FIRST and FASTER Trials for Genetic Markers in First Trimester

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Dr. Joshua Copel: "Here we are again at AIUM and congratulations Beryl, I know you’ve already talked once to OBGYN.net about the Fry award and what it means. And of course, a lot of that comes from your work in detecting Down syndrome but what we’ve heard just before we sat down to talk was that a lot of people here have been reporting on nuchal screening and where that’s going. We thought we’d spend a couple of minutes talking about FIRST and FASTER and should people be doing nuchal screening?"

Dr. Beryl Benacerraf: "I think nuchal screening has become very important. It was pioneered by Kypros Nicolaides in London, and I think, that it’s probably somehow related to the nuchal fold that I observed earlier in the early 1980’s for second trimester fetuses. I think that it may actually be even more powerful in the first trimester than it ever was in the second trimester for the detection of chromosomal abnormalities."

Dr. Joshua Copel: "The data from the U.S., at least from Haddow’s report a few years ago in the New England Journal of Medicine, suggested that the power of first trimester - and that’s 11 to 14 weeks screening as Nicolaides has been doing - that the sensitivity for detecting Down’s syndrome wasn’t as great as Nicolaides found. Nicolaides reports 60%-80% sensitivity and Haddow was a lot lower."

Dr. Beryl Benacerraf: "I think that what Nicolaides recommends is that there be special training so that everybody would perform the measurement exactly the same way under very specific circumstances. By teaching people how to make the measurement and very, very uniform, they seem to have a better sensitivity and specificity for using it in a detection of Down’s syndrome, and I think perhaps that may be the key. Now I know that there are some large studies going on in the United States now that will answer the question as to whether or not this really works in a large scale."

Dr. Joshua Copel: "We certainly hope that it will, and there are two trials. We’re involved in one at Yale called the FIRST trial and the other’s called the FASTER trial. FASTER combines first and second trimester markers and the FIRST trial is focusing on first trimester markers, serum screening, and nuchal translucency screening. What’s your experience been with screening so far?"

Dr. Beryl Benacerraf: "I’d like to do more of it, the only problem is that we often don’t get the patients coming in that early for ultrasounds. Unfortunately, a lot of insurance companies don’t pay for multiple scans during pregnancy, particularly when there’s not a finite indication at the time such as bleeding or some sort of emergent reason. We don’t get the patients at that time so much; we tend to get the patients in for the standard structural survey at 16-18 weeks where of course we can do another type of screening for chromosomal abnormalities. But I’d like to see them coming in earlier so we could get an opportunity to do the earlier screening."

Dr. Joshua Copel: "It would be great if we had the chance to get the patients in for that early scan. I think you’re right, we have a major battle with the payers even after this is shown and then I think it will be shown with good training in the United States to have similar results to what they found in the U.K. I think we’ll still have the battle of trying to show that it improves outcomes."

Dr. Beryl Benacerraf: "I think it will, and I think that unfortunately in this area, the Europeans are ahead of us in their willingness to do ultrasounds more liberally in an area where I think it is useful."

Dr. Joshua Copel: "I think it is important to emphasize that there are training programs available here in the United States, Johns Hopkins is one place and Cedars-Sinai has been offering the courses. After the course is complete, people have to send in fifty images for scoring by a certified center in order to receive their seal of approval as being able to do this in a reliable and reproducible manner. And that as you said, has really been the cornerstone of Nicolaides success in nuchal translucency screening in the first trimester. It sometimes seems to people that it’s kind of silly that we have to reinvent the wheel and redo the studies here in the United States but I think there’s value to tests showing it as well."

Dr. Beryl Benacerraf: "I think it’s important to validate it here in the United States because we’re actually beginning to show that there are some differences in different ethnic groups, particularly for certain measurements that we’re doing and certain features of the fetus. So it is important to look at whatever we’re doing specifically with a respect to populations."

Dr. Joshua Copel: "So we should maybe get crown-rump lengths and nuchal thickness in African-American, Hispanic, and Asian populations as part of this analysis?"

Dr. Beryl Benacerraf: "I think so."

Dr. Joshua Copel: "Is there anything else? If a patient has come to you and had a nuchal thickness that was abnormal, had a chorionic villus sample (which of course you sent to New Haven for the CVS)?"

Dr. Beryl Benacerraf: "Of course."

Dr. Joshua Copel: "And it’s normal, any follow-up studies that you recommend?"

Dr. Beryl Benacerraf: "Absolutely, I think that the thickened nuchal translucency is associated with lots of other abnormalities other than chromosomal abnormalities, particularly heart defects and as well as many syndromes. So I would recommend a very careful structural survey between 16 and18 weeks along with an echocardiogram probably between 18 and 20 weeks."

Dr. Joshua Copel: "That was something that we noticed but didn’t have the statistical power to prove and then John Hyatt with Kypros Nicolaides has now very nicely shown with large data sets that increased risk of congenital heart disease. That’s an important message for us to be sure people have."

Dr. Beryl Benacerraf: "Exactly, I agree."

Dr. Joshua Copel: "Thank you very much for taking the time to speak with OBGYN.net "

Dr. Beryl Benacerraf: "Thank you for inviting me."