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Lee J.J.,Childrens Hospital Boston | Escher J.C.,Erasmus University Rotterdam | Shuman M.J.,Childrens Hospital Boston | Forbes P.W.,Clinical Research Program | And 7 more authors.
Inflammatory Bowel Diseases | Year: 2010

Background: This study was designed to elucidate the contribution of parental height to the stature of children with inflammatory bowel disease (IBD), who often exhibit growth impairment. Accordingly, we compared patients' final adult heights and target heights based on measured parental heights and examined predictors of final adult height in pediatric IBD patients. Methods: We prospectively analyzed the growth of 295 patients diagnosed between ages 1 and 18 (211 Crohn's disease [CD], 84 ulcerative colitis [UC]) and their family members (283 mothers, 231 fathers, 55 siblings). Results: Twenty-two percent had growth impairment (height for age Z-score <-1.64, equivalent to <5th percentile on growth curve) in more than 1 measurement since diagnosis; most growth-impaired patients had CD (88% CD versus 12% UC). Parents of the growth-impaired group had lower mean height Z-scores compared to parents of nongrowth-impaired patients (-0.67 versus 0.02 for mothers [P < 0.001]; -0.31 versus 0.22 for fathers [P = 0.002]). For 108 patients who reached adult heights and had available parental heights, the growth-impaired group continued to demonstrate lower adult height Z-scores (-1.38 versus 0.07; P < 0.001). Adult heights were within 1 SD of target heights even for the growth-impaired group. Only 11.3% remained persistently growth-impaired in adulthood. Multivariate regression analysis demonstrated lower parental height and minimum patient height Z-score as significant predictors of lower final adult height in IBD. Conclusions: Parental height is a powerful determinant of linear growth even in the presence of chronic inflammation, and should be an integral part of the evaluation of growth in IBD children. © 2010 Crohn's & Colitis Foundation of America, Inc. Source


Mehta N.M.,Critical Care Medicine | Raphael B.,Hepatology and Nutrition | Quinn N.,Clinical and Translational Study Unit | Mitchell P.D.,Harvard University | And 2 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2014

Objectives: The aim of the study was to examine the agreement of multifrequency bioelectric impedance analysis (BIA) and anthropometry with reference methods for body composition assessment in children with intestinal failure (IF). Methods: We conducted a prospective pilot study in children 14 years or younger with IF resulting from either short bowel syndrome or motility disorders. Bland-Altman analysis was used to examine the agreement between BIA and deuterium dilution in measuring total body water (TBW) and lean body mass (LBM), and between BIA and dual-energy x-ray absorptiometry (DXA) techniques in measuring LBM and fat mass (FM). FM and percent body fat (%BF) measurements by BIA and anthropometry were also compared in relation to those measured by deuterium dilution. Results: Fifteen children with IF, median (interquartile range) age 7.2 (5.0, 10.0) years, and 10 (67%) boys, were studied. BIA and deuterium dilution were in good agreement with a mean bias (limits of agreement) of 0.9 (≤3.2 to 5.0) for TBW (L) and 0.1 (≤5.4 to 5.6) for LBM (kg) measurements. The mean bias (limits) for FM (kg) and %BF measurements were 0.4 (≤3.8 to 4.6) kg and 1.7 (≤16.9 to 20.3)%, respectively. The limits of agreement were within 1 standard deviation of the mean bias in 12 of 14 (86%) subjects for TBW and LBM, and in 11 of 14 (79%) for FM and %BF measurements. Mean bias (limits) for LBM (kg) and FM (kg) between BIA and DXA were 1.6 (≤3.0 to 6.3) kg and ≤0.1 (≤3.2 to 3.1) kg, respectively. Mean bias (limits) for FM (kg) and %BF between anthropometry and deuterium dilution were 0.2 (≤4.2 to 4.6) and ≤0.2 (≤19.5 to 19.1), respectively. The limits of agreement were within 1 standard deviation of the mean bias in 10 of 14 (71%) subjects. Conclusions: In children with IF, TBW and LBM measurements by Multifrequency BIA method were in agreement with isotope dilution and DXA methods, with small mean bias and clinically acceptable limits of agreement. In comparison with deuterium dilution, BIA was comparable to anthropometry for FM and %BF assessments with small mean bias, but the limits of agreement were large. BIA is a reliable method for TBW and LBM assessments in population studies; however, its reliability in individual patients, especially for FM assessments, cannot be guaranteed. Copyright © 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Source


Gordon C.M.,Childrens Hospital Boston | Gordon L.B.,Hasbro Childrens Hospital | Gordon L.B.,Harvard University | Snyder B.D.,Harvard University | And 10 more authors.
Journal of Bone and Mineral Research | Year: 2011

Hutchinson-Gilford progeria syndrome (HGPS) is a rare segmental premature aging disorder that affects bone and body composition, among other tissues. We sought to determine whether bone density and structural geometry are altered in children with HGPS and whether relationships exist among these parameters and measures of skeletal anthropometry, body composition, and nutrition. We prospectively enrolled 26 children with HGPS (ages 3.1 to 16.2 years). Outcomes included anthropometric data; bone age; areal bone mineral density (aBMD) and body composition by dual-energy X-ray absorptiometry (DXA); volumetric bone mineral density (vBMD), strength-strain index (SSI), and bone structural rigidity calculated from radial transaxial peripheral quantitative computed tomographic (pQCT) images; serum bone biomarkers and hormonal measures; and nutrition assessments. Children with HGPS had low axial aBMD Z-scores by DXA, which improved after adjustment for height age, whereas differences in radial vBMD by pQCT were less striking. However, pQCT revealed distinct abnormalities in both novel measures of bone structural geometry and skeletal strength at the radius compared with healthy controls. Dietary intake was adequate, confirming that HGPS does not represent a model of malnutrition-induced bone loss. Taken together, these findings suggest that the phenotype of HGPS represents a unique skeletal dysplasia. Copyright © 2011 American Society for Bone and Mineral Research. Source


Pappa H.M.,Center for Inflammatory Bowel Disease | Saslowsky T.M.,Center for Inflammatory Bowel Disease | Filip-Dhima R.,Clinical Research Program | Difabio D.,Clinical and Translational Study Unit | And 4 more authors.
American Journal of Gastroenterology | Year: 2011

Objectives: There are very few published studies of agents having the potential to improve bone health in children with inflammatory bowel disease (IBD). The objective of this study was to establish the efficacy and safety of intranasal calcitonin in improving bone mineral density (BMD) in young patients with IBD and to define additional factors that impact bone mineral accrual. Methods: We conducted a randomized, placebo-controlled, double-blind clinical trial in 63 participants, ages 8-21 years, with a spinal BMD Z-score ≤-1.0 s.d. measured by dual energy X-ray absorptiometry. Subjects were randomized to 200 IU intranasal calcitonin (n=31) or placebo (n=32) daily. All received age-appropriate calcium and vitamin D supplementation. Subsequent BMD measurements were obtained at 9 and 18 months. Results: Intranasal calcitonin was well tolerated. Adverse event frequency was similar in both treatment groups, and such events were primarily minor, reversible, and limited to the upper respiratory tract. The BMD Z-score change documented at screening and 9 months and screening and 18 months did not differ between the two therapeutic arms. In participants with Crohn's disease, the spinal BMD Z-score improved between screening and 9 months (change in spine BMD Z-score (ΔZSBMD)(9-0)) in the calcitonin group (ΔZSBMD(9-0)calcitonin =0.21 (0.37), ΔZSBMD(9-0)placebo =-0.15 (0.5), P=0.02); however, this was only a secondary subgroup analysis. Bone mineral accrual rate during the trial did not lead to normalization of BMD Z-score in this cohort. Factors favoring higher bone mineral accrual rate were lower baseline BMD and higher baseline body mass index Z-score, improvement in height Z-score, higher serum albumin, hematocrit and iron concentration, and more hours of weekly weight-bearing activity. Factors associated with lower bone mineral accrual rate were more severe diseaseas indicated by elevated inflammatory markers, need for surgery, hospitalization, and the use of immunomodulatorsand higher daily caffeine intake. Conclusions: Intranasal calcitonin is well tolerated but does not offer a long-term advantage in youth with IBD and decreased BMD. Bone mineral accrual rate remains compromised in youth with IBD and low BMD raising concerns for long-term bone health outcomes. Improvement in nutritional status, catch-up linear growth, control of inflammation, increase in weight-bearing activity, and lower daily caffeine intake may be helpful in restoring bone density in children with IBD and low BMD. © 2011 by the American College of Gastroenterology. Source


Pappa H.M.,Center for Inflammatory Bowel Diseases | Mitchell P.D.,Clinical Research Center | Jiang H.,Clinical Research Center | Kassiff S.,Center for Inflammatory Bowel Diseases | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Vitamin D insufficiency [serum 25-hydroxyvitamin D (25OHD) concentration less than 20 ng/ml] is prevalent among children with inflammatory bowel disease (IBD), and its treatment has not been studied. Objective: The aim of this study was to compare the efficacy and safety of three vitamin D repletion regimens. Design and Setting: We conducted a randomized, controlled clinical trial from November 2007 to June 2010 at the Clinical and Translational Study Unit of Children's Hospital Boston. The study was not blinded to participants and investigators. Patients: Eligibility criteria included diagnosis of IBD, age 5-21, and serum 25OHD concentration below 20 ng/ml. Seventy-one patients enrolled, 61 completed the trial, and two withdrew due to adverse events.Intervention: Patients received orally for 6 wk: vitamin D 2, 2,000 IU daily (arm A, control); vitamin D3, 2,000 IU daily (arm B); vitamin D2, 50,000 IU weekly (arm C); and an age-appropriate calcium supplement. Main Outcome Measure: We measured the change in serum 25OHD concentration (Δ25OHD) (ng/ml). Secondary outcomes included change in serum intact PTH concentration (ΔPTH) (pg/ml) and the adverse event occurrence rate. Results: After 6 wk, Δ25OHD ± SE was: 9.3 ∓ 1.8 (arm A); 16.4 ± 2.0 (arm B); 25.4 ± 2.5 (arm C); P (A vs. C) = 0.0004; P (A vs. B) = 0.03. ΔPTH ± SE was -5.6 ± 5.5 (arm A); -0.1 ± 4.2 (arm B); -4.4 ± 3.9 (arm C); P = 0.57. No participant experienced hypercalcemia or hyperphosphatemia, and the prevalence of hypercalciuria did not differ among arms at follow-up. Conclusions: Oral doses of 2,000 IU vitamin D3 daily and 50,000 IU vitamin D2 weekly for 6 wk are superior to 2,000 IU vitamin D 2 daily for 6 wk in raising serum 25OHD concentration and are well-tolerated among children and adolescents with IBD. The change in serum PTH concentration did not differ among arms. Copyright © 2012 by The Endocrine Society. Source

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