Harper Keel spent the first few minutes of the appointment on the 12th floor of UCHealth University of Colorado Hospital (UCH) fast asleep. When she woke up, she fussed briefly, then had a quick snack courtesy of her mom, Melissa. After a good burp, she observed as her sister Cali, 2, correctly pointed out a sealed IV needle and a roll of Coban self-adherent wrap on the table.
Harper, two months old, was participating in a major research study that could change the way pregnant women eat. The study is just the latest of nearly two decades of University of Colorado School of Medicine research that seeks to understand the influences of maternal obesity, diet and other factors on the short- and long-term health of their babies. In addition, earlier this year the study’s leaders and several dozen other CU researchers launched an initiative called Building Better Babies. It’s an organizing principle for the diverse lab and clinical efforts aimed at improving the long-term health of the next generation by improving that of pregnant moms and infants through the age of two.
“If the conditions as the baby develops are adverse, then the risk of developing diseases later – obesity, cardiovascular disease, cancer, neuropsychological disorders – is much higher,” said Thomas Jansson, MD, PhD, chief of the CU School of Medicine’s Division of Reproductive Sciences, who with CU neonatology researcher Theresa Powell, PhD, is spearheading Building Better Babies. “Using precious health care dollars to invest in pregnant women and infants is an enormously good business proposal and really an outstanding investment in public health.”
The goal is ambitious: to change how medicine is practiced, as Jansson put it, by placing “much more emphasis on prevention of major childhood and adult diseases by targeted intervention in pregnancy and in infancy.”
The work in pursuit of that goal is diverse. Among the Building Better Babies efforts include a study led by CU psychiatry professor Amanda Law, PhD, that’s exploring the role of the placenta to better understand why babies born after a pregnancy complicated by virus infection, preeclampsia, or a limited supply of nutrients and oxygen end up with much higher risk of developing schizophrenia later in life. Another study, led by Camille Hoffman, MD, is using supplements of choline, which plays important roles in communications among neurons and other cells, to see if potential future schizophrenia can be snuffed out in utero. And Erica Mandell, DO, is looking at the role of vitamin D in lung development. And then there’s the study Harper and her mom, Melissa, participate in.
Melissa Keel, 36, a fit emergency room nurse living in Highlands Ranch with husband, Sean, and infant daughter, Cali, was 28 weeks pregnant and about to sink her teeth into an old-fashioned glazed at a LaMar’s Donuts when the phone rang. The news wasn’t good: despite a healthy first pregnancy and, she thought, second one, too, a blood test showed her to have gestational diabetes mellitus (GDM).
She didn’t eat the donut.
Her physician in Littleton connected her with Linda “Lynn” Barbour, MD, MSPH, who runs the OB diabetes clinic at UCH. Barbour, Teri Hernandez, PhD, RN and Jed Friedman, PhD had been investigating the links between maternal obesity and diet and the health of babies and future adults since the early 2000s. Among those health problems include higher risk of obesity, diabetes, high cholesterol, heart disease, and nonalcoholic fatty liver disease, the last of which is now the leading cause of liver transplants in the United States, Friedman said, occurring in about 40 percent of obese children.
Their $4.2 million study, funded by the National Institutes of Health and, more recently additionally supported by Janssen, seeks to lay the scientific foundations for a new, better diet for women with gestational diabetes, in particular, and for pregnant women in general. For Keel, it would involve having everything she ate – three meals and three snacks – all meals prepared by the CCTSI Bionutrition Core kitchen in UCHealth’s Leprino Building, delivered to Highlands Ranch every three days.
In addition to the usual finger pricks required to check her blood glucose four times a day, the study also includes wearing a continuous glucose monitor twice for several days, some pokes to withdraw blood and two fat samples, a body-composition measurement in a Bod Pod, the donation of her placenta for researchers to check out the molecular specifics of how it processed and moved nutrients to Harper, a breast milk sample with a similar goal, and the collection of both mom and baby stool samples for Friedman’s ambitious effort to link the gut microbiome’s makeup and influence on Harper’s growth and metabolism to the different diets.
As a nurse, none of this concerned her. What did raise flags initially was the idea of the study extending to her baby during the first year of life. The big question, Keel said, was, “What are they going to do to my baby? I didn’t want anything done that was going to harm her.”
The research team explained that Harper would donate stool and blood samples, but that the blood draws would happen at birth and then at 12 months, when she would have it tested in clinic anyway. Harper would also have her size measured manually and spend a few minutes in a Pea Pod (a BodPod for babies), do an optional MRI to check her liver for fat, and do a DEXA scan at 12 months to assess her body composition.
Keel decided to do it, both for her own baby and others down the line.
All the sophisticated testing and analysis aside, this study is really about food. It compares the diet typically suggested for women with gestational diabetes – one low in carbohydrates, which the body turns into sugars, and higher in fat – with one that cuts back on the fat and adds complex carbohydrates of the sorts you find in beans, chick peas, brown rice and whole-grain pastas. (Specifically, both diets have 15 percent protein; the low-carbohydrate diet has 40 percent carbohydrate and 45 percent fat; the complex-carb diet has 60 percent carbohydrates and 25 percent fat. Both diets have the same number of calories.)
The CU team came up with the complex-carb diet and have called it CHOICE: Choosing Healthy Options in Carbohydrate Energy. The idea behind it has its roots in Hernandez’s background as a cardiac nurse in Dallas, where she came across many seriously ill patients who, it turned out, had eaten “a lot of fat, a lot of fast food, a lot of oversized portions.”
After coming to CU, she met Barbour in the early 2000s, became fascinated with metabolic research in pregnancy and decided to work on a PhD with Barbour as her mentor. She recognized the recommended diet for women with gestational diabetes to be all too similar to what her cardiac patients had been eating in Texas.
“The advice was, ‘Don’t eat carbs,’ and give them free rein to eat as much fat as possible because it will control blood sugar,” Hernandez said. “Your sugars might look great for a time, but essentially, it reminded me of what my heart patients were eating.”
What’s bad for heart patients isn’t good for gestating babies, either. Too much fat – in particular triglycerides and free fatty acids born of saturated and trans fats – have been shown to drive chubbier babies. (results from Barbour, Friedman and Hernandez’s research funded by the NIH about a decade ago have recently shown that maternal triglycerides are, as Barbour put it, “an unrecognized but significant risk to babies being born with excess fat,” which in turn is linked to future obesity and related health problems).
Hernandez wondered about the evidence behind the low-carbohydrate diet. It turned out there was very little of it. Essentially, she concluded, the standby diet harked back to century-old trial-and-error approaches with type-1 diabetes patients. Back before insulin injections, patients would cut back on carbohydrates until their sugar stabilized. More recently, research showed that low-carb diets in women with gestational diabetes would also decrease their blood sugar levels immediately after they ate – at least for a while. While fatty foods didn’t immediately boost blood sugar, we know now that they can make mothers resistant to their own insulin and result in higher sugars later.
Hernandez created the CHOICE diet based on American Heart Association guidelines for a heart-healthy diet. She, Barbour, Friedman and colleagues conducted pilot studies which are now published showing that the CHOICE diet tamped down on blood glucose as effectively as the higher-fat diet, but with the added benefit of cutting down on the free fatty acids in the mom’s bloodstream. Furthermore, after being on the diet for at least 6 weeks, fasting glucoses were actually lower on the CHOICE rather than the low-carb diet and the mother’s sensitivity to her own insulin was better. The National Institutes of Health recognized the potential of the work and backed a five-year, $3.2 million follow-up study. Janssen later added about $1 million to expand and accelerate the pace of the work.
They’re about halfway to the study goal of 50-60 moms-to-be with GDM, Hernandez said. That may not sound like a huge number, but given scope of effort – from food prep and delivery to multiple visits by mother and baby – it’s ambitious.
“The study we’re doing will probably never happen again,” Hernandez said. “It’s extremely expensive and extremely difficult to pull off. A lot of investigators don’t have the resources of a Bionutrition team and a facility like the metabolic kitchen, which can prepare all the meals for all of these mothers for the remainder of pregnancy.”
If the data back up the team’s hunches, the study stands a good chance of becoming the core pillar of new dietary guidelines for women with GDM – and perhaps for pregnant women in general. The evidence so far is strong enough that it’s changing the advice given to pregnant moms at UCH.
“We definitely tell women to avoid not only simple carbohydrates, but also excess fat, especially saturated fats,” Barbour said. “Hopefully we’ll prove that without a doubt with these studies.”
Melissa Keel was randomized to the standard low-carb fat diet for gestational diabetes patients during the last eight weeks of her pregnancy. It involved care packages of chicken, pork, steak, chicken tacos, turkey sandwiches, chips, grapes, strawberries, salads and more, all measured to the gram. There was also a list of approved indulgences; she went for the occasional small vanilla cone at McDonalds.
It worked: Keel’s blood sugar stayed in check, and Harper was born a healthy 7 pounds (Cali had been 11 ounces heavier). How it worked as compared to similar moms on the higher complex carbohydrate, lower fat CHOICE diet remains a question for future scientific analysis – which hinges on more pregnant moms diagnosed with GDM signing up. Keel suggests going for it.
“I would recommend this study to anybody who’s been diagnosed with gestational diabetes and meets the criteria,” she said. “It’s such a great experience.”
For more information on the CHOICE gestational diabetes study, visit http://www.infantgoldresearch.org/choice-study/.