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Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study
Sibylle Koletzko1, Hye-Seung Lee, Andreas Beyerlein
1*Dr. v. Hauner Children's Hospital, University Munich Medical Center, Munich, Germany †Health Informatics Institute, Department of Paediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA ‡Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany §Department of Clinical Sciences, Lund University, Skane University Hosptial, Malmo, Sweden ||Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Aurora, CO, USA ¶Medicity Laboratory, University of Turku, Turku, Finland #Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland **Pacific Northwest Diabetes Research Institute, Seattle WA, USA ††Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora CO, USA ‡‡Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta GA, USA §§Department of Paediatrics, Turku University Hospital, Turku, Finland ||||Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland ¶¶Departments of Physiology, University of Turku, Turku, Finland.
Insights
Cesarean birth (C-section) did not increase the risk of celiac disease (CD) or CD autoimmunity (CDA) in children. This large study found no significant association after accounting for various factors, suggesting C-section is not a risk factor for these conditions.
Area of Science:
- Immunology
- Pediatrics
- Gastroenterology
Background:
- Cesarean section (C-section) delivery is linked to immune-mediated diseases in offspring.
- The relationship between delivery mode and celiac disease (CD) and CD autoimmunity (CDA) requires further investigation.
Purpose of the Study:
- To investigate the association between mode of delivery (C-section vs. vaginal birth) and the development of CD and CDA in a multinational birth cohort.
- To analyze maternal and child characteristics influencing the mode of delivery and disease outcomes.
Main Methods:
- A multinational birth cohort (TEDDY study) of infants with specific HLA genotypes was followed from 2004-2010.
- Children were screened annually for transglutaminase autoantibodies to identify CDA and CD.
- Cox proportional hazard regression models were used to calculate hazard ratios (HRs) for CDA and CD based on delivery mode, adjusting for covariates.
Main Results:
- Of 6087 singletons, 26% were born via C-section. CDA developed in 16% and CD in 6% of the cohort.
- Initially, C-section was associated with a lower risk for CDA (HR=0.85) and CD (HR=0.75).
- After adjusting for country, sex, HLA-genotype, family history of CD, maternal education, and breastfeeding duration, these associations lost statistical significance for both CDA and CD.
Conclusions:
- Cesarean section delivery is not associated with an increased risk of developing celiac disease or CD autoimmunity in offspring.
- The initial observed association between C-section and reduced risk for these conditions was not significant after adjusting for confounding factors.
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.
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