Appropriate biochemical parameters in first-trimester screening for Down syndrome.

Area of Science:

• Maternal-fetal medicine
• Biochemistry
• Genetics

Background:

• First-trimester Down syndrome screening relies on maternal serum markers.
• Accurate distribution parameters are crucial for risk estimation.
• Previous studies have varied in methodology and marker inclusion.

Purpose of the Study:

• To calculate maternal serum marker distribution parameters for Down syndrome risk estimation in the first trimester.
• To evaluate the effectiveness of different marker combinations and ultrasound in screening.
• To establish updated parameters for improved first-trimester Down syndrome risk assessment.

Main Methods:

• Meta-analysis of 44 series combining data for PAPP-A, free beta-hCG, AFP, and uE3.
• Levels expressed as multiples of the normal median (MOM) for gestational age.
• Cubic regression fitted for PAPP-A; weighted means calculated for other markers.

Main Results:

• Median PAPP-A MOM increases with gestation, with a fitted equation for weekly estimation.
• Estimated median Down syndrome values: free beta-hCG 1.98 MOM, AFP 0.79 MOM, uE3 0.74 MOM.
• Screening at 9-11 weeks with PAPP-A and free beta-hCG yields 64.6% detection at 5% FPR; adding markers increases detection to 70.1%.

Conclusions:

• First-trimester screening with PAPP-A and free beta-hCG is effective.
• Incorporating additional serum markers and nuchal translucency ultrasound significantly improves Down syndrome detection rates.
• Updated distribution parameters enhance the accuracy of first-trimester Down syndrome risk assessment.