Neonatology

Doctors working together to find treatments for autoimmune encephalitis

Children’s and Regeneron partner in exome sequencing study

Children’s National, in partnership with the Regeneron Genetics Center (RGC, a subsidiary of Regeneron Pharmaceuticals, Inc.), has announced the launch of a major three-year research study that will examine the links between undiagnosed disease and an individual’s genetic profile.

The program, directed by Children’s National Geneticist Carlos Ferreira Lopez, M.D., and coordinated by Genetic Counselor Lindsay Kehoe, hopes to include as many as 3,000 patients in its initial year and even greater numbers in the following two years.

During the course of the study, RGC will conduct whole exome sequencing (WES) to examine the entire protein-coding DNA in a patient’s genome. Children’s National geneticists will analyze and screen for certain findings that are known to be potentially causative or diagnostic of disease. Children’s National scientists and providers will confirm preliminary research findings in a lab certified for Clinical Laboratory Improvement Amendments (CLIA), per federal standards for clinical testing, and refer any confirmatory CLIA-certified cases to appropriate clinicians at Children’s National for further care.

According to Marshall Summar, M.D., Chief of Genetics and Metabolism at Children’s National, the WES study could finally provide patients and their families with the medical answers they have been looking for, allowing for treatment appropriate to their specific genetic condition.

Because pediatric diseases can often elude diagnosis, they can pose a number of detrimental effects to patients and their families, including treatment delays, multiple time- and cost-intensive tests, and stress from lingering uncertainty regarding the illness. With this genomic data, Regeneron will be able to utilize findings to continue its efforts to improve drug development.

Since its inception in 2014, the RGC has strategically partnered with leading medical institutions to utilize human genetics data to speed the development and discovery of new and improved therapies for patients in need.

Premature birth may alter critical cerebellar development linked to learning and language

Diffusion tensor imaging teases out subtle injury to cerebral and cerebellar white matter that is not evident with conventional MRI, allowing researchers to quantify brain tissue microstructure and classify white matter integrity.

Diffusion tensor imaging teases out subtle injury to cerebral and cerebellar white matter that is not evident with conventional MRI, allowing researchers to quantify brain tissue microstructure and classify white matter integrity.

Premature birth can interrupt a key period of brain development that occurs in the third trimester, which has the potential to impact a child’s long-term learning, language, and social skills. A recent case-control study published in The Journal of Pediatrics applied diffusion tensor magnetic resonance imaging (DTI) to zoom in on the microstructures comprising the critical cerebellar neural networks related to learning and language, and found significant differences between preterm and full-term newborns.

“The third trimester, during which many premature births occur, is typically when the developing cerebellum undergoes its most dramatic period of growth. Normally, the cerebellar white matter tracts that connect to the deep nuclei are rich in pathways where nerve fibers cross. Those connections permit information to flow from one part of the brain to another. It is possible that premature birth leads to aberrant development of these critical neural networks,” says Catherine Limperopoulos, Ph.D., director of the Developing Brain Research Laboratory at Children’s National Health System and senior study author.

One in 10 American babies is born prematurely. The brain injury that infants born prematurely experience is associated with a range of neurodevelopmental disabilities, including some whose influence isn’t apparent until years later, when the children begin school. Nearly half of extremely preterm infants go on to experience long-term learning, social, and behavioral impairments.

While conventional magnetic resonance imaging (MRI) can detect many brain abnormalities in newborns, a newer technique called DTI can tease out even subtle injury to cerebral and cerebellar white matter that is not evident with conventional MRI. White matter contains axons, which are nerve fibers that transmit messages. With DTI, researchers can quantify brain tissue microstructure and describe the integrity of white matter.

The research team compared imaging from 73 premature infants born before 32 weeks gestation who weighed less than 1,500 grams with 73 healthy newborns born to mothers who delivered at full term after 37 weeks. After the newborns had been fed, swaddled, and fitted with double ear protection, the imaging was performed as they slept. Nurses monitored their heart rates and oxygen saturation. Their brain abnormalities were scored as normal, mild, moderate, or severe.

All of the full-term newborns had normal brain MRIs as did 44 (60.3 percent) of the preemies.

The preemies had significantly higher fractional anisotropy in the cerebellum, the part of the brain that processes incoming information from elsewhere in the brain, permitting coordinated movement as well as modulating learning, language, and social skills. Alterations in cerebellar microarchitecture was associated with markers for illness severe enough to require surgery – such as correcting abnormal blood flow caused by the failure of the ductus arteriosus to close after birth and to remedy a bowel disease known as necrotizing enterocolitis. The risk factors also are associated with compromised cardiorespiratory function and low Apgar score at five minutes, Limperopoulos and co-authors write. The Apgar score is a quick way to gauge, one minute after birth, how well the newborn withstood the rigors of childbirth. It is repeated at five minutes to describe how the newborn is faring outside of the womb.

“In previous studies, we and others have associated cerebellar structural injury in preterm infants with long-term motor, cognitive, and socio-affective impairments. This is one of the first studies to provide a detailed report about these unexpected alterations in cerebellar microstructural organization,” she adds. “We postulate that the combination of premature birth and early exposure of the immature developing cerebellum to the extrauterine environment results in disturbed micro-organization.”

Additional research is warranted in larger groups of patients as well as long-term follow up of this cohort of newborns to determine whether this microstructural disorganization predicts long-term social, behavioral, and learning impairments.

“A large number of these prematurely born newborns had MRI readings in the normal range. Yet, we know that these children are uniquely at risk for developing neurodevelopmental disabilities later in life. With additional study, we hope to identify interventions that could lower those risks,” Limperopoulos says.

Related resources: The Journal of Pediatrics editorial

Children’s National NICU reduces chest x-rays, unintended extubations

nicu-reduces-xrays

Children’s National is taking the lead in safety and quality improvement by initiating two protocols in its neonatal intensive care unit (NICU) aimed at reducing chest X-rays and unintended extubations (UE). Through these efforts, the Neonatology and Radiology divisions have decreased the X-ray radiation dose levels to as low as reasonably achievable (ALARA), reduced the number of unintended extubations, and found significant cost-savings. Notably, the Children’s National team was awarded an Honorable Mention for their abstract submission on UE efforts at the Children’s Hospitals Neonatal Consortium Quality Symposium in September.

Evaluating effectiveness of the chest x-ray

Chest X-rays in the NICU are one of the top five unnecessary tests, according to the American Academy of Pediatrics. While they may be used to help with procedures, such as verifying placement of endotracheal tubes (ETT) and central venous catheters, they don’t increase efficacy or safety, and they have been found to increase the use of hospital resources.

There were concerns of an increased incidence of UEs and potential excess radiation exposure, and that’s when the NICU team at Children’s National developed a new protocol. It restricted the use of routine chest X-rays used to confirm ETT placement for all stable intubated patients.

Chest X-rays are now performed twice a week, instead of daily, or following a change in status, for stable ventilated patients. The team realized that daily chest X-rays might not be needed and that reducing their frequency would also decrease the likelihood of patients self-extubating during the procedure. Dropping the additional procedures was believed to be non-disruptive.

To measure the effectiveness of the new protocol, the team used Trendstar billing data to track the number of single chest X-rays for all NICU patients per patient day. It also used that data to show the total net charge for a single chest X-ray.

Taking measures to decrease unintended extubations

Unintended extubations are the fourth most common event in the NICU and are associated with hypoxia, ventilator-associated pneumonia, intraventricular hemorrhage, code events, and increased length of stay. In fact, UEs almost double the length of stay versus patients who do not experience UEs, and the cost of care increases by $34,000 per patient.

Realizing these detrimental effects, the Children’s NICU team launched a quality improvement project to reduce UE rates from a median of 0.6 events to less than 0.3 events per 100 vent days, and in turn its associated complications, by December 2016.

To accomplish this, the staff and stakeholders formed the Stop UNintended Extubations (SUN) Team to address key drivers such as consistent taping and re-taping practices, appropriate sedation of patients, standardizing practices around moving intubated patients, and more. The team designed and tested a UE Rick Scale to assess the likelihood of extubation, and each key driver was assigned several actionable interventions for high-risk patients to escalate and address cases prior to potential UE events. Interventions included team safety huddles and debriefs, risk reports, staff education, tube placement corrections, and taping standards among others.

The outcomes

The new X-ray protocol reduced the rate of chest X-rays and showed a 27 percent cost-savings for babies with longer NICU stays. The change also decreased the patient radiation doses to ALARA. The team will continue to track the data as it will review the rates again in December 2016.

The UE quality initiative calculated UE rates based on the number of total ventilator days less the number of tracheostomy days. Within a month of starting the project, the unintended extubation rate decreased from 1.18 to .59 events per 100 vent days. Within five months, the NICU reached its lowest rate below their benchmark median at 0.41 events per 100 vent days, and the number of days between events increased from a high of days prior to the project to a high of 33 days. The team continues to test the UE Risk Scale in order to validate it for external use.

ECMO

Children’s National gains international recognition for lifesaving ECMO treatment

ecmo

In 1984, Children’s National Health System became the first stand-alone children’s hospital to offer Extracorporeal Membrane Oxygenation (ECMO), one of the most advanced forms of life support for patients experiencing acute failure of the cardio-respiratory system. This year, for the fourth time, Children’s National received the “Excellence in Extracorporeal Life Support Award” from the Extracorporeal Life Support Organization (ELSO), an international consortium of centers offering ECMO.

The Excellence in Extracorporeal Life Support Award, started in 2006, recognizes centers that demonstrate an exceptional commitment to evidence-based processes and quality measures, staff training and continuing education, patient satisfaction, and ongoing clinical research.

ECMO allows time for the patient’s lungs or heart to heal by using a heart-lung machine to oxygenate and remove carbon dioxide outside the body over a period of time.

ECMO at Children’s National

Children’s National houses one of the only ECMO programs in the Washington, DC, area. At Children’s, the ECMO program is in the division of Neonatology but closely connected to the Advanced Cardiac Therapies and Heart Transplant Program and the team using Ventricular Assist Devices (VADs) in children. At the time of the interview for this article, the ECMO and VAD Program Manager, Gary Oldenburg, MS, RRT-NPS, said there were currently three ECMO patients and one VAD patient admitted to Children’s.

Oldenburg attributes the success of the program to the quality of patient care, favorable outcomes compared with like-institutions, competency in ECMO training and specialist education, as well as experts in the field who contribute back to the profession of ECMO.

One expert, Billie Lou Short, M.D., Chief of Neonatology at Children’s National, is a pioneer in the use of ECMO for newborns, has been involved with ECMO since its inception, and started the program at Children’s. Oldenburg is on the steering committee with ELSO and also is involved with the Education and Logistics Committee within ELSO.

Also on the team, there are two groups of respiratory therapists and nurses who have specialized training in ECMO, one that is exclusively working with ECMO patients and another that is part-time, borrowed from their home departments.

Children’s National will host the 33rd Annual Children’s National Symposium on ECMO and Advanced Therapies for Respiratory Failure, in Keystone, Colorado, February 26 – March 2, 2017.

Children’s receives $3M research grant from Mallinckrodt

Mallinckrodt Pharmaceuticals has awarded a $3 million Healthcare Advancement Grant to Children’s National Health System, supporting a research initiative focused on pediatric patients in the intensive care setting.

In the U.S., 20 percent of hospitalized children are cared for in the pediatric intensive care unit (ICU). Yet this is an under-researched patient population with layers of complexity. These patients face a 2.5 to 5 percent mortality rate, with 5 to 10 percent serious morbidity rate, and the morbidity and mortality rates double within three years.

Children’s National is uniquely qualified to address this opportunity, with its level IV neonatal ICU, ranked third in the nation by U.S. News and World Report in its 2016-2017 Best Children’s Hospitals survey. Home to the Children’s Research Institute and the Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National is one of the nation’s top National Institute of Health (NIH)-funded pediatric institutions. It is a member of the Collaborative Pediatric Critical Care Research Network of the NIH and enjoys strong partnerships with major universities in the Washington, DC, area, providing data-generation resources. The institution plans to mine data from this myriad of sources and more to unearth knowledge and improve outcomes.

Children’s National has identified three priorities to launch and execute this multi-year initiative, specifically:

  • Establish a Critical Care Outcomes Research Initiative team
  • Build on existing partnerships and expand to acquire additional data
  • Build outcomes research studies in the critical care arena

“We applaud Mallinckrodt for their forward thinking as we begin this important research initiative that will help meet the challenges faced by seriously ill pediatric patients,” said Robin Steinhorn, M.D., Senior Vice President for the Center for Hospital-Based Specialties. “We firmly believe the combination of this generous research grant, our many collaborative relationships and Children’s National’s renowned research enterprise will lead to improved outcomes for children in the future.”

Neonatology updates: U.S. News ranking, skin-to-skin snuggling

June 21, 2016 – Children’s National ranked in top 20 in every specialty
U.S. News & World Report 2016-17 Best Children’s Hospital Survey ranks Children’s National Health System in the top 20 in every specialty, which makes Children’s one of just four pediatric hospitals in the country—and the only one in the region—to earn this recognition. Children’s ranked among the top 10 in three specialties: Neonatology (No. 3), neurology/neurosurgery (No. 8), and orthopaedics (No. 9).

Oct. 23, 2015 – Parental stress before and after skin-to-skin contact in the NICU
While stable parent-child bonds are key to healthy child development, achieving such bonding can be complicated for parents of babies born prematurely. Interim results from an ongoing study conducted in the neonatal intensive care unit indicate that skin-to-skin “snuggling” between mothers and babies can lower maternal stress levels.

Patient centered family conferences can boost satisfaction with pediatric ICU care

PDF Version

What’s Known
Family conferences in the pediatric intensive care unit (PICU) cover difficult decisions made on behalf of critically ill children, such as starting or withdrawing life support, placing a tracheostomy, or repeating bone marrow transplantation. Family satisfaction is a national quality indicator for determining excellence of care, and families rate communication as one of physicians’ most important skills. Researchers sought to clarify the association between the patient-centered nature of physicians’ communication patterns and the degree to which parents were satisfied with decision making during family conferences in the PICU.

What’s New
A research team led by Children’s National Health System staff recorded 39 family conferences to dissect the dynamics of the conversations. The conferences averaged 45 minutes in length, and the medical team spoke 73 percent of the time. Physicians contributed 89 percent of the dialogue; bedside nurses spoke 2 percent of the conversation. The team used the Roter Interaction Analysis System and a related patient-centeredness score to evaluate the conversations. A patient centeredness score higher than 0.75 predicted parental satisfaction, controlling for the length of the conference, the severity of the child’s illness, race, and socioeconomic status.

Skills: Partnering and activation, asking for patient opinion, asking for understanding

  • Doctor: What do you think would help?
  • Doctor: Do you follow me?
  • Doctor: Let me make sure I’ve got what you meant. Your preference would be to place the trachif we can’t get the breathing tube out on this third try?

Questions for Future Research
Q: How do parents’ perceptions change when additional members of the medical team speak during family conferences?
Q: How does the manner in which parents process information, e.g., cognitive processing vs. psychomotor processing, impact their preference for more patient-centered family conferences?

Source: “Parent Satisfaction With Communication is Associated With Physician’s Patient-Centered Communication Patterns During Family Conferences.” T.W. October,P.S. Hinds, J. Wang , Z.B. Dizon, Y.I. Cheng, and D.L. Roter. Published by Pediatric Critical Care Medicine June 17, 2016.

Unlocking the ‘black box’ of NICU monitors to protect vulnerable preemies

MiningdatafromNICUmonitors

What’s Known
Around the world, some 15 million infants are born prematurely each year. Babies born prematurely can spend their first weeks to months of life in the neonatal intensive care unit (NICU) tethered to machines that closely monitor vital signs, such as breathing and heart rate.

After discharge, preemies have a very high risk of returning to the NICU, often due to breathing difficulties, such as experiencing excessively long pauses between breaths. Such acute life-threatening events are a major cause of preemies’ hospital readmission and may result in death.

What’s New
During infants’ NICU stays, cardiorespiratory monitors amass a mountain of data about each child. Through the unprecedented collaboration of researchers working in various divisions of Children’s National Health System, the team was able to unlock that black box of information by creating algorithms to extract data and by using retrospective analyses to tease out new insights. This multidisciplinary team has been able to predict with a greater degree of precision which babies are at higher risk of returning to the NICU after discharge. What these most vulnerable preemies have in common is the degree of maturation of their autonomic nervous system, which controls such involuntary actions as heart rate and breathing. The sympathetic nervous system, which the body leverages as it copes with the stress of life-threatening events (ALTE), also plays a role in these infants’ heightened vulnerability. Being able to identify these newborns earlier has the potential to lower readmissions and save lives.

Questions for Future Research
Q: How can further computer-based analyses of NICU monitor data be used to determine how preemies respond to routine activities, such as feeding to predict which infants have compromised cardiorespiratory systems?
Q: How can we develop a test to assess all premature infants for physiologic readiness for safe NICU discharge and, thus, prevent ALTE and sudden death in this vulnerable population?

Source: “Vagal Hypersensitivity in Premature Infants and Risk of Hospital Readmission Due to Acute Life-Threatening Events (ALTE).” G. Nino, R. Govindan, T. AlShargabi, M. Metzler, R. Joshi, G. Perez, A.N. Massaro, R. McCarter, and A. du Plessis. Presented during the 2016 Pediatric Academic Societies Annual Meeting, Baltimore, MD. May 2, 2016.

The search for precise blood biomarkers of neonatal brain injury

Bloodbiomarkers

PDF Version

What’s Known:
Hypoxic-ischemic encephalopathy (HIE) is characterized by reduced blood and oxygen flow to a baby’s brain around birth and may cause neurologic disability or death. It occurs most commonly after intrauterine asphyxia brought on by such difficulties as circulatory problems, placental abruption, or inflammatory processes. Newborns with HIE may suffer seizures, difficulty feeding, and disturbed control of heart rate and breathing. Cooling therapy, which is the standard of care, offers some protection to the developing brain, but up to 50 percent of HIE-affected infants still have poor outcomes.

What’s New:
Research scientists at Children’s National Health System are involved in a multi-center clinical trial to determine if erythropoietin (EPO), a hormone naturally secreted by the kidneys and commonly used to treat anemia, helps to prevent brain injury in these infants. The trial, called the HEAL Study (High Dose Erythropoietin for Asphyxia and Encephalopathy), is exploring whether EPO, given in addition to hypothermia, further lowers the risk of brain injury in HIE-affected babies. As a part of this study, researchers at Children’s National are leading the investigation to identify biomarkers of brain injury. Biomarkers are telltale chemicals in the blood and are used in tests that evaluate whether patients have suffered a heart attack. While available biomarkers warn when the heart, kidney, or liver is in trouble, there is no blood biomarker that signals ongoing brain injury. Such blood biomarkers could help to determine which infants are responding to treatment as well as to precisely identify which HIE-affected infants are still struggling and require additional treatments, such as EPO, to protect the brain and improve outcomes.

Questions for Future Research: 

  • Does EPO, in tandem with hypothermia, improve long- term neurodevelopmental outcomes in newborns with HIE?
  • Which biomarkers, or panel of biomarkers, best reflect the timing and severity of neonatal brain injury?
  • Can biomarkers direct which types of treatments are best for specific patients and when they should be used?

Source: “Plasma Biomarkers of Brain Injury in Neonatal HIE (Hypoxic-Ischemic Encephalopathy).” A.N. Massaro, Y. Wu, T.K. Bammler, A. Mathur, R.C. McKinstry, T. Chang, D.E. Mayock, S. Mulkey, K. Van Meurs, L. Dong, R. Ballard, and S. Juul. Presented during the 2016 Pediatric Academic Societies Annual Meeting, Baltimore, MD. May 3, 2016.