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Male Biological Clock May Be Ticking For Down Syndrome In Offspring

Columbia University Medical Center Study Demonstrates Father's Age Makes a Difference in Chance of Genetic Abnormalities

New York, NY (May 7, 2003)

Although research has shown that babies born to older mothers are at greater risk of having genetic abnormalities such as Down syndrome, it's long been thought that the mother's age was the sole determining risk factor. A new study by researchers at the Columbia University Medical Center at NewYork-Presbyterian Hospital shows that the father's age also plays an important risk-determining role in the incidence of this genetic abnormality.

The report appears in the June issue of the Journal of Urology. According to the study's author, Harry Fisch, M.D., director of the Male Reproductive Center at Columbia University Medical Center and associate clinical professor of Urology at Columbia University College of Physicians & Surgeons, the findingsnot only add to our knowledge about the incidence of Down syndrome, but also may represent a paradigm for other genetic abnormalities in the children of older fathers. Considering that the population of parents in the U.S. is older than ever before, the paternal age effect is significant and should be addressed during prenatal counseling. Couples preparing for family planning need to be aware that advanced parental age may not only result in increasing difficulties with fertility for the parents, but also that children born to older fathers may have a higher risk of genetic abnormalities.

Down syndrome, or trisomy 21, is a common congenital abnormality that affects 1 out of 800 to 1000 newborns. The influence of maternal age on increased risk of this most common nonlethal trisomy disorder has been known since the 1930's. The rate of Down syndrome has been shown to increase in mothers older than age 35. Until now, however, the effect of paternal age has been controversial. Various large U.S. and European epidemiological studies of the disorder have shown no influence between paternal age and Down syndrome, while smaller studies have demonstrated conflicting results. In light of this, in addition to the fact that there is an increasing number of older couples having children, we decided to examine a very large number of cases in order to provide definitive evidence as to whether or not paternal age is indeed a risk factor for Down syndrome, explains Dr. Fisch.

The number of cases evaluated in the Columbia study 3419 is the largest number of Down syndrome cases ever examined for the effect of parental age. The investigators looked at the number of babies born to mothers over age 35 between 1983 and 1997 in New York State, which witnessed a dramatic rise in births to this parental age group. Over this study period, there was an increase of 111 percent and 60 percent, respectively, in the number of mothers and fathers over age 35. Data on the incidence of Down syndrome was obtained from the New York State Department of Health Congenital Malformations Registry and was then compared to parental age for this period.

The incidence of babies born to older mothers increased during the study years. In 1983, 8 percent of all births were to women 35 years of age and older, compared with 17 percent of all births in 1997. Births to mothers older than 40 years of age increased approximately 2.5 times between 1983 and 1997. The greatest change in this time period occurred in both maternal and paternal ages greater than 40 years with a 178 percent and 73 percent increase from 1983 to 1997, respectively.

Dr. Fisch and his colleagues found that the rate of Down syndrome steadily increased with advancing paternal age for the maternal age group of 35 to 39 years. The greatest increase, however, was seen in the maternal age group of 40 years and older with increasing paternal age. The rate of Down syndrome for both maternal and paternal age greater than 40 years is approximately 60 per 10,000 births, which is a six-fold increase compared with maternal and paternal ages less than 35 years of age. In this age group, the paternal contribution to Down syndrome was 50 percent. Men over age 40 were twice as likely to have a Down syndrome child than men less than 20 years old, notes Dr. Fisch. Since older women tend to be have children with older men, the increased incidence of this genetic abnormality in women older than 35 is likely to be the result of a combination effect of maternal and paternal age, rather than the result of maternal age only. This interaction would explain the dramatic increase in Down syndrome that is seen in women older than 35, he points out.

This finding of the paternal age influence on Down syndrome suggests that there is a sperm contribution to the trisomy; increased paternal age may lead to an increased frequency of chromosome abnormalities in sperm, according to Dr. Fisch. Our finding of a paternal contribution to trisomy 21 indicates a structural chromosomal risk than had not previously been appreciated. It is our belief that increased paternal age, as well as maternal age, may be responsible for a wide variety of health problems in children. This effect has been underestimated and warrants further research. The reduced semen quality in older men may increase the risk of genetic abnormalities in their children and some of our current research is seeking to evaluate ways to reduce this risk, he concludes.2452767pubjvb9001&&14:54-11- 5-2004mks200211:41- 7-30-200405_07c_03

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