Concern over proposed prenatal screening changes

New recommendations for prenatal screening programmes to detect Down syndrome could lead to some chromosome abnormalities being missed, UK researchers say. A team based at Salisbury District Hospital looked at the likely effect of the proposal to scrap a type of testing called karyotyping in favour of newer, rapid methods. The results, published early online in the Lancet, suggest that this approach could result in an increase in the number of children born with mental or physical problems in the UK.

Current UK guidelines, issued by the National Institute for Health and Clinical Excellence (NICE) in 2003, say that all pregnant women should be offered one of a number of proven, non-invasive methods of screening for Down syndrome. Women found to be at high risk of carrying a fetus with Down syndrome are then offered a further test, which involves looking at fetal cells obtained using either amniocentesis or CVS (chorionic villus sampling).

In 2004, the UK National Screening Committee (UKNSC) recommended that screening programmes for Down syndrome do not have to include karyotyping, a type of genetic analysis that uses a picture of a person's magnified chromosomes to look for any abnormalities. Down syndrome - which is caused by an extra copy of chromosome 21 (trisomy 21) - can be detected in this way, as can many other types of chromosome abnormality. However, karyotyping can take up to 14 days to carry out, so the UKNSC has recommended that laboratories should use one of two other methods that give results in 24-48 hours. The committee also said that out of the 23 different pairs of human chromosomes, only chromosomes 13, 18 and 21 should be examined in this way.

John Crolla, of the UK Association of Clinical Cytogeneticists, led an investigation of the probable clinical effect of these proposed policy changes. Unlike karyotyping, the other methods - called FISH (fluorescent in situ hybridization) and PCR (polymerase chain reaction) do not involve looking at an entire set of chromosomes. This means that while they can effectively pick up abnormal numbers of chromosomes, PCR and FISH can miss other types of chromosome abnormality.

Crolla and his colleagues looked at data from over 119,500 amniotic fluid and 23,000 chorionic villus samples, analysed by 23 UK genetic testing laboratories during 1999-2004. They found that while FISH and PCR are both efficient at detecting extra copies of chromosomes 21, 18 and 13 in fetal cells, scrapping full karyotype analysis would result in other chromosome abnormalities being missed in one in 100 amniotic fluid samples and one in 40 chorionic villus samples. The authors conclude that the most accurate way of detecting all abnormalities is to combine PCR with karyotyping.

'Replacement of full karyotyping with rapid testing for trisomies 21, 18 and 13 after a positive screen for Down syndrome will result in substantial numbers of liveborn children with hitherto preventable mental or physical handicaps', said Crolla, adding that this represents 'a substantial change in the outcome quality of prenatal testing offered to couples in the UK'. In an accompanying commentary, Wing Cheong Leung, of the University of Hong Kong in China says that most abnormalities not diagnosed by FISH and PCR would be picked up via routine ultrasound scans carried out during pregnancy.