{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:03:50Z","timestamp":1770707030468,"version":"3.49.0"},"reference-count":99,"publisher":"National Institute for Health and Care Research","issue":"30","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["16\/150\/01"],"award-info":[{"award-number":["16\/150\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby\u2019s umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-2\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-3\">\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>This was a controlled interrupted time series study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-4\">\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>The study took place in primary and secondary care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-5\">\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Children born in the UK during 2006\u201318 delivered by caesarean section were compared with a control cohort delivered vaginally.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-6\">\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>In-utero exposure to antibiotics immediately prior to birth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-7\">\n                  <jats:title>Main outcome measures<\/jats:title>\n                  <jats:p>Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-8\">\n                  <jats:title>Data sources<\/jats:title>\n                  <jats:p>The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN\u2013CPRD data set.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-9\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the THIN\u2013CPRD and HES data sets, records of 515,945 and 3,945,351 mother\u2013baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-10\">\n                  <jats:title>Limitations<\/jats:title>\n                  <jats:p>It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-11\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006\u201318 had an impact on the incidence of asthma and eczema in early childhood in the UK.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-12\">\n                  <jats:title>Future work<\/jats:title>\n                  <jats:p>There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-13\">\n                  <jats:title>Study registration<\/jats:title>\n                  <jats:p>This study is registered as researchregistry3736.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-14\">\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.<\/jats:p>\n               <\/jats:sec>","DOI":"10.3310\/zyzc8514","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T10:21:05Z","timestamp":1656930065000},"page":"1-160","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records"],"prefix":"10.3310","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-2459","authenticated-orcid":true,"given":"Dana","family":"\u0160umilo","sequence":"first","affiliation":[{"name":"Institute of Applied Health Research, University of Birmingham, Birmingham, UK"},{"name":"Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, 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