Objectives The aim of this study was to identify risk factors for cardiovascular malformation.

Methods In a case-referent study prospectively collected data were obtained from original medical records. The study included 277 woman who had infants with a severe cardiac defect, and for each case two referents (medical records study) were included. Data on parental age, maternal reproductive history, disease in early pregnancy, reported maternal use of drugs and alcohol, smoking habits, parental occupation, and maternal body mass index (BMI) were extracted. When data were available from Swedish medical health registers, a comparison was made (register study) between all infants with cardiovascular defects (2208) and all infants born (175 768).

Results Maternal diabetes mellitus was associated with an increased risk for cardiovascular malformation [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.36-4.15], as was a high BMI (>29) (OR 1.46, 95%CI 1.12-1.90). A tendency towards an increased risk was found for involuntary childlessness, spontaneous abortion, thyroid drugs, and nonsteroid anti-inflammatory drugs.

Conclusions Some known risk factors for cardiac defects (eg, maternal diabetes mellitus and the use of antiepileptics) could be identified. Other postulated risk factors could not be verified, for example, paternal age and parental occupation. The use of medicinal drugs seems not to be a major factor in the etiology of cardiac defects. It is possible, however, that there is an association with the use of nonsteroid anti-inflammatory drugs or drugs for thyroid disease. The relationship between a high BMI and cardiovascular malformation observed in this study may be explained by impaired maternal glucose tolerance.

Key terms body mass index; cardiac defect; cardiovascular malformation; drugs; parental age; prospective data; prospectively collected data; risk factor