Maternal serum-integrated screening for trisomy 18 using both first- and second-trimester markers

Area of Science:

• Reproductive biology
• Medical diagnostics
• Genetics

Background:

• Trisomy 18 (Edwards syndrome) is a serious chromosomal abnormality.
• Prenatal screening is crucial for early detection and management.
• Integrated serum screening offers a non-invasive approach to assess trisomy risk.

Purpose of the Study:

• To evaluate the performance of an integrated serum screening test for trisomy 18.
• To determine the optimal combination of maternal serum markers and maternal age for risk assessment.
• To establish patient-specific risk for trisomy 18.

Main Methods:

• Utilized published and new data on maternal serum marker levels in trisomy 18 and unaffected pregnancies.
• Derived population parameters from observed marker levels.
• Employed a multivariate Gaussian model to calculate patient-specific trisomy 18 risks.

Main Results:

• The optimal marker combination includes first-trimester pregnancy-associated plasma protein-A and second-trimester alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin.
• At a 1:100 second-trimester risk cutoff, this integrated test detects 90% of trisomy 18 cases with a 0.1% false-positive rate.
• Excluding the first-trimester marker reduced detection to 67% at a similar false-positive rate.

Conclusions:

• The described algorithm demonstrates high efficiency for trisomy 18 detection.
• This integrated serum screening approach should be considered for prenatal programs.
• The findings support the use of combined first and second-trimester markers for improved trisomy 18 screening.