.

Vitamin D Supplementation for Childhood Asthma: A Systematic Review and Meta-Analysis.

Importance There is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes. Objectives The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma. Data Sources We searched MEDLINE, Embase, CENTRAL, and CINAHL through July 2014. Study Selection We included RCTs that evaluated vitamin D supplementation in children versus active control or placebo for asthma. Data Extraction and Synthesis One reviewer extracted data and one reviewer verified data accuracy. We qualitatively summarized the main results of efficacy and safety and meta-analyzed data on comparable outcomes across studies. We used GRADE for strength of evidence. Main Outcome Measures Main planned outcomes measures were ED visits and hospitalizations. As secondary outcomes, we examined measures of asthma control, including frequency of asthma exacerbations, asthma symptom scores, measures of lung function, β2-agonist use and daily steroid use, adverse events and 25-hydroxyvitamin D levels. Results Eight RCTs (one parallel, one crossover design) comprising 573 children aged 3 to 18 years were included. One study (moderate-quality, n = 100) reported significantly less ED visits for children treated with vitamin D. No other studies examined the primary outcome (ED visits and hospitalizations). There was a reduced risk of asthma exacerbations in children receiving vitamin D (low-quality; RR 0.41, 95% CI 0.27 to 0.63, 3 studies, n = 378). There was no significant effect for asthma symptom scores and lung function. The serum 25(OH)D level was higher in the vitamin D group at the end of the intervention (low-quality; MD 19.66 nmol/L, 95% CI 5.96 nmol/L to 33.37 nmol/L, 5 studies, n = 167). Limitations We identified a high degree of clinical diversity (interventions and outcomes) and methodological heterogeneity (sample size and risk of bias) in included trials. Conclusions and Relevance Randomized controlled trials provide some low-quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations. Evidence on the benefits of vitamin D supplementation for other asthma-related outcomes in children is either limited or inconclusive. We recommend that future trials focus on patient-relevant outcomes that are comparable across studies, including standardized definitions of asthma exacerbations.

The Relationship Between Cow’s Milk and Stores of Vitamin D and Iron in Early Childhood

OBJECTIVE: To examine the association between cow’s milk intake on both vitamin D and iron stores in healthy urban preschoolers. METHODS: Healthy children 2 to 5 years of age were recruited from December 2008 through December 2010 through the TARGet Kids! practice-based research network. Cow’s milk intake was measured by parental report. Vitamin D and iron stores were measured by using serum 25-hydroxyvitamin D and ferritin. Bivariate multivariable linear regression was used to examine the effect of cow’s milk intake simultaneously on 25-hydroxyvitamin D and serum ferritin. Analyses were stratified by important clinical variables including skin pigmentation, bottle feeding, vitamin D supplementation, and season. RESULTS: Among 1311 children, increasing cow’s milk consumption was associated with decreasing serum ferritin (P < .0001) and increasing 25-hydroxyvitamin D (P ≤ .0001). Two cups (500 mL) of cow’s milk per day maintained 25-hydroxyvitamin D >75 nmol/L with minimal negative effect on serum ferritin for most children. Children with darker skin pigmentation not receiving vitamin D supplementation during the winter required 3 to 4 cups of cow’s milk per day to maintain 25-hydroxyvitamin D >75 nmol/L. Cow’s milk intake among children using a bottle did not increase 25-hydroxyvitamin D and resulted in more dramatic decreases in serum ferritin. CONCLUSIONS: There is a trade-off between increasing 25-hydroxyvitamin D and decreasing serum ferritin with increasing milk intake. Two cups of cow’s milk per day appears sufficient to maintain healthy vitamin D and iron stores for most children. Wintertime vitamin D supplementation was particularly important among children with darker skin pigmentation.

Association Between Total Duration of Breastfeeding and Iron Deficiency

OBJECTIVE: To determine whether there is an association between the total breastfeeding duration and iron stores, iron deficiency, and iron deficiency anemia in healthy urban children. METHODS: A cross-sectional study of healthy children, aged 1 to 6 years, seen for primary health care between December 2008 and July 2011 was conducted through the TARGet Kids! practice-based research network. Univariate and adjusted regression analyses were used to evaluate an association between total breastfeeding duration and serum ferritin, iron deficiency, and iron deficiency anemia. RESULTS: Included were 1647 healthy children (median age 36 months) with survey, anthropometric, and laboratory data. An association was found between increasing duration of breastfeeding and lower serum ferritin (P = .0015). Adjusted logistic regression analysis revealed the odds of iron deficiency increased by 4.8% (95% confidence interval: 2%–8%) for each additional month of breastfeeding. Exploratory analysis suggested an increasing cumulative probability of iron deficiency with longer total breastfeeding duration with an adjusted odds ratio of 1.71 (95% confidence interval: 1.05–2.79) for iron deficiency in children breastfed over versus under 12 months of age. The relationship between total breastfeeding duration and iron deficiency anemia did not meet statistical significance. CONCLUSIONS: Increased total breastfeeding duration is associated with decreased iron stores, a clinically important association warranting additional investigation.

Modifiable Determinants of Serum 25-Hydroxyvitamin D Status in Early Childhood: Opportunities for Prevention

OBJECTIVES To determine the effect of modifiable dietary intake variables (current vitamin D supplementation and daily cows milk intake) on 25-hydroxyvitamin D level in early childhood and to evaluate the relationship between these modifiable dietary factors and other largely nonmodifiable determinants of vitamin D status including skin pigmentation and season. DESIGN Cross-sectional study. SETTING Primary care pediatric and family medicine practices participating in the TARGet Kids! practice-based research network in Toronto, Ontario, Canada. PARTICIPANTS From December 2008 to June 2011, healthy children 1 to 5 years of age were recruited during a routine physicians visit. INTERVENTIONS Survey, anthropometric measurements, and laboratory data were collected. A multivariable linear regression model was developed to examine the independent effects of vitamin D supplementation and daily volume of cows milk on 25-hydroxyvitamin D level. MAIN OUTCOME MEASURES 25-Hydroxyvitamin D level. RESULTS Blood was obtained in 1898 children. Two modifiable dietary intake variables, vitamin D supplementation and cows milk, increased 25-hydroxyvitamin D level by 3.4 ng/mL (95% CI, 2-4 ng/mL) and 1.6 ng/mL per 250-mL cup per day (95% CI, 1-2 ng/mL), respectively. Two nonmodifiable variables reflecting cutaneous vitamin D synthesis (skin pigmentation and season) were also strongly associated with 25-hydroxyvitamin D status but accounted for a much smaller proportion of the explained variation in 25-hydroxyvitamin D level. The effect of vitamin D supplementation and milk intake on 25-hydroxyvitamin D level appeared similar regardless of skin pigmentation or season. CONCLUSION Two modifiable dietary intake variables (vitamin D supplementation and cows milk intake) are the most important determinants of 25-hydroxyvitamin D status in early childhood.

Office-Based Randomized Controlled Trial to Reduce Screen Time in Preschool Children

OBJECTIVE: To determine if an intervention for preschool-aged children in primary care is effective in reducing screen time, meals in front of the television, and BMI. METHODS: A randomized controlled trial was conducted at a primary care pediatric group practice in Toronto, Canada. Three-year-old children and their parents were randomly assigned to receive a short behavioral counseling intervention on strategies to decrease screen time. The primary outcome 1 year later was parent reported screen time. Secondary outcomes included television in the child’s bedroom, number of meals in front of the television, and BMI. RESULTS: In the intention-to-treat analysis at 1 year, there were no significant differences in mean total weekday minutes of screen time (60, interquartile range [IQR]: 35–120 vs 65, IQR: 35–120; P = .68) or mean total weekend day minutes of screen time (80, IQR: 45–130 vs 90, IQR: 60–120; P = .33) between the intervention and control group. Adjusting for baseline BMI, there was a reduction in the number of weekday meals in front of the television (1.6 ± 1.0 vs 1.9 ± 1.2; P = .03) but no differences in BMI or number of televisions in the bedroom. CONCLUSIONS: This pragmatic trial was not effective in reducing screen time or BMI but was effective in reducing meals in front of the screen. Short interventions focused solely on reducing screen time implemented in the primary care practice setting may not be effective in this age group.