Consanguineous marriage and congenital heart defects: a case-control study in the neonatal period.

The independent effect of consanguinity on the prevalence of congenital heart defects (CHDs), all and specific types, was investigated in newborns admitted to nine hospitals located in Beirut, Lebanon and members of the National Collaborative Perinatal Neonatal Network (NCPNN). Cases were 173 newborns admitted to the Neonatal Intensive Care Units (NICU) of participating hospitals during the 3-year period from January 1, 2000 to December 31, 2002 and diagnosed during their hospital stay as having one or more CHD. Cases with chromosomal abnormalities were excluded. Cases with more than one CHD were assigned one principal malformation. Controls consisted of a random sample of 865 newborns without a CHD admitted to the NICU during the same period. After controlling for confounders, first cousin consanguinity remained significantly associated with an increased risk of CHD: infants born to first cousin marriages had a 1.8 times higher risk of having a CHD diagnosed at birth compared to those born to unrelated parents (95% CI: 1.1-3.1). In particular, first-cousin marriage was a significant risk factor for ventricular septal defect (VSD), atrial septal defect (ASD), hypoplastic left heart (HLH), and single ventricle (SV). No association was found with d-transposition of the great arteries, coarctation, pulmonary atresia (PA), atrioventricular septal defect (AVSD), and tetralogy of Fallot (TOF). The results of this study suggest a familial factor in the multifactorial etiology of CHDs. Additional epidemiologic and family-based genetic studies are needed to understand the complex cause of CHDs.