{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:44:37Z","timestamp":1790127877624,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T00:00:00Z","timestamp":1540512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH (NCI, NICHD)-USA; National Children's Study-USA"},{"name":"Children's Cancer Centre Foundation-Australia"},{"name":"Bluey Day Foundation-Australia"},{"name":"Baxter Family Foundation-Australia"},{"name":"The Rotary Club of North Brighton-Australia"},{"name":"Tour de Cure-Australia"},{"name":"Private philanthropic donations - Australia"},{"name":"Murdoch Children's Research Institute, Australia","award":["M1300049"],"award-info":[{"award-number":["M1300049"]}]},{"name":"Research Council of Norway through its Centres of Excellence funding scheme, Trigon Foundation, Denmark, UK","award":["262700"],"award-info":[{"award-number":["262700"]}]},{"name":"Medical Research Council and the Wellcome Trust","award":["092731"],"award-info":[{"award-number":["092731"]}]},{"name":"the University of Bristol currently provide core support for ALSPAC"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>The \u201cdelayed infection hypothesis\u201d states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population\u2010based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 \u00d7 10<jats:sup>6<\/jats:sup> person\u2010years of follow\u2010up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77\u20130.99) and 0.85: (0.73\u20130.99), respectively. Being later\u2010born was associated with similarly reduced hazards of CL and ALL compared to being first\u2010born; HRs = 0.78: 95% CI: 0.58\u20131.05 and 0.73: 0.52\u20131.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (<jats:italic>p<\/jats:italic> = 0.024) and paternal age (<jats:italic>p<\/jats:italic> = 0.067), respectively, in associations between being later\u2010born and CL, with the lowest risk observed for children born at &lt;3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06\u20130.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.<\/jats:p>","DOI":"10.1002\/ijc.31635","type":"journal-article","created":{"date-parts":[[2018,8,11]],"date-time":"2018-08-11T11:04:01Z","timestamp":1533985441000},"page":"26-33","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C)"],"prefix":"10.1002","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-3873","authenticated-orcid":false,"given":"Ora","family":"Paltiel","sequence":"first","affiliation":[{"name":"Braun School of Public Health and Community Medicine and Department of Hematology Hadassah\u2010Hebrew University  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Lemeshow","sequence":"additional","affiliation":[{"name":"College of Public Health The Ohio State University  Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Statistical consultant, Department of Biomedical Informatics, The Ohio State University, Center for Biostatistics, Retired"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Tikellis","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute Royal Children's Hospital, University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha S.","family":"Linet","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute  Rockville MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Louise","family":"Ponsonby","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute Royal Childrens Hospital, University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Magnus","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health Norwegian Institute of Public Health  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri E.","family":"H\u00e5berg","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health Norwegian Institute of Public Health  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjurdur F.","family":"Olsen","sequence":"additional","affiliation":[{"name":"Centre for Fetal Programming Department of Epidemiology Research, Statens Serum Institut  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta","family":"Granstr\u00f6m","sequence":"additional","affiliation":[{"name":"Centre for Fetal Programming Department of Epidemiology Research, Statens Serum Institut  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Klebanoff","sequence":"additional","affiliation":[{"name":"The Research Institute at Nationwide Children's Hospital, Departments of Pediatrics, Obstetrics and Gynecology, and Epidemiology The Ohio State University  Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Golding","sequence":"additional","affiliation":[{"name":"Centre for Child and Adolescent Health University of Bristol  Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4109-3154","authenticated-orcid":false,"given":"Zdenko","family":"Herceg","sequence":"additional","affiliation":[{"name":"Epigenetics Group International Agency for Research on Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram","family":"Ghantous","sequence":"additional","affiliation":[{"name":"Epigenetics Group International Agency for Research on Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Elizabeth","family":"Hirst","sequence":"additional","affiliation":[{"name":"Nuffield Department of Obstetrics &amp; 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