title: Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies.
abstract: BACKGROUND
  The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies.
  
  
  METHODS
  Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity.
  
  
  RESULTS
  Data were available for 6 cohort and 25 case-control studies, including 11,955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I² = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children < 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I² = 23%).
  
  
  CONCLUSIONS
  Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged < 5 years. This finding could reflect increased exposure to infections in early life in later born children.
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, UK. c.cardwell@qub.ac.uk
authors.forename: Chris R
authors.initials: CR
authors.lastname: Cardwell
authors.forename: Lars C
authors.initials: LC
authors.lastname: Stene
authors.forename: Geir
authors.initials: G
authors.lastname: Joner
authors.forename: Max K
authors.initials: MK
authors.lastname: Bulsara
authors.forename: Ondrej
authors.initials: O
authors.lastname: Cinek
authors.forename: Joachim
authors.initials: J
authors.lastname: Rosenbauer
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: Jannet
authors.initials: J
authors.lastname: Svensson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goldacre
authors.forename: Thomas
authors.initials: T
authors.lastname: Waldhoer
authors.forename: Przemyslawa
authors.initials: P
authors.lastname: Jarosz-Chobot
authors.forename: Suely Ga
authors.initials: SG
authors.lastname: Gimeno
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.forename: Christine L
authors.initials: CL
authors.lastname: Roberts
authors.forename: Roger C
authors.initials: RC
authors.lastname: Parslow
authors.forename: Emma Jk
authors.initials: EJ
authors.lastname: Wadsworth
authors.forename: Amanda
authors.initials: A
authors.lastname: Chetwynd
authors.forename: Girts
authors.initials: G
authors.lastname: Brigis
authors.forename: Brone
authors.initials: B
authors.lastname: Urbonaite
authors.forename: Sandra
authors.initials: S
authors.lastname: Sipetic
authors.forename: Edith
authors.initials: E
authors.lastname: Schober
authors.forename: Gabriele
authors.initials: G
authors.lastname: Devoti
authors.forename: Constantin
authors.initials: C
authors.lastname: Ionescu-Tirgoviste
authors.forename: Carine E
authors.initials: CE
authors.lastname: de Beaufort
authors.forename: Denka
authors.initials: D
authors.lastname: Stoyanov
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
authors.forename: Katja
authors.initials: K
authors.lastname: Radon
authors.forename: Christopher
authors.initials: C
authors.lastname: Glatthaar
authors.forename: Chris C
authors.initials: CC
authors.lastname: Patterson
mesh_terms: D001722:Birth Order; D016022:Case-Control Studies; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008423:Maternal Age; D016017:Odds Ratio