MIAMI BEACH — Contingent screening is an attractive option for prenatal detection of trisomy 21, Dr. Fergal Malone said at the annual meeting of the Society for Maternal-Fetal Medicine.
This screening method was analyzed using data from the First and Second Trimester Evaluation of Risk (FASTER) trial, a National Institute of Child Health and Human Development-funded study of pregnant women who underwent screening in both trimesters.
The outcomes of contingent screening were compared with the outcomes of two other commonly described screening methods: stepwise sequential screening and integrated screening in more than 32,000 women in the FASTER trial population.
The results of the analysis showed that contingent screening had a detection rate of 93%, with a false-positive rate of 4% in a relative comparison of the three methods for detection of trisomy 21 in the FASTER population. The first-trimester detection rate was 65%, with 2% of patients requiring chorionic villus sampling (CVS), and the second-trimester detection rate was 28%, with another 3% of patients requiring amniocentesis.
Only 22% of patients required additional screening in the second trimester, said Dr. Malone of the Royal College of Surgeons in Dublin.
Stepwise sequential screening had a 95% detection rate with a 5% false-positive rate and a 65% early detection rate. But 98% of patients were required to return for second-trimester screening to achieve these target rates.
Integrated screening had a comparable 92% detection rate, with a false-positive rate of 5%. This method provided no early detection, and required that 100% of patients return for second-trimester screening.
The contingent screening approach assigns patients to one of three trisomy 21 risk groups based on the first-trimester ultrasound measurement of nuchal translucence and the first-trimester serum measurement of pregnancy-associated plasma protein-A (PAPP-A) and free β-hCG.
Patients in the highest risk group (greater than 1:30 risk in this study) undergo CVS, those in the lowest risk group (less than 1:1,500 risk) receive no further testing, and those in the borderline risk group (between 1:30 and 1:1,500 risk) undergo quad screening (serum alpha fetoprotein, hCG, unconjugated estriol, and inhibin A) in the second trimester and receive a final risk assessment based on all the measures, with a risk cutoff for further testing of 1:270, Dr. Malone explained.
Stepwise sequential screening divides patients into two risk groups that are based on nuchal translucency, PAPP-A, and free β-hCG measures in the first trimester, with those with a risk of greater than 1:30 receiving immediate CVS, and all others returning for second-trimester quad screening.
Integrated screening consists of nuchal translucency and PAPP-A screening in the first trimester, with no risk assessment given at that time, and quad screening in the second trimester.
A risk assessment that is based upon all the measures is given following the second-trimester screening, with a cutoff of 1:270 for additional screening. This method raises ethical concerns about withholding results during the first trimester and possibly causing a delay in a patient's potential decision to terminate due to aneuploidy.
“While contingent screening appears very attractive, there are some practical issues that need to be considered before endorsing this approach for widespread implementation,” Dr. Malone stressed.
For example, the outcomes reported require that patients precisely follow the risk cutoffs used in this study.
The question is whether a woman with a risk of 1:31 versus the cutoff of 1:30 would forego chorionic villus sampling and wait for second-trimester screening results.
If the patients do not accept and follow these risk cutoff values precisely, the actual observed performance of contingent screening will be less efficient, he explained.
Other practical concerns regarding contingent screening include the effects of borderline-risk patients who fail to return for later screening and the fact that most patients screened by this method would have no neural-tube-defect risk assessment performed; steps would need to be taken to establish alternate methods for such screening, such as sonographic central nervous system anatomy evaluation, or single-marker alpha-fetoprotein testing, he said.
Contingent screening appears to effectively balance the benefits of first-trimester screening while focusing the added value of second-trimester screening measures on just a small segment of the population of pregnant women, Dr. Malone said.
“But before widespread use of this screening can be endorsed, prospective implementation studies will be required to confirm its efficacy in actual clinical practice,” he concluded.