Children's Hospital Colorado

Inside Nutrition: Metabolism in the Growth-Restricted Fetus

Neonatal Intensive Care Unit | January 12, 2017

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The Amino Acid Lab is running full tilt at the Perinatal Research Center (PRC) at Children's Hospital Colorado and the University of Colorado School of Medicine. It runs seven days a week, 24 hours a day.

"We have a lot of samples to process," says retired neonatologist William Hay, MD, the facility's former scientific director.

Hundreds of thousands, in fact. A years-running, never-ceasing deluge of data from humans and animal models has helped researchers like Dr. Hay build an ever-growing understanding of how fetal metabolism works, particularly in the growth-restricted fetus.

Discoveries now will help babies in the future

Through animal and clinical study, Dr. Hay and his team discovered long ago that the high-glucose diets preemies were typically getting in neonatal intensive care units (NICUs) could have serious consequences for the pancreatic system of a growth-restricted infant, already prone to blood sugar imbalance. In the womb, the team showed, infants would be getting far more protein than glucose; with nutrition adjusted accordingly, long-term outcomes vastly improved.

"We pretty much wrote the book on that," Dr. Hay says.

Dr. Hay oversees a variety of colleagues' projects building on his own — work that built on that of his own mentors, University of Colorado physiology professor Giacomo Meschia, MD, and PRC founder Frederick C. Battaglia, MD. These studies, among others, stand to develop increasingly exacting combinations of amino acids and growth factors to target specific areas of growth-restricted physiology.

"We developed the models used all over the world to study glucose metabolism in the placenta and fetus simultaneously."
— William Hay, MD

For example, growth restriction reduces the amount of muscle mass per body length. And although the muscle cells might get bigger, after birth they don't divide. Children's Colorado neonatologist Laura Brown, MD, works with animal models at the PRC to understand the mechanisms of muscle cell proliferation. More muscle cells equals better muscle mass — an improvement that could reduce the high risk of diabetes that comes with fetal growth restriction.

That risk is the result of lower levels of glucose and oxygen, which inhibits the growth of pancreatic beta cells. To combat that, Children's Colorado neonatologist Paul Rozance, MD, has shown that giving both normal and growth-restricted fetuses more amino acids increases insulin secretion, potentially leading to better growth and improved blood sugar balance later in life.

Meanwhile, PRC researcher Stephanie Wesolowski, PhD, has found that the less glucose a fetal liver gets, the more it produces on its own — one of many adaptations to the conditions of the womb that can cause downstream problems later in life.

Doctors determined to find positive outcomes

Understanding and anticipating these adaptive mechanisms may one day help doctors correct for them, setting babies born from growth-restricted conditions up for the best possible outcomes long-term.

"If there's one thing we've done well in this lab, it's that we've developed from animal studies translational information that we can take into the NICU and improve the health of babies," says Dr. Hay. "I'd love to say these were my own unique ideas, but we work as a group and always have."

Learn more about our neonatal intensive care unit (NICU).

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