OBJECTIVE: To demonstrate the application of an individual atypicality index as an adjunct to first trimester risk assessment for major trisomies by the combined test.

METHODS: Atypicality indices were produced for measurements of fetal nuchal translucency thickness and maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A in 123,998 Danish women who had routine first trimester screening, including risk-assessment for major trisomies. The incidence of adverse pregnancy outcomes, which included miscarriage, intrauterine or neonatal death, or termination of pregnancy, was tabulated according to the screening result risk and atypicality index, which is a measure of the degree to which the profile was atypical.

RESULTS: In both pregnancies with low-risk and high-risk for trisomies, the incidence of adverse pregnancy outcomes increased with increasing atypicality index. In pregnancies with low-risk for trisomies but atypicality index >99%, the incidence of adverse outcomes was 5.1 (95% CI: 3.4 - 7.6) times higher than in low-risk pregnancies with typical measurement profiles, reflected in atypicality index of <80%; similarly, in high-risk pregnancies the incidence of adverse outcomes was 7.9 (95% CI: 4.4 - 14.5) times higher in those with atypicality index >99%, compared to those with an atypicality index of <80%. Using individual profile plots, we were able to demonstrate a transparent and intuitive method for visualisation of multiple variables and as an aid for interpreting the individual combination and level of atypicality.

CONCLUSIONS: Amongst pregnancies undergoing first trimester combined screening and classified as being at low-risk for trisomies, profiles that are typical of normality provide additional reassurance, whereas those with an atypical profile may warrant further investigation. This article is protected by copyright. All rights reserved.