Maternal diabetes: An independent risk factor for major cardiovascular malformations with increased mortality of affected infants

Background: Intensive medical care of women with diabetes has reduced their risks of bearing infants with congenital anomalies. To assess the preventi ve potential of preconceptional care, the data of a population-based study of cardiovascular malformations (CVM) were analyzed to determine the morpho genetic specificity of maternal diabetes risks, the morbidity and mortality of the infants, and maternal characteristics that might affect these risks . Methods: The Baltimore-Washington Infant Study was a case-control study (19 81-1989) that included all live born infants with confirmed CVM; control in fants were a representative sample of the birth cohort. A questionnaire adm inistered in home visits recorded parental information on social, medical, occupational, and environmental factors. For these analyses of preconceptio nal diabetes risks, the case group excluded chromosomal and mendelian disor ders and was divided into 3 developmental categories and 12 diagnostic grou ps. Results: Preconceptional maternal diabetes was strongly associated with CVM of early embryonic origin (odds ratio [OR] = 4.7, 95% confidence interval [CI] 2.8-7.9) and with cardiomyopathy (OR = 15.1, 95% Cl 5.5-41.3), but not with obstructive and shunting defects (OR = 1.4, 95% Cl 0.7-3.0). There wa s heterogeneity within these developmental categories: among laterality def ects, diabetes was associated only with cardiovisceral and atrioventricular discordance (OR = 10.0, 95% Cl 3.7-27.0); among outflow tract anomalies, t he risk was strongly associated with normally related great arteries (OR = 6.6, 95% Cl 3.2-13.3) but riot with simple transpositions; and among atriov entricular septal defects, diabetes was associated with the complete but no t with the partial forms (OR = 22.8, 95% CI 7.4-70.5). The association in e arly CVM was strongest among infants with multisystem, predominantly VACTER L, anomalies. All-cause mortality of infants with CVM was 39% among those w ith diabetic mothers and 17.8% in those with nondiabetic mothers. Deceased infants of diabetic mothers were also more likely to have extracardiac anom alies (P = 0.041), to be born prematurely (P = 0.007), and to have low birt h weight (P = 0.011). Multivariate analyses of maternal factors revealed no significant confounders of the diabetes associations. Conclusions: The evidence of diabetes-induced major cardiac defects is of u rgent clinical significance, The effectiveness of early preconceptional car e in the prevention of congenital anomalies has been demonstrated repeatedl y. (C) 2001 Wiley-Liss, Inc.