Beth Tarini

Getting to know SPR’s future President, Beth Tarini, M.D., MS

Beth Tarini

Quick. Name four pillar pediatric organizations on the vanguard of advancing pediatric research.

Most researchers and clinicians can rattle off the names of the Academic Pediatric Association, the American Academy of Pediatrics and the American Pediatric Society. But that fourth one, the Society for Pediatric Research (SPR), is a little trickier. While many know SPR, a lot of research-clinicians simply do not.

Over the next few years, Beth A. Tarini, M.D., MS, will make it her personal mission to ensure that more pediatric researchers get to know SPR and are so excited about the organization that they become active members. In May 2019 Dr. Tarini becomes Vice President of the society that aims to stitch together an international network of interdisciplinary researchers to improve kids’ health. Four-year SPR leadership terms begin with Vice President before transitioning to President-Elect, President and Past-President, each for one year.

Dr. Tarini says she looks forward to working with other SPR leaders to find ways to build more productive, collaborative professional networks among faculty, especially emerging junior faculty. “Facilitating ways to network for research and professional reasons across pediatric research is vital – albeit easier said than done. I have been told I’m a connector, so I hope to leverage that skill in this new role,” says Dr. Tarini, associate director for Children’s Center for Translational Research.

“I’m delighted that Dr. Tarini was elected to this leadership position, and I am impressed by her vision of improving SPR’s outreach efforts,” says Mark Batshaw, M.D., Executive Vice President, Chief Academic Officer and Physician-in-Chief at Children’s National. “Her goal of engaging potential members in networking through a variety of ways – face-to-face as well as leveraging digital platforms like Twitter, Facebook and LinkedIn – and her focus on engaging junior faculty will help strengthen SPR membership in the near term and long term.”

Dr. Tarini adds: “Success to me would be leaving after four years with more faculty – especially junior faculty – approaching membership in SPR with the knowledge and enthusiasm that they bring to membership in other pediatric societies.”

SPR requires that its members not simply conduct research, but move the needle in their chosen discipline. In her research, Dr. Tarini has focused on ensuring that population-based newborn screening programs function efficiently and effectively with fewer hiccups at any place along the process.

Thanks to a heel stick to draw blood, an oxygen measurement, and a hearing test, U.S. babies are screened for select inherited health conditions, expediting treatment for infants and reducing the chances they’ll experience long-term health consequences.

“The complexity of this program that is able to test nearly all 4 million babies in the U.S. each year is nothing short of astounding. You have to know the child is born – anywhere in the state – and then between 24 and 48 hours of birth you have to do testing onsite, obtain a specific type of blood sample, send the blood sample to an off-site lab quickly, test the sample, find the child if the test is out of range, get the child evaluated and tested for the condition, then send them for treatment. Given the time pressures as well as the coordination of numerous people and organizations, the fact that this happens routinely is amazing. And like any complex process, there is always room for improvement,” she says.

Dr. Tarini’s research efforts have focused on those process improvements.

As just one example, the Advisory Committee on Heritable Disorders in Newborns and Children, a federal advisory committee on which she serves, was discussing how to eliminate delays in specimen processing to provide speedier results to families. One possible solution floated was to open labs all seven days, rather than just five days a week. Dr. Tarini advocated for partnering with health care engineers who could help model ways to make the specimen transport process more efficient, just like airlines and mail delivery services. A more efficient and effective solution was to match the specimen pick-up and delivery times more closely with the lab’s operational times – which maximizes lab resources and shortens wait times for parents.

Conceptual modeling comes so easily for her that she often leaps out of her seat mid-sentence, underscoring a point by jotting thoughts on a white board, doing it so often that her pens have run dry.

“It’s like a bus schedule: You want to find a bus that not only takes you to your destination but gets you there on time,” she says.

Dr. Tarini’s current observational study looks for opportunities to improve how parents in Minnesota and Iowa are given out-of-range newborn screening test results – especially false positives – and how that experience might shake their confidence in their child’s health as well as heighten their own stress level.

“After a false positive test result, are there parents who walk away from newborn screening with lingering stress about their child’s health? Can we predict who those parents might be and help them?” she asks.

Among the challenges is the newborn screening occurs so quickly after delivery that some emotionally and physically exhausted parents may not remember it was done. Then they get a call from the state with ominous results. Another challenge is standardizing communication approaches across dozens of birthing centers and hospitals.

“We know parents are concerned after receiving a false positive result, and some worry their infant remains vulnerable,” she says. “Can we change how we communicate – not just what we say, but how we say it – to alleviate those concerns?”

ACC19 attendees from Children's National

ACC.19: A focus on pediatric cardiology

ACC19 attendees from Children's National

Dr. Gerard Martin, center, accepts an award before delivering the 2019 Dan G. McNamara Keynote lecture at ACC.19.

“Innovation meets tradition,” is how many attendees and journalists described the American College of Cardiology’s 68th Scientific Sessions (ACC.19), which took place March 16-18, 2019 in New Orleans, La.

Gerard Martin, M.D., F.A.A.P., F.A.C.C., F.A.H.A., a pediatric cardiologist and the medical director of Global Services at Children’s National, supported this narrative by referencing both themes in his 2019 Dan G. McNamara keynote lecture, entitled “Improved Outcomes in Congenital Heart Disease through Advocacy and Collaboration.” Dr. Martin highlighted advancements in the field of pediatric cardiology that took place over the past 15 years, while touting modern advancements – such as pulse oximetry screenings for critical congenital heart disease – that were a result of physician-led advocacy and collaboration.

Dr. Martin’s message was to continue to invest in research and technology that leads to medical breakthroughs, but to remember the power of partnerships, such as those formed by the National Pediatric Cardiology Quality Improvement Collaborative. These alliances, which generated shared protocols and infrastructure among health systems, improved interstage mortality rates between surgeries for babies born with hypoplastic left heart syndrome.

A dozen cardiologists and clinicians from the Children’s National Heart Institute also participated in CME panel discussions or delivered poster presentations to support future versions of this template, touching on early-stage innovations and multi-institution research collaborations. The themes among Children’s National Heart Institute faculty, presented to a diverse crowd of 12,000-plus professional attendees representing 108 countries, included:

Personalized guidelines:

  • Sarah Clauss, M.D., F.A.C.C., a cardiologist, presented “Unique Pediatric Differences from Adult Cholesterol Guidelines: Lipids and Preventive Cardiology,” before Charles Berul, M.D., division chief of cardiology and co-director of the Children’s National Heart Institute, presented “Unique Pediatric Differences from Adult Guidelines: Arrhythmias in Adults with Congenital Heart Disease,” in a joint symposium with the American Heart Association and the American College of Cardiology.
  • Berul, who specializes in electrophysiology, co-chaired a congenital heart disease pathway session, entitled “Rhythm and Blues: Electrophysiology Progress and Controversies in Congenital Heart Disease,” featuring components of pediatric electrophysiology, including heart block, surgical treatment of arrhythmias and sudden death risk.

Early detection:

  • Anita Krishnan, M.D., associate director of the echocardiography lab, presented “Identifying Socioeconomic and Geographic Barriers to Prenatal Detection of Hypoplastic Left Heart Syndrome and Transposition of the Great Arteries” as a moderated poster in Fetal Cardiology: Quickening Discoveries.
  • Jennifer Romanowicz, M.D., a cardiology fellow, and Russell Cross, M.D., director of cardiac MRI, presented the “Neonatal Supraventricular Tachycardia as a Presentation of Critical Aortic Coarctation” poster in FIT Clinical Decision Making: Congenital Heart Disease 2.
  • Pranava Sinha, M.D., a cardiac surgeon, presented the poster “Neuroprotective Effects of Vitamin D Supplementation in Children with Cyanotic Heart Defects: Insights from a Rodent Hypoxia Model” in Congenital Heart Disease: Therapy 2.

Coordinated care:

  • Ashraf Harahsheh, M.D., F.A.C.C., F.A.A.P., a cardiologist with a focus on hyperlipidemia and preventive cardiology, co-presented an update about BMI quality improvement (Q1) activity from the American College of Cardiology’s Adult Congenital and Pediatric Quality Network – BMI Q1 leadership panel.
  • Niti Dham, M.D., director of the cardio-oncology program, and Deepa Mokshagundam, M.D., cardiology fellow, presented the poster “Cardiac Changes in Pediatric Cancer Survivors” in Heart Failure and Cardiomyopathies: Clinical 3.
  • Nancy Klein, B.S.N., R.N., C.P.N., clinical program coordinator of the Washington Adult Congenital Heart program at Children’s National, presented the poster “Improving Completion of Advanced Directives in Adults with Congenital Heart Disease” in Risks and Rewards in Adult Congenital Heart Disease.

Innovation:

  • Jai Nahar, M.D., a cardiologist, moderated “Future Hub: Augmented Cardiovascular Practitioner: Giving Doctors and Patients a New Voice.” The session focused on technical aspects of artificial intelligence, such as language processing and conversational artificial intelligence, as well as how applications are used in patient-physician interactions.
  • Nahar also participated in a key event on the Heart-to-Heart stage, entitled “Rise of Intelligent Machines: The Potential of Artificial Intelligence in Cardiovascular Care.”

“While I enjoyed the significant representation of Children’s National faculty at the meeting and all of the presentations this year, one research finding that I found particularly compelling was Dr. Krishnan’s poster about geographical disparities in detecting congenital heart disease,” says Dr. Berul. “Her research finds obstetricians providing care to women in the lowest quartile of socioeconomic areas were twice as likely to miss a diagnosis for a critical congenital heart defect during a fetal ultrasound, compared to obstetricians providing care for women in the highest quartiles.”

Dr. Krishnan’s study was the collaborative effort of 21 centers in the United States and Canada, and investigated how socioeconomic and geographic factors affect prenatal detection of hypoplastic left heart syndrome and transposition of the great arteries.

“We studied over 1,800 patients, and chose these diseases because they require early stabilization by a specialized team at a tertiary care center,” says Dr. Krishnan, who led the research in conjunction with the Fetal Heart Society Research Collaborative. “We hope that by understanding what the barriers are, we can reduce disparities in care through education and community-based outreach.”

Nichole Jefferson and Patrick Gee

African American stakeholders help to perfect the APOLLO study

Nichole Jefferson and Patrick Gee

Nichole Jefferson and Patrick O. Gee

African Americans who either donated a kidney, received a kidney donation, are on dialysis awaiting a kidney transplant or have a close relative in one of those categories are helping to perfect a new study that aims to improve outcomes after kidney transplantation.

The study is called APOLLO, short for APOL1 Long-Term Kidney Transplantation Outcomes Network. Soon, the observational study will begin to enroll people who access transplant centers around the nation to genotype deceased and living African American kidney donors and transplant recipients to assess whether they carry a high-risk APOL1 gene variant.

The study’s Community Advisory Council – African American stakeholders who know the ins and outs of kidney donation, transplantation and dialysis because they’ve either given or  received an organ or are awaiting transplant – are opening the eyes of researchers about the unique views of patients and families.

Already, they’ve sensitized researchers that patients may not be at the same academic level as their clinicians, underscoring the importance of informed consent language that is understandable, approachable and respectful so people aren’t overwhelmed. They have encouraged the use of images and color to explain the apolipoprotein L1 (APOL1) gene. The APOL1 gene is found almost exclusively in people of recent African descent, however only 13 percent of these people carry the high-risk APOL1 variant that might cause kidney problems.

One issue arose early, during one of the group’s first monthly meetings, as they discussed when to tell patients and living donors about the APOLLO study. Someone suggested the day of the transplant.

“The Community Advisory Council told them that would not be appropriate. These conversations should occur well before the day of the transplant,” recalls Nichole Jefferson.

“The person is all ready to give a kidney. If you’re told the day of transplant ‘we’re going to include you in this study,’ that could possibly stop them from giving the organ,” Jefferson says. “We still remember the Tuskegee experiments. We still remember Henrietta Lacks. That is what we are trying to avoid.”

Patrick O. Gee, Ph.D., JLC, another Community Advisory Council member, adds that it’s important to consider “the mental state of the patient and the donor. As a patient, you know you are able to endure a five- to eight-hour surgery. The donor is the recipient’s hero. As the donor, you want to do what is right. But if you get this information; it’s going to cause doubt.”

Gee received his kidney transplant on April 21, 2017, and spent 33 days in the hospital undergoing four surgeries. His new kidney took 47 days to wake up, which he describes as a “very interesting journey.” Jefferson received her first transplant on June 12, 2008. Because that kidney is in failure, she is on the wait list for a new kidney.

“All I’ve ever known before APOLLO was diabetes and cardiovascular issues. Nobody had ever talked about genetics,” Gee adds. “When I tell people, I tread very light. I try to stay in my lane and not to come off as a researcher or a scientist. I just find out information and just share it with them.”

As he spoke during a church function, people began to search for information on their smart phones. He jotted down questions “above his pay grade” to refer to the study’s principal investigator. “When you start talking about genetics and a mutated gene, people really want to find out. That was probably one of the best things I liked about this committee: It allows you to learn, so you can pass it on.”

Jefferson’s encounters are more unstructured, informing people who she meets about her situation and kidney disease. When she traveled from her Des Moines, Iowa, home to Nebraska for a transplant evaluation, the nephrologist there was not aware of the APOL1 gene.

And during a meeting at the Mayo Clinic with a possible living donor, she asked if they would test for the APOL1 gene. “They stopped, looked at me and asked: ‘How do you know about that gene?’ Well, I’m a black woman with kidney failure.”

Patrick O. Gee received his kidney transplant on April 21, 2017, and spent 33 days in the hospital undergoing four surgeries. His new kidney took 47 days to wake up, which he describes as a “very interesting journey.”

About 100,000 U.S. children and adults await a kidney transplant. APOLLO study researchers believe that clarifying the role that the APOL1 gene plays in kidney-transplant failure could lead to fewer discarded kidneys, which could boost the number of available kidneys for patients awaiting transplant.

Gee advocates for other patients and families to volunteer to join the APOLLO Community Advisory Council. He’s still impressed that during the very first in-person gathering, all researchers were asked to leave the table. Only patients and families remained.

“They wanted to hear our voices. You rarely find that level of patient engagement. Normally, you sit there and listen to conversations that are over your head. They have definitely kept us engaged,” he says. “We have spoken the truth, and Dr. Kimmel is forever saying ‘who would want to listen to me about a genotype that doesn’t affect me? We want to hear your voice.’ ”

(Paul L. Kimmel, M.D., MACP, a program director at the National Institute of Diabetes and Digestive and Kidney Diseases, is one of the people overseeing the APOLLO study.)

Jefferson encourages other people personally impacted by kidney disease to participate in the APOLLO study.

“Something Dr. Kimmel always says is ‘You’re in the room.’ We’re in the room while it’s happening. It’s a line from Hamilton. That’s a good feeling,” she says. “I knew right off, these are not necessarily improvements I will see in my lifetime. I am OK with that. With kidney disease, we have not had advances in a long time. As long as my descendants don’t have to go through the same things I have gone through, I figure I have done my part. I have done my job.”

Kinsley and Dr. Timothy Kane

Case study: Diagnosing a choledochal cyst in utero

Kinsley and Dr. Timothy Kane

The Feigel family worked with Timothy Kane, M.D., the division chief of general and thoracic surgery at Children’s National, to ensure an accurate diagnosis, coordinate a corrective procedure and support a strong recovery for Kinsley, who just celebrated a 5-month milestone.

On Sept. 30, 2018, Elizabeth Feigel gave birth to a healthy baby girl, Kinsley Feigel. Thirty-two days later, Elizabeth and her husband, Steven Feigel, delighted in another hospital moment: Kinsley, who developed a choledochal cyst in utero, was recovering from a surgical procedure to remove an abnormal bile duct cyst, which also required the removal of her gallbladder.

While the series of events, interspersed with multiple hospital visits, would likely create uneasiness in new parents, the Feigel family worked with Vahe Badalyan, M.D., a gastroenterologist at Children’s National Health System, and with Timothy Kane, M.D., the division chief of general and thoracic surgery at Children’s National, to ensure an accurate diagnosis, coordinate a corrective procedure and support a strong recovery for Kinsley, who just celebrated a 5-month milestone.

One of the keys to Kinsley’s success was close communication between her parents and providers.

Dr. Badalyan and Dr. Kane listened to Elizabeth and Steven’s concerns, explained complex medical terms in lay language, and provided background about Kinsley’s presenting symptoms, risk factors and procedures. Instead of second-guessing the diagnosis, Elizabeth and Steven put their trust into and remained in contact with the medical team, sharing updates about Kinsley at home. This parent-physician partnership helped ensure an accurate diagnosis and tailored treatment for Kinsley.

Here is her story.

An early diagnosis

During a 12-week prenatal ultrasound, Elizabeth discovered that Kinsley had an intra-abdominal cyst. Before Elizabeth came to Children’s National for an MRI, she met with several fetal medicine specialists and had a variety of tests, including an amniocentesis to rule out chromosomal abnormalities, such as Down syndrome.

The team at Children’s National didn’t want to prematurely confirm Kinsley’s choledochal cyst in utero, but additional ultrasounds and an MRI helped narrow the diagnosis to a few conditions.

After Kinsley was born, and despite looking like a healthy, full-term baby, she was transported to the neonatal intensive care unit (NICU) at Children’s National. Dr. Badalyan and Dr. Kane analyzed Kinsley’s postnatal sonogram and found the cyst was bigger than they previously thought. Over a five-day period, the medical team kept Kinsley under their close watch, running additional tests, including an additional sonogram. They then followed up with Kinsley on an outpatient basis to better understand and diagnose her cyst.

Outpatient care

Over the next few weeks, Kinsley, Elizabeth and Steven returned to Children’s National to coordinate multiple exams, ranging from an MRI to a HIDA scan. During this period, Elizabeth and Steven remained in contact with Dr. Badalyan. They heard about Kinsley’s lab results and sent updates about her symptoms, including her stool, which helped the medical team monitor her status.

Meanwhile, Dr. Badalyan and Dr. Kane worked closely with the lab to measure Kinsley’s bilirubin levels. Her presenting symptoms and risk factors, she had jaundice and is a female baby of Asian descent, are associated with both choledochal cysts and biliary atresia.

Over time and with the help of Elizabeth, Steven and the pediatric radiologists, Dr. Badalyan and Dr. Kane confirmed Kinsley had a type 1 choledochal cyst, the most common. Originally, the plan was to operate at three to six months, but Dr. Kane needed to expedite the procedure and operate on Kinsley at one month due to a rise in her bilirubin, a sign of progressive liver disease.

Higher bilirubin levels are common in newborns and remain elevated at about 5 mg/dL after the first few days of birth, but Kinsley’s levels peaked and remained elevated. Instead of her bile flowing into her intestine, her choledochal cyst reduced the flow of bile, which accumulated and started to pour back into her liver. The timing of the surgery was as important as the procedure.

The surgery

On Oct. 31, Halloween, Kinsley had laparoscopic surgery to remove the choledochal cyst. Approximately five to seven patients per year undergo choledochal cyst removal at Children’s National. Smaller infants typically undergo removal of a choledochal cyst using a large incision (or open procedure). Kinsley was the smallest baby at Children’s National to have this type of surgery performed by minimally invasive laparoscopic surgery, which required a few 3-mm incisions – the size of coriander seeds.

Some hospitals use the da Vinci robot, which starts at 8-mm incisions, the size of a small pearl, to conduct this procedure on infants, but this method cannot effectively be done in very small infants. Instead, Dr. Kane prefers to stitch sutures by hand. This technique keeps the incisions small and is technically demanding, but Dr. Kane doesn’t mind (he views this as an advanced technical skill). The goal for this surgery was to cut out the abnormal piece of Kinsley’s common bile duct, comprised of the cyst, remove  this and then sew the bile duct to the small intestine (duodenum), creating a digestive pathway. The new digestive tube allows for bile to flow from her liver through the common hepatic duct, in place of the pathway where the cyst formed, and into her intestine.

Like other surgeries, Dr. Kane needed to adapt the procedure, especially with Kinsley’s size: Taking too much from the bile duct would create a tight space, and could create obstruction, blocking bile, while leaving too much room could create leakage and spilling of the bile, requiring a follow-up surgical procedure within a week or two of the original operation.

Dr. Kane had a few options in mind before he operated. He didn’t know which would be most suitable until the operation, but he remained open and prepared for all three. Adopting this mindset, instead of having one procedure in mind, has helped Dr. Kane with precise and tailored surgeries, which often result in the best procedure and a stronger recovery period for young patients.

After 4.5 hours, the surgery, a two-part procedure – removing the cyst and recreating a functional bile duct – was complete.

Kinsley moved into the recovery unit, where she rested and recovered under close medical supervision for five days. During the first few days, she didn’t have liquids or milk, but she did have two bedside nurses monitoring her status in addition to surgeons making regular rounds. Elizabeth and Steven were relieved: The diagnosis and surgery were over.

Managing risk factors

Before Kinsley left the hospital, Elizabeth and Steven scheduled a follow-up visit to ensure Kinsley was recovering well and avoided risk of infection, such as cholangitis, which can occur suddenly and become chronic.

Following Kinsley’s post-surgical bloodwork in early November, Dr. Badalyan noticed Kinsley’s white blood count was high, signaling infection, and he immediately brought the family back to the hospital. To help her body fight the infection, Kinsley received antibiotics and intravenous fluids. She stayed in the hospital for five days. Fortunately, cholangitis is easy to treat with antibiotics; the key is to detect it early.

Kinsley returned home in time for Thanksgiving. She came back to the hospital for biweekly visits. At this point, she was filling out, reaching a 2-month milestone and nearing a full recovery. She returned for follow-up visits in December and January – and has been healthy ever since. She will continue to make routine visits during her first year to ensure her white blood count remains in a healthy range.

Investing in youth resilience

Dr. Badalyan and Dr. Kane envision a healthy future for Kinsley. They don’t expect she’ll need additional operations. Her parents are also looking on the bright side: Since gallbladders aren’t essential for survival or long-term health outcomes, and since many people can easily live without them, Kinsley may be at an advantage. Elizabeth thinks Kinsley may be more cautious about lifestyle choices to support living without a gallbladder, which also support longevity.

Another perspective noted by Dr. Badalyan and Dr. Kane is Kinsley’s resilience factor. Having the surgery earlier brought unique challenges, but her age makes it easier for Kinsley to bounce back as her body rapidly develops. Her tissues were healthy, compared to adult patients undergoing surgery with chronic liver problems or heart disease, which puts her at an advantage for a faster healing process. Dr. Badalyan also mentions that while it’s good for her Kinsley and her family to continue to monitor risks for infections, she won’t have gallstones.

Elizabeth also started to notice something that Kinsley’s doctors likely wouldn’t pick up on: Her personality seems to be a result of her hospital experience and stay. Kinsley’s an easy baby. She eats well and sleeps well, which Elizabeth credits to being around clinicians and to learning the art of self-soothing, a skill she likely acquired while recovering from surgery.

This month, Kinsley has another adventure. She’ll travel with her parents to visit extended family in Seattle, Napa Valley, Calif. and West Virginia. She has several relatives and family friends, all of whom are looking forward to meeting her.

DNA Molecule

Test your knowledge of APOL1’s role in kidney health

Matthew Oetgen, M.D., discusses an image of a patient’s spine.

Eliminating unnecessary radiation exposure from spinal radiography

Matthew Oetgen, M.D., discusses an image of a patient’s spine.

Chief of Orthopaedics and Sports Medicine Matthew Oetgen, M.D., discusses an image of a patient’s spine.

If a child arrives at the pediatric orthopaedic specialist for an idiopathic scoliosis evaluation without an adequate radiographic image of his or her spine, it’s often necessary to order yet another imaging study for accurate assessment.

A study published in the Journal of the American Academy of Orthopaedic Surgeons found that in a 6 month period, almost half (43 percent) of patients referred for evaluation required a repeat radiograph due to missing or poor quality existing images.

“Repeating the radiograph means these kids received another exposure to radiation, too,” says Matthew Oetgen, M.D., the study’s lead author and chief of Orthopaedic Surgery and Sports Medicine at Children’s National Health System. “It’s frustrating because in many cases, a simple change in how the initial radiograph was taken could have prevented the need for more imaging studies.”

Dr. Oetgen and the study authors note that there is currently no standardized protocol for spinal radiography of suspected idiopathic scoliosis. However, a few basic criteria could greatly reduce the number of repeat images necessary. Radiographic images that allow for proper evaluation of idiopathic scoliosis and reduce radiation exposure include:

  • A full coronal view of the spine including skull base and pelvis
  • The iliac crest as an indicator of skeletal maturity
  • A full-length lateral view of the spine

Study authors also reinforced the need to do everything possible to reduce radiation exposure for children through proper use of protective shielding for reproductive organs and digital radiograph technology.

“Orthopaedic surgeons and pediatricians share the responsibility to ensure children are exposed to as little iatrogenic radiation as possible,” Dr. Oetgen concludes. “All physicians should be sure that the radiology facilities they refer patients to for spinal radiography employ every technology and safety measure available to limit radiation exposure. Additionally, we can and should work with radiologists to define evaluation criteria and improve what’s captured by radiography on the first try.”

Preemie Baby

Getting micro-preemie growth trends on track

Preemie Baby

According to Children’s research presented during the Institute for Healthcare Improvement 2018 Scientific Symposium, standardizing feeding practices – including the timing for fortifying breast milk and formula with essential elements like zinc and protein – improves growth trends for the tiniest preterm infants.

About 1 in 10 infants is born before 37 weeks gestation. These premature babies have a variety of increased health risks, including deadly infections and poor lung function.

Emerging research suggests that getting their length and weight back on track could help. According to Children’s research presented during the Institute for Healthcare Improvement 2018 Scientific Symposium, standardizing feeding practices – including the timing for fortifying breast milk and formula with essential elements like zinc and protein – improves growth trends for the tiniest preterm infants.

The quality-improvement project at Children’s National Health System targeted very low birth weight infants, who weigh less than 3.3 pounds (1,500 grams) at birth. These fragile infants are born well before their internal organs, lungs, brain or their digestive systems have fully developed and are at high risk for ongoing nutritional challenges, health conditions like necrotizing enterocolitis (NEC) and overall poor development.

The research team measured progress by tracking the micro-preemies’ mean delta weight Z-score for weight gain, which measures nutritional status.

“In this cohort, mean delta weight Z-scores improved by 43 percent, rising from -1.8 to the goal of -1.0, when we employed an array of interventions. We saw the greatest improvement, 64 percent, among preterm infants who had been born between 26 to 28 weeks gestation,” says Michelande Ridoré, MS, Children’s NICU quality-improvement program lead who presented the group’s preliminary findings. “It’s very encouraging to see improved growth trends just six months after introducing these targeted interventions and to maintain these improvements for 16 months.”

Within Children’s neonatal intensive care unit (NICU), micro-preemies live in an environment that mimics the womb, with dimmed lighting and warmed incubators covered by blankets to muffle extraneous noise. The multidisciplinary team relied on a number of interventions to improve micro-preemies’ long-term nutritional outcomes, including:

  • Reducing variations in how individual NICU health care providers approach feeding practices
  • Fortifying breast milk (and formula when breast milk was not available), which helps these extra lean newborns add muscle and strengthen bones
  • Early initiation of nutrition that passes through the intestine (enteral feeds)
  • Re-educating all members of the infants’ care teams about the importance of standardized feeding and
  • Providing a decision aid about feeding intolerance.

Dietitians were included in the daily rounds, during which the multidisciplinary team discusses each infant’s care plan at their room, and used traffic light colors to describe how micro-preemies were progressing with their nutritional goals. It’s common for these newborns to lose weight in the first few days of life.

  • Infants in the “green” zone had regained their birth weight by day 14 of life and possible interventions included adjusting how many calories and protein they consumed daily to reflect their new weight.
  • Infants in the “yellow” zone between day 15 to 18 of life remained lighter than what they weighed at birth and were trending toward lower delta Z-scores. In addition to assessing the infant’s risk factors, the team could increase calories consumed per day and add fortification, among other possible interventions.
  • Infants in the “red” zone remained below their birth weight after day 19 of life and recorded depressed delta Z-scores. These infants saw the most intensive interventions, which could include conversations with the neonatologist and R.N. to discuss strategies to reverse the infant’s failure to grow.

Future research will explore how the nutritional interventions impact newborns with NEC, a condition characterized by death of tissue in the intestine. These infants face significant challenges gaining length and weight.

Institute for Healthcare Improvement 2018 Scientific Symposium presentation

  • “Improved growth of very low birthweight infants in the neonatal intensive care unit.”

Caitlin Forsythe, MS, BSN, RNC-NIC, NICU clinical program coordinator, Neonatology, and lead author; Michelande Ridoré, MS, NICU quality-improvement program lead; Victoria Catalano Snelgrove, RDN, LD, CNSC, CLC, pediatric clinical dietitian; Rebecca Vander Veer, RD, LD, CNSC, CLC, pediatric clinical dietitian; Erin Fauer, RDN, LD, CNSC, CLC, pediatric clinical dietitian; Judith Campbell, RNC, IBCLC, NICU lactation consultant; Eresha Bluth, MHA, project administrator; Anna Penn, M.D., Ph.D., neonatologist; Lamia Soghier, M.D., MEd, Medical Unit Director, Neonatal Intensive Care Unit; and Mary Revenis, M.D., NICU medical lead on nutrition and senior author; all of Children’s National Health System.

Photo of nurses in the cardiac intensive care unit at Children's National

Can pyruvate support metabolic function following heart surgery?

Photo of nurses in the cardiac intensive care unit at Children's National

Nurses rush a child to the cardiac intensive care unit at Children’s National Health System.

Can pyruvate, the end product of glycolysis, help improve cardiovascular function in children who have cardiopulmonary bypass surgery and suffer from low cardiac output syndrome (LCOS)? This question is one that Rafael Jaimes, Ph.D., a staff scientist at Children’s National Heart Institute, a division of Children’s National Health System, is studying, thanks to a two-year grant from the American Heart Association.

The competitive grant awards Dr. Jaimes with $110,000 to study how pyruvate may help improve cardiac output among pediatric patients with LCOS. The compound aims to stimulate metabolic function, now treated by inotropic agents, such as dobutamine and milrinone. These agents ensure optimal delivery of oxygen from the heart to the brain, as well as to other organs in the body, following heart surgery. While these agents help patients with cardiac dysfunction, there is still a critical need for safe and effective therapies.

“If there’s any detriment in cardiac output, the heart’s function begins to degrade,” explains Dr. Jaimes. “You see a downward spiral effect with reduced cardiac output because the heart is dependent on its own perfusion. It needs to pump blood throughout the body to survive.”

This is where the pyruvate study, and the grant, will be applied: Can pyruvate target the essential muscle of the heart and reverse this cardiac destabilization – and as soon as possible?

“By increasing the metabolic output of the heart’s local muscle, cardiac output increases,” Dr. Jaimes explains. “That’s going to lead to better recovery.”

Better recovery could be measured by how fast a child recovers from heart surgery as well as how much time they spend in the hospital, clinically referred to as throughput. A faster recovery could also influence a child’s quality of life and reduce overall health care costs.

Based on preliminary data that shows pyruvate improves cardiac function in experimental models after ischemic insult, which is what happens when pediatric patients undergo cardiac surgery, Dr. Jaimes believes the results will likely replicate themselves in his preclinical models.

To start, he’ll test pyruvate using 100 blood samples and discarded tissue from patients. The blood samples will be tested for metabolic markers, including measured pyruvate levels.

Part of what encouraged Dr. Jaimes to study how this compound could complement or replace standard therapies was the encouragement he received from his mentors in the field.

“Nobody has looked into using pyruvate for almost 30 years,” says Dr. Jaimes. “It’s not commercially favorable, there’s no patent on it, it doesn’t have a lot of marketability and there are no financial incentives, so it’s been put aside.”

As part of a discussion with cardiologists at a medical conference in Washington, Dr. Jaimes brought up the idea of using pyruvate for pediatric heart surgeries and received positive feedback.

“Once everyone’s eyes lit up, I knew I was on to something,” says Dr. Jaimes about the encouragement he received to pursue this study.

“You put lactate and glucose in your IV solutions,” adds Dr. Jaimes. “Pyruvate is an essential nutrient. It’s almost an essential sugar so there’s no reason not to put it in. If these cardiologists are intrigued by the project, maybe the American Heart Association will be, too.”

In addition to funding the study, which could support future research about how metabolic makers in the blood can be stimulated to fast-track recovery following heart surgery, the American Heart Association grant is specific to pediatric health outcomes.

“The current state of pharmaceutical treatment for patients recovering from cardiac surgery is designed and created for adults,” says Dr. Jaimes. “From our research in pediatrics, we know that children aren’t small adults.”

Dr. Jaimes explains that children are different on an anatomical and physiological level. Their cells even look and function different, compared to adult cells, because they haven’t matured yet.

While congenital heart defects are rare, they affect 1 percent, or 40,000 births worldwide, they often require multiple surgeries throughout a child’s lifespan. LCOS impacts 25 percent of patients following cardiopulmonary bypass and the timing of treatment is important. In severe cases, insufficient cardiac output following surgery could impact a child’s long-term development, ranging from reasoning, learning, attention and executive function, to developing age-appropriate language and social skills.

“The metabolic insufficiencies I’m looking at, which may help improve the muscle function of the heart, are just one piece of a bigger puzzle in pediatric cardiology,” notes Dr. Jaimes about ongoing research at Children’s National Heart Institute. “We already know pyruvate is safe. We just have to see if it’s effective in supporting a patient’s recovery in the intensive care unit.”

Dr. Jaimes will work with his research mentor Nikki Posnack, Ph.D., assistant professor at the Children’s National Heart Institute, on this preclinical study throughout the grant’s lifecycle, which starts in early January 2019 and ends in late December 2020.

Matthew Oetgen examines a patient

Surgical home program for spinal fusion achieves long-term success

Matthew Oetgen examines a patient

“Our primary goal was to improve the value of care for children with scoliosis and their families,” says Dr. Oetgen. “Even better, we’ve shown that this model can be used consistently over time to maintain the benefits it delivers to this patient population.”

“Creating an effective process that benefits patients, is sustainable long term and doesn’t increase costs is one of the most challenging parts of any new procedure, both in health care and beyond,” says Matt Oetgen, M.D., chief of Orthopaedic Surgery and Sports Medicine at Children’s National.

Dr. Oetgen’s team accomplished this feat when building the Children’s National Spinal Fusion Surgical Home. The team used LEAN process mapping at the outset to engage a broad group of care providers who established a collaborative environment that empowered and engaged everyone to take ownership over a new care pathway for every patient who undergoes posterior spinal fusion surgery at the hospital.

This unique model designed using proven business process development tools has allowed patients require fewer pain medications after surgery and have shorter stays in the hospital. Even better, the team has maintained the integrity of the pathway consistently over a longer period of time than any other pediatric spinal fusion care model to date.

“Our primary goal was to improve the value of care for children with scoliosis and their families,” says Dr. Oetgen, who was the study’s lead author. “Even better, we’ve shown that this model can be used consistently over time to maintain the benefits it delivers to this patient population.”

The team conducted a retrospective analysis of prospective data from all patients (213) undergoing posterior spinal fusion at Children’s National Health System from 2014 to 2017, a period of time that captures nearly one year  before implementation of the new pathway and 2.5 years after implementation. The outcomes were reported in the Journal of Bone and Joint Surgery.

As pressure builds to increase the value of care, many hospital systems are trying standardized care pathways for many complex conditions, in an effort to decrease care variability, improve outcomes and decrease cost. Previous research has shown the effectiveness of a variety of standardized pathways with wide ranging goals for spinal fusion procedures, however, most published studies have focused only on the initial success of these pathways. This study is the first to look at the implementation over a period of 2.5 years to gauge whether the process and its effectiveness could be maintained long term.

The authors attribute physician buy-in across disciplines and strict adherence to pathway processes as key to the success of this model. In addition, the team created standardized educational procedures for onboarding new care providers and implemented standardized electronic order sets for both orthopaedic and anesthesia services to make the pathway easy to maintain with little deviation over time. Lean process mapping at the outset included a broad group of care providers who established a collaborative environment that empowered and engaged the entire team to take ownership over the new process.

“We used proven business models for culture change that were critical to the success of this program,” Dr. Oetgen says. “We’re proud of the model we have created and think it would work well in other pediatric hospitals with similar patient populations.”

bacteriophage

Phage therapy draws renewed interest to combat drug-resistant microbes

bacteriophage

In the face of growing antibiotic resistance and few antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

The married professors were spending their Thanksgiving holiday in Egypt when the husband, Thomas L. Patterson, Ph.D., got very sick very quickly, experiencing fever, nausea and a racing heartbeat. By the time Patterson was accurately diagnosed with a highly multi-drug resistant bacterial infection, he was near death. His wife, Steffanie Strathdee, Ph.D., promised to “leave no stone unturned.’”

What happened next is the ultimate infectious disease feel good story: Strathdee, part of an All-Star team of infectious disease experts and epidemiologists, concocted a cocktail of viruses that killed the superbug and saved Patterson’s life.

“He was going to die,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases at Children’s National Health System. “Because of her epidemiology background – and because she loves him – Patterson became the first patient successfully treated with bacteriophages.”

Dr. DeBiasi explains that all viruses take over cells and use their machinery for their own purposes. In order to escape, viruses blow up the cell. Bacteriophages are viruses that target bacteria, taking over their machinery and ultimately killing the bacterial host.

“Infection is a race between the body’s immune response and the bacteria replicating themselves,” she adds. “Bacteria have to continually replicate. If you knock out 90 percent of them with phage therapy, that gives the immune system a fighting chance to win the race.”

She was so inspired by the team’s ingenuity that DeBiasi, program vice-chair, invited them to recount the story during IDWeek2018, held Oct. 3 to Oct. 7, 2018, in San Francisco. During the closing plenary, Patterson, a professor of psychiatry, and Strathdee, associate dean of Global Health Sciences, will be joined by Robert T. “Chip” Schooley, M.D., (all of University of California, San Diego), to discuss the clinical aspects and efficacy of phage therapy.

About 50 years ago, the U.S. military had investigated leveraging phages but ultimately placed that research portfolio on the back burner. Now, in the face of growing antibiotic resistance and few experimental antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

“The technology has been around for 50 years. We’re going back to old things because we’re so desperate,” Dr. DeBiasi adds.

The tricky thing with phages is that each bacterium needs its own tailored phage therapy.

Children’s National is working with Adaptive Phage Therapeutics, a company based in Gaithersburg, Maryland, that developed the phage used to save Patterson, in order to help build out that library of phages, each ready to be directed to do battle against a specific pathogen.

“We have been consultants to them to think about what would be a good clinical trial, particularly in a pediatric population,” Dr. DeBiasi says.

Children’s National has been collecting and sending isolates from patients with neurogenic bladder who experience urinary tract infections to shore up the phage library in anticipation of a clinical trial. The work builds on Children’s experience as the first center to use phage therapy in a pediatric patient, a 2-year-old who had multidrug-resistant Pseudomonas aeruginosa infection complicated by bacteremia/sepsis.

Nikki Gillum Posnack

Do plastic chemicals contribute to the sudden death of patients on dialysis?

Nikki Gillum Posnack

Nikki Posnack, Ph.D., assistant professor with the Children’s National Heart Institute, continues to explore how repeat chemical exposure from medical devices influences cardiovascular function.

In a review published in HeartRhythm, Nikki Posnack, Ph.D., an assistant professor at the Children’s National Heart Institute, and Larisa Tereshchenko, M.D., Ph.D., FHRS, a researcher with the Knight Cardiovascular Institute at Oregon Health and Science University, establish a strong foundation for a running hypothesis: Replacing BPA- and DEHP- leaching plastics for alternative materials used to create medical devices may help patients on dialysis, and others with impaired immune function, live longer.

While Drs. Tereshchenko and Posnack note clinical studies and randomized controlled trials are needed to test this theory, they gather a compelling argument by examining the impact exposure to chemicals from plastics used in dialysis have on a patient’s short- and long-term health outcomes, including sudden cardiac death (SCD).

“As our society modifies our exposure to plastics to mitigate health risks, we should think about overexposure to plastics in a medical setting,” says Posnack. “The purpose of the review in HeartRhythm is to gather data about the impact chemical compounds, leached from plastic devices, have on cardiovascular outcomes for patients spending prolonged periods of time in the hospital.”

In this review, the authors explore chemical risk exposures in a medical setting, starting with factors that influence sudden cardiac death (SCD) among dialysis patients.

Why study dialysis patients?

SCD in dialysis patients accounts for one-third of deaths in this population. This prompts a need to develop prevention strategies, especially among patients with end-stage renal disease (ESRD).

The highest mortality rate observed among dialysis patients is during the first year of hemodialysis, a dialysis process that requires a machine to take the place of the kidneys and remove waste from the bloodstream and replenish it with minerals, such as potassium, sodium and calcium. During this year, mortality during hemodialysis is observed more frequently during the first three months of treatment, especially among older patients.

Possible reasons for an increased risk of an earlier death include chemical exposure, which is casually associated with altered cardiac function, as well as genetic risks for irregular heart rhythms and heart failure. In the HeartRhythm review, Drs. Tereshchenko and Posnack analyze factors that influence mortality:

Hemodialysis treatment, dialysis, is associated with plastic chemical exposure

Drs. Tereshchenko and Posnack note that dialysis tubing and catheters are commonly manufactured using polyvinyl chloride (PVC) polymers. The phthalate plastics used to soften PVC can easily leech if exposed to lipid-like substances, like blood. Research shows phthalate chemical concentrations increase during a four-hour dialysis.

Di(2-ethylhexyl) phthalate (DEHP) is a common plastic used to manufacture dialysis tubes, thanks to its structure and economy.

Bisphenol-A (BPA) is another common material used in medical device manufacturing. From the membranes of medical tools to resins, or external coatings and adhesives, BPA leaves behind a chemical residue on PVC medical devices.

In reviewing the research, the authors find dialysis patients are often exposed to high levels of DEHP and BPA. The amount of exposure to these chemicals varies in regards to room temperature, time of contact, other circuit coatings and the flow rate of dialysis. A faster flow rate correlates with reductions in chemical leaching and lower mortality rates.

Plastic chemical exposure is casually associated with altered cardiac function

Drs. Tereshchenko and Posnack note a causal relationship already exists between chemicals absorbed from plastics and cardiovascular outcomes.

Dr. Posnack’s previous research found BPA concentrations impaired electrical conduction in neonatal cardiomyocytes – young, developing heart cells – potentially altering the heart’s normal rhythm and function.

To the best of their knowledge, no clinical research has been conducted on DEHP exposure and SCD. However, proof-of-concept models find in vivo phthalate exposure alters autonomic regulation, which can slow down natural heart-rate rhythm and create a lag in recovery time to stressful stimuli. For humans, this type of stressful stimulation would be equivalent to recovering from a bike ride, car accident, or in this case, ongoing dialysis treatment with impaired immune function.

In other models, BPA exposure has been shown to cause bradycardia, or a delayed heart rate. In excised whole heart models, BPA has also been shown to alter cardiac electrical activity.

Abnormal electrophysiological substrate in end-stage renal disease

Since the heart and kidneys work in tandem to transport blood throughout the body, and manage vital functions, such as our heart rate, blood flow and breathing, the authors cite additional factors that lead to ongoing heart and kidney problems, with a look at end-stage renal disease (ESRD).

General heart-function kidney risks include abnormal electrophysiological (EP) substrate, the underlying electrical activity of the cardiac tissue, and genetic risk factors, including the TBX3 gene, a gene associated with a unique positioning of the heart and SCD.

“We don’t want to cite alarm about having a medical procedure or about relying on external help, such as dialysis, for proper kidney function,” says Posnack. “Especially since dialysis is a life-saving medical intervention for patients with inadequate kidney function.”

Pre-existing abnormal EP substrate interacts with plastic chemical exposure in incident dialysis, which increases risk of SCD in genetically predisposed ESRD patients

To summarize their findings, Drs. Tereshchenko and Posnack list a handful of support areas, starting with observations about reductions in cardiovascular mortality and SCD following kidney transplants. They note hemodialysis catheters are associated with larger DEHP exposure and a higher risk of SCD, compared to arteriovenous fistulas, highways surgically created to connect blood from the artery to the vein.

Drs. Posnack and Tereshchenko also note a correlative observation about higher SCD rates observed six hours after hemodialysis, when peak levels of DEHP and BPA are circulating in the bloodstream.

To compare and control for these factors among dialysis patients, the researchers cite different mortality patterns with hemodialysis and peritoneal dialysis. Patients on hemodialysis experience higher mortality during the first year of treatment, compared to peritoneal dialysis, who have higher mortality rates after the second year of treatment. Hemodialysis relies on a machine to take the place of kidney function, while peritoneal dialysis relies on a catheter, a small tube surgically inserted into the stomach.

“Our goal is to build on our previous research findings by analyzing variables that have yet to be studied before, and to update the field of medicine in the process,” says Dr. Posnack. “This includes investigating the cardiovascular risks of using BPA- and DEHP-materials to construct medical devices. Ultimately, we hope to determine whether plastic materials contribute to cardiovascular risks, and investigate whether patients might benefit from the use of alternative materials for medical devices.

Drs. Tereshchenko and Posnack note that despite the associations between chemical exposure from medical devices and increased cardiovascular risks, there are no restrictions in the United States on the use of phthalates and BPA chemicals used to manufacture medical devices.

Their future research will explore how replacing BPA- and DEHP-leaching plastics influence mortality and morbidity rates of ESRD patients on dialysis, as well as other patients exposed to repeat chemical exposure, such as patients having cardiac surgery.

“We want to make sure we identify and then work to minimize any potential risks of plastic exposure in a medical setting,” adds Dr. Posnack. “Our goal is to put the health and safety of patients first.”

Dr. Posnack’s research is funded by two grants (R01HL139472, R00ES023477) from the National Institutes of Health.

Tory Peitz and Victoria Catalano

Making weight: Ensuring that micro preemies gain pounds and inches

Tory Peitz and Victoria Catalano

Tory Peitz, R.N., (left) and Victoria Catalano, RDN, LD, CNSC, CLC, (right) Pediatric Dietitian Specialist in the Neonatal Intensive Care Unit at Children’s National Health System, measure the length of a micro preemie who weighed 1.5 pounds at birth.

A quality-improvement project to standardize feeding practices for micro preemies – preterm infants born months before their due date –  helped to boost their weight and nearly quadrupled the frequency of lactation consultations ordered in the neonatal intensive care unit (NICU), a multidisciplinary team from Children’s National Health System finds.

According to the Centers for Disease Control and Prevention, about 1 in 10 infants in 2016 was preterm, born prior to completing 37 gestational weeks of pregnancy. Micro preemies are the tiniest infants in that group, weighing less than 1,500 grams and born well before their brain, lungs and organs like the liver are fully developed.

As staff reviewed charts for very low birth weight preterm infants admitted to Children’s NICU, they found dramatic variation in nutritional practices among clinicians and a mean decline in delta weight Z-scores, a more sensitive way to monitor infants’ weight gain along growth percentiles for their gestational age. A multidisciplinary team that included dietitians, nurses, neonatologists, a lactation consultant and a quality-improvement leader evaluated nutrition practices and determined key drivers for improving nutrition status.

“We tested a variety of strategies, including standardizing feeding practices; maximizing intended delivery of feeds; tracking adequacy of calorie, protein and micronutrient intake; and maximizing use of the mother’s own breast milk,” says Michelande Ridoré, MS, a Children’s NICU quality-improvement lead who will present the group’s findings during the Virginia Neonatal Nutrition Association conference this fall. “We took nothing for granted: We reeducated everyone in the NICU about the importance of the standardized feeding protocol. We shared information about whether infants were attaining growth targets during daily rounds. And we used an infographic to help nursing moms increase the available supply of breastmilk,” Ridoré says.

On top of other challenges, very low birth weight preterm infants are born very lean, with minimal muscle. During the third trimester, pregnant women pass on a host of essential nutrients and proteins to help satisfy the needs of the fetus’ developing muscles, bones and brain. “Because preterm infants miss out on that period in utero, we add fortification to provide preemies with extra protein, phosphorus, calcium and zinc they otherwise would have received from mom in the womb,” says Victoria Catalano, RDN, LD, CNSC, CLC, a pediatric clinical dietitian in Children’s NICU and study co-author. Babies’ linear growth is closely related to neurocognitive development, Catalano says. A dedicated R.N.  is assigned to length boards for Children’s highest-risk newborns to ensure consistency in measurements.

Infants who were admitted within the first seven days of life and weighed less than 1,500 grams were included in the study. At the beginning of the quality-improvement project, the infants’ mean delta Z-score for weight was -1.8. By December 2018, that had improved to -1.3. And the number of lactation consultation ordered weekly increased from 1.1 to four.

“We saw marked improvement in micro preemies’ nutritional status as we reduced the degree of variation in nutrition practices,” says Mary Revenis, M.D., NICU medical lead on nutrition and senior author for the research. “Our goal was to increase mean delta Z-scores even more. To that end, we will continue to test other key drivers for improved weight gain, including zinc supplementation, updating infants’ growth trajectories in the electronic medical record and advocating for expanded use of birth mothers’ breast milk,” Dr. Revenis says.

In addition to Ridoré, Catalano and Dr. Revenis, study co-authors include Caitlin Forsythe MS, BSN, RNC-NIC, lead author; Rebecca Vander Veer RD, LD, CNSC, CLC, pediatric dietitian specialist; Erin Fauer RDN, LD, CNSC, CLC, pediatric dietitian specialist; Judith Campbell, RN, IBCLC, NICU lactation consultant; Eresha Bluth MHA; Anna Penn M.D., Ph.D., neonatalogist; and Lamia Soghier M.D., Med., NICU medical unit director.

Graph showing magnesium reduces arrhythmia risk

Magnesium helps prevent postsurgical arrhythmias in pediatric patients

Graph showing magnesium reduces arrhythmia risk

Magnesium (Mg) helps reduce arrhythmias, irregular heart rhythms, in adults. It also helps alleviate the symptoms of postoperative atrial fibrillation, or AFib, which can lead to blood clots, stroke and heart failure. Can it help prevent postsurgical arrhythmias in pediatric patients with congenital heart disease?

New research from Children’s National Health System finds a 25- or 50-mg dose of Mg used during congenital heart surgery (CHS) helps prevent arrhythmias, especially junctional ectopic tachycardia (JET) and atrial tachycardia (AT), common arrhythmias following CHS, according to a study published in the August 2018 edition of The Journal of Thoracic and Cardiovascular Surgery.

To reach this conclusion, the researchers separated 1,871 CHS patients from Children’s National into three groups: a control group of 750 patients who had surgery without Mg, a group of 338 patients receiving a 25-mg /kg dose of Mg during surgery and a group of 783 patients receiving a 50-mg/kg dose of Mg during surgery. The data looked at CHS cases over eight years, from 2005 to 2013, to determine if Mg administration during surgery alleviates postoperative arrhythmias and if the amount, measured by a 25- or 50-mg/kg dose, makes a difference.

“This study, the first conducted in pediatric patients, finds administering magnesium during congenital heart surgery reduces the likelihood of postsurgical arrhythmias,” says Charles Berul, M.D., a study author and the chief of cardiology at Children’s National. “We don’t detect a dose-dependent relationship, which means a small or larger amount of magnesium is equally effective at preventing arrhythmias following surgery.”

The researchers found that up to one-third of CHS patients experience postoperative arrhythmias, with JET and AT accounting for more than two-thirds of arrhythmias following CHS. They note that despite the administration of Mg during surgery, there continues to be a high incidence of postoperative arrhythmias – affecting 18 percent or about one in five CHS patients.

“We hope this study guides future research to see if adding new or additional agents to magnesium eliminates, or further reduces, postoperative arrhythmias,” notes Dr. Berul. “For now, we’re happy to find an algorithm to put into practice and to share with other medical centers, as a way to help pediatric patients recover from congenital heart surgery—stronger, faster and with a reduced risk of complications.”

The researchers note that postoperative arrhythmias impact the recovery period of CHS, increase the duration of intubation and CICU stay and prolong hospital stay.

Emergency Department Check in

Missed opportunities for STI screening in the ED

Emergency Department Check in

Researchers found that even though young women with pelvic inflammatory disease (PID) are at increased risk for also being infected with syphilis and human immunodeficiency virus (HIV), few adolescent females diagnosed with PID in U.S. pediatric emergency departments (ED) undergo laboratory tests for HIV or syphilis.

Sexually transmitted infections (STIs) are on the rise in the U.S., reaching unprecedented highs in recent years for the three most common STIs reported in the nation: chlamydia, gonorrhea and syphilis. Nearly half of the 20 million new STI cases each year are in adolescents aged 15 to 24, according to the Department of Health & Human Services. In particular, about two in five sexually active teen girls has an STI.

These infections can be far more than an embarrassing nuisance; some can cause lifelong infertility. According to the Centers for Disease Control and Prevention, undiagnosed STIs cause infertility in more than 20,000 women each year.

A new retrospective cohort study led by researchers at Children’s National Health System and published online July 24, 2018, in Pediatrics shines a stark spotlight on missed opportunities for diagnosis. Researchers found that even though young women with pelvic inflammatory disease (PID) are at increased risk for also being infected with syphilis and human immunodeficiency virus (HIV), few adolescent females diagnosed with PID in U.S. pediatric emergency departments (ED) undergo laboratory tests for HIV or syphilis.

A team of Children’s researchers reviewed de-identified data from the Pediatric Health Information System, a database that aggregates encounter-level data from 48 children’s hospitals across the nation. From 2010 through 2015, there were 10,698 diagnosed cases of PID among young women aged 12 to 21. Although HIV and syphilis screening rates increased over the study period, just 27.7 percent of these women underwent syphilis screening, 22 percent were screened for HIV, and only 18.4 percent underwent lab testing for both HIV and syphilis.

Screening rates varied dramatically by hospital, with some facilities screening just 2 percent of high-risk young women while others tested more than 60 percent.

HIV screening was more likely to occur among:

  • Women admitted to the hospital, compared with those discharged from the ED (adjusted odds ratio [aOR] of 7.0)
  • Uninsured women, compared with women with private insurance (1.6 aOR)
  • Non-Latino African American women, compared with non-Latino white women (1.4 aOR)
  • Women seen at small hospitals with fewer than 300 beds (1.4 aOR)
  • Women with public insurance compared with women with private insurance (1.3 aOR)
  • 12-year-olds to 16-year-olds, compared with older adolescents (1.2 aOR)

Syphilis screening was more likely to occur for:

  • Women admitted to the hospital (4.6 aOR)
  • Non-Latino African American women (1.8 aOR)
  • Uninsured women (1.6 aOR)
  • Women with public insurance (1.4 aOR)
  • 12-year-olds to 16-year-olds (1.1 aOR)

“We know that 20 percent of the nearly 1 million cases of PID that are diagnosed each year occur in young women, with the majority of diagnoses made in EDs. It is encouraging that HIV and syphilis screening rates for women with PID increased over the study period. However, our findings point to missed opportunities to safeguard young women’s reproductive health,” says Monika K. Goyal, M.D., M.S.C.E., assistant professor of Pediatrics and Emergency Medicine and the study’s senior author. “Such discrepancies in screening across the 48 hospitals we studied underscore the need for a standardized approach to sexually transmitted infection (STI) screening.”

Untreated STIs can cause PID, an infection of a woman’s reproductive organs that can complicate her ability to get pregnant and also can cause infertility. Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended that all women diagnosed with PID be tested for HIV. The CDC’s treatment guidelines also recommend screening people at high risk for syphilis.

“Syphilis infection rates have steadily increased each year, and it is now most prevalent among young adults,” Dr. Goyal says. “Future research should examine how STI screening can be improved in emergency departments, especially since adolescents at high risk for STIs often access health care through EDs. We also should explore innovative approaches, including electronic alerts and shared decision-making to boost STI screening rates for young women.”

In addition to Dr. Goyal, Children’s study co-authors include Lead Author, Amanda Jichlinski, M.D.; and co-authors, Gia Badolato, M.P.H., and William Pastor, M.A., M.P.H.

Research reported in this news release was supported by the National Institute of Child Health and Human Development under K23 award number HD070910.

Lamia Soghier and Billie Lou Short

The ‘secret sauce’ for high-performing NICUs

Lamia Soghier and Billie Lou Short

Quoting the literature, Lamia Soghier, M.D., Children’s NICU medical unit director, and Billie Lou Short, M.D., chief of Children’s Division of Neonatology, write that hospitals with strong performance-improvement programs share eight critical factors in common.

Leaders of neonatal intensive care units (NICUs) across the nation share the same play books as they strive to provide safe, high-quality medical and surgical care for vulnerable newborns. A growing number of quality collaborations share best practices and evidence-based guidelines across the nation in the hopes of replicating quality and safety success stories while minimizing harms.

Still, NICUs that use similar interventions in similar fashions often do not achieve identical results.

“This unexplained variability in outcomes between NICUs begs the question: What is the secret sauce? Why do some NICUs consistently outshine others in spite of the application of the same ‘potentially best practices,’ ” the leaders of Children’s award-winning NICU ask in an editorial published online July 12, 2018, by Archives of Disease in Childhood (ADC) – Fetal & Neonatal edition.

Quoting the literature, Lamia Soghier, M.D., Children’s NICU medical unit director, and Billie Lou Short, M.D., chief of Children’s Division of Neonatology, write that hospitals with strong performance-improvement programs share eight critical factors in common:

  • Strong performance-improvement leadership at the administrative and executive levels
  • Boards of Trustees who are actively involved and provide continuity in vision regardless of changes in senior hospital leadership
  • An effective oversight structure that avoids duplicating efforts
  • Expert performance-improvement staff who are trained in quality and safety and able to carry out projects successfully
  • Physicians who are involved and held accountable
  • Staff who are actively involved
  • Effective use of data in decision-making
  • Effective communication strategies for all stakeholders

The “‘secret sauce’ may lie in establishing systems that promote the culture of quality and safety rather than waiting for a reduction in morbidity,” write Drs. Soghier and Short.

For the second year running, Children’s neonatology division ranked No. 1 among NICUs ranked by U.S. News & World Report. Despite challenges inherent in being a “busy level IV NICU in a free-standing children’s hospital with a rapidly growing capacity, higher levels of complex patients, [the] presence of trainees on rounds and routine 3:1 and 2:1 staffing models,” Children’s NICU has continued to have the lowest rates of such objective quality measures as central line-associated bloodstream infections and unintended extubations, they write.

“We attribute our success to direct involvement of all levels of leadership in our unit in [performance improvement] PI initiatives, a dedicated local PI team, quality trained medical unit director, engagement of front-line staff in PI, the presence of local subject-matter experts, multidisciplinary diverse team both within the NICU and with other departments that bring an array of experiences and opinions and a supportive data infrastructure through local information technology, and use of the Children’s Hospital Neonatal Database that allows benchmarking to other non-delivery NICUs, Drs. Soghier and Short write. “Our team finds motivation in solving local issues routine in our work, and leadership prioritises these issues and promotes engagement of front-line staff.”

The commentary was a companion to “Using a Composite Morbidity Score and Cultural Survey to Explore Characteristics of High Proficiency Neonatal Intensive Care Units,” also published by ADC Fetal & Neonatal.

Making the grade: Children’s National is nation’s Top 5 children’s hospital

Children’s National rose in rankings to become the nation’s Top 5 children’s hospital according to the 2018-19 Best Children’s Hospitals Honor Roll released June 26, 2018, by U.S. News & World Report. Additionally, for the second straight year, Children’s Neonatology division led by Billie Lou Short, M.D., ranked No. 1 among 50 neonatal intensive care units ranked across the nation.

Children’s National also ranked in the Top 10 in six additional services:

For the eighth year running, Children’s National ranked in all 10 specialty services, which underscores its unwavering commitment to excellence, continuous quality improvement and unmatched pediatric expertise throughout the organization.

“It’s a distinct honor for Children’s physicians, nurses and employees to be recognized as the nation’s Top 5 pediatric hospital. Children’s National provides the nation’s best care for kids and our dedicated physicians, neonatologists, surgeons, neuroscientists and other specialists, nurses and other clinical support teams are the reason why,” says Kurt Newman, M.D., Children’s President and CEO. “All of the Children’s staff is committed to ensuring that our kids and families enjoy the very best health outcomes today and for the rest of their lives.”

The excellence of Children’s care is made possible by our research insights and clinical innovations. In addition to being named to the U.S. News Honor Roll, a distinction awarded to just 10 children’s centers around the nation, Children’s National is a two-time Magnet® designated hospital for excellence in nursing and is a Leapfrog Group Top Hospital. Children’s ranks seventh among pediatric hospitals in funding from the National Institutes of Health, with a combined $40 million in direct and indirect funding, and transfers the latest research insights from the bench to patients’ bedsides.

“The 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver exceptional care across a range of specialties and deserve to be highlighted,” says Ben Harder, chief of health analysis at U.S. News. “Day after day, these hospitals provide state-of-the-art medical expertise to children with complex conditions. Their U.S. News’ rankings reflect their commitment to providing high-quality care.”

The 12th annual rankings recognize the top 50 pediatric facilities across the U.S. in 10 pediatric specialties: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology. Hospitals received points for being ranked in a specialty, and higher-ranking hospitals receive more points. The Best Children’s Hospitals Honor Roll recognizes the 10 hospitals that received the most points overall.

This year’s rankings will be published in the U.S. News & World Report’s “Best Hospitals 2019” guidebook, available for purchase in late September.

child in wheelchair with mom

Potential to replace race as a risk factor for kidney-transplant failure

child in wheelchair with mom

Right now, more than 100,000 adult and pediatric patients in the U.S. are waiting for a life-saving kidney donation. Thirteen of them die each day while awaiting a transplant. However, a significant portion of kidneys from deceased donors are discarded because they literally don’t make the grade – a scoring system known as the kidney donor profile index (KDPI) that aims to predict how long a donor kidney will last in an intended recipient based on a variety of factors, including the donor’s age, size and health history.

Ethnicity and race are also part of that scoring system, explains Marva Moxey-Mims, M.D., FASN, chief of the Division of Nephrology at Children’s National Health System. That’s partly because research over the years has suggested that kidneys from certain racial groups, including African-Americans, may not have the same longevity as those from other groups.

But race might not be the right marker to consider, Dr. Moxey-Mims counters. More recent studies have shown that a particular gene known as APOL1 might better predict risk of kidney-transplant failure. APOL1 high-risk variants are associated with a wide range of kidney diseases, with retrospective studies suggesting that they could be a key cause of failure in some donated kidneys. Although this gene is found almost exclusively in people of recent African descent, only about 13 percent of that population has high-risk APOL1 variants that might cause kidney problems.

“Instead of putting all African-American donor kidneys in one proverbial ‘bucket,’ we might be able to use this gene to determine if they truly carry a higher risk of early failure,” Dr. Moxey-Mims says.

To more definitively confirm whether this gene could be used as a proxy for heightened kidney-failure risk, Dr. Moxey-Mims and colleagues across the country are participating in the APOL1 Long-Term Kidney Transplantation Outcomes Network (APOLLO) study, she and Dr. Barry Freedman explain in a perspective published online April 27, 2018, in Clinical Journal of the American Society of Nephrology. The APOLLO study will tap people accessing the hundreds of transplant centers scattered across the nation, prospectively genotyping deceased and living African-American kidney donors as well as kidney-transplant recipients to assess whether they carry high-risk APOL1 gene variants. Living donors and transplant recipients will be followed for years to gauge how their kidneys fare over time.

The researchers, Dr. Moxey-Mims explains, hope to answer whether the APOL1 high-risk gene variants in donor kidneys could replace race as a risk factor when calculating the KDPI score and whether recipients’ own APOL1 gene variants impact transplant failure risk. They also hope to better understand the risk to living donors. “If a living donor has an increased risk of kidney failure,” she adds, “he or she can make a more educated decision about whether to donate a kidney.”

Dr. Moxey-Mims plays a pivotal role as the chair of the study’s steering committee, a group made up of the study’s principal investigators at all 13 clinical sites and the Data Coordinating Center, as well as the program officials from the National Institutes of Health funding institutes (National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, and National Institute on Minority Health and Health Disparities). She will play a key part in helping to ensure that the study stays on track with recruitment goals, as well as publicizing the study at national meetings.

The study also includes a Community Advisory Council, a group made up of stakeholders in this study: 26 African-Americans who either have donated a kidney, received a kidney donation, are on dialysis awaiting a kidney transplant, or have a close relative in one of those categories. This group has helped to steer the study design in multiple ways, Dr. Moxey-Mims explains. For example, they have worked with study leaders to simplify the language on consent forms, helped to delineate which data study participants might want to receive when the study is completed, and helped to publicize the study in their communities by giving talks at churches and other venues.

Eventually, Dr. Moxey-Mims says APOLLO study researchers hope that clarifying the role of the APOL1 gene in kidney-transplant failure could lead to fewer discarded kidneys, which could boost the number of available kidneys for patients awaiting transplants.

“Down the road, the pool of patients awaiting transplant might have access to more kidneys because available organs aren’t getting a bad score simply because the donor is African-American,” she says. “We hope this might shorten the wait for some patients and their families who are desperate to get that call that a kidney is finally available.”

Financial support for research reported in the post was provided by the National Institutes of Health under grant numbers R01 DK084149, R01 DK070941 and U01 DK116041.

An-Massaro

Keeping an eye on autonomic function for infants with HIE

An-Massaro

“By including heart rate variability measurements and other markers of autonomic function in our current predictive armamentarium,” says An Massaro, M.D., “we may be able to offer new hope for infants with HIE.”

In about two to three in every 1,000 full-term births, babies develop a neurological condition called hypoxic ischemic encephalopathy (HIE) when their brains receive insufficient oxygen. HIE can be a devastating condition, leading to severe developmental or cognitive delays or motor impairments that become more evident as the child grows older. Despite improvements in care – including therapeutic hypothermia, a whole-body cooling method administered shortly after birth that can slow brain damage – about half of children with this condition die from neurological complications by age 2.

Finding ways to identify children with the most severe HIE could help researchers focus their efforts and provide even more intense neuroprotective care, explains An Massaro, M.D., a neonatologist at Children’s National Health System. But thus far, it’s been unclear which symptoms reflect the extent of HIE-induced brain damage.

That’s why Dr. Massaro and colleagues embarked on a study published in the May 2018 issue of Journal of Pediatrics. The team sought to determine whether dysfunction of the autonomic nervous system (ANS) – the auto-pilot part of the nervous system responsible for unconscious bodily functions, such as breathing and digestion – reflected in routine care events can be used as a marker for brain injury severity.

The researchers collected data from 25 infants who were treated for HIE with therapeutic hypothermia at Children’s National. Thanks to multi-modal monitoring, these babies’ medical records hold a treasure trove of information, explains Rathinaswamy B. Govindan, Ph.D., a staff scientist in Children’s Advanced Physiological Signals Processing Lab.

In addition to including continuous heart rate tracings and blood pressure readings that are standard for many infants in the neonatal intensive care unit (NICU), they also recorded cerebral near infrared spectroscopy, a monitor that measures brain tissue oxygen levels. The investigators performed detailed analyses to evaluate how these monitor readings change in response to a variety of routine care events, such as diaper changes, heel sticks, endotracheal tube manipulations and pupil examinations.

The researchers stratified these infants based on how dysfunctional their ANS behaved by using heart rate variability as a marker: The fewer natural fluctuations in heart rate, the more damaged their ANS was thought to be. And they also used non-invasive brain magnetic resonance imaging (MRI) to determine brain damage. They then compared this information with the babies’ physiological responses during each care event.

Their findings show that infants with impaired ANS, based on depressed heart rate variability before the care event, had significantly different responses to these care events compared with babies with intact ANS.

  • For stimulating interventions, such as diaper changes and heel sticks, both heart rate and blood pressure increased in babies with intact ANS but decreased in babies with impaired ones.
  • Shining a light in their pupils led to an expected decreased heart rate with stable blood pressure in ANS-intact infants, but in ANS-impaired infants, there was no responsive change in heart rate and, additionally, a decrease in blood pressure was observed.
  • Responses were similar between the two groups during breathing tube manipulations, except for a slight increase in heart rate a few minutes later in the ANS-impaired group.

These results, Govindan explains, suggest that a real-time, continuous way to assess ANS function may offer insights into the expected physiological response for a given infant during routine NICU care.

“This is exactly the type of additional information that intensivists need to pinpoint infants who may benefit from additional neuroprotective support,” he says. “Right now, it is standard practice to monitor brain activity continuously using electroencephalogram and to check the status of the brain using MRI to assess the response to therapeutic cooling. Neither of these assessments can be readily used by neonatologists at the bedside in real-time to make clinical decisions.”

Assessing ANS function in real-time can help guide neuroprotective care in high-risk newborns by providing insight into the evolving nature of brain damage in these infants, Dr. Massaro adds.

Beyond simply serving as a biomarker into brain injury, poor ANS function also could contribute to the development of secondary injury in newborns with HIE by stymieing the normal changes in heart rate and blood pressure that help oxygenate and heal injured brains. The researchers found that the cumulative duration of autonomic impairment was significantly correlated with the severity of brain injury visible by MRI in this group of infants.

“By including heart rate variability measurements and other markers of autonomic function in our current predictive armamentarium,” says Dr. Massaro, “we may be able to offer new hope for infants with HIE.”

In addition to Dr. Massaro, the Senior Author, study co-authors include Lead Author, Heather Campbell, M.D.; Rathinaswamy B. Govindan, Ph.D., Children’s Advanced Physiological Signals Processing Lab; Srinivas Kota, Ph.D.; Tareq Al-Shargabi, M.S.; Marina Metzler, B.S.; Nickie Andescavage, M.D., Children’s neonatalogist; Taeun Chang, M.D., Children’s neonatal and fetal neurologist; L. Gilbert Vezina, M.D., attending in Children’s Division of Diagnostic Imaging and Radiology; and Adré J. du Plessis, M.B.Ch.B., M.P.H., chief of Children’s Division of Fetal and Transitional Medicine.

This research was supported by the Clinical and Translational Science Institute at Children’s National under awards UL1TR000075 and 1KL2RR031987-01 and the Intellectual and Developmental Disabilities Research Consortium within the National Institutes of Health under award P30HD040677.

Baby in the NICU

Getting to the heart of cardiac output

Baby in the NICU

To keep infants in the neonatal intensive care unit (NICU) as healthy as possible, it’s important to keep close tabs on their vital signs. During their NICU stay, most babies have continuous monitoring of their blood pressure, respiratory rate and blood oxygen saturation. And although continuous monitoring of heart rate is also typically standard, other information about heart function – such as cardiac output, a measure of how well the heart is pumping blood – remains a challenge to obtain in these vulnerable babies.

Clinical markers like blood pressure, heart rate and urine output are available, but they are indirect measures of cardiac output, how much blood the heart pumps per minute. Less invasive techniques, such as Doppler ultrasound, can be imprecise. Respiratory mass spectrometry or catheterization would provide more precision by directly calculating cardiac output but carry risks or are not feasible for neonates.

Clinicians at Children’s National Health System hypothesized that COstatus monitors could offer a way to directly measure cardiac output among neonates. The COstatus monitor – a minimally invasive way to measure hemodynamics – captures cardiac output, total end diastolic volume, active circulation volume and central blood volume.

The research team tested the approach by leveraging ultrasound dilution: Injecting saline, which has an ultrasound velocity of 1533m/second, slows the ultrasound velocity of blood from its normal rate of 1580m/second and produces a dilution curve.

“It is feasible to directly measure neonatal cardiac output by ultrasound dilution via the COstatus monitor in the first two weeks of life with no adverse events,” says Khodayar Rais-Bahrami, M.D., a Children’s neonatologist and senior author for the research presented during the Pediatric Academic Societies 2018 annual meeting. “When we took consecutive measurements, we saw very little variance in the parameters.”

The COstatus monitor uses an extracorporeal loop that is connected to arterial and venous catheters. The 12 neonates included in the study already had umbilical venous catheters as well as either a peripheral arterial line or umbilical arterial catheter. The infants ranged in weight from 0.72 to 3.74 kg and were born at 24 to 41.3 gestational weeks.

The infants’ cardiac output was measured 54 times from 1 to 13 days of life. Up to two measurement sessions occurred daily for a maximum of four days. The mean cardiac output was 0.43 L/minute with a mean cardiac index of 197mL/kg/minute.

Future research will describe normal cardiac output ranges for neonates as well as how these measurements evolve during the first week of life.

In addition to Dr. Rais-Bahrami, study co-authors include Simranjeet S. Sran, M.D., and Mariam Said, M.D., a Children’s neonatologist.

Preemie Baby

Brain food for preemies

Preemie Baby

Babies born prematurely – before 37 weeks of pregnancy – often have a lot of catching up to do. Not just in size. Preterm infants typically lag behind their term peers in a variety of areas as they grow up, including motor development, behavior and school performance.

New research suggests one way to combat this problem. The study, led by Children’s researchers and presented during the Pediatric Academic Societies 2018 annual meeting, suggests that the volume of carbohydrates, proteins, lipids and calories consumed by very vulnerable premature infants significantly contributes to increased brain volume and white matter development, even though additional research is needed to determine specific nutritional approaches that best support these infants’ developing brains.

During the final weeks of pregnancy, the fetal brain undergoes an unprecedented growth spurt, dramatically increasing in volume as well as structural complexity as the fetus approaches full term.

One in 10 infants born in the U.S. in 2016 was born before 37 weeks of gestation, according to the Centers for Disease Control and Prevention. Within this group, very low birthweight preemies are at significant risk for growth failure and neurocognitive impairment. Nutritional support in the neonatal intensive care unit (NICU) helps to encourage optimal brain development among preterm infants. However, their brain growth rates still lag behind those seen in full-term newborns.

“Few studies have investigated the impact of early macronutrient and caloric intake on microstructural brain development in vulnerable preterm infants,” says Katherine Ottolini, lead author of the Children’s-led study. “Advanced quantitative magnetic resonance imaging (MRI) techniques may help to fill that data gap in order to better direct targeted interventions to newborns who are most in need.”

The research team at Children’s National Health System enrolled 69 infants who were born younger than 32 gestational weeks and weighed less than 1,500 grams. The infants’ mean birth weight was 970 grams and their mean gestational age at birth was 27.6 weeks.

The newborns underwent MRI at their term-equivalent age, 40 weeks gestation. Parametric maps were generated for fractional anisotropy in regions of the cerebrum and cerebellum for diffusion tensor imaging analyses, which measures brain connectivity and white matter tract integrity. The research team also tracked nutritional data: Grams per kilogram of carbohydrates, proteins, lipids and overall caloric intake.

“We found a significantly negative association between fractional anisotropy and cumulative macronutrient/caloric intake,” says Catherine Limperopoulos, Ph.D., director of Children’s Developing Brain Research Laboratory and senior author of the research. “Curiously, we also find significantly negative association between macronutrient/caloric intake and regional brain volume in the cortical and deep gray matter, cerebellum and brainstem.”

Because the nutritional support does contribute to cerebral volumes and white matter microstructural development in very vulnerable newborns, Limperopoulos says the significant negative associations seen in this study may reflect the longer period of time these infants relied on nutritional support in the NICU.

In addition to Ottolini and Limperopoulos, study co-authors include Nickie Andescavage, M.D., Attending, Children’s Neonatal-Perinatal Medicine; and Kushal Kapse.