The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concen- IntroductionDown's syndrome is the most common congenital cause of severe mental retardation, with an incidence at birth of about 1-3 per 1000. The current method of antenatal screening is to select women for a diagnostic amniocentesis on the basis of advanced age. Age is, however, a poor basis for screening and has had little impact on the incidence at birth. With age as a basis for screening only about 30% of all Down's syndrome pregnancies can be detected by carrying out amniocentesis on the 5% of women most at risk-that is, those aged 36 years or greater-though in practice fewer than 15% of affected pregnancies are detected because fewer than half of these older women actually have amniocentesis.' Additional antenatal screening tests such as maternal serum measurements of c fetoprotein and unconjugated oestriol can increase the rate of detection to about 45% if the 5% of pregnant

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Technical terms and abbreviations are used throughout this report. The meaning is usually clear from the context but a glossary is provided for the non-specialist reader. In some cases usage differs in the literature but the term has a constant meaning throughout this review. Glossary Affected pregnancies Pregnancies in which the foetus has Down's syndrome. Cutoff level The value of a screening variable which distinguishes screen positive from screen negative results. Detection rate The proportion of affected pregnancies with screen positive results (also known as the sensitivity). This is independent of the prevalence of pregnancies with Down's syndrome. False-negatives Affected pregnancies with screen negative results. False-positives Unaffected pregnancies with screen positive results. False-positive rate The proportion of unaffected pregnancies with screen positive results. When specified as the complement of the false-positive rate-that is, 100%-falsepositive rate (%), it is called the specificity. This is independent of the prevalence of pregnancies with Down's syndrome. Multiple of the median The serum marker concentration for a woman divided by the median concentration value for unaffected pregnancies of the same gestational age. Odds of being affected given a positive result Self-defined-for example, an odds of being affected given a positive result of 1:20 means that among women with screen positive results there will, in expectation, be one affected pregnancy and 20 unaffected pregnancies. This is dependent on the detection and false-positive rates of the test and the prevalence of pregnancies with Down's syndrome. The odds of being affected given a positive result expressed as a proportion (in this example 1/21) is the positive predictive value of the screening test. Risk This can be expressed in two ways: (a) as an odds (for example, 1:3-that is, one affected pregnancy for every three unaffected pregnancies) (b) as a proportion (for example, the odds of 1:3 expressed as a proportion would be one-quarter-that is, one affected pregnancy out of a total of four pregnancies). Screening The systematic application of a test or inquiry to identify individuals at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action, among persons who have not sought medical attention on account of symptoms of that disorder.

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