Serum marker truncation limits in first trimester antenatal screening for trisomy 18

To assess whether the accuracy of risk estimation in antenatal screening for trisomy 18 using the Combined test can be improved by revising the truncation limits of two serum markers.

In an audit of data from 420 trisomy 18 and 573,754 unaffected singleton pregnancies screened at the Wolfson Institute of Preventive Medicine, London (March 2003 to June 2017), the accuracy of risk estimation was assessed by inspection of a validation plot (the median predicted late first trimester Combined test risk plotted against observed prevalence within categories of predicted risk estimates). Using validation and probability plots, we assessed whether the revised pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (free β-hCG) truncation limits led to more accurate risk estimation and improved screening performance.

With the lower truncation limits currently used for PAPP-A and free β-hCG (0.15 and 0.30 multiples of the median [MoM], respectively), risk was underestimated. Revised lower truncation limits of 0.05 MoM for both PAPP-A and free β-hCG led to greater accuracy, with an increase in the number of trisomy 18 pregnancies detected (from 85.4% to 90.2%) for a small increase in the false-positive rate (from 0.20% to 0.29%) at a 1 in 100 late first trimester risk cut-off.

The revised truncation limits for PAPP-A and free β-hCG increase the accuracy of trisomy 18 risk estimation and improve screening performance using the Combined test. Validation and probability plots are useful in setting screening marker truncation limits.