Babies born to mothers with diabetes may have subtle structural differences in their hearts that could influence their risk of heart disease later in life. A large-scale study of more than 25,000 newborns in Denmark found that infants exposed to maternal diabetes in the womb had thicker heart walls and smaller left ventricles. Researchers are now investigating whether these changes persist into adulthood and how they might affect long-term heart health.
People born to mothers with diabetes are more likely to develop heart disease as adults. To get to the heart of this matter, researchers needed the help of thousands of babies.
Scanning more than 25,000 newborns in Denmark revealed subtle anatomical differences in the hearts of babies born to mothers with both pre-existing and gestational diabetes, according to new research published in Diabetes Care.
“Whether these differences are relevant later in life hinges on the question of whether they will persist – and whether they will get worse,” says senior author Heather Boyd, an epidemiologist at Denmark’s Statens Serum Institut.
As in the womb, so in the world
“The traditional way of understanding pregnancy complications was that if the mother and baby could get through the pregnancy, everything would be fine,” Heather Boyd says. “It was all done and dusted once you delivered the baby and everybody survived.”
“We are starting to realise that this is not true – that what happens to both mom and baby during pregnancy often affects later life,” she says.
Previous studies suggest that children born to mothers with diabetes “have higher risks of cardiovascular disease when they grow up and a substantially increased risk of heart defects,” she explains. “But is this hereditary? Or is it triggered by what happened in the uterus?”
To find out, Heather Boyd and colleagues searched for evidence of how diabetes affects the heart at the very start of life.
The Copenhagen Baby Heart Study examined more than 25,000 newborns born between 2016 and 2018 in three hospitals in Denmark’s capital. Researchers performed echocardiography – scanning with ultrasound to map the structure and function of the heart – of each baby before two months of age. “It was an absolutely monumental undertaking” that required the collaboration of dozens of specialists, medical students, and sonographers, Heather Boyd says.
The researchers were most interested in the left ventricle: “the pumping chamber of the heart,” she explains. “We were looking at how thick the walls of that chamber were, how big that chamber is internally and also its systolic and diastolic function – how good the heart is at pushing blood out and how good it is at relaxing and refilling with blood.”
Measuring the anatomy of the heart is a true challenge in this population, Heather Boyd says. “The infant heart is really tiny,” and some cardiac landmarks of newborns are “just millimetres thick”. A difference of 0.1 millimetres – about the thickness of a strand of human hair – can represent 5% of the size of a newborn’s left ventricle wall.
Less than 1% of the babies included in the study were born to mothers with pre-existing diabetes, and about 2.5% had mothers who developed gestational diabetes during pregnancy. The 97% of babies born to mothers without diabetes provided a benchmark for normal heart development.
Thicker walls and faster heartbeat
Comparing the babies of mothers with diabetes with babies with normal blood glucose control revealed subtle but potentially important differences in the left ventricle, Heather Boyd says.
“The walls of the left ventricle were thicker among babies born to mothers with diabetes,” she says. “In this study, that meant that the internal volume of the chamber was smaller.”
But were these differences purely structural, or did they affect the function of the heart as well?
“The amount of blood being pumped out in each stroke was less than for the babies born to mothers without diabetes,” Heather Boyd says. But their tiny hearts were working overtime to compensate. “Their hearts filled up with blood faster and beat faster.”
The differences were more pronounced for babies born to mothers with pre-existing diabetes but were also present for babies whose mothers experienced gestational diabetes.
In the short term, these babies’ hearts seemed to be keeping up with the body’s demand for fresh, oxygenated blood. “Most of these babies were not referred for any kind of follow-up based on their echocardiograms,” Heather Boyd explains. “Right now, their hearts are functioning just fine.”
But if these differences persist or get worse as the babies grow, it could increase their risk of heart disease as adults. “If you go through life with heart walls that are too thick, eventually you will stop being able to compensate.”
Do these changes last?
Scientists have yet to pin down the mechanism behind these cardiac differences among babies who experience diabetes in the womb, Heather Boyd says. “We know that if the mother has higher glucose levels, it crosses the placenta, meaning that the babies are producing more insulin to deal with it.”
“But how that translates to changes in the structure of infant hearts is hard to say,” she explains.
Heather Boyd and her team are following up the babies from the study to see how their hearts have grown. “We are calling them back in to see whether the children on the extreme ends at birth are still on the extreme ends now when they are almost 10 years old,” she says.
If the structural differences are still present, researchers will need to consider what interventions – if any – could improve the children’s heart health.
In Denmark, Heather Boyd says, little more can be done for the mother during pregnancy to make the environment in the womb more favourable. “Women with pre-existing and gestational diabetes are probably one of the most closely monitored groups of pregnant women,” she explains. With consistent access to insulin and support from government-funded healthcare, women in Denmark are generally very effective at keeping their blood glucose regulated. In countries without these advantages, the anatomical differences in the babies’ hearts may be more pronounced when the mothers’ blood glucose fluctuates more dramatically, she says.
And implementing routine scanning in early childhood – such as the echocardiograms Heather Boyd and her team are performing with the growing kids – for the children of mothers with diabetes could flag any abnormalities in heart structure and function decades before heart disease develops.
For now, the focus is on monitoring the children born to mothers with diabetes and reducing their other risk factors for heart disease, Heather Boyd says. It is a back-to-basics approach: “making sure the blood pressure is within normal range, making sure they get enough exercise and making sure they do not start smoking.”
