Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies.
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Cardwell Chris R, Stene Lars C, Joner Geir, Bulsara Max K, Cinek Ondrej, Rosenbauer Joachim, Ludvigsson Johnny, Svensson Jannet, Goldacre Michael J, Waldhoer Thomas, Jarosz-Chobot Przemyslawa, Gimeno Suely Ga, Chuang Lee-Ming, Roberts Christine L, Parslow Roger C, Wadsworth Emma Jk, Chetwynd Amanda, Brigis Girts, Urbonaite Brone, Sipetic Sandra, Schober Edith, Devoti Gabriele, Ionescu-Tirgoviste Constantin, de Beaufort Carine E, Stoyanov Denka, Buschard Karsten, Radon Katja, Glatthaar Christopher, Patterson Chris C
Аннотация
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%).
CONCLUSION: 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.