Background: interruption of the aortic arch (IAA) is a rare but severe anom
aly associated with major intracardiac defects and with multisystem noncard
iac malformations, recently linked to chromosome deletion of 22q11.2.
Methods: The Baltimore-Washington Infant Study (1981-1989), a population-ba
sed epidemiologic study of cardiovascular malformations, evaluated 53 infan
ts with IAA in comparison with 3,572 controls. Risk factors for the anatomi
c subtypes were evaluated in 14 cases of]AA type A and 32 cases of IAA type
B, but no molecular genetic tests were available. The distribution of asso
ciated cardiac defects was similar for both types.
Results: DiGeorge syndrome (DGS) occurred more frequently in IAA type B. Ca
se-control comparisons demonstrated that infants in both groups were growth
retarded at birth. A family history of noncardiac defects occurred only in
IAA type 8 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 = 10) and for those without (n = 19) DGS: a family histor
y of noncardiac defects [odds ratio [OR] = 7.2, 95% confidence interval [CI
] = 1.5-39.2) and maternal use of aspirin during the critical period (OR =
4.8, 95% CI = 1.3-25.4) occurred with DGS, while previous stillbirth (OR =
9.4, 95% CI = 1.3-53.1), bleeding during pregnancy (OR = 3.7, 95% CI = 1.4-
11.4), and maternal exposure to arts/crafts paints (OR = 4.8, 95% CI = 1.3-
17.4) were associated in those without DGS.
Conclusions: These findings confirm the heterogeneity of IAA and of the typ
e 8 subtype. Risk factors specific for cases with DGS may open a window to
further investigations of the etiology of IAA and of the associated molecul
ar genetic abnormalities. (C) 2000 Wiley-Liss, Inc.