SCREENING OF MATERNAL SERUM FOR FETAL DOWNS-SYNDROME IN THE FIRST-TRIMESTER

Background Screening of maternal serum to identify fetuses with Down's syndrome is now routinely offered during the second trimester of preg nancy. Prenatal screening by means of serum assays or ultrasonographic measurements, either alone or in combination, may also be possible in the first trimester. Methods We measured serum alpha-fetoprotein, unc onjugated estriol, human chorionic gonadotropin (hCG), the free beta s ubunit of hCG, and pregnancy-associated protein A in 4412 women (82 pe rcent of whom were 35 years of age or older) who came to 16 prenatal d iagnostic centers for chorionic-villus sampling or early amniocentesis at 9 to 15 weeks of gestation, Ultrasound measurements of fetal nucha l translucency were also reported. Fetal chromosomal analysis was perf ormed in all pregnancies, Altogether, there were 61 fetuses with Down' s syndrome. Results A total of 48 pregnancies affected by Down's syndr ome and 3169 unaffected pregnancies were identified before 14 weeks of gestation; the rates of detection of Down's syndrome for the five ser um markers were as follows: 17 percent for alpha-fetoprotein, 4 percen t for unconjugated estriol, 29 percent for hCG, 25 percent for the fre e beta subunit of hCG, and 42 percent for pregnancy-associated protein A, at false positive rates of 5 percent. The results of the measureme nts of serum hCG and its free beta subunit were highly correlated. Whe n used in combination with the serum concentration of pregnancy-associ ated protein A and maternal age, the detection rate was 63 percent for hCG (95 percent confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit (95 percent confidence interval, 45 to 74 p ercent). Measurements of nuchal translucency varied considerably betwe en centers and could not be reliably incorporated into our calculation s. Conclusions Screening for Down's syndrome in the first trimester is feasible, with use of measurements of pregnancy-associated protein A and either hCG or its free beta subunit in maternal serum. (C)1998, Ma ssachusetts Medical Society.