News - 11 april 1998

1111 BMJ VOLUME 316 11 APRIL 1998 www.bmj.com The largest study yet to be carried out on serum screening for Down’s syndrome has shown that it can be performed accurately during the first trimester of pregnancy, confirming previous findings and backing the opinion of many leading specialists that tests should be carried out earlier. The study, carried out in the United States, screened 4412 pregnant women (82% aged 35 and over) for serum concentrations of a range of markers associated with Down’s syndrome: α fetoprotein, unconjugated oestriol, human chorionic gonadotrophin, the free β subunit of human chorionic gonadotrophin, and pregnancy associated protein A. Ultrasound measurements of fetal nuchal translucency—a fold at the back of the neck that is thicker in fetuses with Down’s syndrome— were also reported. Fetal chromosomal analysis identified 61 fetuses with Down’s syndrome, while 48 were identified with screening before 14 weeks of gestation. When the tests for human chorionic gonadotrophin and its free β subunit were each used in combination with the test for pregnancy associated protein A, the detection rate was 63% and 60% respectively (New England Journal of Medicine 1998;338:955-61). James Haddow, medical director of the Foundation for Blood Research in Scarborough, Maine, and lead author of the paper, said: “Our study provides evidence that first trimester screening of maternal serum to determine the risk of fetal Down’s syndrome is feasible, with use of measurements of pregnancy associated protein A and either human chorionic gonadotrophin or its free β subunit in maternal serum.” Results also clarified for the first time that intact human chorionic gonadotrophin and its free β subunit were useful markers—with detection rates of 29% and 25% respectively. The issue affects many women. About 2.5 million pregnant women are now screened for Down’s syndrome each year in the United States. Nearly all of this testing is carried out in the second trimester. Women who have a positive screening result then go on to have chorionic villus sampling or amniocentesis to diagnose whether the fetus has Down’s syndrome. There are clear advantages to screening earlier—the psychological impact of identifying an affected pregnancy may be reduced, and a termination of pregnancy would be associated with a lower risk to the mother because it could be carried out by suction. “Testing in the first trimester gives women information on which to make decisions earlier. This is a clear plus,” pointed out Dr Haddow. Leading British experts are calling for the widespread introduction of earlier screening for Down’s syndrome. Howard Cuckle, professor of reproductive epidemiology at the Centre for Reproductive Growth and Development at the University of Leeds, said: “This study confirms previous research. We have known for several years that it is possible to carry out serum screening earlier.” Professor Cuckle’s unit—the Leeds antenatal screening service—has offered first trimester screening for Down’s syndrome for some time. They measure serum concentrations of pregnancy associated protein A, free β human chorionic gonadotrophin, α fetoprotein, and oestriol. A combination of these, with measurements of nuchal translucency, achieves detection rates of 80-90%. “But we have to perform these tests on a privately funded basis. The NHS will not pay for first trimester testing,” he said. The NHS has been waiting for a report from the NHS research and development programme before making a decision on funding earlier testing for Down’s syndrome. This report from the Health Technology Assessment programme has just come out but does not include the latest study in the New England Journal of Medicine. It concludes that there needs to be carefully monitored pilot screening programmes before a decision is made to introduce first trimester screening into general routine practice in Britain (Health Technology Assessment 1998;2(1)). But Professor Cuckle said: “It’s a proven area—with the accuracy of earlier testing well shown. This new US study adds further to the evidence—which is now overwhelming. It is wrong not to make this available to pregnant women.” Trial supports earlier screening for Down’s syndrome