(874) How common are fetal genetic abnormalities in “low-risk” patients undergoing genetic testing?

Objective: While amniocentesis and chorionic villus sampling (CVS) are typically performed in those with risk factors, they should be offered to all patients. Our aim was to evaluate the rate of chromosomal abnormalities or copy number variants (CNVs) in patients at low risk who chose to undergo diagnostic testing.

Study Design: This was a retrospective review of low-risk patients who underwent invasive testing from 2016-2022. “Low-risk” was defined as those without abnormal screening tests for aneuploidy or single gene disorders. Those with ultrasound abnormalities prior to invasive testing, no prior genetic screening test, and those who terminated for reasons unrelated to genetic diagnosis were excluded. Advanced maternal age (AMA) (age ≥35) patients with normal non-invasive prenatal test (NIPT) were considered low-risk, due to the high sensitivity of NIPT for age-related chromosomal abnormalities. The primary outcome was the rate of genetic abnormalities in low-risk patients. Analysis was done using Fisher’s exact.

Results: 668 patients at a median age of 37 (35-40) underwent invasive testing. 77.2% underwent amniocentesis, 21.9% CVS, and 0.9% both. 97% had normal karyotype and microarray. 20 patients (3%) had abnormal genetic testing, including 4 with abnormal karyotype (all inherited rearrangements) and 16 with abnormal microarray. Of the 16 abnormal microarrays, two (12.5%) were considered pathogenic or potentially pathogenic. Genetic findings are shown in Table 1. Overall, three patients (0.4%) chose to terminate the pregnancy due to genetic results. The rate of AMA was not different in those with and without genetic abnormalities (86.9% vs 75%; p=0.25).

Conclusion:

Genetic screening can identify a population at very low-risk of abnormalities on karyotype or microarray. While most patients in this population had normal genetic testing, clinically significant abnormalities were encountered. These results reinforce the importance of offering invasive testing to all patients, regardless of risk, especially in those who would consider abortion.