title: Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C).
abstract: BACKGROUND
  Evidence relating childhood cancer to high birthweight is derived primarily from registry and case-control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium.
  
  
  METHODS
  We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥ 4.0 vs. < 4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort.
  
  
  RESULTS
  A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥ 4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥ 3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02].
  
  
  CONCLUSIONS
  Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored.
authors.affiliation: Department of Hematology, Braun School of Public Health, Hadassah-Hebrew University, Jerusalem, Israel.
authors.forename: Ora
authors.initials: O
authors.lastname: Paltiel
authors.affiliation: Department of Environmental and Genetic Epidemiology, Murdoch Children's Research Institute, Royal Childrens Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Tikellis
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, UK.
authors.forename: Martha
authors.initials: M
authors.lastname: Linet
authors.affiliation: Centre for Child & Adolescent Health, School of Social & Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Golding
authors.affiliation: Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, UK.
authors.forename: Stanley
authors.initials: S
authors.lastname: Lemeshow
authors.affiliation: Division of Biostatistics, The Ohio State University Center for Biostatistics, Columbus, Ohio, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.affiliation: Centre for Physical Activity and Nutrition, Deakin University, Burwood, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Lamb
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway.|Department of Global Public Health and Community Care, University of Bergen, Bergen, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stoltenberg
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Siri E
authors.initials: SE
authors.lastname: Håberg
authors.affiliation: Department of Epidemiology Research, Center for Fetal Programming, Statenserum Institute, Copenhagen, Denmark.
authors.forename: Marin
authors.initials: M
authors.lastname: Strøm
authors.affiliation: Department of Epidemiology Research, Center for Fetal Programming, Statenserum Institute, Copenhagen, Denmark.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Granstrøm
authors.affiliation: ALSPAC (Children of the 90s), School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Northstone
authors.affiliation: Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, UK.|The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Klebanoff
authors.affiliation: Department of Environmental and Genetic Epidemiology, Murdoch Children's Research Institute, Royal Childrens Hospital, University of Melbourne, Melbourne, Australia.|Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Milne
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra, Barcelona, Spain.|IMIM (Hospital del Mar Research Institute), Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|U823, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute Albert Bonniot, INSERM (National Institute of Health and Medical Research), Grenoble, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|IMIM (Hospital del Mar Research Institute), Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Department of Nutrition, National School of Public Health, Athens, Greece.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: School of Medicine, Ewha Medical Research Center, Department of Preventive Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Ha
authors.affiliation: Department of Environmental and Genetic Epidemiology, Murdoch Children's Research Institute, Royal Childrens Hospital, University of Melbourne, Melbourne, Australia; The George Institute for Global Health, University of Oxford, Oxford, UK.|Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.|International Agency for Research on Cancer, Lyon, France.
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001315:Australia / Q000453:epidemiology; D001724:Birth Weight; D002648:Child; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007557:Israel / Q000453:epidemiology; D008297:Male; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology*; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
keywords: Childhood cancer; cohort studies; leukemia; pooled analysis.