Thesis: Ultrasonographic markers for aneuploidy

Jeroen Pennings, PhD
[email protected]

On Monday the 1st of June, Fedja Vos defended her PhD thesis at the University of Groningen, the Netherlands. In her thesis "Ultrasonography of the fetal nose, maxilla, mandible and forehead as markers for aneuploidy," Fedja describes several anatomical features in the fetal facial profile identifying aneuploid fetuses Down and Edwards syndrome (DS and ES) in ultrasound (US) investigations performed beyond the first trimester.

Currently, first trimester screening for trisomy 21, 18 and 13 is offered to all pregnant women in the Netherlands. However, only an estimated 30% of Dutch women actually apply for the test. As a consequence, fetuses with chromosomal anomalies are often undetected until the pregnant woman has the routine 20-weeks scan in the second trimester. Despite the advantages of first trimester screening, there is currently a need for tools and measurements that can help the ultrasonographer in affirming or weakening the suspicion of a chromosomal anomaly.

As part of the studies in this thesis, a group of fetuses was measured retrospectively, which allowed inclusion of a large number of DS and ES fetuses from multiple centers. In the group of fetuses with DS, 86% had a strongly abnormal prenasal thickness (PT) to nasal bone length (NBL) ratio, and even 95% had an abnormal PT-NBL ratio and/or prefrontal space ratio (PFSR). Of the fetuses with Edwards syndrome, 88% had an abnormal PT-NBL ratio. Measurement of the fetal profile (FP) line, to assess the position of the mandible opposed to the forehead, is often positive in DS and negative in ES so this can differentiate between Down and Edwards syndrome. The conclusion of this thesis is that using relatively simple measurements in the fetal profile during the 20-weeks scan, the suspicion of a chromosomal anomaly like DS and ES can be substantiated.

A substantial part of this thesis is on the development of three-dimensional (3D) US, including a comparison of the merits and limitations compared to conventional two-dimensional (2D) US. Overall, this part of the work shows that although 3D US allows some advantages, markers such as the PT-NBL ratio, PFSR and FP line can be reliably used as screening markers in 2D US examinations. These profile markers can, therefore, theoretically be part of routine US investigation, provided the markers are measured in an as-good-as-possible mid-sagittal image of the fetal profile.

View the full thesis here.