Risk for XXXX associated with maternal and paternal age.

@entity1 @entity1778 @entity981 @entity3052
UNASSIGNED: The role of reproductive factors, such as parental age, in the pathogenesis of @entity1778 is being intensively examined; the results of individual studies are controversial. This meta-analysis aims to quantitatively synthesize the published data on the association between parental age and risk of two major distinct @entity1778 in the offspring. Eligible studies were identified and pooled relative risk (RR) estimates were calculated using random-effects models, separately for childhood @entity981 ( @entity981 ) and @entity3052 ( @entity3052 ). Subgroup analyses were performed by study design, geographical region, adjustment factors; sensitivity analyses and meta-regression analyses were also undertaken. 77 studies (69 case-control and eight cohort) were deemed eligible. Older maternal and paternal age were associated with increased risk for @entity981 (pooled RR  =  1.05, 95  % CI 1.01-1.10; pooled RR  =  1.04, 95  % CI 1.00-1.08, per 5  year increments, respectively). The association between maternal age and risk of @entity3052 showed a U-shaped pattern, with symmetrically associated increased risk in the oldest (pooled RR  =  1.23, 95  % CI 1.06-1.43) and the youngest (pooled RR  =  1.23, 95  % CI 1.07-1.40) extremes. Lastly, only younger fathers were at increased risk of having a @entity1 with @entity3052 (pooled RR  =  1.28, 95  % CI 1.04-1.59). In conclusion, maternal and paternal age represents a meaningful risk factor for @entity1778 , albeit of different effect size by @entity1778 subtype. Genetic and socio-economic factors may underlie the observed associations. Well-adjusted studies, scheduled by large consortia, are anticipated to satisfactorily address methodological issues, whereas the potential underlying genetic mechanisms should be elucidated by basic research studies.
