Cesarean Section and Chronic Immune Disorders
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Epidemiological studies show an association between cesarean section delivery and chronic immune disorders such as asthma, which are associated with an increased risk of viral infections.
“Epidemiological studies have shown an association between CS delivery and chronic immune disorders, such as asthma (Sevelsted et al., 2015), which are associated with an increased risk of viral infections (Juhn, 2014).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Sevelsted et al., 2015
Cites
1 retracted
Cucchiara, S., Stronati, L., & Aloi, M. (2012) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31826a857f · Cited by 36 · see citing works
RetractedDominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774 · see citing works
Beasley, R. W. (1998) · The Lancet · doi:10.1016/s0140-6736(97)07302-9 · Cited by 3,773 · see citing works
The effect of infections on susceptibility to autoimmune and allergic diseases.
Bach, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020100 · Cited by 2,714 · see citing works
The Danish National Hospital Register. A valuable source of data for modern health sciences.
Andersen, T. F., Madsen, M., Jørgensen, J. O. L., Mellemkjoer, L., & Olsen, J. H. (1999) · PubMed · Cited by 2,034 · see citing works
The Danish Civil Registration System. A cohort of eight million persons.
Pedersen, C. B., Gøtzsche, H., Møller, J. O., & Mortensen, P. B. (2006) · PubMed · Cited by 1,623 · see citing works
Family size, infection and atopy: the first decade of the 'hygiene hypothesis'
Strachan, D. (2000) · Thorax · doi:10.1136/thorax.55.suppl_1.s2 · Cited by 1,183 · see citing works
Childhood Asthma after Bacterial Colonization of the Airway in Neonates
Bisgaard, H. F., Hermansen, M. N., Buchvald, F. F., Loland, L., Halkjær, L. B., Bønnelykke, K., Brasholt, M., Heltberg, A., Vissing, N. H., Thorsen, S. V., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa052632 · Cited by 1,005 · see citing works
Self-citationDevelopment of allergen-specific T-cell memory in atopic and normal children
Prescott, S. L., Macaubas, C., Smallacombe, T. B., Holt, B. J., Sly, P. D., & Holt, P. G. (1999) · The Lancet · doi:10.1016/s0140-6736(98)05104-6 · Cited by 896 · see citing works
Bisgaard, H., Li, N., Bonnelykke, K., Chawes, B. L. K., Skov, T., Paludan-Müller, G., Stokholm, J., Smith, B., & Krogfelt, K. A. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.04.060 · Cited by 786 · see citing works
Self-citationAPPROPRIATE TECHNOLOGY FOR BIRTH
Moore, B. (1985) · The Lancet · doi:10.1016/s0140-6736(85)90673-7 · Cited by 762 · see citing works
A meta‐analysis of the association between Caesarean section and childhood asthma
Thavagnanam, S., Fleming, J., Bromley, A., Shields, M. D., & Cardwell, C. R. (2008) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2007.02780.x · Cited by 651 · see citing works
Cardwell, C. R., Stene, L. C., Joner, G., Cinek, O., Svensson, J., Goldacre, M. J., Parslow, R. C., Pozzilli, P., Brigis, G., Stoyanov, D., et al. (2008) · Diabetologia · doi:10.1007/s00125-008-0941-z · Cited by 590 · see citing works
Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section
Smaill, F. M., & Grivell, R. M. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007482.pub3 · Cited by 575 · see citing works
Appropriate technology for birth
(1986) · The Indian Journal of Pediatrics · doi:10.1007/bf02760430 · Cited by 523 · see citing works
Perspectives on the causes of childhood leukemia
Wiemels, J. L. (2012) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2012.01.007 · Cited by 513 · see citing works
Cesarean Birth in the United States: Epidemiology, Trends, and Outcomes
MacDorman, M. F., Menacker, F., & Declercq, E. R. (2008) · Clinics in Perinatology · doi:10.1016/j.clp.2008.03.007 · Cited by 468 · see citing works
Althabe, F., Sosa, C., Belizán, J. M., Gibbons, L., Jacquérioz, F., & Bergel, E. F. (2006) · Birth · doi:10.1111/j.1523-536x.2006.00118.x · Cited by 377 · see citing works
Mode of Delivery – Effects on Gut Microbiota and Humoral Immunity
Huurre, A., Kalliomäki, M. A., Rautava, S., Rinne, M., Salminen, S., & Isolauri, E. (2007) · Neonatology · doi:10.1159/000111102 · Cited by 354 · see citing works
The environment within: how gut microbiota may influence metabolism and body composition
Vrieze, A., Holleman, F., Zoetendal, E. G., de Vos, W. M., Hoekstra, J. B. L., & Nieuwdorp, M. (2010) · Diabetologia · doi:10.1007/s00125-010-1662-7 · Cited by 344 · see citing works
Caesarean section delivery and the risk of allergic disorders in childhood
Renz‐Polster, H., David, M., Buist, A. S., Vollmer, W. M., O’Connor, E., Frazier, E. A., & Wall, M. A. (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02356.x · Cited by 339 · see citing works
Adlerberth, I., Lindberg, E., Åberg, N., Hesselmar, B., Saalman, R., Strannegård, I., & Wold, A. E. (2005) · Pediatric Research · doi:10.1203/01.pdr.0000191137.12774.b2 · Cited by 317 · see citing works
Cesarean section and development of the immune system in the offspring
Cho, C. E., & Norman, M. (2013) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2012.08.009 · Cited by 301 · see citing works
Cesarean Delivery Is Associated With Celiac Disease but Not Inflammatory Bowel Disease in Children
Decker, E., Engelmann, G., Findeisen, A., Gerner, P., Laass, M. W., Ney, D., Posovszky, C., Hoy, L., & Hornef, M. W. (2010) · PEDIATRICS · doi:10.1542/peds.2009-2260 · Cited by 275 · see citing works
Pregnancy Outcome and Risk of Celiac Disease in Offspring: A Nationwide Case-Control Study
Mårild, K., Stephansson, O., Montgomery, S., Murray, J. A., & Ludvigsson, J. F. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.09.047 · Cited by 218 · see citing works
The health implications of birth by Caesarean section
Hyde, M. J., Mostyn, A., Modi, N., & Kemp, P. R. (2011) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2011.00195.x · Cited by 214 · see citing works
Asthma at 8 years of age in children born by caesarean section
Roduit, C., Scholtens, S., de Jongste, J. C., Wijga, A. H., Gerritsen, J., Postma, D. S., Brunekreef, B., Hoekstra, M. O., Aalberse, R. C., & Smit, H. A. (2008) · Thorax · doi:10.1136/thx.2008.100875 · Cited by 202 · see citing works
Bodansky, H. J., Staines, A. S., Stephenson, C. R., Haigh, D., & Cartwright, R. (1992) · BMJ · doi:10.1136/bmj.304.6833.1020 · Cited by 200 · see citing works
Cesarean section and offspringʼs risk of inflammatory bowel disease: A national cohort study
Bager, P., Simonsen, J., Nielsen, N. M., & Frisch, M. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21805 · Cited by 185 · see citing works
Pistiner, M., Gold, D. R., Abdulkerim, H., Hoffman, E. B., & Celedon, J. C. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.05.007 · Cited by 180 · see citing works
Prenatal and neonatal risk factors for childhood myeloid leukemia.
Cnattingius, S., Zack, M. M., Ekbom, A., Gunnarskog, J., Linet, M. S., & Adami, H. (1995) · PubMed · Cited by 124 · see citing works
Caesarean section increases the risk of hospital care in childhood for asthma and gastroenteritis
Håkansson, S., & Källén, K. (2003) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.2003.01667.x · Cited by 121 · see citing works
Umbilical cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery
Gitau, R., Menson, E. N., Pickles, V., Fisk, N. M., Glover, V. A. S., & MACLACHLAN, N. A. (2001) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(01)00298-6 · Cited by 120 · see citing works
Mathis, D. J., & Benoist, C. O. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01084.x · Cited by 91 · see citing works
Rostgaard, K. (2008) · Epidemiologic Perspectives & Innovations · doi:10.1186/1742-5573-5-7 · Cited by 87 · see citing works
Profound Deficit of IL10 at Birth in Children Who Develop Childhood Acute Lymphoblastic Leukemia
Chang, J. S.-M., Zhou, M., Buffler, P. A., et al. (2011) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-11-0162 · Cited by 76 · see citing works
MacArthur, A. C., McBride, M. L., Spinelli, J. J., et al. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm339 · Cited by 75 · see citing works
Labor: An immunologically beneficial process for the neonate
Thilaganathan, B., Meher‐Homji, N. J., & Nicolaides, K. H. (1994) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(94)90145-7 · Cited by 68 · see citing works
Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy
Følsgaard, N. V., Chawes, B., Rasmussen, M. A., Bischoff, A. L., Carson, C. G., Stokholm, J., Pedersen, L., Hansel, T. T., Bønnelykke, K., Brix, S., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201108-1471oc · Cited by 67 · see citing works
Self-citationThe Influence of Mode of Delivery on Hematologic Values in the Umbilical Vein
Nikischin, W., Peter, M., & Oldigs, H. D. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000291831 · Cited by 47 · see citing works
Perinatal risk factors for neuroblastoma
McLaughlin, C. C., Baptiste, M. S., Schymura, M. J., Zdeb, M. S., & Nasca, P. C. (2008) · Cancer Causes & Control · doi:10.1007/s10552-008-9243-5 · Cited by 38 · see citing works
Cesarean Section and Development of the Immune System in the Offspring
Cho, C. E., & Norman, M. (2014) · Obstetric Anesthesia Digest · doi:10.1097/01.aoa.0000443385.07422.6a · Cited by 34 · see citing works
Human growth and chronic disease: A memorial to Jim Tanner
Barker, D. J. P. (2012) · Annals of Human Biology · doi:10.3109/03014460.2012.712717 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G. A. D., Gasbarrini, A., & Mele, M. C. (2019) · Microorganisms · doi:10.3390/microorganisms7010014 · Cited by 3,462 · see citing works
Milani, C., Duranti, S., Bottacini, F., Casey, E., Turroni, F., Mahony, J., Belzer, C., Delgado Palacio, S., Arboleya Montes, S., Mancabelli, L., et al. (2017) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00036-17 · Cited by 1,950 · see citing works
The central nervous system and the gut microbiome
Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K. (2016) · Cell · doi:10.1016/j.cell.2016.10.027 · Cited by 1,513 · see citing works
The microbiome in early life: Implications for health outcomes
Tamburini, S., Shen, N., Wu, H. C., & Clemente, J. C. (2016) · Nature Medicine · doi:10.1038/nm.4142 · Cited by 1,213 · see citing works
Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer
Dominguez-Bello, M. G., De Jesus-Laboy, K. M., Shen, N., Cox, L. M., Amir, A., Gonzalez, A., Bokulich, N. A., Song, S. J., Hoashi, M., Rivera-Vinas, J. I., et al. (2016) · Nature Medicine · doi:10.1038/nm.4039 · Cited by 1,014 · see citing works
Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19
Silvin, A., Chapuis, N., Dunsmore, G., Goubet, A.-G., Dubuisson, A., Derosa, L., Almire, C., Hénon, C., Kosmider, O., Droin, N., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.002 · Cited by 834 · see citing works
Maturation of the gut microbiome and risk of asthma in childhood
Stokholm, J., Blaser, M. J., Thorsen, J., Rasmussen, M. A., Waage, J., Vinding, R. K., Schoos, A.-M. M., Kunøe, A., Fink, N. R., Chawes, B. L., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02573-2 · Cited by 614 · see citing works
Self-citationThe Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.10.002 · Cited by 555 · see citing works
Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus
Wang, J., Zheng, J., Shi, W., Du, N., Xu, X., Zhang, Y., Ji, P., Zhang, F., Jia, Z., Wang, Y., et al. (2018) · Gut · doi:10.1136/gutjnl-2018-315988 · Cited by 452 · see citing works
Wilson, R. D., Caughey, A. B., Wood, S. L., Macones, G. A., Wrench, I. J., Huang, J., Norman, M., Pettersson, K., Fawcett, W. J., Shalabi, M. M., et al. (2018) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2018.09.015 · Cited by 315 · see citing works
Wampach, L., Heintz-Buschart, A., Fritz, J. V., Ramiro-Garcia, J., Habier, J., Herold, M., Narayanasamy, S., Kaysen, A., Hogan, A. H., Bindl, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07631-x · Cited by 292 · see citing works
Torres, J., Hu, J., Seki, A., Eisele, C., Nair, N., Huang, R., Tarassishin, L., Jharap, B., Cote-Daigneault, J., Mao, Q., et al. (2020) · Gut · doi:10.1136/gutjnl-2018-317855 · Cited by 218 · see citing works
Targeting the gut‐skin axis—Probiotics as new tools for skin disorder management?
Szántó, M., Dózsa, A., Antal, D., Szabó, K., Kemény, L., & Bai, P. (2019) · Experimental Dermatology · doi:10.1111/exd.14016 · Cited by 189 · see citing works
Viral Infections, the Microbiome, and Probiotics
Harper, A., Vijayakumar, V., Ouwehand, A. C., ter Haar, J., Obis, D., Espadaler, J., Binda, S., Desiraju, S., & Day, R. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.596166 · Cited by 177 · see citing works
Fostering of advanced mutualism with gut microbiota by Immunoglobulin A
Sutherland, D. B., Suzuki, K., & Fagarasan, S. (2016) · Immunological Reviews · doi:10.1111/imr.12384 · Cited by 115 · see citing works
Cesarean delivery and infant cortisol regulation
Martinez, L. D., Glynn, L. M., Sandman, C. A., Wing, D. A., & Davis, E. P. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104862 · Cited by 32 · see citing works
- Authors
- Sevelsted, A., Stokholm, J., Bønnelykke, K., & Bisgaard, H.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Bisgaard, Hans
- Venue
- PEDIATRICS
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2015-01-01
- Volume
- 135
- Issue
- 1
- Pages
- e92-e98
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- OpenAlex
- W2147725723
- Cited by
- 482
- References
- 44
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 36 · 2023: 44 · 2022: 43 · 2021: 61 · 2020: 54 · 2019: 47 · 2018: 43 · 2017: 45 · 2016: 46 · 2015: 24 · 2014: 1
- FWCI
- 41.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PEDIATRICS (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- cesarean section, childhood asthma, connective tissue diseases, juvenile idiopathic arthritis, inflammatory bowel disease, immunodeficiency, leukemia, type 1 diabetes, psoriasis, celiac disease, allergy, immune system maturation, environmental risk factors, incidence trends
- MeSH terms
- Adolescent, Cesarean Section, Child, Child, Preschool, Chronic Disease, Female, Humans, Immune System Diseases, Infant, Infant, Newborn, Male
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review