Posts

Bella when she was sick

Preserving brain function by purposely inducing strokes

Bella when she was sick

Born to young parents, no prenatal testing had suggested any problems with Bella’s brain. But just a few hours after birth, Bella suffered her first seizure – one of many that would follow in the ensuing days. After brain imaging, her doctors in Iowa diagnosed her with hemimegalencephaly.

Strokes are neurologically devastating events, cutting off life-sustaining oxygen to regions of the brain. If these brain tissues are deprived of oxygen long enough, they die, leading to critical loss of function – and sometimes loss of life.

“As physicians, we’re taught to prevent or treat stroke. We’re never taught to inflict it,” says Taeun Chang, M.D., director of the Neonatal Neurology and Neonatal Neurocritical Care Program at Children’s National Hospital.

That’s why a treatment developed at Children’s National for a rare brain condition called hemimegalencephaly is so surprising, Dr. Chang explains. By inflicting controlled, targeted strokes, Children’s National physician-researchers have treated five newborns born with intractable seizures due to hemimegalencephaly before they’re eligible for epilepsy surgery, the standard of care. In the four surviving infants, the procedures drastically reduced or completely relieved the infants of hemimegalencephaly’s characteristic, uncontrollable seizures.

The most recent patient to receive this life-changing procedure is Bella, a 13-month-old from Iowa whose treatment at Children’s National began within her second week of life. Born to young parents, no prenatal testing had suggested any problems with Bella’s brain. But just a few hours after birth, Bella suffered her first seizure – one of many that would follow in the ensuing days. After brain imaging, her doctors in Iowa diagnosed her with hemimegalencephaly.

A congenital condition occurring in just a handful of children born worldwide each year, hemimegalencephaly is marked by one brain hemisphere growing strikingly larger and dysplastic than the other, Dr. Chang explains. This abnormal half of the brain is highly vascularized, rippled with blood vessels needed to support the seizing brain. The most conspicuous symptoms of hemimegalencephaly are the numerous seizures that it causes, sometimes several in the course of an hour, which also may prevent the normal half of the brain from developing and learning.

Prior studies suggest early surgery achieves better developmental outcomes with one study reporting as much as a drop of 10-20 IQ points with every month delay in epilepsy surgery.

The standard treatment for unilateral megalencephaly is a dramatic procedure called a hemispherectomy, in which surgeons remove and disconnect the affected half of the brain, allowing the remaining half to take over its neurological duties. However, Dr. Chang says, implementing this procedure in infants younger than 3 months of age is highly dangerous.  Excessive, potentially fatal blood loss is likely in infants younger than 3 months who have a highly vascularized brain in the setting of an immature coagulation system. That leaves their doctors with no choice but to wait until these infants are at least 3 months old, when they are more likely to survive the surgery.

However, five years ago, Dr. Chang and her colleagues came up with a different idea when a newborn continued to have several seizures per hour despite multiple IV seizure medications: Because strokes cause irreversible tissue death, it might be possible to effectively incapacitate the enlarged hemisphere from within by inflicting a stroke on purpose. At the very least, this “functional embolization” might buy time for a traditional hemispherectomy, and slow or halt ongoing brain damage until the infants are able to withstand surgery. Ideally, this procedure may be all some children need, knocking out the offending hemisphere completely so they’d never need a hemispherectomy, which has late complications, such as hydrocephalus.

A pediatrician friend of Bella’s paternal grandparents read a story on Children’s National website about Darcy, another baby who’d received functional embolization a year earlier and was doing well. She contacted Dr. Chang to see if the procedure would be appropriate for Bella.

Within days, Bella and her family headed to Washington, D.C., to prepare for functional embolization herself. Within the first weeks of life, Bella underwent three separate procedures, each three to four hours long. Under real-time fluoroscopic and angiographic guidance, interventional neuroradiologist Monica Pearl, M.D., threaded a micro-catheter up from the baby’s femoral artery through the complex network of blood vessels all the way to her brain. There, in targeted branches of her cerebral arteries, Dr. Pearl strategically placed liquid embolic agent to obstruct blood flow to the abnormal half of Bella’s brain.

Immediately after the first procedure, the team had to contend with the same consequences that come after any stroke: brain swelling that can cause bleeding and herniation, complicated further by the already enlarged hemisphere of Bella’s brain. Using neuroprotective strategies learned from treating hundreds of brain-injured newborns, the neonatal neurocritical care team and the neonatal intensive care unit (NICU) minimized the brain swelling and protected the normal half of the brain by tightly controlling the brain temperature, her sugar and electrolyte levels, her blood pressure and coagulation system.

As the brain tissue in the oversized hemisphere died, so did the seizures that had plagued Bella since birth. She has not had a seizure since she left Children’s National more than one year ago. Her adoptive parents report that Bella is hitting many of the typical developmental milestones for her age: She’s getting ready to walk, blowing kisses and saying a few words. Physical, speech and occupational therapy will keep her moving in the right direction, Dr. Chang says.

“We believe that Children’s National is the only place in the world that’s treating newborns in this way to preserve their futures,” Dr. Chang says. “We’re privileged to be able to care for Bella and other kids with this rare condition.”

Bella’s transfer and successful procedures required the support and collective efforts of many within the hospital organization including William D. Gaillard, M.D., and his surgical epilepsy team; interventional neuroradiology with Dr. Monica Pearl; Neurosurgery; Neonatology and the NICU; social work; and even approval from Robin Steinhorn, M.D., senior vice president of the Center for Hospital-Based Specialties, and David Wessel, M.D., executive vice president and Chief Medical Officer.

“While obvious credit goes to the medical team who saved Bella’s future and the neonatal intensive care nurses who provided exceptional, intensive, one-on-one care, Bella’s team of supporters extend to all levels within our hospital,” Dr. Chang adds.

Also read:

View:

Oluigbo and Myseros neurosurgery

Working miracles to control seizures and preserve brain power in newborns

Oluigbo and Myseros neurosurgery

In the spring of 2017, a multidisciplinary team applied an innovative approach to help preserve function in the working right hemisphere of a baby who experienced her first seizure hours after birth.

When orderly early fetal brain development is disturbed in one half of the brain, infants can be born with hemimegalencephaly—a rare occurrence—that results in one of the brain’s two hemispheres being oversized, heavy and malformed. This brain malformation arises early in the fetal period of life, is not inherited and is associated with seizures early in life.

Children with hemimegalencephaly can develop horrible seizures within the first hours or days of life. According to published research, every month these infants experience uncontrolled seizures correlates to a steep decline in IQ.

Because these types of seizures do not respond to multiple anti-seizure medications—medicines which may also cause worrisome side effects of their own in neonates—care teams attempt to schedule surgery as soon as feasible to remove or disconnect the hemisphere triggering the damaging seizures. “The ‘bad’ brain does not sustain any function and it interferes with the ‘good’ brain doing what it needs to do,” says William D. Gaillard, M.D., chief of Children’s division of Epilepsy and Neurophysiology and chief of Neurology.

Hemispherectomy is intricate surgery on an organ that is softer than normal and crisscrossed with a tangle of blood vessels that supply the damaged hemisphere with blood. Because of the risks of life-threatening blood loss in very young infants, the dramatic surgery is usually not performed until babies are at least 3 months old and weigh at least 10 pounds.

The challenge: The vulnerable babies who most need relief, infants who have been seizing since early life, are too young for the operation.

Neurosurgeons have clamped the carotid artery that supplies blood to the brain to minimize blood loss when the hemisphere is surgically removed. Dr. Gaillard says knowledge of that approach led the team to think: What if we use embolization—blocking blood supply to targeted locations in the brain—to achieve the same effect?  The plan effectively destroys the malformed brain from within, neutralizing its ability to cause the seizures.

“It was eye-opening for us to think about actually inflicting brain injury as a way of treating something in the brain that was causing seizures. That is really novel in itself: We’re thinking out of the box in applying existing techniques in a different age group. The conventional thinking with newborns is to let them be; their seizures don’t look that bad,” says Taeun Chang, M.D., director of Children’s Neonatal Neurology and Neonatal Neurocritical Care Program.

“We have evidence to suggest this is a safe and effective way of avoiding recurrent seizures and minimizing the need to give these infants potentially toxic medications so early in life. Ultimately, this helps a select group of babies who need the surgery to get to the point of being old enough to have it—all the while, sparing the healthy part of their brain,” Dr. Gaillard adds.

Darcy hemimegalencephaly

Once the embolization ended Darcy’s most severe seizures, the little girl could make eye contact, started smiling, and then graduated from smiling to full laughs. In weekly physical therapy, the infant works on tummy time, head control and ensuring her eyes track.

In the spring of 2017, the multidisciplinary team applied the innovative approach to help preserve function in the working right hemisphere of a baby named Darcy Murphy. Darcy experienced her first seizure hours after she was born, and when she arrived at Children’s National had been in and out of two different emergency rooms in another state for the first few weeks of her life.

The team explained to the Murphy family that Darcy was on multiple medications, but her seizures continued unabated. The options included inducing a coma, sending Darcy home despite ongoing seizures or minimally invasive embolization.

“We would not have even posed this if we were not confident in our ability to do the procedure and deal with potential complications,” Dr. Chang says.

“Oh my gosh, as a parent you know what you’re doing is permanent,” says Rachel Murphy, 29, Darcy’s mom said of the decisions that she and husband Ryan, 33, faced for the youngest of their three children. “What if it’s not the right decision? What if in a week they come out with a new procedure you could have done? We were horrified all the time. The nice part with this procedure is the reward is apparent very quickly, and it just gets better. You don’t have to wait two years to know you made the right decision. You can see half a brain is better than the whole thing for this specific child.”

Once the embolization ended Darcy’s most severe seizures, the little girl could initiate and maintain eye contact with family members, started smiling and then graduated from smiling to full laughs. In weekly physical therapy, the infant works on tummy time, head control and ensuring her eyes track.

Children’s multidisciplinary care team includes experts in newborn intensive care (neonatologists) to aggressively manage seizures in the traditional fashion as they occur and to monitor vital signs; a neonatal neurologist/neurointensivist at the bedside and in the Angio suite monitoring Darcy’s brain activity; a neonatal epileptologist; a surgical epilepsy team; an interventional neuroradiologist; neurosurgeons to perform the delicate functional hemispherectomy to remove any residual brain tissue from the bad hemisphere; and physical therapists working to help Darcy achieve maximum function after surgery.

“We were just like one unit in the sense of being able to provide coherent, comprehensive care. It’s about blood pressure management, breathing, electrolytes, making sure everything is right for going to the operating room,” Dr. Chang explains. “Darcy’s case highlights the ways in which Children’s National is different and offers personalized care that is superior to other centers.”

The team, which recently published a case report of two previous serial embolizations followed by hemispherectomy, plans follow-up papers describing EEG manifestations during an acute stroke in a newborn, advice to the field on best practices for the embolization and using cooling to control the planned brain injury during embolization hemispherectomy.

Revised Nov. 7, 2017

Related resources

Chima Oluigbo

A novel way to treat intractable epilepsy caused by hemimegalencephaly

Chima Oluigbo

A multidisciplinary team led by Chima Oluigbo, M.D., F.R.C.S.C., pioneered a novel technique to preserve newborns’ healthy brain tissue, buying time until the infants became old enough to undergo a hemispherectomy.

What’s known

Hemimegalencephaly is an extremely rare birth defect in which one side of the brain grows larger than the other. This anomaly typically leads to severe, recurrent seizures that can be difficult to control solely with medications. While the seizures themselves are detrimental to the developing brain, the amount of medications used to reduce seizure frequency often come with significant side effects and have the potential to hamper brain growth. Hemispherectomy, a radical surgery in which one half of the brain is removed, is often the most successful way to treat severe and intractable epilepsy. However, this surgery can be challenging to perform successfully in very young babies.

What’s new

In this case report, the Children’s National Health System Epilepsy Team led by Chima Oluigbo, M.D., F.R.C.S.C., a pediatric neurosurgeon; Tammy N. Tsuchida, M.D., PhD., a pediatric surgical epileptologist; Monica Pearl, M.D., a pediatric interventional neuroradiologist; Taeun Chang, M.D., a neonatal neurointensivist; and the neonatal intensive care team explored the possibility of using minimally invasive surgery to cut off the blood supply to the brain hemisphere responsible for generating seizures in newborns with hemimegalencephaly. This procedure, they reasoned, could buy time for babies to mature and become more resilient to withstand the future hemispherectomy while also lessening the damage caused by uncontrolled, recurrent seizures. The case report focused on the first two patients with hemimegalencephaly who had sequential procedures to gradually restrict blood flow to the affected brain hemisphere within their first few weeks of life, followed by hemispherectomies at a few months of age. This novel approach significantly lessened their seizures until hemispherectomy, allowing these children to continue to grow and develop seizure-free.

Questions for future research

Q: Which patients are best suited for this surgical procedure?
Q: How can surgeons reduce the risk of excessive blood loss during hemispherectomy caused by the growth of additional blood vessels after flow through the brain’s major vessels has been blocked?
Q: What are the long-term outcomes for infants who undergo these procedures?

Source: “ ‘Endovascular embolic hemispherectomy’: A strategy for the initial management of catastrophic holohemispheric epilepsy in the neonate.” Oluigbo, C., M.S. Pearl, T.N. Tsuchida, T. Chang, C.-Y. Ho and W. D. Gaillard. Published by Child’s Nervous System October 29, 2016.
Drs. DeBiasi and du Plessis

Zika virus, one year later

Drs. DeBiasi and du Plessis

A multidisciplinary team at Children’s National has consulted on 66 Zika-affected pregnancies and births since May 2016.

The first pregnant patient with worries about a possible Zika virus infection arrived at the Children’s National Health System Fetal Medicine Institute on Jan. 26, 2016, shortly after returning from international travel.

Sixteen months ago, the world was just beginning to learn how devastating the mosquito-borne illness could be to fetuses developing in utero. As the epidemic spread, a growing number of sun-splashed regions that harbor mosquitoes that efficiently spread the virus experienced a ballooning number of Zika-affected pregnancies and began to record sobering birth defects.

The Washington, D.C. patient’s concerns were well-founded. Exposure to Zika virus early in her pregnancy led to significant fetal brain abnormalities, and Zika virus lingered in the woman’s bloodstream months after the initial exposure — longer than the Centers for Disease Control and Prevention (CDC) then thought was possible.

The research paper describing the woman’s lengthy Zika infection, published by The New England Journal of Medicine, was selected as one of the most impactful research papers written by Children’s National authors in 2016.

In the intervening months, a multidisciplinary team at Children National has consulted on 66 pregnancies and infants with confirmed or suspected Zika exposure. Thirty-five of the Zika-related evaluations were prenatal, and 31 postnatal evaluations assessed the impact of in utero Zika exposure after the babies were born.

The continuum of Zika-related injuries includes tragedies, such as a 28-year-old pregnant woman who was referred to Children’s National after imaging hinted at microcephaly. Follow-up with sharper magnetic resonance imaging (MRI) identified severe diffuse thinning of the cerebral cortical mantle, evidence of parenchymal cysts in the white matter and multiple contractures of upper and lower extremities with muscular atrophy.

According to a registry of Zika-affected pregnancies maintained by the CDC, one in 10 pregnancies across the United States with laboratory-confirmed Zika virus infection has resulted in birth defects in the fetus or infant.

“More surprising than that percentage is the fact that just 25 percent of infants underwent neuroimaging after birth – despite the CDC’s recommendation that all Zika-exposed infants undergo postnatal imaging,” says Roberta L. DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases and co-director of the Congenital Zika Virus Program at Children’s National. “Clinicians should follow the CDC’s guidance to the letter, asking women about possible exposure to Zika and providing multidisciplinary care to babies after birth. Imaging is an essential tool to accurately monitor the growing baby’s brain development.”

Adré du Plessis, M.B.Ch.B., M.P.H., director of the Fetal Medicine Institute and Congenital Zika Virus Program co-leader, explains the challenges: ”When it comes to understanding the long-term consequences for fetuses exposed to the Zika virus, we are still on the steepest part of the learning curve. Identifying those children at risk for adverse outcomes will require a sustained and concerted multidisciplinary effort from conception well beyond childhood.”

In addition to counseling families in the greater Washington, D.C. region, the Children’s research team is collaborating with international colleagues to conduct a clinical trial that has been recruiting Zika-infected women and their babies in Colombia. Pediatric Resident Youssef A. Kousa, D.O., Ph.D., M.S., and Neurologist Sarah B. Mulkey, M.D., Ph.D., will present preliminary findings during Research and Education Week 2017.

In Colombia as well as the District of Columbia, a growing challenge continues to be assessing Zika’s more subtle effects on pregnancies, developing fetuses and infants, says Radiologist Dorothy Bulas, M.D., another member of Children’s multidisciplinary Congenital Zika Virus Program.

The most severe cases from Brazil were characterized by interrupted fetal brain development, smaller-than-normal infant head circumference, brain calcifications, enlarged ventricles, seizures and limbs folded at odd angles. In the United States and many other Zika-affected regions, Zika-affected cases with such severe birth defects are outnumbered by infants who were exposed to Zika in utero but have imaging that appears normal.

In a darkened room, Dr. Bulas pores over magnified images of the brains of Zika-infected babies, looking for subtle differences in structure that may portend future problems.

“There are some questions we have answered in the past year, but a number of questions remain unanswered,” Dr. Bulas says. “For neonates, that whole area needs assessment. As the fetal brain is developing, the Zika virus seems to affect the progenitor cells. They’re getting hit quite early on. While we may not detect brain damage during the prenatal period, it may appear in postnatal images. And mild side effects that may not be as obvious early on still have the potential to be devastating.”

Dr. Keating and Abigail

Multidisciplinary approach to hydrocephalus care

Reflective of the myriad symptoms and complications that can accompany hydrocephalus, a multidisciplinary team at Children’s National works with patients and families for much of childhood.

The Doppler image on the oversized computer screen shows the path taken by blood as it flows through the newborn’s brain, with bright blue distinguishing blood moving through the middle cerebral artery toward the frontal lobe and bright red depicting blood coursing away. Pitch black zones indicate ventricles, cavities through which cerebrospinal fluid usually flows and where hydrocephalus can get its start.

The buildup of excess cerebrospinal fluid in the brain can begin in the womb and can be detected by fetal magnetic resonance imaging. Hydrocephalus also can crop up after birth due to trauma to the head, an infection, a brain tumor or bleeding in the brain, according to the National Institutes of Health. An estimated 1 to 2 per 1,000 newborns have hydrocephalus at birth.

When parents learn of the hydrocephalus diagnosis, their first question tends to be “Is my child going to be OK?” says Suresh Magge, M.D., a pediatric neurosurgeon at Children’s National Health System.

“We have a number of ways to treat hydrocephalus. It is one of the most common conditions that pediatric neurosurgeons treat,” Dr. Magge adds.

Unlike fluid build-up elsewhere in the body where there are escape routes, with hydrocephalus spinal fluid becomes trapped in the brain. To remove it, surgeons typically implant a flexible tube called a shunt that drains excess fluid into the abdomen, an interim stop before it is flushed away. Another surgical technique, called an endoscopic third ventriculostomy has the ability to drain excess fluid without inserting a shunt, but it only works for select types of hydrocephalus, Dr. Magge adds.

For the third year, Dr. Magge is helping to organize the Hydrocephalus Education Day on Feb. 25, a free event that offers parents an opportunity to learn more about the condition.

Reflective of the myriad symptoms and complications that can accompany hydrocephalus, such as epilepsy, cerebral palsy, cortical vision impairment and global delays, a multidisciplinary team at Children’s National works with patients and families for much of childhood.

Neuropsychologist Yael Granader, Ph.D., works with children ages 4 and older who have a variety of developmental and medical conditions. Granader is most likely to see children and adolescents with hydrocephalus once they become medically stable in order to assist in devising a plan for school support services and therapeutic interventions. Her assessments can last an entire day as she administers a variety of tasks that evaluate how the child thinks and learns, such as discerning patterns, assembling puzzles, defining words, and listening to and remembering information.

Neuropsychologists work with schools in order to help create the most successful academic environment for the child. For example, some children may struggle to visually track across a page accurately while reading; providing a bookmark to follow beneath the line is a helpful and simple accommodation to put in place. Support for physical limitations also are discussed with schools in order to incorporate adaptive physical education or to allow use of an elevator in school.

“Every child affected by hydrocephalus is so different. Every parent should know that their child can learn,” Granader says. “We’re going to find the best, most supportive environment for them. We are with them on their journey and, every few years, things will change. We want to be there to help with emerging concerns.”

Another team member, Justin Burton, M.D., a pediatric rehabilitation specialist, says rehabilitation medicine’s “piece of the puzzle is doing whatever I can to help the kids function better.” That means dressing, going to the bathroom, eating and walking independently. With babies who have stiff, tight muscles, that can mean helping them through stretches, braces and medicine management to move muscles smoothly in just the way their growing bodies want. Personalized care plans for toddlers can include maintaining a regular sleep-wake cycle, increasing attention span and strengthening such developmental skills as walking, running and climbing stairs. For kids 5 and older, the focus shifts more to academic readiness, since those youths’ “full-time job” is to become great students, Dr. Burton says.

The area of the hospital where children work on rehabilitation is an explosion of color and sounds, including oversized balance balls of varying dimensions in bright primary colors, portable basketball hoops with flexible rims at multiple heights, a set of foam stairs, parallel bars, a climbing device that looks like the entry to playground monkey bars and a chatterbox toy that lets a patient know when she has opened and closed the toy’s doors correctly.

“We end up taking care of these kids for years and years,” he adds. “I always love seeing the kids get back to walking and talking and getting back to school. If we can get them back out in the world and they’re doing things just like every other kid, that’s success.”

Meanwhile, Dr. Magge says research continues to expand the range of interventions and to improve outcomes for patients with hydrocephalus, including:

  • Fluid dynamics of cerebrospinal fluid
  • Optimal ways to drain excess fluid
  • Improving understanding of why shunts block
  • Definitively characterizing post-hemorrhagic ventricular dilation.

Unlike spina bifida, which sometimes can be corrected in utero at some health institutions, hydrocephalus cannot be corrected in the womb. “While we have come a long way in treating hydrocephalus, there is still a lot of work to be done. We continue to learn more about hydrocephalus with the aim of continually improving treatments,” Dr. Magge says.

During a recent office visit, 5-year-old Abagail’s head circumference had measured ¼ centimeter of growth, an encouraging trend, Robert Keating, M.D., Children’s Chief of Neurosurgery, tells the girl’s mother, Melissa J. Kopolow McCall. According to Kopolow McCall, who co-chairs the Hydrocephalus Association DC Community Network, it is “hugely” important that Children’s National infuses its clinical care with the latest research insights. “I have to have hope that she is not going to be facing a lifetime of brain surgery, and the research is what gives me the hope.”

The search for precise blood biomarkers of neonatal brain injury

Bloodbiomarkers

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.