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MS WordPerinatologist Corner - C.E.U/C.M.E. Modules
Prenatal Genetic Screening – Serum and Ultrasound
Sponsored by The Indian Health Service Clinical Support Center
9. First trimester screening
What about first trimester screening?
More and more of your clients may be asking about early trimester screening for fetal DS.
What is involved? There are basically two components to first trimester screening: ultrasound for fetal nuchal translucency (NT), and biochemical testing for free beta-HCG and PAPP-A. Free beta-HCG is a different test than the b-HCG pregnancy test with which you are familiar, and is increased in DS pregnancies. PAPP-A stands for “pregnancy associated plasma protein A”, and is decreased in DS pregnancies. NT measures the thin space between the skin and soft tissues at the level of the fetal neck. This structure is enlarged, as a result of localized lymphedema, in many aneuploid fetuses. It is also a subtle structure with many variables affecting accurate measurement. These tests are done between 10 weeks 6 days and 13 weeks 6 days gestation, so exact ultrasound dating is crucial. On the basis of the patient’s age, crown-rump length derived gestational age, NT measurement, and biochemical values, a risk assessment figure is calculated. For instance, you will receive a result similar to this, “these test results indicate a risk of fetal Down syndrome of 1:992, compared to this patient’s age related risk of 1:270”.
First trimester screening offers the advantage of having reassuring information early in the pregnancy. Should the results be abnormal, there is increased time to arrange definitive testing and early decision making, as well as the safety and privacy of earlier termination, should such be desired. Studies done both in the United Kingdom (Fetal Medicine Institute, SURUSS), and now in the United States (FASTER
, BUN), have demonstrated close to a 90% detection rate when these two tests are combined. NT alone, or free beta and PAPP-A alone, each have only about a 70% sensitivity, so both the ultrasound and the biochemical parameters are necessary to attain the most accurate answer. The false positive rate (FPR) for the combined test is low, ranging between 3-6% in the various studies. The SURUSS and FASTER trials also looked at “integrated” testing, integrating results from both the first and the second trimester testing schemes, which resulted in extremely low FPR of 1-3%.
The problems with implementing first trimester screening are those of obtaining quality testing and appropriate follow up. Accurate measurement of the nuchal translucency (with normal values narrowly ranging between 1-2 mm, depending on crown-rump length) is a technically demanding skill. It requires a rigorous certification process and ongoing quality control in order to insure results accurate enough on which to base major clinical decisions. This degree of ultrasound expertise will almost always entail a referral for most of us. Likewise, results of the testing are obtained early enough so that definitive testing via chorionic villus sampling (CVS) at 11-13 weeks is possible. This likewise requires geographic availability of a specialist who performs the tests (only about a third of maternal fetal medicine specialists currently perform CVS). CVS has a subsequent loss rate of approximately 2.5%, but is corrected to an actual loss rate of about 1% when spontaneous loss of abnormal early pregnancies is taken into account.
Some patients may opt not to act on the results but to confirm them with second trimester testing (“integrated testing”). This may add to anxiety and costs. Also, if this latter approach is employed, it will be crucial that your lab corrects routine second trimester MMS results for first trimester results, otherwise a significant number of false positives will be generated. On the other hand, normal early trimester results may reassure many patients and they will not request further testing. Remember that AFP testing for NTD will still need to be done at 15-20 weeks. A thickened nuchal translucency is also a marker for congenital heart disease, so the follow up of such a finding, in the presence of a normal fetal chromosome makeup, mandates later fetal echocardiography at 24-26 weeks.
In Committee Opinion No. 296, ACOG stated:
“First-trimester screening for chromosomal abnormalities offers potential advantages over second-trimester screening. Studies in the 1990s demonstrated an association between chromosomal abnormalities and the ultrasonographic finding of abnormally increased nuchal translucency (an echo-free area at the back of the fetal neck) between 10 and 14 weeks of gestation. First-trimester screening using nuchal translucency, free ß-hCG, and pregnancy-associated plasma protein-A has comparable detection rates and positive screening rates for Down syndrome as second-trimester screening using 4 serum markers (alpha-fetoprotein, ß-hCG, unconjugated estriol, and inhibin-A). Although first-trimester screening for Down syndrome and trisomy 18 is an option, it should be offered only if certain criteria can be met.”
Nevertheless, because of the logistics of implementing the testing, it may not yet be “ready for prime time” in many settings.
