False-negative findings in chorionic villus sampling. An experimental approach and review of the literature

61 fetuses/newborns who had an aberrant karyotype in amniocentesis (AC) or percutaneous umbilical blood sampling (PUBS) were followed-up by chorionic villus sampling (CVS) at birth or after interruption.The overall rate of discrepancies is surprisingly high. Among 46 cases with a non-mosaic numerical aberration in AC or PUBS three had a discrepant finding in placental tissue. This was also true in one of seven cases with non-mosaic structural aberrations and in three of five cases with mosaic structural aberrations. All three cases with a mosaic numerical aberration in AC or PUBS were not represented by CVS and/or lymphocytes or fibroblasts, demonstrating the general problem of the unpredictable prognostic value of mosaicism. Our data suggest, that in case of prenatal diagnosis by CVS, using a combined procedure of short-term (STC) and long-term culture (LTC), in our sample we would have missed one case of 45, X (1·6 per cent). When relying only on STC another two cases, one with 47,+21 and one with 46, XX, der(22) would not have been recognized (4·9 per cent, n=3). All other chromosome aberrations would have been detected by STC alone. On the other hand, one case of 45, X was ‘nearly missed’ because of low-grade mosaicism in AC (45, X[1]/46, XX[19]), whereas in placental tissues and PUBS only 45, X was represented. This study mimics a false-negative rate of about 1:3000 (STC plus LTC) or about 1:1000 (STC alone) for an a priori risk group of two per cent (e.g., advanced maternal age). Copyright © 1998 John Wiley & Sons, Ltd.