Geographic variations in possible risk factors for severe cardiac malformations

The aim of this study was to investigate various putative risk factors in a county in Sweden, described as having a 28% increased prevalence of cardiovascular malformations, and to compare them with the risk factors in two reference counties. Women giving birth in the studied counties differed in age and parity distribution, smoking, and educational level but these differences could not explain the increased risk of cardiovascular malformations in the county, since after stratification for these variables, the risk estimate did not change substantially. A number of potential risk factors were studied in a case/control design: spontaneous abortions, involuntary childlessness, maternal disease, body mass index, medical drug use, alcohol use, parental employment, paternal age, and urban/rural residency. No single factor could be attributed to the increased rate, with the exception of living in a rural district. Nearly all risk factors, however, were stronger in the county studied than those in the reference counties (0.02 > p > 0.01).

The only single putative risk factor that could have contributed to the increased risk for cardiac defects described in the county studied was maternal residency in a rural district. Notably, nearly all potential risk factors studied were stronger in the county studied compared with those in the reference area. A conceivable explanation is that one or more unidentified factors related to rural residency could potentiate prevalent and weak teratogenic risk factors for cardiac defects.