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Down syndrome: It's not just the age factor

Whether or not a pregnant woman will give birth to a child with Down Syndrome is not simply a matter of how old she is. Although it is a fact that as women get older, they are more likely to have a child with Down Syndrome, other factors also play a role. According to Markus Neuhäuser and Sven Krackow, from the Institute of Medical Informatics, Biometry and Epidemiology at University Hospital Essen, in Germany, the risk of a child being born with Down Syndrome is also dependent on how many existing siblings the child has and how big the gap is between the child and his immediate preceding sibling. The research is published in Springer's journal Naturwissenschaften this week.

Neuhäuser and Krackow reviewed and analysed data from 1953 and 1972 (before abortion was widespread). They found that other factors, besides the mother's increasing age, were linked to the number of Down Syndrome cases. Down Syndrome rates were significantly higher in older mothers in their first pregnancy than in older mothers who had already had children. Only late first pregnancies were more likely to produce a Down Syndrome baby, not late second or third pregnancies. In addition, the larger the gap between pregnancies, the higher the rates of Down Syndrome.

Down Syndrome is the result of the genetic abnormality trisomy 21. Trisomy has been the focus of extensive medical research but the exact mechanism is still not understood. One feature common to most trisomies is an increase in frequency of trisomic pregnancies with increasing maternal age. There is strong evidence for uterine selection against genetically disadvantaged embryos. However, as women approach the menopause and the risk of future infertility increases, this selection, or filtering stringency, is expected to relax.

Neuhäuser and Krackow's paper provides evidence that older mothers, who give birth to children with Down Syndrome, have a relaxed stringency of quality control of embryos (o r relaxed filtering stringency), which increases the probability that these women will bring children with developmental defects to full term. They believe that this relaxed filtering stringency is an adaptive maternal response and it might explain why the rate of Down Syndrome accelerates with increasing maternal age.

These findings have important implications for the prevention of abnormal fetal development. The authors conclude that "clearly, identification of the relaxation control mechanisms and therapeutic restoration of a stringent screen holds promise not only for Down Syndrome."


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