Cross-trimester repeated measures testing for Down's syndrome screening: an assessment

Area of Science:

• Prenatal diagnostics
• Biochemical screening
• Maternal serum analysis

Background:

• Down's syndrome screening relies on biochemical markers from maternal serum.
• Optimizing screening performance requires accurate predictive models and validated algorithms.
• Assessing the utility of repeated marker measurements is crucial for enhancing prenatal diagnostics.

Purpose of the Study:

• To estimate the performance of Down's syndrome screening using repeated biochemical markers from first and second trimester maternal serum samples.
• To assess detection and false-positive rates for screening algorithms with repeated measures.
• To develop and test new risk assessment algorithms incorporating multiple sample points.

Main Methods:

• Utilized stored maternal serum samples from Down's syndrome cases and controls.
• Assessed screening performance of published and new risk algorithms.
• Analyzed repeated measurements of human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and pregnancy-associated plasma protein A (PAPP-A).

Main Results:

• Published models showed inconsistencies with test data, leading to performance deterioration with repeated measures.
• Simplified models indicated potential benefit from repeated PAPP-A measurements, but not hCG or uE3.
• Bayesian analysis suggested improved detection and reduced false-positive rates with repeated PAPP-A, particularly with early first-trimester samples.

Conclusions:

• Repeated PAPP-A measurements may enhance Down's syndrome screening, especially when samples are collected early in the first trimester.
• Established modeling methodologies for screening performance assessment may be optimistically biased and require cautious interpretation.
• Further prospective studies and cost-effectiveness analyses are recommended to confirm the benefits of repeated PAPP-A measurements.