title: Risk of congenital malformations among offspring of mothers and fathers with celiac disease: a nationwide cohort study.
abstract: OBJECTIVE
  Many patients with celiac disease experience malabsorption, weight loss, and anemia; undiagnosed celiac disease during pregnancy has been linked with adverse outcomes. Studies of celiac disease and congenital malformations in offspring have been underpowered. We investigated the risk of congenital malformations among the offspring of parents with celiac disease.
  
  
  METHODS
  We performed a nationwide cohort study of data from linked health care registers in Sweden from 1973 through 2009. We collected histopathology data from 28 pathology departments in Sweden to identify individuals with celiac disease (based on the presence of villous atrophy). We estimated the risks of malformations in the offspring of mothers and fathers with and without celiac disease. Logistic regression was used to estimate adjusted prevalence odds ratios (aPORs) with 95% confidence intervals (CIs).
  
  
  RESULTS
  Among 11,382 offspring of mothers with celiac disease, there were 672 cases (5.9%) of malformation compared with 2098 cases (5.1%) among 40,922 offspring of mothers without celiac disease. Similarly, 352 (5.9%) of 6002 offspring of fathers with celiac disease and 1009 (5.1%) of 19,600 offspring of fathers without celiac disease had a malformation. In adjusted analyses, the offspring of mothers or fathers with celiac disease had a slightly increased risk of having children with malformations (for those with mothers with celiac disease: aPOR, 1.15; 95% CI, 1.05-1.26; for those with fathers with celiac disease: aPOR, 1.14; 95% CI, 1.00-1.29). However, these excess risks decreased or vanished entirely when we restricted our data to births since 2000 (for those with mothers with celiac disease: aPOR, 1.11; and 95% CI, 0.79-1.56; for those with fathers with celiac disease: aPOR, 1.01; 95% CI, 0.81-1.26).
  
  
  CONCLUSIONS
  In a nationwide study, we found an increased risk for malformation among the offspring of mothers or fathers with celiac disease. However, the excess risk is small; the upper limits of the CIs for malformation indicate a 29% maximum relative increase.
authors.affiliation: Cancer Epidemiology Unit, CPO-Piemonte and University of Turin, Turin, Italy; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zugna
authors.affiliation: Cancer Epidemiology Unit, CPO-Piemonte and University of Turin, Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Richiardi
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Stephansson
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Ekbom
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Cnattingius
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Sweden. Electronic address: jonasludvigsson@yahoo.com.
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Ludvigsson
mesh_terms: D000293:Adolescent; D000328:Adult; D002446:Celiac Disease / Q000150:complications*; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D015995:Prevalence; D018570:Risk Assessment; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
keywords: Autoimmunity; Celiac; Child; Congenital Malformation; Gluten Intolerance