Economic evaluation of prenatal diagnosis for chromosomal abnormalities 29/1/04. By the Public Health Genetics Unit In many developed countries, current practice in prenatal diagnosis is to offer invasive diagnostic testing procedures (chorionic villus sampling or amniocentesis) to pregnant women considered to have a high risk of carrying a fetus with chromosomal abnormalities.

The most prevalent of such abnormalities that can result in the birth of live affected children are trisomy 21 (Down syndrome), trisomy 18 (Edward's syndrome) and trisomy 13 (Patau's Syndrome).

Background: Chromosome abnormalities

In the US, antenatal guidelines have for some years recommended that invasive testing should be reserved for mothers aged 35 or older (the risk of chromosomal abnormalities increases with maternal age). The restriction was imposed because the invasive procedures carry a 1-2 per cent risk of miscarriage so, on an economic basis, it was considered desirable to balance the probability of the birth of a chromosomally abnormal child with the risk of procedure-related miscarriage.

It is now possible to use antenatal serum testing and ultrasonography to refine risk estimates for chromosomal abnormalities, particularly the most common, Down's syndrome; pregnant women in the US and the UK are now offered routine screening for Down's and are referred for the invasive diagnostic testing methods if their calculated risk of having an affected fetus exceeds a threshold level.

The authors of a recent paper in the Lancet propose that offering the invasive diagnostic procedures only to women with risks above the threshold level has inherent drawbacks, notably the potential discrepancy between risks and benefits assumed in standard economic calculations with the perception of risks and benefits by the pregnant women themselves. The study carried out a cost-utility analysis of amniocentesis and chorionic villus sampling for trisomies 13, 18 and 21 versus no invasive diagnostic testing.

(Cost-utility analysis is an economic technique that compares healthcare costs with benefits gained in terms of Quality-Adjusted Life Years [QALY]. A QALY is one year of life adjusted for its quality, such that a year in perfect health is considered equal to 1.0 QALY, but a year in ill health would be less than 1.0 QALY.)

The researchers combined epidemiological, cost and clinical efficacy data from multiple sources with the probability of different adverse outcomes and preference data from a socio-economically diverse sample of 534 pregnant women aged 16-47 from San Francisco to determine the merit of risk-based thresholds for prenatal diagnostic testing. The researchers used a decision-analytic framework, a method for making a qualitative assessment of multiple contributory factors in order to create an economic evaluation of a procedure.

They conclude that prenatal diagnostic testing is cost-effective irrespective of maternal age or the relative risk of a fetus having a chromosomal abnormality, and argue that offering universal prenatal diagnostic testing can therefore be justified on economic grounds. They do not attempt to assess the cost utility of maternal screening practices such as those used routinely in the UK (serum and ultrasonographic screening), but their results do question the original assumptions underlying the adoption of a threshold below which the lower risk of fetal chromosomal abnormality makes diagnostic testing less beneficial in economic terms.

PHGU comment

The report demonstrates that the cost-effectiveness of prenatal testing for common chromosomal abnormalities such as Down's syndrome is highly sensitive to the preferences of pregnant women for the potential outcomes.

The San Francisco study group of pregnant women generally considered procedure-related miscarriage as preferable to having a baby with Down's syndrome, which heavily influenced the calculated cost per QALY gained for the invasive procedures. Relatively small variation in preference in a different group of women could produce significantly different results.

An accompanying commentary in the Lancet also notes that the women's preferences for health states were recorded early in pregnancy, whereas experience of those health states would probably significantly alter their preference rating for those circumstances. For instance, a pregnant woman with no children might perceive the birth of a child with a chromosomal abnormality as a seriously adverse outcome, whereas in fact she might adjust well to such an event.

The main suggestion of the report, however, is that antenatal guidelines should seek to support fully informed choices on testing options for pregnant women, because individual preferences and concerns have a significant effect on the cost-utility of testing.

Article courtesy of the Public Health Genetics Unit .

Image credit: Anthea Sieveking

Further reading

Harris RA et al. Cost utility of prenatal diagnosis and the risk-based threshold. Lancet 2004 363: 276-282. Abstract

Petrou S and Mugford M. Should prenatal diagnostic testing be offered to all pregnant women on economic grounds? Lancet 2003 363:258-259. Commentary