The incremental yield of chromosomal microarray analysis in fetuses with isolated ARSA and normal karyotype: cohort study and meta-analysis of the literature

Aberrant right subclavian artery (ARSA) is a relatively rare ultrasonographic marker that has been associated with trisomy 21 and 22q11.2 deletion. Its predictive accuracy, however, remains arbitrary as published cohorts do not present consistent findings. This study aimed to evaluate the probability of abnormal chromosomal microarray analysis (CMA) results in a substantial cohort of pregnancies with isolated ARSA and to review the literature to identify the incremental yield of CMA abnormalities in fetuses with isolated ARSA and a normal karyotype. We screened 5,932 pregnancies that performed their antenatal screening in our hospital between 2021 and 2024. Cases that were identified with ARSA underwent a detailed anomaly and cardiac scan and they were offered amniocentesis. In all cases conventional karyotype and CMA was performed. Only cases with low-risk first trimester screening result were included in the study. A literature search was performed in several databases, covering the period from inception to April 2025, for original publications in English that detail the rate and characteristics of microscopic and submicroscopic aberrations in fetuses with isolated ARSA and a normal karyotype. Overall, we identified 82 ARSA cases with low risk first trimester screening results that did not present other ultrasonographic markers (major or minor). The results of conventional karyotype and CMA were normal in all cases (0/82,0%). In all cases a healthy neonate was delivered without any obvious congenital anomalies. The literature search yielded 9 additional relevant papers, encompassing 638 cases of isolated ARSA, of which 10 cases of pathogenic or likely pathogenic Copy Number Variants (CNV) were detected, resulting to an incremental CMA yield of 0.86% (95% CI 0.20–3.68%) over conventional karyotype. No cases of CMA genetic aberrations in fetuses detected with isolated ARSA and normal karyotype were detected in our cohort. Our meta-analysis revealed a CMA incremental diagnostic yield of 0.86% over conventional karyotype. However, such a result should be interpreted with caution necessitating comprehensive pre-test counseling that addresses the diagnostic benefits of microarray testing compared to standard karyotyping in both structurally normal fetuses and those with isolated ARSA. In this view and despite the incremental yield associated with isolated ARSA, such a marker may not serve as a clear indication for CMA testing. Nevertheless, should such a finding be detected, background risk and parental preferences must be considered.