Cytogenetic diagnoses after chorionic villus sampling are less reliable in very‐high‐ or very‐low‐risk pregnancies

Abstract

An increasing number of cytogenetic prenatal diagnoses are performed on chorionic villus samplings. The accuracy of this method is influenced by chromosomal mosaicism, mostly confined to direct preparation methods. Especially those investigators who have experienced false-negative and false-positive findings propagate the combined use of direct and culture methods. Yet large collaborative studies have shown that in approximately two-thirds of diagnostic cases only one procedure is applied. Moreover, the accuracy of a cytogenetic investigation depends not only on the ontogenetic origin of the tissues investigated, but also on interacting factors such as the 'a priori risk' and the 'predictive value of a cytogenetic finding'. On this basis a differentiated prenatal diagnostic procedure is discussed, including either sole short-term culture (STC), combined STC and long-term culture (LTC), primary amniocentesis (AC), or primary percutaneous umbilical blood sampling (PUBS). The predictive value of the cytogenetic diagnosis from CVS varies significantly dependent on the a priori risk of a chromosome aberration and, in the case of an abnormal karyotype, on the specific chromosome involved. A non-mosaic and 'non-lethal' trisomy detected in STC is highly representative of the embryo/fetus, but there are exceptions of limited predictive value, e.g., trisomy 18. Guided by the strategy of an optional follow-up by LTC, AC, or PUBS in 1317 successive CV samplings, we are not aware of a false-negative diagnosis, but probably had one false-positive diagnosis: 47,XXY after STC; 46,XY after LTC. When referring to the rate of fetuses with an unbalanced karyotype expected in the different indication groups, a relative increase of false-positive findings in the very-low-risk group (maternal age < or = 35 years of age) and of false-negative findings in the very-high-risk group (abnormal ultrasonographic findings) of pregnant women when only performing CVS becomes obvious. Because of this dilemma, AC or--especially in the latter group--PUBS might be primarily offered to these indication groups instead of CVS.

Accuracy of cytogenetic findings on Chorionic Villus Sampling (CVS)—diagnostic consequences of CVS Mosaicism and non-Mosaic Discrepancy in Centres contributing to EUCROMIC 1986–1992

“…As discussed by Tomkins and Vekemans (1989), Lippman et al (1992), and Kennerknecht et al (1993), predictive values are prevalence-dependent. While Tomkins and Vekemans stressed that positive predictive value increases with increasing a priori risk, Kennerknecht et al (1993) emphasized that for pregnancies with a very high a priori risk there is an increased risk of false-negative findings (decreased negative predictive value), and vice versa for pregnancies with a very low a priori risk.…”

“…h Caspari et al (1994); the publication includes four additional cases from years when the centre was not reporting to EUCROMIC. i Kennerknecht et al (1991); also included in Kennerknecht et al (1993). j Leschot et al (1988).…”

“…k Eiben et al (1988); also included in Caspari et al (1994). l Kennerknecht et al (1993). m Identical to case D08, Schlesinger et al (1990).…”

“…While Tomkins and Vekemans stressed that positive predictive value increases with increasing a priori risk, Kennerknecht et al (1993) emphasized that for pregnancies with a very high a priori risk there is an increased risk of false-negative findings (decreased negative predictive value), and vice versa for pregnancies with a very low a priori risk. They encountered 3/1277 CV samples with a normal karyotype after direct CVS preparation, but a non-mosaic abnormality in the fetus proper; all three pregnancies were ascertained because of abnormal ultrasonographic findings.…”

Fluoreszenz-in-situ-Hybridisierung (FISH) an nichtkultivierten Amnionzellen zur Diagnostik häufiger Chromosomenstörungen

“…Ein schnelleres Ergebnis innerhalb von 1-2 Tagen erhält man durch die Kurzzeitkultivierung von Choriongewebe. Jedoch ist bei dieser Methode eine mögliche Diskrepanz zwischen Embryoblast und Trophoblast zu beachten, sodass für die diagnostische Sicherheit dennoch eine Langzeitkultivierung erforderlich ist [6,17,13,14]. …”