Prospective study evaluating performance of first‐trimester combined screening for trisomy 21 using repeat sampling of maternal serum markers PAPP‐A and free β‐hCG

• Published in: Ultrasound in obstetrics & gynecology Vol. 40; no. 3; pp. 276 - 281
• Main Authors: Ekelund, C., Wright, D., Ball, S., Kirkegaard, I., Nørgaard, P., Sørensen, S., Friis‐Hansen, L., Jørgensen, F. S., Tørring, N., Bech, B. H., Petersen, O. B., Tabor, A.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-09-2012; Wiley
• Subjects: Adult; Biological and medical sciences; Biomarkers - blood; Chorionic Gonadotropin, beta Subunit, Human - blood; Chromosome aberrations; combined first‐trimester screening; Denmark; Down Syndrome - blood; Down Syndrome - diagnosis; Down Syndrome - diagnostic imaging; Female; free beta‐hCG; Gynecology. Andrology. Obstetrics; Humans; maternal serum markers; Medical genetics; Medical sciences; nuchal translucency; Nuchal Translucency Measurement; PAPP‐A; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A - analysis; Prenatal Diagnosis - methods; Prospective Studies; Risk Assessment; screening for trisomy 21; Ultrasonography, Prenatal; Denmark; Chromosomal aberration; Performance evaluation; Trisomy; maternal serum markers; Gynecology; Samplings; Biological marker; Aneuploidy; First trimester; Pregnancy associated plasma protein A; Down syndrome; Medical screening; Obstetrics; Pregnancy; Human chorionic gonadotrophin; Mother; Nuchal translucency; PAPP-A; free beta-hCG; Sampling; screening for trisomy 21; combined first-trimester screening
• ISSN: 0960-7692; 1469-0705
• DOI: 10.1002/uog.12266

Objective
To prospectively evaluate the performance of first‐trimester combined screening for trisomy 21 using the biochemical markers pregnancy‐associated plasma protein‐A (PAPP‐A) and free beta‐human chorionic gonadotropin (free β‐hCG) obtained before and at the time of the nuchal translucency (NT) scan.
Methods
Three fetal medicine departments in Denmark participated in the study. Screening for trisomy 21 was set up as a two‐step approach with blood sampling performed before the NT scan (early sample) and again at the time of the NT scan (late sample). PAPP‐A and free β‐hCG were measured on both the early and late samples. Age‐standardized detection and false‐positive rates for different screening protocols were calculated.
Results
We collected two blood samples in 27 pregnancies affected by trisomy 21 and in 3891 control pregnancies. The early samples were taken between gestational ages 8 + 0 and 13 + 6 weeks, and the late samples between 11 + 3 and 14 + 6 weeks. The median interval between the samples was 17 (range, 1–40) days. We found a significantly better estimated screening performance when using early sampling vs late sampling (P < 0.05). With a risk cut‐off of 1 in 100, at the time of the risk assessment the estimated detection and false‐positive rates when using the early sample were 91% (95% CI, 81–98%) and 1.6% (95% CI, 1.3–2.0%), respectively. For fixed false‐positive rates the highest detection rates were achieved using both blood samples. When comparing early sampling vs double sampling there was no significant difference in screening performance.
Conclusion
In combined first‐trimester screening for trisomy 21, use of early sampling with measurement of PAPP‐A and free β‐hCG before the time of the NT scan can optimize screening performance. Using maternal serum markers obtained both before and at the time of the NT scan has the potential to further improve performance, but larger studies are needed to confirm this potential. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.