[Second trimester screening for trisomy 21 using ADAM12-S as a maternal serum marker]

Area of Science:

• Biochemistry
• Prenatal Diagnostics
• Genetics

Background:

• Second-trimester screening for trisomy 21 (Down syndrome) is crucial for prenatal diagnostics.
• Maternal serum markers play a key role in improving the accuracy of these screening protocols.

Purpose of the Study:

• To evaluate the utility of disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker for second-trimester Down syndrome screening.
• To develop an optimized prenatal screening protocol incorporating ADAM12-S.

Main Methods:

• Serum samples from 53 pregnancies with trisomy 21 and 621 controls were analyzed for ADAM12-S using time-resolved fluorescence immunoassay (TRFIA).
• Statistical methods, including curve fitting and regression analysis, were employed to optimize the screening model.
• Detection rates (DR) and false positive rates (FPR) were calculated for ADAM12-S alone and in combination with other markers.

Main Results:

• ADAM12-S levels were significantly higher in pregnancies with trisomy 21 compared to controls (P<0.01).
• ADAM12-S alone achieved a 28.3% DR at a 5% FPR.
• Combining ADAM12-S with alpha-fetoprotein (AFP) and free beta-human chorionic gonadotropin (β-HCG) increased the DR to 52.80% from 39.62% (conventional test), with a minimal FPR increase for intermediate-risk pregnancies.

Conclusions:

• ADAM12-S is a valuable maternal serum marker for second-trimester Down syndrome screening when used in conjunction with AFP and free β-HCG.
• The addition of ADAM12-S enhances detection rates, particularly for pregnancies with intermediate risk (1/300-1/1000), while maintaining a reasonable FPR.
• The cost-effectiveness of this combined screening approach is considered favorable.