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Objective To design a trisomy 21 screening protocol for sequential triage in the first trimester, and to evaluate whether it reduces the need for advanced ultrasound scanning to such an extent that this could be dealt with by a limited number of well-trained sonographers only. Methods Screening results of 31 trisomy 21 affected pregnancies and 16 096 unaffected pregnancies from the first trimester screening program of Algemeen Medisch Laboratorium in Antwerp, Belgium, were used to define high-risk, intermediate-risk and low-risk groups. A serum screening result (age, pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG)) of ≥1 : 30 and/or a nuchal translucency thickness (NT) measurement of ≥ 3.5 mm were classified as high risk. A serum screening result of < 1 : 1000 together with an NT of < 3.5 mm were classified as low risk. Other results were considered intermediate risk, for which further advanced ultrasound screening would be indicated. This protocol was then evaluated prospectively in another population of 13 493 first-trimester pregnancies. Results Of the total population, 1.9% was identified as being high risk (14 trisomy 21 pregnancies and 222 unaffected pregnancies; prevalence, 1 : 17), 59.6% was identified as being low risk (three trisomy 21 pregnancies and 9615 unaffected pregnancies; prevalence, 1 : 3206) and 38.4% was identified as being intermediate risk (10 trisomy 21 pregnancies and 6190 unaffected pregnancies; prevalence, 1 : 620). A similar distribution was found in the prospective arm of the study. There was no reduction of overall screening performance compared with our current first-trimester combined screening program. The number of intermediate-risk pregnancies was sufficiently low as to enable advanced ultrasound scanning by well-trained sonographers only. Conclusion In population screening for fetal trisomy 21, sequential triage in the first trimester can be achieved using very simple methods. Pregnancies at high or at low risk can be identified easily and the number of pregnancies at intermediate risk can be reduced sufficiently to enable advanced ultrasound scanning by well-trained sonographers only. A prospective study is needed to evaluate the performance of this approach and to compare its results with current combined or integrated screening algorithms. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Objectives To evaluate the performance of a first-trimester fetal aneuploidy screening program, with a documented underestimation of nuchal translucency thickness measurements (NT) compared to the Fetal Medicine Foundation (FMF) reference range. Methods We analysed the data of Algemeen Medisch Laboratorium (AML) in Antwerp, Belgium, on combined screening with pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (FB-hCG) and NT. NT-multiples of the median (MoM), relative to the FMF reference range, were used for risk calculations. Results The proportion of first-trimester screening tests in the total of serum screening tests increased from 1.3% (125/9424) in 2000 to 53.1% (6577/12 377) in 2003. Only 11.4% (1514/13 267) of NT measurements were performed according to FMF criteria. The 80.8% (21/26) trisomy 21 (T21) detection rate (DR) at cut off 1:300 resulted from maternal serum screening. NT measurements did not add to this DR, but reduced the false-positive rate from 16.8% (2212/13181) to 8.6% (1130/13181). Only 23.8% (5/21) of T21 detections were by FMF trainees. Conclusion Easy access to screening and maternal serum parameters accounted for the majority of T21 detections in our first-trimester combined screening program. Copyright © 2005 John Wiley & Sons, Ltd.

To evaluate maternal serum screening for trisomy 21 (MSS) in Flanders between 1992 and 2002.Data of a large database on the results of MSS, nuchal translucency (NT) and pregnancy outcome were analysed retrospectively.Despite an excellent performance of second trimester MSS at a maternal ageor = 35 years (94.4% detection rate (DR) of trisomy 21 at a false positive rate (FPR) of 22.4%), the proportion of patients above 35 years of age in the study population was significantly lower than in the Flemish general pregnant population (5.5% versus 8.9%, P0.001). In the population screened by MSS and NT, the DR of second trimester MSS at a 5% FPR was 44.4%, which was lower than 66.6% in the population screened by MSS without NT. When nine trisomy 21-affected pregnancies were compared to 3265 normal pregnancies, the mean NT-MoM values were not significantly different (1.16 +/- 0.89 versus 1.00 +/- 0.46, P0.05). Both the findings comply to a sequential screening practice where second trimester MSS is only performed after a normal measurement of NT in the first trimester.In Flanders, the uptake of second trimester maternal serum screening is low in women aged 35 years or more. Its screening performance decreased after the introduction of sequential screening.

Single-step maternal serum screening (MSS) in the first (1MSS) or second (2MSS) trimester at maternal age ≧35 years was evaluated in the North Belgian region Flanders, where difficulties are encountered in the general introduction of combined or integrated screening algorithms. The fetal aneuploidy screening database of General Medical Laboratory AML in Antwerp was searched for 2MSS tests between 1992 and 1999 (α-fetoprotein, β-human chorionic gonadotropin (β-HCG) and unconjugated estriol, cut-off 1:300) and for 1MSS tests between 1999 and 2003 (free β-HCG and pregnancy-associated plasma protein A, cut-off 1:85). At ≧35 years, the detection rate for trisomy 21 (DR) was 93.8% (15/16) for 2MSS and the screen-positive rate (SPR) was 24.5% (504/2061). For 1MSS, these figures were 85.7% (6/7) and 17.7% (109/615) respectively. To detect one trisomy 21, missed by MSS at ≧35 years of age, an additional number of 1,557 and 506 primary invasive procedures would be needed for 2MMS and 1MSS respectively. We conclude that the performance of bothsingle-step 1MSS and 2MSS at maternal age ≧35 years in Flanders is excellent, even without the combination with ultrasound parameters or integration of first and second trimester parameters. The simplicity of both methods allows to consider them valuable options for fetal aneuploidy screening at advanced maternal age, until high quality combined or integrated screening is accessible to all pregnant women in Belgium.

Objectives: To evaluate in fetal aneuploidy screening the desirability of using Fetal Medicine Foundation (FMF) normal medians of nuchal translucency thickness (NT) measurements or performer-specific medians, and whether the NT measurements should be expressed as Delta-NT or Log NT-MoM values. Settings: First trimester-combined screening programme in a low risk population in Flanders, Belgium (Algemeen Medisch Laboratorium, Antwerp). Methods: Pregnancies unaffected by trisomy 21 (T21) were screened by FMF-trained or other ultrasonographers. Performer-specific NT medians were established for FMF-trained and other ultrasonographers. NCSS Statistical Software was used to establish probability plots for Log NT-MoM and Delta-NT values, relative to performer-specific references or to the FMF-reference. Results: A total of 16,096 pregnancies were evaluated. Six FMF-trainees and five other ultrasonographers each performed between 83 and 658 NT measurements. For the FMF-trainees, FMF-specific NT-MoM medians were close to one at a crown-rump length (CRL) between 50 and 80 mm, whereas the population-specific NT-MoM medians of the other ultrasonographers were close to one at a CRL between 40 and 80 mm. Performer-specific Delta-NT values fitted a Gaussian distribution between the 5th and 90th percentiles, while for the Log NT-MoM values this was between the 10th and 95th percentiles. Conclusion: We conclude that (i) the use of screening would benefit from performer-specific NT-medians based on Log NT-MoM values; (ii) the use of Log NT-MoM values is marginally better than the use of delta-NT MoMs; and (iii) NT measurements are valid at about 10 weeks (crown-rump length 40–45 mm) as well as at 11–13 weeks.

The aim of this study was to evaluate the additional value of dimeric inhibin-A serum concentration in second trimester multiple-marker screening tests for pregnancies affected by Down's syndrome. We anticipated that second trimester maternal serum dimeric inhibin-A concentrations would be altered in pregnancies complicated by fetal Down's syndrome and that dimeric inhibin-A would perform better than one of the three substances analysed in the multiple-marker screening test currently in use. A total of 1156 serum samples were screened for dimeric inhibin-A in parallel with the routine classic triple test screening programme performed on a random obstetric population. Classic triple test performance was compared with detection rates obtained after substitution of unconjugated oestriol by inhibin-A and with the performance of inhibin-A and alpha-fetoprotein alone. Absolute dimeric inhibin-A maternal serum concentrations of Down's syndrome pregnancies were indeed significantly higher than those of normal pregnancies in our screened population. The performance of dimeric inhibin-A in combination with the multiple-marker screening test, however, is limited because of its strong correlation with intact human chorionic gonadotrophin.