Expanded conventional first trimester screening

Area of Science:

• Maternal-fetal medicine
• Prenatal diagnostics
• Biochemical screening

Background:

• Conventional prenatal screening for chromosomal abnormalities like trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) often involves ultrasound and a limited number of serum markers.
• Optimizing screening protocols is crucial for early detection and improved pregnancy outcomes.

Purpose of the Study:

• To evaluate the performance of a comprehensive screening protocol utilizing five serum markers combined with ultrasound for the detection of T21, T18, and T13.
• To assess the detection rates (DR) and false positive rates (FPR) of this expanded screening approach.

Main Methods:

• Analyzed serum samples from 331 unaffected pregnancies, 34 T21, 19 T18, and 8 T13 cases.
• Measured levels of free Beta human chorionic gonadotropin, pregnancy-associated plasma protein A, alpha-fetoprotein, placental growth factor, and dimeric inhibin A.
• Utilized Gaussian distributions to model DR and FPR based on multiples of the median values.

Main Results:

• For T21, the protocol achieved a 98% DR at a 1.2% FPR with a 1/300 risk cut-off, and a 99% DR at a 2.6% FPR with a 1/1000 cut-off.
• For T18/13, a 95% DR was observed at a 0.5% FPR with a 1/150 cut-off, and a 97% DR at a 1.2% FPR with a 1/500 cut-off.
• The screening incorporated nuchal translucency and nasal bone measurements.

Conclusions:

• An expanded conventional screening test incorporating five serum markers and ultrasound demonstrates high detection rates and low false positive rates for common trisomies.
• This protocol complements cell-free DNA (cfDNA) screening strategies and offers additional benefits, such as identifying pregnancies at risk for early-onset preeclampsia.