Maternal midpregnancy glucose linked to increased risk of congenital heart disease

1. Maternal midpregnancy glucose levels were associated with having an infant with a tetralogy of Fallot.

Evidence Rating Level: 3 (Average)

Study Rundown: Untreated gestational diabetes or diabetes mellitus preexistent to pregnancy can have devastating affects on the fetus. In the short term, poor glycemic control can lead to major birth defects, spontaneous abortions, neonatal metabolic complications (like hypoglycemia and hypocalcemia), hematologic complications (like polycythemia), respiratory distress, and increased fetal head size (macrosomia), which can increase the risk of birth injury. Long-term effects on offspring include increased risk for obesity, altered glucose metabolism, and even neurodevelopmental changes. While the association between maternal type 2 or gestational diabetes and congenital heart disease has been well described, subclinical abnormalities in glucose and insulin are common and could also serve as risk factors. In this study, researchers looked for a link between two different congenital heart disease phenotypes, tetralogy of Fallot and transposition of the great arteries, and maternal midpregnancy serum glucose and insulin levels

Maternal glucose level was associated with increased odds of having an infant with a tetralogy of Fallot heart malformation even after accounting for age, ethnicity, and adjusting maternal serum insulin. There was no link between maternal glucose levels and a transposition of the great arteries malformation. Strengths include the use of maternal serum insulin levels in regression models–this is one of the first studies to assess the effect of maternal serum insulin on the risk for congenital heart disease. One limitation of this study was the timing of blood sample collection—fetal cardiac development is largely completed by the second trimester when these blood samples were drawn. Future studies might prospectively collect maternal blood samples in the first trimester to further support the connection between poor maternal glucose regulation and cardiac development.

Click to read the study in JAMA Pediatrics

Relevant Reading: Congenital heart disease in infants of diabetic mothers

In-Depth [case-control]: Researchers conducted a secondary analysis of a previously collected, population-based cohort of pregnant women in California. Women were separated by congenital heart disease phenotype (tetralogy of Fallot, n = 55; transposition of the great arteries, n = 42; and no heart disease, n = 180). Multivariable logistic regression models assessed serum insulin and glucose levels at 15-18 weeks gestational age and offspring congenital heart disease.

Serum glucose levels were higher among infants of mothers with tetralogy of Fallot (97.0 vs. 91.5 mg/dL, p = 0.01) compared to controls. In regression models, maternal blood glucose levels were associated with increased odds of having an offspring with tetralogy of Fallot (aOR = 7.54, 95% CI 2,30-24.69).

Image: PD

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