Study Finds Maternal Diet May Have Long-Lasting Effects for Offspring

The diet a mother consumes while pregnant may increase the risk for non-alcoholic fatty liver disease (NAFLD) in the offspring, new research shows.

Alarmingly, one in 10 infants and toddlers are already obese, and one in five youth are both obese and at-risk for childhood diabetes, NAFLD, and psychosocial disorders. Many theories explain this dramatic increase, including increased food availability and sedentary lifestyles. The fact that these increases manifested only recently indicates that environmental and behavioral influences, especially those during the first 1000 days of life, rather than genetic causes, are driving this epidemic.

A western-style diet (WSD) high in fat and simple sugars may initiate outcomes that begin in the fetus and persist in-utero and then through the offspring’s childhood and adulthood. These outcomes may include not only NAFLD, but inflammation-related disorders including obesity, diabetes, and cardiovascular disease, researchers found.

“This is an increasing public health issue,” says Michael Nash, PhD, study lead author and a third-year medical student in the University of Colorado School of Medicine. “At this point, some higher estimates suggest that up to 30% of youth in this country are approaching obesity. Knowing that a western-style maternal diet may be a contributing factor, we need to be looking at this from an early intervention angle.”

Studying diet exposures

Nash and his co-researchers based their study on a multi-institutional research collaboration initiated nearly 15 years ago to study the effects of maternal diet on offspring physiology, beginning before birth, using a translational primate model. Nash, a student in the MD/PhD program, conducted his PhD thesis work in this area.

In this study, researchers looked at in-utero cells and immune and liver cells from 3-year-old juvenile offspring of mothers that were fed either a chronic WSD or a standard control diet for several years prior to pregnancy. Importantly, the offspring exposed to maternal WSD were fed a control diet for two and a half years postnatally before studying their cells.

Through their analysis, they found several striking differences. They observed that hematopoietic stem and progenitor cells exposed to a maternal WSD were programmed in-utero to a pro-inflammatory response that continued in juvenile cells. This pro-inflammatory response persisted for more than two years after the juveniles were weaned to a control diet.

Nash noted that the WSD was high in fat and simple sugars, including fructose, “which has been shown in our studies and many others to a harmful thing to eat that can remove the benefits of an otherwise healthy diet,” Nash explains. “It’s also not so much only about the amount of fat or sugar in the diet, but the balance of fat or ratio of different fats.”

Researchers found that juvenile bone marrow cells and fetal liver cells exposed to a maternal WSD had increased levels of oleic acid, which is significant because oleic acid can trigger production of certain inflammatory cells, although future work is needed to understand the mechanisms.

Improving the maternal diet

Nash adds that while the findings may seem stark, “showing that even if offspring have a healthy diet, they still can be stuck in this pro-inflammatory state, but our previous research suggests that applying an antioxidant to the maternal diet on top of a western-style diet can actually resolve much of the liver damage in the fetus. We saw prevention of liver fibrosis, prevention of liver fat accumulation, and prevention of other immune cell dysregulation.

“So, our hypothesis currently is that oxidative stress is not only a major factor that may be contributing to liver damage, inflammation, and stem cell reprogramming, but that oxidative stress may be treatable by consuming an anti-oxidant.”

However, he cautions against pursuing a “magic pill” approach of taking an antioxidant but continuing to consume a WSD high in fat and simple sugars and low in protein and fiber.

“There’s a concern that it would be easy to think, ‘Oh, I’ll just take this antioxidant and don’t need to change my diet,’” Nash says. “In reality, we don’t know appropriate dosages and we don’t know every little bit about how it works. We don’t know if it can reverse stem cell reprogramming. So, it’s more important that we’re talking about how, as a society, we can work to improve the maternal diet as a means of prevention, rather than only trying to reverse the diseases once they have begun.”