LAUSR

The accuracy of a prenatal screening test is determined by the detection rate (proportion of affected individuals with a positive result) and the false-positive rate (the proportion of unaffected individuals with a positive result) [1]. Any modification in the method of screening, including a change in the screening protocol, that improves the detection rate and reduces the false-positive rate is desirable, provided it is affordable, since it improves efficacy and reduces the harm and distress arising from alerting people with false-positive results. DNA analysis of maternal plasma in prenatal screening for trisomies 21, 18, and 13 (affected pregnancies) has a high detection rate and a low false-positive rate, but it is costly and there is a technical failure rate ranging from about 9–0.2% depending on DNA method and the definition of a failed test [2,3]. These limitations have prompted a sequential testing approach to screening, in which women first have a conventional screening test such as the Combined test (the measurement of pregnancyassociated plasma protein-A and free beta-human chorionic gonadotrophin together with the ultrasound marker nuchal translucency, and maternal age); those with a risk of having an affected pregnancy above a specified level have a plasma DNA analysis performed. Because the DNA test has a high detection rate (about 98%), only about 2% of affected pregnancies are missed in the women who have a sequential DNA test, but the false-positive rate is substantially reduced, so that women offered an invasive diagnostic test (e.g. amniocentesis) have a high probability of having an affected pregnancy. Two screening protocols have been proposed to implement the sequential approach: the recall method and the reflex method.