The best marker combination using the integrated screening test approach for detecting various chromosomal aneuploidies.
OBJECTIVE
To evaluate the cross-trimester multiple marker correlation and the minimum marker combination needed for detecting various chromosomal aneuploidies.


METHODS
Parturient women with singleton pregnancies who underwent non-interventional sequential screening test and followed prospectively were recruited. They all underwent first trimester combined nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotrophin (f-betahCG), followed by second trimester measurement of unconjugated estriol (uE3), human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP). Pearson correlation was applied to compute any cross-trimester marker correlation and logistic regression analysis was used to determine the minimum marker combination for detecting various categories of chromosomal aneuploidies.


RESULTS
The current study included 552 normal and 43 chromosomal-affected pregnancies (24 Down's syndrome [DS], 7 Turner's syndrome, 8 Edward's syndrome, 4 Klinefelter syndrome and 5 triploidy) for which the results of both the screening tests and the pregnancy outcome were available. In the normal cases, a significant correlation was found between f-betahCG and hCG (r=0.52), as well as between PAPP-A and uE3 (r=0.174). In DS pregnancies, the NT correlated with both hCG (r=0.45) and uE3 (r=-0.39). In Turner's syndrome, uE3 correlated both with PAPP-A (r=0.97) and f-betahCG (r=0.97). No other significant correlations were found. Furthermore, with the exception of f-betahCG and hCG in the unaffected cases, all other markers correlation appeared very weak. For detecting all the above categories of aneuploidies, the combination of NT, PAPP-A and uE3 and the maternal age background risk were found adequate, with a 74% detection rate (DR) for a 5% false positive rate (FPR). For DS only, the combination of maternal age-related background risk and the combination of NT, PAPP-A, hCG and AFP yielded a 79% DR for a 5% FPR.


CONCLUSIONS
The current study agrees with a previous report that, overall, there is no strong correlation between first and second trimester markers. The extension of the integrated test for detecting various categories of common chromosomal aneuploidies using NT, PAPP-A and uE3 deserves further evaluation.
Maymon
Ron
R
Department of Obstetrics and Gynecology, Assaf Harofe Medical Center, Israel. intposgr@post.tau.ac.il
Sharony
Reuven
R
Grinshpun-Cohen
Julia
J
Itzhaky
Deganit
D
Herman
Arie
A
Reish
Orit
O
D000328:Adult; D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D002869:Chromosome Aberrations; D003663:Decision Trees; D004964:Estriol / Q000097:blood; D005260:Female; D006801:Humans; D007557:Israel; D009333:Neck / Q000000981:diagnostic imaging / Q000196:embryology; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D014463:Ultrasonography; D000509:alpha-Fetoproteins / Q000378:metabolism
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; D011266:Pregnancy-Associated Plasma Protein-A; D004964:Estriol