Maternal serum screening for fetal Down syndrome in women less than 35 years of age using alpha-fetoprotein, hCG, and unconjugated estriol: a prospective 2-year study.

OBJECTIVE: To evaluate prospectively maternal serum screening with alpha-fetoprotein (AFP), hCG, and unconjugated estriol (uE3) as a screen for fetal Down syndrome.

METHODS: Women less than 35 years of age were offered screening between 15-20 weeks' gestation. Screening results calculated by an algorithm to be equal to or greater than 1:274 (the risk of a 35-year-old for fetal Down syndrome at the second trimester) were considered positive. If gestational age was confirmed by ultrasonography, genetic counseling and amniocentesis were offered.

RESULTS: In the first 2 years of our program, 9530 women were screened, of which 686 (7.2%) were found to be screen-positive. Ultrasonographic examination explained the abnormal values in 379 (4.0%). The remaining 307 (3.2%) received genetic counseling and 214 (2.2%) elected amniocentesis or CVS. Four cases of fetal Down syndrome and one de novo chromosomal marker were detected. In three additional cases of fetal Down syndrome, triple-analyte screening failed to identify the pregnancies to be at increased risk. None of the seven cases of fetal Down syndrome would have been detected through screening with maternal serum alpha-fetoprotein (MSAFP) and age alone.

CONCLUSIONS: Measurement of MSAFP, hCG, and uE3 in women less than 35 years old is an effective screening test for fetal Down syndrome, with a sensitivity of 57% in our study and an amniocentesis rate (false-positive rate) of 3.2%.