Pedigree-based Analysis of Inherited and Noninherited Risk Factors of Congenital Heart Defects

Background: Although congenital heart defect (CHD) pedigrees are rare, they are generally taken as evidence of the existence of a genetic etiologic mechanism or environmental factors common to family members, or a combination of both. Therefore, the analysis of CHD pedigrees is important for bridging the gap in our knowledge of its etiology.

Aims: To assess the prevalence of CHD and evaluate the nongenetic factors in the CHD patients and healthy controls in the pedigrees.

Study design: Observational retrospective study.

Subjects: Twenty-three CHD pedigrees were involved in the prevalence statistics; thirty-nine CHD cases and fifty-two healthy controls in the CHD pedigrees were included in the family-based noninherited factors analysis.

Outcome measures: The three-degree relatives and overall CHD prevalence were calculated. Thirty-four noninherited risk factors were compared between the CHD and control groups, first by univariate analysis and later by multivariable logistic stepwise regression analysis.

Results: The CHD prevalence of the probands' relatives in all pedigrees was 8.0%, and it was 10.9%, 2.9% and 11.9% in first-, second- and third-degree relatives, respectively. The three risk factors, including maternal febrile illnesses (OR=14.2, 95%CI: [1.5 - 133.7]), influenza (OR=6.9 [2.0 - 23.6]) and air pollution (OR=13.5 [2.6 - 70.5]), were strongly associated with a higher risk of CHD in our sample.

Conclusions: For the cluster and high prevalence of CHD in the collected pedigrees, our study confirms that genetic factors play a major role in the pathogenesis of CHD, while environmental factors, such as maternal febrile illnesses, influenza and air pollution, may also increase the burden of risk for CHD pathogenesis.