Fetal cardiac effects of maternal hyperglycemia during pregnancy.
Maternal diabetes mellitus is associated with increased teratogenesis, which can occur in pregestational type 1 and type 2 diabetes. Cardiac defects and with neural tube defects are the most common malformations observed in fetuses of pregestational diabetic mothers. The exact mechanism by which diabetes exerts its teratogenic effects and induces embryonic malformations is unclear. Whereas the sequelae of maternal pregestational diabetes, such as modulating insulin levels, altered fat levels, and increased reactive oxygen species, may play a role in fetal damage during diabetic pregnancy, hyperglycemia is thought to be the primary teratogen, causing particularly adverse effects on cardiovascular development. Fetal cardiac defects are associated with raised maternal glycosylated hemoglobin levels and are up to five times more likely in infants of mothers with pregestational diabetes compared with those without diabetes. The resulting anomalies are varied and include transposition of the great arteries, mitral and pulmonary atresia, double outlet of the right ventricle, tetralogy of Fallot, and fetal cardiomyopathy.A wide variety of rodent models have been used to study diabetic teratogenesis. Both genetic and chemically induced models of type 1 and 2 diabetes have been used to examine the effects of hyperglycemia on fetal development. Factors such as genetic background as well as confounding variables such as obesity appear to influence the severity of fetal abnormalities in mice. In this review, we will summarize recent data on fetal cardiac effects from human pregestational diabetic mothers, as well as the most relevant findings in rodent models of diabetic cardiac teratogenesis.
Corrigan
Niamh
N
UCD School of Medicine and Medical Science, University College, Dublin 2, Ireland.
Brazil
Derek P
DP
McAuliffe
Fionnuala
F
D000818:Animals; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics; D016640:Diabetes, Gestational / Q000097:blood / Q000235:genetics; D005260:Female; D005333:Fetus; D006442:Glycated Hemoglobin / Q000032:analysis; D006330:Heart Defects, Congenital / Q000097:blood / Q000209:etiology / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood / Q000235:genetics
D006442:Glycated Hemoglobin