Risk of asthma in children diagnosed with bronchiolitis during infancy: protocol of a longitudinal cohort study linking emergency department-based clinical data to provincial health administrative databases.

INTRODUCTION: The Canadian Bronchiolitis Epinephrine Steroid Trial (CanBEST) and the Bronchiolitis Severity Cohort (BSC) study enrolled infants with bronchiolitis during the first year of life. The CanBEST trial suggested that treatment of infants with a combined therapy of high-dose corticosteroids and nebulised epinephrine reduced the risk of admission to hospital. Our study aims to-(1) quantify the risk of developing asthma by age 5 and 10 years in children treated with high-dose corticosteroid and epinephrine for bronchiolitis during infancy, (2) identify risk factors associated with development of asthma in children with bronchiolitis during infancy, (3) develop asthma prediction models for children diagnosed with bronchiolitis during infancy. METHODS AND ANALYSIS: We propose a longitudinal cohort study in which we will link data from the CanBEST and BSC study with routinely collected data from provincial health administrative databases. Our outcome is asthma incidence measured using a validated health administrative data algorithm. Primary exposure will be treatment with a combined therapy of high-dose corticosteroids and nebulised epinephrine for bronchiolitis. Covariates will include type of viral pathogen, disease severity, medication use, maternal, prenatal, postnatal and demographic factors and variables related to health service utilisation for acute lower respiratory tract infection. The risk associated with development of asthma in children treated with high-dose corticosteroid and epinephrine for bronchiolitis will be assessed using multivariable Cox proportional hazards regression models. Prediction models will be developed using multivariable logistic regression analysis and internally validated using a bootstrap approach. ETHICS AND DISSEMINATION: Our study has been approved by the ethics board of all four participating sites of the CanBEST and BSC study. Finding of the study will be disseminated to the academic community and relevant stakeholders through conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN56745572; Post-results.

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.

Effect of asthma exacerbation during pregnancy in women with asthma: a population-based cohort study.

The association between asthma exacerbation during pregnancy and adverse maternal and child health outcomes have not been investigated appropriately. Our objective was to determine the short- and long-term intergenerational effect of asthma exacerbation in pregnant women with asthma.A population cohort study was conducted using data from the Ontario asthma surveillance system and population-level health administrative data. Asthma exacerbation in pregnant women with asthma was defined as at least one of the following criteria: at least five physician visits, or one emergency department visit or one hospital admission for asthma during pregnancy. Pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders were identified using International Classification of Disease codes (9th and 10th revisions).The cohort consisted of 103 424 singleton pregnancies in women with asthma. Asthma exacerbation in pregnant women with asthma was associated with higher odds of pre-eclampsia (OR 1.30, 95% CI 1.12-1.51) and pregnancy-induced hypertension (OR 1.17, 95% CI 1.02-1.33); babies had higher odds of low birthweight (OR 1.14, 95% CI 1.00-1.31), preterm birth (OR 1.14, 95% CI 1.01-1.29) and congenital malformations (OR 1.21, 95% CI 1.05-1.39). Children born to women with asthma exacerbation during pregnancy had elevated risk of asthma (OR 1.23, 95% CI 1.13-1.33) and pneumonia (OR 1.12, 95% CI 1.03-1.22) during the first 5 years of life.Asthma exacerbation during pregnancy in women with asthma showed increased risk of pregnancy complications, adverse perinatal outcomes and early childhood respiratory disorders in their children, indicating that appropriate asthma management may reduce the risk of adverse health outcomes.

Patterns of health care use related to respiratory conditions in early life: A birth cohort study with linked administrative data.

OBJECTIVES: To identify distinctive patterns of respiratory-related health services use (HSU) between birth and 3 years of age, and to examine associated symptom and risk profiles. METHODS: This study included 729 mother and child pairs enrolled in the Toronto site of the Canadian Healthy Infant Longitudinal Development study in 2009-2012; they were linked to Ontario health administrative databases (2009-2016). A model-based cluster analysis was performed to identify distinct groups of children who followed a similar pattern of respiratory-related HSU between birth and 3 years of age, regarding hospitalization, emergency department (ED) and physician office visits for respiratory conditions and total health care costs (2016 Canadian dollars). RESULTS: The majority (estimated cluster weight = 0.905) showed a pattern of low and stable respiratory care use (low HSU) while the remainder (weight = 0.095) showed a pattern of high use (high HSU). From 0 to 3 years of age, the low- and high-HSU groups differed in mean trajectories of total health care costs ($783 per 6 months decreased to $114, vs $1796 to $177, respectively). Compared to low-HSU, the high-HSU group was associated with a constant risk of hospitalizations, early high ED utilization and physician visits for respiratory problems. The two groups differed significantly in the timing of wheezing (late onset in low-HSU vs early in high-HSU) and future total costs (stable vs increased). CONCLUSIONS: One in ten children had high respiratory care use in early life. Such information can help identify high-risk young children in a large population, monitor their long-term health, and inform resource allocation.

Temperament Is Associated With Outdoor Free Play in Young Children: A TARGet Kids! Study.

OBJECTIVE: Outdoor free play is important for preschoolers' physical activity, health, and development. Certain temperamental characteristics are associated with obesity, nutrition, and sedentary behaviors in preschoolers, but the relationship between temperament and outdoor play has not been examined. This study examined whether there is an association between temperament and outdoor play in young children. METHODS: Healthy children aged 1 to 5 years recruited to The Applied Research Group for Kids (TARGet Kids!), a community-based primary care research network, from July 2008 to September 2013 were included. Parent-reported child temperament was assessed using the Childhood Behavior Questionnaire. Outdoor free play and other potential confounding variables were assessed through validated questionnaires. Multivariable linear regression was used to determine the association between temperament and outdoor play, adjusted for potential confounders. RESULTS: There were 3393 children with data on outdoor play. The association between negative affectivity and outdoor play was moderated by sex; in boys, for every 1-point increase in negative affectivity score, mean outdoor play decreased by 4.7 minutes per day. There was no significant association in girls. Surgency was associated with outdoor play; for every 1-point increase in surgency/extraversion, outdoor play increased by 4.6 minutes per day. CONCLUSIONS: Young children's temperamental characteristics were associated with their participation in outdoor free play. Consideration of temperament could enhance interventions and strategies to increase outdoor play in young children. Longitudinal studies are needed to elucidate the relationship between children's early temperament and physical activity.

Re-Evaluation of Serum Ferritin Cut-Off Values for the Diagnosis of Iron Deficiency in Children Aged 12-36 Months.

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.

Laboratory reference intervals in the assessment of iron status in young children.

OBJECTIVES: The primary objective was to establish reference intervals for laboratory tests used to assess iron status in young children using the Clinical and Laboratory Standards Institute guidelines. A secondary objective was to compare the lower limit of the reference interval with the currently recommended cut-off value for haemoglobin and serum ferritin in children 1-3 years of age. METHODS: Blood samples were obtained from healthy children recruited during scheduled health supervision visits with their primary care physician. For our primary objective, outliers were removed; age partitions were selected and analysis of variance and pairwise comparisons were made between adjacent partitions; reference intervals and 90% CIs were calculated. For our secondary objective, we determined the proportion of children misclassified using the lower limit reference interval compared with the cut-off value. RESULTS: Samples from 2305 male and 2029 female participants (10 days to 10.6 years) were used to calculate age and sex-specific reference intervals for laboratory tests of iron status. There were statistically significant differences between adjacent age partitions for most analytes. Approximately 10% of children 1-3 years of age were misclassified (underestimated) using the lower limit of the reference intervals rather than the currently recommended cut-off values for haemoglobin and serum ferritin. IMPLICATIONS AND RELEVANCE: Clinical laboratories may consider adopting published paediatric reference intervals. Reference intervals may misclassify (underestimate) children with iron deficiency as compared with currently recommended cut-off values. Future research on decision limits derived from clinical studies of outcomes is a priority.

Risk factors, practice variation and hematological outcomes of children identified with non-anemic iron deficiency following screening in primary care setting.

OBJECTIVES: To determine the prevalence, risk factors, physician practice patterns and longitudinal hematological outcome of children following screening for non-anemic iron deficiency (NAID). METHODS: The present analysis was a longitudinal cohort study invovling healthy children one to five years of age. Descriptive statistics were used to describe the prevalence, risk factors, practice patterns and hematological outcome of children identified with NAID. The association between NAID and potential risk factors were examined using multivariate logistic regression analysis. RESULTS: Of 2276 children undergoing screening, 155 had NAID, corresponding to a prevalence of 7% (95% CI 5.95% to 8.05%). Risk factors significantly associated with NAID included: younger age (OR 1.08 [95% CI 1.06 to 1.11]), higher body mass index z-score (OR 1.22 [95% CI 1.01 to 1.48]), longer duration of breastfeeding (OR 1.05 [95% CI 1.01 to 1.08]) and increased volume of cow's milk intake (OR 1.13 [95% CI 1.01 to 1.26]). An assessment of practice patterns revealed that for 37% of children, an intervention for NAID was documented; and for 8.4% a physician-ordered follow-up laboratory test was completed to re-evaluate iron status. A total of 58 (37%) children underwent a follow-up laboratory test, of whom 38 (65.5%) had resolution of NAID, 15 (25.9%) had persistence of NAID and two (3.4%) had progression of NAID to anemia. CONCLUSION: NAID is common in early childhood and is associated with modifiable risk factors. Substantial practice variation exists in the management of NAID. Further research is necessary to understand the benefits of screening for NAID and evidence-informed practice guidelines may reduce practice variation in the management of NAID in early childhood.

OBJECTIFS: Déterminer la prévalence, les facteurs de risque, les profils de pratique des médecins, et les résultats hématologiques longitudinaux des enfants après le dépistage diagnostiqué d'une carence en fer sans anémie (CFSA). MÉTHODOLOGIE: La présente analyse était une étude de cohorte longitudinale d'enfants en santé de un à cinq ans. Les chercheurs ont utilisé les statistiques descriptives pour décrire la prévalence, les facteurs de risque et les résultats hématologiques d'enfants atteints d'une CFSA diagnostiquée. Ils ont utilisé l'analyse de régression logistique multivariée pour examiner l'association entre la CFSA et les facteurs de risque potentiels. RÉSULTATS: Des 2 276 enfants faisant l'objet du dépistage, 155 étaient atteints d'une CFSA, pour une prévalence de 7 % (95 % IC 5,95 % à 8,05 %). Les facteurs de risque qui s'associaient de manière significative à une CFSA incluaient un âge plus jeune (RC 1,08 [95 % IC 1,06 à 1,11]), un écart réduit plus élevé de l'indice de masse corporelle (RC 1,22 [95 % IC 1,01 à 1,48]), un allaitement de plus longue durée (RC 1,05 [95 % IC 1,01 à 1,08]) et une plus grande consommation de lait de vache (RC 1,13 [95 % IC 1,01 à 1,26]). L'évaluation des profils de pratique a révélé que 37 % des enfants avaient subi une intervention consignée pour soigner la CFSA, et que des médecins avaient demandé un test de laboratoire de suivi pour réévaluer le statut en fer de 8,4 % des cas. Au total, 58 enfants (37 %) ont subi un test de laboratoire de suivi, dont 38 (65,5 %) ont guéri, 15 (25,9 %) ont présenté une CFSA persistante et deux (3,4 %) ont vu leur CFSA se transformer en anémie. CONCLUSION: La CFSA, courante dans la petite enfance, s'associe à des facteurs de risque modifiables. On remarque une variation importante de la pratique pour la prise en charge de la CFSA. D'autres recherches s'imposent pour comprendre les avantages de son dépistage. De plus, des directives de pratique factuelles réduiraient peut-être les variations dans les pratiques de prise en charge de la CFSA pendant la petite enfance.

An internal pilot study for a randomized trial aimed at evaluating the effectiveness of iron interventions in children with non-anemic iron deficiency: the OptEC trial.

BACKGROUND: The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted. The objectives of this internal pilot study were to obtain reliable estimate of parameters (standard deviation and design factor) to recalculate the sample size and to assess the adherence rate and reasons for non-adherence in children enrolled in the pilot study. METHODS: The first 30 subjects enrolled into the OptEC trial constituted the internal pilot study. The primary outcome of the OptEC trial is the Early Learning Composite (ELC). For estimation of the SD of the ELC, descriptive statistics of the 4 month follow-up ELC scores were assessed within each intervention group. The observed SD within each group was then pooled to obtain an estimated SD (S2) of the ELC. Correlation (ρ) between the ELC measured at baseline and follow-up was assessed. Recalculation of the sample size was performed using analysis of covariance (ANCOVA) method which uses the design factor (1- ρ(2)). Adherence rate was calculated using a parent reported rate of missed doses of the study intervention. CONCLUSION: The new estimate of the SD of the ELC was found to be 17.40 (S2). The design factor was (1- ρ2) = 0.21. Using a significance level of 5%, power of 80%, S2 = 17.40 and effect estimate (Δ) ranging from 6-8 points, the new sample size based on ANCOVA method ranged from 32-56 subjects (16-28 per group). Adherence ranged between 14% and 100% with 44% of the children having an adherence rate ≥ 86%. Information generated from our internal pilot study was used to update the design of the full and definitive trial, including recalculation of sample size, determination of the adequacy of adherence, and application of strategies to improve adherence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01481766 (date of registration: November 22, 2011).

Optimizing early child development for young children with non-anemic iron deficiency in the primary care practice setting (OptEC): study protocol for a randomized controlled trial.

BACKGROUND: Three decades of research suggests that prevention of iron deficiency anemia (IDA) in the primary care setting may be an unrealized and unique opportunity to prevent poor developmental outcomes in children. A longitudinal study of infants with IDA showed that the developmental disadvantage persists long term despite iron therapy. Early stages of iron deficiency, termed non-anemic iron deficiency (NAID), provide an opportunity for early detection and treatment before progression to IDA. There is little research regarding NAID, which may be associated with delayed development in young children. The aim of this study is to compare the effectiveness of four months of oral iron treatment plus dietary advice, with placebo plus dietary advice, in improving developmental outcomes in children with NAID and to conduct an internal pilot study. METHODS/DESIGN: From a screening cohort, those identified with NAID (hemoglobin ≥110 g/L and serum ferritin <14 µg/L) are invited to participate in a pragmatic, multi-site, placebo controlled, blinded, parallel group, superiority randomized trial. Participating physicians are part of a primary healthcare research network called TARGet Kids! Children between 12 and 40 months of age and identified with NAID are randomized to receive four months of oral iron treatment at 6 mg/kg/day plus dietary advice, or placebo plus dietary advice (75 per group). The primary outcome, child developmental score, is assessed using the Mullen Scales of Early Learning at baseline and at four months after randomization. Secondary outcomes include an age appropriate behavior measure (Children's Behavior Questionnaire) and two laboratory measures (hemoglobin and serum ferritin levels). Change in developmental and laboratory measures from baseline to the end of the four-month follow-up period will be analyzed using linear regression (analysis of covariance method). DISCUSSION: This trial will provide evidence regarding the association between child development and NAID, and the effectiveness of oral iron to improve developmental outcomes in children with NAID. The sample size of the trial will be recalculated using estimates taken from an internal pilot study. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov (identifier: NCT01481766 ) on 22 November 2011.

Efficacy of oral iron therapy in improving the developmental outcome of pre-school children with non-anaemic iron deficiency: a systematic review.

OBJECTIVE: To systematically review the efficacy and safety of oral Fe therapy in pre-school children (1­5 years) with non-anaemic Fe deficiency, determined by children's developmental and haematological status and the incidence of reported side-effects. DESIGN: A random-effects model was used to show mean differences with 95% confidence intervals of developmental and haematological scores between Fe-treated and non-treated groups. SETTING: MEDLINE, EMBASE, Cochrane library and bibliographies of identified articles were searched up to September 2011. Randomized and observational studies were assessed by two reviewers independently. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment and completeness of follow-up. SUBJECTS: From the titles of 743 articles, full text review was completed on forty-six and two randomized trials of acceptable quality met the inclusion criteria. The two trials included a total of sixty-nine children. RESULTS: One study showed a statistically significant difference in the post-treatment Mental Developmental Index score among children who received oral Fe therapy v. no therapy (mean difference56?3, 95% CI 1?5, 11?0, P value not provided). Both studies showed significant improvement in serum ferritin level (mg/l: mean difference551? 1, 95% CI 33?6, 68?6, P,0?01 and mean difference517?1, 95% CI 7?5, 26?6, P value not provided, respectively) in children who received Fe therapy. CONCLUSIONS: Evidence is insufficient to recommend oral Fe therapy to children with non-anaemic Fe deficiency. There is urgent need of conducting adequately powered, randomized trials examining the efficacy of oral Fe therapy in pre-school children with non-anaemic Fe deficiency.

Health and nutritional status of children of adolescent mothers: experience from a diarrhoeal disease hospital in Bangladesh.

AIM: The study aimed at assessing clinical and nutritional features and socioeconomic characteristics of the first birth-order children (1-48 months) of adolescent mothers. METHODS: Five hundred and thirty-nine first birth-order children of both sexes, aged 1-48 month(s) were studied. All study children had adolescent mothers aged < or =19 years (when attending hospital), who attended (as a patient) the Dhaka hospital of ICDDR, B during 2000-2005. A similar group of children (n = 540) of mothers aged 25-29 years (when attending hospital) constituted the comparison group. RESULTS: Malnutrition indicated by underweight [OR 2.3, 95% CI 1.7-3.1, p < 0.001], stunting [OR 2.1, 95% CI 1.5-2.8, p < 0.001], wasting [OR 1.8, 95% CI 1.3-2.7, p = 0.001], infancy (<12 months old) [OR 2.8, 95% CI 2.1-3.9, p < 0.001], duration of hospitalization (> or =48 h) [OR 1.6, 95% CI 1.2-2.2, p = 0.001], DPT immunization [OR 1.8, 95% CI 1.3-2.5, p = 0.001] and maternal illiteracy (no formal schooling) [OR 1.5, 95% CI 1.1-2.0, p = 0.007] were significantly associated with children of adolescent mothers, after adjusting for co-variates in the logistic regression analysis. Similar results were also observed when different indices of malnutrition (stunting, underweight or wasting) were added separately to the different models. CONCLUSION: Children of adolescent mothers are likely to be more malnourished, have lesser opportunities for DPT immunization and have longer duration of hospitalization. Adolescent mothers were also more likely to be illiterate. Therefore, the development of preventive and therapeutic strategies will be required to reduce morbidity and improve the health and nutrition status of both children and their adolescent mothers.