Gentler treatment for addicted infants

by Anna Simon

Source photo by Evan Amos.

Babies born with opioid dependence are inconsolable. They quit cold turkey at birth and start withdrawing within days. Jennifer Hudson sought a way to ease their agony. “I watched babies suffer,” says Hudson, director of newborn services at GHS. Symptoms of withdrawal hit hard several days after birth: massive weight loss, seizures, tremors, fever, vomiting, diarrhea, irritability, sleeplessness, breathing problems, apnea, rashes, and more. It’s called Neonatal Abstinence Syndrome, or NAS. The Children’s Hospital Association calls it a public health crisis.

When Hudson came to GHS, babies of mothers who were being treated for addiction to opiate-based drugs such as heroin or prescription painkillers had to exhibit symptoms before treatment could begin. This remains standard practice at many hospitals. By the time full-blown symptoms of NAS developed, the health of these babies deteriorated rapidly with complications that often led to months in intensive care. “It felt unethical,” she says. If doctors know that a mother is being treated with a long-acting opioid, such as methadone, during pregnancy, then why, she wondered, can’t treatment start at birth, before the agony of withdrawal begins? She went to a hospital pediatric pharmacist with an idea.

Simply put, the idea was a kinder, gentler approach to treating infants with NAS. For the past eight years, under Hudson’s leadership, withdrawal treatment has started at birth for babies born at GHS, when mothers are known to have used long-acting opioids during late pregnancy. Rather than long stays in intensive care, these NAS babies typically go home after one week to bond with their families and continue to receive a slow medication wean at home. Outpatient physicians and visiting nurses monitor the four-week home treatment process. This makes for healthier babies, happier families, and lower costs, Hudson says.

The casualties and costs of NAS

One NAS infant is born every hour, or 3.39 per 1,000 hospital births per year in the U.S., according to the Journal of the American Medical Association (JAMA) data for 2009. That’s three times the rate in 2000, as opiod drug use rises. In South Carolina, 5.4 of every 1,000 hospital births in 2012 were NAS babies, according to the state’s Office of Research and Statistics. The numbers add up to more dollars taken from pockets of families and taxpayers. Average hospital charges for NAS newborns in 2009 were $53,400, compared to $9,500 for all other hospital births, and Medicaid was the primary payer for over 75 percent of charges, JAMA reported. The Protecting Our Infants Act of 2015 asks Congress for coordinated national efforts to curb rising drug use in pregnant women and to seek solutions for these babies.

In 2013, a research team led by Rachel Mayo, a public health sciences professor at Clemson University, joined Hudson in a new research partnership to evaluate her approach to treating NAS babies. The partnership, which is one of a growing number of collaborations between Clemson researchers and GHS clinicians, is designed to provide data on the effectiveness of an intervention used at GHS for nearly a decade.

“Dr. Hudson wanted to partner with researchers who know how to evaluate programs to see if this is more effective than the current standard of care,” says Mayo, whose research focuses on women’s and children’s health.

If the team finds that the gentler intervention adopted under Hudson’s leadership at GHS produces better outcomes than traditional treatment, they’ll pursue answers to a second question as well: Can this method be used as effectively at other hospitals across South Carolina?

Windsor Sherrill, associate vice president for health research at Clemson and chief science officer at GHS, introduced Hudson and Mayo. “Babies born with drug dependence are usually treated in neonatal intensive care units, and this is expensive,” Sherrill says. “This treatment alternative has incredible promise for improved outcomes and cost savings.”

Rachel Mayo (right) with a student: “It’s important for us not to judge,” she says about the many circumstances of addiction.

Photo by Craig Mahaffey.

Is there a better way?

Eight years of data gathered on opioid-dependent babies born at GHS is under analysis by Mayo’s research team, which includes Sherrill; Liwei Chen, a biostatistician and epidemiologist in Clemson’s Department of Public Health Sciences; Lori Dickes, an economist with Clemson’s Strom Thurmond Institute; and Brad Dalton, a medical doctor and postdoctoral fellow at Clemson. Their work is supported in part by a $1.3 million grant from the South Carolina Department of Health and Human Services.

The researchers will look at the retrospective studies and health outcomes in terms of cost, safety, and relative effectiveness compared to the current traditional standard of care, Mayo says. They want to learn whether outcomes are different for NAS babies born at GHS compared to hospitals in the rest of the state and whether the GHS model can be replicated in other South Carolina hospitals.

So far, the team sees several potential advantages to the GHS approach, in addition to the cost savings of infants leaving the hospital sooner. Dalton says that increased maternal interaction, breastfeeding, and bonding with the family in the comfort of the home appear to decrease the withdrawal symptoms. “Anything that can get the baby home sooner is going to be more beneficial for the family as a whole,” he says.

Mothers of NAS babies aren’t necessarily the stereotypical drug addicts portrayed on prime-time television shows. A pregnant car wreck victim could need painkillers, Dalton says. Or a woman might be on painkillers for a back injury before becoming pregnant, Mayo says.

“It doesn’t take long to become dependent or addicted. It’s important for us not to judge,” Mayo says.

Hudson explains another complicating factor. “When a mother is using heroin or prescription painkillers illegally, it’s often safer to transition to a long-acting opioid during pregnancy,” she says. “This removes craving and helps a mother control drug-seeking behaviors that are often risky. The downside, though, is that the baby’s system gets used to having that medication every day and is at significant risk for withdrawal after birth.”

Support is provided for the mother and the entire family to help the baby through infancy and early childhood so that when he starts school he is ready to succeed, Mayo says. The researchers also can delve into the long-term implications of this intervention because some of the babies born at GHS who are in the study now are in second grade.

The eight years of data on GHS babies could help fill gaps in current knowledge about the effects of drugs on a fetus, Mayo adds. A report in Pediatrics, the official journal of the American Academy of Pediatrics, cites “an urgent need for studies of long-term outcomes in these children.”

Over time, the data also can help researchers learn more about the impact of ongoing family drug abuse on these children, evaluate school readiness and behavioral problems such as Attention Deficit Disorder, and look at the incidence of placements with the state’s Department of Social Services, foster homes, and incarceration, Hudson says.

Mayo says that the project is one of the most rewarding she’s been involved in, because of the “potential to turn things around” for our youngest citizens.

Healing tendons, joints, and bones

While Hudson, Mayo, and their team find ways to help some of the state’s youngest patients, another Clemson-GHS research team is focused on the problems of aging, working to slow the progression of osteoarthritis, helping patients with massive rotator cuff or shoulder tendon tears, and developing implants for patients with bone and cartilage defects.

Jeremy Mercuri received his graduate degrees in Clemson’s Department of Bioengineering. Its strength in the study of biomaterials helped him pursue his passion: advanced medical devices. He worked in the medical device industry for a short time both before and after receiving his doctorate. But the ability to interact with medical clinicians through the GHS partnership, coupled with his motivation to improve upon the technologies being developed in the industry, lured Mercuri back to Clemson as an assistant professor of bioengineering.

“I wanted to be sure our research had an opportunity to have real-world impact down the road, to improve people’s lives, improve patient outcomes,” Mercuri says. The partnership adds “clinical relevancy to work being done in our Ortho-X lab”—Clemson’s laboratory of Orthopaedic Tissue Regeneration and Orthobiologics.

“It’s not research in a vacuum,” Mercuri says. “In terms of developing biomaterials, we can do cool things in the lab, but the ultimate goal is to develop technologies that can get to the patient. I have a wonderful group of hardworking and motivated graduate and undergraduate students who are really driving these projects forward.”

Reviving damaged tissue

Mercuri’s lab is working on multiple orthopedic tissue regeneration projects, partnering with doctors at the Steadman Hawkins Clinic of the Carolinas, which is part of GHS, and with clinicians at the Department of Maternal-Fetal Medicine, part of the GHS Women’s Hospital.

One project, still in the early “petri dish stage,” already has shown promising potential to help patients stave off hip and knee replacements, Mercuri says. The research involves the use of a relatively new source of young stem cells that are gathered, with patients’ consent, from amniotic membrane, a tissue that is discarded after babies are born. His goal is to repurpose these discarded cells to slow, and possibly halt, the progression of osteoarthritis.

Another project would repair massive rotator cuff or shoulder tendon tears using the patients’ own stem cells. Stem cells from the patients’ fat would be isolated in the operating room during the tendon repair surgery. Other material from the patient’s body would be molded into a scaffold in the operating room during the surgery. Stem cells would be attached to the scaffold and the structure would be placed into the repair site, where the stem cells would be turned into tendon, forming cells to aid repair of the injury.

“It all comes from the patient’s body and happens in the operating room during the surgical procedure,” Mercuri says. That should lower the risk of rejection, “and hopefully would result in more optimal healing and less risk of transmitting disease.” This work also is in the petri dish stage and he hopes to move to representative animal models within the year.

A third project, in a very early, pre-petri stage, involves the development of a biomaterial that could be implanted in patients with both cartilage and bone defects, such as those that occur in someone injured from a fall or other trauma. This new biomaterial would need the ability to mimic both bone and cartilage, Mercuri says. He and Steadman Hawkins clinicians hope to create an off-the-shelf material that can be manufactured on a large scale.

“We’re doing the research and the science, but we’re also looking ahead at being able to scale it up for manufacturing to make it available to the masses. We’re trying to help as many patients as possible,” Mercuri says.

Bridging the clinical and the academic

Mercuri builds bridges to connect the academic and clinical worlds for his students too, through a curriculum that includes student interaction with GHS clinicians “so they can truly understand the importance of bringing relevancy back to the lab,” Mercuri says. His students—undergraduates and graduate students—also get exposure to research in his labs.

In addition to his lab on the Clemson campus, Mercuri, like the numerous other Clemson faculty involved in research with GHS partners, also has lab space at Greenville Health System’s Patewood Medical Campus. “It’s a great facility. I absolutely love it,” Mercuri says. “It’s a great environment that supports collaboration between clinicians and researchers.”

His lab is near GHS orthopedic physicians at the Steadman Hawkins Clinic of the Carolinas, and he’s been able to be in the operating room with them to see firsthand what surgery looks like for patients with osteoarthritis in their knees. He’s also witnessed other surgical procedures related to his research.

“Bringing the different mindsets together is a great way to develop new ideas to solve problems. It’s very mind opening,” Mercuri says. “It’s added value all the way around.”

Health in a land-grant tradition

Why has Clemson University, with its deep roots in agriculture, engineering, and the land-grant tradition, forged a bold new identity for itself in the arena of health care?

For one thing, Clemson’s land-grant mission has long included working in local communities to improve health, says Windsor Sherrill. For another, the faculty has developed a strong interest in topics relevant to medicine and health. Approximately 125 Clemson faculty members conduct health-related research, which has become one of the university’s strategic focus areas, Sherrill says.

Clemson and the Greenville Health System (GHS) are now research partners, with Furman University and the University of South Carolina, in the nation’s first shared academic health center, a formal relationship announced in late 2013.

“We are better together,” Sherrill says. “GHS has clinical ideas and challenges. Clemson brings the health research expertise to help study the problem, solve the problems through research and publication.”

“GHS is committed to furthering Clemson’s one-of-a-kind health research,” says Spence M. Taylor, vice president of physician engagement for GHS and president of Greenville Health System Clinical University.

Photo of Windsor Sherrill by Craig Mahaffey.

Shaping health care leaders

More than 13,000 people employed at GHS have participated in surveys that will provide thought-provoking data for Marissa Shuffler, an assistant professor of industrial organizational psychology at Clemson. Shuffler, who is interested in leadership development, had barely settled into her faculty position in 2013 when a casual conversation opened the door to a research partnership with GHS Vice President Tod Tappert, chief of staff and chief learning officer for the health system, and Sharon Wilson, director of conscious leadership development at GHS.

GHS has taught conscious leadership, a concept based on social and emotional intelligence or self-awareness, for years. Shuffler will analyze the effectiveness and the stickiness of the method and the message. The findings will be useful for GHS, “and hopefully for health care at a broader level,” Shuffler says.

“Health care is an industry that is experiencing tremendous change. The pace of change is accelerating rapidly, and that invites what we often describe as a stress-rich environment. When things are moving fast, that opportunity to strengthen the muscle of self-awareness is really important,” Tappert says.

Shuffler brings “a sense of rigor” and research knowledge, and GHS offers “a large population that can be studied over time,” Tappert says. “From a data perspective, we offer a lot of value. Greenville Health System is an organization that is committed to developing and growing our leaders.”

The partnership with Clemson supports GHS’s mission—to “heal compassionately, teach innovatively, and improve constantly,” Tappert says. The research “will benefit our commitment to patients and their families.”

(For more about Marissa Shuffler’s work, see What kind of leadership will take us to Mars?)

Building a healthier state

From the newly born to those debilitated by the effects of aging, the wide spectrum of research produced through the Clemson-GHS partnership can provide new knowledge that is spurred by actual need and applicable to real life, Sherrill says.

The partnership includes four primary areas: nursing education, health care research, population health management, and health workforce development. A biomedical collaboration between Clemson and GHS goes back to 1990 and is “one of the huge success stories,” Sherrill says. “We want to replicate that partnership. Health research and education is now an intentional focus area across the university.”

Plans include expansion of the undergraduate nursing program to accommodate more students and a graduate nurse practitioner program to prepare students to work with underserved and primary care populations, Sherrill says.

The knowledge acquired through these research partnerships will benefit the people of South Carolina through improvements in health care delivery, a better-prepared health care workforce, and healthier outcomes for the population. “This is building a healthier state,” Sherrill says.

Jennifer Hudson is a medical doctor and director of newborn services at Greenville Health System. Rachel Mayo is a professor of public health sciences at Clemson University. Windsor Sherrill is an associate vice president for health research at Clemson and chief science officer at GHS. Brad Dalton is a medical doctor at GHS and postdoctoral fellow at Clemson. Spence M. Taylor is a medical doctor and vice president of physician engagement at Greenville Health System and president of Greenville Health System Clinical University. Jeremy Mercuri is an assistant professor of bioengineering at Clemson. Marissa Shuffler is an assistant professor of industrial organizational psychology at Clemson. Tod Tappert is vice president, chief of staff, and chief learning officer at GHS. Anna Simon is a writer based in Pendleton, South Carolina.