Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities: Improving Efficacy using the Combined First Trimester Screening Algorithm as well as Individual Risk Parameters

Fetal Diagn Ther. 2019;45(6):424-429. doi: 10.1159/000492152. Epub 2018 Sep 10.

Abstract

Aim: To examine the performance of the combined First Trimester Screening (cFTS) algorithm when outliers of 4 risk parameters (maternal age, nuchal translucency (NT) thickness, PAPP-A and β-hCG) were included in the classification of "high-risk".

Methods: A retrospective analysis of singleton pregnancies undergoing cFTS between 2008 and 2011 in Denmark. Abnormal karyotypes were classified as trisomy 21 (T21), trisomy 13 (T13) and trisomy 18 (T18), sex chromosome aberrations and atypical abnormal karyotypes.

Results: cFTS was completed in 193,638 pregnancies. In 10,205 (5.3%) cases, cytogenetic or molecular analysis was performed pre- or postnatally. An abnormal karyotype was seen in 1,122 (11.0%). The algorithm identified 87% of T21, 80% of T13, 75% of T18, 79% of sex chromosome aberrations and 35% of atypical abnormal karyotypes. Additional classification of a single risk parameter outlier (low PAPP-A or free β-hCG (< 0.2 MoMs), high β-hCG (≥5.0 MoMs), maternal age ≥45 years or NT ≥3.5 mm) as being at high-risk would have improved detection rates to 88, 80, 81, 81 and 37% respectively. The screen positive rate increased from 4.4 to 4.8%.

Discussion: Addition of outliers of the 4 parameters used in cFTS algorithm will lead to a statistically significant increase in detection rates for chromosomal abnormality.

Keywords: Chromosomal anomaly; Combined first trimester screening; Prenatal diagnosis; Prenatal screening.

MeSH terms

  • Adult
  • Algorithms
  • Chromosome Disorders / diagnosis
  • Dänemark
  • Down Syndrome / diagnosis
  • Female
  • Humans
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Diagnosis / methods*
  • Retrospective Studies
  • Risk Factors
  • Trisomy 13 Syndrome / diagnosis
  • Trisomy 18 Syndrome / diagnosis
  • Trisomy*