PRENATAL SCREENING FOR DOWNS-SYNDROME USING INHIBIN-A AS A SERUM MARKER

The value of measuring inhibin-A (alpha beta(A) dimer) with human chor ionic gonadotrophin (total or the sub-units free alpha-hCG and free be ta-hCG separately), alpha-fetoprotein (AFP), and unconjugated oestriol (uE(3)) was examined to determine the effect on the performance of se rum screening for Down's syndrome between 15 and 22 weeks of pregnancy . The study was based on stored serum samples from 77 Down's syndrome singleton pregnancies and 385 unaffected singleton pregnancies, matche d for maternal age, gestational age, and duration of storage of the sa mple, supplemented by data from 970 white women with unaffected pregna ncies. Inhibin-A was elevated in the serum of women with Down's syndro me pregnancies with a median of 1.79 multiples of the median (MOM). Us ing the four serum markers AFP, uE(3), total hCG, and inhibin-a, in ad dition to maternal age, 70 per cent of Down's syndrome pregnancies wer e detected for a 5 per cent false-positive rate compared with 59 per c ent with the conventional triple test (AFP, uE(3), and total hCG with maternal age). If the estimate of gestational age were based on an ult rasound scan examination, the detection rate would be 77 per cent [95 per cent confidence interval (CI) 69-85 per cent] using the four serum markers including inhibin-A, compared with 67 per cent with the tripl e test or 79 per cent (95 per cent CI 71-87 per cent) if marker values were adjusted for maternal weight. If the detection rate were kept at 70 per cent and the gestational age were estimated by an ultrasound s can examination, the four-marker test would reduce the false-positive rate from 6.1 per cent using the triple test to 2.9 per cent. The resu lts were virtually the same if free beta-hCG was used instead of total hCG. The inhibin-A-based four-marker test is the most effective metho d of prenatal screening for Down's syndrome suitable for routine use. If the extra cost required to carry out the inhibin-A test were less t han about pound 3 per woman screened, the four-marker test including i nhibin-A would be financially cost-effective.