Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies.
Cardwell CR., Stene LC., Joner G., Bulsara MK., Cinek O., Rosenbauer J., Ludvigsson J., Jané M., Svensson J., Goldacre MJ., Waldhoer T., Jarosz-Chobot P., Gimeno SG., Chuang LM., Parslow RC., Wadsworth EJ., Chetwynd A., Pozzilli P., Brigis G., Urbonaite B., Sipetic S., Schober E., Devoti G., Ionescu-Tirgoviste C., de Beaufort CE., Stoyanov D., Buschard K., Patterson CC.
OBJECTIVE: The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS: Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS: Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I(2) = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS: There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.