Chromosomal abnormalities and pregnancy outcomes in 350 pregnancies with prenatally diagnosed aberrant right subclavian artery: a phenotype-based retrospective cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Aberrant right subclavian artery (ARSA) is the most frequent aortic-arch branching variant on prenatal sonography, and its clinical relevance is governed by the phenotypic context in which it is detected. Genotype–phenotype interpretation remains complicated by uneven genetic testing uptake and the additional anomaly burden carried in non-isolated cases.Methods This retrospective single-center cohort comprised 350 singleton pregnancies in which ARSA was diagnosed prenatally at a tertiary perinatology center between January 2020 and April 2025. Cases were classified as isolated ARSA (n = 200), ARSA with soft markers (n = 80), or non-isolated ARSA (n = 70). The primary outcome was chromosomal abnormalities, reported with explicit denominator separation: whole-cohort prevalence and diagnostic yield among invasively tested fetuses. The 22q11.2 deletion case definition required dual confirmation by FISH and chromosomal microarray analysis (CMA). Marker- and anomaly-specific yields were examined to identify findings most strongly linked to chromosomal and adverse pregnancy outcomes.Results Genetic evaluation acceptance varied by phenotype (75.0% isolated, 92.5% soft markers, 92.9% non-isolated; p < 0.001). Whole-cohort chromosomal-abnormality prevalence was 4.5%, 17.5%, and 32.9%; diagnostic yield among invasively tested fetuses was 6.0%, 18.9%, and 35.4%. Trisomy 21 was the most frequent abnormality across phenotypes. Five 22q11.2 deletions (1/1/3 across phenotypes) fulfilled the dual-confirmation criteria; all three non-isolated 22q11.2 cases harbored a conotruncal cardiac anomaly. Marker co-occurrence (≥2 markers, 43.8% of soft-markers) and concurrent major anomalies (≥2, 44.3% of non-isolated) drove yield. Live-birth rates were 97.5%, 87.5%, and 71.4% (p < 0.001). On multivariable logistic regression, ARSA with soft markers (adjusted OR 4.52; 95% CI 1.86–10.96) and non-isolated ARSA (adjusted OR 10.51; 95% CI 4.52–24.44) remained independent predictors of chromosomal abnormality (optimism-corrected AUC 0.708). A compound phenotype (major anomaly + ≥2 soft markers) was present in 25.7% of non-isolated fetuses.Conclusions Phenotype-based classification of prenatal ARSA reveals a significant risk gradient for chromosomal abnormality and adverse pregnancy outcome, with co-occurring markers and conotruncal anomalies emerging as the strongest individual signals. The findings support risk-concordant counseling: conservative invasive testing in confirmed isolated ARSA, intensified evaluation when soft markers co-occur, and a compound-phenotype-aware, anatomy-directed approach, including CMA and 22q11.2-targeted testing for conotruncal lesions, in the non-isolated subgroup.
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7162951395