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Inside Nutrition: Metabolism in the Growth-Restricted and Compromised Fetus and Newborn


Dr. William Hay works on research in the lab, pouring blue liquid from one container to another.

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

The Perinatal Research Center has been producing a never-ceasing deluge of data from humans and animal models that have helped researchers around the world build an ever-growing understanding of how fetal metabolism works, particularly in the growth-restricted and compromised fetus and newborn.

Discoveries now will help babies in the future

Through animal and clinical study, the group of scientists at the Perinatal Research Center 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 and that trying to give extra glucose to the IUGR fetus only made their condition worse. With nutrition adjusted to better balance protein with glucose, long-term outcomes vastly improved.

Work that continues at the Perinatal Research Center is a direct extension of the research done by the individuals that founded the Perinatal Research Center, University of Colorado physiology professor Giacomo Meschia, MD, and Perinatal Research Center founder Frederick C. Battaglia, MD. These studies, among others, stand to develop increasingly exacting combinations of nutrients and growth factors to target specific areas of growth-restricted physiology. Ongoing work will also determine how these growth factors and nutrients, including micronutrients such as selenium, are impacted by conditions of organ injury and inflammation.

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 Perinatal Research Center 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.

Additionally, Jane Stremming, MD, a neonatologist at Children’s Hospital Colorado, works with animal models at the PRC to understand how IGF-1, which is an important growth hormone for the fetus, promotes fetal growth and development of skeletal muscle, because IGF-1 is a potential treatment to increase growth and lean muscle mass in the IUGR fetus. Adding to these studies focusing on IGF-1, Children's Colorado neonatologist  Alicia White, MD, investigates the complex interactions of insulin and IGF-1, as both of these important fetal growth hormones are often abnormal in large for gestational age, IUGR, and preterm neonates.

The risk for diabetes 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, Perinatal Research Center 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.

Perinatal Research Center studies even extend to investigations of micronutrients. For example, severe neonatal infection, or sepsis, results in death or long-term health consequences for many infants. To improve outcomes after neonatal sepsis, Children's Colorado neonatologist Laurie Sherlock, MD, is studying the role of the micronutrient selenium on immune function in infancy.

Children’s Colorado neonatologist, Clyde Wright, MD, is demonstrating how the growth-restricted fetus develops fundamental changes in their innate immune system. Developing a better understanding of these changes may lead to interventions that will prevent life-threatening infections in the early neonatal period.

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.

Updated: June 2, 2021

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