Maternal Type 1 Diabetes an Outsized Red Flag for Child Heart Defect Risk

Maternal type 1 diabetes (T1D) emerged as the larger contributor to the child’s risk of congenital heart defect (CHD) when considering maternal diabetes and weight status together, a Finnish population-based cohort study found.

The odds of having a child born with any CHD were several-fold higher for women with T1D compared with no maternal diabetes (OR 3.77, 95% CI 3.26-4.36). To a weaker extent, type 2 diabetes (T2D; OR 1.92, 95% CI 1.34-2.75) and gestational diabetes (GD; OR 1.07, 95% CI 1.01-1.14) were also linked with some excess CHD in newborns.

Meanwhile, there was no significant association between maternal obesity (OR 1.00, 95% CI 0.94-1.07) or overweight (OR 0.98, 95% CI 0.93-1.03) and any CHD, reported Riitta Turunen, MD, PhD, of New Children’s Hospital, Helsinki University Hospital, and University of Helsinki in Finland.

“This cohort study emphasizes T1D as a risk factor associated with offspring CHDs, whereas GD and maternal overweight and obesity were associated with a smaller increase in risk, at least in this high-resource setting with universal antenatal care. However, with increasing prevalence of GD and maternal overweight, the risk at the population level is substantial,” the authors wrote in JAMA Network Open.

From 2006 to 2016, maternal T1D stayed stable at a 0.7% prevalence, whereas GD rose in prevalence from 10.3% to 19.2% and T2D from 0.1% to 0.3%. Maternal overweight increased from 20.3% to 22.2% and maternal obesity from 10.7% to 13.3%, according to the Finnish report.

Study authors said that even though “there clearly is a hereditary component associated with CHD,” maternal overweight, obesity, and pregestational and gestational diabetes may be considered potentially modifiable maternal risk factors.

“It has been shown that standard treatment of maternal diabetes is associated with reduced risk of anatomical malformations in offspring. Thus, primary prevention of maternal overweight and obesity and careful treatment of PGD [pregestational diabetes] may hold the opportunity to reduce the burden of disease,” Turunen’s group suggested.

Notably, going beyond associations with CHDs as a whole, the researchers found that each maternal risk factor could be tied to individual CHD subtypes in children:

• Maternal T1D was associated with increased odds of transposition of great arteries, left ventricular outflow tract (LVOT) obstruction, right ventricular outflow tract (RVOT) obstruction, isolated atrial septal defect, isolated ventricular septal defects (VSDs), and other septal defects
• Maternal overweight was associated with LVOT obstruction but appeared somewhat protective against VSDs
• Maternal obesity was associated with complex defects, LVOT obstruction, and RVOT obstruction
• Maternal underweight was strongly associated with increased odds of pulmonary venous anomalies

“These results may suggest that maternal diabetes and overweight or obesity have distinct teratogenic mechanisms given that associated changes in odds were different for many CHD subgroups, and in some cases even opposite,” Turunen and colleagues noted.

They cautioned, however, that the surprising relationship between maternal overweight and offspring VSDs may have been affected by imprecise recording of the true prevalence of isolated VSD, which is difficult to estimate.

“In general, our study indicated that maternal overweight and obesity were associated with smaller increases in CHD odds in offspring than previously reported,” the group maintained. “We speculate that this may be due to our comprehensive data on maternal diabetes, which likely accounts for a larger part of the risk in individuals with overweight and obesity than previously thought.”

The study was based on nationwide registry data on a birth cohort from Finland consisting of all children born from 2006 to 2016 (n=620,751) and their mothers.

Boys made up 51% of the cohort. An isolated CHD, defined as a CHD without diagnoses for chromosomal aberrations, syndromes, or any other major extracardiac anomaly, was recorded in 1.7%.

The retrospective, observational study relied on a database with some self-reported variables such as height and weight, Turunen’s team noted. Other study limitations include the limited sample of children in each CHD subgroup and missing data such as smoking status, pregnancy terminations, and miscarriages.