Maternal pre-existing and gestational diabetes and the risk of bicuspid aortic valve in the offspring

Abstract

Abstract Background Approximately 6% of all pregnancies in Denmark are affected by maternal pre-existing or gestational diabetes. Maternal diabetes is a well-known risk factor for congenital heart defects. Among the most common congenital heart defects is bicuspid aortic valve (BAV), which is present in 0.8% of newborns. Familial clustering of BAV is seen in 30-40%, but the heritability is not completely understood and since most cases are sporadic, a multifactorial aetiology has been proposed. The association between maternal diabetes and BAV in the offspring has been sparsely investigated previously. Purpose The purpose was to assess the prevalence of BAV in newborns born to mothers with pre-existing or gestational diabetes compared with children born to mothers without diabetes. Method Systematic, standardized transthoracic echocardiography was performed within 60 days of birth in over 25,000 newborns included in a population-based, multicentre, cohort study between 2016 and 2018. Maternal diabetes-status was collected from obstetrical records maintained by the obstetrical departments of the participating hospitals, supplemented by records from a nationwide registry covering patients contacts with private and public hospitals since 1976. Maternal diabetes was categorized as type 1, type 2, or gestational diabetes (GDM) using the ICD-10 codes DO240, DO241, and DO244, respectively. The exposed newborns were compared with newborns not exposed to maternal diabetes. Results In total, the cohort consisted of 25,553 new-borns of whom 24,707 (96.7%) were not exposed to diabetes, 648 (2.5%) were exposed to GDM, and 198 were exposed to pre-existing diabetes; 136 (0.5%) to type 1 and 62 (0.2%) to type 2 diabetes. Median gestational age was 281 days (interquartile range (IQR) 273;287), median age at examination was 11 days (IQR 7;15), and 48% were female. None of the newborns exposed to pre-existing diabetes had a BAV. Nine (1.4%) new-borns exposed to GDM, and 179 (0.7%) newborns not exposed to diabetes were found to have a BAV, corresponding to a relative risk of 1.92 (95%CI 0.99-3.73), p= 0.056. Conclusion Exposure to maternal diabetes is associated with an increased risk of congenital heart disease. In our large cohort of unselected newborns, the association between diabetes and BAV did not reach statistical significance, but the numerically observed twice higher risk of BAV in children born to women with gestational diabetes is nevertheless intriguing and deserves future attention.