Comprehensive comparison of fetal right and left atrial isomerism: cardiac and extracardiac malformations, diagnostic accuracy, and survival outcomes
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Right atrial isomerism (RAI) and left atrial isomerism (LAI) are subtypes of heterotaxy syndrome with distinct cardiovascular and visceral anomalies. Accurate prenatal differentiation is essential for risk stratification and clinical decision-making. However, most existing data are derived from postnatal or mixed-age cohorts. This study uniquely focuses on prenatally diagnosed cases with postnatal confirmation and longitudinal outcome analysis. Methods: In this retrospective cohort study, fetuses prenatally diagnosed with heterotaxy syndrome between 2016 and 2022 were reviewed and categorized as either RAI or LAI based on fetal echocardiography and postnatal confirmation. Systematic ultrasound assessments evaluated cardiac position, structural defects, systemic and pulmonary venous return, visceral organ arrangement, and spleen morphology. Postnatal outcomes, including surgical interventions and one-year survival, were analyzed. Statistical comparisons, Kaplan-Meier survival curves, and multivariable Cox regression analyses were performed. A diagnostic algorithm for subtype differentiation was also developed. Results: A total of 63 fetuses were enrolled, including 38 with RAI and 25 with LAI. Live birth was achieved in 26 RAI cases (68.4%) and 12 LAI cases (48.0%). Among liveborn infants, postnatal survival was notably better in the RAI group: 17 of 26 (65.4%) survived beyond infancy, compared to only 4 of 12 (33.3%) in the LAI group. Systemic venous anomalies, especially juxtaposition of the aorta and inferior vena cava (94.7% in RAI vs. 4.0% in LAI, P<0.001), and anomalous pulmonary venous return (44.7% vs. 12.0%, P=0.007) were significantly more frequent in RAI. In contrast, LAI was more often associated with polysplenia (72.0% vs. 18.4%, P<0.001), left ventricular outflow tract obstruction (LVOTO; 32.0% vs. 10.5%, P=0.032), and sinus rhythm preservation (88.0% vs. 57.9%, P=0.008). Diagnostic accuracy of prenatal ultrasound was high for most anomalies, with better detection of systemic and pulmonary venous anomalies in LAI. One-year survival was significantly higher in RAI (65.4%) than it was in LAI (33.3%) (P=0.018). Multivariate analysis identified RAI as an independent protective factor [hazard ratio (HR) =0.42, 95% confidence interval (CI): 0.18–0.98, P=0.044], whereas single ventricle, unbalanced atrioventricular septal defects (AVSD), and anomalous pulmonary venous return (APVR) were predictors of poor outcome. Conclusions: Fetuses with RAI and LAI exhibit distinct anatomical and prognostic profiles. Although RAI presents with more severe cardiovascular malformations, it is paradoxically associated with better survival. Comprehensive ultrasound assessment and the use of a diagnostic algorithm can improve prenatal classification and guide individualized perinatal management.
Authors: Fa Shu, Yao Peng, Yang He, Caihong Chang, Qiangqiang You, Jiaqi Zhang
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4416613838