Immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have shown a parallel increase in prevalence during recent decades in westernized countries. The rate of cesarean delivery has also increased in this period and has been associated with the development of some of these diseases.
Mature children born by cesarean delivery were analyzed for risk of hospital contact for chronic immune diseases recorded in the Danish national registries in the 35-year period 1977–2012. Two million term children participated in the primary analysis. We studied childhood diseases with a suspected relation to a deviant immune-maturation and a debut at young age. The effect of cesarean delivery on childhood disease incidences were estimated by means of confounder-adjusted incidence rate ratios with 95% confidence intervals obtained in Poisson regression analyses.
Children delivered by cesarean delivery had significantly increased risk of asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies, and leukemia. No associations were found between cesarean delivery and type 1 diabetes, psoriasis, or celiac disease.
Cesarean delivery exemplifies a shared environmental risk factor in early life associating with several chronic immune diseases. Understanding commonalities in the underlying mechanisms behind chronic diseases may give novel insight into their origin and allow prevention.
Comments
Re:Cesarean Section and Idiopathic Nephrotic Syndrome
Dear Editor, We thank Professor Kaneko and colleagues for their interest in our study (1) and their suggestion, that idiopathic nephrotic syndrome (INS) in childhood may be associated with delivery by cesarean section in a similar manner as the childhood immunological diseases that we investigated in our nationwide study. We therefore defined INS as in- or outpatient hospitalizations with ICD10 diagnosis "DN04" or ICD8 diagnosis "58199". A 35-year period from 1977- 2012 was analyzed. Among the 1.9 million term children (aged 0-15 years) followed for 23 million person years of observation, we found 749 cases of INS in Denmark. The incidence rate ratio of INS was significantly increased with delivery by cesarean section, confounder adjusted IRR 1.36 [1.10 - 1.68]; p=0.0052 (confounders: birth weight, season of birth, gender, parity, maternal age, maternal disease). The significant finding in spite of the very low number of cases indeed validates the suspicion from Kaneko and colleagues. Age of onset was relatively evenly distributed with median age 5.6 (IQR 3.1-9.4). We did not find any difference in association to cesarean section by age of onset. Birth by cesarean section is associated with increased risk of several chronic immune diseases in the children including INS, suggesting a shared environmental risk factor in early life.
1. Sevelsted A, Stokholm J, B?nnelykke K, Bisgaard H. Cesarean section and chronic immune disorders. Pediatrics. 2015 Jan;135(1):e92-8.
Conflict of Interest:
None declared
Cesarean Section and Idiopathic Nephrotic Syndrome
Dear Editor,
We read with great interest the article entitled "Cesarean Section and Chronic Immune Disorders" by Dr. Sevelsted, et al.1 They concluded that children delivered by cesarean delivery had significantly increased risk of asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies, and leukemia. It may be speculated that cesarean delivery is mediated by changes in microbiome of the newborn because the gut microbiota plays a key role in the development of immune systems.2 There are also numerous reports suggesting an association between idiopathic nephrotic syndrome (INS) and allergy3 and the recent review implies causal relationship between the risk of INS and an altered gut microbiota.4 Taken together, we hypothesize that there is also a link between cesarean section and an increased risk of INS and investigated our patients' records with interesting results: among 42 children with INS seen at our hospital during the past 10 years, the number of cesarean delivery was as high as 12 (28.6%) while general proportion in Japan was reported to be 17.4% in 2010; it jumped up to 43.8% in patients whose onset of INS was before 3 years of age. Therefore, it is worthwhile to include the INS in the further study to investigate the causal link between cesarean section and the risk of chronic immune disorders.
References
1.Sevelsted A, Stokholm J, Bonnelykke K, Bisgaard H. Cesarean section and chronic immune disorders. Pediatrics. 2015;135(1):e92-98
2.Hansen CH, Andersen LS, Krych L, et al. Mode of delivery shapes gut colonization pattern and modulates regulatory immunity in mice. J Immunol. 2014;193(3):1213-1222.
3.Abdel-Hafez M, Shimada M, Lee PY, Johnson RJ, Garin EH. Idiopathic nephrotic syndrome and atopy: is there a common link? Am J Kidney Dis. 2009;54(5):945-953.
4.Uy N, Graf L, Lemley KV, Kaskel F. Effects of gluten-free, dairy-free diet on childhood nephrotic syndrome and gut microbiota. Pediatr Res. 2015;77(1-2):252-255.
Conflict of Interest:
None declared