Chromosomal abnormalities and pregnancy outcomes in 350 pregnancies with prenatally diagnosed aberrant right subclavian artery: a phenotype-based retrospective cohort study.

摘要

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.