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OBJECTIVE: The American Academy of Pediatrics recommends developmental surveillance and screening in early childhood in primary care. The 18-month visit may be an ideal time for identification of children with delays in language and communication, or symptoms of autism spectrum disorder (ASD). Little is known about the predictive validity of developmental screening tools administered at 18 months. Our objective was to examine the predictive validity of the Infant Toddler Checklist (ITC) at the 18-month health supervision visit, using school readiness at kindergarten age as the criterion measure. METHODS: We designed a prospective cohort study, recruiting in primary care in Toronto, Canada. Parents completed the ITC at the 18-month visit. Teachers completed the Early Development Instrument (EDI) when the children were in Kindergarten, age 4-6 years. We calculated screening test properties with 95% confidence intervals (CIs). We used multivariable logistic and linear regression analyses adjusted for important covariates. RESULTS: Of 293 children (mean age 18 months), 30 (10.2%) had a positive ITC including: concern for speech delay (n = 11, 3.8%), concern for other communication delay (n = 13, 4.4%), and concern for both (n = 6, 2.0%). At followup (mean age 5 years), 54 (18.4%) had overall EDI vulnerability, 19 (6.5%) had vulnerability on the 2 EDI communication domains. The ITC sensitivity ranged from 11% to 32%, speci- ficity from 91% to 96%, false positive rates from 4% to 9%, PPV from 16% to 35%, NPV from 83% to 95%. A positive ITC screen and ITC concern for speech delay were associated with lower scores in EDI communication skills and general knowledge (β = -1.08; 95% CI: -2.10, -0.17; β = -2.35; 95% CI: -3.63, -1.32) and EDI language and cognitive development (β = -0.62; 95% CI: -1.25, -0.18; β = -1.22; 95% CI: -2.11, -0.58). CONCLUSIONS: The ITC demonstrated high specificity suggesting that most children with a negative ITC screen will demonstrate school readiness at 4-6 years, and low false positive rates, minimizing over-diagnosis. The ITC had low sensitivity highlighting the importance of ongoing developmental surveillance and screening. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background The majority of children in North America consume cow-milk daily. Children aged >2 y are recommended to consume reduced-fat (0.1–2%) cow-milk to lower the risk of obesity. Objectives To evaluate the relation between cow-milk fat consumption and adiposity in children aged 1–18 y. Methods Embase (Excerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), MEDLINE, Scopus, and Cochrane Library databases from inception to August 2019 were used. The search included observational and interventional studies of healthy children aged 1–18 y that described the association between cow-milk fat consumption and adiposity. Two reviewers extracted data, using the Newcastle–Ottawa Scale to assess risk of bias. Meta-analysis was conducted using random effects to evaluate the relation between cow-milk fat and risk of overweight or obesity. Adiposity was assessed using BMI z -score (zBMI). Results Of 5862 reports identified by the search, 28 met the inclusion criteria: 20 were cross-sectional and 8 were prospective cohort. No clinical trials were identified. In 18 studies, higher cow-milk fat consumption was associated with lower child adiposity, and 10 studies did not identify an association. Meta-analysis included 14 of the 28 studies (n  = 20,897) that measured the proportion of children who consumed whole milk compared with reduced-fat milk and direct measures of overweight or obesity. Among children who consumed whole (3.25% fat) compared with reduced-fat (0.1–2%) milk, the OR of overweight or obesity was 0.61 (95% CI: 0.52, 0.72; P  < 0.0001), but heterogeneity between studies was high (I 2 = 73.8%). Conclusions Observational research suggests that higher cow-milk fat intake is associated with lower childhood adiposity. International guidelines that recommend reduced-fat milk for children might not lower the risk of childhood obesity. Randomized trials are needed to determine which cow-milk fat minimizes risk of excess adiposity. This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42018085075). [ABSTRACT FROM AUTHOR]

Health care policy positions breastfeeding as an important part of the solution to household food insecurity; however, there are critical gaps in our knowledge of the relationship between breastfeeding duration (exposure variable) and household food insecurity (outcome variable). Our objective was to examine this relationship. A cross-sectional study was conducted from 2008 to 2016 of healthy urban children (N = 3838) who were 0 to 3 years old and recruited from The Applied Research Group for Kids (TARGet Kids!), a practice-based research network in Toronto, Canada. Total breastfeeding duration was collected from parent-reported questionnaires. Household food insecurity was measured using 1-item and 2-item food insecurity screens. Multivariable regression analysis was performed adjusting for prespecified covariates. The median total breastfeeding duration was 10.5 months (interquartile range, 6.0–14.0), and 14.7% of households were food insecure. After adjusting for child characteristics (age, sex), maternal characteristics (age, ethnicity, education, employment), and family characteristics (number of children, single parent family, neighborhood equity score), there was no significant association between total breastfeeding duration and household food insecurity (odds ratio, 0.99; 95% confidence interval, 0.98–1.01). Although low-income families had an increased odds of being household food insecure (P ≤.001), we found no significant association between total breastfeeding duration and household food insecurity at varying income levels. We found no association between breastfeeding duration and household food insecurity, regardless of family income. Although breastfeeding is associated with improved child health outcomes and considered to be part of the solution to household food insecurity, interventions focused on social determinants may provide more promising targets for the prevention of household food insecurity. [ABSTRACT FROM AUTHOR]

Background: Little is known about nutrition outcomes in preschoolers associated with breastfeeding duration beyond 12 mo of age. Objective: The aim was to examine the association between total breastfeeding duration and nutrition outcomes at 3 to 5 y of age. Design: A cross-sectional study in healthy children, ages 3-5 y, recruited from 9 primary care practices in Toronto was conducted through the TARGet Kids! (The Applied Research Group for Kids) research network. Parents completed standardized surveys, including the Nutrition Screening for Every Preschooler (NutriSTEP) used to assess nutrition risk. Results: A total of 2987 children were included. Ninety-two percent of children were breastfed, and the mean ± SD breastfeeding duration was 11.4 ± 8.4 mo. The prevalence of nutrition risk (score >20) was 17.0%. We examined breastfeeding duration as a continuous variable.With the use of restricted cubic spline modeling, we confirmed a nonlinear relation between breastfeeding duration and NutriSTEP score, dietary intake and eating behavior subscores, and sugar-sweetened beverage and sweet-savory snack consumption. Segmented linear regression was used to examine this nonlinear relation in a piecewise approach. We found a decreasing trend in NutriSTEP score for children who were breastfed for 0-6 mo (β = -0.14; 95% CI: -0.29, 0.004), a significant decrease in NutriSTEP score for children breastfed for 6-12 mo (β = -0.20; 95% CI: -0.33, -0.07), and no significant change after 12 mo (β = 0.09; 95% CI: -0.07, 0.24) and beyond. The mean ± SD NutriSTEP scores were 17.1 ± 7.4 for no breastfeeding, 15.9 ± 6.5 for breastfeeding >0-6 mo, 13.9 ± 6.2 for >6-12 mo, 13.7 ± 6.3 for >12-18 mo, 14.6 ± 6.7 for >18-24 mo, and 14.3 ± 6.8 for >24-36 mo. Conclusions: Breastfeeding for ≤12 mo was associated with decreased nutrition risk and healthier eating behaviors and dietary intake at 3-5 y of age. We found insufficient evidence of additional benefit for breastfeeding beyond 12 mo of age. [ABSTRACT FROM AUTHOR]

Background: Accelerated postnatal growth is an important predictor for obesity risk. It is unknown whether early-life obesity-related risk factors affect body mass index (BMI) growth rates during distinct growth periods from early infancy through preschool years. Objective: We examined whether breastfeeding duration, maternal BMI, and birth weight are associated with growth trajectories of age- and sex-standardized WHO BMI z scores (zBMIs) in young children. Design: Children (n = 5905) in The Applied Research Group for Kids (TARGet Kids!) prospective cohort study underwent repeated measures of weight and length or height from birth to 10 y of age. Piecewise linear mixed models were used to determine whether zBMI growth rates differ for each risk factor during periods of growth between birth and 1, 3, 18, 36, and 72 mo of age. Results: Children who were breastfed <6 mo compared with >6 mo showed a higher growth rate between 1-3 and 3-18 mo, resulting in higher standardized BMIs (zBMIs) of +0.24, +0.12, and +0.19 at 18, 36, and 72 mo, respectively. Maternal BMI (in kg/m²) ≥30 compared with <30 resulted in higher growth rates between 1-3 and 36-72 mo and higher zBMIs of +0.22, +0.14, +0.18, and +0.41 at 3, 18, 36, and 72 mo, respectively. Infants weighing <2.5 kg at birth (compared with 2.5-4 kg) experienced higher growth rates between 1-3 and 3-18 mo but had lower zBMIs at all time points (zBMI: -1.45 to -0.21). Infants weighing ≥4 kg at birth (compared with 2.5-4 kg) had significantly lower growth rates in the first 3 mo but higher zBMIs at all time points (zBMI: +1.16 to +0.27). Conclusion: Differences in zBMI growth rates by breastfeeding duration, maternal BMI, and birth weight are seen in early infancy and contribute to differences in zBMI, which persist into midchildhood. [ABSTRACT FROM AUTHOR]

Background: Most Canadian children do not meet the recommended dietary intake for vitamin D. Objectives: The aims were to test how much vitamin D from food is needed to maintain a healthy serum 25-hydroxyvitamin D3 [25(OH)D3] status from fall to spring in young children and to examine musculoskeletal outcomes. Design: Healthy children aged 2-8 y (n = 51) living in Montreal, Canada, were randomly assigned to 1 of 2 dietary vitamin D groups (control or intervention to reach 400 lU/d by using vitamin D- fortified foods) for 6 mo, starting October 2014. At baseline and at 3 and 6 mo, anthropometric characteristics, vitamin D metabolites (liquid chromatography-tandem mass spectrometry), and bone biomarkers (IDS-iSYS, Immunodiagnositc Systems; Liaison; Diasorin) were measured and physical activity and food intakes surveyed. At baseline and at 6 mo, bone outcomes and body composition (dual-energy X-ray absorptiometry) were measured. Cross-sectional images of distal tibia geometry and muscle density were conducted with the use of peripheral quantitative computed tomography scans at 6 mo. Results: At baseline, participants were aged 5.2 ± 1.9 (mean ± SD) y and had a body mass index z score of 0.65 ± 0.12; 53% of participants were boys. There were no differences between groups in baseline serum 25(OH)D3 (66.4 ± 13.6 nmol/L) or vitamin D intake (225 ± 74 lU/d). Median (IQR) compliance was 96% (89-99%) for yogurt and 84% (71-97%) for cheese. At 3 mo, serum 25(OH)D3 was higher in the intervention group (P < 0.05) but was not different between groups by 6 mo. Although lean mass accretion was higher in the intervention group (P < 0.05), no differences in muscle density or bone outcomes were observed. Conclusions: The consumption of 400 IU vitamin D/d from fall to spring did not maintain serum 25(OH)D3 concentration or improve bone outcomes. Further work with lean mass accretion as the primary outcome is needed to confirm if vitamin D enhances lean accretion in healthy young children. This trial was registered at www.clinicaltrials.gov as NCT02387892. [ABSTRACT FROM AUTHOR]

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]

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]

Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) are important in child development. The primary objective of this study was to investigate the associations between dietary intakes of n-3 LCPUFA and red blood cell (RBC) n-3 LCPUFA in young children. Healthy children, (2–8 y) underwent RBC fatty acid profiling. Dietary intakes were parent-reported over 6 mo using three 24 h dietary intake assessments and three 30 d food frequency questionnaires (FFQ). Participants (n = 49, 5.6 ± 1.9 y), were 59% male, and had a body mass index (BMI) z-score of 0.65 ± 0.84. Dietary n-3 LCPUFA intakes were not different over time. RBC docosahexaenoic acid (DHA) positively correlated with average DHA from the 24 h recalls. RBC DHA and eicosapentaenoic acid (EPA) positively correlated with average n-3 LCPUFA-rich fish intake from the FFQ. RBC appear to reflect long-term stable intakes of n-3 LCPUFA during growth in healthy young children. [ABSTRACT FROM AUTHOR]

Background: Cow milk consumption in childhood has been associated with increased height, which is an important measure of children's growth and development. Many parents are choosing noncow milk beverages such as soy and almond milk because of perceived health benefits. However, noncow milk contains less protein and fat than cow milk and may not have the same effect on height. Objective: We sought to determine whether there is an association between noncow milk consumption and lower height in childhood and assess whether cow milk consumption mediates the relation between noncow milk consumption and height. Design: This was a cross-sectional study of 5034 healthy Canadian children aged 24-72 mo enrolled in the Applied Research Group for Kids cohort. The primary exposure was the volume of noncow milk consumption (number of 250-mL cups per day). The primary outcome was height, which was measured as height-for-age z score. Multivariable linear regression was used to determine the association between noncow milk consumption and height. A mediation analysis was conducted to explore whether cow milk consumption mediated the association between noncow milk consumption and height. Results: There was a dose-dependent association between higher noncow milk consumption and lower height (P < 0.0001). For each daily cup of noncow milk consumed, children were 0.4 cm (95% CI: 0.2, 0.8 cm) shorter. In the mediation analysis, lower cow milk consumption only partially mediated the association between noncow milk consumption and lower height. The height difference for a child aged 3 y consuming 3 cups noncow milk/d relative to 3 cups cow milk/d was 1.5 cm (95% CI: 0.8, 2.0 cm). Conclusions: Noncow milk consumption was associated with lower childhood height. Future research is needed to understand the causal relations between noncow milk consumption and height. [ABSTRACT FROM AUTHOR]

Background: Fortified cow milk is a material contributor of vitamin D and dietary fat in children. Recommendations for children >2 y of age advise reduced milk-fat consumption to reduce childhood obesity, yet the relation between lower milk fat, vitamin D stores, and body mass index (BMI) is unclear. Objectives: The primary objective was to explore the association between milk-fat percentage and both BMI z score (zBMI) and venous 25-hydroxyvitamin D [25(OH)D]; the secondary objective was to assess whether milk volume consumed modified this relation. Design: This was a cross-sectional analysis. Healthy urban children aged 12-72 mo were recruited from 9 primary health care practices within The Applied Research Group for Kids (TARGet Kids!) research group in Toronto, Canada. We used adjusted bivariate linear regression to examine the relation between milk-fat percentage and child 25(OH)D and zBMI concurrently. Effect modification by milk volume consumed on the evaluated relations was explored with the use of an interaction term in the statistical model. Results: Among the 2745 included children there was a positive association between milk-fat percentage and 25(OH)D (P = 0.006) and a negative association between milk-fat percentage and zBMI (P < 0.0001). Participants who drank whole milk had a 5.4-nmol/L (95% CI: 4.32, 6.54) higher median 25(OH)D concentration and a 0.72 lower (95% CI: 0.68, 0.76) zBMI score than children who drank 1% milk. Milk volume consumed modified the effect of milk-fat percentage on 25(OH)D (P = 0.003) but not on zBMI (P = 0.77). Conclusions: Whole milk consumption among healthy young children was associated with higher vitamin D stores and lower BMI. Longitudinal and interventional studies are needed to confirm these findings. TARGet Kids! was registered at clinicaltrials.gov as NCT01869530. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is fundamental for bone health. A high proportion of Canadian 2- to 8-y-olds do not meet the Estimated Average Requirement (EAR) of 400 IU/d. Objective: The objective was to determine whether vitamin D intakes consistent with the EAR or Recommended Dietary Allowance (RDA), through fortification of additional dairy products, would result in higher vitamin D status in young children. Design: Participants aged 2-8 y (n = 77; Montreal, Canada) were randomly assigned to 1 of 3 dietary vitamin D targets (control; EAR: 400 IU/d; or RDA: 600 IU/d) for 12 wk (January to April 2014). Anthropometric measurements, demographic characteristics, dietary intakes, fasting serum parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], and ionized calcium were compared by using mixed-model ANOVA. Results: Participants' mean ± SD age was 5.1 ± 1.9 y; 54.5% were boys with body mass index z scores of 0.50 ± 0.85. Compliance was 85% overall. No differences were observed in baseline dietary vitamin D intakes or serum 25(OH)D. At 12 wk, the EAR and RDA groups had significantly higher vitamin D intakes [median (IQR): control, 227 (184-305) IU/d; EAR, 410 (363-516) IU/d; and RDA, 554 (493-653) IU/d; P < 0.05] and serum 25(OH)D concentrations (control: 55.8 ± 12.3 nmol/L; EAR: 64.1 ± 10.0 nmol/L; and RDA: 63.7 ± 12.4 nmol/L; P < 0.05) than the control group. Ninety-six percent of children in the EAR and RDA groups and 67% of the control group had 25(OH)D concentrations ≥50 nmol/L. Conclusion: Increasing the vitamin D intakes of young children through fortification of alternative dairy products results in significantly higher serum concentrations of 25(OH)D and a significantly greater proportion of children with serum 25(OH)D ≥50 nmol/L during periods of minimal ultraviolet B radiation exposure. This trial was registered at clinicaltrials.gov as NCT02097160 and had Health Canada Temporary Marketing Authorization Letters for both products (TM-13-0432 and TM-13-0433). [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between the timing of infant cereal introduction between 4 and 6 months of age and growth and dietary intake in later childhood.Study Design: A longitudinal cohort study was conducted among healthy children 0-10 years of age participating in The Applied Research Group for Kids cohort study between June 2008 and August 2019 in Toronto, Canada.Results: Of 8943 children included, the mean (SD) age of infant cereal introduction was 5.7 (2.1) months. In the primary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.17 greater body mass index z score (95% CI 0.06-0.28; P = .002) and greater odds of obesity (OR 1.82; 95% CI 1.18-2.80; P = .006) at 10 years of age. In the secondary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.09 greater height-for-age z score (95% CI 0.04-0.15; P = .002) at 1 year of age, an association that was not observed at 5 or 10 years of age. Children who were introduced to infant cereal at 4 vs 6 months had greater nutrition risk which was primarily determined by a less-favorable eating behavior score at 18 months to 5 years of age (0.18 units higher; 95% CI 0.07-0.29; P = .001).Conclusions: Introduction of infant cereal at 4 vs 6 months was associated with greater body mass index z score, greater odds of obesity, similar height-for-age z score, and less favorable eating behavior. These findings support recommendations for introducing solid food around 6 months of age. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether safety warnings issued by health regulatory agencies regarding desmopressin treatment influenced treatment rates among children. Patient population and methods: We conducted a time-series analysis using health administrative data from Ontario, Canada, between January 1, 2003 and March 31, 2010. We examined desmopressin prescribing rates among children (<13 years) and investigated the impact of a United States Food and Drug Administration warning (December 2007) and a subsequent Health Canada warning (July 2008) on these rates. A secondary analysis stratified rates according to route of administration. Results: On average, quarterly desmopressin treatment rates were 29.8% lower following the two warnings (4.7 per 1000 population) compared with the period prior to warnings being issued (6.7 per 1000 population). Structural break analyses identified a significant decrease in overall desmopressin prescribing rates in Q3 2008, with the 95% confidence interval (CI) spanning both safety warnings (Q4 2007 to Q1 2009). A secondary analysis of prescribing rates for oral formulations found consistent results (structural break Q4 2008, 95% CI Q2 2007 to Q2 2009). The average quarterly prescribing rate of intranasal formulations declined by 73.1% following the warnings compared with the period preceding the warnings. Conclusion: Safety warnings issued by regulatory agencies dramatically influenced desmopressin use among Ontario’s children. [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 assess the mechanisms accounting for the transfer of risk from one generation to the next, especially as they relate to maternal adverse childhood experiences and infant physical and emotional health outcomes.Study Design: Participants were 501 community mother-infant dyads recruited shortly after the birth and followed up at 18 months. Mothers retrospectively reported on their adverse childhood experiences. The main outcome measures were parent-reported infant physical health and emotional problems. Potential mechanisms of intergenerational transmission included cumulative biomedical risk (eg, prenatal and perinatal complications) and postnatal psychosocial risk (eg, maternal depression, single parenthood, marital conflict).Results: Four or more adverse childhood experiences were related to a 2- and 5-fold increased risk of experiencing any biomedical or psychosocial risk, respectively. There was a linear association between number of adverse childhood experiences and extent of biomedical and psychosocial risk. Path analysis revealed that the association between maternal adverse childhood experiences and infant physical health operated specifically through cumulative biomedical risk, while the relationship between adverse childhood experiences and infant emotional health operated specifically through cumulative psychosocial risk. This pattern was not explained by maternal childhood disadvantage or current neighborhood poverty.Conclusions: Maternal adverse childhood experiences confer vulnerability to prenatal, perinatal, and postnatal psychosocial health. The association between adverse childhood experiences and offspring physical and emotional health operates through discrete intermediary mechanisms. [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]

Objective: There is concern that obstetric interventions (prelabor cesarean section and induced delivery) are drivers of late preterm (LP) birth. Our objective was to evaluate the independent association between obstetric interventions and LP birth and explore associated independent maternal and fetal risk factors for LP birth. Study Design: In this population-based cross-sectional study, the BORN Information System was used to identify all infants born between 34 and 40 completed weeks of gestation between 2005 and 2012 in Ontario, Canada. The association between obstetric interventions (preterm cesarean section and induced delivery) and LP birth (34 to 36 completed weeks' gestation vs 37 to 40 completed weeks' gestation) was assessed using generalized estimating equation regression. Results: Of 917,013 births between 34 and 40 weeks, 49,157 were LP (5.4%). In the adjusted analysis, “any obstetric intervention” (risk ratio [RR], 0.65; 95% confidence interval [CI], 0.57–0.74), induction (RR, 0.71; 95% CI, 0.61–0.82) and prelabor cesarean section (RR, 0.66; 95% CI, 0.59–0.74) were all associated with a lower likelihood of LP vs term birth. Several independent potentially modifiable risk factors for LP birth were identified including previous cesarean section (RR, 1.28; 95% CI, 1.16–1.40), smoking during pregnancy (RR, 1.28; 95% CI, 1.21–1.36) and high material (RR, 1.1; 95% CI, 1.03–1.18) and social (RR, 1.09; 95% CI, 1.02–1.16) deprivation indices. Conclusion: After accounting for differences in maternal and fetal risk, LP births had a 35% lower likelihood of obstetric interventions than term births. Obstetric care providers may be preferentially avoiding induction and prelabor cesarean section between 34 and 37 weeks' gestation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Acute meningitis is a relatively common phenomenon in children. Identifying which children are most likely to have bacterial meningitis vs. self-limiting aseptic meningitis is important, as these children require investigation and antibiotic treatment. Objective: Our aim was to systematically identify and review the quality and performance of published clinical prediction rules (CPRs) for children with suspected bacterial meningitis. Methods: Medline and Embase were searched for CPRs involving children 0–18 years of age with suspected bacterial meningitis, with cerebral spinal fluid (CSF) culture used as the reference diagnostic standard. CPR quality was assessed using 17 previously published items. CPR performance was evaluated using sensitivity, negative likelihood ratio, and the treatment frequency that would result if the rule was used. Results: Eleven studies involving 6675 children with acute meningitis fulfilled all inclusion criteria and were entered in the study. They all describe the derivation or validation of six unique CPRs. A rigorously developed, high-performing, and well-validated CPR ready for clinical use to guide which children with suspected bacterial meningitis should be hospitalized and treated with intravenous antibiotics and which can be safely discharged home was not identified. Areas for quality improvement for future CPR studies include prospective validation using standardized inclusion criteria, adequate blinding, predictor reproducibility assessment, and meticulous follow-up of outcomes. The Bacterial Meningitis Score had the highest quality and performance and is the best candidate for prospective validation. Conclusions: Until consistently high methodological quality and diagnostic performance are demonstrated through prospective validation, caution is warranted in the routine clinical use of existing CPRs for children with suspected bacterial meningitis. [Copyright &y& Elsevier]

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 0e18 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. @2013 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

In adults, cardiometabolic conditions manifest differently by ethnicity with South Asians particularly predisposed. Whether these differences arise in childhood remains narrowly explored. To address this evidence gap, we examined whether children of different ethnicities display differences in cardiometabolic risk (CMR). A cross-sectional analysis was conducted among 5557 children (3–11 years). Multivariable linear regression models adjusted for age, sex, z-body mass index, and demographic factors were used to estimate differences in CMR outcomes between children with parents that self-reported European ancestry (reference group) and one of 13 other ethnicities (African, Arab, East Asian, Latin American, South Asian, Southeast Asian, Mixed Ethnicities, and Other). The primary outcome was a CMR score, calculated as the sum of age- and sex-standardized waist circumference, systolic blood pressure (SBP), glucose, log-triglycerides, and inverse high-density lipoprotein cholesterol (HDL-C), divided by √5. Lower mean CMR scores were observed among children with African (β = −0.62, 95% CI: −0.92; −0.32) and East Asian (β = −0.41, 95% CI: −0.68, −0.15) ancestry compared to children with European ancestry. Children with South Asian ancestry had higher SBP (β = 2.25, 95% CI: 1.27, 3.22) and non-HDL-C (β = 0.17, 95% CI: 0.07, 0.26) than children with European ancestry. Ethnic differences in CMR were observed in early and middle childhood. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Measuring ethnicity accurately is important for identifying ethnicity variations in disease risk. We evaluated the degree of agreement and accuracy of maternal ethnicity measured using the new standardized closed-ended geographically based ethnicity question and geographic reclassification of open-ended ethnicity questions from the Canadian census. Methods: A prospectively designed study of respondent agreement of mothers of healthy children aged 1–5 years recruited through the TARGet Kids! practice-based research network. For the primary analysis, the degree of agreement between geographic reclassification of the Canadian census maternal ethnicity variables and the new geographically based closed-ended maternal ethnicity variable completed by the same respondent was evaluated using a kappa analysis. Results: Eight hundred sixty-two mothers who completed both measures of ethnicity were included in the analysis. The kappa agreement statistic for the two definitions of maternal ethnicity was 0.87 (95% confidence interval, 0.84–0.90) indicating good agreement. Overall accuracy of the measurement was 93%. Sensitivity and specificity ranged from 83% to 100% and 96% to 100%, respectively. Conclusions: The new standardized closed-ended geographically based ethnicity question represents a practical alternative to widely used open-ended ethnicity questions. It may reduce risk of misinterpretation of ethnicity by respondents, simplify analysis, and improve the accuracy of ethnicity measurement. [Copyright &y& Elsevier]