Four‐marker serum screening for Down's syndrome

Abstract

The value of measuring the separate sub‐units of human chorionic gonadotrophin (free α‐hCG and free β‐hCG) instead of total hCG together with alpha‐fetoprotein (AFP) and unconjugated oestriol (uE₃) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples relating to 75 singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the serum sample, supplemented by data from 970 white women with unaffected pregnancies. Using the four serum markers AFP, uE₃, free β‐hCG, and free α‐hCG, in addition to maternal age, 65 per cent of Down's syndrome pregnancies were detected for a 5 per cent false‐positive rate compared with 59 per cent with the conventional triple test (AFP, uE₃, total hCG with maternal age). If gestation was based on an ultrasound scan examination, the detection rate was 72 per cent using the four serum markers compared with 67 per cent with the triple test. As an alternative illustration, if the detection rate was kept at 60 per cent and gestation was estimated by an ultrasound scan examination the four‐marker test reduced the false‐positive rate by one‐third from 3 per cent using the triple test to 2 per cent with the four‐marker test. Screening performance was hardly affected by adjusting marker levels for maternal weight. The four‐marker test is, both from a medical and from a financial perspective, the most effective method of prenatal screening for Down's syndrome suitable for routine use.