First Trimester Screening

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 1stΔ Free Beta 1stΔ Biochem/NT ONTD Screening Maximizing 1stΔ Screening NT hCG Free Beta hCG 1stΔ Papp-A NB 1975 80 85 90 95 2000 2004

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 11-14 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 18-20 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 11-14 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

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 2ndΔ 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