Discordant Post-natal Patterns in Fetuses With Heterotaxy Syndrome: A Retrospective Single-Centre Series on Outcome After Fetal Diagnosis

Abstract

Objective: Cardiac and extra-cardiac anomalies in 46 pre-natally diagnosed cases of heterotaxy were compared to post-natal anatomical patterns in order to reveal discordant findings. Second, the outcome of these fetuses was evaluated.

Methods: Fetuses with heterotaxy, diagnosed in a tertiary referral centre, were analysed retrospectively. Based on the foetal abdominal situs view, right atrial isomerism (RAI) and left atrial isomerism (LAI) were defined as foetal sub-types. Post-natally, discordant anatomical patterns for broncho-pulmonary branching, atrial appendage morphology, and splenic status were further clarified with CT scans. In summary, the spectrum of pre-natally and post-natally detected cardiac and extra-cardiac anomalies is systematically reviewed. Necessary surgical interventions and mid-long-term outcomes were compared between the two sub-types in surviving infants.

Results: A total of 46 fetuses with heterotaxy were included; LAI was diagnosed in 29 (63%) fetuses and RAI was diagnosed in 17 (37%) fetuses. Extra-cardiac anomalies were noted in 35% of fetuses. Seven out of the 29 fetuses (24%) with LAI had atrio-ventricular block (AVB) and four of these cases presented with hydrops. Twenty nine out of the 46 participating fetuses (63%) were live births, with 62% in the LAI group and 65% in the RAI group. Five fetuses were lost to follow-up. At the age of 1 year, the overall survival of live births [estimate (95% CI)] was 67% (48; 92%) in patients with LAI and 55% (32; 94%) in patients with RAI. At the age of 5 years, the estimates were 67% (48; 92%) in the LAI group and 46% (24-87%) in the RAI group. The median survival (first quartile; third quartile) was 11.1 (0.1; 14) years for patients with LAI and 1.3 (0.09; NA) years for patients with RAI. Of 17 children who had undergone cardiac surgery, five (29%) children achieved a bi-ventricular repair and 12 (70%) children achieved a uni-ventricular palliation. Three were primarily palliated, but converted to bi-ventricular thereafter. Foetal subtype definition of heterotaxy based on the abdominal situs and post-natal thoracic imaging studies showed a discordant pattern of broncho-pulmonary branching and atrial appendage anatomy in 40% of our live-born children.

Conclusion: Heterotaxy is a rare and complex condition with significant morbidity and mortality related to severe cardiac and extra-cardiac associations. Accurate pre-natal diagnosis can help identify the fetuses at risk and allow for timely intervention in a multi-disciplinary setting. Further studies are warranted to shed light on the exact sub-type definition in fetuses with heterotaxy and the presence of discordant post-natal patterns.

Keywords: cardiac surgery; discordant pattern; foetal echocardiography; heterotaxy; isomerism; outcome.

FIGURE 1

Flowchart of patients with the pre-natal diagnosis of heterotaxy in this cohort. LAI, left atrial isomerism; RAI, right atrial isomerism; TOP, termination of pregnancy; LTFU, lost to follow up; IUFD, intrauterine fetal demise; LB, livebirth. *These two fetuses were excluded from further analysis.

FIGURE 2

Left atrial isomerism by foetal MRI. (A) Arrow yellow: right-sided stomach (B) arrow white: bilateral liver, (C) arrowhead white: left-sided gallbladder, (D) arrowhead yellow: left-sided spleen. Gestational age at MRI is 20 weeks + 0 day.

FIGURE 3

The Kaplan–Meier survival curve of patients with a pre-natal diagnosis of left and right atrial isomerism. LAI, left atrial isomerism; RAI, right atrial isomerism.

FIGURE 4

Bronchial tree anatomy and the sub-type of isomerism by neonatal thoracic CT. Arrow white, left isomerism of tracheal bifurcation with bi-lobar lungs.

FIGURE 5

Concordant pattern of broncho-pulmonary branching confirmed by post-mortem MRI in the left atrial isomerism cohort. Arrows: white, bilateral liver; yellow, right-sided stomach. Arrowheads: white, right atrium with insertion of vena cava superior, but without vena cava inferior, yellow, vena azygos supplying blood of the lower body half. Gestational age at MRI is 23 weeks + 4 days.