Vitamin D supplementation and gross motor development: A 3-year follow-up of a randomized trial.

BACKGROUND: Vitamin D status during pregnancy, early childhood and season-at-birth are implicated in gross motor development (GMD). AIM: To test whether vitamin D intake in infancy and season-at-birth affect GMD in early childhood. STUDY DESIGN: 3-year follow up study of a single-center trial. SUBJECTS: Healthy infants (n = 116) were allocated to 400 (standard-of-care), 800 or 1200 IU/day of vitamin D3 supplementation from 1 to 12 months; n = 70 returned for follow-up at 3-years. OUTCOME MEASURES: The main outcome was GMD using the Peabody Developmental Motor Scales-2 which includes gross motor quotient (GMQ) and stationary, locomotion and object manipulation subtests. RESULTS: GMQ scores were normal (≥85) in 94 %. An interaction between dosage group and season-at-birth (p = 0.01) was observed for GMQ and stationary standardized score; among winter/spring born children, the 1200 IU/d scored higher vs. 400 and 800 IU/d groups. Object manipulation standardized score was higher (p = 0.04) in children in the 1200 vs. 400 IU/d group, without interaction with season-at-birth. CONCLUSIONS: GMD in young children who received 400 IU/d of supplemental vitamin D in infancy is not influenced by season-at-birth. This dose of vitamin D of 400 IU/d as recommended in North America adequately supports GMD. The modest enhancement in GMD with 1200 IU/d in winter/spring born children requires further study.

Survey of public library use in the Ambulatory Clinic in the Children's Hospital Winnipeg.

Introduction: Recent studies highlight synergies for families receiving early childhood literacy support from their health care provider and public library, with more reading at home and higher quality book-sharing interactions. Our primary objective was to determine the percentage of Children's Hospital Winnipeg Ambulatory Clinic's patients who had ever used a public library. The clinic has a longstanding early-childhood literacy program and serves remote communities and low-income Winnipeg families. Methods: A structured survey was administered to parents or legal guardians by the first author. It explored library barriers and covariates that might affect library use. Analysis included descriptive statistics and a logistic regression model for predictors of library use. Results: Ninety-seven nearly consecutive surveys were administered, half prior to the COVID-19 pandemic. Most respondents were female, from Winnipeg, and in the two lowest neighbourhood income quintiles. Roughly half (46.4%) of children had used a library. Most respondents wanted health care providers to promote literacy and provide information about public libraries, and more supported in-clinic distribution of books. The number of children per household positively predicted library use, possibly a proxy for experience with community resources. About 2/3 of respondents believed that library fines should be abolished. Most identified other barriers, for example, inconvenient hours, distance, or concerns about COVID-19. Conclusion: Less than half of surveyed families used public libraries, citing multiple barriers, including fines. Moreover, not all health care providers can offer new books and anticipatory guidance. Clinics that promote use of public libraries may therefore represent a low-cost, stand-alone alternative.

Patterns of Bone Mineral Accretion and Sex Differences in Healthy Term Vitamin D Replete and Breastfed Infants From Montreal, Canada: Bone Mass Reference Data.

Infancy is a period of rapid bone growth and mineral accretion; nonetheless, reference data remain scarce for this age group. The purpose of this report is to generate reference data for bone mass in breastfed vitamin D replete infants and investigate patterns of bone mineral accretion and sex differences. This is a secondary analysis from a double-blinded randomized controlled trial (NCT00381914). Healthy term breastfed (exclusively or mixed) infants were randomized to different doses of oral vitamin D supplementation (400-1600 IU/d) and followed prospectively from 1 to 12 mo. Plasma 25-hydroxyvitamin D (LC-MS/MS), bone mineral content (BMC; whole body (WB) and lumbar spine (LS)) and bone mineral density (BMD; LS) were measured at 1, 3, 6, 9, and 12 mo by dual-energy x-ray absorptiometry (Hologic Discovery 4500A) with no effect of supplementation on bone outcomes. For the purpose of this analysis, 63 infants with adequate plasma 25-hydroxyvitamin D ≥ 50 nmol/L at baseline, were included. Differences over time and between sexes were tested using mixed model repeated measures ANOVA. Infants (31 males, 32 females) were 39.5 ± 1.1 wk gestational age at birth and appropriate for gestational age. WB BMC, LS BMC, and LS BMD increased by 143.2%, 116.8%, and 31.1% respectively across infancy. WB BMC was higher (4.2% - 9.4%; p = 0.03) in males than in females across the study. After adjusting WB BMC for weight, length or head BMC, sex differences were not evident. LS BMC and LS BMD did not vary by sex. LS BMD growth charts for both sexes combined, were generated using LMS chartmaker. WB BMC more than doubles during the first year of life confirming the importance of skeletal growth and the need for age-specific reference data in infancy. Sex differences in BMC, if any, are mostly driven by differences in body size.

CYP24A1 and SLC34A1 Pathogenic Variants Are Uncommon in a Canadian Cohort of Children with Hypercalcemia or Hypercalciuria.

OBJECTIVES: Biallelic pathogenic variants in CYPA24A1 and SLC34A1 are causes of idiopathic infantile hypercalcemia. Pathogenic variants in both may also give rise to hypercalciuria with nephrocalcinosis or nephrolithiasis without previous hypercalcemia (renal group). Our objective was to examine the frequency of CYP24A1 or SLC34A1 variants in children with early hypercalcemia or late-onset hypercalciuria. METHOD: Forty-one children from 7 centers across Canada were recruited. Local investigations were undertaken. The serum was evaluated by liquid chromatography tandem-mass spectrometry for the ratio of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3, (25-OH-D3:24,25-(OH)2D3), an elevation pathognomonic for the loss of function of the CYP24A1 enzyme. Mutational analyses were undertaken. Family cascade screening was performed if pathogenic variants were detected in probands. RESULTS: Twenty-nine children had early-onset hypercalcemia; none had elevated 25-OH-D3:24,25-(OH)2D3 or variants. Interestingly, 2 of 12 in the renal group had elevated 25-OH-D3:24,25-(OH)2D3 and presented as preadolescents. In case 1, cascade testing revealed a sibling and parent with asymptomatic pathogenic variants in CYP24A1. Four CYP24A1 pathogenic variants were identified in these 2 probands: 3 have been described in European populations, and 1 is a rare variant in exon 7 (c931delC) that is likely pathogenic. No SLC34A1 pathogenic variants were detected. CONCLUSION: In Canada, pathogenic variants in CYP24A1 appear to manifest with late-onset hypercalciuria and its sequelae. The 25-OH-D3:24,25-(OH)2D3 ratio is an excellent tool for screening for biallelic pathogenic variants in CYP24A1. We confirm that cascade testing is important for these variants.

Prevalence of high blood pressure among Canadian Children: 2017 American Academy of Pediatrics guidelines with the Canadian Health Measures Survey.

BACKGROUND: We assess the impact of the 2017 American Academy of Pediatrics (AAP) guidelines on the prevalence of high blood pressure (BP) in generally healthy Canadian children and identify risk factors associated with high BP (elevated, stage 1, or stage 2 at a single visit). METHODS: A cohort of 7,387 children aged 6 to 18 years in the Canadian Health Measures Survey (CHMS, 2007 to 2015) had BPTru oscillometry with centiles and stages assigned using both the 2017 AAP guidelines and the 2004 Fourth Report from the National Institute of Health/National Heart Lung and Blood Institute (NIH/NHLBI). RESULTS: Although both shifted upwards significantly, mean population systolic BP and diastolic BP percentiles are now 24.2 (95% confidence interval: 23.3 to 25.2) and 46.4 (45.3 to 47.6). As a result, the population prevalence of high BP increased from 4.5% (3.9 to 5.2, NIH/NHLBI) to 5.8% (5.0 to 6.6, AAP), less than in US children measured by auscultation (14.2%, 13.4 to 15.0). Children with high BP were more likely to be overweight/obese, to be exposed to prenatal/household smoking, and to have hypertriglyceridemia, without differences in dietary salt, infant breastfeeding, neonatal hospitalizations, or exercise frequency. CONCLUSION: The 2017 AAP guidelines increase the prevalence of high BP in Canadian children; Canadian prevalence appears lower than in the USA. This may reflect differences in measurement methods or in the prevalence of childhood overweight/obesity between countries, that is, 31.1% (28.9 to 33.3) versus 40.6% (39.5 to 42.0), respectively. Those with high BP were more likely to have other cardiac risk factors, including overweight/obesity, prenatal/household smoking exposure, and hypertriglyceridemia.

Assessing childhood health outcome inequalities with area-based socioeconomic measures: a retrospective cross-sectional study using Manitoba population data.

BACKGROUND: Socioeconomic gradients in health exist in Canada. Although multiple Canadian area-based socioeconomic measures (ABSM) have been developed, none have been specifically validated against pediatric outcomes. Our objective was to compare the strength of association between key pediatric health outcomes and a number of ABSM, including income quintile. METHODS: This was a retrospective cross-sectional assessment of the association between socioeconomic status (SES) measured by ABSM and 20 specific pediatric health outcomes. Data from the Manitoba Population Research Data Repository were used for residents aged 0-19 years from 2010 to 2015. Outcomes included birth-related events (e.g. mortality), vaccination uptake, hospitalizations, and teen pregnancy. Regression goodness of fit was used to assess the strength of individual associations. Inequality was measured by slope index of inequality (SII) and relative index of inequality (RII). RESULTS: Overall, 19 of 20 outcomes had socioeconomic gradients identified by SII and RII. The multidimensional CAN-Marg indices had the best explanatory power in standard regression models. The simplest ABSM-income quintile-detected 16 of 19 confirmed inequalities, more than any other single measure. CONCLUSIONS: At all ages, many pediatric health outcomes in Manitoba were associated with significant socioeconomic inequalities; while income quintile detected most, CAN-Marg composite indices had the best explanatory power.

WHO height charts can be safely substituted when calculating BP Z-scores in a North American clinic setting.

OBJECTIVES: The Public Health Agency of Canada has officially adopted growth charts from the World Health Organization (WHO); nevertheless, North American blood pressure (BP) Z-scores and percentiles still depend on height Z-scores based on growth charts from the US Centers for Disease Control (CDC), which may differ significantly, particularly in toddlers. Since many practitioners simply replace CDC height scores with WHO equivalents for diagnosing hypertension, we explore the impact of this substitution on BP Z-scores in real-world BPs measured on more than 22,000 children aged 2 to 18 years. METHODS: We report agreement between two different measures of the same quantity as Bland-Altman limits of agreement (LOA). RESULTS: In toddlers aged 2 to 5 years, WHO height Z-scores are systematically lower with a bias (mean error) of -0.30 SD, and the 95% LOA range from -0.51 to -0.10 SD. Despite this difference, systolic BP Z-scores were nearly identical (bias = 0.06, LOA = 0.02 to 0.10). For older children and diastolic BP Z-scores, the errors were smaller still, and agreement was equally good for hypotensive, normotensive and hypertensive measurements. CONCLUSIONS: Clinicians may safely use WHO height charts when calculating BP Z-scores or percentiles against the National Institute of Health's National Heart, Lung, and Blood Institute reference data.

Prevalence and Severity of High Blood Pressure Among Children Based on the 2017 American Academy of Pediatrics Guidelines.

Importance: Based on the new 2017 blood pressure guidelines, the prevalence of high blood pressure (BP) among adults has increased from 32% to 46%. Based on new norms and diagnostic thresholds that better align with adult definitions, new clinical practice guidelines were also published for children. The American Academy of Pediatrics clinical practice guidelines for the management of elevated BP in children replace the 2004 fourth report from the National Heart, Lung, and Blood Institute. Objectives: To assess the consequences of the American Academy of Pediatrics clinical practice guidelines for the management of elevated BP in children on the prevalence and severity of elevated BP among children and to characterize risk factors for children with new-onset hypertension or a worsening in clinical stage ("reclassified upward"). Design, Setting, and Participants: This study applied both sets of guidelines to classify BP in 15 647 generally healthy, low-risk children aged 5 to 18 years from National Health and Nutrition Examination Surveys (from January 1, 1999, to December 31, 2014). In the case-control portion of the study, children whose BP was reclassified upward (cases) were matched for sex, age, and height with controls with normal BP. Anthropometric and laboratory risk factors were compared, and age- and sex-specific z scores for weight, waist circumference, and body mass index were calculated. Blood pressure was measured by auscultation by trained personnel. After the child rested quietly for 5 minutes, 3 to 4 consecutive BP readings were recorded. Main Outcomes and Measures: Blood pressure percentiles and clinical classification based on either the 2017 American Academy of Pediatrics guidelines or the 2004 National Heart, Lung, and Blood Institute report. Results: Among the 15 647 children in the study (7799 girls and 7848 boys; mean [SD] age, 13.4 [2.8] years), based on the American Academy of Pediatrics guidelines, the estimated (weighted) population prevalence of elevated BP increased from 11.8% (95% CI, 11.1%-13.0%) to 14.2% (95% CI, 13.4%-15.0%). Overall, 905 of 15 584 children (5.8%) had newly diagnosed hypertension (n = 381) or a worsening in clinical stage (n = 524), which represents a substantial increase in disease burden for the health care system. Children whose BP was reclassified upward were more likely to be overweight or obese, with higher z scores for weight, waist circumference, and body mass index. The prevalence of abnormal laboratory test results was also increased, with adverse lipid profiles and increased hemoglobin A1c levels (prediabetes). Conclusions and Relevance: Clustering of cardiovascular risk factors in otherwise healthy US children suggests that those whose BP was reclassified represent a high-risk population whose cardiovascular risk may previously have been underestimated.

Assessment of pedometer accuracy in capturing habitual types of physical activities in overweight and obese children.

BACKGROUND: Currently, there is a limited amount of research exploring physical activity measurement tools in overweight and obese (OW/OB) children using pedometers. Thus, our objective was to determine the accuracy of one spring-levered (SC-T2) and two piezoelectric pedometers (NL-1000 and Piezo) in OW/OB children. METHODS: A total of 26 boys and 34 girls (n = 60) participated. Pedometer step-counts were compared to observed step counts for walking (walking, stair ascent and decent) and hopping tests. Pedometer accuracies were compared with Friedman tests while Bland-Altman plots were used to establish the accuracy of each pedometer against direct observations. RESULTS: Boys (n = 26) and females (n = 34) were 96 and 91% OB, respectively. The two piezoelectric pedometers (NL-1000 and Piezo) were accurate for walking and stair climbing tasks, however all pedometers were inaccurate for hopping tests. Averaged over all three walking activities, the NL-1000 was the most accurate with 6.7% median error (interquartile range (IQR): 0.0-13.3); followed by the Piezo with 10.0% median error (IQR: 3.3-18.1); SC-T2 was the least accurate with -14.7% median error (IQR: -54.8-3.5). CONCLUSION: These results support the use of the piezoelectric pedometers for walking and stair climbing types of activities, which are typical for OW/OB children in a nonlaboratory setting.

LMS tables for waist-circumference and waist-height ratio Z-scores in children aged 5-19 y in NHANES III: association with cardio-metabolic risks.

BACKGROUND: In adults, anthropometric measures of central adiposity, such as waist-height ratio (WHtR) and waist circumference (WC), are more strongly associated with cardio-metabolic risks than BMI. METHODS: To provide similar quantitative tools for North American children, we created smoothed centile charts and LMS tables for WHtR and WC based on data from the US National Health and Nutrition Survey, cycle III (NHANES III, N = 11,930 aged 2-24 y 1988-1994). RESULTS: Applying these reference charts to subsequent NHANES survey cycles, 1999-2012) demonstrated a significant mean increase in both Z-scores of approximately 0.30 SD. In measuring the strength of the association between anthropometric measures and cardio-metabolic risk factors, a unit change in Z-scores for WHtR, WC, and BMI significantly increased the odds of an adverse outcome in all cases (1.18-2.03, P < 0.0001). Z-scores for both measures of central adiposity were significantly more strongly associated with cardio-metabolic comorbidities than BMI-Z. CONCLUSION: Since Z-scores permit standardized comparisons across ages and genders, they are useful measures of central adiposity in both clinical or research settings. By providing LMS tables for children and adolescents based on North American reference data, we hope to provide quantitative tools for the study of obesity and its complications.

Vitamin D status is associated with bone mineral density and bone mineral content in preschool-aged children.

This study examined the associations between vitamin D status, bone mineral content (BMC), areal bone mineral density (aBMD), and markers of calcium homeostasis in preschool-aged children. Children (n=488; age range: 1.8-6.0 y) were randomly recruited from Montreal. The distal forearm was scanned using a peripheral dual-energy X-ray absorptiometry scanner (Lunar PIXI; GE Healthcare, Fairfield, CT). A subset (n=81) had clinical dual-energy X-ray absorptiometry (cDXA) scans (Hologic 4500A Discovery Series) of lumbar spine (LS) 1-4, whole body, and ultradistal forearm. All were assessed for plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations (Liaison; Diasorin), ionized calcium (ABL80 FLEX; Radiometer Medical A/S), and dietary vitamin D and calcium intakes by survey. Age (p<0.001) and weight-for-age Z-score (p<0.001) were positively associated with BMC and aBMD in all regression models, whereas male sex contributed positively to forearm BMC and aBMD. Having a 25(OH)D concentration of >75 nmol/L positively associated with forearm and whole body BMC and aBMD (p<0.036). Sun index related to (p<0.029) cDXA forearm and LS 1-4 BMC and whole-body aBMD. Nutrient intakes did not relate to BMC or aBMD. In conclusion, higher vitamin D status is linked to higher BMC and aBMD of forearm and whole body in preschool-aged children.

Osteocalcin, but not deoxypyridinoline, increases in response to isoflurane-induced anaesthesia in young female guinea pigs.

The effect of the inhaled anaesthetic isoflurane was investigated on bone biomarkers, both during maturation and on minerals and glucose postpartum. Female guinea pigs (n = 10) were anaesthetized during maturation (5 and 9 weeks) and postpartum (26 weeks of age) with isoflurane during dual-energy X-ray absorptiometry scanning. Blood collection was performed at all ages before and after anaesthesia for measurement of plasma osteocalcin (OC), total deoxypyridinoline (tDPD), and cortisol. Postpartum measurements also included: blood ions, acid-base parameters and glucose, plasma minerals, total alkaline phosphatase (tALP), and albumin. Plasma OC concentration almost doubled after exposure to isoflurane at 5 weeks (30.1 ± 5.0-57.9 ± 11.2 nmol/L, p < 0.001) and at 9 weeks (29.1 ± 7.5-62.9 ± 15.9 nmol/L, p < 0.001), but did not change postpartum (3.7 ± 3.3-4.3 ± 3.9 nmol/L, p = 0.88). There was no effect of isoflurane exposure on plasma tDPD at any age. Plasma cortisol increased after exposure to isoflurane at 9 weeks (1859.6 ± 383.2-2748.0 ± 235.3 nmol/L, p < 0.01) and postpartum (3376.7 ± 322.2-4091.6 ± 195.6 nmol/L, p < 0.001) but not at 5 weeks (2088.3 ± 326.4-2464.1 ± 538.0 nmol/L, p > 0.05). Blood ionized Ca(2+), Na(+) and plasma total Ca did not change, whereas plasma albumin decreased, and inorganic phosphate (PO4) and Cl(-) increased upon exposure to isoflurane. Isoflurane decreased tALP (43.2 ± 6.6-40.2 ± 5.9 IU/L, p = 0.01) and increased glucose (7.5 ± 0.6-10.9 ± 1.7 mmol/L, p < 0.0001) postpartum. Isoflurane inflates the assessment of a bone-derived biomarker, OC, during rapid growth, but not following pregnancy when formation is very low. Measurements prior to anaesthesia are recommended to reflect normal metabolism.

High vitamin D status before conception, but not during pregnancy, is inversely associated with maternal gestational diabetes mellitus in guinea pigs.

BACKGROUND: Whether there is a dose-dependent effect of maternal dietary cholecalciferol during pregnancy on maternal glucose tolerance is unknown. In addition, circulating osteocalcin is increased by 1,25-dihydroxyvitamin D [1,25(OH)2D] and may improve glucose homeostasis. OBJECTIVE: This study was designed to test whether dietary cholecalciferol during pregnancy dose-dependently affects maternal glucose tolerance and maternal and neonatal glucose concentrations in relation to plasma osteocalcin and body composition. METHODS: Female guinea pigs (n = 45; 4 mo old) were randomly assigned to 5 doses of cholecalciferol (0, 0.25, 0.5, 1, or 2 IU/g diet) fed from mating to delivery. Plasma vitamin D metabolites, minerals, and osteocalcin, and blood glucose were measured before mating, at midgestation (day 42), and at day 2 postpartum in sows and in 2-d-old pups. At day 50 of pregnancy (early third trimester), a 3-h oral-glucose-tolerance test (OGTT) (2 g/kg) was conducted. Body composition was measured before mating and at day 2 postpartum in sows and in pups. RESULTS: A positive dose-response to dietary cholecalciferol was observed for change in maternal plasma 25-hydroxyvitamin D [25(OH)D] through pregnancy (P < 0.0001), with 1,25(OH)2D increasing by 198% in the 1-IU/g group by midgestation vs. a reduction of 43.6% in the 0-IU/g group (P = 0.05). Twenty-four (54.5%) sows had gestational diabetes mellitus (GDM) on the basis of nonfed glucose and 39 (88.6%) had GDM on the basis of 2-h OGTT glucose concentrations. There were no group differences in maternal OGTT or changes in glucose, minerals, osteocalcin concentrations, and body composition. Pre-mating 25(OH)D was inversely related to 3-h area under the curve for blood glucose from the OGTT (r = -0.31, P = 0.05). In guinea pig pups, although both 25(OH)D (P < 0.0001) and 1,25(OH)2D (P < 0.0001) followed a dose-response to maternal diet, glucose, osteocalcin, minerals, and body composition were not altered. CONCLUSIONS: Dietary vitamin D intake during pregnancy in guinea pigs does not affect the already high rate of GDM, whereas higher prepregnancy vitamin D status appears to be protective.

Dietary vitamin D during pregnancy has dose-dependent effects on long bone density and architecture in guinea pig offspring but not the sows.

BACKGROUND: The effects of vitamin D during pregnancy on maternal and neonatal bone health remain unclear. OBJECTIVE: This study was designed to test whether dietary vitamin D dose-dependently affects maternal and neonatal bone health. METHODS: Female guinea pigs (n = 45; 4 mo old) were randomly assigned at mating to receive 1 of 5 doses of vitamin D3 (cholecalciferol; 0, 0.25, 0.5, 1, or 2 IU/g diet) throughout pregnancy. Plasma vitamin D metabolites, mineral homeostasis, bone biomarkers, and bone mass were tested in sows throughout pregnancy and in 2-d-old pups. Microarchitecture and histology of excised bone were conducted postpartum. RESULTS: By 3 wk of pregnancy, plasma 25-hydroxyvitamin D [25(OH)D] followed a positive dose-response, whereas 1,25-dihydroxyvitamin D [1,25(OH)2D] reached a plateau if vitamin D was ≥0.5 IU/g diet. Weight gain, areal bone mineral density (aBMD), volumetic bone mineral density (vBMD), and bone biomarkers did not differ among maternal groups. A positive dose-response was observed for mean ± SEM pup plasma concentrations of 25(OH)D (10.5 ± 1.50 to 113 ±11.6 nmol/L) and 1,25(OH)2D (123 ± 13.8 to 544 ± 53.3 pmol/L). Pup weight, plasma minerals, and osteocalcin were not different; plasma deoxypyridinoline was lower in the 1- and 0.25-IU/g groups than in all other groups. Pup femur aBMD was higher (9.2-13%; P = 0.04) in the 2-IU/g group than in all other groups except for the 0-IU/g group. Tibia and femur vBMD of pups responded to maternal diet in a U-shaped pattern. The femoral growth plate was 7.9% wider in the 0-IU/g group than in the 1-IU/g group. CONCLUSIONS: Maternal vitamin D supplementation dose-dependently altered pup long bone architecture and mineral density in a manner similar to vitamin D deficient rickets whereas maternal bone was stable. These data reinforce that inadequate maternal vitamin D intake may compromise neonatal bone health and that exceeding recommendations is not advantageous.

Osteocalcin is higher across pregnancy in Caucasian women with gestational diabetes mellitus.

OBJECTIVE: The purpose of this study was to investigate circulating concentrations of osteocalcin, a bone-derived protein, while accounting for 25-hydroxyvitamin D (25(OH)D) throughout pregnancy, and whether early gestation concentrations and changes in osteocalcin predict the subsequent diagnosis of gestational diabetes mellitus (GDM). METHODS: This was a nested case-control study involving 48 GDM and 48 control pregnant Caucasian women (matched for age, season of conception, pre-pregnancy body mass index and pregnancy length). Maternal serum osteocalcin was measured by enzyme-linked immunosorbent assay and 25(OH)D by chemiluminescence throughout pregnancy (11-13 weeks, 24-28 weeks and predelivery). Differences between groups were compared by mixed model analysis of variance. Predictors of diagnosis of GDM were explored using generalized estimating equation models. Neonatal general health outcomes were also compared between groups. RESULTS: Serum osteocalcin was higher across pregnancy (p=0.006) in women with GDM vs. controls, whereas serum 25(OH)D was not different (p=0.80). Both biomarkers increased with time across pregnancy (p<0.0001). However, serum osteocalcin during early pregnancy and changes in its concentration from early to mid gestation did not predict the development of GDM. There were no significant differences in anthropometry and APGAR (appearance, pulse, grimace, activity, respiration) scores in neonates of controls and cases. CONCLUSIONS: Serum osteocalcin is elevated in Caucasian women with GDM throughout pregnancy, but was not predictive of the onset of GDM. Larger trials evaluating the role of osteocalcin and the development of GDM appear warranted.

Normative data and predictors of leg muscle function and postural control in children.

INTRODUCTION: At the present there are limited tools available to measure muscle function in young children. Ground reaction force plates measure lower-body function and postural control in older children and adults. The purpose of this study was threefold: 1) develop normative data for evaluating global muscle development; 2) determine the reproducibility of ground reaction force plates for assessing muscle function in preschool-age children; and 3) identify predictors of skeletal muscle function. METHODS: Children's (n = 81, 1.8 to 6.0 yr; M = 52%) muscle function and postural control was measured for jump (JMP), sit-to-stand (STS), and both undistracted and distracted body sway tests using a ground reaction force plate (Kistler 9200A). Whole body composition used dual-energy x-ray absorptiometry (Hologic 4500A Discovery Series). Plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations were measured by chemiluminescence (Liaison, Diasorin, Mississauga, ON, Canada) as well as ionized calcium (ABL80 FLEX, Radiometer Medical A/S). Demographics, and anthropometry were collected. ANOVA and linear regression were used to identify predictors. Reproducibility was assessed by intersubject coefficient of variation. RESULTS: Age was a consistent predictor in all models; body size or fat and lean mass were important predictors in 3 of the models - STS peak force, STS peak power, and JMP peak power. STS was the most reproducible maneuver (average coefficient of variation =15.7%). Distracted body sway testing was not appropriate in these youngsters. CONCLUSION: The novel data presented in this study demonstrate a clear age (developmental) effect without any effect of sex on muscle function and postural control in young children. Lean muscle mass was important in some models (STS peak force and JMP peak power). The STS test was the best of the 4 maneuvers.

A family-centered lifestyle intervention to improve body composition and bone mass in overweight and obese children 6 through 8 years: a randomized controlled trial study protocol.

BACKGROUND: Childhood obesity gives rise to health complications including impaired musculoskeletal development that associates with increased risk of fractures. Prevention and treatment programs should focus on nutrition education, increasing physical activity (PA), reducing sedentary behaviours, and should monitor bone mass as a component of body composition. To ensure lifestyle changes are sustained in the home environment, programs need to be family-centered. To date, no study has reported on a family-centered lifestyle intervention for obese children that aims to not only ameliorate adiposity, but also support increases in bone and lean muscle mass. Furthermore, it is unknown if programs of such nature can also favorably change eating and activity behaviors. The aim of this study is to determine the effects of a 1 y family-centered lifestyle intervention, focused on both nutrient dense foods including increased intakes of milk and alternatives, plus total and weight-bearing PA, on body composition and bone mass in overweight or obese children. METHODS/DESIGN: The study design is a randomized controlled trial for overweight or obese children (6-8 y). Participants are randomized to control, standard treatment (StTx) or modified treatment (ModTx). This study is family-centred and includes individualized counselling sessions on nutrition, PA and sedentary behaviors occurring 4 weeks after baseline for 5 months, then at the end of month 8. The control group receives counselling at the end of the study. All groups are measured at baseline and every 3 months for the primary outcome of changes in body mass index Z-scores. At each visit blood is drawn and children complete a researcher-administered behavior questionnaire and muscle function testing. Changes from baseline to 12 months in body fat (% and mass), waist circumference, lean body mass, bone (mineral content, mineral density, size and volumetric density), dietary intake, self-reported PA and sedentary behaviour are examined. DISCUSSION: This family-centered theory-based study permits for biochemical and physiological assessments. This trial will assess the effectiveness of the intervention at changing lifestyle behaviours by decreasing adiposity while enhancing lean and bone mass. If successful, the intervention proposed offers new insights for the management or treatment of childhood obesity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01290016.

Bone mineral density measured by a portable X-ray device agrees with dual-energy X-ray absorptiometry at forearm in preschool aged children.

Dual-energy X-ray absorptiometry (DXA) measures of bone mineral density (BMD) are generally not feasible in fieldwork. The present study determined the agreement between BMD measured by DXA and portable peripheral DXA in preschool aged children. Fifty-seven children (4.2 ± 1.0 yr) had their nondominant distal forearm scanned using a peripheral DXA scanner (PIXI; GE Medical Systems Lunar, Madison, WI) at their daycare and a DXA (4500A Discovery Series; Hologic Inc., Bedford, MA) at our research clinic. Correlation analysis, one-way analysis of variance, and Bland-Altman plots were performed to examine the agreement between measurements. Data were also divided into tertiles for cross-classification analysis and calculation of kappa coefficients. Distal forearm BMD measured by PIXI was significantly correlated with DXA measures of total forearm BMD (r > 0.51; p < 0.001), proximal 1/3 BMD (r > 0.41; p < 0.001), mid-BMD (r > 0.37; p < 0.001), and ultradistal (UD) BMD (r > 0.57; p < 0.001). Cross-classification in the same or adjacent tertile between measures (UD forearm: 96.5%; UD radius: 94.4%; total forearm: 87.7%; total radius: 84.2%) resulted in weighted kappa coefficients of 0.46, 0.58, 0.42, and 0.43, respectively. Bland-Altman plots further clarified these agreements as all had low bias (UD forearm: bias = 0.003 ± 0.002; UD radius: -0.015 ± 0.021; total forearm: -0.062 ± 0.027; total radius: -0.077 ± 0.026). These results demonstrate that portable DXA measures of forearm BMD agree moderately with DXA.

Glycogen storage disease type III in Inuit children.

Glycogen storage disease type III (GSD III) was diagnosed in 4 Inuit children (3 confirmed, 1 suspected case) at our institution over the last decade. This rare autosomal recessive disease, which results from a deficiency of the debranching enzyme required for complete degradation of the glycogen molecule, has not been previously described in this population. The possible clinical presentations are heterogeneous, as is the spectrum of severity of this disease. The long-term sequelae can be severe, including recurrent hypoglycemia, hepatic cirrhosis and progressive muscle weakness. These 4 cases would suggest an increased prevalence of GSD III in the Inuit population. Therefore, it is important for health care providers caring for this population to consider and recognize this rare but serious disease.

Osteopenia and fractures in cystinotic children post renal transplantation.

Many of the end-organ effects of cystinosis are known to be risk factors for osteopenia; these include deposition of cystine crystals in bone, hypothyroidism, diabetes mellitus, primary hypogonadism, urinary phosphate wasting, and chronic renal failure. While transplantation may correct the latter, it exposes the child to other risk factors for diminished bone mass, notably the use of high-dose glucocorticoids. Our objective was to determine if these multiple risk factors translate into an increased occurrence of osteopenia, as measured by dual-energy X-ray absorptiometry (DEXA), and/or fractures in this population. We examined the charts, X-rays, and bone mineral density (BMD) of all cystinotic patients post renal transplant for whom this information was available. Lumbar spine BMD was measured by DEXA scan (Hologic 4500). Z-scores were corrected for growth parameters using previously published reference data. Fracture history and pertinent serum markers of bone metabolism were also analyzed. Of the 63 renal transplants performed at our institution, 11 children were transplanted due to cystinosis. Nine of these patients, 5 male and 4 female, had had BMD evaluations, with an average age of 14.3 years (range 5-17 years) at the time of initial BMD post transplant. The mean interval between transplant and BMD evaluation was 39 months (range 3-90 months). Surprisingly, 7 of 9 patients had normal uncorrected BMD values (z-scores -1.92 to +0.02) and 7 of 9 patients had normal corrected values (z-scores -1.20 to +1.93). Three patients suffered from a total of eight fractures. Of the 3 fracture patients, 2 had normal BMD. All patients maintained good graft function and had normal calcium/phosphate mineral status. Of note, 3 of 5 male patients had evidence of primary testicular failure at earlier ages than often described, and this may be an unrecognized risk factor for bone disease in this population. Despite the numerous risk factors for developing osteopenia, these results suggest that the majority of cystinotic patients post renal transplant do not experience reduced bone mineral content as measured by DEXA. However, the significant fracture history among these patients demonstrates that DEXA cannot be used to assess fracture risk in patients with nephropathic cystinosis.