As a Neonatal Intensive Care Unit (NICU) nurse in the late 1990s, Katherine Gregory, PhD, RN, grew at the same time concerned and curious about necrotizing enterocolitis (NEC), a sometimes fatal infectious disease of the newborn gut affecting preterm infants. The condition, one of the most serious complications of preterm birth, can cause severe infection, neurodevelopmental impairment, intestinal perforations, malnutrition, prolonged hospitalization and even death.
For Gregory and her NICU colleagues, the most challenging aspect of treating newborns with NEC was that there were only vague and nonspecific signs and symptoms prior to disease onset. Thus, they could not predict or prevent it, and, once symptoms manifested, the disease could be at an advanced stage and progress quickly. “I would care for babies who survived the early stages of prematurity and seemed to be faring well, who would suddenly become catastrophically ill,” recalled Gregory.
Searching for A Warning Sign
Her time working in the NICU inspired Gregory to launch a research project to examine the physiology and pathological processes related to NEC in search of a biomarker, a biological substance that indicates the presence of a disease or a pathogen. “The NICU team caring for preterm infants needed to be able to measure something that would give us a warning sign that the disease was imminent so we could be better prepared,” said Gregory.
Gregory, now a senior nurse scientist at BWH, has devoted her career to researching gastrointestinal health and disease in newborns. In 2006, Gregory earned her PhD from Boston College. Her doctoral dissertation focused on her studies to find a clinical predictor for NEC that would enable clinicians to better anticipate, diagnose and prevent the condition. In 2010, Gregory was awarded a K23 career development award from the National Institutes of Health to further her investigation of the infant gastrointestinal tract.
In collaboration with a multidisciplinary research team, Gregory successfully measured a biomarker for NEC called intestinal fatty acid binding protein (iFABP), a protein specific to intestinal inflammation and injury. She found that elevated levels of iFABP appeared in urine within three and seven days before the onset of NEC symptoms. Her work was published in The Journal of Pediatrics in 2014. Gregory and her team hope to build on this work by conducting a study that will explore different approaches to using markers of inflammatory disease in the clinical setting. “We have made some progress towards understanding NEC,” said Gregory. “However, this disease remains a major contributor to morbidity and mortality for preterm infants, so we have more work to do.”
Understanding the Infant Microbiome
Another area of focus for Gregory is the investigation of the preterm infant microbiome. The microbiome is the accumulation of bacteria, viruses and other microorganisms that live on and within everyone – and outnumber human cells 10 to 1. As she and other researchers have learned, these microorganisms appear to play a significant role in health and disease. Gregory is particularly interested in the early acquisition process during which the microbiome is established and evolves. According to Gregory, environmental factors including method of birth, nutrition, the care environment and exposure to antibiotics all influence this acquisition process. They can also influence the development of a child’s immune system and other health factors.
“The microbiome of the preterm infant is particularly curious,” said Gregory, explaining that when newborns’ first few months of life are spent in a NICU, they are not exposed to the same environmental factors as healthy newborns, and this affects the pattern of colonization of their microbiome. “One of my major research questions is whether there are things we can do to more positivity influence this colonization process to result in more optimal health for our NICU patients.”
Gregory is currently conducting an observational analysis on the influence of nutrition in premature infants to learn how it impacts the acquisition of the microbiome. She is analyzing the intestinal microbiome based on the infant’s nutritional history and exposure to mother’s breast milk, infant formula, or donor milk. According to Gregory, these changes are best seen longitudinally. If she had the funding, she says she would carry out her research over several years in order to more accurately measure the influence of nutrition on the infant and early childhood microbiome. Focusing in on breast milk, which has its own microbiome, would add a new layer of complexity to the study, as its microorganisms can be affected by a multitude of factors, including the duration of gestation, preterm birth and/or the mother’s diet and health.
Microbiome studies are complex and multi-faceted, requiring an intense level of collaboration from investigators in informatics, micro- and molecular biology and immunology over a long period of time. “It is a privilege to work alongside many fantastic collaborators,” said Gregory.
Helping Shape Other Nurses’ Research
In addition to her role as principal investigator in her own research studies, Gregory mentors clinical nurses from BWH, providing guidance around study design and best practices as they establish their own research projects. She has guided clinical nurses on studies in many different areas, including bathing, best practices for late preterm newborns and audiovisual technology allowing premature infants and mothers to connect with one another when separated during hospitalization.
“Being a mentor to other nurses and helping them make strides in their own research projects is very rewarding because it has the potential to improve clinical practice and patient care,” said Gregory. “We need more nurses conducting research. Nurses are trained to be intellectually curious and observant about patients and families. They are excellent at collecting and analyzing data, and finding meaning in research results and communicating these results to others.” These attributes, she added, which are required of nurses in their day-to-day clinical roles, are also key characteristics of good researchers.
As a mentor, Gregory supports nurses who work with patients in various clinical settings across the lifespan. In her own research, however, she remains focused on patients whose lives are just beginning. “I have always been passionate and committed to the science of newborn care,” she says. “This work is unique because of the opportunity to positively influence the health of our smallest patients for the duration of their lives.”