{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:05:32Z","timestamp":1792011932294,"version":"4.4.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,4,7]],"date-time":"2018-04-07T00:00:00Z","timestamp":1523059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001732","name":"Danish National Research Foundation","doi-asserted-by":"publisher","award":["DNRF108"],"award-info":[{"award-number":["DNRF108"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Danish Council for Independent Research","doi-asserted-by":"publisher","award":["DFF4183-00316"],"award-info":[{"award-number":["DFF4183-00316"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The bacillus Calmette-Gu\u00e9rin (BCG) vaccine against tuberculosis might reduce the non\u2013tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85\u20131.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86\u20131.16).<\/jats:p>\n                    <jats:p>Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45\u20130.94); the HR for children who had a non\u2013BCG-vaccinated mother was 1.10 (95% CI, 0.93\u20131.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54\u20130.99] in children born by cesarean section vs 1.10 [95% CI, 0.92\u20131.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95\u20133.43), whereas the HR was 0.94 (95% CI, 0.82\u20131.08) for children born at term (P = .05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpids\/piy029","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T07:09:28Z","timestamp":1519974568000},"page":"213-220","source":"Crossref","is-referenced-by-count":64,"title":["BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children: A Randomized Clinical Multicenter Trial"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-153X","authenticated-orcid":false,"given":"Lone Graff","family":"Stensballe","sequence":"first","affiliation":[{"name":"Child and Adolescent Clinic, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej, Copenhagen \u00d8, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Ravn","sequence":"additional","affiliation":[{"name":"Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej, Copenhagen S, Denmark"},{"name":"OPEN, Odense Patient Data Explorative Network, Odense University Hospital\/Department of Clinical Research, University of Southern Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina Marie","family":"Birk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Copenhagen University Hospital, Hvidovre, Kettegaard All\u00e9, Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Kj\u00e6rgaard","sequence":"additional","affiliation":[{"name":"Research Unit Womens\u2019 and Childrens\u2019 Health, Child and Adolescent Clinic, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen \u00d8, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas N\u00f8rrelykke","family":"Nissen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Copenhagen University Hospital, Hvidovre, Kettegaard All\u00e9, Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte Thybo","family":"Pihl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kolding Hospital, Skovvangen, Kolding and Institute of Regional Health Research, University of Southern Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth Marianne","family":"Th\u00f8stesen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kolding Hospital, Skovvangen, Kolding and Institute of Regional Health Research, University of Southern Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorm","family":"Greisen","sequence":"additional","affiliation":[{"name":"Neonatal Department, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen \u00d8, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorthe Lisbeth","family":"Jeppesen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Copenhagen University Hospital, Hvidovre, Kettegaard All\u00e9, Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poul-Erik","family":"Kofoed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kolding Hospital, Skovvangen, Kolding and Institute of Regional Health Research, University of Southern Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Pryds","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Copenhagen University Hospital, Hvidovre, Kettegaard All\u00e9, Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"S\u00f8rup","sequence":"additional","affiliation":[{"name":"Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej, Copenhagen S, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Aaby","sequence":"additional","affiliation":[{"name":"Bandim Health Project, Statens Serum Institut, Copenhagen S, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Stabell","family":"Benn","sequence":"additional","affiliation":[{"name":"OPEN, Odense Patient Data Explorative Network, Odense University Hospital\/Department of Clinical Research, University of Southern Denmark"},{"name":"Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Copenhagen S, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,7]]},"reference":[{"key":"2019101003054497000_CIT0001","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/infdis\/jir240","article-title":"Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period","volume":"204","author":"Aaby","year":"2011","journal-title":"J Infect Dis"},{"key":"2019101003054497000_CIT0002","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1097\/INF.0b013e3182458289","article-title":"Small randomized trial among low-birth-weight children receiving bacillus Calmette-Gu\u00e9rin vaccination at first health center contact","volume":"31","author":"Biering-S\u00f8rensen","year":"2012","journal-title":"Pediatr Infect Dis J"},{"key":"2019101003054497000_CIT0003","doi-asserted-by":"crossref","first-page":"i5170","DOI":"10.1136\/bmj.i5170","article-title":"Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review","volume":"355","author":"Higgins","year":"2016","journal-title":"BMJ"},{"key":"2019101003054497000_CIT0004","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12889-015-1497-8","article-title":"Child survival and BCG vaccination: a community based prospective cohort study in Uganda","volume":"15","author":"Nankabirwa","year":"2015","journal-title":"BMC Public Health"},{"key":"2019101003054497000_CIT0005","doi-asserted-by":"crossref","first-page":"17537","DOI":"10.1073\/pnas.1202870109","article-title":"Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes","volume":"109","author":"Kleinnijenhuis","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019101003054497000_CIT0006","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1093\/infdis\/jiu508","article-title":"Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial","volume":"211","author":"Jensen","year":"2015","journal-title":"J Infect Dis"},{"key":"2019101003054497000_CIT0007","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.cct.2015.04.006","article-title":"Bacillus Calmette-Gu\u00e9rin immunisation at birth and morbidity among Danish children: a prospective, randomised, clinical trial","volume":"42","author":"Th\u00f8stesen","year":"2015","journal-title":"Contemp Clin Trials"},{"key":"2019101003054497000_CIT0008","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1136\/archdischild-2016-310760","article-title":"BCG vaccination at birth and early childhood hospitalisation: a randomised clinical multicentre trial","volume":"102","author":"Stensballe","year":"2016","journal-title":"Arch Dis Child"},{"key":"2019101003054497000_CIT0009","volume-title":"The Danish childhood vaccination programme","author":"Statens Serum Institut"},{"key":"2019101003054497000_CIT0010","first-page":"263","article-title":"The Danish National Hospital Register. A valuable source of data for modern health sciences","volume":"46","author":"Andersen","year":"1999","journal-title":"Dan Med Bull"},{"key":"2019101003054497000_CIT0011","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/1403494811401482","article-title":"The Danish national patient register","volume":"39","author":"Lynge","year":"2011","journal-title":"Scand J Public Health"},{"key":"2019101003054497000_CIT0012","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1016\/j.vaccine.2004.10.022","article-title":"Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000\u20132002","volume":"23","author":"Roth","year":"2005","journal-title":"Vaccine"},{"key":"2019101003054497000_CIT0013","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/ni.2961","article-title":"Nonspecific effects of neonatal and infant vaccination: public-health, immunological and conceptual challenges","volume":"15","author":"Aaby","year":"2014","journal-title":"Nat Immunol"},{"key":"2019101003054497000_CIT0014","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1128\/IAI.01611-06","article-title":"Strain-dependent variation in Mycobacterium bovis BCG-induced human T-cell activation and gamma interferon production in vitro","volume":"75","author":"Aguirre-Blanco","year":"2007","journal-title":"Infect Immun"},{"key":"2019101003054497000_CIT0015","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1016\/j.vaccine.2012.01.053","article-title":"The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda","volume":"30","author":"Anderson","year":"2012","journal-title":"Vaccine"},{"key":"2019101003054497000_CIT0016","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/pr.2016.142","article-title":"Nonspecific effect of BCG vaccination at birth on early childhood infections: a randomized, clinical multicenter trial","volume":"80","author":"Kjaergaard","year":"2016","journal-title":"Pediatr Res"},{"key":"2019101003054497000_CIT0017","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1136\/bmj.299.6710.1259","article-title":"Hay fever, hygiene, and household size","volume":"299","author":"Strachan","year":"1989","journal-title":"BMJ"},{"key":"2019101003054497000_CIT0018","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/nm.4039","article-title":"Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer","volume":"22","author":"Dominguez-Bello","year":"2016","journal-title":"Nat Med"},{"key":"2019101003054497000_CIT0019","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1126\/science.aad9378","article-title":"How colonization by microbiota in early life shapes the immune system","volume":"352","author":"Gensollen","year":"2016","journal-title":"Science"},{"key":"2019101003054497000_CIT0020","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/cid\/ciu354","article-title":"Measles vaccination in the presence or absence of maternal measles antibody: impact on child survival","volume":"59","author":"Aaby","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2019101003054497000_CIT0021","doi-asserted-by":"crossref","first-page":"6436","DOI":"10.1016\/j.vaccine.2015.08.035","article-title":"Maternal benefits of immunization during pregnancy","volume":"33","author":"Swamy","year":"2015","journal-title":"Vaccine"},{"key":"2019101003054497000_CIT0022","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1016\/S0264-410X(03)00342-6","article-title":"Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants","volume":"21","author":"Siegrist","year":"2003","journal-title":"Vaccine"},{"key":"2019101003054497000_CIT0023","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.phrp.2012.01.008","article-title":"Effect of maternal immune status on responsiveness of bacillus Calmette-Gurin vaccination in mouse neonates","volume":"3","author":"Choi","year":"2012","journal-title":"Osong Public Health Res Perspect"},{"key":"2019101003054497000_CIT0024","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.vaccine.2014.12.015","article-title":"Factors associated with tuberculosis infection, and with anti-mycobacterial immune responses, among five year olds BCG-immunised at birth in Entebbe, Uganda","volume":"33","author":"Lule","year":"2015","journal-title":"Vaccine"},{"key":"2019101003054497000_CIT0025","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.vaccine.2010.10.047","article-title":"Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation","volume":"29","author":"Elliott","year":"2010","journal-title":"Vaccine"},{"key":"2019101003054497000_CIT0026","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.vaccine.2016.11.079","article-title":"Maternal BCG scar is associated with increased infant proinflammatory immune responses","volume":"35","author":"Mawa","year":"2017","journal-title":"Vaccine"},{"key":"2019101003054497000_CIT0027","first-page":"221","article-title":"Meeting of the Strategic Advisory Group of Experts on immunization, April 2014\u2014conclusions and recommendations","volume":"89","year":"2014","journal-title":"Wkly Epidemiol Rec"},{"key":"2019101003054497000_CIT0028","volume-title":"Resultats des experiences de vaccination par le BCG poursuivies dans le Norrbotten (Su\u00e8de) (Septembre 1927\u2013D\u00e9cembre 1931)","author":"Naeslund","year":"1932"},{"key":"2019101003054497000_CIT0029","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1136\/adc.2009.157537","article-title":"The non-specific effects of vaccines","volume":"95","author":"Shann","year":"2010","journal-title":"Arch Dis Child"},{"key":"2019101003054497000_CIT0030","first-page":"2122","article-title":"Non-specific effects of BCG vaccination on morbidity among children in Greenland: a population-based cohort study","volume":"45","author":"Haahr","year":"2016","journal-title":"Int J Epidemiol"},{"key":"2019101003054497000_CIT0031","first-page":"2131","article-title":"Commentary: BCG has no beneficial non-specific effects on Greenland. An answer to the wrong question","volume":"45","author":"Benn","year":"2016","journal-title":"Int J Epidemiol"},{"key":"2019101003054497000_CIT0032","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/ije\/dyx044","article-title":"Non-specific effects of BCG vaccination on morbidity among children in Greenland\u2014an answer to a relevant question","volume":"46","author":"Haahr","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2019101003054497000_CIT0033","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1016\/j.vaccine.2016.03.100","article-title":"Adverse reactions to the bacillus Calmette-Gu\u00e9rin (BCG) vaccine in new-born infants\u2014an evaluation of the Danish strain 1331 SSI in a randomized clinical trial","volume":"34","author":"Nissen","year":"2016","journal-title":"Vaccine"}],"container-title":["Journal of the Pediatric Infectious Diseases Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jpids\/article-pdf\/8\/3\/213\/30125122\/piy029.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jpids\/article-pdf\/8\/3\/213\/30125122\/piy029.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T03:14:53Z","timestamp":1570677293000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpids\/article\/8\/3\/213\/4964630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,7]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,4,7]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpids\/piy029","relation":{},"ISSN":["2048-7207"],"issn-type":[{"value":"2048-7207","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2018,4,7]]}}}