REDUCING THE NEED FOR AMNIOCENTESIS IN WOMEN 35 YEARS OF AGE OR OLDERWITH SERUM MARKERS FOR SCREENING

Background. As maternal age advances, the risk of fetal Down's syndrom e increases. Pregnant women 35 years of age or older are routinely off ered amniocentesis because of this risk. Recently, maternal serum mark ers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who wer e identified by screening measurements in serum might prove a useful a lternative to the current practice. Methods. We studied 5385 women wit h singleton pregnancies who were 35 years of age or older and were und ergoing routine amniocentesis. Along with information about the pregna ncy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual est imates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known. Results. If amniocente sis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cas es of Down's syndrome (89 percent) would have been identified; 25 perc ent of the unaffected pregnancies would also have been identified as b eing at high risk for Down's syndrome (false positives). Seven of 15 f etuses (47 percent) with other trisomies, 11 of 25 (44 percent) with s ex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screeni ng would have made 75 percent of the amniocenteses unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower . Conversely, these rates would be higher if the cutoff were set lower . Conclusions. Prenatal screening of serum to generate individual esti mates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current t esting practices.