First-trimester screening for trisomy 21 by free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A: impact of maternal and pregnancy characteristics.
OBJECTIVE
To use multiple regression analysis to define the contribution of maternal variables that influence the measured concentration of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), and the interaction between these covariates, in first-trimester biochemical screening for trisomy 21.


METHODS
This was a multicenter study of prospective screening for trisomy 21 by a combination of fetal nuchal translucency thickness, and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks of gestation. In the pregnancies subsequently found to have trisomy 21 and in those with no obvious chromosomal abnormality, we used multiple regression analysis to account for pregnancy characteristics that influence the measured concentrations of free beta-hCG and PAPP-A. We fitted Gaussian distributions to the distribution of log multiples of the median (MoM) values in trisomy 21 and in unaffected pregnancies.


RESULTS
There were 491 cases of trisomy 21 and 96 803 chromosomally normal pregnancies. Compared with values in Caucasian women, those who were parous, non-smokers and those who conceived spontaneously, PAPP-A was 57% higher in women of Afro-Caribbean origin, 3% higher in South Asians, 9% higher in East Asians, 2% higher in nulliparous women, 17% lower in smokers and 10% lower in those conceiving by in-vitro fertilization (IVF). Free beta-hCG was 12% higher in women of Afro-Caribbean origin, 9% lower in South Asians, 8% higher in East Asians, 2% higher in nulliparous women, 4% lower in smokers and 9% higher in those conceiving by IVF. In screening for trisomy 21 by maternal age and serum free beta-hCG and PAPP-A the estimated detection rate was 65% for a false-positive rate of 5%.


CONCLUSIONS
In first-trimester biochemical screening for trisomy 21 it is essential to adjust the measured values of free beta-hCG and PAPP-A for maternal and pregnancy characteristics.
Kagan
K O
KO
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Wright
D
D
Spencer
K
K
Molina
F S
FS
Nicolaides
K H
KH
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis* / Q000208:ethnology; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000208:ethnology; D006801:Humans; D008875:Middle Aged; D048208:Nuchal Translucency Measurement / Q000379:methods; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A