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

Am J Med Genet A. 2007 Dec 15;143A(24):2904-9. doi: 10.1002/ajmg.a.32071.


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.

MeSH terms

  • Adult
  • Congenital Abnormalities / etiology*
  • Diabetes Complications / diagnosis*
  • Diabetes Complications / epidemiology
  • Diabetes, Gestational / diagnosis*
  • Diabetes, Gestational / epidemiology
  • Female
  • Humans
  • Infant, Newborn
  • Obesity / complications*
  • Pregnancy
  • Pregnancy Complications / diagnosis*
  • Pregnancy Complications / epidemiology
  • Pregnancy Outcome