‘Quadruple Test’ Offers Best Prediction For Down’S Syndrome

Authors of a research letter in this week’s issue of THE LANCET highlight how screening for Down’s syndrome based on maternal age and four markers in maternal blood should be used worldwide-the quadruple test is far more effective than screening based on maternal age alone.

Screening for Down’s syndrome is widely practised early in the second trimester of pregnancy (weeks 14 to 22). The quadruple test calculates the risk of a Down’s syndrome term pregnancy from maternal age and the concentration of four markers in maternal blood (alphafetoprotein, unconjugated oestriol, human chorionic gonadotropin, and and inhibin A). This test is used throughout the world but it is not yet the standard test in the UK National health Service.

Nicholas Wald from Barts and The London School of Medicine and Dentistry, UK, and colleagues assessed the performance of antenatal blood screening for Down’s syndrome with the quadruple test in around 46,000 pregnancies from 14 UK hospitals between 1996 and 2001. Those women who screened positive were offered diagnostic amniocentesis or chorionic villus sampling to confirm a Down’s pregnancy.

81% (71 of 88) Down’s syndrome pregnancies were detected by the quadruple screening test; of 46 105 unaffected pregnancies, 3200 tested positive-a 7% false-positive rate. With maternal age alone (ie. when the four maternal blood markers were ignored), and using a maternal age of 35 years or over to select women for a diagnostic test, only 51% of cases were detected; the false-positive rate was 14%. The quadruple test was also better than screening reliant on the measurement of two or three blood markers.

Nicholas Wald comments: “Our results, from a routine screening service, confirm the value of early second trimester serum screening over screening by use of maternal age alone, in contradiction to recent opinion, and lend support to the decision of the UK government to offer serum screening to all pregnant women. We have also confirmed that in the second trimester the quadruple test is sufficiently more effective than the double or triple tests that it should be regarded as the test of choice at this time of pregnancy.”

In an accompanying Commentary (p 794), Peter Benn from the University of Connecticut, USA, concludes: “Wald and co-workers’ report further supports their 1988 recommendation that serum-screening replace advanced maternal age as the primary screen for Down’s syndrome in the second trimester. Use of maternal age as a primary criterion for offering amniocentesis results in very high rates of this invasive testing and is a suboptimum use of resources. Each woman’s choice to accept or reject chorionic villus sampling or amniocentesis should be based on counselling that uses the best possible estimate of her personal risk for fetal aneuploidy. Policy advisory groups in other countries should follow the UK initiative and abandon obsolete guidelines that have advocated offering amniocentesis to all women aged 35, or more, without routinely incorporating serum and ultrasound screening into their risk assessment.”