[Second trimester screening for trisomy 21 using ADAM12-S as a maternal serum marker].
OBJECTIVE
To investigate the value of a disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker in second trimester screening for trisomy 21 (Down syndrome, DS), and to develop an appropriate prenatal DS screening protocol.


METHODS
Serum samples were collected from 53 pregnant women carrying a trisomy 21 fetus and 621 pregnant women with matched gestational age and weight carrying a healthy fetus. ADAM12-S concentrations were determined with a time-resolved fluorescence immunoassay (TRFIA). Curve fitting by weighted regression and other statistical methods were conducted, and the model was optimized for prenatal trisomy 21 screening program in second trimester. ADAM12-S alone or in combination with other two- or three-combination test was selected as a serum marker for prenatal second-trimester screening of trisomy 21 by calculation of detection rate (DR) and false positive rate (FPR).


RESULTS
By comparison, the median multiple of the median (MoM) value of ADAM12-S in DS pregnancy group was higher than that of the control group (P< 0.01). When FPR = 5%, the DR of ADAM12-S was 28.3%, and the positive and negative likelihood ratios were 5.66 and 0.75, respectively. The DR of three-combination test of ADAM12-S, alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotropin (β-HCG) has increased to 52.80% from 39.62% of the conventional two-combination test (AFP and free β-HCG). For women with a risk between 1/300 and 1/1000 by two-combination test for DS, the DR has increased from 39.62% to 47.12%, but FPR only increased by 0.8% after adding ADAM12-S as a maternal serum marker.


CONCLUSIONS
Considering the increased DR of pregnancies with a risk between 1/300 and 1/1000 in second trimester, ADAM12-S may provide a feasible maternal serum maker when combined with AFP and free β-HCG. The cost-effectiveness ratio is reasonable.
Prenatal Diagnostic Center, Nanjing Medical University Affiliated Maternal and Child Health Hospital, Nanjing, Jiangsu 210004, P.R. China.
Tao
T
Jiang
Ling
L
Lv
Bing
B
Yang
Yi-jun
YJ
Sun
Xiao-juan
XJ
Zhang
Yun
Y
Sun
Qian-jun
QJ
Xu
Zheng-feng
ZF
Xu
D051722:ADAM Proteins / Q000097:blood*; D000072199:ADAM12 Protein; D015415:Biomarkers / Q000097:blood; D019483:Disintegrins / Q000097:blood; D004314:Down Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods
D015415:Biomarkers; D019483:Disintegrins; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human