Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities

Abstract

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping.In the UK, RAD is recommended as a standalone approach in DSSP, whereas the US guidelines recommend that RAD be followed up by karyotyping. A cost-effectiveness (CE) analysis of RAD in various DSSP is lacking. There is a debate over the significance of chromosome abnormalities (CA) detected with karyotyping but not using RAD. Our objectives were to compare the CE of RAD versus karyotyping, to evaluate the clinically significant missed CA and to determine the impact of detecting the missed CA. We performed computer simulations to compare six screening options followed by FISH, PCR or karyotyping using a population of 110 948 pregnancies. Among the safer screening strategies, the most cost-effective strategy was contingent screening with QF-PCR (CE ratio of $24 084 per Down's syndrome (DS) detected). Using karyotyping, the CE ratio increased to $27 898. QF-PCR missed only six clinically significant CA of which only one was expected to confer a high risk of an abnormal outcome. The incremental CE ratio (ICER) to find the CA missed by RAD was $66 608 per CA. These costs are much higher than those involved for detecting DS cases. As the DSSP are mainly designed for DS detection, it may be relevant to question the additional costs of karyotyping.

Prenatal diagnosis of 21 trisomy by quantification of methylated fetal DNA in maternal blood: study on 10 pregnancies

“…The methods of obtaining fetal biological material for prenatal diagnosis are chorionic villus sampling (I trimester), amniocentesis and cordocentesis (II trimester of pregnancy). All the invasive methods to obtaining fetal cells could induce bleeding, miscarriage and fetal malformations (3,4). However, classic prenatal chromosome analysis has the advantage of 100% accuracy, allowing the detection of chromosomal abnormalities in the resolution limit of optical microscopy.…”

Genetic polymorphisms of loci D18S53, D18S59, and D18S488 in fetuses from a Chinese Tianjin Han population

“…Gekas et al (2011) studied the prenatal diagnostic programs for 110,948 pregnant women and found that QF-PCR could save US$3494 in diagnosing a single Down's syndrome case, compared with karyotype analysis. Therefore, it is necessary to establish a QF-PCR diagnostic program in line with the population characteristics of Tianjin.…”

Rapid Prenatal Diagnosis of Common Numerical Chromosomal Abnormalities by High-Resolution Melting Analysis of Segmental Duplications

“…There is still no consensus on whether such rapid aneuploidy detection (RAD) methods should be used as standalone approaches for prenatal chromosomal testing (Caine et al, 2005;Boormans et al, 2009;de Jong et al, 2009;Ogilvie et al, 2009;Hills et al, 2010;Gekas et al, 2011). Opponents of RAD methods suggest that these assays may miss chromosomal abnormalities other than targeted aneuploidies, and those which result from RAD screening should be followed up with karyotyping (Test and Technology Transfer Committee, 2000;Caine et al, 2005;de Jong et al, 2009).…”

“…Opponents of RAD methods suggest that these assays may miss chromosomal abnormalities other than targeted aneuploidies, and those which result from RAD screening should be followed up with karyotyping (Test and Technology Transfer Committee, 2000;Caine et al, 2005;de Jong et al, 2009). However, proponents argue that chromosomal abnormalities with adverse outcomes missed by RAD are rare, because prenatal chromosomal diagnosis is mainly offered to pregnant women at a high risk who are selected by prenatal screening programs targeting trisomies 21 and 18 (Boormans et al, 2009;Ogilvie et al, 2009;Gekas et al, 2011). However, this debate has not hampered the widespread use of well-recognized RAD methods, and, indeed, many new RAD methods have also emerged in recent years (Vialard et al, 2011;Yan et al, 2011;Dan et al, 2012;Guo et al, 2012). Technically, each RAD method possesses both advantages and limitations.…”