First-trimester screening for chromosomal abnormalities.

There is extensive evidence that effective screening for major chromosomal abnormalities can be provided in the first trimester of pregnancy. Randomized studies have established that the risk of miscarriage from chorionic villus sampling in the first trimester is the same as for amniocentesis in the second trimester. Prospective studies have demonstrated that screening by a combination of fetal nuchal translucency (NT) and maternal serum free-beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) can identify 90% of fetuses with trisomy 21 and other major chromosomal abnormalities for a false-positive rate of 5%. This is superior to the 30% detection rate achieved by maternal age and 65% by second-trimester maternal serum biochemistry. A further improvement in the effectiveness of first-trimester screening is likely to be achieved by a risk-orientated two-stage approach. In this, the patients are subdivided into a high-risk group, requiring invasive testing, a low-risk group, which can be reassured that an abnormality is unlikely, and an intermediate-risk group (risk of 1 in 101 to 1 in 1000), in which further assessment is performed by first-trimester ultrasound examination (for presence/absence of the nasal bone or presence/absence of tricuspid regurgitation or normal/abnormal Doppler velocity waveform in the ductus venosus), and chorionic villus sampling is performed if their adjusted risk becomes 1 in 100 or more. As with all aspects of good clinical practice, those performing first-trimester scans should be appropriately trained and their results subjected to external quality assurance. This process was well established by the Fetal Medical Foundation several years ago and is widely accepted internationally.