Consanguinity, Maternal Age, and Maternal Diabetes as Potential Risk Factors for Congenital Heart Diseases: A Nested Case Control Study from Saudi Arabia

Background: Several risk factors have been implicated as possible causes of congenital heart diseases (CHD), some are genetic and others are environmental. Previous studies have suggested presence of association with consanguinity, but most investigators have not addressed the association with specific diagnostic categories of CHD such as Patent Ductus Arteriosus and Tetralogy of Fallot, nor quantifying the magnitude of the effect sizes simultaneously attributed to gender, maternal age and maternal diabetes. Methods: Using Saudi Arabia CHD registry data, we compared the odds of having Patent Ductus Arteriosus (PDA) and Tetralogy of Fallot (TOF) for families with consanguineous marriages and those of unrelated parents. Since maternal age is a possible confounder the comparisons are made by first constructing maternal age strata and then pooling the estimated odds ratio across age strata. The data included (n=429) mothers with (n=259) consanguineous marriages. Results: The prevalence of CHD was significantly higher for boys in consanguineous marriages (OR=3.7, 95% CI: 1.05-12.78). The prevalence of CHD for girls was also higher in consanguineous marriages, but the difference from that of non-related marriages did not reach significance (OR=1.84, 95% CI: 0.758-4.490). The joint effect of the risk factors on the CHD was assessed using the logistic regression models. Conclusions: The association between CHD and consanguinity may be due to underlying genetic factors and/or environmental factors common among siblings of the same family.