If a fetus has a greater-than-normal amount of swelling at the back of the neck (nuchal translucency), there is a higher likelihood that the baby will have Down Syndrome. The current screening recommendation involves sampling maternal serum and studying three or four analytes to determine risk for neural tube defects, other trisomies (usually trisomy 18), and Down syndrome. An abnormal screening result is an indication for invasive testing by amniocentesis or chorionic villus sampling to confirm the diagnosis. This testing involves a low risk for loss of the pregnancy. The detection rate for Down syndrome using this method is 50 to 60 percent, with a 3 to 5 percent false positive rate.
First trimester ultrasound screening for nuchal translucency (NT), either alone or in combination with maternal serum markers, can identify more Down syndrome fetuses and is more cost effective than the currently used second trimester screening. That is the conclusion of a study supported in part by the Agency for Healthcare Research and Quality (National Research Service Award training grant T32 HS00086).
However, if the combined first trimester ultrasound and blood screening strategy was recommended today, there would neither be enough laboratory capacity for the blood screening nor ultrasonologists who are trained to perform NT, caution the researchers who conducted the study. They calculated that the benefit of NT ultrasound alone to identify each additional Down syndrome case would outweigh the cost by nearly five to one. The benefit of adding to the ultrasound a first-trimester serum screen (for pregnancy-associated plasma protein A [PAPP-A] and free beta-human chorionic gonadotropin [b-hCG] fragments) would still outweigh the cost by nearly two to one for each additional Down syndrome fetus identified.
These calculations are based on a screening decision model the researchers developed to apply to the entire population of the United States and the 4 million infants born here each year. They designed a decision tree to compare four possible screens for Down syndrome: current second-trimester expanded AFP test during amniocentesis (low AFP and estriol and high b-hCG correlate with Down syndrome); first trimester NT screen; first trimester serum screen; and combined first trimester NT and serum screen. The combined screen identified 3,833 Down syndrome fetuses, the NT screen alone 3,413, and the first-trimester serum screen, 2,993 compared with 2,446 identified by the currently used expanded AFP screen.
No comparison was made with second trimester maternal serum screening using four analytes (where inhibin-A is added to the other three currently used). Data on detection rates and false positives were obtained from currently available literature. The authors acknowledge that there are limited data on NT and first trimester screening detection rates and false positives which could alter the magnitude of the effect. Prospective studies are recommended to test the currently published sensitivity and specificity of the new tests in a larger, more diverse group of pregnant women.
More details are in "Nuchal translucency and first trimester biochemical markers for Down syndrome screening: A cost-effectiveness analysis," by Aaron B. Caughey, M.D., M.P.P., M.P.H., Miriam Kuppermann, Ph.D., M.P.H., Mary E. Norton, M.D., and A. Eugene Washington, M.D., M.Sc., in the November 2002 American Journal of Obstetrics and Gynecology 187, pp. 1239-1245.
Editor's Note: This summary originally appeared in the March 2003 issue of Research Activities. The original summary contained some inaccuracies; it has been corrected and is being reprinted here to correct any misrepresentation of the study findings. We apologize for any confusion this may have caused.