A Stanford study shows that pregnant women with elevated blood-sugar levels are at greater risk for having babies with congenital heart defects.
Pregnant women with elevated blood-sugar levels are more likely to have babies with congenital heart defects, even if their blood sugar is below the cutoff for diabetes, according to a new study from the Stanford University School of Medicine and Stanford Children's Health.
The study, published online Oct. 12 in JAMA Pediatrics, extends the scope of prior findings on the connection between maternal diabetes and fetal heart defects. It is the first to show the link in women without a diabetes diagnosis.
"Diabetes is the tail end of a spectrum of metabolic abnormalities," said James Priest, MD, the study's lead author and a postdoctoral scholar in pediatric cardiology. "We already knew that women with diabetes were at significantly increased risk for having children with congenital heart disease. What we now know, thanks to this new research, is that women who have elevated glucose values during pregnancy that don't meet our diagnostic criteria for diabetes also face an increased risk." Priest treats patients with congenital heart defects at the Children's Heart Center at Lucile Packard Children's Hospital Stanford.
Pregnancy normally involves metabolic changes that make blood sugar — glucose — more available to the fetus than to the mother, an important adaptation for ensuring that the fetus gets enough nourishment. However, in some women, especially those who are obese or who have a family history of diabetes, these changes progress too far, to the point that the mother develops gestational diabetes. Although the risks of gestational diabetes have been well-studied, less attention has been paid to smaller metabolic changes in pregnancy.
The blood samples were collected at different times of the day, and the women were not asked to fast before sample collection. The researchers measured the women's levels of glucose, the main form of blood sugar, and insulin, a hormone that controls blood sugar.
The scientists used a mathematical model that accounted for both glucose and insulin levels, and was adjusted for the woman's age and ethnicity and whether she had diabetes. In the model, higher glucose levels were correlated with the odds of having a baby with tetralogy of Fallot, but not with dextrotransposition of the great arteries. In the model, however, the relationship with insulin levels was not significant for either birth defect.
Glucose is a fundamental fuel for cells, Priest noted, so it is unlikely that it is high glucose itself that damages the fetal heart. "It has to act via some mechanism," he said, adding that the cell's machinery for handling glucose overlaps with important developmental signaling mechanisms, such as the insulin-like growth factor receptors.
Most of the time we don't have any idea what causes a baby's heart defect. I aim to change that.
The work is an example of Stanford Medicine's focus on precision health by generating care that is proactive, predictive and personalized.