Risk factors for heart disease associated with abnormal sidedness

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Abstract
Background: The purpose of this study is to obtain information on potential familial and environmental risk factors for liveborn cases of heart disease associated with abnormal visceral and vascular sidedness, heterotaxy heart disease, so that hypotheses about this congenital cardiovascular malformation (CCVM) and its risk factors can be generated. We describe the characteristics of infants with heterotaxy heart malformations and case‐control comparisons of interview data obtained on parental socio‐demographic characteristics, occupational and household environmental exposures.Methods: Cases and controls are drawn from the Baltimore Washington Infant Study (BWIS) a population based case control study of CCVM diagnosed in the region from 1981–89.Results: Maternal diabetes (OR = 5.5, 95% CI = 1.6–19.1) and family history of malformations (OR = 5.1, 95% CI = 2.0–12.9) are strongly associated with cardiac disorders of sidedness. Cocaine use by mothers during the first trimester is associated with heterotaxy heart disease with odds of 3.7 (95% CI = 1.3–10.7). Cases of isolated dextrocardia shared risk factors with other heterotaxy malformations. The odds of a twin proband having heterotaxy heart disease is 4.8 (95% CI = 1.9–11.8) compared to singleton births. Twin probands are predominantly monozygotic twins in contrast to twin probands in other congenital cardiovascular malformations.Conclusions: Our findings are consistent with a role for multiple genetic factors in the development of left‐right axis formation and with variable cardiac phenotypes according to gene expression and possible gene‐environment interactions. Association with monozygotic twinning and with parental cocaine use may point to additional mechanistic clues for future research. Teratology 66:242–248, 2002.