Trisomy accounted for 41% of miscarriages: chromosomal abnormalities linked to age seen in most miscarriages

VANCOUVER, B.C. -- Chromosomal abnormalities accounted for more than half of 1,103 miscarriages karyotyped in a recent study, and the majority of abnormalities in women aged over 40 years were trisomic.

Overall, trisomy accounted for 41% of the miscarriages, which occurred between 1998 and 2001. Triploidy was involved in 9%. Seven percent of the miscarriages were monosomic, 1% were tetraploid, and 4% had structural abnormalities. The remaining 38% of miscarriages were considered chromosomally normal, but some likely also had genetic abnormalities that could not be detected by cytogenetic analysis, Wendy P. Robinson, Ph.D., said during the annual meeting of the Teratology Society.

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"I would argue we're only seeing the really big genetic changes here," she said. "I'm certain there have got to be at least some other genetic defects--either smaller chromosomal changes or point mutations that contribute to some of these remaining normals," commented Dr. Robinson of the department of medical genetics at the University of British Columbia, Vancouver.

Whereas maternal age is considered the leading risk factor for trisomy, monosomy X is often the result of loss of a paternal chromosome, and such abnormalities are increased when the father is subfertile, said Dr. Robinson.

Trisomy 21 has been the subject of extensive research in its association with Down syndrome, however, little is known about the causes of trisomy in general.

"We're left with this fact that trisomy increases with maternal age, but we can't find a lot that's associated with it," said Dr. Robinson.

One popular theory is that increased rates of miscarriage in older age are the result of follicular depletion, in which the ovarian follicular pool is reduced as women get closer to menopause. Others theorize that there is an epigenetic "aging" of chromosomes.

Many environmental factors have been looked at as causes of trisomy 21, including effects of caffeine, tobacco, and alcohol. One of the most compelling studies on environmental influences on chromosomes is recent research involving mice exposed to an estrogenic compound called bisphenol A (BPA), which is widely used in the production of polycarbonate plastics, including everything from clear plastic water bottles to baby bottles and dental sealants.

In the study, exposure to deteriorating containers made of BPA caused a dramatic increase in chromosome segregation errors in the mice (Curr. Biol. 13[7]:546-53, 2003).

"This suggests that environmental exposures can indeed contribute to risk of trisomy," said Dr. Robinson. "This material leaches from clear plastic bottles and since almost all infant formula bottles are made of this, there should really be further research on the effects in humans."

Other factors that can contribute to chromosomal abnormalities that cause miscarriage include previous spontaneous abortions or miscarriages, with less chromosomal errors seen once the number of previous miscarriages exceeds five or six, said Dr. Robinson.

While the number of chromosome findings linked to miscarriages continues to increase, a combination of improved detection rates and increasing maternal age likely plays a large role in the increase.

"Maternal age is the overwhelming risk factor for trisomy, so in populations where the average maternal age is higher, this will be seen more, and improved technologies will also likely detect more cases," she said.