Genetic Ultrasound Following 1st Trimester Nuchal Translucency Screening

First-trimester screening for Downs syndrome has been reported in a number of studies. The most recent study, reported in the New England Journal of Medicine in November, 2005, found that the combination of measuring the nuchal skin fold and obtaining maternal blood for analysis of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A identified 82% of fetuses with Down syndrome, with a screen-positive rate of 5%. The following illustrates this concept.


The first-trimester test involves measuring the skin fold behind the neck of the fetus between 11 weeks and 13 weeks 6 days. Blood is then drawn from the mother and analyzed for free-beta hCG and PAPP-A. Once this is done the risk for Down syndrome is computed.

In a study reported by the same group of investigators at the 25th Annual Meeting of the Society for Maternal-Fetal Medicine, in Reno, NV in February, 2005, they found that the fetuses with trisomy 21 not identified with first-trimester screening, all were identified with Genetic Ultrasound (Sonography) during their second-trimester ultrasound examination. The following is an abstract from this study:

First and Second Trimester Evaluation of Risk (FASTER) Trial: The Role of Second Trimester Genetic Sonography

Fergal Malone1, David A. Nyberg2, John Vidaver3, Robert Ball4, Christine H. Comstock5, George Saade6, Richard Berkowitz7, Susan Gross8, Lorraine Dugoff9, Sabrina Craigo10, Ilan E. Timor11, Stephen R. Carr12, Honor M. Wolfe13, Jacob Canick12, Mary E. D'alton1 

American Journal of Obstetrics and Gynecology Volume 191, Issue 6 (Supplement), Page S3 (December 2004)  

Objective: To evaluate the role of 2nd trimester genetic sonography in a population that has already undergone 1st trimester Combined screening and 2nd trimester Quad screening.

Study Design: Unselected singleton pregnancies at 15 centers had 1st trimester Combined screening at 10-13 wks (nuchal translucency, PAPP-A, fbhCG), and 2nd trimester Quad screening at 15-18 wks (AFP, hCG, uE3, inhibin-A). Patients remaining at their local FASTER site for antenatal care also had a detailed genetic sonogram at 15 to 23 wks, to evaluate for major structural fetal anomalies and minor markers for aneuploidy. 

Results: 8,533 patients had detailed 2nd trimester genetic sonography, including 62 cases of Trisomy-21. 1st trimester combined screen detected 84% (52/62) of T-21 (6.6% FPR); 2nd trimester Quad screen detected 88% (53/60) (11% FPR). In the 3 T-21 cases undetected by these screens, multiple markers were detected in 2 and a major cardiac defect in 1, so that no T-21 were missed by the overall screening program. Use of likelihood ratios (LR) from the genetic sonogram to modify the risk of screening tests, resulted in higher detection rates for both 1st and 2nd trimester screens (92% and 93% respectively), and reduced the FPRs to 5.6% and 7.4% respectively. 

Conclusion: The use of likelihood ratios from 2nd trimester genetic sonography improves the performance of 1st and 2nd trimester screens, by significantly reducing the FPR with further increases in detection rates.   

Marker

Sensitivity

FPR

LR

95% CI

Major anomaly

18%(11/62)

1.3%

14

7.5-23.4

Nuchal fold >5

37% (11/30)

3.5%

11

6.5-17.3

Echogenic bowel

14% (8/58)

0.5%

28

14.2-59.5

Short femur

24% (14/59)

2.8%

8.5

5.2-13.5

Short humerus

7.4% (2/27)

1.2%

6.2

1.6-24.3 

Echogenic focus

27% (15/56)

4.6%

5.8

3.8-9.1

Pyelectasis

6.9% (4/58)

1.2%

5.8

2.3-15.8

1 or more markers

59%(36/61)

11%

5.5

4.5-6.9

2 or more markers

26% (16/61)

1.0%

26

15.9-40.8

3 or more markers

6.6% (4/61)

0.1%

73

21.5-224

No markers

34% (21/62)

89%

0.4

0.27-0.54