SCREENING FOR DOWN-SYNDROME DURING FIRST-TRIMESTER - A PROSPECTIVE-STUDY USING FREE BETA-HUMAN CHORIONIC-GONADOTROPIN AND PREGNANCY-ASSOCIATED PLASMA-PROTEIN-A

Objectives: Early screening for Down syndrome is desirable so that mor e time is left for intervention in the event of a positive test. In re trospective first trimester studies, maternal serum free p-human chori onic gonadotropin and pregnancy-associated plasma protein A have been reported as useful markers. Our objective was to confirm these results in a prospective study carried on an unselected population. Design an d Methods: In a cohort of pregnant women recruited prospectively betwe en 9 and 13 weeks' gestation, we measured maternal free beta-human cho rionic gonadotropin and pregnancy-associated plasma protein A in all a ffected pregnancies and 500 representative unaffected pregnancies. Ser um concentrations were transformed to multiples of the median value in normal pregnancies of the same length of gestation, and rates of dete ction of various combinations of the markers were estimated by multiva riate analysis. Results: Down syndrome was observed in 18 fetuses from the 10,160 women recruited. Levels of free beta-human chorionic gonad otropin were elevated in affected pregnancies with an overall median v alue 1.8 times the median of women with normal pregnancies while pregn ancy-associated plasma protein A was significantly diminished (0.51 mu ltiples of the median). At a fixed false-positive risk of 10%, 33% (11 -55), 50% (27-73), 44% (11-67), and 67% (45-89) of the affected pregna ncies would have been detected (95% CI) with maternal age alone or com bined with with free beta-human chorionic gonadotropin, pregnancy-asso ciated plasma protein A or both, respectively. Conclusions: We confirm in a prospective noninterventional study that maternal serum free bet a-human chorionic gonadotropin and pregnancy-associated plasma protein A can be used in the first trimester of pregnancy to screen for Down syndrome with a performance similar to second trimester screening prog rams.