ADVANCED MATERNAL AGE AND THE RISK OF DOWN-SYNDROME CHARACTERIZED BY THE MEIOTIC STAGE OF THE CHROMOSOMAL FUROR - A POPULATION-BASED STUDY

The identification of DNA polymorphisms makes it possible to classify trisomy 21 according to the parental origin and stage (meiosis I [MI], meiosis II [MII], or postzygotic mitotic) of the chromosomal error. S tudying the effect of parental age on these subgroups could shed light on parental exposures and their timing. From 1989 through 1993, 270 i nfants with trisomy 21 and 267 randomly selected control infants were ascertained in a population-based, case-control study in metropolitan Atlanta. Blood samples for genetic studies were obtained from case inf ants and their parents. Using logistic regression, we independently ex amined the association between maternal and paternal age and subgroups of trisomy 21 defined by parental origin and meiotic stage. The distr ibution of trisomy 21 by origin was 86% maternal (75% MI and 25% MII), 3% paternal (50% MI and 50% MII), and 5% mitotic. Compared with women <25 years of age, women greater than or equal to 40 years old had an odds ratio of 5.2 (95% confidence interval, 1.0-27.4) for maternal MI (MMI) errors and 51.4 (95% confidence interval, 2.3-333.0) for materna l MII (MMII) errors. Birth-prevalence rates for women greater than or equal to 40 years old were 4.2/1,000 births for MMI errors and 1.9/1,0 00 births for MMII errors. These results support an association betwee n advanced maternal age and both MMI and MMII errors. The association with MI does not pinpoint the timing of the error; however, the associ ation with MII implies that there is at least one maternal age-related mechanism acting around the time of conception.