‘Hidden’ Outcomes of Prematurity

Researchers in the laboratory of Marlowe Eldridge, MD, MSME, have found that young adults born prematurely but who are otherwise healthy may still have ventilatory impairments that manifest in low-oxygen environments.

Their study, recently published as a Correspondence in the New England Journal of Medicine, is the first to recognize “hidden” ventilatory dysfunction in this population—raising new questions about the long-term clinical consequences of prematurity.

A Surprising Response to Low Oxygen

In his lab, Dr. Eldridge (above, at left with scientists Melissa Bates, PhD, and Emily Farrell, PhD) takes an integrative approach to cardiopulmonary physiology.
In his lab, Dr. Eldridge (above, at left with scientists Melissa Bates, PhD, and Emily Farrell, PhD) takes an integrative approach to cardiopulmonary physiology.

As part of their work on “Comprehensive Characterization of Intrapulmonary Arteriovenous Pathways in Health,” a grant from the National Institutes of Health–National Heart, Lung and Blood Institute (NIH–NHLBI), the team was investigating pulmonary vascular responses to hypoxia (lower than normal oxygen) and hyperoxia (higher than normal oxygen) in healthy young adults born prematurely.

Interestingly, during exposure to hypoxia, the investigators noticed something unusual: one participant entered respiratory depression—the opposite of what normally happens in a healthy adult.

The team created an additional comprehensive study to investigate whether others in the cohort would have similar abnormal responses to low oxygen.

Those participants were recruited from The Newborn Lung Project, a longitudinal cohort study of premature infants born in Wisconsin and Iowa led by UW Population Health Sciences professor Mari Palta, PhD. Members of the project’s first cohort were born in the 1980s and are now in their early 20s.

Investigators found that, as a group, these adults—born prematurely but otherwise clinically normal—had substantially reduced ventilatory responses to low oxygen compared to term-born adults.

Potential Hidden Health Issues

According to scientist Melissa Bates, PhD, earlier studies in rodents suggest that these ventilatory impairments may stem from abnormal development of carotid chemoreceptors, the cells that drive the breathing response to changes in arterial oxygen.

People who don’t have a robust drive to breathe in low-oxygen environments are at increased risk of altitude sickness, sleep-disordered breathing, and vulnerability to complications with certain types of anesthesia.

The study raises questions about potential hidden health issues in a population of adults who collectively survive severe prematurity. It also underscores the value of cohort studies like the Newborn Lung Project.

“These adults appear clinically normal; you don’t notice these abnormalities until they’re stressed,” Dr. Bates explained. “It’s an example of a critical developmental window, where certain exposures can have a lifelong impact on physiology.”

An Integrative Approach to Cardiopulmonary Physiology

The study also demonstrates what makes Dr. Eldridge’s laboratory unique.

“Ours is one of the few laboratories that takes an integrative approach to cardiopulmonary physiology, including heart, lungs, and breathing control,” Dr. Eldridge said. With that approach, investigators can consider the broader physiological context beyond specific biological structures.

Currently, the lab is focusing on other aims of the NIH grant: examining pulmonary vasoreactivity under certain physiologic conditions such as exercise, bronchopulmonary dysplasia (a chronic lung disease often found in very low-birth-weight infants) and high-altitude pulmonary edema.

The team is also in the second year of another NIH–NHLBI-funded grant, “Right Heart-Pulmonary Vascular Interaction in Young Adults with a History of Bronchopulmonary Dysplasia.” For this project, the lab has teamed up with several investigative teams from Medical Physics, Radiology, Biomedical Engineering, and Cell and Regenerative Biology, to take an integrative approach to determine the long-term sequelae of this condition.

Future work aims to better characterize the role of carotid bodies in this population, and investigate breathing responses to exercise, carbon dioxide or other stimuli.

Cohort studies are the key to that research, Dr. Bates said. “There are so many questions [about this population] we can ask, both from a physiological approach and from an epidemiological approach.”