Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease

Abstract

Background—Maternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort.Methods and Results—In a national cohort study, we identified 2 025 727 persons born from 1978 to 2011; among them were 7296 (0.36%) persons exposed to maternal pregestational diabetes mellitus. Pregestational diabetes mellitus was identified by using the National Patient Register and individual-level information on all prescriptions filled in Danish pharmacies. Persons with CHD (n=16 325) were assigned to embryologically related cardiac phenotypes. The CHD prevalence in the offspring of mothers with pregestational diabetes mellitus was 318 per 10 000 live births (n=232) in comparison with a baseline risk of 80 per 10 000; the adjusted relative risk for CHD was 4.00 (95% confidence interval, 3.51–4.53). The association was not modified by year of birth, maternal age at diabetes onset, or diabetes duration, and CHD risks associated with type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes mellitus did not differ significantly. Persons born to women with previous acute diabetes complications had a higher CHD risk than those exposed to maternal diabetes mellitus without complications (relative risk, 7.62; 95% confidence interval, 5.23–10.6, and relative risk, 3.49; 95% confidence interval, 2.91–4.13, respectively; P=0.0004). All specific CHD phenotypes were associated with maternal pregestational diabetes mellitus (relative risk range, 2.74–13.8).Conclusions—The profoundly increased CHD risk conferred by maternal pregestational diabetes mellitus neither changed over time nor differed by diabetes subtype. The association with acute pregestational diabetes complications was particularly strong, suggesting a role for glucose in the causal pathway.

Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012

“…However, in France, experts recommend restricting GDM screening to women presenting with certain risk factors, which could explain the lower prevalence in this study [11]. In a recent large-scale, nationwide Danish cohort, the risk of cardiac malformations was moderately increased in GDM pregnancies [20]. We found similar results, but showed that this increase was significant only in women with insulintreated GDM.…”

Transitional hemodynamics in infants of diabetic mothers by targeted neonatal echocardiography, electrocardiography and peripheral flow study

“…Moreover, maternal overweight or unrecognized alterations of glucose metabolism before pregnancy could have contributed to this increased incidence in both groups. Hyperglycemia, altered lipid metabolism and non-enzymatic glycosylation of proteins are responsible of increased oxidative stress and activation of apoptotic cascade, resulting in adverse effects on embryogenesis [3,4,16]. These mechanisms can alter the neural crest cell migration involved in cardiac structural development [17].…”

“…Infants of diabetic mothers (IDM) are exposed to an increased risk of structural cardiovascular abnormalities due to multifactorial conditions caused by exposure to prenatal hyperglycemia, alterations of the vascular system and epigenetic mechanisms [3,4].…”

Congenital Heart Diseases in Children: Incidence, Risk Factors, Mortality

“…Ассоциация сахарного диабета и ВПС возможна при гипергликемии до 7 нед гестации [4,34]. По резуль-татам исследований последних лет эти данные полностью подтверждаются [35]. При этом установлено, что тип сахарного диабета значения не имеет [35].…”

“…По резуль-татам исследований последних лет эти данные полностью подтверждаются [35]. При этом установлено, что тип сахарного диабета значения не имеет [35].…”