Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study

for the TEDDY Study Group

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. Methods: From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. Results: Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development. Conclusion: C-section is not associated with increased risk for CDA or CD in the offspring.

Original languageEnglish (US)
Pages (from-to)417-424
Number of pages8
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume66
Issue number3
DOIs
StatePublished - Mar 1 2018

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Celiac Disease
Cesarean Section
Autoimmunity
Confidence Intervals
Nonparametric Statistics
HLA-DR3 Antigen
HLA-DR4 Antigen
Education
Pregnancy
Transglutaminases
Immune System Diseases
Maternal Age
Finland
Parity
Breast Feeding
Proportional Hazards Models
Sweden
Birth Weight
Autoantibodies
Gestational Age

Keywords

  • celiac disease autoimmunity
  • mode of delivery
  • screening
  • tissue transglutaminase
  • vaginal delivery

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

Cite this

Cesarean Section on the Risk of Celiac Disease in the Offspring : The Teddy Study. / for the TEDDY Study Group.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 66, No. 3, 01.03.2018, p. 417-424.

Research output: Contribution to journalArticle

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title = "Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study",
abstract = "Objective: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. Methods: From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. Results: Of 6087 analyzed singletons, 1600 (26{\%}) were born by C-section (Germany 38{\%}, United States 37{\%}, Finland 18{\%}, Sweden 16{\%}), and the remaining were born vaginally without instrumental support; 979 (16{\%}) had developed CDA and 343 (6{\%}) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95{\%} confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95{\%} CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91; 95{\%} CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95{\%} CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development. Conclusion: C-section is not associated with increased risk for CDA or CD in the offspring.",
keywords = "celiac disease autoimmunity, mode of delivery, screening, tissue transglutaminase, vaginal delivery",
author = "{for the TEDDY Study Group} and Sibylle Koletzko and Lee, {Hye Seung} and Andreas Beyerlein and Aronsson, {Carin A.} and Michael Hummel and Edwin Liu and Ville Simell and Kalle Kurppa and {\AA}ke Lernmark and William Hagopian and Marian Rewers and She, {Jin Xiong} and Olli Simell and Jin-Xiong She and Ziegler, {Anette G.} and Jeffrey Krischer and Daniel Agardh and Patricia Gesualdo and Michelle Hoffman and Rachel Karban and Jill Norris and Adela Samper-Imaz and Andrea Steck and Kathleen Waugh and Hali Wright and Desmond Schatz and DIane Hopkins and Leigh Steed and Jamie Thomas and Janey Adams and Katherine Silvis and Michael Haller and Melissa Gardiner and Richard McIndoe and Ashok Sharma and McIndoe, {Richard A} and Sharma, {Ashok Kumar} and Anderson, {Stephen W.} and Laura Jacobsen and Ziegler, {Anette G.} and Ezio Bonifacio and Sandra Hummel and Kristina Foterek and Nicole Janz and Mathilde Kersting and Annette Knopff and Claudia Peplow and Roswith Roth and Marlon Scholz and Joanna Stock",
year = "2018",
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doi = "10.1097/MPG.0000000000001682",
language = "English (US)",
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pages = "417--424",
journal = "Journal of Pediatric Gastroenterology and Nutrition",
issn = "0277-2116",
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TY - JOUR

T1 - Cesarean Section on the Risk of Celiac Disease in the Offspring

T2 - The Teddy Study

AU - for the TEDDY Study Group

AU - Koletzko, Sibylle

AU - Lee, Hye Seung

AU - Beyerlein, Andreas

AU - Aronsson, Carin A.

AU - Hummel, Michael

AU - Liu, Edwin

AU - Simell, Ville

AU - Kurppa, Kalle

AU - Lernmark, Åke

AU - Hagopian, William

AU - Rewers, Marian

AU - She, Jin Xiong

AU - Simell, Olli

AU - She, Jin-Xiong

AU - Ziegler, Anette G.

AU - Krischer, Jeffrey

AU - Agardh, Daniel

AU - Gesualdo, Patricia

AU - Hoffman, Michelle

AU - Karban, Rachel

AU - Norris, Jill

AU - Samper-Imaz, Adela

AU - Steck, Andrea

AU - Waugh, Kathleen

AU - Wright, Hali

AU - Schatz, Desmond

AU - Hopkins, DIane

AU - Steed, Leigh

AU - Thomas, Jamie

AU - Adams, Janey

AU - Silvis, Katherine

AU - Haller, Michael

AU - Gardiner, Melissa

AU - McIndoe, Richard

AU - Sharma, Ashok

AU - McIndoe, Richard A

AU - Sharma, Ashok Kumar

AU - Anderson, Stephen W.

AU - Jacobsen, Laura

AU - Ziegler, Anette G.

AU - Bonifacio, Ezio

AU - Hummel, Sandra

AU - Foterek, Kristina

AU - Janz, Nicole

AU - Kersting, Mathilde

AU - Knopff, Annette

AU - Peplow, Claudia

AU - Roth, Roswith

AU - Scholz, Marlon

AU - Stock, Joanna

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Objective: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. Methods: From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. Results: Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development. Conclusion: C-section is not associated with increased risk for CDA or CD in the offspring.

AB - Objective: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. Methods: From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. Results: Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development. Conclusion: C-section is not associated with increased risk for CDA or CD in the offspring.

KW - celiac disease autoimmunity

KW - mode of delivery

KW - screening

KW - tissue transglutaminase

KW - vaginal delivery

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