The Clinical Definition of Children With Medical Complexity: A Modified Delphi Study.

BACKGROUND AND OBJECTIVES: Children with medical complexity (CMC) comprise a subgroup of children with severe chronic diseases. A conceptual definition for CMC has been formulated, but there is no agreement on criteria to fulfill each of the 4 proposed domains: diagnostic conditions, functional limitations, health care use, and family-identified needs. Our objective with this study was to identify a standardized definition of CMC. METHODS: Through a scoping review of the CMC literature, we identified potential criteria to fulfill each domain. These were incorporated into an electronic survey that was completed by a geographic and professionally varied panel of 81 American and Canadian respondents with expertise in managing CMC (response rate 70%) as part of a 4-iteration Delphi procedure. Respondents were asked to vote for the inclusion of each criterion in the definition, and for those with quantitative components (eg, hospitalization rates), to generate a consensus threshold value for meeting that criterion. The final criteria were analyzed by a committee and collapsed when situations of redundancy arose. RESULTS: Of 1411 studies considered, 132 informed 55 criteria for the initial survey, which was presented to 81 respondents. Consensus for inclusion was reached on 48 criteria and for exclusion on 1 criterion. The committee collapsed those 48 criteria into 39 final criteria, 1 for diagnostic conditions, 2 for functional limitations, 13 for health care use, and 23 for family needs. CONCLUSIONS: These results represent the first consensus-based, standardized definition of CMC. Standardized identification is needed to advance understanding of their epidemiology and outcomes, as well as to rigorously study treatment strategies and care models.

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy.

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (-1.09 ± 1.53 versus -1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (-0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (-1.77 ± 1.22) compared to those without (-1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip -0.98 ± 0.95 versus -0.28 ± 1.06, p = 0.010; TB -1.36 ± 1.10 versus -0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15-2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02-4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Changes in Adiposity without Impacting Bone Health in Nine- to Twelve-Year-Old Children with Overweight and Obesity after a One-Year Family-Centered Lifestyle Behavior Intervention.

Background: Few family-centered lifestyle interventions (FCLIs) for children with overweight or obesity (OW/OB) have assessed regional adiposity and bone health. This study assessed changes in adiposity in 9- to 12-year olds with OW/OB in a 1-year FCLI. Methods: Children were randomized to FCLI (six registered dietitian-led sessions) or no intervention (Control, CTRL). The FCLI focused on physical activity, nutrition education, and behavioral counseling children with families present. Assessments occurred at baseline and every 3 months for 1 year to assess changes in waist circumference (WC), body mass index for age-and-sex Z-scores (BAZ), body composition (dual-energy x-ray absorptiometry), and cardiometabolic biomarkers. Mixed models were used to determine the effects of group and time or group-by-time interactions for all outcomes. Results: Sixty children (age: 11.1 ± 1.1 years, BAZ: 2.7 ± 0.6) were enrolled; 55 participants (n = 28 CTRL, n = 27 FCLI) completed the study. There were no between group differences from baseline to follow-up for any measure. The FCLI group had significant decreases in BAZ over 12 months (-0.18 ± 0.27, p = 0.03) but not CTRL (-0.05 ± 0.32, p = 0.92). WC and android fat mass did not change in FCLI (p > 0.20) but increased in CTRL (p < 0.02). Whole body bone area, content, and areal bone mineral density (aBMD) increased in both groups (p < 0.010); whole body aBMD Z-score decreased by 5.8% and 1.6% in CTRL and FCLI, respectively (p < 0.001). There were no significant within group changes in biomarkers. Conclusion: The FCLI resulted in small reductions in BAZ and a plateau in android fat mass, which suggest that FCLIs are suitable as an intervention for 9- to 12-year-old children with OW/OB. Clinical Trial Registration number: NCT01290016.

Improvement in Serum Vitamin D Following Dental Rehabilitation to Treat Severe Early Childhood Caries.

Purpose: The purpose of this study was to investigate changes in 25-hydroxyvitamin D (25(OH)D) levels in children with severe early childhood caries (S-ECC) following rehabilitative surgery using general anesthesia (GA). Methods: Children with S-ECC were recruited on the day of surgery for a prospective study investigating changes in nutritional status and well-being before and after surgery. Venipunctures for 25(OH)D were performed while children were in the operating room, and parents completed a questionnaire regarding nutritional intake, oral health, quality of life, and family demographics. Participants returned at a minimum of three months for a follow-up venipuncture, questionnaire, and dental examination. Analyses included descriptive, bivariate, and multivariable regression analyses. A P-value of ≤ 0.05 was significant. Results: Overall, 150 children participated, with a mean age of 47.7±14.1 months. The mean baseline 25(OH)D concentration was 49.8±16.9 nmol/L, with 17 percent having deficient levels. Overall, 106 returned for follow-up. Paired t-tests revealed significant improvements in the mean 25(OH)D levels following rehabilitation (50.1±17.1 nmol/L versus 61.2±18.7, P<0.001). The proportion with optimal and adequate 25(OH)D levels increased from 9.2 percent to 24.1 percent and from 48.3 percent to 67.8 percent, respectively, while those classified as deficient decreased from 17.2 percent to 8.1 percent from baseline to follow-up. Conclusions: Significant improvements in vitamin D concentrations were observed following dental rehabilitation. This provides additional evidence of the association between oral health and nutritional status.

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.

Evaluating and optimizing bone health in children with chronic health conditions.

Paediatric health care providers (HCPs) play an important role in optimizing bone health. Early intervention is essential to maximize the accrual of peak bone mass in adolescence and young adulthood and to reduce osteoporosis and fracture risk later in life. Children and adolescents with chronic health conditions may have several risk factors for poor bone health, including underlying inflammatory conditions, reduced weight-bearing activity, delayed puberty, and inadequate intake of calcium and vitamin D. Some medications-particularly glucocorticoids-can compromise bone mass and place a child at risk for fragility fractures. This practice point describes a targeted approach to identifying bone health risk factors in children and youth with chronic health conditions, highlights office initiatives aimed at optimizing bone mass accrual, and links HCPs to useful web-based tools and medical references. Indications for referral to a bone health specialist and bone-specific pharmacotherapeutic interventions are also reviewed.

L'évaluation et l'optimisation de la santé osseuse chez les enfants ayant des affections chroniques.

Les professionnels de la santé des enfants jouent un rôle important dans l'optimisation de la santé osseuse. Il est essentiel d'intervenir rapidement pour maximiser le pic de masse osseuse à l'adolescence et au début de l'âge adulte et d'ainsi réduire le risque d'ostéoporose et de fractures plus tard dans la vie. Les enfants et les adolescents ayant une affection chronique peuvent présenter plusieurs facteurs de risque de mauvaise santé osseuse, notamment des maladies inflammatoires sous-jacentes, des activités avec mise en charge limitées, un retard pubertaire et un apport insuffisant de calcium et de vitamine D. Certains médicaments, et particulièrement les glucocorticoïdes, peuvent compromettre la masse osseuse et exposer l'enfant à un risque de fractures de fragilisation. Le présent point de pratique décrit une approche ciblée pour déterminer les facteurs de risque liés à la santé osseuse chez les enfants et les adolescents ayant une affection chronique, expose les mesures à prendre en cabinet pour optimiser l'acquisition de la masse osseuse et propose des outils en ligne utiles et des références médicales à l'intention des professionnels de la santé des enfants. Les indications pour diriger les patients vers un spécialiste de la santé osseuse et pour procéder à des interventions pharmacologiques visant les os sont également abordées.

Comparison of Socioeconomic Disparities in Pump Uptake Among Children With Type 1 Diabetes in 2 Canadian Provinces With Different Payment Models.

Importance: Insulin pumps improve glycemic control and quality of life in children with type 1 diabetes (T1D). Canada's provinces have implemented universal pediatric programs to improve access. However, these programs provide differing financial coverage, allowing for unique cross-jurisdictional comparisons. Objective: To evaluate possible socioeconomic status (SES) disparities in pump uptake in Québec, where pumps are fully funded, with those in Manitoba, where pumps are partially funded. Design, Setting, and Participants: Using health administrative databases and a clinical registry, parallel, population-based cohort studies of children with diabetes were conducted from April 1, 2011, in Québec, and April 1, 2012, in Manitoba, until March 31, 2017. In analysis conducted from July 1, 2019, to November 30, 2021, multivariable Cox proportional hazards regression models were applied to study the association between pump uptake and SES, defined using validated area-based material and social deprivation indices. Children aged 1 to 17 years with T1D were identified using a validated definition in administrative data (Québec) and a clinical registry (Manitoba). Those using pumps before the initiation of provincial programs were excluded. Exposures: Socioeconomic status. Main Outcomes and Measures: Insulin pump uptake. Results: A total of 2919 children with T1D were identified in Québec: 1550 male (53.1%), mean (SD) age at diagnosis, 8.3 (4.4) years, and 1067 (36.6%) were using a pump. In Manitoba, 636 children were identified: 364 male (57.2%), mean (SD) age at diagnosis, 8.8 (4.4) years, and 106 (16.7%) were using a pump. In Québec, the mean age at diagnosis of T1D was lower in children using the pump compared with those not using a pump (7.6 [4.1] vs 8.7 [4.5] years); sex distribution was similar (562 [52.7%] vs 988 [53.3%] male). No differences in mean (SD) age at diagnosis (8.8 [4.4] vs 8.8 [4.3] years) or sex (57 [53.8%] vs 307 [57.9%] male) were noted in both groups in Manitoba. Increasing material deprivation was associated with decreased pump uptake in both Québec (adjusted hazard ratio [aHR] 0.89; 95% CI, 0.85-0.93) and Manitoba (aHR, 0.70; 95% CI, 0.60-0.82). Inclusion of ethnic concentration did not change this association. Socioeconomic disparities in pump uptake were greater in Manitoba than Québec (P = .006 by t test; Cochran Q, 8.15; P = .004; I2 = 87.7%; 95% CI, 52.5%-96.8%). Conclusions and Relevance: The results of this study suggest that the program of full coverage for pumps available in Québec partially mitigates observed SES disparities in uptake and may be a model to improve access for all children with T1D.

Improvement in Iron and Iron-Related Nutritional Status Following Pediatric Dental Surgery To Treat Severe Early Childhood Caries.

Purpose: To investigate improvement in iron and iron-related nutritional status of children with severe-early childhood caries (S-ECC) following dental rehabilitation under general anesthesia (GA). Methods: Children with S-ECC were recruited into a prospective study investigating changes in nutritional status before and after surgery. Parents completed a questionnaire, as their child had a venipuncture while under GA. Children returned for follow-up at a minimum of three months postsurgery, and parents completed a follow-up questionnaire and their child had an additional venipuncture and dental examination. Statistical analyses included descriptive, bivariate, and multivariable regression analyses. Results: A total of 150 children participated (mean age 47.7±14.1 months). The mean baseline ferritin concentration was 27.9±19.1 µg/L, while mean iron and hemoglobin levels were 12.3±4.3 µmol/L and 107.5±9.2 g/L, respectively. Overall, 53 percent were anemic, 30 percent had iron deficiency (ID), and 20 percent had iron deficiency anemia (IDA) at baseline. In total, 106 participants returned for follow-up. Paired t-tests revealed significant improvements in ferritin (27.0±18.4 µg/L versus 34.3±18.2 µg/L, P<0.001) and hemoglobin (108.2±8.3 g/L versus 123.7±9.4 g/L, P<0.001) levels. There was a 16 percent reduction in children with ID (P<0.001) and a 20 percent reduction in children experiencing IDA (P=0.011) from baseline to follow-up. Multivariable regression revealed that follow-up ferritin levels were associated with baseline ferritin concentrations, red meat intake, and difficulty purchasing food because of cost. Conclusions: Improvements in iron and iron-related nutritional status were observed post GA. Dental surgery for S-ECC may contribute to improved children's eating practices and resolve oral inflammation, thus leading to better nutritional status.

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.

A Validated Risk Prediction Model for Bone Fragility in Children With Acute Lymphoblastic Leukemia.

Although bone fragility may already be present at diagnosis of pediatric acute lymphoblastic leukemia (ALL), routine performance of dual-energy X-ray absorptiometry (DXA) in every child is not universally feasible. The aim of this study was to develop and validate a risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤ -2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation. Children with ALL (4-18 years), treated according to the Dutch Childhood Oncology Group protocol (DCOG-ALL9; model development; n = 249) and children from the Canadian Steroid-Associated Osteoporosis in the Pediatric Population cohort (STOPP; validation; n = 99) were included in this study. Multivariable logistic regression analyses were used to develop the prediction model and to confirm the association of low LS BMD at diagnosis with symptomatic fractures during and shortly after cessation of ALL treatment. The area under the receiver operating characteristic curve (AUC) was used to assess model performance. The prediction model for low LS BMD at diagnosis using weight (ß = -0.70) and age (ß = -0.10) at diagnosis revealed an AUC of 0.71 (95% CI, 0.63-0.78) in DCOG-ALL9 and 0.74 (95% CI, 0.63-0.84) in STOPP, and resulted in correct identification of 71% of the patients with low LS BMD. We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR 5.9; 95% CI, 3.2-10.9) and with symptomatic fractures (OR 1.7; 95% CI, 1.3-2.4) that occurred between diagnosis and 12 months following treatment cessation. In meta-analysis, LS BMD at diagnosis (OR 1.6; 95% CI, 1.1-2.4) and the 6-month cumulative glucocorticoid dose (OR 1.9; 95% CI, 1.1-3.2) were associated with fractures that occurred in the first year of treatment. In summary, a prediction model for identifying pediatric ALL patients with low LS BMD at diagnosis, as an important indicator for bone fragility, was successfully developed and validated. This can facilitate identification of future bone fragility in individual pediatric ALL patients. © 2021 American Society for Bone and Mineral Research (ASBMR).

Subcutaneous fat necrosis associated with hypercalcemia in neonates with neonatal encephalopathy treated with therapeutic hypothermia.

Subcutaneous fat necrosis of the newborn (SFNN) is a rare, self-resolving panniculitis. The onset of skins lesions occurs within the first week of life, with a median age of onset around day 6 of life (range 1-70). About 50% of neonates with SFNN will develop hypercalcemia in the first month though some present later. Typically, SFNN develops prior to hypercalcemia. Only half of the neonates have classic symptoms of hypercalcemia; routine screening for hypercalcemia is recommended for neonates with SFNN or at-risk. The mechanism for hypercalcemia is usually aberrant 1,25-dihydroxyvitamin D synthesis in the necrotic tissue increasing intestinal absorption of calcium. Prompt recognition and treatment is required, often in hospital. Treatment options are low calcium-vitamin D formula or sometimes intravenous bisphosphonates. Regular monitoring post-intervention is required when normalizing the diet. Outcomes are good with routine surveillance and interventions. A multidisciplinary team approach (neonatologists, pediatric endocrinologists and nephrologists, dieticians) is optimal.

World Health Organization growth standards: How do Canadian children measure up?

BACKGROUND: World Health Organization (WHO) growth standards for children aged 0 to 5 years describe growth under optimal conditions and were adopted for use in Canada in 2012. We are seeking to validate these charts in a well-characterized, longitudinal cohort of healthy, Canadian youngsters, assess tracking over time, and evaluate the prognostic implications of early growth. METHODS: Data from 2,795 mother-infant dyads from the CHILD birth cohort were classified by feeding modality at 6 months as exclusively breastfed, partially breastfed, or formula-fed. WHO z-scores (z) were calculated at birth, 3 months, 1 year, and 3 years. Receiver operator characteristics (ROC) assessed the predictive performance of early weight (WT), weight-for-length (WfL), or body mass index (BMI) z-scores for overweight/obesity at 3 years. RESULTS: Compared to WHO standards, Canadian children at birth had lower median WfLz (-0.73) and BMIz (-0.29), with more positive scores by 3 years (WfLz=BMIz=0.58). At both 1 and 3 years, formula feeding was associated with higher scores than breastfeeding, even after regression adjustment for covariates. Head circumference z-score was typically positive at all times and regardless of feeding modality. At 1 year, ROC area under the curve was 0.79 for WTz, WfLz, and BMIz, and BMIz>0.88 identified children with increased risk of overweight/obesity (BMIz >2) at age 3 years (20.3% versus 3.0%, P<0.001). CONCLUSIONS: Compared to WHO growth charts, Canadian children at 3 years show an upward shift in BMIz and WfLz, particularly when formula-fed. Infant growth parameters may identify infants with increased risk of overweight/obesity at age 3 years; early recognition may allow targeting infants at higher risk.

Zoledronic Acid vs Placebo in Pediatric Glucocorticoid-induced Osteoporosis: A Randomized, Double-blind, Phase 3 Trial.

CONTEXT: Glucocorticoids (GCs) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures. OBJECTIVE: This study aims to determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO). METHODS: Children aged 5 to 17 years with GIO were enrolled in this multinational, randomized, double-blind, placebo-controlled phase 3 trial (ClinicalTrials.gov NCT00799266). Eligible children were randomly assigned 1:1 to 6 monthly IV ZA 0.05 mg/kg or IV placebo. The primary end point was the change in lumbar spine bone mineral density z score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed. RESULTS: Thirty-four children were enrolled (mean age 12.6 ±â€…3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures (VFs). LSBMDZ increased from -2.13 ±â€…0.79 to -1.49 ±â€…1.05 on ZA, compared with -2.38 ±â€…0.90 to -2.27 ±â€…1.03 on placebo (least squares means difference 0.41 [95% CI, 0.02-0.81; P = .04]); when corrected for height z score, the least squares means difference in LBMDZ was 0.75 [95% CI, 0.27-1.22; P = .004]. Two children on placebo had new low-trauma VF vs none on ZA. Adverse events (AEs) were reported in 15 of 18 children (83%) on ZA, and in 12 of 16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths or treatment discontinuations due to treatment-emergent AEs. CONCLUSION: LSBMDZ increased significantly on ZA compared with placebo over 1 year in children with GIO. Most AEs occurred after the first infusion.

Osteoporotic Fractures and Vertebral Body Reshaping in Children With Glucocorticoid-treated Rheumatic Disorders.

CONTEXT: Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders. OBJECTIVE: This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders. METHODS: Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping. RESULTS: A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean -0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (-0.6, SD 0.9). CONCLUSION: VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.

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.