Combating Obesity in the Womb: U.K. Study Treats Pregnant Women With Diabetes Drug

July 8, 2011— -- How far will we go to prevent childhood obesity? U.K. researchers are bringing the battle against obesity to babies still in the womb.

In this novel approach, which will ultimately enlist 400 pregnant women in the U.K., obese pregnant women will be given the diabetes drug Metformin in hopes of reducing their infant's chance of developing heart disease, obesity and type 2 diabetes later in life.

The study, funded by the U.K. government, will be one of the most extensive tests to date of a concept known as fetal programming -- changing the environment of the womb to affect the health of the child.

Doctors already use "fetal programming" in less extreme ways by encouraging pregnant women to take prenatal supplements, make dietary changes, and avoid drug and alcohol use. This study promises to introduce a whole new level that might one day be commonplace: using medications that the mother otherwise wouldn't need in order to tweak the fetal environment.

Natural fetal programming "is a complex process that's evolved over millions of years to help a fetus adapt to the world it will ... encounter after birth," says Dr. Alison Stuebe, an assistant professor of maternal fetal medicine at UNC-Chapel Hill. "It is the way the mother 'tells' her baby what the world outside will be like."

Obese women tend to have higher blood sugar during pregnancy, and these high levels of blood sugar essentially "tell" the fetus that it needs to make a lot of insulin for itself. As a result, infants born to obese mothers tend to be heavier and produce more insulin. Research shows that these bigger babies grow up into children and adults who are at increased risk for obesity, heart disease and type 2 diabetes.

By giving obese mothers-to-be the diabetes drug Metformin -- even though they do not have diabetes -- researchers will be lowering their glucose levels, hopefully mitigating the negative effects of maternal obesity.

It will take years to determine if this intervention pays off. In the short term, however, how big these infants are at birth will serve as a preliminary marker of how well the Metformin is adjusting fetal environment.

Fetal Programming -- Tweaking the Womb for Healthier Babies?

Fetal programming was first discussed when U.K. epidemiologist David Barker noted that infants born to malnourished mothers who had lived through the WWII Dutch "hunger winter" had an increased risk of heart disease later in life.

Ironically, research has since confirmed that both overeating and undereating during pregnancy can increase an infant's risk of obesity and heart disease later in life, but for very different reasons. Instead of having too much blood sugar, babies born to underweight mothers are programmed to believe the world has little food and hence they must retain calories at all costs, says Dr. Hye Heo, a fetal programming expert at Montefiore Medical Center, who's currently working on the effects of feast and famine on infant outcomes in rats.

"At this stage in the research, we're still trying to understand what is being altered in the womb, why there is some kind of memory [in the fetus] that persists and results in alterations in the way we develop later on in life," Heo says.

Obesity and insulin levels have been the most popular topics in fetal programming research, but researchers are also looking at the effects of other hormones in flux during pregnancy.

Research presented at the Endocrine Society's annual meeting this June found that high levels of stress during pregnancy adversely affects not only the fetus, but the offspring of that fetus.

The study, done in rats, found that high levels of the stress hormone glucocorticoid late in the pregnancy increased the infants' likelihood of developing diabetes and heart disease in adulthood. Male rats born to stressed mothers, in turn, seemed to pass problems on, fathering infants who were more likely to suffer from growth problems in the womb.

Other research, currently underway at the Maternal-Fetal Medicine Units Network (part of the National Institute of Child Health and Human Development), looks at thyroid hormones in mothers and IQ in their children. Even borderline low thyroid levels during pregnancy have been tied to lower IQ scores in young children, so researchers are experimenting with supplementing thyroid hormone in deficient mothers, says Dr. Stuebe, of UNC-Chapel Hill.

The Ethics of Medicating Mommy

There's a reason much of the research in fetal programming has been done in rats -- giving pregnant women medication of any kind is a touchy topic. This is why the U.K. trial has met with some controversy, as doctors will be dosing mothers with drugs that they don't strictly need.

But the trial may not be as far a leap into the unknown as it seems, doctors point out:

"Metformin is not a new drug and has been given to pregnant women for years to control diabetes in pregnancy," says Dr. Alan Peaceman, chief of the division of maternal fetal medicine at Northwestern Memorial Hospital.

While diet and exercise would be the preferred intervention for obese mothers, "patients often find this difficult, especially during pregnancy. Thus, Metformin may provide an alternative option for these women with similar lifelong benefits to the fetus," adds Dr. Victoria Bae-Jump, assistant professor of gynecology oncology at UNC-Chapel Hill.

Doctors seem more concerned that this type of fetal programming intervention can only provide a partial answer to the problem of maternal obesity.

"Ultimately, it's unlikely that a single pill or nutrient is going to override all the effects of maternal obesity on infant development," says Stuebe. There are so many environmental factors in play -- poverty, abuse, stressful environments, she says, that "I'm skeptical of a magic pill to counteract all that."