Programmed for Weight Gain

Infants born to overweight or underweight mothers have a predisposition to obesity later in life
Sarbattama Sen
“I’ve developed a passion for finding ways to improve outcomes for obese mothers and their infants,” says Sarbattama Sen. Photo: Kelvin Ma
November 9, 2012

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In the winter of 1944–45, toward the end of World War II, a German blockade of food and fuel plunged Nazi-occupied Holland into famine. For eight months, over what came to be known as the Hunger Winter, 4.5 million Dutch citizens subsisted on meager diets, as little as 600 calories a day, or less than a third of the average adult’s requirements. More than 20,000 starved to death.

Nineteen years later, 300,000 boys born to women during the Hunger Winter entered the Dutch Army, providing startling data that linked the recruits’ exposure to the famine while in their mothers’ wombs with their tendency to be overweight as adults. The recruits whose mothers endured the famine during the first two trimesters of pregnancy were far more likely to become obese later in life than their peers whose mothers had enough to eat during the early months of their pregnancies.

The Hunger Winter provided some of the earliest evidence for the now well-accepted Barker Hypothesis, the theory that the maternal environment has profound long-term consequences for infants. In industrialized nations like the United States, too many calories—not too few—pose the greater health risk. Two-thirds of American women, many of whom are of reproductive age, are overweight or obese. Scientists are just starting to investigate how the historically unprecedented numbers of overweight mothers may be affecting their children’s chances of growing up to be obese adults. Just as too little food during fetal development is linked to increased risk for obesity as an adult, so is maternal obesity.

A recent Tufts study reviews current research on the relationship between a mother’s diet and the child’s weight later in life. The paper, published online in Physiology and Behavior, was written by Sarbattama Sen, a neonatologist and investigator in the Mother Infant Research Institute at Tufts Medical Center, and Susan Roberts, professor of nutrition and of psychiatry and director of the Energy Metabolism Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging, and their students, Ariel Carpenter, A10; Jessica Hochstadt, A08, N11; Juli Huddleston, N10; Vladimir Kustanovich, N10; and Ashley Reynolds, N11.

Maternal nutrition may play an important role in the obesity epidemic, notes Sen, who is also an assistant professor of pediatrics at the School of Medicine. She sat down with Tufts Now to discuss her research.

Tufts Now: What are the long-term consequences of a mother’s diet on her infant?

Sarbattama Sen: Infants born to mothers on both ends of the spectrum—mothers who are undernourished as well as over nourished—end up having similar predispositions to obesity later in life. As we discuss in the review article, researchers are investigating the biological mechanisms by which maternal malnutrition may be linked with metabolic changes in the offspring. It’s interesting because we are not accustomed to thinking about obesity as “malnutrition,” but it really is. New data from our lab and from others points to striking differences in dietary composition and levels of micronutrients between obese and lean individuals.

Historically, there have been a lot more mothers who have been undernourished than over nourished, so there is a lot more known about that and how that leads to obesity. There’s not as much data about obese mothers and how this might propagate obesity to the next generation.

How do scientists think that happens?

I don’t think there is a unifying hypothesis, but epidemiological studies have made the connection between maternal weight and obesity later in life. The most likely mechanism is through changes in the genes involved in laying down fat in the infant’s body. Babies born to obese mothers aren’t just bigger, they have more fat and less muscle than babies born to women of average weight.

Research in animals has found that maternal obesity disrupts the development of regions in the brain that regulate appetite and also influences the brain’s reward system. This implies that children of obese mothers may be predisposed to craving foods higher in fat and calories or find it harder to feel satiated.

Some research implicates inflammation—the harmful, chronic low-grade immune response associated with obesity—but exactly how that alters fetal metabolism still isn’t known.

What has your research shown?

I did some research work looking at rats fed traditional Western diets high in fat, sugar and calories. Their litters were very different from those of the control groups. Pups born to mothers fed a Western diet had higher body fat and evidence of metabolic dysfunction as early as two weeks of life. We found that pups born to mothers fed this Western diet, but supplemented with an antioxidant, had lower levels of body fat and improved metabolic status, similar to those pups whose mothers were fed a control diet. That was my first exposure to this area of study, and I’ve developed a passion for finding ways to improve outcomes for obese mothers and their infants. Before we are even born, aspects of our long-term health and well-being are programmed. I want to know how we can intervene to improve both maternal and fetal health.

How might you do that?

We’re looking at three different types of interventions. We can help women adhere better to the new weight guidelines that recommend that women who are obese or overweight before pregnancy gain less weight during pregnancy. The reality is they often end up gaining more weight than their leaner counterparts. We’re also looking at how we can alter nutritional supplementation in these women and whether that affects outcome. The third thing is to identify infants very early who are at risk of becoming obese based on family history. There’s been a lot of data that growing very quickly early in life is linked with later development of obesity. If we recognize that mom’s obese and dad’s obese, we need to make sure this baby’s growth trajectory is not accelerated.

Is it possible today’s obesity epidemic has its roots in maternal nutrition?

If you look at maps from the Centers for Disease Control and Prevention between 1997 and 2005, there has been a striking change very quickly.  In 1997, most of the country had a BMI less than 25.  In 2005, 66 percent of adults were overweight and obese. I think you can’t attribute such a huge change over such a small period of time to intergenerational issues. The genesis of the obesity crisis has been a source of much debate, but undoubtedly it was in large part due to very rapid social changes that occurred in the 1970s, ’80s and ’90s—changes in agriculture, changes in eating habits, changes in society. People perform less physical activity in their daily lives now, and they also eat more processed foods.

But now we’re seeing that we have a critical mass of people who are obese, and those effects are being felt in very different ways than we anticipated. One of those ways is that we have, for the first time, a large proportion of women of reproductive age who are obese, and we’re now seeing the effects on their children. We can’t say the genesis of the epidemic was intergenerational—it undoubtedly has many causes—but now we are seeing the effects of this epidemic on the next generation.

Jacqueline Mitchell can be reached at jacqueline.mitchell@tufts.edu.