{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:32:20Z","timestamp":1790688740049,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["GTN1065494"],"award-info":[{"award-number":["GTN1065494"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN1065494"],"award-info":[{"award-number":["GTN1065494"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN1065494"],"award-info":[{"award-number":["GTN1065494"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN1045668"],"award-info":[{"award-number":["GTN1045668"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN1045668"],"award-info":[{"award-number":["GTN1045668"]}]},{"name":"Australian National Health and Medical Research Council","award":["1034254"],"award-info":[{"award-number":["1034254"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN1064629"],"award-info":[{"award-number":["GTN1064629"]}]},{"name":"DHB Foundation"},{"DOI":"10.13039\/501100010983","name":"Health Research Fund of Central Denmark Region","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF18OC0052029"],"award-info":[{"award-number":["NNF18OC0052029"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Danish Council for Independent Research","doi-asserted-by":"crossref","award":["DFF-6110-00019"],"award-info":[{"award-number":["DFF-6110-00019"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008016","name":"Financial Markets Foundation for Children","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008016","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Raine Foundation Clinician Research Fellowship"},{"DOI":"10.13039\/501100002141","name":"Public Health England","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002141","name":"Public Health England","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council"},{"name":"Medical Research Council"},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013961","name":"Robertson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013961","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013961","name":"Robertson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013961","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency\/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary\/secondary <jats:italic>International Classification of Diseases<\/jats:italic>, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%\u201329%) were by CS, of which 727,755 (43%, range 38%\u201357%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09\u20131.12, <jats:italic>p<\/jats:italic> &lt; 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12\u20131.13, <jats:italic>p<\/jats:italic> &lt; 0.001) and emergency CS (HR 1.09, 95% CI 1.06\u20131.12, <jats:italic>p<\/jats:italic> &lt; 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1003429","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T18:31:54Z","timestamp":1605810714000},"page":"e1003429","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1806-1894","authenticated-orcid":true,"given":"Jessica E.","family":"Miller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Goldacre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6434-8290","authenticated-orcid":true,"given":"Hannah C.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Zeltzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1984-4575","authenticated-orcid":true,"given":"Marian","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Nowell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4453-623X","authenticated-orcid":true,"given":"Rachael","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4904-2872","authenticated-orcid":true,"given":"Kim W.","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-4127","authenticated-orcid":true,"given":"Parveen","family":"Fathima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9223-0767","authenticated-orcid":true,"given":"Nicholas","family":"de Klerk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Strunk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Nassar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-1991","authenticated-orcid":true,"given":"Lars H.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8304-4302","authenticated-orcid":true,"given":"David P.","family":"Burgner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"issue":"10155","key":"pmed.1003429.ref001","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0140-6736(18)31928-7","article-title":"Global epidemiology of use of and disparities in caesarean sections","volume":"392","author":"T Boerma","year":"2018","journal-title":"Lancet"},{"issue":"10155","key":"pmed.1003429.ref002","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/S0140-6736(18)31930-5","article-title":"Short-term and long-term effects of caesarean section on the health of women and children","volume":"392","author":"J Sandall","year":"2018","journal-title":"Lancet"},{"issue":"10155","key":"pmed.1003429.ref003","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/S0140-6736(18)32407-3","article-title":"Strategic measures to reduce the caesarean section rate in Brazil","volume":"392","author":"GM Occhi","year":"2018","journal-title":"Lancet"},{"issue":"2","key":"pmed.1003429.ref004","doi-asserted-by":"crossref","first-page":"e0148343","DOI":"10.1371\/journal.pone.0148343","article-title":"The increasing trend in caesarean section rates: global, regional and national estimates: 1990\u20132014","volume":"11","author":"AP Betran","year":"2016","journal-title":"PLoS ONE"},{"key":"pmed.1003429.ref005","article-title":"Monitoring and interventions are needed to reduce the very high Caesarean section rates in Vietnam","author":"HTN Giang","year":"2018","journal-title":"Acta Paediatr"},{"issue":"10184","key":"pmed.1003429.ref006","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/S0140-6736(18)32386-9","article-title":"Maternal and perinatal mortality and complications associated with caesarean section in low-income and middle-income countries: a systematic review and meta-analysis","volume":"393","author":"S Sobhy","year":"2019","journal-title":"Lancet"},{"issue":"2","key":"pmed.1003429.ref007","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.jaci.2015.07.040","article-title":"Cesarean section and disease associated with immune function","volume":"137","author":"K Kristensen","year":"2016","journal-title":"J Allergy Clin Immunol"},{"issue":"21","key":"pmed.1003429.ref008","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1001\/jama.2015.16176","article-title":"Planned cesarean delivery at term and adverse outcomes in childhood health","volume":"314","author":"M Black","year":"2015","journal-title":"JAMA"},{"issue":"1","key":"pmed.1003429.ref009","doi-asserted-by":"crossref","first-page":"5091","DOI":"10.1038\/s41467-018-07631-x","article-title":"Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential","volume":"9","author":"L Wampach","year":"2018","journal-title":"Nat Commun"},{"issue":"4","key":"pmed.1003429.ref010","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nri.2017.7","article-title":"Dysbiosis and the immune system","volume":"17","author":"M Levy","year":"2017","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"pmed.1003429.ref011","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1097\/INF.0000000000001778","article-title":"Association between mode of delivery and risk of infection in early childhood: a cohort study","volume":"37","author":"N Christensen","year":"2018","journal-title":"Pediatr Infect Dis J"},{"key":"pmed.1003429.ref012","article-title":"Gestation at birth, mode of birth, infant feeding and childhood hospitalization with infection. Acta Obstet Gynecol Scand","author":"JP Bentley","year":"2018"},{"issue":"5","key":"pmed.1003429.ref013","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1136\/archdischild-2011-300607","article-title":"Hospitalisation for bronchiolitis in infants is more common after elective caesarean delivery","volume":"97","author":"HC Moore","year":"2012","journal-title":"Arch Dis Child"},{"key":"pmed.1003429.ref014","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12887-016-0591-0","article-title":"Gestational age, mode of birth and breastmilk feeding all influence acute early childhood gastroenteritis: a record-linkage cohort study","volume":"16","author":"JP Bentley","year":"2016","journal-title":"BMC Pediatr"},{"issue":"2","key":"pmed.1003429.ref015","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1097\/INF.0000000000002197","article-title":"Term Elective Cesarean Delivery and Offspring Infectious Morbidity: A Population-Based Cohort Study","volume":"38","author":"T Wainstock","year":"2019","journal-title":"Pediatr Infect Dis J"},{"key":"pmed.1003429.ref016","article-title":"Association of gestational age and growth measures at birth with infection-related admissions to hospital throughout childhood: a population-based, data-linkage study from Western Australia","author":"JE Miller","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"2","key":"pmed.1003429.ref017","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/ije\/dyx272","article-title":"Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort study","volume":"47","author":"JE Miller","year":"2018","journal-title":"Int J Epidemiol"},{"issue":"1","key":"pmed.1003429.ref018","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10654-018-0356-1","article-title":"The Danish Medical Birth Register","volume":"33","author":"M Bliddal","year":"2018","journal-title":"Eur J Epidemiol"},{"issue":"5","key":"pmed.1003429.ref019","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1467-842X.1999.tb01297.x","article-title":"Population-based linkage of health records in Western Australia: development of a health services research linked database","volume":"23","author":"CD Holman","year":"1999","journal-title":"Aust N Z J Public Health"},{"issue":"4","key":"pmed.1003429.ref020","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1093\/ije\/dyx015","article-title":"Data Resource Profile: Hospital Episode Statistics Admitted Patient Care (HES APC)","volume":"46","author":"A Herbert","year":"2017","journal-title":"Int J Epidemiol"},{"key":"pmed.1003429.ref021","unstructured":"Scotland ISD. ISD Scotland National Data Dictionary, Maternity Inpatient and Day Case (SMR02) 2019 [cited 2019 May 01]. Available from: https:\/\/www.ndc.scot.nhs.uk\/Data-Dictionary\/SMR-Datasets\/SMR02-Maternity-Inpatient-and-Day-Case\/."},{"key":"pmed.1003429.ref022","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential","volume":"7","author":"M Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"key":"pmed.1003429.ref023","volume-title":"New South Wales Mothers and Babies 2015","author":"Centre for Epidemiology and Evidence","year":"2016"},{"issue":"49","key":"pmed.1003429.ref024","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1057\/hsq.2011.3","article-title":"Linking maternity data for England, 2005\u201306: methods and data quality","author":"N Dattani","year":"2011","journal-title":"Health Stat Q"},{"issue":"1","key":"pmed.1003429.ref025","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/ije\/dyu222","article-title":"Modelling recurrent events: a tutorial for analysis in epidemiology","volume":"44","author":"LD Amorim","year":"2015","journal-title":"Int J Epidemiol"},{"key":"pmed.1003429.ref026","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13223-019-0367-9","article-title":"The association between caesarean section and childhood asthma: an updated systematic review and meta-analysis","volume":"15","author":"B Darabi","year":"2019","journal-title":"Allergy Asthma Clin Immunol"},{"issue":"4","key":"pmed.1003429.ref027","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity Analysis in Observational Research: Introducing the E-Value","volume":"167","author":"TJ VanderWeele","year":"2017","journal-title":"Ann Intern Med"},{"issue":"7184","key":"pmed.1003429.ref028","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1136\/bmj.318.7184.642","article-title":"Socioeconomic differences in childhood consultation rates in general practice in England and Wales: prospective cohort study","volume":"318","author":"S Saxena","year":"1999","journal-title":"BMJ"},{"key":"pmed.1003429.ref029","unstructured":"Caesarean section (NICE clinical guideline 132): National Institute for Health and Care Excellence; November 2011 [updated June 2018; cited 2019 April 01]. Available from: https:\/\/www.nice.org.uk\/guidance\/cg132."},{"key":"pmed.1003429.ref030","unstructured":"Gynecology DSfOa. Danish Society for Obstetrics and Gynecology\u2014Antibiotics in Obstetrics Guidelines 2012 [cited 2019 May 01]. Available from: http:\/\/gynobsguideline.dk\/sandbjerg\/120425%20ANTIBIOTIKA%20endelig%2025%204%2012.pdf."},{"key":"pmed.1003429.ref031","unstructured":"Gynaecologists TRAaNZCoOa. Prophylactic antibiotics in obstetrics and gynaecology 2011 [cited 2019 May 01]. Available from: https:\/\/www.ranzcog.edu.au\/RANZCOG_SITE\/media\/RANZCOG-MEDIA\/Women%27s%20Health\/Statement%20and%20guidelines\/Clinical%20-%20General\/Prophylactic-antibiotics-in-obstetrics-and-gynaecology-(C-Gen-17)-Review-July-2016.pdf?ext=.pdf."},{"issue":"2","key":"pmed.1003429.ref032","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1471-0528.2010.02729.x","article-title":"Current debate on the use of antibiotic prophylaxis for caesarean section","volume":"118","author":"RF Lamont","year":"2011","journal-title":"BJOG"},{"key":"pmed.1003429.ref033","volume-title":"Perinatal statistics series no. 34","author":"Australian Institute of Health and Welfare 2018","year":"2018"},{"issue":"1","key":"pmed.1003429.ref034","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1038\/s41467-019-09252-4","article-title":"Perinatal factors affect the gut microbiota up to four years after birth","volume":"10","author":"F Fouhy","year":"2019","journal-title":"Nat Commun"},{"key":"pmed.1003429.ref035","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ebiom.2016.05.031","article-title":"Development of Upper Respiratory Tract Microbiota in Infancy is Affected by Mode of Delivery","volume":"9","author":"A Bosch","year":"2016","journal-title":"EBioMedicine"},{"key":"pmed.1003429.ref036","first-page":"1","article-title":"The global numbers and costs of additionally needed and unnecessary caesarean sections performed per year: overuse as a barrier to universal coverage","volume":"30","author":"LBJ Gibbons","year":"2010","journal-title":"World health report"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003429","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T18:33:06Z","timestamp":1605810786000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003429"}},"subtitle":[],"editor":[{"given":"Gordon C.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1003429","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,19]]}}}