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Unraveling the Mystery of Necrotizing Enterocolitis One Sample at a Time

by Jennifer Ware

Image of a premature infant's feet in a incubator

Unraveling the Mystery of Necrotizing Enterocolitis One Sample at a Time

by Jennifer Ware

A pre-term baby will likely face a myriad of health challenges in the weeks and months after birth. In addition, 1-in-20 neonates will also develop necrotizing enterocolitis (NEC) - a devastating, life-threatening inflammation of the intestines. The exact origins of this condition are still unknown, but it may result from a colonization of bad bacteria which is often picked up during the babies’ hospital stay. If not promptly diagnosed and treated, NEC can lead to tissue death and a 50% mortality rate in those that require surgery. This is something that does not sit well with Medical University of South Carolina Clinical and Translational Research Scholar Katherine Chetta, M.D., and something that she has made her mission to change. 

As part of a multi-center study focused on determining NEC’s causation, Dr. Chetta studies stool, breast milk, urine, and blood from enrolled Neonatal Intensive Care Unit (NICU) babies searching for a biomarker that signals NEC. Although the search for the exact cause is ongoing, there is a promising hero in the fight for prevention: breast milk. 

“Our big goal is to better utilize mom’s milk in order to help our babies because we know it is protective,” says Dr. Chetta. “It has a lot of neurodevelopmental benefits and so we’re interested to see how milk interacts with the baby’s gut and prevents NEC.” 

Dr. Chetta’s group receives milk samples from mothers enrolled in the study, as well as donors, and the North Charleston Mother’s Milk Bank. She and the research collaborators at Darby Children’s Research Center then analyze the milk samples to best determine how to preserve them, using mass spectrometry to see what’s in the milk as well as observe how the milk interacts with the epithelium via laboratory models made from gut cells collected from discarded materials obtained from surgeries. 

As the research progresses and more departments join the cause, results continue to show promise. “With our donated samples, we have to pasteurize them, which gets rid of any extra beneficial bacteria, so that benefit kind of goes away,” says Dr. Chetta. “But there are other things in human milk that we know help the microbiome. There are special sugars called human milk oligosaccharides, and those all are different from mom to mom. We know those are beneficial – it’s better than formula for our preterm babies – but we don’t exactly know how it plays into their health benefits.” 

Dr. Chetta finds that the collaboration has also been key in helping more moms of pre-term babies explore breast feeding if they’re able to. “Anything that we can do to increase moms’ milk into the study and to help these babies is our goal. We work within our center, we work with other institutions in our center that work with other centers,” says Dr. Chetta. “There’s a lot of different people that are working on it from a lot of different angles – even fellows are involved. One of our trainees developed a pathway with Women, Infants and Children (WIC) to provide new moms a personal hospital-grade electric breast pump immediately after discharge to aid in breastfeeding support.” 

The desire to work together in the fight against NEC doesn’t just stay within MUSC and has resulted in the group’s partnering with various centers, the government and industry sponsors. “From a clinical standpoint, physicians and nurses can always call us if they have any kind of clinical questions about what they’re seeing in their NICU or what the latest guidelines are – we always like to help give advice and education on the latest recommendations for breast milk and why it’s so beneficial,” says Dr. Chetta. “From an education standpoint, if someone is interested in starting a project with us, we’re always open to that. Even when it comes to sharing data, we can help them work through their Institutional Review Boards and combine the data to look at how moms’ milk impacts babies.”

Dr. Chetta’s breast milk research also aligns with her involvement in another International multi-center study focused on getting FDA approval for a probiotic benefitting pre-term babies’ gut microbiome. 

This multi-pronged approach is all in a day’s work for Dr. Chetta and her mission. “We have a lot of stuff going on, but we’re always interested in branching out and doing more things across the community,” she says. “We just have to be advocates for getting these solutions for our babies, but it will happen.”


September 2023

Pediatrics Press

Image of a person holding a newborn baby's hand

MUSC Department of Pediatrics’ Groundbreaking Infant-First Research Results in Patents

by Jennifer Ware

Dorothea Jenkins, M.D., can recall the moment she made the connection between vagus nerve stimulation and the impact it could have on the neonates she treats. “I was attending a brain stimulation seminar lecture discussing the parameters of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) with human volunteers,” says Dr. Jenkins. “As soon as I heard the details of the study, I was like ‘Oh – we’ve got to do this in babies, and I know exactly what motor skill we can work on!’” 

It was this lightbulb moment that led to Dr. Jenkins’ groundbreaking, infant-first study that had a 70% success rate in at-risk babies and culminated in a registered patent on both the innovative technology as well as the cranial nerve system for feeding. 

The vagus nerve, a crucial part of the autonomic nervous system, plays a vital role in regulating various bodily functions, including heart rate, digestion, and even immune responses. Researchers have long recognized its potential therapeutic applications, and over the years vagus nerve stimulation has been used successfully in the treatment of various medical conditions in adults, such as epilepsy and depression (explored by MUSC’s Dr. Mark George in 2006). 

However, Dr. Jenkins saw a unique opportunity to harness the power of taVNS to address the specific health challenges faced by infants born pre-term or with a brain injury. “One of the first skills that newborns have to master is feeding – the sequence of sucking and swallowing milk, and then breathing. It takes 22 muscles, and they have to do all of that within 1-2 seconds and not aspirate, so this is a significant motor sequence that they have to learn,” says Dr. Jenkins. “Now, if you’re born at term, you’ve got it as a reflex. But if you’re born preterm or if you have a brain injury as a term baby, you may not have that reflex. We were having a large number of babies who were getting gastrostomy tubes put in because they could not learn this skill and were not able to feed fully.” 

Dr. Jenkins began her research journey with a simple yet profound question: Could taVNS be used to not only help these babies learn to feed, but also positively impact the neuroplasticity of their brains? Using a non-invasive device positioned on the ear branch of the infant’s vagus nerve, Dr. Jenkins and her team would stimulate the baby during the sucking and swallowing phase of feeding. The results were nothing short of miraculous. When used once a day, babies were able to get to full feeds in two weeks, and when the device was used twice a day, babies were able to achieve full feeds in an average of 8 days.

Dr. Jenkins was also able to measure the success of the technique through extensive brain imaging. “We utilized MRI scans with modified barium swallows before and after so we could look at the mechanics of swallowing as well as what we were hoping to generate, which was neuroplasticity in the brain,” she says. “What we saw, with the help of Dr. Hunter Moss’ (MUSC, Neuroscience) analysis, was that the corticospinal tracts – the major motor tracks – were significantly more complex and stronger in the babies who got the full feeds.”

During the study, Dr. Jenkins noted that some of the infants born to diabetic mothers were not responding as well to the treatment. “Those babies are exposed to a lot of glucose in utero, which is a pro-oxidant, so it creates a lot of oxidative stress on the baby’s brain and often leads to them not being able to learn to feed,” she says. After looking at the data from the brain scans, Dr. Jenkins realized the infants born to diabetic mothers had low antioxidant levels. Based on extensive past research on mitigating oxidative stress, Dr. Jenkins then pre-treated the infants for four days with N-acetyl cysteine to get the antioxidant level improved in the brain. “Whereas previously only 25% of those babies were getting to full feeds, by improving the antioxidant level and then adding taVNS we were able to get 70% of them to full feeds,” she says. 

In addition to improving immediate health outcomes, Dr. Jenkins also envisions the long-term impact taVNS can have in feeding and other areas. “Our goal is to use taVNS to improve breastfeeding - which is different than bottle feeding - and I think that would be a huge game changer for a lot of infants and their mothers who get discouraged when babies aren’t learning to breastfeed,” she says. “It’s very expensive to keep babies in the hospital to teach them to feed, so I think the ability to hasten that and get them home is good for family bonding and their development.”

 

June 2023

Pediatrics Press

MUSC Launches First Medical Legal Partnership

by Jennifer Ware

Imagine your child has been diagnosed with cancer and requires inpatient treatment. Most people would be consumed with comforting and supporting their loved one through treatment and recovery. But for others, concerns such as transportation to the hospital, the ability to miss work to attend appointments, the ability to care for their other children or the financial pressure of having to pay medical bills adds a level of vulnerability that may be difficult, if not impossible, to overcome.

In an effort to address social determinants of health and build an integrated care system that can assess and assist those facing these situations, Angela LaRosa, M.D. and Children’s and Women’s ICCE Administrator Amy Hauser have partnered with Charleston Pro Bono and Charleston Legal Aid to create MUSC’s first Medical Legal Parnership (MLP).

MLPs are rising in importance as the healthcare industry continues to focus on social determinants of health. Some determinants, like food insecurity or transportation, can be addressed via hospital intervention, but others, like housing eviction and educational advocacy, lie outside the spectrum of care providers can feasibly provide on their own. Legal teams and medical staff can work together to help patients navigate the legal challenges that impact patient health.

The importance of creating an MLP at MUSC developed for Dr. LaRosa over the decades-long span of her career. “I’ve been in Developmental and Behavioral Pediatrics for 20 years and it’s not just the medical portion of it – we’re trained to focus on the social history and adverse child experiences as well,” she says. “It was seeing patients continue to be in a cycle that they almost couldn’t get out of because they didn’t have financial stability or whatever else they needed to go to the next level. The thing that really struck me is that legal assistance should be available to everyone whether they had the money to hire an attorney or not. We needed to create a safety net for these families.”

Amy Hauser had her first experience with MLPs years ago when she was a pediatric nurse at Children’s Healthcare in Atlanta. One patient, a young child, was repeatedly visiting the emergency room for debilitating asthma. “The child lived in subsidized public housing, and the housing was not kept up - had rodents, mold, etc. - which was exacerbating their asthma. It wasn’t good for the child and not good for us as a healthcare system as well,” she recalls. “Through the MLP we were able to find the family appropriate housing, make sure they had the right equipment and medical supplies, and as a result, the child’s visits dramatically decreased.”

The need for MLPs in America is tremendous – one in six families live in poverty and research demonstrates that on average, these households experience between 1 to 3 unaddressed legal needs that negatively impact their health. In the Charleston County area, 13.4% of residents have an income below the poverty line, placing them at major risk for food insecurity and other complications.

When it came to creating the MLP here at MUSC, Dr. LaRosa explains that the “why” was well known: “We know that there’s data to suggest having Medical Legal Partnerships improves patient outcomes.” The next step was to find a dedicated individual who could provide the connection between the provider and the legal point of contact. “Amy Hauser was absolutely instrumental in getting the funding for a dedicated social worker,” she continues. “It took us a long time to find just the right person, but we did and now we’re ready to roll the program out.”

Providers wishing to submit a patient for referral would first reach out through Proficient. The MLP social worker then conducts an assessment in person or virtually/over the phone using a list of questions from an app that was specially designed by students at Georgetown University School of Law in Washington, D.C. If the patient is determined to be eligible for legal aid, they are then connected with either Charleston Pro Bono or Charleston Legal Access.

Though the program is piloting in just one division, the hopes are to expand it across MUSC as a whole. “We’re going to start with Developmental Pediatrics, get it ingrained there, and then we’ll begin expanding it out,” says Amy Hauser. “Our ultimate goal is to have it in Children’s and Women’s, and as it grows and we can show the successes, this is the type of program we would love to see expand through the entire MUSC health system.”

And by combining legal expertise and services with medical care, Dr. LaRosa hopes that MUSC’s MLP can disrupt the cycle of returning people to the unhealthy conditions that would otherwise bring them right back to the clinic or hospital. “If you’re a patient in the hospital, your outcome is being affected by the psychosocial factors. And as physicians, if we do not address those, we’re never really going to get the best outcomes for our patients.”

 

March 2023

Pediatrics Press

Peds GI Division Chief Dr. Benjamin Kuhn and Pediatric Dietician Amber Johnson consult in the hospital

Dr. Kuhn's Vision to Make Pediatric GI Division the Premiere Care Center of South Carolina

by Jennifer Ware

Unless they’re experiencing an issue, not many people think about the self-contained uniqueness of the GI tract. But it’s that aspect that drew MUSC Pediatric Gastroenterology Division Chief Dr. Benjamin Kuhn to the field in the first place. “What I find fascinating about Gastroenterology is that the entire GI tract is technically outside the body,” he says. “From your mouth to the end, it’s a hollow tube that travels throughout your body: you put into what you think you need for nutrition or hydration, and your body knows what to absorb or eliminate.”

It's this fascination and passion that’s inspired Dr. Kuhn to tirelessly work to position MUSC not only as the most comprehensive Pediatric GI and Hepatology care center in South Carolina, but one of the best in the nation.

One recent major coup: the acquisition of a Pediatric GI Motility Specialist. “When patients struggle with intestinal motility issues, the symptoms can range from being unable to eat or swallow food to difficulty with bowel movements,” says Dr. Kuhn. “When the motion of the intestines is not right, lots of problems can ensue.”

Particularly complicated cases can require the attention of a Pediatric GI Motility Specialist, which Dr. Kuhn says is a highly technical role both expertise wise as well as technology wise. “The ability to test and measure the motility or the motion of the GI tract, as well as evaluate and manage patient care and keep up with advancements year over year is incredibly valuable,” he says. “Previously there used to be a certain threshold required for patients to undergo that degree of testing and expert care, which up until now we would have had to refer out of state. There has been an unmet need for this specialty in Charleston as well as the entire state of South Carolina, and it’s amazing that we’ll be able to offer it here at MUSC.”

Dr. Kuhn is equally proud of the division’s current team of six physicians and four nurse practitioners. “Our Pediatric Inflammatory Bowel Disease Center, which is managed by Dr. Carmine Suppa, is top notch,” he says. “One of the emerging technologies that MUSC is an early adopter of is ultrasound to detect changes in the bowel brought on by inflammatory bowel disease. Dr. Suppa is one of the few practitioners in the state trained to be able to do so. It can be done in office during a visit and be a quick, non-painful way to evaluate someone’s disease activity.”

In addition to comprehensive general pediatric gastroenterology care, MUSC’s division also offers multidisciplinary clinics for inflammatory bowel disease, aerodigestive care, intestinal failure, eosinophilic esophagitis as well as having the only pediatric liver transplant center in South Carolina.

What makes being at the helm of such a thriving center of excellence even more of an achievement is that originally Dr. Kuhn was determined NOT to go into medicine. “I studied biology and genetics at Cornell, and after I graduated, I worked in a lab. And that’s fully what I intended on doing as a career,” he says. “But after becoming a research associate at Penn State College of Medicine, which was more clinical/patient based, I realized that there was more to this than just lab work. I went to the Philadelphia College of Osteopathic Medicine, then returned to Penn State Children’s Hospital for my Pediatrics residency.”

After completing his fellowship at Cincinnati Children’s Hospital for Pediatric Gastroenterology, Dr. Kuhn landed at Geisinger Health System in Pennsylvania. He eventually made regional director of Pediatrics, and the position’s multidisciplinary team building experience prepared him for his role as Division Chief at MUSC.

“I’m very excited to be a part of this division and MUSC as a whole. Our team continues to grow in breadth and depth of services offered, and there’s so much more on the horizon,” he says. “MUSC is an amazing children’s health system with world class care. When one division succeeds, we all succeed. And it’s our patients who benefit the most."