{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:02Z","timestamp":1792788722726,"version":"4.5.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["108\/0001"],"award-info":[{"award-number":["108\/0001"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["108\/0001"],"award-info":[{"award-number":["108\/0001"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clarendon Fund Scholarships and the Nuffield Department of Population Health"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Several studies have reported that birth by caesarean section is associated with increased risk of lower respiratory tract infections in the child, but it is unclear whether this applies to any caesarean section or specifically to planned caesareans. Furthermore, although infections of the upper respiratory tract are very common during childhood, there is a scarcity of studies examining whether caesarean is also a risk factor for this site of infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We obtained data from two UK cohorts: the Millennium Cohort Study (MCS) and linked administrative datasets of the population of Wales through the Secure Anonymised Information Linkage (SAIL) databank. The study focused on term-born singleton infants and included 15,580 infants born 2000\u20132002 (MCS) and 392,145 infants born 2002\u20132016 (SAIL). We used information about mode of birth (vaginal delivery, assisted vaginal delivery, planned caesarean and emergency caesarean) from maternal report in the MCS and from hospital birth records in SAIL. Unplanned hospital admission for lower respiratory tract infection (LRTI) was ascertained from maternal report in the MCS and from hospital record ICD codes in SAIL. Information about admissions for upper respiratory tract infection (URTI) was available from SAIL only. Cox regression was used to estimate hazard ratios for each outcome and cohort separately while accounting for a wide range of confounders. Gestational age at birth was further examined as a potential added, indirect risk of planned caesarean birth due to the early delivery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>The rate of hospital admission for LRTI was 4.6 per 100 child years in the MCS and 5.9 per 100 child years in SAIL. Emergency caesarean was not associated with LRTI admission during infancy in either cohort. In the MCS, planned caesarean was associated with a hazard ratio of 1.39 (95% CI 1.03, 1.87) which further increased to 1.65 (95% CI 1.24, 2.19) when gestational age was not adjusted for. In SAIL, the adjusted hazard ratio was 1.10 (95% CI 1.05, 1.15), which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for. The rate of hospital admission for URTI was 5.9 per 100 child years in SAIL. Following adjustments, emergency caesarean was found to have a hazard ratio of 1.09 (95% CI 1.05, 1.14) for hospital admission for URTI. Planned caesarean was associated with a hazard ratio of 1.11 (95% CI 1.06, 1.16) which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The risk of severe LRTIs during infancy is moderately elevated in infants born by planned caesarean compared to those born vaginally. Infants born by any type of caesarean may also be at a small increased risk of severe URTIs. The estimated effect sizes are stronger if including the indirect effect arising from planning the caesarean birth for an earlier gestation than would have occurred spontaneously. Further studies are needed to confirm these results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0246832","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T17:18:23Z","timestamp":1613495903000},"page":"e0246832","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Caesarean section and severe upper and lower respiratory tract infections during infancy: Evidence from two UK cohorts"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8027-4164","authenticated-orcid":true,"given":"Neora","family":"Alterman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Kurinczuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Quigley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"pone.0246832.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0148343","article-title":"The Increasing Trend in Caesarean Section Rates: Global, Regional and National Estimates: 1990\u20132014","author":"AP Betr\u00e1n","year":"2016"},{"key":"pone.0246832.ref002","unstructured":"Government Statistical Service. NHS Maternity Statistics, England: 1998\u201399 to 2000\u201301. 2002."},{"key":"pone.0246832.ref003","unstructured":"NHS Digital. NHS Maternity Statistics, England 2017\u201318. NHS Maternity Statistics, England. 2018."},{"key":"pone.0246832.ref004","unstructured":"World Health Organization. WHO Statement on casarean Section Rate. Geneva; 2015."},{"issue":"6","key":"pone.0246832.ref005","doi-asserted-by":"crossref","first-page":"e1562","DOI":"10.1542\/peds.2013-1737","article-title":"Gestational Age, Birth Weight, and Risk of Respiratory Hospital Admission in Childhood","volume":"132","author":"S Paranjothy","year":"2013","journal-title":"Pediatrics"},{"issue":"2","key":"pone.0246832.ref006","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1136\/archdischild-2015-308723","article-title":"Admission to hospital for bronchiolitis in England: trends over five decades, geographical variation and association with perinatal characteristics and subsequent asthma","volume":"101","author":"CA Green","year":"2016","journal-title":"Arch Dis Child"},{"issue":"5","key":"pone.0246832.ref007","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"},{"issue":"2","key":"pone.0246832.ref008","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/INF.0000000000000552","article-title":"Caesarean section and hospitalization for respiratory syncytial virus infection: a population-based study","volume":"34","author":"K Kristensen","year":"2015","journal-title":"Pediatr Infect Dis J"},{"issue":"8","key":"pone.0246832.ref009","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1136\/archdischild-2011-301458","article-title":"Mode of delivery may be the risk factor for infant infectious morbidity","volume":"97","author":"CL Roberts","year":"2012","journal-title":"Arch Dis Child"},{"issue":"1","key":"pone.0246832.ref010","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1186\/1471-2458-10-757","article-title":"A retrospective population-based cohort study identifying target areas for prevention of acute lower respiratory infections in children","volume":"10","author":"HC Moore","year":"2010","journal-title":"BMC Public Health"},{"issue":"2","key":"pone.0246832.ref011","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":"2","key":"pone.0246832.ref012","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ppul.23908","article-title":"Hospital admissions for lower respiratory tract infections in children born moderately\/late preterm","volume":"53","author":"P Haataja","year":"2018","journal-title":"Pediatr Pulmonol"},{"issue":"11","key":"pone.0246832.ref013","doi-asserted-by":"crossref","first-page":"e1003429","DOI":"10.1371\/journal.pmed.1003429","article-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","volume":"17","author":"JE Miller","year":"2020","journal-title":"PLOS Med"},{"key":"pone.0246832.ref014","first-page":"1","article-title":"The effect of medical and operative birth interventions on child health outcomes in the first 28 days and up to 5 years of age: A linked data population-based cohort study","author":"LL Peters","year":"2018","journal-title":"Birth"},{"issue":"8","key":"pone.0246832.ref015","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/S1473-3099(16)00150-X","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","volume":"16","author":"JE Miller","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"June","key":"pone.0246832.ref016","first-page":"1","article-title":"Lower respiratory tract disorder hospitalizations among children born via elective early-term delivery","volume":"7058","author":"KD Tickell","year":"2015","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"3","key":"pone.0246832.ref017","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.jaci.2015.05.005","article-title":"Early-term birth is a risk factor for wheezing in childhood: A cross-sectional population study","volume":"136","author":"MO Edwards","year":"2015","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"pone.0246832.ref018","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/j.1651-2227.2004.tb02990.x","article-title":"Neonatal respiratory morbidity risk and mode of delivery at term: influence of timing of elective caesarean delivery","volume":"93","author":"V Zanardo","year":"2004","journal-title":"Acta Paediatr"},{"key":"pone.0246832.ref019","first-page":"49","article-title":"The respiratory consequences of early-term birth and delivery by caesarean sections","volume":"19","author":"SJ Kotecha","year":"2016","journal-title":"Paediatr Respir Rev"},{"issue":"3","key":"pone.0246832.ref020","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1740-8709.2008.00176.x","article-title":"Breastfeeding protects against infectious diseases during infancy in industrialized countries. A systematic review","volume":"5","author":"L Duijts","year":"2009","journal-title":"Matern Child Nutr"},{"issue":"1","key":"pone.0246832.ref021","doi-asserted-by":"crossref","DOI":"10.1111\/mcn.12263","article-title":"Breastfeeding and infant hospitalisation: analysis of the UK 2010 Infant Feeding Survey","volume":"13","author":"S Payne","year":"2017","journal-title":"Matern Child Nutr"},{"key":"pone.0246832.ref022","author":"A Cullis","year":"2007","journal-title":"A Technical Report Infant Mortality in the Millennium Cohort Study (MCS) Sample Areas"},{"key":"pone.0246832.ref023","article-title":"The Millennium Cohort Study: Technical Report on Sampling","author":"I Plewis","year":"2007","journal-title":"Centre for Longitudinal Studies"},{"key":"pone.0246832.ref024","unstructured":"Centre for Longitudinal Studies. Millennium Cohort Study [Internet]. [cited 2019 Jul 16]. Available from: https:\/\/cls.ucl.ac.uk\/cls-studies\/millennium-cohort-study\/"},{"issue":"1","key":"pone.0246832.ref025","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/1472-6963-9-157","article-title":"The SAIL Databank: building a national architecture for e-health research and evaluation","volume":"9","author":"D V Ford","year":"2009","journal-title":"BMC Health Serv Res"},{"issue":"1","key":"pone.0246832.ref026","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1472-6947-9-3","article-title":"The SAIL databank: linking multiple health and social care datasets","volume":"9","author":"RA Lyons","year":"2009","journal-title":"BMC Med Inform Decis Mak"},{"key":"pone.0246832.ref027","volume-title":"Births in Wales 2017: Data from the National Community Child Health Database","author":"Statistics for Wales","year":"2018"},{"key":"pone.0246832.ref028","unstructured":"NHS Wales Informatics Service. Handling patient details [Internet]. NHS Wales Informatics Service; 2017 [cited 2018 Nov 7]. Available from: http:\/\/www.wales.nhs.uk\/nwis\/page\/52552"},{"key":"pone.0246832.ref029","unstructured":"Office for National Statistics. Deaths registered in England and Wales: 2017 [Internet]. [cited 2018 Dec 5]. Available from: https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/birthsdeathsandmarriages\/deaths\/bulletins\/deathsregistrationsummarytables\/2017"},{"key":"pone.0246832.ref030","unstructured":"Public health Wales. Congenital Anomaly Register and Information Service (CARIS) [Internet]. [cited 2018 Nov 7]. Available from: http:\/\/www.caris.wales.nhs.uk\/home"},{"issue":"2","key":"pone.0246832.ref031","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1471-0528.2006.01203.x","article-title":"Agreement between hospital records and maternal recall of mode of delivery: evidence from 12 391 deliveries in the UK Millennium Cohort Study","volume":"114","author":"MA Quigley","year":"2007","journal-title":"BJOG"},{"issue":"6","key":"pone.0246832.ref032","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/1471-0528.12177","article-title":"Which women are at an increased risk of a caesarean section or an instrumental vaginal birth in the UK: an exploration within the Millennium Cohort Study","volume":"120","author":"HN Essex","year":"2013","journal-title":"BJOG"},{"key":"pone.0246832.ref033","article-title":"Millennium Cohort Study\u2014Ethical review and consent","author":"P Shepherd","year":"2019"},{"issue":"9","key":"pone.0246832.ref034","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1097\/INF.0b013e31829b7e43","article-title":"Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years","volume":"32","author":"EK Miller","year":"2013","journal-title":"Pediatr Infect Dis J"},{"issue":"11","key":"pone.0246832.ref035","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1093\/aje\/kwr242","article-title":"Delivery by Cesarean section and early childhood respiratory symptoms and disorders: the Norwegian mother and child cohort study","volume":"174","author":"MC Magnus","year":"2011","journal-title":"Am J Epidemiol"},{"issue":"6","key":"pone.0246832.ref036","doi-asserted-by":"crossref","first-page":"e20170933","DOI":"10.1542\/peds.2017-0933","article-title":"Epidemiology and Risk Factors of Infection in Early Childhood","volume":"141","author":"NH Vissing","year":"2018","journal-title":"Pediatrics"},{"key":"pone.0246832.ref037","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3389\/fmicb.2013.00391","article-title":"Epidemiology of virus-induced wheezing\/asthma in children","volume":"4","author":"Y Inoue","year":"2013","journal-title":"Front Microbiol."},{"issue":"1","key":"pone.0246832.ref038","doi-asserted-by":"crossref","first-page":"e1002494","DOI":"10.1371\/journal.pmed.1002494","article-title":"Long-term risks and benefits associated with cesarean delivery for mother, baby, and subsequent pregnancies: Systematic review and meta-analysis.","volume":"15","author":"OE Keag","year":"2018","journal-title":"PLOS MedJan 23"},{"key":"pone.0246832.ref039","article-title":"Caesarean section NICE clinical guideline (CG132)","author":"National Collaborating Centre for Women\u2019s and Children\u2019s Health","year":"2011"},{"key":"pone.0246832.ref040","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1471-2393-11-43","article-title":"The timing of elective caesarean delivery between 2000 and 2009 in England","volume":"11","author":"I Gurol-Urganci","year":"2011","journal-title":"BMC Pregnancy Childbirth"},{"issue":"2","key":"pone.0246832.ref041","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1001\/archpedi.159.2.167","article-title":"Validity of maternal report of acute health care use for children younger than 3 years","volume":"159","author":"D D\u2019Souza-Vazirani","year":"2005","journal-title":"Arch Pediatr Adolesc Med"},{"issue":"343","key":"pone.0246832.ref042","doi-asserted-by":"crossref","first-page":"343ra82","DOI":"10.1126\/scitranslmed.aad7121","article-title":"Antibiotics, birth mode, and diet shape microbiome maturation during early life","volume":"8","author":"NA Bokulich","year":"2016","journal-title":"Sci Transl Med"},{"issue":"1","key":"pone.0246832.ref043","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1053\/j.semperi.2006.01.006","article-title":"Physiology of Fetal Lung Fluid Clearance and the Effect of Labor","volume":"30","author":"L Jain","year":"2006","journal-title":"Semin Perinatol"},{"issue":"2","key":"pone.0246832.ref044","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.clp.2008.03.006","article-title":"Elective cesarean section: its impact on neonatal respiratory outcome","volume":"35","author":"A Ramachandrappa","year":"2008","journal-title":"Clin PerinatolJun"},{"issue":"26","key":"pone.0246832.ref045","doi-asserted-by":"crossref","first-page":"11971","DOI":"10.1073\/pnas.1002601107","article-title":"Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns","volume":"107","author":"MG Dominguez-Bello","year":"2010","journal-title":"Proc Natl Acad Sci"},{"issue":"7776","key":"pone.0246832.ref046","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41586-019-1560-1","article-title":"Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth","volume":"574","author":"Y Shao","year":"2019","journal-title":"Nature"},{"issue":"5","key":"pone.0246832.ref047","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1503\/cmaj.121189","article-title":"Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months","volume":"185","author":"MB Azad","year":"2013","journal-title":"CMAJ"},{"issue":"3","key":"pone.0246832.ref048","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nm.4272","article-title":"Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery","volume":"23","author":"DM Chu","year":"2017","journal-title":"Nat Med"},{"key":"pone.0246832.ref049","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":"pone.0246832.ref050","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.1016\/S0163-4453(17)30196-2","article-title":"The respiratory microbiome and respiratory infections","volume":"74","author":"SA Unger","year":"2017","journal-title":"J Infect"},{"key":"pone.0246832.ref051","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fimmu.2018.00226","article-title":"Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome","volume":"9","author":"W Fonseca","year":"2018","journal-title":"Front Immunol"},{"issue":"4","key":"pone.0246832.ref052","doi-asserted-by":"crossref","first-page":"e837","DOI":"10.1542\/peds.2006-2256","article-title":"Breastfeeding and Hospitalization for Diarrheal and Respiratory Infection in the United Kingdom Millennium Cohort Study","volume":"119","author":"MA Quigley","year":"2007","journal-title":"Pediatrics"},{"issue":"12","key":"pone.0246832.ref053","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.jclinepi.2011.03.007","article-title":"Accurate reporting of expected delivery date by mothers 9 months after birth","volume":"64","author":"G Poulsen","year":"2011","journal-title":"J Clin Epidemiol"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0248548","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246832","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T17:18:53Z","timestamp":1613495933000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246832"}},"subtitle":[],"editor":[{"given":"Umberto","family":"Simeoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,16]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0246832","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,16]]}}}