title: Growth trajectories and bone mineral density in anti-tissue transglutaminase antibody-positive children: the Generation R Study.
abstract: OBJECTIVE
  Increased levels of anti-tissue transglutaminase (tTG) have been associated with reduced weight and bone mineral density (BMD) in symptomatic patients with celiac disease. Little is known about the effects of these antibodies in patients with subclinical or other forms of celiac disease. We examined associations between anti-tTG positivity and growth and BMD.
  
  
  METHODS
  In a population-based prospective cohort study, serum samples were collected from children (median age, 6 years; n = 4442) and analyzed for anti-tTG. All children were born between April 2002 and January 2006 and were not previously diagnosed with celiac disease. Children were categorized as anti-tTG negative (<7 U/mL, n = 4249) or anti-tTG positive (≥7 U/mL, n = 57). Children's levels of anti-tTG were further categorized on the basis of ≥10 times upper limit of normal (70 U/mL). Height, weight, and body mass index (BMI) age- and sex-adjusted standard deviation scores (SDS) ([observed value - mean]/SD) were obtained by using Dutch reference growth charts. BMD was measured by dual-energy x-ray absorptiometry. Multivariable linear regression and linear mixed models were performed.
  
  
  RESULTS
  Children who tested positive for anti-tTG had reduced growth in weight SDS/year (reduction of 0.05; 95% CI, reductions of 0.09-0.01) and BMI SDS/year (reduction of 0.10; 95% CI, reductions of 0.18-0.01) from 6 months until 6 years, compared with children without anti-tTG; they also tended to have reduced growth in height from 6 months until 6 years (reduction of 0.02 SDS/year; 95% CI, reductions of 0.06-0.02). Children who tested positive for anti-tTG were shorter (0.29 SDS shorter; 95% CI, reductions of 0.55-0.04 SDS), weighed less (0.38 SDS less; 95% CI, reductions of 0.64-0.12), and had lower BMIs (0.26 SDS less; 95% CI, reductions of 0.49-0.03) and BMDs (0.26 SDS less; 95% CI, reductions of 0.45-0.08) at 6 years of age than anti-tTG negative children.
  
  
  CONCLUSIONS
  Anti-tTG positive children without gastrointestinal symptoms have lower BMDs and reduced growth trajectories until they are 6 years old. This suggests that subclinical or potential celiac disease can affect BMD and growth.
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Michelle A E
authors.initials: MA
authors.lastname: Jansen
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Romy
authors.initials: R
authors.lastname: Gaillard
authors.affiliation: Department of Pediatric Gastroenterology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Escher
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Herbert
authors.initials: H
authors.lastname: Hooijkaas
authors.affiliation: Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. Electronic address: h.a.moll@erasmusmc.nl.
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Moll
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D001827:Body Height; D015992:Body Mass Index; D001835:Body Weight; D015519:Bone Density; D002446:Celiac Disease / Q000473:pathology*; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D044967:Serum / Q000737:chemistry; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D000906:Antibodies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Development; Food Allergy; Generation R Study; Pediatric