Infrequently studied congenital anomalies as clues to the diagnosis of maternal diabetes mellitus

Abstract

The aim of this study was to identify congenital anomalies (CA) among infants of women with diabetes mellitus (DM) that, even though infrequent or infrequently reported, may suggest diabetic teratogenesis. Using 1976-2005 data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we compared the frequency of selected CA among 130 infants with CA born to women with pregestational DM (PGDM) and 30,009 infants with CA whose mothers had normal glucose tolerance (NGT). To identify which CA were not only significantly more frequent among infants of mothers with PGDM, but also more specific, we calculated the quotient of their frequencies (frequency ratio: FR). The same analysis was made using data from 927 infants of mothers with gestational DM (GDM). Among the studied defects, several were statistically significantly more frequent among infants of PGDM mothers than among infants of mothers with NGT, although the specificity of their association with DM varied, as indicated by the values of the FR. These included: anorectal atresia/stenosis (FR = 2.81; P = 0.03), hallucal polydactyly (FR = 3.62; P = 0.002), heterotaxy (FR = 5.70; P = 0.049), hypertrophic cardiomyopathy (HCM) (FR = 61.60; P = 0.000000), multicystic dysplastic kidneys (MDK) (FR = 5.13; P = 0.0002), and thymus aplasia/hypoplasia (FR = 29.62; P = 0.000001). The only CA significantly more frequent among infants of women with GDM were HCM (FR = 8.60; P = 0.002) and MDK (FR = 1.80; P = 0.01). Our results suggest that maternal PGDM should be suspected in children with hallucal polydactyly, anorectal atresia/stenosis, heterotaxy, or aplasia/hypoplasia of the thymus. The presence of transient HCM or MDK in a newborn suggests maternal PGDM or GDM. These observations are important in view of the increasing worldwide frequency of DM and the high proportion of individuals with DM in whom the condition remains undiagnosed. (c) 2007 Wiley-Liss, Inc.

Genetic and environmental influence on diabetic rat embryopathy

“…We conclude that the fetal genome controls the embryonic dysmorphogenesis in diabetic pregnancy by instigating a threshold level for the teratological insult and that the maternal genome controls the teratogenic insult by (dys)regulating the maternal metabolism. diabetes in pregnancy; congenital abnormalities; teratology; animal experimentation; aldose reductase; glyceraldehyde-3-phosphate dehydrogenase; sonic hedgehog homolog; ret proto-oncogene; glial-derived neurotrophic factor; antioxidative enzymes THE INCIDENCE OF CARDIOVASCULAR, skeletal, urinary, gastrointestinal, and caudal dysgenesis-related defects is higher in offspring of women with preexisting diabetes compared with infants of nondiabetic women (4,18,27,38). Despite extensive research and optimized clinical care, diabetic embryopathy has remained etiologically enigmatic and difficult to prevent (40).…”

Preconception care for women with diabetes and prevention of major congenital malformations

“…Almost any organ can be involved in malformations associated with maternal diabetes, including the cardiac and outflow tract, central nervous system, and the craniofacial, gastrointestinal, musculoskeletal, and urogenital systems (Ewart-Toland et al, 2000;Moore et al, 2000;Loffredo et al, 2001;Spilson et al, 2001, Wang et al, 2002Wren et al, 2003;Nielsen et al, 2005, Frias et al, 2007Lisowski et al, 2010). The types of anomalies seen are similar in infants of women with either DM1 or DM2 (Towner et al, 1995;Schaefer-Graf et al, 2000;Farrell et al, 2002, Dunne et al, 2003Macintosh et al, 2006).…”

Diabetic Embryopathy: A Developmental Perspective from Fertilization to Adulthood

“…Various studies have investigated the RF for specific phenotypic subtypes, comprising bilateral renal agenesis/hypogenesis (RF = 11.91) [Correa et al, 2008] and multicystic dysplastic kidneys (RF = 6.15) [Frías et al, 2007].…”