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A cluster of hypoplastic left heart malformation in Baltimore, Maryland
1Department of Cardiology, Children's National Medical Center, 111 Michigan Avenue, N.W., Washington, DC, 20010, USA. kkuehl@cnmc.org.
Insights
Spatial analysis identified a Baltimore cluster of hypoplastic left heart (HLH) with increased prevalence and industrial solvent, dioxin, and PCB air releases. Both genetic and environmental factors likely contribute to this congenital cardiovascular malformation.
Area of Science:
- Cardiovascular Science
- Environmental Epidemiology
- Pediatric Cardiology
Background:
- Congenital cardiovascular malformations (CCVMs) of the left heart, such as hypoplastic left heart syndrome (HLH), exhibit familial recurrence.
- Previous studies linked CCVMs to parental occupational/leisure solvent exposure, diabetes, and family history.
- Spatial analysis can reveal environmental risk factors for CCVMs.
Purpose of the Study:
- To identify geographical clusters of hypoplastic left heart syndrome (HLH).
- To investigate potential environmental risk factors associated with HLH clusters.
- To explore the interplay of genetic and environmental factors in HLH etiology.
Main Methods:
- Spatial analysis was employed to detect clusters of HLH.
- A nested case-control cohort included 77 HLH cases and 1894 controls in Maryland and D.C. (1981-1989).
- Nonparametric and regression analyses incorporated personal and spatial variables.
Main Results:
- A Baltimore region showed HLH prevalence twice the expected rate, with 30 of 77 cases.
- This cluster exhibited a disproportionate number of male HLH cases.
- The cluster area had documented industrial air releases of solvents, dioxin, and PCBs.
Conclusions:
- Spatial analysis delineated an urban region with increased HLH prevalence.
- Within the cluster, excess male HLH cases coincided with industrial environmental exposures.
- Both genetic predisposition and environmental factors are proposed contributors to HLH.
Abstract:
Congenital cardiovascular malformations (CCVMs) of the left side of the heart show familial recurrence of various forms of obstructive malformations, including hypoplastic left heart (HLH), interrupted aortic arch, coarctation of the aorta, and aortic stenosis. In a previous population-based study in the Baltimore-Washington region, these malformations were associated with parental reports of occupational or leisure solvent exposure, overt diabetes, and family history of CCVM in first-degree relatives. Spatial analysis in this well-characterized study population may augment self-reported data by revealing additional associations with potential environmental risk factors. We used spatial analysis to identify clusters of HLH as a group. The study population included all live-born cases of hypoplastic left heart syndrome diagnosed in the first year of life between 1981 and 1989 and a random sample of unaffected infant controls matched by year and hospital of birth. The nested case-control cohort in this spatial analysis included 77 HLH cases and 1894 controls in Maryland and the District of Columbia. Nonparametric and regression analyses included personal variables from the interview data set as well as spatial variables. A region of Baltimore was identified that contained HLH at twice the expected frequency based on the distribution of population younger than 5 years of age. The region included 30 of 77 geocoded cases of HLH in the cohort and is significant by spatial scanning at p = 0.056. Within this region, male cases of HLH were disproportionately present compared to females. This cluster is in a region of Baltimore with industrial release of solvents, dioxin, and polychlorinated biphenyls in air. Outside the cluster, HLH is associated with family history of CCVM in a first-degree relative, maternal exposure to miscellaneous solvents, paternal anesthesia, maternal art painting, aspirin ingestion, and maternal diabetes. Inside the cluster, father's painting and exposure to sympathomimetic drugs were associated risk factors. Spatial analysis of HLH cases delineated an urban region with increased prevalence of this left heart malformation. Within this region, excess male cases of HLH occurred, and industrial release to air of solvents, dioxin, and polychlorinated biphenyl compounds was documented. We propose that both genetic and environmental factors contribute to the phenotype of HLH.
