Birth abnormality rates could increase if proposed changes to prenatal testing go ahead

A proposed change to the type of prenatal genetic testing offered to couples in the UK could result in certain chromosome abnormalities being missed, suggests a study published online today (Thursday June 30, 2005) by The Lancet.

In 2004, the UK National Screening Committee (UKNSC) recommended that new screening programmes for Down’s syndrome* do not have to include karyotyping—a process that generates a picture of a person’s 23 chromosome pairs. Karyotyping can detect a range of numerical or structural genetic chromosome abnormalities, but can take up to 14days to produce a result. The UKNSC recommended that instead, prenatal diagnosis of genetic abnormalities should use one of two rapid techniques called FISH (fluorescence in-situ hybridisation) or PCR (polymerase chain reaction) that can give a result in 24–48hours. However, FISH and PCR can only detect the common alterations in copy number, principally trisomies (extra copies), of chromosomes 21, 18, 13, X, and Y.

John Crolla (UK Association of Clinical Cytogeneticists) and colleagues assessed the probable clinical effect of these proposed policy changes. 23 genetic laboratories in the UK that provide prenatal diagnostic services submitted amniotic fluid and chorionic villus tissue** data from 1999 to 2004 to the study authors. In total, the laboratories submitted over 119500 amniotic fluid and 23000 chorionic villus samples. The researchers analysed all abnormal karyotypes by reason for referral and assessed how efficient FISH and/or PCR rapid tests were for the detection of all chromosome abnormalities. While FISH and PCR were both efficient at detecting trisomies 21, 18, and 13, they found that withdrawal of full karyotype analysis from patients screened for Down’s syndrome would lead to other chromosome abnormalities (not including sex chromosome abnormalities) being undetected in one in 100 and one in 40 amniotic fluid and chorionic villus samples, respectively. The authors calculated that, from the missed abnormalities, 293 (30%) of1006 amniotic fluid samples and 152 (45%) of 327 chorionic villus samples were associated with an abnormal mental or physical outcome. The authors suggest that prenatal genetic testing should use PCR plus karyotyping as the most efficient means of detecting all clinically significant chromosome abnormalities.

Dr Crolla states: “Replacement of full karyotyping with rapid testing for trisomies 21, 18, and 13 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.”

n an accompanying CommentWing Cheong Leung (University of Hong Kong, China) points out that most abnormalities not diagnosed by FISH and PCR would be picked up via routine ultrasound scans.