Age related detection and false positive rates when screening for Down's Syndrome in the first trimester using fetal nuchal translucency and maternal serum free βhCG and PAPP-A

Abstract

Objective To determine how first trimester detection rates for Down's Syndrome vary with maternal age and to calculate the predictive value of an increased risk report at various maternal ages.

Design Mathematical modelling of first trimester screening performance using fetal nuchal translucency and maternal serum free βhCG and pregnancy associated plasma protein-A (PAPP-A).

Methods From within the Gaussian distributions of each marker in normal pregnancies and those affected by Down's Syndrome a series of 15,000 marker multiple of the medians were obtained for each group. These markers were then used to calculate the risks of Down's Syndrome using maternal ages ranging from 15 to 49 and the background risk of Down's Syndrome at each age. Using a 1 in 300 risk cutoff (at time of sampling) the false positive rate and detection rate was assessed at each year of maternal age. The predictive value of a positive result was calculated using Baye's theorem.

Outcome measures False positive rates and detection rates at each year of maternal age between 15 and 49; the predictive value of a positive result for each maternal age between 15 and 49.

Results At 15 years of age the detection rate was 77% at a 1.9% false positive rate, 84% at a 4% false positive rate at age 30, rising to 100% at a 67% false positive rate at age 49. The probability of Down's Syndrome once identified with an increased risk was 1:34 at 15 years, 1:29 at 30 years and 1:6 at 49 years.

Conclusions As with second trimester biochemical screening, the detection rate and false positive rate vary considerably with age. However, detection rates across all ages are significantly higher than with second trimester screening. The risk of a positive screening result being a Down's pregnancy is considerably greater than with second trimester screening with an average probability of 1:29, compared with 1:55 in the second trimester. This information may be useful in counselling women with an increased risk result in first trimester screening.