Abnormal karyotypes in semi-direct chorionic villus preparations of women with different cytogenetic risks

Abstract

Among 3499 cytogenetically investigated semi‐direct chorionic villus samples, 219 (6·3 per cent) abnormal karyotypes were encountered. The karyotypes were considered certainly abnormal (generalized abnormal with high probability) in 109 cases (3·1 per cent), and in 110 cases (3·1 per cent) uncertainly abnormal (potentially confined to the placenta), requiring further investigation. Of these 110 uncertain abnormalities, the cytogenetic result turned out to be finally abnormal representing generalized abnormality in 36 cases (32·7 per cent), finally normal representing confined placental mosaicism (CPM) in 69 cases (62·7 per cent), and remained undetermined in 5 instances (4·5 per cent). The rate of the numbers of certainly abnormal and all (certainly+uncertainly) abnormal results, the certainty rate, and that of generalized abnormalities and all abnormalities (generalized abnormalities+CPM cases), the predictive value, are strongly correlated with the cytogenetic risk. Therefore, we advise chorionic villus sampling for cytogenetic investigation only in women with a cytogenetic risk equal to or exceeding that of a 40‐year‐old pregnant woman. Because of the high rate of prenatal follow‐up investigations after the finding of uncertain results in semi‐direct villi, semi‐direct and cultured villi should be karyotyped simultaneously. Copyright © 1998 John Wiley & Sons, Ltd.

Four years' cytogenetic experience with the culture of chorionic villi

“…The negative predictive value is 100% since we had no cases with false negative results. The positive predictive value of 66% in this study is comparable to the results of Breed et al (1990), the US collaborative study (Ledbetter et al, 1992) and Los et al (1998), which were 64, 68.4 and 67.8%, respectively. The positive predictive value of 75% in the EUCROMIC study (Hahnemann and Vejerslev, 1997a) is somewhat higher.…”

Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration

“…So in only 3.3% of the cases with positive NIPT results, CVS will not give definitive results and further testing in amniotic fluid will be necessary. This figure does not appear to be very different from the situation where CVS is done due to high aneuploidy risk (women with abnormal first trimester screening results or advanced maternal age), where circa 2% of the cases require follow up karyotyping in amniotic fluid if only STC-villi are investigated [11]. Therefore, it seems to be appropriate to offer CVS as a confirmatory test if NIPT is positive for trisomy 13, 18, or 21 ( Figure 2).…”

“…Since Flori et al [10] showed that the cellfree fetal DNA in maternal plasma is derived from the outer cell layer of CV, the cytotrophoblast, detection of CPM with NIPT is to be expected at the same rate as is found with cytogenetic investigations of the cytotrophoblast of CV. This showed to be~2% in high-risk pregnancies in our center [11]. Therefore, it is recommended to confirm a positive NIPT result by invasive prenatal testing, preferably by amniocentesis (a joint European Society of Human Genetics [ESHG]/American Society of Human Genetics [ASHG] position statement) [12].…”

“…For trisomies that are mostly involved in CPM type 3, an amniocentesis will always be the confirmatory procedure of choice. These confirmatory studies not only need to include chromosomal investigations, but also molecular testing for uniparental disomy if an imprinted chromosome (6,7,11,14,15,20) is involved. Moreover, cytogenetic studies should include the investigation of both uncultured as well as cultured cells, the latter for detection of an exceptional case of tissue specific mosaicism that may be missed in uncultured cells, as was shown before [31].…”

“…However, in such cases it is important to realize that although fetal ultrasound abnormalities are to be expected in case of a fetal trisomy, their absence does not exclude that the fetus is affected with trisomy mosaicism. Moreover, if an imprinted chromosome (6,7,11,14,15,20) is involved, there is a risk for uniparental disomy, which causes disease that may not be detectable with ultrasound investigations and which may be a reason for invasive testing [41].…”