First-trimester combined ultrasound and biochemical screening for Down syndrome in routine clinical practice

To assess the effectiveness of combined ultrasound and biochemical (CUB) screening for chromosome abnormalities in singleton pregnancies in a routine antenatal clinic and laboratory setting.

Women whose pregnancies fell within the gestational age range of 11 to 14 weeks by ultrasound assessment were offered CUB screening on the basis of measurement of nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (FbetahCG) and pregnancy-associated plasma protein A (PAPP-A). NT measurements were obtained using a standardised method defined by the Fetal Medicine Foundation and FbetahCG, and PAPP-A were measured using the DELFIA immunoassay system. Each screening marker measurement was converted to a multiple of the appropriate gestational median and a risk was derived using previously published parameters for each marker in chromosomally abnormal and unaffected pregnancies. A combined risk of Down syndrome and of trisomy 18/13, incorporating the maternal age risk, was calculated for all women. Invasive diagnostic testing was offered to women whose combined risk exceeded the cut-off risk of 1 in 250 (term).

Five thousand and eighty-four women accepted a first-trimester screening test for Down syndrome, representing 75% of the eligible booking population. Out of the population eligible for CUB screening at the time of booking, NT measurements were obtained from 93% at the first clinic visit and 7% had to return for a second attempt. After excluding women who defaulted on a return visit, satisfactory NT measurements were obtained in 99.5% of pregnancies. Fifteen cases of Down syndrome and eleven pregnancies with other chromosome abnormalities were ascertained. The detection rate for Down syndrome was 93% (14/15) at a false-positive rate of 5.9% and for all chromosome abnormalities it was 96% (25/26) at an overall false-positive rate of 6.3%.

CUB screening offers a significant improvement in sensitivity over second-trimester biochemical screening and is deliverable within a routine prenatal clinical setting.