Congenital heart disease—a problem with the heart that exists at birth—is a leading cause of death among infants in the US. Sadly, there are many risk factors: infections, genetics, environmental factors, maternal diet, body mass and glucose intolerance, maternal age at the time the child is born, and more. The trickiest may be maternal age, however, as it’s not something women can necessarily control as they are preparing to have children.

A paper published in Nature by Schulkey et al of Washington University has provided evidence that maternal exercise may limit the risk of congenital heart failure due to maternal age. The findings suggest that older women who are interested in having children may be able to cut the risk of their infants developing heart problems through regular exercise.

The researchers wanted to determine whether the maternal age effect is due to changes in the mother or in the oocyte (the egg). To find out, the investigators used mice that were missing one copy of the Nkz2-5 gene, which made the mice predisposed to heart defects known as ventricular septal defects. This particular defect, in which the chambers of the heart are not properly separated, is the most common defect in this strain of mice. The second most common defect, atrial septal defects, did not appear frequently enough to allow statistical conclusions.

The researchers used a procedure known as “reciprocal ovarian transplantation,” wherein the ovaries of young female mice were implanted in older mice and vice versa. To account for maternal diet and body mass/glucose intolerance, two of the primary environmental factors that have been demonstrated to influence the health of offspring in human epidemiological studies, one group of the mice were all fed a high-fat diet.

The mice on the high-fat diet showed deficits in glucose tolerance and high blood sugar, but the offspring of those mothers did not show a higher incidence of the relevant heart defect. A logistic regression analysis probing the interaction between diet and age similarly did not demonstrate an effect. This means that having a high-fat diet didn’t increase the risk of offspring with heart defects, regardless of the mother’s age.

To probe the effects of exercise, running wheels were placed in the cages of the females at the start of breeding, and the mice were at liberty to run whenever they chose to do so throughout their lifespan. Though this early exposure to exercise had no effect on the offspring of younger female mice, it did lower the risk of heart defects in the offspring of older female mice.

The authors were intrigued by this finding, but they thought it would be challenging to apply to a human. Women would need to start exercising at menarche, well before they would know the age when they would have children. So in order to check whether a more practical course of action would be effective, the researchers conducted a similar experiment with the mothers instead starting exercise late in their adulthood. The investigators found that this late onset exercise reduced the risk of heart defects as effectively as early onset of exercise.

It’s important to note that exercise decreased the risk of heart defects in the offspring but did not eliminate it, a finding that is consistent with the accepted model of congenital heart defects. This suggests multiple factors influence their prevalence.

While it’s not clear how relevant Nkz2-5 mutants are to all humans, the results indicate that women who choose to have children later in life may be able to reduce their child’s risk of heart defects. Simply engaging in some form of exercise once they’ve decided to have a child may provide some protection.

Nature, 2015. DOI: 10.1038/nature14361 (About DOIs).