This document was published more than 2 years ago. The nature of the evidence may have changed.
A more recent review of the literature is reported in Methods of Early Prenatal Diagnosis, SBU report 182, published 2006.
Annually, 8 000 samples from amniotic fluid or the placenta are analyzed for the purpose of detecting chromosomal abnormalities in the fetus. The dominant chromosomal abnormality is Down syndrome, in which an extra chromosome 21 is present (trisomy 21). Since the incidence of Down syndrome and some other chromosomal abnormalities increases with maternal age, pregnant women above the age of 35 years are informed more thoroughly about such analysis. Analysis may also be conducted when the mother is below 35 years of age, eg, in cases of genetic predisposition, if abnormalities are suspected following ultrasound examination, or if the expectant mother is concerned that her child may have a chromosomal abnormality. The standard method is karyotyping, which is used to determine the complete chromosomal composition of the cells. This procedure takes approximately 2 weeks. Quantitative fluorescence polymerase chain reaction (QF-PCR) is a recent method of chromosomal analysis. The advantage of QF-PCR is that the results can be obtained within 2 days, ie, approximately 12 days faster than with karyotyping. Since testing of the amniotic fluid and placenta can be carried out, at the earliest, in gestational weeks 14 and 10 respectively, the major advantage of QF-PCR is rapid analysis. Hence, in cases where analysis shows a chromosomal abnormality in the fetus, the parents are given more time to decide whether or not to terminate the pregnancy. In contrast to karyotyping, in QF-PCR not all of the chromosomes are analyzed, but analysis is limited to chromosomes 13, 18, 21, X, and Y. These five chromosomes have been selected because they are involved in more than 90 percent of all severe chromosomal abnormalities that are detected by prenatal diagnosis.
The results from two studies that compare QF-PCR to karyotyping have shown that the method has a good potential to detect abnormalities in chromosomes 13, 18, and 21. However, one of the studies has reported isolated false negative cases with regard to the sex chromosomes (X and Y). With current practice, approximately 12 to 16 chromosomal abnormalities are detected annually in Sweden in chromosomes other than the five selected, and these cannot be identified with the use of QF-PCR. As with all analyses that involve samples of amniotic fluid or the placenta, the collection procedure itself involves an increased risk for miscarriage (approximately 0.5-1 percent).
QF-PCR is not as labor intensive as karyotyping. The cost per analysis for QF-PCR totals approximately 1 250 SEK compared to 4 600 SEK for karyotyping. If QF-PCR should be used as a complement to karyotyping the costs would increase by approximately 7 million SEK per year. If QF-PCR should replace karyotyping the costs would decrease by 26-30 million SEK per year. Increased costs for educating maternal health services staff in giving parents adequate information, has not been taken into consideration in this estimation.
There is strong scientific evidence for the capacity of QF-PCR to identify chromosomal abnormalities in the five chromosomes 13, 18, 21, X and Y with good accuracy (Evidence grade 1)*. The documentation is insufficient to assess the cost-effectiveness of the method. It is of great importance that health service providers discuss the ethical implications and the economic consequences of the method before it replaces karyotyping.
*Grading of the level of scientific evidence for conclusions. The grading scale includes four levels;
Evidence grade 1 = strong scientific evidence,
Evidence grade 2 = moderately strong scientific evidence,
Evidence grade 3 = limited scientific evidence,
Evidence grade 4 = insufficient scientific evidence.
This summary is based on a report prepared at SBU in collaboration with Prof. Magnus Nordenskjöld, Karolinska University Hospital, Stockholm. It has been reviewed by Assoc. prof. Ulf Kristoffersson, Lund University Hospital, Lund and Prof. Jan Wahlström, Sahlgrenska University Hospital, Göteborg.
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New references in update June 23, 2004: 1–3.
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