Reducing the Need for Amniocentesis in Women 35 Years of Age or Older with Serum Markers for Screening

Abstract

Background. As maternal age advances, the risk of fetal Down's syndromeincreases. Pregnant women 35 years of age or older are routinely offeredamniocentesis because of this risk. Recently, maternal serum markershave been reported to be useful in screening for Down's syndrome,primarily in younger women. We therefore investigated whether offeringamniocentesis only to selected women 35 years of age or older who wereidentified by screening measurements in serum might prove a usefulalternative to the current practice.Methods. We studied 5385 women with singleton pregnancies who were 35years of age or older and were undergoing routine amniocentesis. Alongwith information about the pregnancy, we obtained a serum sample formeasurement of alpha-fetoprotein, unconjugated estriol, and humanchorionic gonadotropin. Individual estimates of the risk of Down'ssyndrome in the fetus were calculated for each pregnancy before thekaryotype was known.Results. If amniocentesis had been reserved for the women calculated tohave a risk greater than 1 in 200 of having a fetus with Down'ssyndrome, 48 of the 54 cases of Down's syndrome (89 percent) would havebeen identified; 25 percent of the unaffected pregnancies would alsohave been identified as being at high risk for Down's syndrome (falsepositives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) withmiscellaneous chromosomal abnormalities would also have been detected.In practice, such screening would have made 75 percent of theamniocenteses unnecessary, along with a proportion of theamniocentesis-associated fetal losses. If the cutoff for the risk ofDown's syndrome were set higher than 1 in 200, both the rate ofdetection and the false positive rate would be lower. Conversely, theserates would be higher if the cutoff were set lower.Conclusions. Prenatal screening of serum to generate individualestimates of the risk of Down's syndrome in the fetus can provide abasis for decision making in the cases of women 35 years of age orolder, as it does in younger pregnant women, and is an alternative tocurrent testing practices.