Caesarean Delivery and Risk of Chronic Inflammatory Diseases (Inflammatory Bowel Disease, Rheumatoid Arthritis, Coeliac Disease, and Diabetes Mellitus): A Population Based Registry Study of 2,699,479 Births in Denmark During 1973–2016

Abstract

Background

Chronic inflammatory diseases in childhood and early adult life share aetiological factors operating from birth and onwards. In this study, we use data from the national Danish health registers to evaluate the risk of developing four common, immune-mediated hospital-diagnosed childhood chronic inflammatory diseases.

Methods

A national population-based registry study. Data from the Danish Medical Birth Registry and the Danish National Patient Registry from January 1973 to March 2016 were linked at a personal level to evaluate any potential associations between caesarean section and development of Inflammatory bowel diseases, rheumatoid arthritis, coeliac disease and diabetes mellitus among the offspring. A model adjusted for parental age at birth, decade of birth, gender of child, and parents’ chronic inflammatory disease status was used.

Results

This register-based national cohort study of 2672708 children with information on delivery mode found an increased risk of diabetes, arthritis, coeliac disease, and inflammatory bowel disease for both girls and boys after caesarean section compared with vaginal delivery. The higher risk was present at least 40 years after delivery. In a subgroup analysis, both acute and elective caesarean section was associated with an increased risk of developing a chronic inflammatory disease.

Conclusions

Being born by caesarean section leads to increased host susceptibility for chronic inflammatory diseases that last for decades. This finding should be further addressed in future studies with the aim to support the development of new strategies for prevention, treatment, and maybe even cure.

Keywords:

• caesarean delivery
• population study
• vaginal birth
• chronic inflammatory disease
• inflammatory bowel diseases
• rheumatoid arthritis
• coeliac disease

Abbreviations

CI, Confidence intervals; CID, Chronic inflammatory disease; CD, Coeliac disease; CRS, The Danish Civil Registration System; CS, Caesarean section; HR, Hazard ratio; IBD, Inflammatory bowel disease; ICD10, International Classification of Diseases, 10th revision; MBR, The Danish Medical Birth Register; NPR, The Danish National Patient Register; OR, Odds ratio; RA, Rheumatoid arthritis; DM, Diabetes mellitus.

Transparency Statement

VA affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

Ethics

Studies on data registries (that do not include biological material) should not be notified to the ethics committee in Denmark.

Data Sharing Statement

Data is stored at Open Patient data Explorative Network (OPEN). Bona fide researchers can apply to use the dataset by applying to [email protected].

Author Contributions

Contributor and guarantor information: VA conceived the research and VA, AG, and SM wrote the first draft of the manuscript. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Funding

This work was funded by The Danish Rheumatism Association (Gigtforeningen) (R104-A2195-B760). The funders did not influence the conduct of the study, analysis, interpretation of the data, the writing of this report, or the decision to publish.

Disclosure

Professor Vibeke Andersen reports grants from The Danish Rheumatism Association (Gigtforeningen), during the conduct of the study. The authors report no other conflicts of interest in this work.