Left heart obstructions [LHO] as a subset of congenital cardiovascular malformations [CCVM] are thought to be a group linked by a common genetic substrate. We explored possible gene environment interactions by spatial analysis of the three major LHO, aortic stenosis [AS], coarctation of the aorta [CoAo], and hypoplastic left heart [HLH].
Using a case control series of congenital cardiovascular malformations and population based controls, we analyzed spatial distribution of hypoplastic left heart syndrome, in infants diagnosed before one year of age. Statistical analysis included spatial distribution and extensive personal sociodemographic, occupational exposures, and life style exposure factors as well as family history of cardiac or other malformations. Cases and controls were mapped in the State of Maryland and the District of Columbia in the United States, including the years 1981 through 1989.
83 cases of hypoplastic left heart and 1990 controls were included. 16 cases of hypoplastic left heart syndrome occurred in clusters identified by spatial scanning using a Bernoulli method with respect to controls. Of these clusters, the largest was significant with chi square 40.3, p.000. Variables significant by non parametric analysis for case control status for HLH were entered into a multiple regression model. Family history of cardiac malformation and maternal exposure to solvents were predictive of case status. The clusters of hypoplastic left heart syndrome were characterized by low levels of paternal education only when assessed using HLH cases only. Only 9 controls were found within the cluster so confirmatory assessment of characteristics of the spatial region of the cluster could not be made using control data. These characteristics of the clusters of HLH differ from our findings for clusters of AS or CoAo. The HLH clusters are geographically distinct from those of AS and overlap with some clusters of CoAo. CoAo and AS are present in clusters characterized by being in regions of cropland or orchard. Both CoAo and AS in this dataset predominantly distributed in white populations.
The differences in spatial distribution of HLH compared to AS and CoAo may suggest that the genetic risk for HLH differs from that of AS or CoAo. Alternatively, the environmental exposures in different geographic regions may result in different phenotypes by gene environment interactions with common genes for these three congenital left heart obstructions.
(1) Children's National Medical Center
(2) Georgetown University Medical Center