Screening for Down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: a prospective longitudinal study.

OBJECTIVES: To compare nuchal translucency and second-trimester maternal serum measurements as alternative methods of antenatal screening for Down syndrome in a low-risk population and to evaluate the consequence of combining the results in the estimation of risk.
DESIGN: In a consecutive series of 4130 women aged less than 38 years with a singleton pregnancy, we examined both the detection rate of Down syndrome by nuchal translucency measurement at 10-14 weeks and maternal serum screening by human chorionic gonadotrophin and alpha-fetoprotein at 14-18 weeks. Women with a nuchal translucency measurement of > or = 3 mm and women with a maternal serum screening-derived risk > or = 1/250 were recommended to have amniocentesis. A second-trimester detailed ultrasound scan was also performed in all women. The outcome of all pregnancies was recorded prospectively and the detection rate and false-positive rate of different screening strategies were retrospectively analyzed.
RESULTS: Out of the 4130 pregnancies that were followed (mean maternal age, 30.1 years), 12 cases of Down syndrome were observed (0.28%), all detected prenatally. Seven of 12 cases had a nuchal translucency measurement of > or = 3 mm (58%), and six out of 10 cases with available maternal serum screening had a calculated risk of > or = 1/250 (60%). Four of the five Down syndrome cases with a nuchal translucency measurement of < 3 mm were detected by subsequent maternal serum screening. At a threshold giving 5% of positive tests, the sensitivity of nuchal translucency, maternal serum screening and combined risk screening were 75%, 60% and 90%, respectively.
CONCLUSIONS: In screening for Down syndrome, an approach which combines the results from first-trimester nuchal translucency and second-trimester biochemistry is effective and increases the detection rate compared to the use of any single test. However, this strategy is likely to raise the false-positive rate and the interpretation of maternal serum screening-derived risk should be combined with the first-trimester nuchal translucency measurement.