Document Type


Date of Degree

Fall 2010

Degree Name

PhD (Doctor of Philosophy)

Degree In


First Advisor

Burns, Trudy L

First Committee Member

Mahoney, Larry T

Second Committee Member

Murray, Jeffrey C

Third Committee Member

Romitti, Paul A

Fourth Committee Member

Scholz, Thomas D


Congenital heart defects (CHDs) constitute a major proportion of clinically significant birth defects and are an important component of pediatric cardiovascular disease. Atrioventricular septal defects (AVSDs) include a range of anomalies characterized by atrial, ventricular, and atrioventricular (AV) valve defects. AVSDs commonly occur in the presence of a syndrome, most frequently Down syndrome; they also occur in isolation and are referred to as non-syndromic AVSDs (NSAVSDs). These studies were performed to evaluate for presence of an intermediate phenotype in parents and siblings of a child with a NSAVSD, risk factors associated with NSAVSDs, and prognostic risk factors for left AV valve replacement following primary repair of an AVSD.

It was shown that the mean body surface area-standardized AV septal length (AVSL) was significantly shorter in the NSAVSD parents and siblings than in parents and siblings of syndromic AVSD case and control children. Using age- and gender-adjusted body surface area-standardized AVSL, it was determined that there was evidence for two component distributions in parents and siblings of NSAVSD children, suggesting the presence of an intermediate. Broadening the definition of AVSD to include those with a shortened AVSL may increase the power of genetic association and mapping studies to identify susceptibility genes.

Risk factors associated with NSAVSD were examined using the 1997-2005 National Birth Defects Prevention Study database. Mothers who actively smoked or were exposed to passive smoke anytime from one month prior to pregnancy through the end of the first trimester were more likely to have an infant with a NSAVSD. There was a suggestive association between AVSDs and use of antibacterial, antifungal, and antiviral medications. Additional investigations are warranted to investigate associations with specific medications as well as to uncover possible gene-environment interaction effects that may modify these risks in order to develop improved primary prevention strategies.

Using the Pediatric Cardiac Care Consortium database, factors associated with time to first reoperation and time to replacement following primary AVSD repair were evaluated. Type of AVSD repair, closure of the mitral valve cleft, moderate to severe postoperative left AV valve regurgitation, and presence of postoperative complete heart block were associated with earlier time to reoperation after adjusting for age and weight at AVSD repair. Down syndrome and presence of postoperative mitral stenosis were associated with earlier time to replacement. Prognostic risk factors following left AV valve replacement in children who had previously undergone AVSD repair were also identified. A prosthetic valve size to body weight ratio of greater than 3 and the presence of Down syndrome were identified as predictors of in-hospital death following left AV valve replacement.

By adding to our knowledge of the AVSD familial and environmental risk factors from these studies, we will be able to (1) improve genetic counseling, (2) identify other family members for genetic testing, (3) begin to devise primary prevention strategies, and (4) improve treatment modalities. By recognizing prognostic factors which influence survival, optimal patient care can be devised which will not only improve treatment modalities, but also long-term survival.


Atrioventricular Septal Defect, Left Atrioventricular Valve Repair, Left Atrioventricular Valve Replacement, Phenotype, Prognostic Factor, Risk Factor


xv, 275 pages


Includes bibliographical references (pages 232-275).


Copyright 2010 Sonali Subhashchandra Patel