Screening for Down's syndrome

Down's syndrome (DS) is the commonest cause of severe mental retardation in children. It is the result of trisomy of chromosome 21 which is usually a random event though it is commoner in older mothers. DS can be diagnosed by chorionic villus sampling (CVS) and amniocentesis followed by karyotyping. Because of the risks associated with these invasive procedures, they can only be offered to a high-risk group. At one time the sole basis for identifying this increased risk was maternal age, but within the past ten years a series of biochemical and ultrasound abnormalities have been shown in DS pregnancies. The biochemical abnormalities include changes in the levels of most fetal and placental products in the maternal circulation. The best-known of these changes are the reduced levels of alphafetoprotein (AFP) and oestriol (E3) and increased levels of human chorionic gonadotrophin (hCG). The mechanism underlying these biochemical phenomena is unknown. Screening programmes involving the measurement of hCG and AFP, with or without additional parameters such as E3, at 15-18 weeks of pregnancy can typically identify 60% or more of cases of DS with a screen-positive rate of 5%. The combined risk derived from the various biochemical parameters, together with maternal age, is calculated by one of a number of computer programmes which have been developed for this purpose. There has been considerable discussion as to the exact biochemical tests which should be used for DS screening. This had led to controversy as to whether measurement of E3 has a place, and whether or not measurement of the free beta-subunit of hCG should replace measurement of the intact molecule. A notable recent development is the suggestion that measurement of the urinary beta-core of the hCG could be a highly discriminatory marker. A number of factors can affect the results of biochemical screening for DS. These include maternal weight, gestational age, ethnic origin, smoking, and diabetes. In addition, abnormal levels of the biochemical products may be found in other chromosome abnormalities.