{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:30:10Z","timestamp":1790688610399,"version":"4.1.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"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":["GTN572742"],"award-info":[{"award-number":["GTN572742"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN106594"],"award-info":[{"award-number":["GTN106594"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN1064829"],"award-info":[{"award-number":["GTN1064829"]}]},{"name":"Australian National Health and Medical Research Council","award":["GTN1175744"],"award-info":[{"award-number":["GTN1175744"]}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To assess the risk of severe childhood infections within families, we conducted a sibling analysis in a population-based cohort study with genealogical linkage. We investigated the sibling risk of hospitalization with common infections, a marker of severity. We hypothesized that having siblings hospitalized for infection would increase the proband\u2019s risk of admission with infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Study design<\/jats:title>\n<jats:p>We used population data on Western Australian live-born singletons and their siblings between 1980 and 2014. Measures of infection were infection-related hospitalizations from discharge diagnostic codes. Exposure was having a sibling who had an infection-related hospitalization. Outcomes were infection-related hospitalizations in the child\/proband. Probands were followed until an infection-related hospitalization admission (up to the first three), death, 18th birthday, or end of 2014, whichever occurred first. Infection risks were estimated by adjusted Cox proportional hazard models for multiple events.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of 512,279 probands, 142,915 (27.9%) had infection-related hospitalizations; 133,322 (26.0%) had a sibling with a previous infection-related hospitalization (i.e. exposed). Median interval between sibling and proband infection-related hospitalizations was 1.4 years (inter-quartile range 0.5\u20133.7). Probands had a dose-dependent increase in risk if sibling\/s had 1, 2, or 3+ infection-related hospitalizations (adjusted hazard ratio, aHR 1.41, 95% CI 1.39\u20131.43; aHR 1.65, 1.61\u20131.69; aHR 1.83, 1.77\u20131.90, respectively). Among siblings with the same clinical infection type, highest sibling risks were for genitourinary (aHR 2.06, 1.68\u20132.53), gastrointestinal (aHR 2.07, 1.94\u20132.19), and skin\/soft tissue infections (aHR 2.34, 2.15\u20132.54). Overall risk of infection-related hospitalization was higher in children with more siblings and with older siblings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In this population-based study, we observed an increased risk of infection-related hospitalization in children whose siblings were previously hospitalized for infection. Public health interventions may be particularly relevant in families of children hospitalized with infection.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0250181","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T17:45:19Z","timestamp":1619631919000},"page":"e0250181","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["The familial risk of infection-related hospitalization in children: A population-based sibling study"],"prefix":"10.1371","volume":"16","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":"Kim W.","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"de Klerk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Burgner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"issue":"6","key":"pone.0250181.ref001","doi-asserted-by":"crossref","first-page":"e158","DOI":"10.1097\/INF.0000000000001134","article-title":"Trends in Infectious Disease Hospitalizations in US Children, 2000 to 2012","volume":"35","author":"T Goto","year":"2016","journal-title":"Pediatr Infect Dis J"},{"issue":"2","key":"pone.0250181.ref002","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1542\/peds.2007-1392","article-title":"Infectious disease hospitalizations among infants in the United States","volume":"121","author":"KL Yorita","year":"2008","journal-title":"Pediatrics"},{"issue":"10","key":"pone.0250181.ref003","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1473-3099(06)70601-6","article-title":"Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?","volume":"6","author":"D Burgner","year":"2006","journal-title":"Lancet Infect Dis"},{"key":"pone.0250181.ref004","doi-asserted-by":"crossref","first-page":"l5784","DOI":"10.1136\/bmj.l5784","article-title":"Stress related disorders and subsequent risk of life threatening infections: population based sibling controlled cohort study","volume":"367","author":"H Song","year":"2019","journal-title":"BMJ"},{"issue":"5","key":"pone.0250181.ref005","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/ije\/dyu118","article-title":"Sibship structure and risk of infectious mononucleosis: a population-based cohort study","volume":"43","author":"K Rostgaard","year":"2014","journal-title":"Int J Epidemiol"},{"key":"pone.0250181.ref006","unstructured":"Australia P. Population of Western Australia 2020 [cited 2020 May 1]. http:\/\/www.population.net.au\/population-of-western-australia\/."},{"issue":"1","key":"pone.0250181.ref007","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/ije\/dym136","article-title":"Cohort profile: The Western Australian Family Connections Genealogical Project","volume":"37","author":"EJ Glasson","year":"2008","journal-title":"Int J Epidemiol"},{"issue":"3","key":"pone.0250181.ref008","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1017\/S0950268803008513","article-title":"Sibling familial risk ratio of meningococcal disease in UK Caucasians","volume":"130","author":"E Haralambous","year":"2003","journal-title":"Epidemiol Infect"},{"issue":"3","key":"pone.0250181.ref009","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/01.inf.0000254148.09831.7f","article-title":"Infection is the major component of the disease burden in aboriginal and non-aboriginal Australian children: a population-based study","volume":"26","author":"KS Carville","year":"2007","journal-title":"Pediatr Infect Dis J"},{"issue":"4","key":"pone.0250181.ref010","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1071\/AH080766","article-title":"A decade of data linkage in Western Australia: strategic design, applications and benefits of the WA data linkage system","volume":"32","author":"CD Holman","year":"2008","journal-title":"Aust Health Rev"},{"issue":"5","key":"pone.0250181.ref011","doi-asserted-by":"crossref","first-page":"e10603","DOI":"10.1371\/journal.pone.0010603","article-title":"Genetic influences on incidence and case-fatality of infectious disease","volume":"5","author":"L Petersen","year":"2010","journal-title":"PLoS One"},{"key":"pone.0250181.ref012","doi-asserted-by":"crossref","first-page":"j3862","DOI":"10.1136\/bmj.j3862","article-title":"Non-specific effects of measles, mumps, and rubella (MMR) vaccination in high income setting: population based cohort study in the Netherlands","volume":"358","author":"S Tielemans","year":"2017","journal-title":"BMJ"},{"key":"pone.0250181.ref013","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"},{"key":"pone.0250181.ref014","unstructured":"Pink B. An Introduction to Socio-Economic Indexes for Areas (SEIFA). In: Statistics. ABo, editor. Canberra: Australian Bureau of Statistics.; 2006."},{"issue":"2","key":"pone.0250181.ref015","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/biomet\/68.2.373","article-title":"On the regression analysis of multivariate failure time data","volume":"68","author":"RL Prentice","year":"1981","journal-title":"Biometrika"},{"issue":"4","key":"pone.0250181.ref016","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"},{"key":"pone.0250181.ref017","unstructured":"StataCorp. STATA Statistical Software: Release 13. 13.0 ed. College Station, TX:2013."},{"issue":"2","key":"pone.0250181.ref018","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0020-2452(98)80001-8","article-title":"Twin studies for the analysis of heritability of infections diseases","volume":"96","author":"A Jepson","year":"1998","journal-title":"B I Pasteur"},{"issue":"4","key":"pone.0250181.ref019","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1542\/peds.2006-0373","article-title":"Population-based study of the impact of childcare attendance on hospitalizations for acute respiratory infections","volume":"118","author":"M Kamper-Jorgensen","year":"2006","journal-title":"Pediatrics"},{"key":"pone.0250181.ref020","unstructured":"Statistics ABo. Childhood Education and Care (cat. no. 4402.0). Australia: 2008 June 2008. Report No."},{"issue":"1 Pt 1","key":"pone.0250181.ref021","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0091-6749(00)90171-4","article-title":"The environmental predictors of allergic disease","volume":"105","author":"E von Mutius","year":"2000","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"pone.0250181.ref022","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/cei.12077","article-title":"Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially","volume":"172","author":"AM Hughes","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"pone.0250181.ref023","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12866-015-0477-6","article-title":"Having older siblings is associated with gut microbiota development during early childhood","volume":"15","author":"MF Laursen","year":"2015","journal-title":"BMC Microbiol"},{"issue":"4","key":"pone.0250181.ref024","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1365-3016.1994.tb00482.x","article-title":"A population database for maternal and child health research in Western Australia using record linkage","volume":"8","author":"FJ Stanley","year":"1994","journal-title":"Paediatr Perinat Epidemiol"},{"key":"pone.0250181.ref025","unstructured":"Gee V HQ, Ernstzen AN. Perinatal Statistics in Western Australia, 2005: Twenty third Annual Report of the Western Australian Midwives\u2019 Notification System. Department of Health, Western Australia, 2007."},{"issue":"7184","key":"pone.0250181.ref026","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"},{"issue":"6","key":"pone.0250181.ref027","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1542\/peds.104.6.1251","article-title":"Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and parent beliefs","volume":"104","author":"RL Watson","year":"1999","journal-title":"Pediatrics"},{"issue":"22","key":"pone.0250181.ref028","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1001\/jama.282.22.2125","article-title":"The heritability of otitis media: a twin and triplet study","volume":"282","author":"ML Casselbrant","year":"1999","journal-title":"JAMA"},{"issue":"12","key":"pone.0250181.ref029","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1164\/rccm.200703-435OC","article-title":"Heredity versus environment in tuberculosis in twins: the 1950s United Kingdom Prophit Survey Simonds and Comstock revisited","volume":"176","author":"EA van der Eijk","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0250181.ref030","unstructured":"Statistics ABo. Migration, Australia 2013\u201314 2015 [6\/11\/2015]. http:\/\/www.abs.gov.au\/ausstats\/abs@.nsf\/mf\/3412.0\/."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T17:46:17Z","timestamp":1619631977000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250181"}},"subtitle":[],"editor":[{"given":"Sreeram V.","family":"Ramagopalan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,28]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0250181","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,28]]}}}