Three-stage contingent screening for Down syndrome.

To demonstrate the potential value of three-stage sequential screening for Down syndrome. Protocols were considered in which maternal serum pregnancy associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (hCG) measurements were taken on all women in the first trimester. Those women with very low Down syndrome risks were screened negative at that stage and nuchal translucency (NT) was measured on the remainder and the risk reassessed. Those with very low risk were then screened negative and those with very high risk were offered early diagnostic testing. Those with intermediate risks received second-trimester maternal serum alpha-fetoprotein, free beta-hCG, unconjugated estriol and inhibin-A. Risk was then reassessed and those with high risk were offered diagnosis. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling using Monte-Carlo simulation. The modelling suggests that, with full adherence to a three-stage policy, overall detection rates of nearly 90% and false-positive rates below 2.0% can be achieved. Approximately two-thirds of pregnancies are screened on the basis of first-trimester biochemistry alone, five out of six women complete their screening in the first trimester, and the first-trimester detection rate is over 60%. Three-stage contingent sequential screening is potentially highly effective for Down syndrome screening. The acceptability of this protocol and its performance in practice, should be tested in prospective studies.

Wright D ，Bradbury I ，Cuckle H ，Gardosi J ，Tonks A ，Standing S ，Benn P ... -  《PRENATAL DIAGNOSIS》

Predicting the result of additional second-trimester markers from a woman's first-trimester marker profile: a new concept in Down syndrome screening.

To describe a method for deciding whether an individual's first-trimester Down syndrome screening test result justifies further testing in the second trimester. Statistical modelling was used to estimate the distribution of second-trimester marker profiles for a given first-trimester profile and hence the probability of a final positive result, using a 1 in 250 term cut-off. A multi-variate log Gaussian model was used with published parameters. Markers were maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin (hCG) at 10 weeks, nuchal translucency at 11 weeks, and second-trimester maternal serum alpha-fetoprotein, total hCG, unconjugated estriol and inhibin-A. To illustrate the method, the model was applied to a published series of 24 Down syndrome and 367 unaffected pregnancies. Modelling predicts that for 63% Down syndrome and 0.4% unaffected pregnancies having first-trimester tests, there is a 50% or more probability of a final positive result. A step-wise sequential screening policy based on immediate prenatal diagnosis for those with high probability and second-trimester testing for the remainder would have a 90% detection rate and 1.7% false-positive rate. Modelling also predicts 8.0% Down syndrome and 89% unaffected pregnancies with probabilities below 3%. A contingent screening policy restricting second-trimester testing to those with 3-49% probabilities would have an 88% detection rate and 1.4% false-positive rate. Predicting the probability of a positive final result from the first-trimester marker profile has potential utility, either as a decision aide for individual women or as a formal part of screening policy in selecting a subset of women for second-trimester testing.

Maymon R ，Cuckle H ，Jones R ，Reish O ，Sharony R ，Herman A ... -  《PRENATAL DIAGNOSIS》

Comparison of first-trimester contingent screening strategies for Down syndrome.

To assess the relative performance of a multi-stage first-trimester screening protocol for fetal Down syndrome. Data from 10,767 women who underwent combined ultrasound and biochemistry (BC) screening in the first trimester were reanalyzed using a contingent model approach. Amongst the 10,854 fetuses with known outcome, 32 had Down syndrome, 232 had other abnormalities and 10,590 were unaffected. Nuchal translucency (NT), BC and combined (NT-BC) gestational age-specific risks were calculated for each individual using The Fetal Medicine Foundation risk calculation algorithms (Mixture Model and Biochemistry). Individual patients were categorized as at low, high or intermediate risk according to one of the following three strategies. In 'Strategy-NT-BC' initial screening was performed using both NT and BC. In 'Strategy-BC' initial screening was undertaken using maternal serum markers followed by NT assessment in those with an intermediate risk (1 : 51 < risk <or= 1:1000) while in 'Strategy-NT' initial screening was undertaken using NT followed by serum marker assessment in those with an intermediate risk (1 : 51 < risk <or= 1:1000). The nasal bone was assessed in those with an intermediate risk as the final stage in each of the three strategies. Those with an adjusted risk of 1 in 100 or higher after nasal bone assessment were reclassified as high risk. Detection and false-positive rates were compared between differing strategies in our local population, and this analysis was also performed with the maternal age for our population standardized to the distribution found in England and Wales. In our local population the detection rate for a 5% false-positive rate using a combined screening policy (NT-BC) was 88% (95% CI, 75.3-98.9%), and 2.3% had an absent nasal bone. The respective detection rate and false-positive rate of the three multi-stage screening strategies were: Strategy-NT-BC: 87.5 and 2.5%; Strategy-BC: 87.5 and 5%; Strategy-NT: 84.4 and 2.9%. In the contingent Strategy-BC only 29% of those initially screened using serum markers required an NT scan. If the model were applied to a hypothetical obstetric population standardized to the maternal age distribution in England and Wales, the detection and false-positive rates of the same three screening strategies would be: Strategy-NT-BC: 86.2 and 1.9%; Strategy-BC: 82.8 and 4%; Strategy-NT: 75.8 and 2.3%, respectively. First-trimester contingent screening provides detection and false-positive rates comparable to those achieved using combined screening, but could be used to significantly reduce the number of scans performed.

Sahota DS ，Leung TY ，Chan LW ，Law LW ，Fung TY ，Chen M ，Lau TK ... -  《-》

Comparison of serum markers in first-trimester down syndrome screening.

Canick JA ，Lambert-Messerlian GM ，Palomaki GE ，Neveux LM ，Malone FD ，Ball RH ，Nyberg DA ，Comstock CH ，Bukowski R ，Saade GR ，Berkowitz RL ，Dar P ，Dugoff L ，Craigo SD ，Timor-Tritsch IE ，Carr SR ，Wolfe HM ，D'Alton ME ，First and Second Trimester Evaluation of Risk (FASTER) Trial Research Consortium ... -  《OBSTETRICS AND GYNECOLOGY》

First- and second-trimester evaluation of risk for Down syndrome.

Ball RH ，Caughey AB ，Malone FD ，Nyberg DA ，Comstock CH ，Saade GR ，Berkowitz RL ，Gross SJ ，Dugoff L ，Craigo SD ，Timor-Tritsch IE ，Carr SR ，Wolfe HM ，Emig D ，D'Alton ME ，First and Second Trimester Evaluation of Risk (FASTER) Research Consortium ... -  《OBSTETRICS AND GYNECOLOGY》