Atypicality index: avoiding false reassurance in prenatal screening

ABSTRACT Objective To demonstrate the application of the atypicality index as an adjunct to first‐trimester risk assessment for major trisomies by the combined test. Methods This was a study of 123 998 Danish women with a singleton pregnancy who underwent routine first‐trimester screening, including risk assessment for major trisomies. An atypicality index, which is a measure of the degree to which a profile is atypical, was produced for measurements of fetal nuchal translucency thickness and maternal serum free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A. The incidence of adverse pregnancy outcome, including miscarriage, intrauterine death and termination of pregnancy, was tabulated according to the screening result and atypicality index. Results In pregnancies with low risk and those with high risk for major trisomies according to the combined screening test, the incidence of adverse pregnancy outcome increased with increasing atypicality index. In pregnancies with a low risk for trisomies and atypicality index of ≥ 99%, the incidence of adverse outcome was 5.1 (95% CI, 3.4–7.6) times higher compared with that in low‐risk pregnancies with a typical measurement profile, reflected by an atypicality index of