Prenatal Testing in the Genomic Age: Clinical Outcomes, Quality of Life, and Costs

To use a decision-analytic model to assess a comprehensive set of outcomes of prenatal genetic testing strategies among women of varying ages.

We assessed outcomes of six testing strategies incorporating diagnostic testing with chromosomal microarray, multiple marker screening, cell-free DNA screening, and nuchal translucency screening alone, in combination, or in sequence. Clinical outcomes included prenatal detection or birth of a neonate with a significant chromosomal abnormality and diagnostic procedures performed. Other outcomes included maternal quality-adjusted life-years and costs. Sensitivity analyses were conducted to examine the robustness of the findings.

At all ages assessed, screening strategies starting with multiple marker screening offered the highest detection rate when all chromosomal abnormalities were considered. Incorporating cell-free DNA as an optional secondary screen decreased the number of diagnostic procedures, but also decreased the number of abnormalities diagnosed prenatally, resulting in a similar number of procedures per case diagnosed at age 30 years; the option of secondary cell-free DNA screening becomes more favorable at older ages. Multiple marker screening with optional follow-up diagnostic testing was the most effective (highest quality-adjusted life-years) and least expensive strategy at ages 20-38 years. At age 40 years or older, cell-free DNA screening was optimal with an incremental cost-effectiveness ratio of $73,154 per quality-adjusted life-year.

When considering all detectable chromosome problems as well as patient preferences and baseline risks, multiple marker screening with the option of diagnostic testing for screen-positive results is the optimal strategy for most women. At age 40 years and older, cell-free DNA as a primary screen becomes optimal and is cost-effective.

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