It's time to rethink prenatal screening strategies.(The Master Class)

Every practicing obstetrician faces a dilemma when deciding how best to advise patients about undergoing screening for Down syndrome. Technology is advancing rapidly. Patients look to us for up-to-date guidance about which screening method is the most appropriate, most accurate, and safest. For them, the issue is laden with emotion and expectation. Society looks to us to consider monetary elements of the equation as well.

The time has come to rethink how we assess Down syndrome risk, factoring in the knowledge that biochemical and ultrasound screening approaches now give us detection rates as high as 80%-90%, with false-positive rates of about 5%.

With this excellent screening performance, should we continue to offer invasive testing to women at risk on the basis of age alone, without modifying that risk by using newer analytes and giving them a more accurate assessment? In my opinion, the answer is no.

In 1979, the decision was made to use age 35 years as a cutoff for performing amniocentesis, a limit that was arbitrarily selected due to logistical concerns. At the time, there were very few resources available to perform amniocenteses, and ultrasound as we know it had not been "invented." Amniocentesis was a new and incompletely evaluated technique. Genetics labs were just beginning to become available, and there were relatively few physicians trained in cytogenetics or invasive testing. In addition, the data on the age-specific risk of trisomy 21 were still limited.

By today's standards, patient age does not meet the criteria of a good screening test. Using the customary cutoff of age 35, only 30%-40% of trisomy 21 pregnancies will be detected, and 7.5%-14% of women will be considered at risk. Compare this to newly developed first-trimester screening of all patients using the combined approach of biochemistry (pregnancy-associated plasma protein A and free [beta]-HCG) and nuchal translucency. This has a detection rate of approximately 80%-85% with a 5% false positive rate. In women over age 35, a detection rate of 92% can be obtained, with a false positive rate of 16%.

If we compare the present approach of offering all women over age 35 invasive testing to one in which combined screening in the first trimester is performed initially and invasive testing is offered only in women with a risk greater than 1 in 270, the benefits of each can be evaluated.

In a theoretical population of 10,000 women over age 35 years, 1 in 100 pregnancies will have Down syndrome. With our present approach of offering invasive testing to these patients, we would detect all 100 Down syndrome pregnancies but would potentially perform 10,000 procedures. Assuming a procedure-induced loss rate of 1 in 200, 50 unaffected pregnancies would be lost secondary to the invasive procedure.