A screening program for trisomy 21 at 10-14 weeks using fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A

Objective To examine the potential impact of combining maternal age with fe tal nuchal translucency thickness and maternal serum free beta-human chorio nic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP -A) in screening for trisomy 21 at 10-14 weeks of gestation. Methods Maternal serum free beta-hCG and PAPP-A were measured by Kryptor, a random access immunoassay analyzer using time-resolved amplified cryptate emission, in 210 singleton pregnancies with trisomy 21 and 946 chromosomall y normal controls, matched for maternal age, gestation and sample storage t ime. In all cases the fetal crown-rump length and nuchal translucency thick ness had been measured by ultrasonography at 10-14 weeks of gestation and m aternal blood had been obtained at the time of the scan. The distributions (in multiples of the median; MoM) of free beta-hCG and PAPP-A (corrected fo r maternal weight) and fetal nuchal translucency (NT) were determined in th e trisomy 21 group and the controls. Likelihood ratios for the various mark er combinations were calculated and these were used together with the age-r elated risk for trisomy 21 in the first trimester to calculate the expected detection rate of affected pregnancies, at a fixed false-positive rate, in a population with the maternal age distribution of pregnancies in England and Wales. Results In a population with the maternal age distribution of pregnancies i n England and Wales, it was estimated that, using the combination of matern al age, fetal nuchal translucency thickness and maternal serum free beta-hC G and PAPP-A, the detection of trisomy 21 pregnancies would be 89% at a fix ed false-positive rate of 5%. Alternatively, at a fixed detection rate of 7 0%, the false-positive rate would be 1%. The inclusion of biochemical param eters added an additional 16% to the detection rate obtained using NT and m aternal age alone. Conclusions Rapid diagnostic technology like Kryptor, which can provide aut omated reproducible biochemical measurements within 30 min of obtaining a b lood sample, will allow the development of interdisciplinary one-stop clini cs for early fetal assessment. Such clinics will be able to deliver improve d screening sensitivity, vapidly and more efficiently, leading to reduced p atient anxiety and stress.