Background: Interruption of the aortic arch (IAA) is a rare but severe anomaly associated with major intracardiac defects and with multisystem noncardiac malformations, recently linked to chromosome deletion of 22q11.2.
Methods:
The Baltimore-Washington Infant Study (1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989), a population-based epidemiologic study of cardiovascular malformations, evaluated 53 infants with IAA in comparison with 3,572 controls. Risk factors for the anatomic subtypes were evaluated in 14 cases of IAA type A and 32 cases of IAA type B, but no molecular genetic tests were available. The distribution of associated cardiac defects was similar for both types.
Results: DiGeorge syndrome (DGS) occurred more frequently in IAA type B. Case-control comparisons demonstrated that infants in both groups were growth retarded at birth. A family history of noncardiac defects occurred only in IAA type B cases and included relatives with cleft lip and/or cleft palate. Candidate risk factors were associated only in type B cases and differed for those with (n Ο 10) and for those without (n Ο 19) DGS: a family history of noncardiac defects (odds ratio [OR] Ο 7.2, 95% confidence interval [CI] Ο 1.5-39.2) and maternal use of aspirin during the critical period (OR Ο 4.8, 95% CI Ο 1.3-25.4) occurred with DGS, while previous stillbirth (OR Ο 9.4, 95% CI Ο 1.3-53.1), bleeding during pregnancy (OR Ο 3.7, 95% CI Ο 1.4 -11.4), and maternal exposure to arts/crafts paints (OR Ο 4.8, 95% CI Ο 1.3-17.4) were associated in those without DGS.
Conclusions: These findings confirm the heterogeneity of IAA and of the type B subtype. Risk factors specific for cases with DGS may open a window to further investigations of the etiology of IAA and of the associated molecular genetic abnormalities.