Genetics & Rare Diseases News Archives

Marius George Linguraru giving a lecture on AI

Artificial – and accelerated – intelligence: endless applications to expand health equity

April 24, 2024

In the complex world of pediatric diseases, researchers need access to data to develop clinical trials and the participation of vulnerable patients to develop new devices and therapies. Both are in short supply, given that most children are born healthy, and most severe pediatric diseases are rare.

That creates a dilemma: how do researchers build a foundation to advance new treatments? Enter artificial intelligence (AI).

“AI is the equalizer: accelerated intelligence for sick kids. No other advance on the horizon holds more promise for improving equity and access to pediatric healthcare when diseases are rare and resources are limited,” says Marius George Linguraru, D.Phil., M.A., M.Sc., the Connor Family Professor in Research and Innovation and principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI). “AI will shrink the distance between patient and provider, allowing our physicians and scientists to provide targeted healthcare for children more efficiently. The possibilities are endless.”

Why we’re excited

By pioneering AI innovation programs at Children’s National Hospital, Dr. Linguraru and the AI experts he leads are ensuring patients and families benefit from a coming wave of technological advances. The team is teaching AI to interpret complex data that could otherwise overwhelm clinicians. Their work will create systems to identify at-risk patients, forecast disease and treatment patterns, and support complex clinical decisions to optimize patient care and hospital resources. Already, the AI team at SZI has developed data-driven tools touching nearly every corner of the hospital:

AI for rheumatic heart disease (RHD): In partnership with Children’s National cardiology leaders, including Craig Sable, M.D., the Uganda Heart Institute and Cincinnati Children’s Hospital, the AI team has developed an algorithm that can use low-cost, portable ultrasound imaging to detect RHD in children and young adults, a disease that takes nearly 400,000 lives annually in limited-resource countries. Early testing shows the AI platform has the same accuracy as a cardiologist in detecting RHD, paving the way for earlier treatment with life-saving antibiotics. This year, Children’s National physicians will be in Uganda, screening 200,000 children with local cardiology experts and AI technology.
Newborn screening for genetic conditions with mGene: Working with Rare Disease Institute clinicians and Chief of Genetics and Metabolism Debra Regier, M.D., the AI team has built technology to detect rare genetic disorders, using an algorithm and a smartphone camera to identify subtle changes in facial features. Tested on patients from over 30 countries and published in The Lancet Digital Health, the application helps screen children for advanced care when a geneticist may not be within reach. With funding from the National Institutes of Health, Children’s National and its research partners are piloting a newborn screening program in the Democratic Republic of the Congo.
Pediatric brain tumors: To improve and personalize the treatment decisions for children with brain tumors, Dr. Linguraru’s team is working with Brain Tumor Institute Director Roger Packer, M.D., the Gilbert Family Distinguished Professor of Neurofibromatosis, on algorithms that can characterize and measure brain tumors with unprecedented precision. The team recently won the International Pediatric Brain Tumor Segmentation Challenge, distinguishing the Children’s National algorithm as among the best in the world.
Ultra-low field magnetic resonance imaging (MRI): With a grant from the Bill & Melinda Gates Foundation, the AI team is working alongside Children’s Hospital Los Angeles, King’s College London and the UNITY Consortium to expand global brain imaging capacity. The consortium is helping clinicians in limited-resource countries improve the treatment of neonatal neurological conditions, using AI to boost the quality of ultra-low field MRI and expand access to this portable and more affordable imaging option.
Federated learning: Children’s National has collaborated with NVIDIA and other industry leaders to accelerate AI advances through federated learning. Under this approach, institutions share AI models rather than data, allowing them to collaborate without exposing patient information or being constrained by essential data-sharing restrictions. The SZI team was the only pediatric partner invited to join the largest federated learning project of its kind, studying the lungs of COVID-19 patients. Details were published in Nature Medicine.

Children’s National leads the way

Looking ahead, the Children’s National AI team is pursuing a wide range of advances in clinical care. To support patients treated at multiple clinics, they are developing systems to harmonize images from different scanners and protocols, such as MRI machines made by different manufacturers. Similar work is underway to analyze pathology samples from different institutions consistently.

Automation is also making care more efficient. For example, using data from 1 million chest X-rays, the team is collaborating with NVIDIA to develop a conversational digital assistant that will allow physicians to think through 14 possible diagnoses.

Dr. Linguraru says he and his colleagues are galvanized by the jarring statistic that one in three children with a rare disease dies before age 5. While well-implemented AI initiatives can change outcomes, he says the work must be done thoughtfully.

“In the future, patients will be evaluated by human clinicians and machines with extraordinary powers to diagnose illness and determine treatments,” Dr. Linguraru said. “Our team at Children’s National is leading conversations about the future of pediatric healthcare with a focus on safety, resource allocation and basic equity.”

Learn more about our AI initiatives

Innovation leaders at Children’s National Hospital are building a community of AI caregivers through educational and community-building events. At the inaugural Symposium on Artificial Intelligence in 2023 at the Children’s National Research & Innovation Campus, experts from Virginia Tech, JLABS, Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere laid out a vision for using data to advance pediatric medicine. The symposium will return on Sept. 6.

Dr. Linguraru is the program chair of MICCAI 2024, the top international meeting on medical image computing and computer-assisted intervention and the preeminent forum for disseminating AI developments in healthcare. The conference is an educational platform for scientists and clinicians dedicated to AI in medical imaging, with a focus on global health equity. It will take place for the first time in Africa on Oct. 6-10.

Novel cell therapy treatments offer promise to immune-compromised children

April 18, 2024

teenager receiving an intravenous infusion

In a first-of-its-kind clinical trial, researchers found that intravenous therapies made from virus-specific T-cells (VST) can effectively treat immunocompromised pediatric patients, far surpassing the current standard of care, according to new research published in Nature Communications.

More than 60% of patients in the phase 2 clinical trial led by investigators from Children’s National Hospital and Huntsman Cancer Institute responded to the innovative VST therapy. This new treatment uses blood from healthy donors to manufacture a highly specialized immune therapy that, when given to immune-compromised patients, prompts their immune system to fight off potentially life-threatening viruses, including cytomegalovirus, Epstein-Barr and adenovirus. Without this therapy, estimates suggest that less than 30% of patients would recover, using standard protocols.

“A vast majority of our patients not only responded to the therapy, but they were able to come off their antivirals, which come with extensive side effects,” said Michael Keller, M.D., the paper’s first author and the Translational Research Laboratory director at the Children’s National Cell Enhancement and Technologies for Immunotherapy (CETI) program. “This promising data suggests hope for patients with rare immune-compromising diseases that leave them vulnerable to so much in the world.”

The study brings together experts from the Pediatric Transplantation and Cell Therapy Consortium (PTCTC) and the Primary Immune Deficiency Treatment Consortium (PIDTC) to create the first multi-center, pediatric-consortium trial of adoptive T-cell therapies for viruses. It also represents one of the first to include critically ill patients, who are often excluded from research.

Children’s National leads the way

Working alongside Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research (CCIR), Dr. Keller and the CCIR team helped build an internationally recognized program, pioneering therapies to prevent complications from viral infections in immunocompromised patients. This includes patients with congenital immune deficiency and others who have undergone bone marrow transplantation for malignancies or non-malignant conditions, such as sickle cell disease.

While doctors can treat some immune-compromised patients for infections with standard antivirals, a small fraction don’t respond. Children’s National is one of a handful of hospitals in the country that has options. Over the last several decades, researchers have found ways to develop VST therapies made from banked T-cells, a more advanced application of how donated red blood cells are used to treat anemia.

In 2017, Drs. Keller and Bollard started collaborating with Michael Pulsipher, M.D.—now with Intermountain Primary Children’s Hospital and the Huntsman Cancer Institute at the University of Utah—to create a multi-institute clinical study. They combined the expertise at Children’s National in producing and banking cell therapy products with the community built around the PTCTC. Ultimately, they launched a clinical trial that was open to 35 centers in the U.S., enrolling 51 patients at 22 hospitals from 2018-2022.

“We wanted to prove that this potentially life-saving therapy could be given safely at regional pediatric centers that had never been able to use this approach before,” said Dr. Pulsipher, who served as the study’s co-principal investigator with Dr. Keller. “We united top experts in this area from the PTCTC and PIDTC and successfully treated some of the most challenging patients ever treated with this approach. Our findings helped define who can benefit the most from this therapy, paving the way for commercial development.”

The Good Manufacturing Practices (GMP) laboratory at Children’s National, led by Patrick Hanley, Ph.D., provided suitable VST therapies for 75 of 77 patients who requested to join the study. Clinical responses were achieved in 62% of patients who underwent stem cell transplants and in 73% of patients who were treated with VST and evaluated one month after their infusion. The paper laid out risks and clinical factors impacting outcomes when third-party donors are used to manufacture the VST therapies.

What’s ahead

Given that researchers are only beginning to develop cell therapies, work remains to understand the many ways they interact with the immune system. In a separate paper also recently published in Nature Communications, members of the multi-institute team documented a case of an infant with severe combined immune deficiency, who faced extremely rare side effects when the VST treatment interfered with her donor bone marrow graft. The case led the team to work with the Food and Drug Administration to identify criteria for VST donors enrolled in this study to mitigate complications.

In the decade ahead, Dr. Bollard sees promise in cell therapies for patients with cancer, immune deficiencies after transplant and dozens of other disorders, including genetic and autoimmune diseases. “Future studies will continue to look at ways to optimize the manufacturing, the administration and the long-term outcomes for these therapies—and to enhance the lifelong impact on our patients,” she said. “When we pair human ingenuity with the power of technology, I see tremendous potential.”

Acknowledgments: This study was funded with a nearly $5 million grant from the California Institute of Regenerative Medicine and was run through the operations center at the Children’s Hospital of Los Angeles, where Dr. Pulsipher was formerly on faculty.

Inequity complicates care for children with tracheostomies

April 5, 2024

Study finds healthcare inequities complicate care of children with tracheostomies.

Approximately 4,000 children in the United States annually undergo tracheostomies, a lifesaving procedure for severe respiratory compromise or upper-airway obstruction. While children with tracheostomies are living longer because of technological advances, their caretakers encounter a variety of issues once at-home care begins, as reported in a study published in Qualitative Health Research.

The study identified lingering problems from the lack of equitable access to appropriate support for patient families and caregivers. Jules Sherman, M.F.A., director of the Biodesign Program at Children’s National Innovation Ventures, led the research in collaboration with Kyle L. Bower, Ph.D., a researcher and instructor at The University of Georgia, and Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National.

The big picture

Interview subjects were 11 primary caregivers of children ages 16 months to 11 years who had a tracheostomy and were supported by multiple lifesaving devices at home such as a ventilator, humidifier and other required medical supplies.

Subjects were questioned about influences and relationships they believed impacted the trajectory of care given to children with tracheostomies. Three themes emerged:

Insufficient peer support: Caregivers struggled to find groups who shared similar experiences to help them navigate the uncertainty surrounding their child’s medical care, and content on social media peer groups sometimes heightened their sense of worry.
Ineffective trach-care training:
- For families — Caregivers said the trach-care training they received at their respective hospitals did not reflect real-time situations at home, resulting in high levels of anxiety, multiple home emergency situations and routine calls to 911.
- Home health nurses — Caregivers shared instances of poor decision-making by at-home nurses in emergency situations, lack of communication with primary caregivers and lack of respect for their input.
Challenges facing integrated care: The absence of cohesion between medical professionals, durable medical equipment (DME) companies and insurance providers creates many challenges for caregivers. Due to the excessive cost of lifesaving medical devices and negative interactions by caregivers with insurance companies and DMEs, some caregivers reported turning to the black market to purchase needed medical supplies.

Why it matters

In the United States, 60 percent of children with tracheostomies are readmitted to the hospital for tracheostomy-associated respiratory infection within the first six months of the surgery. This study highlights systemic failures and inequities within the healthcare system, beginning at the hospital and following affected families into their homes, indicating that improvements in the support system, training and healthcare coverage are sorely needed.

The need for a better tracheostomy solution was introduced to Children’s National’s Innovation Ventures by two hospital physicians who are otolaryngologists, Habib Zalzal, M.D. and Rahul Shah, M.D., M.B.A. Followed by an initial market study and design by design firm Archimedic, study author, Sherman, continues working with clinicians at Children’s National and engineers at the University of Oregon and University of Maryland to enhance the prototype developed at Children’s National. The device, called as Trach Sense, is designed to detect accidental decannulation and obstruction events, which are leading causes of tracheostomy-related complications.

This study was supported by the Food and Drug Administration grants P50FD006430 and P50FD007965. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement, by the FDA, Department of Health and Human Services or the U.S. government.

First global clinical trial achieves promising results for hypochondroplasia

March 15, 2024

Trial participant Mia Maric is measured by Dr. Andrew Dauber.

Researchers from Children’s National Hospital presented findings from the first clinical trial of the medication vosoritide for children with hypochondroplasia – a rare genetic growth disorder. The results were presented at the 2024 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting.

The big picture

Recently approved to increase linear growth and open growth plates in children with achondroplasia, vosoritide is a C-type natriuretic peptide analog that binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation by inhibiting the ERK1/2-MAPK pathway.

“Vosoritide directly targets the pathway in the growth plate that is affected by the genetic mutation causing hypochondroplasia,” said Andrew Dauber M.D., M.M.Sc., chief of Endocrinology at Children’s National and lead author of the study.

During the phase 2 trial, researchers found vosoritide increased the growth rate in children with hypochondroplasia, allowing them to grow on average an extra 1.8 cm per year.

The patient benefit

Ivan Maric’s 11-year-old daughter, Mia, has been participating in the trial for the last 18 months. In 2022, they moved from Croatia to be part of the study.

“This has been life-changing for Mia,” Maric said. “Soon after receiving the initial doses, we immediately noticed growth. Now, she can independently manage everyday tasks such as washing her hair and reaching the sink to wash her hands.”

What’s next

Vosoritide treatment may work as a precision therapy to improve growth in multiple genetic conditions that interact with the ERK1/2-MAPK pathway.

“This study provides a proof of principle that this medicine will work for these children and supports further research in this area,” said Dr. Dauber. “I was excited to see how well tolerated the medication was and how some patients had excellent responses.”

This clinical trial funded by BioMarin is the first-of-its-kind to treat children with genetic short stature who do not have achondroplasia. Other growth-related conditions included in this phase 2 trial were Noonan syndrome, NPR2 mutations and Aggrecan mutations.

Additional authors from Children’s National: Anqing Zhang, Ph.D., Roopa Kanakatti Shankar, M.D., Kimberly Boucher, R.N., Tara McCarthy, B.A., Niusha Shafaei, B.A., Raheem Seaforth, B.A., Meryll Grace Castro, M.S., and Niti Dham, M.D.

Pioneering research center aims to revolutionize prenatal and neonatal health

February 29, 2024

1 2 3 4

Catherine Limperopoulos, Ph.D., was drawn to understanding the developing brain, examining how early adverse environments for a mother can impact the baby at birth and extend throughout its entire lifetime. She has widened her lens – and expanded her team – to create the new Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital.

“Despite the obvious connection between mothers and babies, we know that conventional medicine often addresses the two beings separately. We want to change that,” said Dr. Limperopoulos, who also directs the Developing Brain Institute. “Given the current trajectory of medicine toward precision care and advanced imaging, we thought this was the right moment to channel our talent and resources into understanding this delicate and highly dynamic relationship.”

Moving the field forward

Since its establishment in July 2023, the new research center has gained recognition through high-impact scientific publications, featuring noteworthy studies exploring the early phases of human development.

Dr. Limperopoulos has been at the forefront of groundbreaking research, directing attention to the consequences of maternal stress on the unborn baby and the placenta. In addition, under the guidance of Kevin Cook, Ph.D., investigators published a pivotal study on the correlation between pain experienced by premature infants in the Neonatal Intensive Care Unit and the associated risks of autism and developmental delays.

Another area of research has focused on understanding the impact of congenital heart disease (CHD) on prenatal brain development, given the altered blood flow to the brain caused by these conditions during this period of rapid development. Led by Josepheen De Asis-Cruz, M.D., Ph.D., a research team uncovered variations in the functional connectivity of the brains of infants with CHD. In parallel, Nickie Andescavage, M.D., and her team employed advanced imaging techniques to identify potential biomarkers in infants with CHD, holding promise for guiding improved diagnostics and postnatal care. Separately, she is investigating the impact of COVID-19 on fetal brain development.

In the months ahead, the team plans to concentrate its efforts on these areas and several others, including the impact of infectious disease, social determinants of health and protecting developing brains from the negative impacts of maternal stress, pre-eclampsia and other conditions prevalent among expectant mothers.

Assembling a team

Given its robust research plan and opportunities for collaboration, the center pulled together expertise from across the hospital’s faculty and has attracted new talent from across the country, including several prominent faculty members:

Daniel Licht, M.D., has joined Children’s National to build a noninvasive optical device research group to better care for children with CHD. Dr. Licht brings decades of experience in pediatric neurology, psychiatry and critical care and is recognized internationally for his expertise in neurodevelopmental outcomes in babies with CHD.
Katherine L. Wisner, M.S., M.D., has accumulated extensive knowledge on the impact of maternal stress on babies throughout her career, and her deep background in psychiatry made her a natural addition to the center. While Dr. Wisner conducts research into the urgent need to prioritize maternal mental health, she will also be treating mothers as part of the DC Mother-Baby Wellness Initiative — a novel program based at Children’s National that allows mothers to more seamlessly get care for themselves and participate in mother-infant play groups timed to align with their clinical appointments.
Catherine J. Stoodley, B.S., M.S., D.Phil., brings extensive research into the role of the cerebellum in cognitive development. Dr. Stoodley uses clinical studies, neuroimaging, neuromodulation and behavioral testing to investigate the functional anatomy of the part of the brain responsible for cognition.
Katherine M. Ottolini, M.D., attending neonatologist, is developing NICU THRIVE – a research program studying the effects of tailored nutrition on the developing newborn brain, including the impact of fortifying human milk with protein, fat and carbohydrates. With a grant from the Gerber Foundation, Dr. Ottolini is working to understand how personalized fortification for high-risk babies could help them grow.

Early accolades

The new center brings together award-winning talent. This includes Yao Wu, Ph.D., who recently earned the American Heart Association’s Outstanding Research in Pediatric Cardiology award for her groundbreaking work in CHD, particularly for her research on the role of altered placental function and neurodevelopmental outcomes in toddlers with CHD. Dr. Wu became the third Children’s National faculty member to earn the distinction, joining an honor roll that includes Dr. Limperopoulos and David Wessel, M.D., executive vice president and chief medical officer.

Interim Chief Academic Officer Catherine Bollard, M.D., M.B.Ch.B., said the cross-disciplinary collaboration now underway at the new center has the potential to make a dramatic impact on the field of neonatology and early child development. “This group epitomizes the Team Science approach that we work tirelessly to foster at Children’s National,” Dr. Bollard said. “Given their energetic start, we know these scientists and physicians are poised to tackle some of the toughest questions in maternal-fetal medicine and beyond, which will improve outcomes for our most fragile patients.”

Next-generation genomics testing holds key to undiagnosed rare disease

February 28, 2024

Before and after pictures of the patient's improved gait Seth Berger, M.D., Ph.D., felt the pull to dig deeper when he started reading the chart. An 11-year-old boy had an abnormal gait and couldn’t even walk in a straight line down the sidewalk to go trick-or-treating. Yet workups with neurology, orthopedics and an exome analysis of the patient’s genetic code did not provide a diagnosis. He had been getting worse for roughly three years.

With one of the largest clinical genetics departments in the country, Children’s National Hospital receives more than 10,000 visits a year from patients like this middle schooler. Often, they are children and caregivers who are searching for answers and follow-up support for diagnoses of genetic disorders, which impact so few people that only highly trained geneticists and genetic counselors can get to the root of the disorder.

“In genetics, we are finding layers of understanding. A negative clinical test is not always the final answer because the significance of variants can often be missed or misunderstood,” said Dr. Berger, a medical geneticist and principal investigator in the Center for Genetics Medicine Research at Children’s National. “It can take extensive research and a deep knowledge of the limits of certain tests to reach a diagnosis.”

The fine print

On page 4 of the patient’s genetics report, Dr. Berger found a reference to a pair of variants with no known clinical impact. Dr. Berger recognized that the genes referenced could affect proteins that drive potentially treatable neurological outcomes.

Dr. Berger ordered further testing, including biochemical testing of the patient’s blood and a phenylalanine loading challenge, a test that measures how the body metabolizes certain amino acids. With the results, he confirmed a recessive GCH1 deficiency in the patient was causing a condition called DOPA-responsive dystonia, a disorder that causes involuntary muscle contractions, tremors and uncontrolled movements. Laura Schiffman Tochen, M.D., director of the Movement Disorders Program at Children’s National, started the patient on levodopa-carbidopa — a drug combination used to treat Parkinson’s disease and other neurological disorders — and within two hours the boy showed improvement. His gait was almost normal.

Why we’re excited

Dr. Berger presents at conferences on this case and several other medical mysteries that he’s recently solved in his clinical practice and his role at the Pediatric Mendelian Genomics Research Center, a Children’s National program immersed in a federally funded research study to better understand how differences in genetic material can affect human health. As part of his work, he’s joined the GREGoR project (Genomic Research to Elucidate the Genetics of Rare Disease), which hopes to increase the number of genetic disorders where a cause can be identified. The elite genetics consortium includes nationally recognized research centers – the University of California at Irvine, Broad Institute, University of Washington, Baylor University, Stanford University, Invitae and Children’s National – which are working together to harness cutting-edge genomics sequencing capabilities. They hope to enroll thousands in their research, funded by the National Institutes of Health.

“It’s truly stunning what genetic sequencing can find. The outcomes can be life-changing,” said Dr. Berger. “These cases with life-altering diagnoses don’t come along every day, but when they do, they make the hunt to find answers all the more worthwhile.”

The endovascular embolic hemispherectomy team.

New hemimegalencephaly procedure is all about teamwork

February 23, 2024

Children’s National experts pioneered a novel approach of inducing strokes to stop seizures and improve neurodevelopmental outcomes in newborns under three months old with hemimegalencephaly (HME). The procedure, called an endovascular embolic hemispherectomy, can be safely used to provide definitive treatment of HME-related epilepsy in neonates and young infants. Monica Pearl, M.D., neurointerventional radiologist, and Panagiotis Kratimenos, M.D., Ph.D., neonatologist, discuss why having a multidisciplinary team skilled at this procedure is the reason we’re the only center in the world capable of providing this treatment.

The history behind the novel hemimegalencephaly procedure

February 23, 2024

Traditionally, when a baby is diagnosed with hemimegalencephaly (HME), doctors turn to a hemispherectomy at 3 months of age, which involves surgically removing half of a baby’s brain. At Children’s National Hospital, our doctors pioneered the endovascular embolic hemispherectomy, an approach using induced controlled strokes to eliminate the affected part of the brain, halting seizures. Monica Pearl, M.D., neurointerventional radiologist, and Tammy Tsuchida, M.D., Ph.D., neonatal neurologist, talk about this life-changing procedure.

Angelique and family pose in front of their house

Inducing strokes to better treat babies with hemimegalencephaly

February 23, 2024

When a family from Texas received a shocking diagnosis for their newborn daughter, they knew there was one place they needed to go – Children’s National Hospital in Washington, D.C. At birth, Angelique was diagnosed with a rare and devastating condition known as hemimegalencephaly (HME) which causes uncontrollable and frequent seizures. Monica Pearl, M.D., neurointerventional radiologist, and the team at Children’s National have pioneered an approach to treat HME, where they induce controlled strokes to eliminate the affected part of the brain, halting seizures in their tracks. They’re the only team in the world doing this work. Angelique’s parents knew the clock was ticking — every day they waited meant irreversible damage to their daughter’s developing brain.

desktop computer showing the CNRI Annual Report

Driving pediatric breakthroughs through 2023

February 15, 2024

desktop computer showing the CNRI Annual Report The Children’s National Research Institute released its 2022-2023 Academic Annual Report. In the report, a summary of the past academic year highlights the accomplishments of each of the institute’s research centers, provides research funding figures and exalts some of the institute’s biggest milestones.

The stories in the report are a testament to the hard work and dedication of everyone at the Children’s National Research Institute.

We celebrated five decades of leadership and mentorship of Naomi Luban, M.D., and her incredible accomplishments in the W@TCH program, which have been instrumental in shaping the future of pediatric research.

We also celebrated innovation, highlighting our recent FDA award to lead a pediatric device consortium, which recognizes our commitment to developing innovative medical devices that improve the lives of children.

Breakthroughs at the Research & Innovation Campus continued as our researchers worked tirelessly to develop new treatments and therapies that will transform the lives of children and families around the world.

Taking a look at the breakthroughs happening in our now six research centers, we spotlighted the following stories:

Reflecting on decades of progress in the blood, marrow and cell therapy programs at Children’s National. Our researchers have made significant strides in this field, and we are proud to be at the forefront of these life-saving treatments.
In genetic medicine, we continue to be a beacon of hope for families facing rare and complex conditions. Our researchers are making incredible breakthroughs that are changing the landscape of pediatric medicine.
We are also proud to share the $90 million award received from an anonymous donor to support pediatric brain tumor research. The predominant focus of this award is to develop new treatments that will improve outcomes for children with this devastating disease.
This year, we opened a new Center that enhances our research capabilities in the field of Prenatal, Neonatal & Maternal Health Research. We are excited about the possibilities this new center will bring and look forward to the discoveries that will emerge from it.
In addition, we are driving future pandemic readiness with the NIH funded Pediatric Pandemic Network. Our researchers are using cutting-edge technology and innovative approaches to prepare for the next pandemic and protect children.
We are also exploring the potential of artificial intelligence (AI) in pediatric breakthroughs. Our researchers are using machine learning and other AI techniques to develop new treatments and therapies that will transform the lives of children.

Children’s National in the News: 2023

January 18, 2024

Explore some of the notable medical advancements and stories of bravery that defined 2023, showcasing the steadfast commitment of healthcare professionals at Children’s National Hospital and the resilient spirit of the children they support. Delve into our 2023 news highlights for more.

1. COVID during pregnancy dramatically increases the risk of complications and maternal death, large new study finds

According to a study published in British Medical Journal Global Health, women who get COVID during pregnancy are nearly eight times more likely to die and face a significantly elevated risk of ICU admission and pneumonia. Sarah Mulkey, M.D., prenatal-neonatologist neurologist, discussed findings based on her work with pregnant women and their babies.
(Fortune)

2. Rest isn’t necessarily best for concussion recovery in children, study says

A study led by Christopher Vaughan, Psy.D., pediatric neuropsychologist, suggests that — despite what many people may presume — getting kids back to school quickly is the best way to boost their chance for a rapid recovery after a concussion.
(CNN)

3. Pediatric hospital beds are in high demand for ailing children. Here’s why

David Wessel, M.D., executive vice president, chief medical officer and physician-in-chief, explained that one reason parents were still having trouble getting their children beds in a pediatric hospital or a pediatric unit after the fall 2022 respiratory surge is that pediatric hospitals are paid less by insurance.
(CNN)

4. Anisha Abraham details impact of social media use on children: ‘True mental health crisis’

Anisha Abraham, M.D., M.P.H., chief of the Division of Adolescent and Young Adult Medicine, joined America’s Newsroom to discuss the impact social media access has had on children’s mental health.
(FOX News)

5. Saving Antonio: Can a renowned hospital keep a boy from being shot again?

After 13-year-old Antonio was nearly killed outside his mom’s apartment, Children’s National Hospital went beyond treating his bullet wounds. Read how our Youth Violence Intervention Program team supported him and his family during his recovery.
(The Washington Post)

6. Formerly conjoined twins reunite with doctors who separated them

Erin and Jade Buckles underwent a successful separation at Children’s National Hospital. Nearly 20 years later they returned to meet with some of the medical staff who helped make it happen.
(Good Morning America)

7. Asthma mortality rates differ by location, race/ethnicity, age

Shilpa Patel, M.D., M.P.H., medical director of the Children’s National IMPACT DC Asthma Clinic, weighed in on a letter published in Annals of Allergy, Asthma & Immunology, asserting that the disparities in mortality due to asthma in the United States vary based on whether they occurred in a hospital, ethnicity or race and age of the patient.
(Healio)

8. How one Afghan family made the perilous journey across the U.S.-Mexico border

After one family embarked on a perilous journey from Afghanistan through Mexico to the U.S.-Mexico border, they eventually secured entry to the U.S. where Karen Smith, M.D., medical director of Global Services, aided the family’s transition and provided their daughter with necessary immediate medical treatment.
(NPR)

9. When a child is shot, doctors must heal more than just bullet holes

With the number of young people shot by guns on the rise in the U.S., providers and staff at Children’s National Hospital are trying to break the cycle of violence. But it’s not just the physical wounds though that need treating: young victims may also need help getting back on the right track — whether that means enrolling in school, finding a new group of friends or getting a job.
(BBC News)

10. This 6-year-old is a pioneer in the quest to treat a deadly brain tumor

Callie, a 6-year-old diagnosed with diffuse intrinsic pontine glioma, was treated with low-intensity focused ultrasound (LIFU) at Children’s National Hospital and is the second child in the world to receive this treatment for a brain tumor. LIFU is an emerging technology that experts like Hasan Syed, M.D., and Adrianna Fonseca, M.D., are trialing to treat this fatal childhood brain tumor.
(The Washington Post)

11. F.D.A. approves sickle cell treatments, including one that uses CRISPR

The FDA approved a new genetic therapy, giving people with sickle cell disease new opportunities to eliminate their symptoms. David Jacobsohn, M.B.A., M.D., confirmed that Children’s National Hospital is one of the authorized treatment centers and talked about giving priority to the sickest patients if they are on Vertex’s list.
(The New York Times)

12. 6-year-old fulfils wish to dance in the Nutcracker

After the potential need for open-heart surgery threatened Caroline’s Nutcracker performance, Manan Desai, M.D., a cardiac surgeon, figured out a less invasive procedure to help reduce her recovery time so she could perform in time for the holidays.
(Good Morning America)

The best of 2023 from Innovation District

December 27, 2023

2023 with a lightbulb Advanced MRI visualization techniques to follow blood flow in the hearts of cardiac patients. Gene therapy for pediatric patients with Duchenne muscular dystrophy. 3D-printed casts for treating clubfoot. These were among the most popular articles we published on Innovation District in 2023. Read on for our full list.

1. Advanced MRI hopes to improve outcomes for Fontan cardiac patients

Cardiac imaging specialists and cardiac surgeons at Children’s National Hospital are applying advanced magnetic resonance imaging visualization techniques to understand the intricacies of blood flow within the heart chambers of children with single ventricle heart defects like hypoplastic left heart syndrome. The data allows surgeons to make critical corrections to the atrioventricular valve before a child undergoes the single ventricle procedure known as the Fontan.
(3 min. read)

2. Children’s National gives first commercial dose of new FDA-approved gene therapy for Duchenne muscular dystrophy

Children’s National Hospital became the first pediatric hospital to administer a commercial dose of Elevidys (delandistrogene moxeparvovec-rokl), the first gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD). Elevidys is a one-time intravenous gene therapy that aims to delay or halt the progression of DMD by delivering a modified, functional version of dystrophin to muscle cells.
(2 min. read)

3. New model to treat Becker Muscular Dystrophy

Researchers at Children’s National Hospital developed a pre-clinical model to test drugs and therapies for Becker Muscular Dystrophy (BMD), a debilitating neuromuscular disease that is growing in numbers and lacks treatment options. The work provides scientists with a much-needed method to identify, develop and de-risk drugs for patients with BMD.
(2 min. read)

4. First infants in the U.S. with specially modified pacemakers show excellent early outcomes

In 2022, five newborns with life-threatening congenital heart disease affecting their heart rhythms were the first in the United States to receive a novel modified pacemaker generator to stabilize their heart rhythms within days of birth. Two of the five cases were cared for at Children’s National Hospital. In a follow-up article, the team at Children’s National shared that “early post-operative performance of this device has been excellent.”
(2 min. read)

5. AI: The “single greatest tool” for improving access to pediatric healthcare

Experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere came together to discuss how pediatric specialties can use AI to provide medical care to kids more efficiently, more quickly and more effectively at the inaugural symposium on AI in Pediatric Health and Rare Diseases, hosted by Children’s National Hospital and the Fralin Biomedical Research Institute at Virginia Tech.
(3 min. read)

6. AAP names Children’s National gun violence study one of the most influential articles ever published

The American Academy of Pediatrics (AAP) named a 2019 study led by clinician-researchers at Children’s National Hospital one of the 12 most influential Pediatric Emergency Medicine articles ever published in the journal Pediatrics. The findings showed that states with stricter gun laws and laws requiring universal background checks for gun purchases had lower firearm-related pediatric mortality rates but that more investigation was needed to better understand the impact of firearm legislation on pediatric mortality.
(2 min. read)

7. Why a colorectal transition program matters

Children’s National Hospital recently welcomed pediatric and adult colorectal surgeon Erin Teeple, M.D., to the Division of Colorectal and Pelvic Reconstruction. Dr. Teeple is the only person in the United States who is board-certified as both a pediatric surgeon and adult colorectal surgeon, uniquely positioning her to care for people with both acquired and congenital colorectal disease and help them transition from pediatric care to adult caregivers.
(3 min. read)

8. First-of-its-kind holistic program for managing pain in sickle cell disease

The sickle cell team at Children’s National Hospital received a grant from the Founders Auxiliary Board to launch a first-of-its-kind, personalized holistic transformative program for the management of pain in sickle cell disease. The clinic uses an inter-disciplinary approach of hematology, psychology, psychiatry, anesthesiology/pain medicine, acupuncture, mindfulness, relaxation and aromatherapy services.
(3 min read)

9. Recommendations for management of positive monosomy X on cell-free DNA screening

Non-invasive prenatal testing using cell-free DNA (cfDNA) is currently offered to all pregnant women regardless of the fetal risk. In a study published in the American Journal of Obstetrics and Gynecology, researchers from Children’s National Hospital provided context and expert recommendations for maternal and fetal evaluation and management when cfDNA screening is positive for monosomy X or Turner Syndrome.
(2 min. read)

10. Innovation in clubfoot management using 3D anatomical mapping

While clubfoot is relatively common and the treatment is highly successful, the weekly visits required for Ponseti casting can be a significant burden on families. Researchers at Children’s National Hospital are looking for a way to relieve that burden with a new study that could eliminate the weekly visits with a series of 3D-printed casts that families can switch out at home.
(1 min. read)

11. Gender Self-Report seeks to capture the gender spectrum for broad research applications

A new validated self-report tool provides researchers with a way to characterize the gender of research participants beyond their binary designated sex at birth. The multi-dimensional Gender Self-Report, developed using a community-driven approach and then scientifically validated, was outlined in a peer-reviewed article in the American Psychologist, a journal of the American Psychological Association.
(2 min. read)

12. Cardiovascular and bone diseases in chronic kidney disease

In a study published by Advances in Chronic Kidney Disease, a team at Children’s National Hospital reviewed cardiovascular and bone diseases in chronic kidney disease and end-stage kidney disease patients with a focus on pediatric issues and concerns.
(1 min. read)

Shaping the future of pediatric endocrinology

December 22, 2023

“Select patients will have the opportunity to participate in research studies focused on cutting-edge genomic investigations into their growth disorders,” says Youn Hee Jee, M.D., M.Med., endocrinologist.

“We’re dedicated to unraveling the mysteries that families have long sought answers to,” says Andrew Dauber, M.M.Sc., M.D., chief of Endocrinology at Children’s National Hospital. “There are numerous endocrine and genetic conditions with the potential to impact a child’s growth. That’s why we’ve assembled a team of leading endocrinologists and geneticists to create a new Growth Specialty Clinic and address these issues with a fresh perspective.”

This team, combined with the expertise of the hospital’s translational scientists, is making significant progress in identifying the causes of a variety of growth disorders and developing innovative treatments. And at the core of this work, Dr. Dauber says, is a recognition of the unique impact endocrine disorders have on each individual child.

What’s unique

Leveraging the expertise of Medical Geneticists Natasha Shur, M.D., and Deepika Burkardt, D.O., from the Children’s National Rare Disease Institute – the largest clinical genetics program in the United States – the growth clinic taps into substantial knowledge in the genetics of growth.

Dr. Shur emphasizes the commitment to providing answers for these families. “This collaborative effort goes beyond diagnosis; it opens doors to potential treatment options.”

The Growth Specialty Clinic is for children with severe undiagnosed growth disorders that are suspected to have a genetic etiology and children with rare genetic diagnoses who would benefit from the expertise of practitioners more familiar with those disorders. It is also closely linked to the Center for Genetic Medicine Research.

“Select patients will have the opportunity to participate in research studies focused on cutting-edge genomic investigations into their growth disorders,” says Youn Hee Jee, M.D., M.Med., endocrinologist.

In one case, Dr. Jee identified a new genetic cause of an overgrowth syndrome. Rare genetic conditions known as generalized overgrowth syndromes manifest as excessive body growth during fetal life and/or childhood, frequently resulting in tall stature. She is investigating the mechanisms that promote healthy bone growth.

Additionally, Dr. Jee identified a new genetic cause of short stature. Her research showed that the identified genetic cause impairs the recycling of essential proteins for growth, expanding our knowledge of human growth.

Moving the field forward

“We’re taking innovative approaches to treatment by leveraging our insights into the genetic origin of each patient’s growth disorder,” says Dr. Dauber.

In the brief time since the clinic’s launch, several new diagnoses and treatment pathways have already been offered. In one single-patient study, researchers were able to successfully overcome the patient’s growth hormone resistance using a targeted approach, and the patient has shown significant catch-up growth after one year of treatment.

Children’s National is also at the forefront of other groundbreaking research, launching novel clinical trials that are advancing the field of endocrinology:

Vosoritide clinical trial: Children’s National has the first clinical trial in the world testing Vosoritide in children with certain genetic causes of short stature. Researchers have enrolled approximately 50 subjects with exciting preliminary results for patients with Noonan syndrome, Aggrecan gene mutations and NPR2 gene mutations. All 24 hypochondroplasia patients have completed the 18-month trial. Dr. Dauber intends to present results at the 2024 American College of Medical Genetics meeting in Toronto.
Hypochondroplasia study: Children’s National is the first site to launch BioMarin’s new natural history study for children with hypochondroplasia which will also be a lead into their future Phase 3 trial.

Read more about our advances in Diabetes & Endocrinology.

illustration of laser damaging the plasma membrane

The microscopic world of cell healing: A window into future therapies

November 29, 2023

illustration of laser damaging the plasma membrane from Advanced Science cover Unraveling how cells mend after injury serves as a key to unlocking potential therapies. Recent findings from the Center for Genetic Medicine Research at Children’s National Hospital offered surprising insights into the cell’s healing mechanisms by illuminating the intricate cellular responses to various types of injuries.

The study, featured on the back cover of the latest issue of Advanced Science, found that cells respond in distinct ways depending on the type of injury, such as a traumatic muscle tear that creates a large injury or tiny holes in the cell membrane caused by pathogenic proteins. Daniel Bittel, DPT, Ph.D., a research postdoctoral fellow at the Center for Genetic Medicine Research, said that cells are routinely injured from even everyday activities, such as walking up a flight of stairs.

“Injuries often involve damage to the plasma membrane,” Bittel said. “We wanted to investigate how healing happens at the subcellular level to better understand diseases and develop targeted therapies. We were especially curious about muscle cells because, interestingly, healthy ones get stronger the more that they are injured.”

The fine print

Using the center’s unique, custom-built microscope, the research team zoomed in on the process of cellular healing to watch how cells activate repair after injuries. Using a laser to damage the plasma membrane, they mimicked mechanically induced trauma. They also used a pathogen-derived protein to create nanoscale pinprick injuries in a cell’s plasma membrane that resemble those that are seen after strenuous muscle exertion.

Then, they watched as cells went to work within seconds, engaging healing mechanisms tailored to the type of injury. In the case of a cell facing numerous pinpricks along the cell membrane, it immediately deployed the endocytic pathway used by the cells to eat and drink. This process helped remove the injurious agents and the tiny holes they made. However, with a larger mechanical injury, the cells demonstrated patience, allowing the plasma membrane to seal before clearing up the damage by the same endocytic pathway.

The big picture

The paper is part of an ongoing body of research on cell injury that will inform future investigations into a wide range of pediatric health issues including muscular dystrophies, injuries to neurons, orthopedic injuries from sports and other mechanical damage to tissues.

Jyoti Jaiswal, M.Sc., Ph.D., senior investigator at the Center for Genetic Medicine Research, said this work is foundational in the development of new therapies. “Knowing where the problem lies will help us figure out what therapy will work best and target the therapy to address the specific deficit,” he said. “This work will pave the way to help tailor therapies and tackle diseases more effectively.”

NexTGen team assembles to delve into progress on CAR T-cell therapies

November 21, 2023

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The international NexTGen team assembled at the Children’s National Research & Innovation Campus for their annual meeting to share progress made in their first full year of work on the $25-million Cancer Grand Challenge, focused on creating a CAR T-cell therapy for pediatric solid tumors.

“It was invigorating to bring the whole team together from our eight institutions in the U.S., U.K. and France, as we uncover opportunities in our research and share the headway that we have made,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research and interim chief academic officer at Children’s National Hospital. “Breakthroughs happen when Team Science collaborates, and that is exactly what is happening here with the NexTGen team.”

Why we’re excited

Over the course of two days, more than 85 team members met to discuss the six work packages that are coming together, with the ambitious goal of making CAR T-cell therapies the standard of care for solid tumors within the next decade:

Discovery of new targets
The tumor microenvironment
Component engineering
Integration and modeling
Clinical studies
Data integration

Each work package includes a patient advocate – individuals with a personal connection to cancer as a family member or survivor – who offers their invaluable perspectives on the research and treatment process. Many attended the meeting, sitting alongside the oncologists, immunologists, mathematicians, molecular biologists and other leading experts.

The big picture

The Cancer Grand Challenges are funded by grants from the National Cancer Institute, Cancer Research U.K. and the Mark Foundation for Cancer Research. Their goal is to drive progress against cancer by empowering global leaders in the research community to take on tough challenges and think differently.

“They call it a ‘grand challenge’ for a reason,” Dr. Bollard said. “It’s going to take the effort and expertise of all these individuals to make a new therapy a reality. I have confidence that we can do it.”

FDA approves muscular dystrophy drug built on Children’s National research

October 27, 2023

Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease.

Boys with Duchenne muscular dystrophy (DMD) have a clinically proven, new treatment option with the Food and Drug Administration’s approval of vamorolone, a steroidal-type, anti-inflammatory drug developed based on research performed at Children’s National Hospital.

Created by ReveraGen BioPharma Inc., vamorolone has a molecular structure similar to traditional corticosteroids, which are currently used to treat DMD. Yet its structure was found to be chemically different enough to reduce unwanted side effects, including brittle bones and reduced stature. Nearly two decades ago, ReveraGen leaders – President and CEO Eric Hoffman, Ph.D., and Vice President for Research Kanneboyina Nagaraju, D.V.M., Ph.D. – launched research efforts into the drug when they led the Center for Genetic Medicine Research at Children’s National. They worked with then-Chief Academic Officer Mark Batshaw, M.D., on the new clinical option.

“Throughout my career, I have treated children with DMD, and I have seen over time how their shorter heights and brittle bones impact them physically and emotionally – in terms of their self-esteem and ability to participate in activities,” Dr. Batshaw said. “This drug should help these boys function more effectively and prevent certain long-term complications.”

The patient benefit

Muscular dystrophy includes a group of degenerative genetically inherited neuro-muscular diseases that strike only boys. DMD is the most common, severe and life-threatening form of muscular dystrophy. ReveraGen studied vamorolone for patients ages two years and up in the hopes of providing a new, FDA-approved treatment option for these children. In clinical trials, daily treatment with vamorolone improved muscle strength and stature with results comparable to prednisolone, but without some of the most impactful side effects of steroids, particularly the stunted growth and weakened bones.

Children’s National Hospital leads the way

Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer for Children’s National, said Drs. Hoffman and Nagaraju’s work on the drug paved the way for entrepreneurship at the hospital, as they were the first faculty members to launch a spin-off company. Since then, more than 130 faculty members have been named as inventors on 132 patents. Children’s National is now home to Innovation Ventures, the hospital’s intellectual property development and commercialization arm, which provides guidance and resources to academic entrepreneurs who introduce a concept for pediatric medical products.

“We cannot wait to see the tremendous effort behind vamorolone in the hands of patients and clinicians treating Duchenne muscular dystrophy,” Eskandanian said. “Today’s FDA approval for ReveraGen shows the importance of supporting clinicians and researchers who are developing solutions to advance healthcare for children.”

Why we’re excited

Hoffman said the drug has been through a series of clinical trials showing advantages over the current treatment options. In 2024, Catalyst Pharma will market vamorolone under the trade name Agamree in the United States.

“Vamorolone was developed using a different business model and drug development approach, including partnerships with the National Institutes of Health, Department of Defense, the European Commission and more than a dozen international nonprofit foundations,” Dr. Hoffman said. “The collaborative, community-engaged approach—including 32 academic clinical sites in 11 countries — and the participation of hundreds of DMD families led to this approval today.”

Patient and doctor demoing Rare-CAP technology

M.D. in your pocket: New platform allows rare disease patients to carry medical advice everywhere

October 13, 2023

When someone has a rare disease, a trip to the emergency room can be a daunting experience: Patients and their caregivers must share the particulars of their illness or injury, with the added burden of downloading a non-specialist on the details of a rare diagnosis that may change treatment decisions.

Innovators at Children’s National Hospital and Vanderbilt University Medical Center, supported by Takeda, are trying to simplify that experience using a new web-based platform called the Rare Disease Clinical Activity Protocols, or Rare-CAP. This revolutionary collection of medical information allows patients to carry the latest research-based guidance about their rare disorders in their phones, providing a simple QR code that can open a trove of considerations for any medical provider to evaluate as they work through treatment options for someone with an underlying rare disease.

“No one should worry about what happens when they need medical help, especially patients with rare diseases,” said Debra Regier, M.D., division chief of Genetics and Metabolism at Children’s National and Rare-CAP’s lead medical advisor. “We built this new tool because I have watched as my patient-families have wound up in an emergency room — after all, kids get sprains or fractures — but they don’t have the expertise of a rare disease specialist with them. My hope is that they’re going to pull out their phones and access Rare-CAP, which will explain their rare disease to a new provider who can provide more thoughtful and meaningful care.”

The big picture

A rare disease is defined as any disorder that affects less than 200,000 people in the United States. Some 30 million Americans are believed to be living with one of the 7,000 known rare disorders tracked by the National Organization of Rare Diseases (NORD). Led by Dr. Regier, the Rare Disease Institute at Children’s National is one of 40 NORD centers for excellence in the country that provide care, guidance and leadership for the wide array of disorders that make up the rare disease community.

While a key goal of Rare-CAP is to bolster patient self-advocacy, the platform will also allow medical providers to proactively search for protocols on rare diseases when they know they need specialized advice from experts at Children’s National, a network of tertiary care centers and patient organizations.

As a leading values-based, R&D-driven biopharmaceutical company, Takeda has committed $3.85 million to the project to help activate meaningful change and empower a brighter future for rare disease communities, providing a unique understanding of the struggle that patients and caregivers face when they need care.

“Our team, alongside the medical and rare disease community, saw the need for a single portal to collect standardized care protocols, and we are thrilled to see this innovative tool come to life,” said Tom Koutsavlis, M.D., head of U.S. Medical Affairs at Takeda. “People with rare diseases and their caregivers need faster access to authoritative medical information that providers anywhere can act on, this will lead to improving the standard of care, accelerating time to diagnosis and breaking down barriers to increase equitable access.”

The patient benefit

The creators of Rare-CAP imagined its use in a wide range of settings, including emergency rooms, surgical suites, dental offices, urgent care offices and school clinics. The platform will eventually profile thousands of rare diseases and lay out the implications for care, while also creating a dynamic conversation among users who can offer updates based on real-world experience and changes in medical guidance.

“Our patients are unique, and so is this tool,” Dr. Regier said. “As we roll out Rare-CAP, we believe it is just the beginning of the conversation to expand the platform and see its power for the patient and provider grow, with each entry and each new rare disease that’s added to the conversation.”

Imaging reveals altered brain chemistry of babies with CHD

October 9, 2023

Researchers at Children’s National Hospital used magnetic resonance spectroscopy to find new biomarkers that reveal how congenital heart disease (CHD) changes an unborn baby’s brain chemistry, providing early clues that could someday guide treatment decisions for babies facing lifelong health challenges.

Published in the Journal of the American College of Cardiology, the findings detail the ways that heart defects disrupt metabolic processes in the developing brain, especially during the third trimester of pregnancy when babies grow exponentially.

“Over the past decade, our team has been at the forefront of developing safe and sophisticated ways to measure and monitor fetal brain health in the womb,” said Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal and Maternal Health Research at Children’s National. “By tapping into the power of advanced imaging, we were able to measure certain maturational components of the brain to find early biomarkers for newborns who are going to struggle immediately after birth.”

The fine print

In one of the largest cohorts of CHD patients assembled to date, researchers at Children’s National studied the developing brains of 221 healthy unborn babies and 112 with CHD using magnetic resonance spectroscopy, a noninvasive diagnostic test that can examine chemical changes in the brain. They found:

Those with CHD had higher levels of choline and lower levels of N-Acetyl aspartate-to-choline ratios compared to healthy babies, potentially representing disrupted brain development.
Babies with more complex CHD also had higher levels of cerebral lactate compared to babies with two ventricle CHD. Lactate, in particular, is a worrying signal of oxygen deprivation.

Specifically, elevated lactate levels were notably increased in babies with two types of heart defects: transposition of the great arteries, a birth defect in which the two main arteries carrying blood from the heart are switched in position, and single ventricle CHD, a birth defect causing one chamber to be smaller, underdeveloped or missing a valve. These critical heart defects generally require babies to undergo heart surgery not long after birth. The elevated lactate levels also were associated with an increased risk of death, highlighting the urgency needed for timely and effective interventions.

The research suggests that this type of imaging can provide a roadmap for further investigation and hope that medicine will someday be able to better plan for the care of these children immediately after their delivery. “With important clues about how a fetus is growing and developing, we can provide better care to help these children not only survive, but thrive, in the newborn period and beyond,” said Nickie Andescavage, M.D., Children’s National neonatologist and first author on the paper.

The big picture

CHD is the most common birth defect in the United States, affecting about 1% of all children born or roughly 40,000 babies each year. While these defects can be fatal, babies who survive are known to be at significantly higher risk of lifelong neurological deficits, including lower cognitive function, poor social interaction, inattention and impulsivity. The impact can also be felt in other organ systems because their hearts did not pump blood efficiently to support development.

Yet researchers are only beginning to pinpoint the biomarkers that can provide information about which babies are going to struggle most and require higher levels of care. The National Institutes of Health (NIH) and the District of Columbia Intellectual and Developmental Disabilities Research Center supported the research at Children’s National to improve this understanding.

“For many years we have known that the brains of children with severe heart problems do not always develop normally, but new research shows that abnormal function occurs already in the fetus,” said Kathleen N. Fenton, M.D., M.S., chief of the Advanced Technologies and Surgery Branch in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). “Understanding how the development and function of the brain is already different before a baby with a heart defect is born will help us to intervene with personal treatment as early as possible, perhaps even prenatally, and improve outcomes.”

Note: This research and content are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The NIH provided support for this research through NHLBI grant R01HL116585 and the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant P50HD105328.

Children’s National Hospital at the 2023 American Academy of Pediatrics meeting

October 3, 2023

There will be over 20 Children’s National Hospital-affiliated participants at this year’s American Academy of Pediatrics National Conference and Exhibition. The meeting will take place in Washington, D.C., from October 20 – October 24. We have compiled their sessions into a mini schedule below.

Date	Time	Presenter	Title	Division
10/20/2023	8:30 AM	Vanessa Madrigal, M.D., M.S.C.E.	Section on Cardiology & Cardiac Surgery Program: Day 1	Critical Care
10/20/2023	2:30 PM	Kibileri Williams, M.B.B.S	Appy Hour: a Current Update on Pediatric Appendicitis	Surgery
10/20/2023	3:30 PM	Roopa Kanakatti Shankar, M.D., M.S.	Precocious Puberty: Puberty Suppression or Not?	Endocrinology
10/21/2023	7:30 AM	Allison Markowsky, M.D.	What is Trending in the Newborn Nursery: Controversies and Evidence	Hospital Medicine
10/21/2023	8:00 AM	Jessica Herstek, M.D.	Joint Program: Council on Clinical Information Technology and Council on Quality Improvement and Patient Safety	Medical Informatics
10/21/2023	8:00 AM	Nazrat Mirza, M.D., Sc.D.	Section on Obesity Program	IDEAL Clinic (Obesity Program)
10/21/2023	8:00 AM	Hans Pohl, M.D.	Section on Urology Program: Day 2	Urology
10/21/2023	9:00 AM	Anil Darbari, M.D., M.B.B.S., M.B.A.	Constipation: Getting it to Work Out in the End	Gastroenterology, Hepatology and Nutrition
10/21/2023	9:00 AM	Kibileri Williams, M.B.B.S	Appy Hour: a Current Update on Pediatric Appendicitis	Surgery
10/21/2023	1:30 PM	Olanrewaju (Lanre) Falusi, M.D.	Educational Program and Annual Assembly for Medical Students, Residents, and Fellowship Trainees	Pediatrician
10/21/2023	2:00 PM	Brian Reilly, M.D.	Noise 201 – More than Headphones!	Otolaryngology
10/21/2023	2:00 PM	Erin Teeple, M.D.	Hernias, Hydroceles, and Undescended Testicles: When to Wait and When to Operate	Surgeon
10/21/2023	3:30 PM	Amanda Stewart, M.D.	Section on Emergency Medicine Program: Day 2	Emergency Medicine
10/21/2023	3:30 PM	Shideh Majidi, M.D., M.S.C.S.	Healthcare Disparities in Management of Type 1 Diabetes and Diabetes Technology	Endocrinology
10/21/2023	3:30 PM	Natasha Shur, M.D.	Genetic Testing Boot Camp	Geneticist (RDI)
10/21/2023	5:00 PM	Danielle Dooley, M.D., M.Phil	Connecting School Systems and Health Systems: Successes and Opportunities	Pediatrician
10/22/2023	8:00 AM	Jaytoya Manget, DNP, FNP	Pediatricians and School Attendance: Innovative Approaches to Prevent Chronic Absenteeism
10/22/2023	8:00 AM	Simone Lawson, M.D.	Section on Emergency Medicine Program: Day 3	Emergency Medicine
10/22/2023	8:00 AM	Hans Pohl, M.D.	Section on Urology Program: Day 3	Urology
10/22/2023	1:00 PM	Lenore Jarvis, M.D., M.Ed.	Section on Early Career Physicians Program
10/22/2023	5:00 PM	Brian Reilly, M.D.	Pediatric Hearing Loss: What’s New in Diagnostics, Prevention and Treatments	Otolaryngology
10/23/2023	8:00 AM	Rosemary Thomas-Mohtat, M.D.	Point-of-Care Ultrasound Fundamentals Course	Emergency Medicine
10/23/2023	9:00 AM	Matthew Oetgen, M.D., M.B.A.	Section on Radiology Program: Imaging Diagnosis and Management of Osteoarticular Infections	Orthopaedic Surgery and Sports Medicine
10/23/2023	9:00 AM	Christina Feng, M.D.	Masses for the Masses: Abdominal Masses in Children	Surgeon
10/23/2023	9:00 AM	Narendra Shet, M.D.	Section on Radiology Program: Imaging Diagnosis and Management of Osteoarticular Infections	Radiology
10/23/2023	9:00 AM	Shireen Atabaki, M.D., M.P.H.	Section on Advances in Therapeutics and Technology Program	Telemedicine
10/23/2023	1:00 PM	Brian Reilly, M.D.	Pediatric Otolaryngology: Back to Basics	Otolaryngology
10/23/2023	1:00 PM	Sonali Basu, M.D.	Point-of-Care Ultrasound Critical Competency Course	CCM
10/23/2023	1:00 PM	Vanessa Madrigal, M.D.	Joint Program: Section on Bioethics, Section on LGBT Health and Wellness and Section on Minority Health, Equity, and Inclusion	Critical Care
10/23/2023	2:00 PM	Rebecca Persky, M.D.	Menstrual Disorders: Primary or Secondary Amenorrhea	Endocrinology
10/23/2023	5:00 PM	Christina Feng, M.D.	Masses for the Masses: Abdominal Masses in Children	Surgeon
10/24/2023	9:00 AM	Vanessa Madrigal, M.D.	Section Showcase: Applying Ethics Principles and Tools To Advocate for Vulnerable Populations	Critical Care

Andrea L. Gropman, M.D., FAAP, FACMG, FANA, named as the Margaret O’Malley Professor of Genetic Medicine

September 25, 2023

Children’s National Hospital named Andrea L. Gropman, M.D., FAAP, FACMG, FANA, as the Margaret O’Malley Professor of Genetic Medicine at Children’s National Hospital.

Dr. Gropman serves as Chief of the Division of Neurogenetics and Developmental Pediatrics at Children’s National Hospital. She is also a Professor of Pediatrics and Professor of Neurology at George Washington School of Medicine and Health Sciences.

About the award

Dr. Gropman joins a distinguished group of Children’s National physicians and scientists who hold an endowed chair. The Margaret O’Malley Professor of Genetic Medicine is one of 47 endowed chairs at Children’s National.

Professorships support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s forethought to advance and sustain knowledge.

Dr. Gropman’s research focuses on neuroimaging, inborn errors of metabolism such as urea cycle disorders and mitochondrial disorders, and neurogenetics. She is the principal investigator of the Urea Cycle Disorders Consortium (UCDC) and the UCDC imaging consortium. She is the deputy clinical director of the Mito EpiGen Program.

Thomas and Mary Alice O’Malley, through their vision and generosity, are ensuring that Dr. Gropman and future holders of this professorship will launch bold, new initiatives to rapidly advance the field of pediatric genetic medicine, elevate our leadership and improve the lifetimes of children with genetic diseases.

About the donors

Tom and Mary Alice O’Malley have partnered with Children’s National to improve the lives of patients with urea cycles disorders for more than two decades. In 2003, their transformational philanthropy helped launch the Urea Cycle Disorders Consortium. This pioneering network grew to include 16-sites worldwide. It garnered 20 years of funding from the NIH’s Rare Diseases Clinical Research Network — the only center to sustain continuous funding over this period. This consortium’s research has yielded multiple effective treatment strategies, including government approval of three lifesaving therapies.

“The O’Malley family’s steadfast generosity helped us grow into the robust community of investigators and families we are today,” says Dr. Gropman. “They transformed care for UCD patients everywhere.”