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. 2004 Feb 28;84(6):823–833. doi: 10.1016/0002-8703(72)90077-4

Intrauterine virus infections and congenital heart disease

James C Overall Jr a,b,∗
PMCID: PMC7119417  PMID: 4361535

Abstract

The etiologic basis for the vast majority of cases of congenital heart disease remains largely undefined. Viruses have been considered to be likely candidates since the recognition of the association between intrauterine rubella and congenital heart disease. Although the pathogenesis of cardiovascular defects is poorly understood, information gained from the study of congenital rubella syndrome suggests that mechanisms such as focal endothelial cell damage, resulting in obliteration of vascular supply, decreased growth rate, and shortened survival time of certain cells, and disturbed DNA replication in cells whose chromosomes were damaged secondary to the effects of virus replication may be operative in the production of defects in the developing fetus. In addition to rubella there is suggestive, but not conclusive, evidence that Coxsackie B3 and B4 virus infections during pregnancy can result in the birth of infants with a variety of types of congenital heart lesions and that intrauterine mumps virus infection may be etiologically related to the postnatal development of endocardial fibroelastosis (EFE). Although there are a number of other viruses that are potential etiologic agents of congenital heart disease, the current status of information is inadequate to allow even suggestive associations to be made. The most profitable areas for future investigation appear to be: (1) the epidemiology of congenital heart disease, (2) prospective studies of the association of maternal viral infection with abnormal offspring, (3) the in-depth virologic investigation of the infant with a cardiac defect, and (4) the development of experimental animal models of congenital heart disease. Successful control of virus-induced congenital heart disease will depend on the results of these investigations and the development of vaccines against the identified causative viruses and/or safe and effective antiviral chemotherapy for the woman in early gestation who is infected with a known teratogenic agent.

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