Performance of first-trimester combined test for Down syndrome in different maternal age groups: reason for adjustments in screening policy?

To evaluate the performance of the first-trimester combined test (FCT) in different maternal age groups and to discuss whether adjustments in screening policies should be made. In this retrospective study data (n = 26 274) from a fetal medicine center on FCT (maternal age, fetal NT, free β-human chorionic gonadotrophin, pregnancy-associated plasma protein-A) were studied. 70.6% of cases was <36 years and 43% of the Down syndrome (DS) cases were detected in this age group. For women <36 years and advanced maternal age (AMA) women (≥36 years) detection rate (DR) and false positive rate (FPR) were 94.5% and 4.1%, and 95.8% and 13.0%, respectively (cut-off 1:200). Lowering the cut-off showed an improved balance in DR and FPR. With increasing maternal age FPR and DR increased and odds of being affected given a positive result (OAPR) decreased. FCT is effective in women <36 and ≥36 years. The balance between FPR and DR is more favourable in women <36 years with comparable OAPR. Although FPR increases with increasing maternal age, performance of FCT in AMA women is more effective than screening based on maternal age alone. Lowering the cut-off to 1:100 in AMA women is suggested to improve screening performance. Routinely offering diagnostic testing to AMA women as a screening policy for the detection of DS seems not reasonable.

Engels MA ，Heijboer AC ，Blankenstein MA ，van Vugt JM ... -  《-》

[Second trimester maternal serum screening for Down's syndrome in women of advanced maternal age: a multi-center prospective study].

Qi QW ，Jiang YL ，Liu JT ，Bian XM ，Li Y ，Lü SM ，Zhu BS ，Wang H ，Xu ZF ，Pan XY ，Cai Y ... -  《-》

Screening for trisomy 18 by maternal age, fetal nuchal translucency, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A.

Kagan KO ，Wright D ，Maiz N ，Pandeva I ，Nicolaides KH ... -  《-》

Effect on Down syndrome screening performance of adjusting for marker levels in a previous pregnancy.

In prenatal screening for Down syndrome, serum marker values can be adjusted using values from a previous pregnancy to avoid the problem of women having a high chance of recurrent false-positive results. We investigate the effect of such adjustment on overall screening performance. Monte Carlo simulation was used to investigate the effect of this adjustment on five widely used screening tests for Down syndrome (Triple, Quadruple, Combined, serum Integrated, Integrated tests). Adjustment for screening marker values (expressed in multiples of the median, (MoM)) in a previous pregnancy improved screening performance. The detection rate for a 1% false-positive rate (FPR) increased from 54 to 59% with the Triple test, from 63 to 68% with the Quadruple test, from 70 [corrected] to 75% for the Combined test, from 70 [corrected] to 76% for the serum Integrated test, and from 85 to 88% for the Integrated test. The FPR for an 85% detection rate decreased from 10 to 7.9%, 7.1 to 4.9%, 4.9 to 3.7%, 4.7 to 2.9% and 1.1 to 0.7% respectively for the five tests. Among women who have had a false-positive result in a previous pregnancy, adjustment substantially lowers the false-positive rate, for example, from 18 [corrected] to 7.3% with the Combined test using a 1 in 250 risk cut-off. MoM adjustment for values in a previous pregnancy improves overall screening performance and substantially reduces the high recurrent false-positive rate. This adjustment can be routinely applied in screening programmes through the screening software used to interpret a woman's screening results.

Wald NJ ，Barnes IM ，Birger R ，Huttly W ... -  《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 ... -  《-》