1. First Trimester Screening
Shannon N. Barringer, MS, CGC
Chairman, Department of Genetic Counseling
UAMS, College of Health Related Professions

2. Prenatal Screening: History
Down Syndrome
AFP Only
1st Δ Free Beta
1st Δ Biochem/NT
ONTD
Screening
Maximizing
1st Δ Screening NT
hCG
Free Beta hCG
1st Δ Papp-A NB

3. First Trimester Screening: On the Horizon
GOALS of this screen:
To increase sensitivity, decrease false-positive rates
To decrease number of “unnecessary” invasive prenatal diagnosis tests.
NOT to increase number of elective abortions.
U/S measurements (NT) and free B-hCG, PAPP-A

4. First Trimester Screening
A method to identify women at risk for having an aneuploid fetus from the general population
Also can identify other birth defects such as congenital heart defects and diaphragmatic hernia
Performed during weeks gestation
Patient Preferences and earlier diagnosis/ reassurance

5. Markers in Pregnancy

6. Nuchal Translucency > 3mm = 30% risk of aneuploidy
50-85% detection, 4.5% false positive
Also associated with CHD, skeletal abnormalities, and diaphragmatic hernia
Measurements must be performed by certified individual!

7. Nuchal Translucency
Figure 10  Nuchal translucency measurement in 326 trisomy 21 fetuses plotted on the normal range for crown–rump length (95th and 5th centiles). FMF, 2003.

8. Increased NT with Normal Chromosomes
Good chance of healthy baby
90% with NT< 4.5 mm
80% with NT between 4.5 to 6.4 mm
45% with NT >6.5 mm
20-30% have adverse pregnancy outcome
IUFD, PTD, low birth weight
Genetic syndromes, skeletal dysplasias, CHD
Risk appears to be proportionate to aneuploid risk
Still provide week U/S and echocardiogram

9. PAPP-A and Free B-hCG 60-68% detection of DS 90% detection of Tri 18
4.5% false positive rate
Also drawn at weeks
Some centers quote 87% detection of DS when combined with maternal age
If both PAPP-A and B-hCG are very low MoM = Increased risk for tri 18, triploidy, fetal anomalies or perinatal complications

10. PAPP-A and Free B-hCG
On average, baby with trisomy 21 will have 2.0 Mom for B-hCG and 0.4 MoM PAPP-A

11. NT, PAPP-A, and B-hCG Krantz, et al (1999) Women < 35 years
87.5% detection DS, 4.5% false positive
100% detection Tri 18, 0.4% false positive
Women 35 years or older
92% detection of DS, 14.3% false positive
100% detection Tri 18, 1.4% false positive

12. Detection Rates-Fetal Down Syndrome
Marker
Timing
Detection Rate
AFP ALONE
> 15 weeks
20%
AFP & hCG
>15 weeks
60%
AFP,hCG,uE3
65-70%
AFP,hCG,uE3,DIA
70-75% NT
11-14 weeks
70-80%
NT, B-hCG, PAPP-A
>85%

13. Other Markers and Screening?
Nasal Bone????
Fetal Cells in Maternal Circulation
Integrated Screening

14. Screening Protocol

15. Advantages of 1st Trimester Screening
Information earlier, more options
Reduce number of invasive procedures
May identify other severe anomalies (or risk for) at time of scan and increased risk of adverse pregnancy outcome—referral for 2nd Δ evals.
Good time to date pregnancy accurately
NT good for multiple gestation

16. Limitations of First Trimester Screening
Accuracy of NT strongly dependant on experience of ultrasonographers
Not all women enter prenatal care in time for screening
Results of screen may arrive too late for CVS or early amnio
Extra cost for first trimester ultrasound
Can not detect NTD or AWD, still need MSAFP

17. Genetic Counseling Nondirective counseling is vital
Informed consent is vital
The patient should undergo detailed counseling regarding first versus second trimester screening
All diagnostic testing options should be discussed

18. ACOG Screening program must meet specific criteria:
Trained, certified, monitored sonographers perform NT
NT alone is not sufficient, biochemistry must be included
Comprehensive genetic counseling must be offered
Access to diagnostic testing if abnormal screen results
Rigorous continual evaluations