SERUM SCREENING FOR DOWNS-SYNDROME BETWEEN 8 AND 14 WEEKS OF PREGNANCY

Objective To determine the value of serum screening for Down's syndrom e at 8-14 weeks of pregnancy using seven potential serum markers (alph a-fetoprotein, unconjugated oestriol, total human chorionic gonadotrop hin (hCG), free alpha-hCG, free beta-hCG, pregnancy associated plasma protein A (PAPP-A), and dimeric inhibin A). Design Stored blood sample s collected from women at about 10 weeks of pregnancy, prior to having a chorionic villus sampling procedure on account of advanced maternal age, were retrieved from pregnancies associated with Down's syndrome and from matched unaffected pregnancies. Setting Twenty-one obstetric centres in nine countries. Subjects Seventy-seven pregnancies associat ed with Down's syndrome each matched with five controls (except in two cases that were matched with four controls) for maternal age (same fi ve year age groups), duration of storage of the serum sample (same cal endar year), and gestational age (usually same week of pregnancy). Res ults The levels of two potential markers differed between affected and unaffected pregnancies sufficiently to be of value in screening-free beta-hCG and PAPP-A. The median free beta-hCG level in affected pregna ncies was 1.79 times the median level for unaffected pregnancies, and the median PAPP-A level was 0.43 times the normal median. These two ma rkers were combined with maternal age to estimate a woman's risk of ha ving a fetus with Down's syndrome. A screening programme that used a r isk cutoff level of 1:300 would detect 63% of affected pregnancies and also classify 5.5% of unaffected pregnancies as screen positive. None of the other five markers added more than 2% detection for the same f alse-positive rate. Conclusion The performance of screening using mate rnal age and serum-free beta-hCG and PAPP-A at 10 weeks of pregnancy w as better than the double test (alpha-fetoprotein and hCG with materna l age) and similar to the triple test (alpha-fetoprotein, unconjugated oestriol and hCG with maternal age) at 15-22 weeks.