Introduction:
Historically, prenatal detection of tetralogy of Fallot (ToF) was poor and around 60% had major extracardiac (ECA) or genetic anomalies. Recently, prenatal detection of ToF has improved, along with a wider range of genetic testing options. Knowledge of outcomes and risk of associated anomalies is crucial for prenatal counselling. We hypothesize that prenatal ToF now has a different risk profile for ECAs and genetic anomalies than previously reported.
Methods:
A retrospective study of all fetuses with a diagnosis of ToF in our Fetal Cardiology program from 2012-2019. ToF type double outlet right ventricle was excluded. Pre and postnatal charts and imaging reports were reviewed for ToF subtype, additional cardiac and non-cardiac diagnoses and outcomes.
Results:
Of 83 cases, 49 had standard ToF, 24 pulmonary atresia (14 with major collateral arteries, 10 without), and 10 absent pulmonary valve. There was ≥1 ECA in 41% (34/83), including 6% (5/83) with 2 and 4% (3/83) with 3. ECA sub-types were: 10 gastrointestinal, 8 neurological, 8 pulmonary, 7 renal, 4 musculoskeletal, and 8 others. Of 76 with genetic testing, 37% (28/76) had genetic anomalies (32% (9/28) Trisomy 21, 29% (8/28) 22q11 deletion, 7% (2/28) Trisomy 18, 7% (2/28) Trisomy 13, and 25% (7/28) other). Additional diagnoses: 4% (3/76) VACTERL spectrum, 1% (1/76) possible teratogenic effect. Right aortic arch was associated with 22q11 deletion (28% (7/25) vs 2% (1/51) p<0.001). ToF with atrioventricular septal defect (AVSD) was strongly associated with Trisomy 21 (100%, 3/3 tested). Those with ≥1 ECA were more likely to have a genetic abnormality (52% (17/33) vs 24% (9/37), p<0.05). Outcomes were: 22% (18/83) termination, 5% (4/83) intrauterine fetal deaths and 72% (60/83) livebirths, with 1 lost to follow-up. Of live births, there were 3% (2/60) neonatal and 7% (4/60) late deaths, and 90% (54/60) were alive at last follow-up (mean age 3.5±2.4 years).
Conclusion:
ECAs are less common in prenatally diagnosed ToF in the modern era, however the rate of genetic diagnoses is similar to previously published data. ToF with right aortic arch and ToF with AVSD in particular have strong genetic associations. Additionally, genetic diagnoses are more common in those with an ECA.
Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching
