A Data-Driven Evaluation of the Size and Content of Expanded Carrier Screening Panels

ABSTRACT Purpose The American College of Obstetricians and Gynecologists (ACOG) proposed seven criteria for expanded carrier screening (ECS) panel design. To ensure that screening for a condition is sufficiently sensitive to identify carriers and reduce residual risk of non-carriers, one criterion requires a per-condition carrier rate greater than 1-in-100. However, it is unestablished whether this threshold corresponds with a loss in clinical detection. The impact of the proposed panel-design criteria on at-risk couple detection warrants data-driven evaluation. Methods Carrier rates and at-risk couple rates were calculated in 56,281 patients who underwent a 176-condition ECS and evaluated for panels satisfying various criteria. Condition-specific clinical detection rate was estimated via simulation. Results Different interpretations of the 1-in-100 criterion have variable impact: a compliant panel would include between 3 and 38 conditions, identify 11%-81% fewer at-risk couples, and detect 36%-79% fewer carriers than a 176-condition panel. If the carrier-rate threshold must be exceeded in all ethnicities, ECS panels would lack prevalent conditions like cystic fibrosis. Simulations suggest that clinical detection rate remains >84% for conditions with carrier rates as low as 1-in-1000. Conclusions The 1-in-100 criterion limits at-risk couple detection and should be reconsidered.