Highlights From The Society of Maternal-Fetal Medicine 24th Annual Clinical Meeting

Peter S. Bernstein, MD, MPH

March 01, 2004

FASTER Trial

The Society of Maternal-Fetal Medicine 24th Annual Clinical Meeting kicked off with the long-awaited results of the First and Second Trimester Evaluation of Risk (FASTER) Trial. There were several abstracts related to this study. The central presentation derived from this protocol confirmed the validity of previous studies that the use of a first-trimester ultrasound determination of the nuchal translucency combined with 2 serum markers is a viable alternative to the traditional second-trimester maternal serum screening for Down syndrome.^[1] This impressive protocol enrolled more than 33,500 women with singleton pregnancies between 10 3/7 and 13 6/7 weeks, at which time they underwent serum screening with pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) combined with an ultrasound examination to determine the fetal nuchal translucency. The results of the first-trimester screen were revealed to study subjects only after they had also undergone a second-trimester screen consisting of the quad test (alpha fetoprotein [AFP], hCG, estriol, and inhibin) between 15 and 18 weeks of gestation. Patients were then followed to determine the outcomes of their pregnancies.

This study design allowed for accurate comparisons of the sensitivities of the 2 screening methods. An additional, critical strength of the study was the rigorous training and ongoing quality control that was demanded of those who obtained nuchal translucencies. In fact, one of the abstracts presented demonstrated very effectively the importance of treating the nuchal translucency as though it were a serum analyte.^[2] The ongoing quality-control measures used as part of the trial included onsite review of images obtained, including centralized assessments of all images acquired in the trial, and the development of center-specific medians for nuchal translucency measurements. All of these procedures had a significant impact on the quality of the measurements obtained in the study.

Among the 33,557 pregnancies, 84 carried fetuses with Down syndrome. The authors found that the first-trimester screen had an 83% sensitivity for detecting Down syndrome when the false-positive rate was 5%. This was similar to the sensitivity of the quad test, which was 79% at a similar false-positive rate of 5%, and superior to the triple screen (AFP, hCG, and estriol). For patients who opt for both the first-trimester screen and the second-trimester quad test, the sensitivity can be expected to improve to nearly 90% when the false-positive rate is 5%. With these levels of sensitivities, the triple screen by itself is no longer an acceptable alternative for Down syndrome screening -- just as the AFP test by itself is no longer considered standard of care.

Interestingly, the screening performance of the first-trimester markers in the FASTER trial varied according to the gestational age at which they were obtained.^[3] The nuchal translucency detection rate increased when it was performed at between 11 and 13 weeks of gestation, whereas the performance of PAPP-A and free beta-hCG deteriorated over the same 3-week period. Overall, the first-trimester screen functioned best when it was performed at 11 weeks of gestation. The authors did not observe a variation in performance of the individual markers used for screening for Down syndrome in the second trimester.

Other findings reported, using the database from the FASTER trial, included the following:

Serum PAPP-A levels below the 5th percentile were associated with subsequent impaired fetal growth and increased perinatal mortality,^[4] thus suggesting a first-trimester origin of these adverse outcomes. The test did not, however, have sufficient positive predictive value to be useful in clinical practice.
Abnormal levels of PAPP-A (below the 5th percentile) and elements of the quad test (inhibin, AFP, or hCG levels ≥ 95th percentile, or estriol levels ≤ 5th percentile) were independently associated with a variety of other adverse outcomes, including spontaneous loss at < 24 weeks of gestation, fetal growth restriction, preterm premature rupture of membranes (PPROM), preeclampsia, preterm labor, and preterm birth.^[5,6] Although these associations were statistically significant, the positive predictive values of these tests are too poor to make them worthwhile clinical tools.
When comparing participants in the FASTER trial who did undergo mid-trimester amniocentesis (1605 patients) to those who did not (26,187 patients) , the procedure-related loss rate at < 24 weeks of gestation was found to be 0.15%, which is substantially less than the typically quoted 0.5% loss rate.^[7] Of note, this study was carried out at tertiary medical centers, and the lower loss rate may relate to the level of experience of those performing the procedures.
A positive first- or second-trimester screen for Down syndrome or trisomy 18 was associated with increased risk of other chromosomal abnormalities and structural anomalies in a variety of organ systems, including the cardiac, pulmonary, genitourinary, and central nervous systems.^[8]
Recent studies have suggested that failure to visualize the nasal bone at the time of the ultrasound for the nuchal translucency is another screening test for chromosomal aneuploidy. This examination was performed in 6316 of the patients enrolled in the FASTER trial.^[9] An acceptable image to screen for the presence of the nasal bone was obtained in about 75% of the patients, and the finding was not associated with Down syndrome. Nine of the 10 fetuses with Down syndrome had the nasal bone visualized, and in the last, an acceptable image could not be obtained. The sensitivity of the test was calculated to 9%. The authors concluded that this was not a useful screening test.
The nearly 400 patients in the FASTER trial who conceived using in vitro fertilization had greater risk of having placenta previa or developing preeclampsia, preterm labor, or placental abruption.^[10] This increased risk persisted even after controlling for maternal age and race, history of aneuploidy, and previous preterm delivery.
The use of sonographer-specific nuchal translucency medians compared with center-specific and overall population ones demonstrated superior screening results for fetal chromosomal aneuploidy.^[11] This finding implies that nuchal translucency measurements are best obtained by sonographers who routinely perform the test and have ongoing quality assessment of their images.

1 2 3 4

Next Section

Cite this: Highlights From The Society of Maternal-Fetal Medicine 24th Annual Clinical Meeting - Medscape - Mar 02, 2004.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

Highlights From The Society of Maternal-Fetal Medicine 24th Annual Clinical Meeting

FASTER Trial

Tables

References

Authors and Disclosures

Authors and Disclosures

Comments

Email This

Feedback