Prenatal detection of Down's syndrome by rapid aneuploidy testing for chromosomes 13,18, and 21 by FISH or PCR without a full karyotype: a cytogenetic risk assessment

Background In 2004, the UK National Screening Committee (UKNSC) recommended that new screening programmes for Down's syndrome need not include karyotyping and can offer prenatal diagnosis for the syndrome with FISH (fluorescence in-situ hybridisation) or PCR as rapid diagnostic tests. The UKNSC also recommended that FISH or PCR tests should only include trisomies 13, 18, and 21. We undertook a retrospective cytogenetic audit to assess the probable clinical effect of these proposed policy changes. Methods 23 prenatal cytogenetic laboratories from the UK public sector submitted data for amniotic fluid or chorionic villus samples referred from April, 1999, to March, 2004. We obtained data for the details of all abnormal karyotypes by reason for referral and assessed the efficiency of FISH and PCR rapid tests for the detection of chromosome abnormalities. Findings Of 119 528 amniotic fluid and 23 077 chorionic villus samples, rapid aneuploidy testing replacement of karyotyping would have resulted in about one in 100 and one in 40 samples having an undetected abnormal karyotype, respectively. Of these missed results, 293 (30%) of 1006 amniotic fluid samples and 152 (45%) of 327 chorionic villus samples were associated with a substantial risk of an abnormal phenotypic outcome. Of 34 995 amniotic fluid and 3049 chorionic villus samples that had karyotyping and a rapid test on the same sample, none of the three technologies was completely reliable to detect an abnormal karyotype, but the best protocol for an interpretable result was PCR and karyotyping or FISH and karyotyping. Interpretation Replacement of full karyotyping with rapid testing for trisomies 13, 18, and 21 after a positive screen for Down's syndrome will result in substantial numbers of liveborn children with hitherto preventable mental or physical handicaps, and represents a substantial change in the outcome quality of prenatal testing offered to couples in the UK.