First-trimester screening for Down syndrome using quadruple maternal biochemical markers

Area of Science:

• Prenatal diagnostics
• Biochemical screening
• Genetics

Background:

• First-trimester preeclampsia screening utilizes placental growth factor (PlGF).
• Biochemical markers are explored for combined Down syndrome screening.
• PlGF, PAPP-A, free β-hCG, and AFP are key maternal serum markers.

Purpose of the Study:

• To evaluate the predictive value of four biochemical markers for Down syndrome.
• To assess the combined efficacy of PAPP-A, free β-hCG, PlGF, and AFP.
• To determine the impact of adding nuchal translucency to biochemical screening.

Main Methods:

• Singleton pregnancies at 11-14 weeks gestation were analyzed.
• Maternal markers were measured and adjusted for gestational age and maternal characteristics.
• Down syndrome risk was calculated using the Fetal Medicine Foundation algorithm and ROC curves.

Main Results:

• The combination of four biomarkers detected 88% of Down syndrome cases with a 13% false-positive rate.
• Adding nuchal translucency increased detection to 96% at a 4% false-positive rate (1:300 cut-off).
• Further improvement to 100% detection was observed at a 6% false-positive rate (1:500 cut-off).

Conclusions:

• Biochemical marker screening in the first trimester identifies approximately 88% of Down syndrome cases.
• Incorporating nuchal translucency significantly enhances detection rates to over 95%.
• A combined approach offers a high-detection, low-false-positive rate for first-trimester Down syndrome screening.