Atypicality index: avoiding false reassurance in prenatal screening

Area of Science:

• Prenatal diagnostics
• Maternal-fetal medicine

Background:

• First-trimester screening is crucial for assessing major trisomies.
• The combined test integrates maternal serum markers and ultrasound measurements.
• An atypicality index quantifies deviations from typical measurement profiles.

Purpose of the Study:

• To evaluate the atypicality index as an adjunct to first-trimester combined screening for major trisomies.
• To assess the association between atypicality index and adverse pregnancy outcomes.

Main Methods:

• A study of 123,998 Danish women with singleton pregnancies.
• Calculation of an atypicality index for nuchal translucency, free β-hCG, and PAPP-A.
• Tabulation of adverse pregnancy outcomes based on screening results and atypicality index.

Main Results:

• Adverse pregnancy outcome incidence increased with higher atypicality index in both low- and high-risk groups.
• In low-risk pregnancies, an atypicality index ≥99% showed a 5.1-fold higher adverse outcome rate compared to <80%.
• In high-risk pregnancies, an atypicality index ≥99% showed a 7.9-fold higher adverse outcome rate compared to <80%.

Conclusions:

• Atypicality index profiles in low-risk pregnancies can provide additional reassurance or indicate further investigation.
• The atypicality index offers a transparent and intuitive visualization of multiple screening variables.
• This method aids in interpreting combined measurements and atypicality levels for improved risk assessment.