To ascertain the value of maternal serum free beta-human choriogonadotropin subunit measurement in Down's syndrome screening and to compare its effectiveness when screening with a variety of biochemical markers, we have evaluated maternal serum free beta-human choriogonadotropin, total human choriogonadotropin, alpha-fetoprotein and unconjugated oestriol in a large multicentre study of over 2800 unaffected cases and 90 affected cases, the largest collection of Down's cases ever reported. Of all the markers identified to date, free beta-human choriogonadotropin is the marker of choice for use in Down's syndrome screening. When used in early gestation (14-16 weeks) in combination with alpha-fetoprotein and maternal age, it will allow the detection of 77% of Down's cases. A side-by-side comparison with the performance of total human choriogonadotropin shows the superior detection efficiency of free beta-human choriogonadotropin. Unconjugated oestriol adds nothing further to the detection rate compared with the use of alpha-fetoprotein and free beta-human choriogonadotropin alone, and its use results in a 1% increase in false positive rate. We conclude that unconjugated oestriol has no value in Down's screening. The superior detection rate obtained using free beta-human choriogonadotropin is a result of superior detection of Down's cases in women under 30 years old, where the free beta-human choriogonadotropin combination detects 100% more cases than does the total human choriogonadotropin combination.
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