The mediation effect of breastfeeding duration on the relationship between maternal preconception BMI and childhood nutritional risk.

BACKGROUND: Higher maternal preconception body mass index (BMI) is associated with lower breastfeeding duration, which may contribute to the development of poor child eating behaviours and dietary intake patterns (components of nutritional risk). A higher maternal preconception BMI has been found to be associated with higher child nutritional risk. This study aimed to determine whether breastfeeding duration mediated the association between maternal preconception BMI and child nutritional risk. METHODS: In this longitudinal cohort study, children ages 18 months to 5 years were recruited from The Applied Research Group for Kids (TARGet Kids!) in Canada. The primary outcome was child nutritional risk, using The NutriSTEP®, a validated, parent-reported questionnaire. Statistical mediation analysis was performed to assess whether total duration of any breastfeeding mediated the association between maternal preconception BMI and child nutritional risk. RESULTS: This study included 4733 children with 8611 NutriSTEP® observations. The mean (SD) maternal preconception BMI was 23.6 (4.4) and the mean (SD) breastfeeding duration was 12.4 (8.0) months. Each 1-unit higher maternal preconception BMI was associated with a 0.081 unit higher nutritional risk (95% CI (0.051, 0.112); p < 0.001) (total effect), where 0.011(95% CI (0.006, 0.016); p < 0.001) of that total effect or 13.18% (95% CI: 7.13, 21.25) was mediated through breastfeeding duration. CONCLUSION: Total breastfeeding duration showed to mediate part of the association between maternal preconception BMI and child nutritional risk. Interventions to support breastfeeding in those with higher maternal preconception BMI should be evaluated for their potential effect in reducing nutritional risk in young children.

Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources.

BACKGROUND: Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines. METHODS: In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6-23 months, 24-59 months, 5-11 years, and 12-17 years, and adults aged 18-65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations. FINDINGS: We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104·4 g/L (90% CI 103·5-105·3) in 924 children aged 6-23 months, 110·2 g/L (109·5-110·9) in 1874 children aged 24-59 months, and 114·4 g/L (113·6-115·2) in 1839 children aged 5-11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122·2 g/L (90% CI 121·3-123·1) in 1741 female adolescents aged 12-17 years and 128·2 g/L (126·4-130·0) in 1103 male adolescents aged 12-17 years. In pooled analyses of adults aged 18-65 years, the fifth centile was 119·7 g/L (90% CI 119·1-120·3) in 3640 non-pregnant females and 134·9 g/L (134·2-135·6) in 2377 males. Fifth centiles in pregnancy were 110·3 g/L (90% CI 109·5-111·0) in the first trimester (n=772) and 105·9 g/L (104·0-107·7) in the second trimester (n=111), with insufficient data for analysis in the third trimester. There were insufficient data for adults older than 65 years. We did not identify ancestry-specific high prevalence of non-clinically relevant genetic variants that influence haemoglobin concentrations. INTERPRETATION: Our results enable global harmonisation of clinical and public health haemoglobin thresholds for diagnosis of anaemia. Haemoglobin thresholds are similar between sexes until adolescence, after which males have higher thresholds than females. We did not find any evidence that thresholds should differ between people of differering ancestries. FUNDING: World Health Organization and the Bill & Melinda Gates Foundation.

Factors associated with COVID-19 vaccination in young children.

OBJECTIVE: To examine factors associated with COVID-19 vaccination (time to vaccination and vaccination status) among healthy young children participating in primary healthcare. METHODS: A cohort study was conducted between November 2021 and September 2022 through the TARGet Kids! primary care research network in Toronto, Canada. Sociodemographic information, child and parent health characteristics, parental vaccine beliefs and child COVID-19 vaccine uptake were collected through parent-reported questionnaires. The primary outcome was time to child COVID-19 vaccination, measured as the time between vaccine availability date and parent-reported child COVID-19 vaccination date. Interval-censored proportional hazard models were used. RESULTS: A total of 267 children age 0 to 13 years were included. The mean child age was 7.6 years, 52.8% (n = 141) were male, 66.5% (n = 141) had mothers of European ethnicity (with missingness), and 68.2% (n = 182) of the children were vaccinated. All parents of vaccinated children had received the COVID-19 vaccination themselves. The rate of vaccination for children was 2% higher with each one-month increase in child age (adjusted HR = 1.02, 95%CI = 1.01-1.03, p < 0.001). Compared to children whose parents had uncertain beliefs, those whose parents had positive beliefs about the importance and safety of COVID-19 vaccination for their children had higher rates of vaccination (adjusted HR = 8.29, 95%CI = 4.25-16.17, p < 0.001; adjusted HR = 5.09, 95%CI = 3.17-8.17, p < 0.001). CONCLUSION: Older child age, parental COVID-19 vaccination, and positive parental beliefs about COVID-19 vaccination were statistically significantly associated with COVID-19 vaccination among healthy young children. Our findings may help to inform policies, practices, and research which aim to strengthen parental vaccine confidence and promote child COVID-19 vaccination.

RéSUMé: OBJECTIF: Examiner les facteurs associés à la vaccination contre la COVID-19 (délai de vaccination et statut vaccinal) chez de jeunes enfants en bonne santé recevant des soins de santé primaires. MéTHODE: Une étude de cohorte a été menée entre novembre 2021 et septembre 2022 par le réseau de recherche en soins primaires TARGet Kids! à Toronto, au Canada. Des données sur le profil sociodémographique, les caractéristiques de santé des enfants et des parents, les convictions parentales à l'égard de la vaccination et la vaccination des enfants contre la COVID-19 ont été recueillies au moyen de questionnaires remplis par les parents. Le résultat principal était le délai de vaccination des enfants contre la COVID-19, mesuré comme étant le temps écoulé entre la date de disponibilité d'un vaccin et la date de vaccination de l'enfant contre la COVID-19 déclarée par le parent. Des modèles de risques proportionnels censurés par intervalle ont été utilisés. RéSULTATS: En tout, 267 enfants de 0 à 13 ans ont été inclus. Ils avaient 7,6 ans en moyenne, 52,8% (n = 141) étaient des garçons, 66,5% (n = 141) avaient une mère d'origine ethnique européenne (avec des données manquantes), et 68,2% (n = 182) étaient vaccinés. Tous les parents des enfants vaccinés étaient eux-mêmes vaccinés contre la COVID-19. Le taux de vaccination des enfants augmentait de 2 % pour chaque mois d'augmentation de l'âge des enfants (rapport de risques instantanés [RRI] ajusté = 1,02, intervalle de confiance [IC] de 95% = 1,01­1,03, p < 0,001). Comparativement aux enfants dont les parents étaient incertains dans leurs convictions, ceux dont les parents croyaient en l'importance et en l'innocuité de la vaccination contre la COVID-19 pour leurs enfants avaient des taux de vaccination plus élevés (RRI ajusté = 8,29, IC de 95% = 4,25­16,17, p < 0,001; RRI ajusté = 5,09, IC de 95% = 3,17­8,17, p < 0,001). CONCLUSION: L'âge plus avancé des enfants, la vaccination parentale contre la COVID-19 et les convictions parentales positives à l'égard de la vaccination contre la COVID-19 présentaient une corrélation significative avec la vaccination contre la COVID-19 chez les jeunes enfants en bonne santé. Nos constats pourraient contribuer à éclairer les politiques, les pratiques et la recherche visant à renforcer la confiance parentale en la vaccination et à promouvoir la vaccination des enfants contre la COVID-19.

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

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

Underweight in the first 2 years of life and nutrition risk in later childhood: a prospective cohort study.

BACKGROUND: Children with underweight in the first 2 years have lower body mass index z-score (zBMI) and height-for-age z-score (HAZ) in later childhood. It is not known if underweight in the first 2 years is associated with nutrition risk in later childhood. OBJECTIVE: (1) Determine the relationship between underweight (zBMI < -2) in the first 2 years and nutrition risk measured by the Nutrition Screening for Toddlers and Preschoolers (NutriSTEP) score from 18 months to 5 years. (2) Explore the relationship between underweight in the first 2 years and the NutriSTEP subscores for eating behaviours and dietary intake from 18 months to 5 years. METHODS: This was a prospective study, including healthy full-term children in Canada aged 0-5 years. zBMI was calculated using measured heights and weights and the WHO growth standards. NutriSTEP score was measured using a parent-completed survey and ranged from 0 to 68. Nutrition risk was defined as a score ≥21. Linear mixed effects models were used. RESULTS: Four thousand nine hundred twenty-nine children were included in this study. At enrolment, 51.9% of participants were male. The prevalence of underweight children was 8.8%. Underweight in the first 2 years was associated with higher NutriSTEP (0.79, 95% CI: 0.29,1.29), higher eating behaviour subscore (0.24, 95% CI: 0.03, 0.46) at 3 years and higher odds of nutrition risk (OR: 1.39, 95% CI: 1.07,1.82) at 5 years. CONCLUSIONS: Children with underweight in the first 2 years had higher nutrition risk in later childhood. Further research is needed to understand the factors which influence these relationships.

Changes in sleep and the prevalence of probable insomnia in undergraduate university students over the course of the COVID-19 pandemic: findings from the U-Flourish cohort study.

BACKGROUND: Sleep problems associated with poor mental health and academic outcomes may have been exacerbated by the COVID-19 pandemic. AIMS: To describe sleep in undergraduate students during the COVID-19 pandemic. METHOD: This longitudinal analysis included data from 9523 students over 4 years (2018-2022), associated with different pandemic phases. Students completed a biannual survey assessing risk factors, mental health symptoms and lifestyle, using validated measures. Sleep was assessed with the Sleep Condition Indicator (SCI-8). Propensity weights and multivariable log-binomial regressions were used to compare sleep in four successive first-year cohorts. Linear mixed-effects models were used to examine changes in sleep over academic semesters and years. RESULTS: There was an overall decrease in average SCI-8 scores, indicating worsening sleep across academic years (average change -0.42 per year; P-trend < 0.001), and an increase in probable insomnia at university entry (range 18.1-29.7%; P-trend < 0.001) before and up to the peak of the pandemic. Sleep improved somewhat in autumn 2021, when restrictions loosened. Students commonly reported daytime sleep problems, including mood, energy, relationships (36-48%) and concentration, productivity, and daytime sleepiness (54-66%). There was a consistent pattern of worsening sleep over the academic year. Probable insomnia was associated with increased cannabis use and passive screen time, and reduced recreation and exercise. CONCLUSIONS: Sleep difficulties are common and persistent in students, were amplified by the pandemic and worsen over the academic year. Given the importance of sleep for well-being and academic success, a preventive focus on sleep hygiene, healthy lifestyle and low-intensity sleep interventions seems justified.

Timing of introduction to solid food, eczema and wheezing in later childhood: a longitudinal cohort study.

BACKGROUND: The timing of introduction to solid food has been associated with eczema and wheezing in childhood. Our aim was to determine whether differences persist within the recommended 4 to 6 month age range. METHODS: A longitudinal cohort study with repeated measures was conducted among children from birth to 10 years of age who were participating in the TARGet Kids! practice based research network in Toronto, Canada. The primary exposure was the timing of introduction to infant cereal as the first solid food. The primary outcome was eczema and the secondary outcome was wheezing collected by parent report using the validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Multinomial generalized estimating equations were used and effect modification by family history of asthma and breastfeeding duration were explored. RESULTS: Of the 7843 children included, the mean (standard deviation) age of introduction to infant cereal was 5.7 (1.9) months. There was evidence for family history of asthma and breastfeeding duration to be effect modifiers in the eczema (P = 0.04) and wheezing (P = 0.05) models. Introduction to infant cereal at 4 vs. 6 months of age was associated with higher odds of eczema (OR 1.62; 95% CI: 1.12, 2.35; P = 0.01) among children without a family history of asthma who were not breastfeeding when solid foods were introduced. Introduction to infant cereal at 4 vs. 6 months of age was associated with a higher odds of wheezing (OR 1.31; 95% CI: 1.13, 1.52; P < .001) among children without a family history of asthma who were breastfeeding when solid foods were introduced. There was little evidence of an association among the remaining strata for either outcome. CONCLUSION: The findings of this study support recommendations to introduce solid food around 6 months of age.

New approaches and technical considerations in detecting outlier measurements and trajectories in longitudinal children growth data.

BACKGROUND: Growth studies rely on longitudinal measurements, typically represented as trajectories. However, anthropometry is prone to errors that can generate outliers. While various methods are available for detecting outlier measurements, a gold standard has yet to be identified, and there is no established method for outlying trajectories. Thus, outlier types and their effects on growth pattern detection still need to be investigated. This work aimed to assess the performance of six methods at detecting different types of outliers, propose two novel methods for outlier trajectory detection and evaluate how outliers affect growth pattern detection. METHODS: We included 393 healthy infants from The Applied Research Group for Kids (TARGet Kids!) cohort and 1651 children with severe malnutrition from the co-trimoxazole prophylaxis clinical trial. We injected outliers of three types and six intensities and applied four outlier detection methods for measurements (model-based and World Health Organization cut-offs-based) and two for trajectories. We also assessed growth pattern detection before and after outlier injection using time series clustering and latent class mixed models. Error type, intensity, and population affected method performance. RESULTS: Model-based outlier detection methods performed best for measurements with precision between 5.72-99.89%, especially for low and moderate error intensities. The clustering-based outlier trajectory method had high precision of 14.93-99.12%. Combining methods improved the detection rate to 21.82% in outlier measurements. Finally, when comparing growth groups with and without outliers, the outliers were shown to alter group membership by 57.9 -79.04%. CONCLUSIONS: World Health Organization cut-off-based techniques were shown to perform well in few very particular cases (extreme errors of high intensity), while model-based techniques performed well, especially for moderate errors of low intensity. Clustering-based outlier trajectory detection performed exceptionally well across all types and intensities of errors, indicating a potential strategic change in how outliers in growth data are viewed. Finally, the importance of detecting outliers was shown, given its impact on children growth studies, as demonstrated by comparing results of growth group detection.

Late preterm birth and growth trajectories during childhood: a linked retrospective cohort study.

BACKGROUND: Evidence suggests that accelerated postnatal growth in children is detrimental for adult cardiovascular health. It is unclear whether children born late preterm (34-36 weeks) compared to full term (≥ 39 weeks), have different growth trajectories. Our objective was to evaluate the association between gestational age groups and growth trajectories of children born between 2006-2014 and followed to 2021 in Ontario, Canada. METHODS: We conducted a retrospective cohort study of children from singleton births in TARGet Kids! primary care network with repeated measures of weight and height/length from birth to 14 years, who were linked to health administrative databases. Piecewise linear mixed models were used to model weight (kg/month) and height (cm/month) trajectories with knots at 3, 12, and 84 months. Analyses were conducted based on chronological age. RESULTS: There were 4423 children included with a mean of 11 weight and height measures per child. The mean age at the last visit was 5.9 years (Standard Deviation: 3.1). Generally, the more preterm, the lower the mean value of weight and height until early adolescence. Differences in mean weight and height for very/moderate preterm and late preterm compared to full term were evident until 12 months of age. Weight trajectories were similar between children born late preterm and full term with small differences from 84-168 months (mean difference (MD) -0.04 kg/month, 95% CI -0.06, -0.03). Children born late preterm had faster height gain from 0-3 months (MD 0.70 cm/month, 95% CI 0.42, 0.97) and 3-12 months (MD 0.17 cm/month, 95% CI 0.11, 0.22). CONCLUSIONS: Compared to full term, children born late preterm had lower average weight and height from birth to 14 years, had a slightly slower rate of weight gain after 84 months and a faster rate of height gain from 0-12 months. Follow-up is needed to determine if growth differences are associated with long-term disease risk.

Validation of Parent-reported Gestational Age Categories for Children Less Than 6 Years of Age.

BACKGROUND: Preterm birth is an important outcome or exposure in epidemiologic research. When administrative data on measured gestational age is not available, parent-reported gestational age can be obtained from questionnaires, which is subject to potential bias. To our knowledge, few studies have assessed the validity of parent-reported gestational age categories, including commonly defined categories of preterm birth. METHODS: We used linked data from primarily healthy children <6 years of age in TARGet Kids! in Toronto, Canada, and ICES administrative healthcare data from April 2011 to March 2020. We assessed the criterion validity of questionnaire-based parent-reported gestational age by calculating sensitivity and specificity for term (≥37 weeks), late preterm (34-36 weeks), and moderately preterm (32-33 weeks) gestational age categories, using administrative healthcare records of gestational age as the criterion standard. We conducted subgroup analyses for various parent and socioeconomic factors that may influence recall. RESULTS: Of the 4684 participants, 97.3% correctly classified the gestational age category according to administrative healthcare data. Parent-reported gestational age sensitivity ranged from 83.7% to 98.5% and specificity ranged from 88.3% to 99.8%, depending on category. For each subgroup characteristic, sensitivity and specificity were all ≥70%. Lower educational attainment, lower family income, father reporting, ≥1 year since birth, ≥2 children, lower parent age, and reported gestational diabetes and/or hypertension were associated with slightly lower sensitivity and/or specificity. CONCLUSIONS: In this linked cohort, parent-reported gestational age categories had high accuracy. Criterion validity varied minimally among some parent and socioeconomic factors. Our findings can inform future quantitative bias analyses.

Validation of a parent proxy-reported beverage screener compared to a 24-hour dietary recall for the measurement of sugar-containing beverage intake among young children.

Measures that can provide reasonably accurate estimates of sugar-containing beverage (SCB) intake among children are needed. The primary objective of this study was to evaluate the relative validity of a short beverage screener (Nutrition and Health Questionnaire, NHQ) compared to a 24-hour recall (Automated Self-Administered 24-h (ASA24) Dietary Assessment Tool-Canada) for assessing parent proxy-reported daily SCB intake among children aged 4-14 years from the TARGet Kids! research network in Toronto, Canada. Children for whom a NHQ completed between March 2018 and June 2019 and an ASA24 completed within one year were included. A total of 471 parents who completed the NHQ beverage screener were also asked to complete the ASA24. One-hundred sixty-three completed the ASA24 and of this group, 109 were analyzed. Estimates of daily intake of 100% juices, sweetened drinks and soda, and total SCBs from the two measures were compared. The mean difference in beverage intake, Spearman correlations, and Bland-Altman plots were estimated for continuous measures. The kappa coefficient, sensitivity, and specificity were calculated for dichotomous measures of any daily intake versus none. The mean difference in total SCB intake between the NHQ and ASA24 was 0.14 cups/day (95% CI 0.01, 0.29) and the correlation was 0.43 (95% CI 0.26, 0.57). Sensitivity and specificity for any daily SCB intake were 0.63 and 0.76, respectively. Overall, parent proxy-reporting of children's total SCB intake from a beverage screener can provide reasonable estimates of SCB intake when detailed dietary assessment is not feasible.

A novel systematic pipeline for increased predictability and explainability of growth patterns in children using trajectory features.

OBJECTIVE: Longitudinal patterns of growth in early childhood are associated with health conditions throughout life. Knowledge of such patterns and the ability to predict them can lead to better prevention and improved health promotion in adulthood. However, growth analyses are characterized by significant variability, and pattern detection is affected by the method applied. Moreover, pattern labelling is typically performed based on ad hoc methods, such as visualizations or clinical experience. Here, we propose a novel pipeline using features extracted from growth trajectories using mathematical, statistical and machine-learning approaches to predict growth patterns and label them in a systematic and unequivocal manner. METHODS: We extracted mathematical and clinical features from 9577 children growth trajectories embedded with machine-learning predictions of the growth patterns. We experimented with two sets of features (CAnonical Time-series Characteristics and trajectory features specific to growth), developmental periods and six machine-learning classifiers. Clinical experts provided labels for the detected patterns and decision rules were created to associate the features with the labelled patterns. The predictive capacity of the extracted features was validated on two heterogenous populations (The Applied Research Group for Kids and the 2004 Pelotas Birth Cohort, based in Canada and Brazil, respectively). RESULTS: Features predictive ability measured by accuracy and F1 score was ≥ 80% and ≥ 0.76 respectively in both cohorts. A small number of features (n = 74) was sufficient to distinguish between growth patterns in both cohorts. Slope, intercept of the trajectory, age at peak value, start value and change of the growth measure were among the top identified features. CONCLUSION: Growth features can be reliably used as predictors of growth patterns and provide an unbiased understanding of growth patterns. They can be used as tool to reduce the effort to repeat analysis and variability concerning anthropometric measures, time points and analytical methods, in the context of the same or similar populations.

Effect of plant milk consumption on childhood growth: protocol for a systematic review.

INTRODUCTION: There has been considerable debate about whether plant milks can support the nutritional requirements of growing children. The proposed systematic review aims to assess the evidence on the relationship between plant milk consumption and growth and nutritional status in childhood. METHODS AND ANALYSIS: Ovid MEDLINE ALL (1946-present), Ovid EMBASE Classic (1947-present), CINAHL Complete (Cumulative Index to Nursing and Allied Health Literature), Scopus, the Cochrane Library and grey literature will be searched comprehensively (from 2000 to present; English language) to find studies that describe the association between plant milk consumption and growth or nutrition in children 1-18 years of age. Two reviewers will identify eligible articles, extract data and assess the risk of bias in individual studies. If a meta-analyses is not conducted, the evidence will be synthesised narratively and the overall certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval is not required for this study since no data will be collected. Results of the systematic review will be published in a peer-reviewed journal. Findings from this study may be useful in informing future evidence-based recommendations about plant milk consumption in children. PROSPERO REGISTRATION NUMBER: CRD42022367269.

Statistical haemoglobin thresholds to define anaemia across the lifecycle.

Detection of anaemia is critical for clinical medicine and public health. Current WHO values that define anaemia are statistical thresholds (5 th centile) set over 50 years ago, and are presently <110g/L in children 6-59 months, <115g/L in children 5-11 years, <110g/L in pregnant women, <120g/L in children 12-14 years of age, <120g/L in non-pregnant women, and <130g/L in men. Haemoglobin is sensitive to iron and other nutrient deficiencies, medical illness and inflammation, and is impacted by genetic conditions; thus, careful exclusion of these conditions is crucial to obtain a healthy reference population. We identified data sources from which sufficient clinical and laboratory information was available to determine an apparently healthy reference sample. Individuals were excluded if they had any clinical or biochemical evidence of a condition that may diminish haemoglobin concentration. Discrete 5 th centiles were estimated along with two-sided 90% confidence intervals and estimates combined using a fixed-effect approach. Estimates for the 5 th centile of the healthy reference population in children were similar between sexes. Thresholds in children 6-23 months were 104.4g/L [90% CI 103.5, 105.3]; in children 24-59 months were 110.2g/L [109.5, 110.9]; and in children 5-11 years were 114.1g/L [113.2, 115.0]. Thresholds diverged by sex in adolescents and adults. In females and males 12-17 years, thresholds were 122.2g/L [121.3, 123.1] and 128.2 [126.4, 130.0], respectively. In adults 18-65 years, thresholds were 119.7g/L [119.1, 120.3] in non-pregnant females and 134.9g/L [134.2, 135.6] in males. Limited analyses indicated 5 th centiles in first-trimester pregnancy of 110.3g/L [109.5, 111.0] and 105.9g/L [104.0, 107.7] in the second trimester. All thresholds were robust to variations in definitions and analysis models. Using multiple datasets comprising Asian, African, and European ancestries, we did not identify novel high prevalence genetic variants that influence haemoglobin concentration, other than variants in genes known to cause important clinical disease, suggesting non-clinical genetic factors do not influence the 5 th centile between ancestries. Our results directly inform WHO guideline development and provide a platform for global harmonisation of laboratory, clinical and public health haemoglobin thresholds.

Breastfeeding support provided by lactation consultants in high-income countries for improved breastfeeding rates, self-efficacy, and infant growth: a systematic review and meta-analysis protocol.

BACKGROUND: It is well established that breast milk offers numerous health benefits for mother and child. Mothers are recommended to exclusively breastfeed their child until 6 months of age, with continued breastfeeding up to 1-2 years of age or beyond. Yet, these recommendations are met less than half of the time in high-income countries. Lactation consultants specialize in supporting mothers with breastfeeding and are a promising approach to improving breastfeeding rates. For lactation consultant interventions to be implemented widely as part of public health policy, a better understanding of their effect on breastfeeding rates and important health outcomes is needed. METHODS: The overall aim of this systematic review is to evaluate the effect of lactation consultant interventions provided to women, compared to usual care, on breastfeeding rates (primary outcome), maternal breastfeeding self-efficacy, and infant growth. A search strategy has been developed to identify randomized controlled trials published in any language between 1985 and April 2023 in CENTRAL, MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science. We will also perform a search of the grey literature and reference lists of relevant studies and reviews. Two reviewers will independently extract data on study design, baseline characteristics, details of the interventions employed, and primary and secondary outcomes using a pre-piloted standardized data extraction form. Risk of bias and quality of evidence assessment will be done independently and in duplicate using the Cochrane Risk of Bias tool and GRADE approach, respectively. Where possible, meta-analysis using random-effects models will be performed, otherwise a qualitative summary will be provided. We will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. DISCUSSION: This review will fill an important gap in the lactation support literature. The findings will be of importance to policymakers who seek to implement interventions to improve breastfeeding rates. TRIAL REGISTRATION: This review has been registered in the PROSPERO database (ID: CRD42022326597).

Factors associated with research participation in a large primary care practice-based pediatric cohort: Results from the TARGet Kids! longitudinal cohort study.

BACKGROUND: All longitudinal cohort studies strive for high participant retention, although attrition is common. Understanding determinants of attrition is important to inform and develop targeted strategies to improve study participation. We aimed to identify factors associated with research participation in a large children's primary care cohort study. METHODS: In this longitudinal cohort study between 2008 and 2020, all children who participated in the Applied Research Group for Kids (TARGet Kids!) were included. TARGet Kids! is a large primary care practice-based pediatric research network in Canada with ongoing data collection at well-child visits. Several sociodemographic, health, and study design factors were examined for their associations with research participation. The primary outcome was attendance of eligible research follow-up visits. The secondary outcome was time to withdrawal from the TARGet Kids! study. Generalized linear mixed effects models and Cox proportional hazard models were fitted. We have engaged parent partners in all stages of this study. RESULTS: A total 10,412 children with 62,655 total eligible research follow-up visits were included. Mean age at enrolment was 22 months, 52% were male, and 52% had mothers of European ethnicity. 68.4% of the participants attended at least 1 research follow-up visit. Since 2008, 6.4% of the participants have submitted a withdrawal request. Key factors associated with research participation included child age, ethnicity, maternal age, maternal education level, family income, parental employment, child diagnosis of chronic health conditions, certain study sites, and missingness in questionnaire data. CONCLUSIONS: Socioeconomic status, demographic factors, chronic conditions, and missingness in questionnaire data were associated with research participation in this large primary care practice-based cohort study of children. Results from this analysis and input from our parent partners suggested that retention strategies could include continued parent engagement, creating brand identity and communication tools, using multiple languages and avoiding redundancy in the questionnaires.

Centre-based childcare in early childhood and growth in later childhood: a prospective cohort study.

BACKGROUND: Attending government-regulated centre-based childcare may influence important health behaviours including dietary quality, physical activity and routines related to child growth. However, the relationship between centre-based childcare and childhood obesity remains unclear. OBJECTIVES: The primary objective was to evaluate the association between centre-based childcare attendance in early childhood and body mass index z-score (zBMI) in later childhood. Secondary objectives included exploring whether family income, child sex, or non-centre-based setting modified these relationships. METHODS: A prospective cohort study of children aged 1 to 10 years who participated in the TARGet Kids! cohort was conducted. Linear mixed-effect modelling was used to evaluate the relationship between centre-based childcare attendance (in hours/week) compared to non-centre-based childcare between 1-4 years of age and zBMI between 4 and 10 years of age. Generalised estimating equation modelling was used to explore weight status categories. Models were adjusted for confounders and effect modification was explored. RESULTS: A total of 3503 children were included. Children who attended centre-based childcare full-time (40 h/week) had 0.11 (95% CI: -0.19, -0.03; p = 0.01) lower zBMI at 4 and 7 years of age and lower odds of overweight and obesity at 4 years (OR 0.78; 95% CI: 0.62, 0.97; p = 0.03), but no evidence of an association was found at 10 years of age. Children from families with income < $50,000CDN who attended centre-based childcare full-time had 0.32 (95% CI: -0.50, -0.14; p = 0.001) lower zBMI and lower odds of overweight and obesity (OR 0.52; 95% CI: 0.28, 0.99; p = 0.05) at 10 years of age. CONCLUSIONS: Attending centre-based childcare in early childhood was associated with a lower zBMI and odds of overweight and obesity in later childhood. These associations were stronger for children from lower income families. Centre-based childcare may be an early intervention for the prevention of childhood obesity. CLINICAL TRIAL: Clinical Trial Registry Number: NCT01869530 (clinicaltrials.gov).

Changes in Pediatric Movement Behaviors During the COVID-19 Pandemic by Stages of Lockdown in Ontario, Canada: A Longitudinal Cohort Study.

BACKGROUND: Children's movement behaviors have been affected by the COVID-19 pandemic; however, little is known regarding movement behavior patterns over time by government-issued lockdowns. Our primary objective was to evaluate how children's movement behaviors changed by stages of lockdown/reopening in Ontario, Canada, from 2020 to 2021. METHODS: A longitudinal cohort study with repeated measures of exposure and outcomes was conducted. The exposure variables were dates from before and during COVID-19 when child movement behavior questionnaires were completed. Lockdown/reopening dates were included as knot locations in the spline model. The outcomes were daily screen, physical activity, outdoor, and sleep time. RESULTS: A total of 589 children with 4805 observations were included (53.1% boys, 5.9 [2.6] y). On average, screen time increased during the first and second lockdowns and decreased during the second reopening. Physical activity and outdoor time increased during the first lockdown, decreased during the first reopening, and increased during the second reopening. Younger children (<5 y) had greater increases in screen time and lower increases in physical activity and outdoor time than older children (≥5 y). CONCLUSIONS: Policy makers should consider the impact of lockdowns on child movement behaviors, especially in younger children.

Paternal BMI in the preconception period, and the association with child zBMI.

BACKGROUND: Rapid growth and excess weight in early childhood are associated with obesity risk. While maternal preconception BMI has been identified as a potential risk factor, the role of paternal preconception BMI is less clear. OBJECTIVES: To examine the association between paternal preconception BMI and age- and sex-standardized WHO BMI z-score (zBMI) growth rates, zBMI, and weight status, in 0- to 10-year-old children. To determine whether these associations differed by child sex and maternal preconception weight status. METHODS: A longitudinal cohort study was conducted through The Applied Research Group for Kids (TARGet Kids!). Children (n = 218) underwent repeated measures of height and weight from birth to 10 years old. Piecewise linear mixed models were used to assess the association between paternal preconception BMI and child zBMI growth rates (zBMI SD units/month) between 0, 4, 30, 48 and 120 months of age. Linear mixed models were used to examine the association with child zBMI, and logistic generalized estimation equations (GEE) were used to assess the association with child weight status. Child sex and maternal preconception weight status were tested as effect modifiers. RESULTS: Paternal preconception BMI was associated with child zBMI growth rate, mean zBMI and weight status in boys, but not girls. A 5 kg/m2 higher paternal preconception BMI was associated with approximately 0.01 zBMI SD unit/month higher growth rate for boys born to mothers with preconception overweight. Higher paternal BMI was associated with higher mean zBMI and increased odds of overweight and obesity in boys, with greater effects seen when mothers had preconception overweight compared to normal weight. CONCLUSION: Paternal preconception BMI was associated with child zBMI growth rate, zBMI and weight status in boys, with greater effects when the biological mother had preconception overweight or obesity. Further understanding of sex differences in paternal preconception weight effects in children is needed.

Body Weight at Age Four Years and Readiness to Start School: A Prospective Cohort Study.

Background: Adolescents with obesity have lower academic performance, but little is known about the association between body weight in early childhood and school readiness. The objective was to examine the association between age- and sex-standardized body mass index (zBMI) and body weight status and school readiness in young children. Methods: A prospective cohort study in Toronto, Canada, was conducted in young children enrolled in TARGet Kids!. Children's weight and height were measured before the start of kindergarten. Children's school readiness was measured by the Early Development Instrument (EDI), a validated teacher-completed instrument that assesses children's skills and behaviors in five developmental domains in kindergarten. Generalized estimating equations, adjusted for relevant confounders, were used in the analysis. Results: The study included 1015 children (1217 observations): 52% were male and mean age at zBMI was 4.2 years [50 months (SD 12.1)] and school readiness was 5.2 years [62.7 months (SD 6.9)]. There was no evidence found that zBMI was associated with school readiness. However, in a post hoc analysis, being classified as overweight or with obesity in kindergarten was associated with twofold higher odds of vulnerability in school readiness and a lower social competence score compared with their normal weight peers. Conclusions: Being classified as overweight or with obesity was associated with poor school readiness in year 2 of kindergarten. Early interventions to promote healthy growth before school entry may help promote development and school readiness in young children. www.clinicaltrials.gov (NCT01869530).