Judges award grants for pediatric medical devices that address cardiovascular, NICU, and orthopaedic and spine device innovations.
Yves d’Udekem, M.D., Ph.D., a pediatric cardiac surgeon recognized for expertise in the most challenging procedures for newborns and children with complex congenital heart disease, has joined Children’s National Hospital as chief of Cardiac Surgery and co-director of the Children’s National Heart Institute.
“Children’s National has the cases and expertise I was looking for,” he says. “Even better, when you visit it’s clear that the entire Heart Institute team is energetic about working together. They’re constantly seeking better ways to do this work and improve how we care for children and their families.”
Dr. d’Udekem comes to Children’s National from The Royal Children’s Hospital in Melbourne, Australia, an institution that has led the advancement of congenital heart disease care and research, performing more than 500 surgical procedures with cardiopulmonary bypass each year.
He has a broad spectrum of pediatric cardiac surgery expertise, with special emphasis in single ventricle congenital heart defects, when one lower chamber of the heart does not develop. One area of his research portfolio includes clinical research into long-term quality of life for people who had Fontan procedures — a critical surgical approach to adapt blood flow for people born with single ventricle heart disease. He has additional expertise in valve repair, artificial hearts and other cardiac assist devices.
“Sometimes it seems like I’ve been born and put on this earth for that single purpose — I have to bring life to patients with single ventricle hearts or assist devices,” he says. He describes his path to pediatric cardiac surgery as serendipity, “It’s more like pediatric cardiac surgery chose me.”
“It is an honor to welcome Yves d’Udekem to the Children’s National Heart Institute,” says David Wessel, M.D., executive vice president and chief medical officer of Hospital and Specialty Services at Children’s National. “He is a surgeon, physician and leader of the highest caliber. I can say without hesitation that Yves’ leadership of our cardiac surgery team will change the lives of hundreds, if not thousands, of children and adults with congenital heart disease.”
In preparation for Dr. d’Udekem’s arrival, the Children’s National Heart Institute and hospital leadership created a framework plan for success that will build on the legacy of excellence established by Richard Jonas, M.D. Dr. Jonas, a world leader in congenital heart surgery who has made significant clinical and academic advances in the field, will continue his award-winning laboratory-based research at Children’s National on neurodevelopmental outcomes for children with congenital heart disease.
Dr. d’Udekem is Belgian-born with Canadian and Australian citizenship. He received his early training in Belgium and Toronto. As an attending cardiac surgeon in Belgium, he operated on both adults and children with congenital heart disease. Dr. d’Udekem then worked with internationally recognized heart surgeon Marc de Leval, M.D., FRCS, and others in London to train in congenital heart surgery at the Great Ormond Street Hospital for Children. From there, he was recruited to The Royal Children’s Hospital in Melbourne, Australia, where he has been ever since.
Dr. d’Udekem has more than 350 research publications and has obtained more than $7 million in grant funding in the past five years for work to create the first research network of Australian children and adults who have undergone the Fontan procedure.
He started seeing patients at Children’s National in mid-September.
Since May 2020, there has been some attention in the general public and the news media to a specific constellation of symptoms seen in children with COVID-19 or who have been exposed to COVID-19. For a time, headlines even called it a “Kawasaki-like” disease. At first glance, both the symptoms and the effective treatments are remarkably similar. However, a new review published in Trends in Cardiovascular Medicine finds that under closer scrutiny, the two conditions have some interesting differences as well.
“At the beginning of this journey, we thought we might be missing actual cases of Kawasaki disease because we identified a few patients who presented late and developed coronary artery abnormalities,” says Ashraf Harahsheh, M.D., senior author of the review article, “Multisystem inflammatory syndrome in children: Is there a linkage to Kawasaki disease?” and a cardiologist at Children’s National Hospital. “But as time passed, children exposed to COVID-19 started to present with a particular constellation of symptoms that actually had some important similarities and distinctions from Kawasaki.”
Similarities between Kawasaki disease and MIS-C
Both disease patterns seem to have a common trigger that provokes the inflammatory cascade reaction in genetically susceptible children, the authors write. However, there is also early evidence that children with each disease have different genetic markers, meaning different populations are genetically susceptible to each disease.
Additionally, the authors found that the massive activation of pro-inflammatory cytokines seen in MIS-C, also known as a “cytokine storm,” overlaps with a similar occurrence seen in Kawasaki disease, adult COVID-19 patients, toxic shock syndrome and some other viral infections.
Primary differences between Kawasaki disease and MIS-C
Overall, when compared to Kawasaki disease, children with MIS-C tend to:
- Present at an older age
- Have a more profound form of inflammation
- Have more gastrointestinal manifestation
- Show different laboratory findings
- Have greater risk of left ventricle dysfunction and shock
Further study of both Kawasaki and MIS-C needed
Despite noted differences, the authors are also careful to credit the documented similarities between Kawasaki disease and MIS-C as a key to the quick identification of the new syndrome in children. The study of Kawasaki disease also gave clinicians a valid basis to begin developing diagnostic recommendations and treatment protocols.
The review’s first author Yue-Hin Loke, M.D., who is also a cardiologist at Children’s National, says, “The quick recognition of MIS-C is only possible because of meticulous research conducted by Dr. Tomisaku Kawasaki, who recently passed away on June 5th, 2020. Even though some aspects of both are still shrouded in mystery, the previous research and clinical advancements made in Kawasaki disease set the stage for our immediate response to MIS-C.”
“Previous research provided key information for cardiologists facing this new syndrome, including the necessity of routine echocardiograms to watch for coronary artery abnormalities (CAAs) and for use of intravenous immunoglobulin (IVIG) to mitigate the development of CAAs,” says Charles Berul, M.D., chief of Cardiology at Children’s National and a co-author. “Both of these factors have played a key role in reducing the mortality of MIS-C to almost zero.”
The authors note that more research is needed to understand both Kawasaki disease and the specifics of MIS-C, but that what is learned about the mechanisms of one can and should inform study and treatment of the other. And in the meantime, caution and continued surveillance of these patients, especially with respect to coronary artery and myocardial function, will continue to improve the long-term outcomes for both syndromes.
The cardiac critical care team at Children’s National Hospital has developed an innovative Tele-Cardiac Critical Care model aiming to keep constant watch over the most fragile children with critical heart disease in the cardiac ICU. The system combines traditional remote monitoring and video surveillance with an artificial intelligence algorithm trained to flag early warning signs that a critically ill infant may suffer a serious event like cardiac arrest while recovering from complex cardiac surgery. This second set of eyes helps bedside teams improve patient safety and quality of care.
These high risk post-operative patients are often neonates or small infants born with the most complex and critical congenital heart diseases that require surgery or interventional cardiac catheterization in their first days or weeks of life. At these early stages after crucial cardiac surgery, these patients can decompensate dangerously fast with few outward physical symptoms.
The AI algorithm (T3) monitors miniscule changes in oxygen delivery and identifies any mismatch with a child’s oxygen needs. It also tracks and displays small changes in vital sign trends that could lead to a serious complication. The cardiac ICU command center staff then analyzes additional patient data and alerts the bedside team whenever needed.
The Tele-Cardiac Critical Care program started two years ago. In that time, the program has contributed to a significant decrease in post-operative cardiac arrest for this patient population.
“It’s easy to see how a model like this could be adapted to other critical care scenarios, including our other intensive care units and even to adult units,” says Ricardo Munoz, M.D., chief of Cardiac Critical Care and executive director of Telehealth. It allows the physicians and nurses to keep constant watch over these fragile patients without requiring a physician to monitor every heartbeat in person for every patient at every hour of the day to maintain optimal outcomes for all of them.”
Dr. Munoz and Alejandro Lopez-Magallon, M.D., medical director of Telehealth and cardiac critical care specialist, presented data from the pilot program at the American Telemedicine Association’s virtual Annual Meeting on June 26, 2020.
The U.S. Department of Defense has awarded $2 million to Children’s National Hospital to study how a family of protease enzymes known as caspases may contribute to brain cell degeneration when activated by prolonged anesthesia and cardiopulmonary bypass during cardiac surgery for congenital heart disease.
This U.S. Army Medical Research Acquisition Activity Award, Anesthesia Neurotoxicity in Congenital Heart Disease, is led by principal investigator Nobuyuki Ishibashi, M.D., with both clinical and basic science co-investigators including Kazue Hashimoto-Torii, Ph.D., (Neuroscience), Richard Jonas, M.D., (Cardiovascular Surgery) and Nina Deutsch, M.D., (Anesthesiology).
While the specific cellular and molecular mechanisms of how anesthesia and cardiac surgery impact cortical development are poorly understood, both seem to impact brain growth and development in young children. The most common neurologic deficit seen in children after CHD surgical repair is the impairment of fine and gross motor skills.
Both anesthetic agents and inflammation like that seen as a result of cardiopulmonary bypass have also been shown to contribute to the activation of a specific group of enzymes that play an essential role in the routine (programmed) death of cells: caspases. However, recent pre-clinical research shows that these enzymes may also contribute to other alterations to cells beyond cell death, including making changes to other cell structures. In pre-clinical models, these changes cause impairments to fine and gross motor skills – the same neurological deficits seen in children with CHD who have undergone procedures requiring prolonged anesthesia and cardiopulmonary bypass.
The research team hypothesizes that caspases are extensively activated as a result of cardiac surgery and while that activation is rarely causing reduced numbers of neurons, the changes that caspase enzymes trigger in neurons are contributing to neurological deficits seen in children with CHD after surgery.
While the study focuses specifically on the impacts of cardiac surgery for correction of a heart defect, the findings could have major implications for any pediatric surgical procedure requiring prolonged anesthesia and/or cardiopulmonary bypass.
Children’s National Hospital in Washington, D.C., was ranked No. 7 nationally in the U.S. News & World Report 2020-21 Best Children’s Hospitals annual rankings. This marks the fourth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide.
In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fourth year in a row.
For the tenth straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.
“Our number one goal is to provide the best care possible to children. Being recognized by U.S. News as one of the best hospitals reflects the strength that comes from putting children and their families first, and we are truly honored,” says Kurt Newman, M.D., president and CEO of Children’s National Hospital.
“This year, the news is especially meaningful, because our teams — like those at hospitals across the country — faced enormous challenges and worked heroically through a global pandemic to deliver excellent care.”
“Even in the midst of a pandemic, children have healthcare needs ranging from routine vaccinations to life-saving surgery and chemotherapy,” said Ben Harder, managing editor and chief of Health Analysis at U.S. News. “The Best Children’s Hospitals rankings are designed to help parents find quality medical care for a sick child and inform families’ conversations with pediatricians.”
The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.
The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.
Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:
- Neonatology (No. 1), led by Division Chief Billie Lou Short, M.D.
- Neurology and Neurosurgery (No. 3), led by Division Chiefs William D. Gaillard, M.D., and Robert F. Keating, M.D.
- Cancer (No. 6), led by Division Chief Jeffrey S. Dome, M.D., Ph.D.
- Nephrology (No. 7), led by Division Chief Marva Moxey-Mims, M.D., FASN
- Orthopedics (No. 9), led by Division Chief Matthew Oetgen, M.D., MBA
- Pulmonology and Lung Surgery (No.9), led by Division Chief Anastassios Koumbourlis, M.D., MPH
- Diabetes and Endocrinology (No. 10), led by Division Chief Andrew Dauber, M.D., MMSC
Many of the neurological deficits seen in children with congenital heart disease (CHD) are related to abnormal white matter development early in life caused by reduced oxygen supply to the brain while in utero. Children with immature white matter at birth also commonly sustain additional white matter injuries following cardiac surgery.
The NIH recently awarded a prestigious R01 grant totaling more than $3.2 million to a collaborative project led by the Center for Neuroscience Research, the Sheikh Zayed Institute for Pediatric Surgical Innovation and the Children’s National Heart Institute at Children’s National Hospital as well as MedStar Washington Hospital Center.
The research, titled “White matter protection in the fetus with congenital heart disease,” looks specifically at whether providing a supplemental amount of the naturally occurring tetrahydrobiopterin (BH4) for pregnant women could rescue white matter development of fetuses with congenital heart disease whose brains aren’t receiving enough oxygen – or suffering from hypoxic-ischemic events.
Previous preclinical studies have shown that this lack of oxygen depletes the brain’s natural BH4 level, and the researchers hypothesize that BH4 levels play a critical role in the growth and development of white matter in the fetal brain by triggering key cellular/molecular processes. Specifically, the study will focus on three aims:
- Establish in a preclinical model the optimal protective regiment for women pregnant with a fetus who has CHD to receive BH4.
- Determine the appropriate approach to deliver BH4 to this population
- Leverage genetic tools and biochemical techniques in the laboratory to better understand where and how BH4 levels play a role in the growth (or lack thereof) of oligodendrocytes—the primary cells of white matter.
This laboratory-based work is the first step to determining if the neurodevelopment of babies born with CHD can be preserved or recovered by addressing key brain development that occurs before the baby is even born. Findings related to congenital heart disease may also translate to other populations where white matter development is affected by hypoxia-ischemia, including premature infants.
The project is led by principal investigator Nobuyuki Ishibashi, M.D., with co-investigators Vittorio Gallo, Ph.D., Joseph Scafidi, D.O., and Mary Donofrio, M.D. as well as colleagues at MedStar Washington Hospital Center.
The Children’s National Research Institute recently released its 2019-2020 academic annual report, titled 150 Years Stronger Through Discovery and Care to mark the hospital’s 150th birthday. Not only does the annual report give an overview of the institute’s research and education efforts, but it also gives a peek in to how the institute has mobilized to address the coronavirus pandemic.
“Our inaugural research program in 1947 began with a budget of less than $10,000 for the study of polio — a pressing health problem for Washington’s children at the time and a pandemic that many of us remember from our own childhoods,” says Vittorio Gallo, Ph.D., chief research officer at Children’s National Hospital and scientific director at Children’s National Research Institute. “Today, our research portfolio has grown to more than $75 million, and our 314 research faculty and their staff are dedicated to finding answers to many of the health challenges in childhood.”
Highlights from the Children’s National Research Institute annual report
- In 2018, Children’s National began construction of its new Research & Innovation Campus (CNRIC) on 12 acres of land transferred by the U.S. Army as part of the decommissioning of the former Walter Reed Army Medical Center campus. In 2020, construction on the CNRIC will be complete, and in 2012, the Children’s National Research Institute will begin to transition to the campus.
- In late 2019, a team of scientists led by Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, traveled to the Democratic Republic of Congo to collect samples from 60 individuals that will form the basis of a new reference genome data set. The researchers hope their project will generate better reference genome data for diverse populations, starting with those of Central African descent.
- A gift of $5.7 million received by the Center for Translational Research’s director, Lisa Guay-Woodford, M.D., will reinforce close collaboration between research and clinical care to improve the care and treatment of children with polycystic kidney disease and other inherited renal disorders.
- The Center for Neuroscience Research’s integration into the infrastructure of Children’s National Hospital has created a unique set of opportunities for scientists and clinicians to work together on pressing problems in children’s health.
- Children’s National and the National Institute of Allergy and Infectious Diseases are tackling pediatric research across three main areas of mutual interest: primary immune deficiencies, food allergies and post-Lyme disease syndrome. Their shared goal is to conduct clinical and translational research that improves what we know about those conditions and how we care for children who have them.
- An immunotherapy trial has allowed a little boy to be a kid again. In the two years since he received cellular immunotherapy, Matthew has shown no signs of a returning tumor — the longest span of time he’s been tumor-free since age 3.
- In the past 6 years, the 104 device projects that came through the National Capital Consortium for Pediatric Device Innovation accelerator program raised $148,680,256 in follow-on funding.
- Even though he’s watched more than 500 aspiring physicians pass through the Children’s National pediatric residency program, program director Dewesh Agrawal, M.D., still gets teary at every graduation.
Understanding and treating the novel coronavirus (COVID-19)
In a short period of time, Children’s National Research Institute has mobilized its scientists to address COVID-19, focusing on understanding the virus and advancing solutions to ameliorate the impact today and for future generations. Children’s National Research Institute Director Mark Batshaw, M.D., highlighted some of these efforts in the annual report:
- Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, is looking at whether or not the microbiome of bacteria in the human nasal tract acts as a defensive shield against COVID-19.
- Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research, and her team are seeing if they can “train” T cells to attack the invading coronavirus.
- Sarah Mulkey, M.D., Ph.D., an investigator in the Center for Neuroscience Research and the Fetal Medicine Institute, is studying the effects of, and possible interventions for, coronavirus on the developing brain.
You can view the entire Children’s National Research Institute academic annual report online.
In contrast to the prevailing view that the novel coronavirus known as COVID-19 does not seriously impact children, a new study finds that children who contract the virus can become very ill—many of them critically so, according to physician researchers at Children’s National Hospital. Their results, published in the Journal of Pediatrics and among the first reports from a U.S. institution caring for children and young adults, shows differences in the characteristics of children who recovered at home, were hospitalized, or who required life support measures. These findings highlight the spectrum of illness in children, and could help doctors and parents better predict which pediatric patients are more likely to become severely ill as a consequence of the virus.
In late 2019, researchers identified a new coronavirus, known as SARS-CoV-2, which causes COVID-19. As the disease spread around the world, the vast majority of reports suggested that elderly patients bear the vast majority of the disease burden and that children are at less risk for either infection or severe disease. However, study leader Roberta DeBiasi, M.D., M.S., chief of the Division of Infectious Diseases at Children’s National, states that she and her colleagues began noticing an influx of children coming to the hospital for evaluation of a range of symptoms starting in mid-March 2020, who were tested and determined to be infected with COVID-19. One quarter of these children required hospitalization or life support.
“It was very apparent to us within the first several weeks of the epidemic that this was a very different situation than our colleagues on the West Coast of the US had described as their experience just weeks before,” DeBiasi says. “Right away, we knew that it was important for us to not only care for these sick children, but to examine the factors causing severe disease, and warn others who provide medical care to children.”
To better understand this phenomenon, she and her colleagues examined the medical records of symptomatic children and young adults who sought treatment at Children’s National for COVID-19 between March 15 and April 30, 2020. Each of these 177 children tested positive using a rapid assay to detect SARS-CoV-2 performed at the hospital. The researchers gathered data on each patient, including demographic details such as age and sex; their symptoms; whether they had any underlying medical conditions; and whether these patients were non-hospitalized, hospitalized, or required critical care.
The results of their analysis show that there was about an even split of male and female patients who tested positive for COVID-19 at Children’s National during this time period. About 25% of these patients required hospitalization. Of those hospitalized, about 75% weren’t considered critically ill and about 25% required life support measures. These included supplemental oxygen delivered by intubation and mechanical ventilation, BiPAP, or high-flow nasal cannula – all treatments that support breathing – as well as other support measures such as dialysis, blood pressure support and medications to treat infection as well as inflammation.
Although patients who were hospitalized spanned the entire age range, more than half of them were either under a year old or more than 15 years old. The children and young adults over 15 years of age, Dr. DeBiasi explains, were more likely to require critical care.
About 39% of all COVID-19 patients had underlying medical conditions, including asthma, which has been highlighted as a risk factor for worse outcomes with this infection. However, DeBiasi says, although underlying conditions were more common as a whole in hospitalized patients – present in about two thirds of hospitalized and 80% of critically ill – asthma didn’t increase the risk of hospitalization or critical illness. On the other hand, children with underlying neurological conditions, such as cerebral palsy, microcephaly, or global developmental delay, as well as those with underlying cardiac, hematologic, or oncologic conditions were significantly more likely to require hospitalization.
In addition, although early reports of COVID-19 suggested that fever and respiratory symptoms are hallmarks of this infection, Dr. DeBiasi and her colleagues found that fewer than half of patients had both concurrently. Those with mild, upper respiratory symptoms, such as runny nose, congestion, and cough were less likely to end up hospitalized than those with more severe respiratory symptoms, such as shortness of breath. The frequency of other symptoms including diarrhea, chest pain and loss of sense of smell or taste was similar among hospitalized and non-hospitalized patients.
Dr. DeBiasi notes that although other East Coast hospitals are anecdotally reporting similar upticks in pediatric COVID-19 patients who become seriously ill, it’s currently unclear what factors might account for differences from the less frequent and milder pediatric illness on the West Coast. Some factors might include a higher East Coast population density, differences between the genetic, racial and ethnic makeup of the two populations, or differences between the viral strains circulating in both regions (an Asian strain on the West Coast, and a European strain on the East Coast).
Regardless, she says, the good news is that the more researchers learn about this viral illness, the better prepared parents, medical personnel and hospitals will be to deal with this ongoing threat.
Other researchers from Children’s National who participated in this study include Xiaoyan Song, Ph.D., M.Sc., Meghan Delaney, D.O., M.P.H., Michael Bell, M.D. , Karen Smith, M.D., Jay Pershad, M.D., Emily Ansusinha, Andrea Hahn, M.D., M.S., Rana Hamdy, M.D., M.P.H., MSCE, Nada Harik, M.D., Benjamin Hanisch, M.D., Barbara Jantausch, M.D., Adeline Koay, MBBS, MS.c., Robin Steinhorn, Kurt Newman, M.D. and David Wessel, M.D.
During the COVID-19 pandemic, telehealth has been crucial in allowing doctors to maintain safe contact with patients who require ongoing medical care without an office visit. Just as important is the role that telehealth is playing to connect care providers with each other to ensure that everyone around the world has the information they need to provide the best care possible for this swift-moving disease.
One good example of this specialist-to-specialist thought leadership connection is the ongoing weekly meeting hosted by the Children’s National Hospital cardiac critical care specialists. Since early in the spread of COVID-19, the Cardiac-ICU team, led by cardiovascular specialists including Ricardo Munoz, M.D., chief of cardiac critical care medicine and executive director of telehealth at Children’s National, have connected pediatric clinicians around the world to discuss how best to care for particularly vulnerable patients with pre-existing heart diseases, and to discuss breaking news in epidemiology of the disease and the effectiveness of various treatment approaches.
The video conference attracts hundreds of physicians and nurses who specialize in pediatric cardiac care from countries all over the world. In the last week of April, the meeting featured a late-breaking session to discuss new pediatric intensive care observations of inflammatory symptoms similar to Kawasaki disease, which were being detected in the United Kingdom, Paris and the United States. While more information is needed about this discovery, the ability of these experts to gather and compare disease phenotypes from country to country facilitates both the additional classification of pediatric-related symptoms and improves how all centers, no matter their location, can prepare to treat children who present locally with these symptoms.
In recent weeks, cardiac physicians and nurses from some of the world’s hardest hit regions, including Italy and Spain, have shared detailed information about their on-the-ground experiences to help colleagues in the U.S. and elsewhere better prepare for new developments.
“This new disease is a moving target, especially when it comes to understanding how it might impact children and adults with existing cardiac disease, particularly those with congenital heart disease,” says Dr. Munoz. “It is extremely important that we learn from each other, especially when we are able to connect with our colleagues in the epicenters of the most serious outbreaks of COVID-19. We are happy to host this important weekly meeting with the goal of helping every specialist keep as many patients with cardiac diseases as safe as possible throughout the global health emergency.”
If you would like to join these weekly telehealth meetings, please send your request to COVIDMultiCICUResponse@childrensnational.org.
The International Consortium for Health Outcomes Measurement (ICHOM) announced the release of a Congenital Heart Disease Standard Set (CHDSS) in late April 2020.
Gerard Martin, M.D., FAAP, FACC, FAHA, cardiologist at Children’s National Hospital, chaired the working group and contributed to the standards’ writing. In ICHOM‘s press release, he noted that, “Having a global set of outcomes that matters most to adult patients and parents of children with congenital heart disease will provide a road map for healthcare professionals and organizations engaged in setting care strategies for this population around the world. I would like to acknowledge the efforts of the Working Group and ICHOM staff for their incredible effort on this project.”
The CHDSS is a minimum core set of standards, comprised of Patient, Parent, and Clinician – Reported Outcome Measures already being collected by most practices in routine clinical care. The CHDSS measures 14 outcomes under the ICHOM framework for comprehensive outcomes measurement. These overarching domains are Overall Health, Social Health, Mental Health, and Physical Health.
Learn more about the CDHSS, the contributors and read the ICHOM press release.
In early March as countries around the globe began to wrestle with how best to tackle the spread of COVID-19, a group of doctors, nurses, researchers and other medical staff from Children’s National Hospital were wrestling with a distinct set of challenges: What to do about the 10 Ugandan children and adults who were currently scheduled for lifesaving heart surgery (and the countless others who would benefit from the continued training of the local heart surgery team) to correct complications of rheumatic heart disease (RHD) during an impending medical mission in the country.
Rheumatic heart disease impacts over 39 million people globally and causes nearly 300,000 deaths per year. RHD is the result of frequent, untreated streptococcal throat infections in childhood that ultimately cause the body’s immune system to repeatedly damage heart valves. It is completely preventable, yet the majority of the world’s children still live in impoverished and overcrowded conditions that predispose them to RHD. Most patients present with advanced valvular heart disease. For example, in Uganda, an RHD registry includes over 600 children with clinical RHD, of which nearly 40% die within four years and the median survival time from enrollment in the registry is only nine months. For these patients, heart surgery is the only viable solution for long-term survival and normal quality of life.
The scheduled trip from Washington was part of a nearly 20-year partnership** between doctors, nurses, researchers and other medical staff in the United States, including Craig Sable, M.D., associate chief of cardiology, and and Pranava Sinha, M.D.,pediatric cardiovascular surgeon, at Children’s National Hospital in Washington, D.C., and the Uganda Heart Institute in Kampala, Uganda. The partnership aims to tackle RHD head-on. It provides surgical skill transfer, allows for treatment of more complex patients, and increases sustainable surgical capacity for Uganda’s RHD patients over time. As a result, over the last 15 years more than 1,000 children have received lifesaving heart surgery in Uganda, with the Uganda Heart Institute (UHI) performing one to two heart valve surgeries every two weeks over the last few years.
COVID-19 was changing the current plan, however. Travel between countries was limited, and the team from the U.S. wouldn’t have been permitted to leave the U.S. and return according to schedule. The trip, and the support teams who were scheduled to arrive to help with the surgeries, were cancelled. The U.S. team members who had already arrived in Uganda were sent home after helping their UHI colleagues set up and prepare for the surgeries as much as possible. Knowing that patients and families were counting on the surgery mission to go forward after waiting for months or years to have surgery for heart valve disease, UHI decided not to cancel the majority of the surgeries. Instead, for the first time, they planned and successfully completed five valve-related cases in a single week – several of them quite complex. The cardiologists and cardiac surgeons from Children’s National who were supposed to be in-country for these procedures were forced to limit their in person assistance to the set-up activities the week prior to surgery and telehealth consult during the procedures.
“It was hard not to be able to stay and work with the UHI team to help these families,” says Dr. Sable. “But we are so proud of the UHI team for meeting this challenge on their own. We knew they had the skills to perform at this volume and complexity. It’s a proud moment to see the team accomplish this major milestone, and to see the patients they cared for thrive.”
The patients are the most important outcome: The five who had successful open-heart surgery are all doing well, either on their way to recovery or already discharged to their communities, where they will, for the first time in memory, be able to play, exercise and go to school or work.
Longer term, this success demonstrates the UHI medical team’s ability to manage greater surgical capacity even when surgical missions from the U.S. resume. The partnership’s goal is to complete at least 1,000 annual operations (both pediatric and adult), with the majority being performed by the local team. Having this capacity available will mean the difference between life and death for many children and adults who have RHD in Uganda and the surrounding countries.
**This work is supported by the Edwards Life Sciences/Thoracic Surgery Foundation, the Emirates Airline Foundation, Samaritan’s Purse Children’s Heart Project and Gift of Life International.
Boys with Duchenne muscular dystrophy (DMD) experience poor muscle regeneration, but the precise reasons for this remain under investigation. An experimental model of severe DMD that experiences a large spike in transforming growth factor-beta (TGFβ) activity after muscle injury shows that high TGFβ activity suppresses muscle regeneration and promotes fibroadipogenic progenitors (FAPs). This leads to replacement of the damaged muscle fibers by calcified and connective tissue, compromising muscle structure and function. While blocking FAP buildup provides a partial solution, a Children’s National Hospital study team identifies correcting the muscle micro-environment caused by high TGFβ as a ripe therapeutic target.
The team’s study was published online March 26, 2020, in JCI Insight.
DMD is a chronic muscle disease that affects 1 in 6,200 young men in the prime of their lives. The disorder, caused by genetic mutations leading to the inability to produce dystrophin protein, leads to ongoing muscle damage, chronic inflammation and poor regeneration of lost muscle tissue. The patients experience progressive muscle wasting, lose the ability to walk by the time they’re teenagers and die prematurely due to cardiorespiratory failure.
The Children’s National team finds for the first time that as early as preadolescence (3 to 4 weeks of age), their experimental model of severe DMD disease showed clear signs of the type of spontaneous muscle damage, regenerative failure and muscle fiber loss seen in preadolescent boys who have DMD.
“In boys, the challenge due to muscle loss exists from early in their lives, but had not been mimicked previously in experimental models,” says Jyoti K. Jaiswal, MSc, Ph.D., principal investigator in the Center for Genetic Medicine Research at Children’s National, and the study’s co-senior author. “TGFβ is widely associated with muscle fibrosis in DMD, when, in fact, our work shows its role in this disease process is far more significant.”
Research teams have searched for experimental models that replicate the sudden onset of symptoms in boys who have DMD as well as its complex progression.
“Our work not only offers insight into the delicate balance needed for regeneration of skeletal muscle, but it also provides quantitative information about muscle stem cell activity when this balanced is disturbed,” says Terence A. Partridge, Ph.D., principal investigator in the Center for Genetic Medicine Research at Children’s National, and the study’s co-senior author.
“The D2-mdx experimental model is a relevant one to use to investigate the interplay between inflammation and muscle degeneration that is seen in humans with DMD,” adds Davi A.G. Mázala, co-lead study author. “This model faithfully recapitulates many features of the complex disease process seen in humans.”
Between 3 to 4 weeks of age in the experimental models of severe DMD disease, the level of active TGFβ spiked up to 10-fold compared with models with milder disease. Intramuscular injections of an off-the-shelf drug that inhibits TGFβ signaling tamped down the number of FAPs, improving the muscle environment by lowering TGFβ activity.
“This work lays the foundation for studies that could lead to future therapeutic strategies to improve patients’ outcomes and lessen disease severity,” says James S. Novak, Ph.D., principal investigator in Children’s Center for Genetic Medicine Research, and co-lead study author. “Ultimately, our goal is to improve the ability of patients to continue to maintain muscle mass and regenerate muscle.”
In addition to Mázala, Novak, Jaiswal and Partridge, Children’s National study co-authors include Marshall W. Hogarth; Marie Nearing; Prabhat Adusumalli; Christopher B. Tully; Nayab F. Habib; Heather Gordish-Dressman, M.D.; and Yi-Wen Chen, Ph.D.
Financial support for the research described in this post was provided by the National Institutes of Health under award Nos. T32AR056993, R01AR055686 and U54HD090257; Foundation to Eradicate Duchenne; Muscular Dystrophy Association under award Nos. MDA295203, MDA480160 and MDA 477331; Parent Project Muscular Dystrophy; and Duchenne Parent Project – Netherlands.
Factoring in the total number of days that extremely preterm infants require supplemental oxygen and tracking this metric for weeks longer than usual improves clinicians’ ability to predict respiratory outcomes according to bronchopulmonary dysplasia (BPD) severity, a research team led by Children’s National Hospital writes in Scientific Reports. What’s more, the researchers defined a brand-new category (level IV) for newborns who receive supplemental oxygen more than 120 days as a reliable way to predict which infants are at the highest risk of returning to the hospital due to respiratory distress after discharge.
About 1 in 10 U.S. infants is born preterm, before 37 weeks gestation, according to the Centers for Disease Control and Prevention. That includes extremely preterm infants who weigh about 1 lb. at birth. These very low birthweight newborns have paper thin skin, frail hearts and lungs that are not yet mature enough to deliver oxygen throughout the body as needed. Thanks to advances in neocritical care, an increasing number of them survive prematurity, and many develop BPD, a chronic lung disease characterized by abnormal development of the lungs and pulmonary vasculature.
“About half of the babies born prematurely will come back to the hospital within the first year of life with a respiratory infection. The key is identifying them and, potentially, preventing complications in this high-risk population,” says Gustavo Nino, M.D., a Children’s National pulmonologist and the study’s lead author.
For decades, the most common way to stratify BPD risk in these vulnerable newborns has been to see if they require supplemental oxygen at 36 weeks corrected gestational age.
“The problem with this classification is it doesn’t take into account the very premature babies who are on oxygen for much longer than other babies. So, we asked the question: Can we continue risk stratification beyond 36 weeks in order to identify a subset of babies who are at much higher risk of complications,” Dr. Nino says.
The longitudinal cohort study enrolled 188 infants born extremely preterm who were admitted to the neonatal intensive care unit (NICU) at Children’s National and tracked their data for at least 12 months after discharge. The team used a multidimensional approach that tracked duration of supplemental oxygen during the newborns’ NICU stay as well as scoring lung imaging as an independent marker of BPD severity. To validate the findings, these U.S.-born newborns were matched with 130 infants who were born preterm and hospitalized at two NICUs located in Bogotá, Colombia.
“Babies who are born very preterm and require oxygen beyond 120 days should have expanded ventilation of the lungs and cardiovascular pulmonary system before going home,” he notes. “We need to identify these newborns and optimize their management before they are discharged.”
And, the babies with level IV BPD risk need a different type of evaluation because the complications they experience – including pulmonary hypertension – place them at the highest risk of developing sleep apnea and severe respiratory infection, especially during the first year of life.
“The earlier we identify them, the better their outcome is likely to be,” Dr. Nino says. “We really need to change the risk stratification so we don’t call them all ‘severe’ and treat them the same when there is a subset of newborns who clearly are at a much higher risk for experiencing respiratory complications after hospital discharge.”
In addition to Dr. Nino, Children’s National study co-authors include Awais Mansoor, Ph.D., staff scientist at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI); Geovanny F. Perez, M.D., pediatric pulmonologist; Maria Arroyo, M.D., pulmonologist; Xilei Xu Chen, M.D., postdoctoral fellow; Jered Weinstock, pediatric pulmonary fellow; Kyle Salka, MS, research technician; Mariam Said, M.D., neonatologist, and Marius George Linguraru, DPhil, MA, MSc, SZI principal investigator and senior author. Additional co-authors include Ranniery Acuña-Cordero, Universidad Militar Nueva Granada, Bogotá, Colombia; and Monica P. Sossa-Briceño and Carlos E. Rodríguez-Martínez, both of Universidad Nacional de Colombia.
Funding for research described in this post was provided by the National Institutes of Health (NIH) under award Nos. HL145669, AI130502 and HL141237. In addition, the NIH has awarded Dr. Nino an RO1 grant to continue this research.
“Fires, tornadoes and other natural disasters are outside of our team’s control. But it is within our team’s control to train neonatal intensive care unit (NICU) staff to master this necessary skill,” says Lisa Zell, BSN, a clinical educator at Children’s National Hospital.
Research into how to create a robust emergency evacuation preparedness plan and continually train staff that was led by Zell was lauded by editors of The Journal of Perinatal & Neonatal Nursing. The journal named the study the “best article” for the neonatal section that the prestigious journal published in 2018-19.
“We all hope for the best no matter what the situation, but we also need to extensively plan for the worse,” says Billie Lou Short, M.D., chief of the division of neonatology at Children’s National. “I’m proud that Lisa Zell and co-authors received this much-deserved national recognition on behalf of the nation’s No. 1 NICU.”
Educators worked with a diverse group within Children’s National to design and implement periodic evacuation simulations.
In addition to Zell and Lamia Soghier, M.D., FAAP, CHSE, Children’s National NICU medical unit director, study co-authors include Carmen Blake, BSN; Dawn Brittingham, MSN; and Ann-Marie Brown, MSN.
Children’s National Hospital is proud to have a number of faculty members who literally wrote the books on pediatric cardiology, neonatology, neurology and pulmonology. These texts, edited by experts Gil Wernovsky, M.D., Gordon Avery, M.D., Ricardo Munoz, M.D., Anastassios Koumbourlis, M.D., MPH, Robert Keating, M.D. and Roger Packer, M.D., have become the definitive references for medical students everywhere.
Through these books, generations of children worldwide will benefit from the expertise at Children’s National:
- Anderson’s Pediatric Cardiology. Wernovsky, G., Anderson, R.H., Kumar, K., Mussatto, K.A., Redington, A.N., Tweddell, J.S., Tretter, J.T. (Eds.). (2019). Philadelphia, PA: Elsevier Publishing.
- Avery’s Neonatology: Pathophysiology and Management of the Newborn. MacDonald, M.G., and Seshia, M.M.K. (Eds.) (2015). Philadelphia, PA: Lippincott Williams & Wilkins.
- Critical Care of Children with Heart Disease: Basic Medical and Surgical Concepts. Munoz, R.A., More, V.O., da Cruz, E.M., Vetterly, C.G., da Silva, J.P. (Eds.). (2010) London, UK: Springer-Verlag London Ltd.
- Diagnostic Tests in Pediatric Pulmonology. Davis, S.D., Koumbourlis, A.C., and Eber, E. (Eds.). (2015) London, UK: Springer-Verlag London Ltd.
- Pulmonary Complications of Non-Pulmonary Pediatric Koumbourlis, A.C., and Nevin, M. (Eds.). (2018) London, UK: Springer-Verlag London Ltd.
- Tumors of the Pediatric Central Nervous system. Keating, R.F., Goodrich, J.T., and Packer, R.J. (Eds.). (2013) New York, NY: Thieme Medical Publishers.
Even though mortality from congenital heart disease (CHD) has declined over the last three decades as diagnosis and treatments have advanced, the chances for a child to survive a CHD diagnosis significantly differs based on the country where he or she is born.
This eye-opening finding is drawn from the first comprehensive study of congenital heart disease across 195 countries, prepared using data from the Global Burden of Diseases, Injuries and Risk Factors Study 2017 (GBD), and recently published in The Lancet.
“Previous congenital heart estimates came from few data sources, were geographically narrow and did not evaluate CHD throughout the life course,” write the authors, known collectively as the 2017 GBD Congenital Heart Disease Collaborators. Co-lead author Meghan D. Zimmerman, M.D., worked on the study while completing her pediatric cardiology and American Heart Association Global Health Fellowships at Children’s National Hospital, and two pediatric cardiologists from Children’s National, Cardiology Associate Chief Craig Sable, M.D., and Gerard Martin, M.D., medical director of Global Services, provided leadership and oversight of this paper. The remaining collaborators are from more than 45 institutions around the world, spanning cardiology, public health and schools of medicine on every continent.
This is the first time the GBD study data was used along with all available data sources and previous publications – making it the most comprehensive study on congenital heart disease burden to date. Key differences between this study and prior estimates include:
- Anatomic groupings of CHD by type, rather than simply categorized as moderate, severe or critical.
- Inclusion of new data sources, including data from screening programs, congenital registries, administrative data and data sources in mortality and survival.
- A control mechanism to account for cases of CHD that remit on their own to reduce the risk of overestimating prevalence.
- Inclusion of all cases of congenital heart disease, including those with chromosomal or genetic anomalies such as Trisomy 21 that often co-occur.
This more comprehensive data set led to findings that showed lower predicted long-term survival, higher remission, and lower prevalence than previous studies that extrapolated evidence from studies of high-income countries. However, it also means these new estimates are a more accurate representation of the current global state of affairs. Overall, the study found:
- A 34.5% decline in deaths from congenital disease between 1990 to 2017.
- Nearly 70% of deaths caused by CHD in 2017 (180,624) were in infants less than one year old.
- Most CHD deaths occurred in countries within the low and low-middle socio-demographic index (SDI) quintiles.
- Mortality rates get lower as a country’s SDI rises.
- Birth prevalence of CHD was not related to a country’s socio-demographic status, but overall prevalence was much lower in the poorest countries of the world. This is because children in these countries do not have access to life saving surgical services.
- Nearly 12 million people are currently living with CHD globally, 18.7% more than in 1990.
- The burden of CHD is not fully realized by just looking at prevalence and mortality. The measure “Years of Life Lost” provides deeper insight into the staggering burden of CHD, taking into account both absolute mortality and age at death.
“In high income countries like the United States, we diagnose some heart conditions prenatally during the 20-week ultrasound,” says Gerard Martin, M.D., a pediatric cardiologist at Children’s National Hospital who contributed to the study. “We catch others right after birth with a pulse oximetry screening for critical congenital heart disease. We can operate to correct a critical issue within the first week of life. And now our CHD kids are growing and thriving through adulthood and having families of their own.”
“For children born in middle- and low-income countries, these data draw stark attention to what we as cardiologists already knew from our own work in these countries – the lack of diagnostic and treatment tools leads to lower survival rates for children born with CHD,” adds Craig Sable, M.D., associate chief of cardiology at Children’s National, another primary contributor. “This is one of the most significant publications I have been a part of as it highlights the substantial loss of life to CHD in infancy around the globe.”
The authors write, “The UN has prioritized reduction of premature deaths from heart disease, but to meet the target of ‘ending preventable deaths of newborns and children under 5 years of age,’ health policy makers will need to develop specific accountability measures that address barriers and improve access to care and treatment.”
The study also includes a 400-page appendix breaking down each area by type of congenital anomaly, world region and country.
The official call for submissions is underway for the premiere annual pediatric medical device competition, sponsored by National Capital Consortium for Pediatric Device Innovation (NCC-PDI). The competition is led by Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital, the A. James Clark School of Engineering at the University of Maryland and non-profit accelerator MedTech Innovator. The three organizations are all an integral part of the FDA-funded NCC-PDI, which aims to facilitate the development, production and distribution of pediatric medical devices. Additional NCC-PDI members include accelerator BioHealth Innovation and design firm Archimedic.
The competition focuses on pediatric devices in three areas of critical need: cardiovascular, orthopedic and spine, and neonatal intensive care (NICU) and is now accepting applications. Contestants will pitch for a share of up to $250K in grant awards and the opportunity to participate in the MedTech Innovator 2020 Accelerator – Pediatric Track.
The first stage of competition will be held on March 23 at the University of Maryland and will include up to 30 companies selected from all submissions received. Up to 10 finalists selected from that event will move on to the “Make Your Medical Device Pitch for Kids!” finals on October 4, 2020 in Toronto, Canada. Finalists from the March qualifying round will be notified in May, 2020.
“While there is a great need for pediatric devices in many specialty areas, the development and commercialization process is very challenging because of the small market size and dynamic characteristics of the patient population,” says Kolaleh Eskandanian, Ph.D., MBA, PMP, vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “To provide pediatric innovators with greater support in meeting these unique challenges, we must go beyond grant funding, which is why we are collaborating with MedTech Innovator to offer an accelerator program with a pediatric track.”
To date, NCC-PDI has mentored over 100 medical device sponsors to help advance their pediatric innovations, notes Eskandanian, with six devices having received either their FDA market clearance or CE marking. She says the success of NCC-PDI’s portfolio companies is attributed to funding, mentorship, support from partners, facilitated interactions between device innovators and potential investors, and being discovered during their presentations at the signature “Make Your Medical Device Pitch for Kids!” competitions.
While advancements have been made in some pediatric specialties, there is still a critical need for novel devices in cardiovascular, orthopedic and spine, and NICU areas. On average over the past decade, only 24 percent of life-saving medical devices approved by FDA – those that go through PMA and HDE regulatory pathways – have an indication for pediatric use. Of those, most are designated for children age 12 or older. “Devices designed specifically for the younger pediatric population are vitally needed and, at this early stage of the intervention, can significantly improve developmental outcomes for a child,” Eskandanian said.
For more information and to apply for the upcoming NCC-PDI pitch competition, visit https://medtechinnovator.org/pediatricapply/.
Enhancing access to resources for pediatric innovators is also one of the aims of the Children’s National Research and Innovation Campus, a first-of-its-kind focused on pediatric healthcare innovation, currently under development on the former Walter Reed Army Medical Center campus in Washington, D.C. and opening in December, 2020. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on site accelerator Johnson and Johnson Innovation – JLABS, the campus will create a rich ecosystem of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization.
When a diagnosis of fetal congenital heart disease causes pregnant moms to test positive for stress, anxiety and depression, powerful imaging can detect impaired development in key fetal brain regions, according to Children’s National Hospital research published online Jan. 13, 2020, in JAMA Pediatrics.
While additional research is needed, the Children’s National study authors say their unprecedented findings underscore the need for universal screening for psychological distress as a routine part of prenatal care and taking other steps to support stressed-out pregnant women and safeguard their newborns’ developing brains.
“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author. “Equally concerning is how prevalent psychological distress is among pregnant women generally. We report for the first time that this challenging prenatal environment impairs regions of the fetal brain that play a major role in learning, memory, coordination, and social and behavioral development, making it all the more important for us to identify these women early during pregnancy to intervene,” Limperopoulos adds.
Congenital heart disease (CHD), structural problems with the heart, is the most common birth defect. Still, it remains unclear how exposure to maternal stress impacts brain development in fetuses with CHD.
The multidisciplinary study team enrolled 48 women whose unborn fetuses had been diagnosed with CHD and 92 healthy women with uncomplicated pregnancies. Using validated screening tools, they found:
- 65% of pregnant women expecting a baby with CHD tested positive for stress
- 27% of women with uncomplicated pregnancies tested positive for stress
- 44% of pregnant women expecting a baby with CHD tested positive for anxiety
- 26% of women with uncomplicated pregnancies tested positive for anxiety
- 29% of pregnant women expecting a baby with CHD tested positive for depression and
- 9% women with uncomplicated pregnancies tested positive for depression
All told, they performed 223 fetal magnetic resonance imaging sessions for these 140 fetuses between 21 and 40 weeks of gestation. They measured brain volume in cubic centimeters for the total brain as well as volumetric measurements for key regions such as the cerebrum, cerebellum, brainstem, and left and right hippocampus.
Maternal stress and anxiety in the second trimester were associated with smaller left hippocampi and smaller cerebellums only in pregnancies affected by fetal CHD. What’s more, specific regions — the hippocampus head and body and the left cerebellar lobe – were more susceptible to stunted growth. The hippocampus is key to memory and learning, while the cerebellum controls motor coordination and plays a role in social and behavioral development.
The hippocampus is a brain structure that is known to be very sensitive to stress. The timing of the CHD diagnosis may have occurred at a particularly vulnerable time for the developing fetal cerebellum, which grows faster than any other brain structure in the second half of gestation, particularly in the third trimester.
“None of these women had been screened for prenatal depression or anxiety. None of them were taking medications. And none of them had received mental health interventions. In the group of women contending with fetal CHD, 81% had attended college and 75% had professional educations, so this does not appear to be an issue of insufficient resources,” Limperopoulos adds. “It’s critical that we routinely to do these screenings and provide pregnant women with access to interventions to lower their stress levels. Working with our community partners, Children’s National is doing just that to help reduce toxic prenatal stress for both the health of the mother and for the future newborns. We hope this becomes standard practice elsewhere.”
Adds Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author: “Our next goal is exploring effective prenatal cognitive behavioral interventions to reduce psychological distress felt by pregnant women and improve neurodevelopment in babies with CHD.”
In addition to Limperopoulos and Wu , Children’s National study co-authors include Kushal Kapse, MS, staff engineer; Marni Jacobs, Ph.D., biostatistician; Nickie Niforatos-Andescavage, M.D., neonatologist; Mary T. Donofrio, M.D., director, Fetal Heart Program; Anita Krishnan, M.D., associate director, echocardiography; Gilbert Vezina, M.D., director, Neuroradiology Program; David Wessel, M.D., Executive Vice President and Chief Medical Officer; and Adré J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Jessica Lynn Quistorff, MPH, Catherine Lopez, MS, and Kathryn Lee Bannantine, BSN, assisted with subject recruitment and study coordination.
Financial support for the research described in this post was provided by the National Institutes of Health under grant No. R01 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.
The amount of blood that the heart pumps in one minute (cardiac output) can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates a paper published online Dec. 17, 2019 in the Journal of Pediatrics and Neonatal Medicine. The research, conducted by Children’s National Hospital faculty, is believed to be the first clinical study of direct cardiac output measurement in newborns.
Right now, cardiac output is measured indirectly in the nation’s neonatal intensive care units (NICU) using newborns’ blood pressure, heart rate, urine output and other indirect measures. However, these techniques can produce imprecise readings in children. And the field lacks a feasible “gold standard” to measure cardiac output in newborns.
The COstatus monitor already uses ultrasound dilution – the expected decrease in the velocity of blood when saline is injected, producing a dilution curve. A Children’s National research team used ultrasound dilution in their small pilot study to gauge the feasibility of directly measuring cardiac output in newborns.
“Infants who stand to benefit most from directly monitoring cardiac hemodynamics are often so sick they already have central venous access,” says Khodayar Rais-Bahrami, M.D., an attending neonatologist at Children’s National and the study’s senior author. “Using the COstatus monitor in these children would enable the clinical team to personalize care based on the newborn’s current hemodynamic status, while introducing minimal fluid during measurements,” Dr. Rais-Bahrami adds.
The research team recruited 12 newborns younger than 2 weeks old who already had central venous and arterial access. The venous line of the arteriovenous AV loop is connected to the umbilical venous catheter while the COstatus monitor’s arterial line is connected to the umbilical arterial catheter. During measurement sessions, two injections of solution are injected into the venous loop, allowing for two measures of cardiac output, cardiac index, active circulating volume index, central blood volume index and systemic vascular resistance index.
Infants enrolled in the pilot study underwent up to two measurement sessions per day for up to four days, for a total of 54 cardiac hemodynamic measurements. The newborns ranged from 720 to 3,740 grams in weight and 24 to 41.3 weeks in gestational age.
The infants’ mean cardiac output was 0.43L/min and increased with gestational age. By contrast, the mean cardiac index was 197mL/kg/min and changed little with infants’ increasing maturity – either by gestational age or postnatal age. Two of the study participants were undergoing therapeutic cooling for hypoxic-ischemic encephalopathy and had their measurements taken during cooling and after rewarming.
“Although this study size is small, it demonstrates that this minimally invasive technique can safely be used in newborns to directly measure cardiac hemodynamics,” says Simranjeet S. Sran, M.D., a Children’s National neonatalogist and the study’s lead author. “This technology may allow for more precise and personalized care of critically ill newborns in a range of disease states – real-world utility in NICUs that serve some of the youngest and sickest newborns,” Dr. Sran adds.
The research team notes that direct measurement by ultrasound dilution revealed a stark increase in cardiac index as infants undergoing therapeutic hypothermia were rewarmed, raising questions about whether indirect measures using other technology, such as echocardiography, underestimate hypothermia’s effect on hemodynamics.
In addition to Drs. Rais-Bahrami and Sran, Mariam Said, M.D., also a Children’s National neonatalogist, was a study co-author.