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 greater than or equal to3 mm and women with a maternal serum screening-derived risk greater than or equal to 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 greater than or equal to3 mm (58%), and six out of 10 cases with available maternal serum screening had a calculated risk of greater than or equal to 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.