Rare chromosomal abnormalities: Can they be identified using conventional first trimester combined screening methods?

Area of Science:

• Prenatal diagnostics
• Genetics
• Maternal-fetal medicine

Background:

• First trimester screening (FTS) is commonly used to assess fetal chromosomal abnormalities.
• Rare chromosomal abnormalities, excluding common trisomies and Turner syndrome, are infrequently detected by standard FTS.
• Evaluating the efficacy of FTS for these rarer conditions is crucial for accurate prenatal diagnosis.

Purpose of the Study:

• To assess the performance of first trimester combined screening (FTS) in detecting rare chromosomal abnormalities.
• To compare the detection capabilities of FTS with nuchal translucency (NT) measurements for rare fetal chromosomal anomalies.
• To determine if FTS offers an advantage over non-invasive prenatal testing (NIPT) for rare chromosomal abnormalities.

Main Methods:

• Analysis of a database of 36,254 singleton pregnancies from 15 US centers.
• Inclusion of pregnancies between 10 3/7 and 13 6/7 weeks gestation.
• Application of a 1:300 risk cut-off for FTS (NT, PAPP-A, fbHCG) to evaluate detection rates for rare chromosomal abnormalities.

Main Results:

• The incidence of rare chromosomal abnormalities (excluding common trisomies and Turner syndrome) was 1.1 in 1000 pregnancies.
• The FTS detection rate for these rare abnormalities was 35% (14 of 40 cases) using a ≥1:300 risk cut-off.
• A significant majority of rare chromosomal abnormalities (65%) had a normal FTS risk (<1:300), and 95% had a normal NT (<3 mm).

Conclusions:

• Traditional FTS methods demonstrate limited effectiveness in identifying the majority of rare fetal chromosomal abnormalities.
• Nuchal translucency-based first trimester screening is not supported as a superior method for detecting rare fetal chromosomal abnormalities compared to NIPT.
• Current FTS protocols are insufficient for the reliable detection of a wide spectrum of rare chromosomal anomalies.