Diabetic Embryopathy

A rare disorder characterized by congenital anomalies or foetal/neonatal complications in an infant that are linked to diabetes in the mother.

Epidemiology

Several reports show that the birth prevalence of congenital malformations can be cut by a third by using strict preconception glycemia control, but the challenge of implementing this approach remains.

Clinical description

Macrosomia is also a common problem among infants of women with established insulin-dependent diabetes mellitus. Excess mortality among infants of women with preexisting insulin-dependent diabetes mellitus is predominantly due to congenital malformations. All types of congenital malformations are involved, but some are more common. Notably, the risk of cardiovascular malformations (CVM) is increased, and specific studies show that preconceptional maternal diabetes is strongly associated with CVM of early embryonic origin and with cardiomyopathy (respective odds ratios are 5 and 15). CVM of early embryonic origin are laterality defects (cardiovisceral and atrioventricular discordance), outflow tract anomalies (an association was found between truncus arteriosus and double outlet right ventricle, and other anomalies with normally related great arteries but no association was found with simple transpositions), and anomalies of the endocardial cushion (an association was found with complete but not with partial forms of atrioventricular septal defects). CMV also include hypertrophic cardiomyopathy, which is generally benign and transient, although it may be lethal if associated with hydrops fetalis, especially in case of severe macrosomia. Other anomalies associated with maternal preconceptional diabetes are renal malformations, especially uni- or bilateral kidney agenesis. These ageneses are described as either isolated or of part of multiple malformation syndromes that are more common in individuals with maternal diabetes: caudal regression syndrome (a rare anomaly of the lower body pole that represents a continuum of congenital malformations ranging from isolated sacral agenesis to absence of the lumbosacral spine and major visceral anomalies) and DiGeorge anomaly (velo-cardio-facial syndrome).

Etiology

Cytogenetic studies of DiGeorge anomaly in individuals with maternal diabetes usually detect no abnormalities (i.e. do not uncover a 22q11 microdeletion).

Genetic counseling

In infants of women with established insulin-dependent diabetes mellitus, the risk of congenital malformations is 10 times higher than that in the general population, and the rate of stillbirths is five times higher than that in the general population.