A screening program for trisomy 21 at 10-14 weeks using fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A.
OBJECTIVE
To examine the potential impact of combining maternal age with fetal nuchal translucency thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in screening for trisomy 21 at 10-14 weeks of gestation.


METHODS
Maternal serum free beta-hCG and PAPP-A were measured by Kryptor, a random access immunoassay analyzer using time-resolved amplified cryptate emission, in 210 singleton pregnancies with trisomy 21 and 946 chromosomally normal controls, matched for maternal age, gestation and sample storage time. In all cases the fetal crown-rump length and nuchal translucency thickness had been measured by ultrasonography at 10-14 weeks of gestation and maternal blood had been obtained at the time of the scan. The distributions (in multiples of the median; MoM) of free beta-hCG and PAPP-A (corrected for maternal weight) and fetal nuchal translucency (NT) were determined in the trisomy 21 group and the controls. Likelihood ratios for the various marker combinations were calculated and these were used together with the age-related risk for trisomy 21 in the first trimester to calculate the expected detection rate of affected pregnancies, at a fixed false-positive rate, in a population with the maternal age distribution of pregnancies in England and Wales.


RESULTS
In a population with the maternal age distribution of pregnancies in England and Wales, it was estimated that, using the combination of maternal age, fetal nuchal translucency thickness and maternal serum free beta-hCG and PAPP-A, the detection of trisomy 21 pregnancies would be 89% at a fixed false-positive rate of 5%. Alternatively, at a fixed detection rate of 70%, the false-positive rate would be 1%. The inclusion of biochemical parameters added an additional 16% to the detection rate obtained using NT and maternal age alone.


CONCLUSIONS
Rapid diagnostic technology like Kryptor, which can provide automated reproducible biochemical measurements within 30 min of obtaining a blood sample, will allow the development of interdisciplinary one-stop clinics for early fetal assessment. Such clinics will be able to deliver improved screening sensitivity, rapidly and more efficiently, leading to reduced patient anxiety and stress.
Spencer
K
K
Clinical Biochemistry Department, Harold Wood Hospital, Essex, UK.
Souter
V
V
Tul
N
N
Snijders
R
R
Nicolaides
K H
KH
D000293:Adolescent; D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis*; D005865:Gestational Age; D006801:Humans; D016014:Linear Models; D008403:Mass Screening / Q000379:methods / Q000458:organization & administration; D008875:Middle Aged; D009333:Neck / Q000000981:diagnostic imaging* / Q000196:embryology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011296:Prenatal Diagnosis / Q000379:methods*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014463:Ultrasonography; D006113:United Kingdom
D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A