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

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]

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]

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]