Atrioventricular septal defects: Possible etiologic differences between complete and partial defects

Background: Recent advances in clinical, pathological, and genetic aspects of atrioventricular septal defects (AVSD) have set the stage for epidemiolo gic investigations into possible risk factors. Previous analyses of the tot al case group of AVSD included complete and partial subtypes without analys is of the subsets. Methods: To address the question of possible morphogenetic heterogeneity of AVSD, the Baltimore-Washington Infant Study data on live-born cases and co ntrols (1981-1989) was reanalyzed for potential environmental and genetic r isk-factor associations in complete AVSD (n = 213), with separate compariso ns to the atrial (n = 75) and the ventricular (n = 32) forms of partial AVS D. Results: Complete and ventricular forms of AVSD had a similar proportion of isolated cases (12.2% and 15.6%, respectively, without associated extracar diac anomalies) and high rates of Down syndrome, whereas the atrial form of partial AVSD included 55% isolated cases. Trisomy 18 occurred in 22% of in fants with the ventricular form, compared with <2% in the other AVSD groups . Analysis of potential risk factors revealed further distinctions. Complet e AVSD as an isolated cardiac defect was strongly associated with maternal diabetes (odds ratio [OR] = 20.6; 95% confidence interval [CI] =5.6-76.4) a nd also with antitussive use (OR = 8.8; CI = 1.2-48.2); there were no stron g associations other than maternal age among Down syndrome infants with thi s type of heart defect. Isolated cases with the atrial type of partial AVSD were associated with a family history of heart defects (OR = 6.2; CI = 1.4 -24.4) and with paternal occupational exposures to ionizing radiation (OR = 5.1; CI = 1.4-27.4), but no risk factors were associated with Down syndrom e. There were no significant associations of any risk factors in the numeri cally small subsets of isolated and Down syndrome cases with the ventricula r form of partial AVSD. Conclusions: These results indicate a similar risk profile of complete AVSD and the ventricular type of partial AVSD, with a possible subset of the la tter due to trisomy 18. Maternal diabetes constituted a potentially prevent able risk factor for the most severe, complete form of AVSD.