Neonatology

stressed mom holding baby

An integrated approach to address perinatal mental health treatment

stressed mom holding baby

Perinatal mood and anxiety disorders (PMADs) are the most common complication of childbirth, with suicide as a leading cause of postpartum deaths.

Perinatal mood and anxiety disorders (PMADs) are the most common complication of childbirth, with suicide as a leading cause of postpartum deaths. PMADs are associated with poor maternal, infant and family outcomes. A new advocacy case study in Pediatrics led by a collaborative team of physicians at Children’s National Hospital describes the creation of the Task Force to formalize collaboration between hospital divisions, promote systems-level change and advocate for health care policy solutions.

Spearheaded by the Division of Emergency Medicine, the Goldberg Center for Community Pediatric Health and the Division of Neonatology at Children’s National, the #1 rated neonatology program in the country, the physicians who led this case study hope it can serve as a model for advocates looking to integrate PMAD screening within their own institutions. Children’s National is currently one of only a few children’s hospitals in the country that have implemented universal PMADs screening.

Lenore Jarvis, M.D., director of advocacy and health policy for the Division of Emergency Medicine at Children’s National, and Lamia Soghier, M.D., medical director of the Neonatal Intensive Care Unit (NICU) and the NICU Quality and Safety Officer at Children’s National, discussed this important work:

Q: What were you looking at with this case study?

A: Dr. Jarvis: This case study describes the implementation and outcomes of a multidisciplinary Perinatal Mental Health Task Force created at Children’s National in Washington, D.C. It was created to promote systems change and health care policy solutions for improved identification and treatment of PMADs.

Using the social-ecological model as a framework, the Task Force addressed care at the individual, interpersonal, organizational, community and policy levels. It then applied lessons learned from division-specific screening initiatives to create best practices and make hospital-wide recommendations.

This foundational work enabled us to build community bridges and break down internal barriers to shift our hospital toward prioritizing perinatal mental health. As a result, screening expanded to multiple hospital locations and the Perinatal Mental Health Screening Tool Kit was created and disseminated within the community. Task Force members also testified in governmental hearings and joined national organizations to inform policy, and Task Force and community collaborations resulted in significant grant funding.

Q: How is this work benefitting patients?

A: Dr. Soghier: Identification and early intervention for PMADs are imperative for improving health outcomes – not only for mothers but for their children and families too. Given the prevalence and negative consequences of untreated PMADs, we continue to innovate to improve the care we provide for infants and their families. We hope that this case study inspires others who value family mental health and are looking to integrate PMAD screening within their institutions.

Q: What are some of the barriers to getting this work implemented more widely?

A: Dr. Jarvis: One important thing to note is that families and medical providers alike may be unaware of how common PMADs truly are. On top of that, they’re unaware of the downstream negative impact it can have on the infant and family.

As a society, we must realize that PMADs can affect paternal caregivers. We need to have resources that also address fathers in addition to culturally and racially competent systems and resources for referral and linkage to care.

A: Dr. Soghier: Within medical systems, fragmented and siloed care delivery systems continue to be a barrier. Medical staff may also feel untrained and uncomfortable with addressing positive PMADs screens. Within the pediatric practice, differential access to services and reimbursement continue to be a concern, especially in a system where the parent is technically “not our patient.”

Identifying PMADs in our families and providing real-time resources and linkage to care has been invaluable to us. Ultimately, we seek to improve the care we provide to our infants and families and improve patient-family outcomes.

Read the full case study in the journal Pediatrics.

Timeline of major Task Force events

Timeline of major Task Force events. CES-D, Center for Epidemiologic Studies Depression Scale; DC, District of Columbia; PCORI, Patient-Centered Outcomes Research Institute.

Representative OFF and DIFF spectra

GABA and glutamate in the preterm neonatal brain

Preterm and sick newborns are at high risk of brain injury that can lead to cognitive delays and behavioral disorders including autism and ADHD. Gamma-aminobutyric acid (GABA) and glutamate system disruptions may underlie these neonatal brain injuries and hence it is important to describe their normative profile in the developing neonatal brain.

In a study led by Sudeepta Basu, M.D., neonatologist at Children’s National Hospital and Assistant Professor of Pediatrics at George Washington University School of Medicine and Health Sciences, specialized GABA editing spectroscopy (MEGA-PRESS) was acquired on a 3Tesla MRI scanner. Although MEGA-PRESS has been used in older subjects, there are challenges in the newborn population that have limited investigations with only a few institutions worldwide. Under the leadership of Catherine Limperopoulos, Ph.D., in the Developing Brain Institute (DBI) at Children’s National, a team of scientists (in particular, Dr. Subechhya Pradhan) have diligently overcome the technical challenges to enable use of this cutting-edge technology for research at the institute.

With this unique capability, Dr. Basu’s team prospectively enrolled 58 healthy newborns to describe the normal GABA and glutamate concentrations in different regions of the developing brain. In a recent article published in the American Journal of Neuroradiology, Dr. Basu reports that GABA and glutamate concentrations were highest in the cerebellum, slightly lower in the basal ganglia, but significantly lower in the frontal lobe.

“Our ability to reliably describe the normal metabolic-neurotransmitter milieu of the developing newborn brain is the first step in filling a critical gap in knowledge,” says Dr. Basu. “We hope to identify early bio-markers of brain injury of cognitive delays and autism and ADHD risk which remains a major challenge until clinical symptoms manifest later in childhood.”

Under the direction of Dr. Limperopoulos, advanced multi-modal high precision MRI protocols have been developed for use in research studies at Children’s National that allows the scientists to identify subtle signs of delayed growth and development of the newborn brain. With the optimization of MEGA-PRESS for newborns, Children’s National is one of a few institutions worldwide capable of investigating the newborn brain neurotransmitters in future research studies.

Read the full article in American Journal of Neuroradiology.

Representative OFF and DIFF spectra

Representative OFF and DIFF spectra.

computer circuit board

Integrating clinical parameters with lung imaging to predict respiratory outcomes in premature babies

computer circuit board

The team will develop an objective framework to predict the risk and assess the severity of respiratory disease in premature babies using non-invasive low-radiation X-ray imaging biomarkers and clinical parameters from the patient bedside.

Children’s National Hospital received a $1.7M award from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) to develop computational tools that integrate continuous clinical parameters with lung imaging to predict respiratory outcomes for babies born severely premature in newborn intensive care unit (NICU) settings.

The multi-disciplinary team of internationally recognized experts in quantitative imaging, machine learning and neonatal respiratory research believes they can improve clinical practice. To get there, they will develop an objective framework to predict the risk and assess the severity of respiratory disease in premature babies using non-invasive low-radiation X-ray imaging biomarkers and clinical parameters from the patient bedside.

“This computational tool will assist clinicians in making critical decisions about the course of therapy and other necessary follow-ups,” said Gustavo Nino, M.D., M.S.H.S., D’A.B.S.M., principal investigator in the Center for Genetic Medicine at Children’s National. “An objective informed decision about the severity of lung disease in prematurity will result in fewer rehospitalizations, better long-term outcomes and life-saving benefits.”

Prematurity is the largest single cause of death in children under five in the world. Lower respiratory tract infections (LRTI) are the top cause of hospitalization and mortality in premature infants. Clinical tools to predict the risk and assess the severity of LRTI in premature babies are needed to allow early interventions that can decrease the high morbidity and mortality in this patient group.

“Our new technology will provide clinicians an accurate, fast and comprehensive summary of the respiratory status of premature babies,” said Dr. Nino. “The data analysis along with the software technology will help determine if a premature baby seen in the NICU can be safely discharged or will require further monitoring and treatment.”

Predictive analytics could help in many ways. For example, there are instances where newborns in the NICU are on the right path with no risks in the future, but there are babies who will come back with severe infections.

“In the first scenario, if we can predict earlier that they’re fine, this could reduce the number of chest X-rays and extra tests, so we assess that this child can be safely sent home,” said Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National. “On the other hand, for kids that may come back to the hospital in the near future, we could predict earlier that they are not that well by looking at images and other continuous measurements such as supplemental oxygen.”

This approach, in essence, is a collection of continuous data from the NICU, which is very complex itself because it needs to be collected every day and fed into a machine learning model that digests the data to identify risk patterns for the health of the lung.

“If we find that there is still a risk, it does not necessarily mean that the child has to stay in the NICU any longer, but they might continue treatment, and we will have to define how this integrates into the clinical management of these patients,” said Linguraru. “If there is something in the data that we can put our finger on, we will know which kids require timely attention, hopefully reducing future adverse situations with potential comorbidities and financial burdens.”

NCC-PDI logo

Pediatric medical device competition takes aim at congenital heart disease

NCC-PDI logo

Consistent with its mission of addressing the most pressing pediatric device needs, this year’s competition focused on innovations in electrophysiology devices that monitor and treat congenital heart disease (CHD) and arrhythmias in pediatric patients.

The National Capital Consortium for Pediatric Device Innovation (NCC-PDI) announces five awardees chosen in its prestigious annual “Make Your Medical Device Pitch for Kids!” competition to share $150,000 in grant funding from the U.S. Food and Drug Administration (FDA) to support the advancement of pediatric medical devices. In an unprecedented decision, the competition judges determined that all five finalists were deserving of a grant award and recognition for the potential patient benefit and commercial viability of their innovations.

Consistent with its mission of addressing the most pressing pediatric device needs, this year’s competition, conducted by NCC-PDI partner MedTech Innovator, focused on innovations in electrophysiology devices that monitor and treat congenital heart disease (CHD) and arrhythmias in pediatric patients. The virtual pediatric pitch event was part of the 9th Annual Symposium on Pediatric Device Innovation.

This year’s pediatric device innovation awardees are:

  • PeriCor – The Children’s Hospital at Montefiore – New York, NY – PeriTorq, a catheter grip tool for use during pediatric cardiac interventional procedures;
  • Inkspace Imaging – Pleasanton, CA – a pediatric cardiac and vascular MRI coil;
  • Karios Technologies – Charlottesville, VA – Tissue Shield, a technology to prevent scar tissue formation (adhesions) on the heart after surgery;
  • Sibel – Niles, IL – ANNE One, ICU-grade wireless sensors for cardiopulmonary monitoring in neonates with congenital heart defects;
  • Starlight Cardiovascular – San Diego, CA – Project Lifeline, a less-invasive way to maintain sufficient circulation in newborns with ductal-dependent circulation that increases safety, procedural success and ease of use.

Congenital heart disease (CHD) affects six out of 1,000 babies born in the U.S. each year and is often complicated by arrhythmias, a condition where the heart beats too rapidly, too slowly or irregularly due to a misfiring of the body’s electrical impulses. While the last decade brought great advances in technologies that improve the care of adult arrhythmias, pediatric patients have been left behind, with only five devices approved for use in children in the same period. As a result, pediatric specialists are often using off-label or improvised devices to treat pediatric arrhythmias, including in the smallest newborns.

“Recognizing this unmet need, NCC-PDI opened the challenge earlier this year to select companies to enter MedTech Innovator’s pediatric accelerator program, made possible by NCC-PDI. The five companies have immensely benefited from the accelerator program and are well-positioned to compete for funding. They have the potential to advance pediatric health and provide a greater standard of care for children living with CHD,” says Kolaleh Eskandanian, Ph.D., M.B.A, P.M.P, vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “For too long, the unique needs of children have been overlooked in pediatric device development. Thanks to the support of the FDA, we are able to build our challenge competitions around the direst unmet needs, which are determined through a thorough needs assessment and market analysis conducted to inform each request for proposal. The funding incentivizes pediatric innovation and helps more companies navigate the path to commercialization.”

NCC-PDI is one of five consortia in the FDA’s Pediatric Device Consortia Grant Program created to support the development and commercialization of medical devices for children, which lags significantly behind the progress of adult medical devices. NCC-PDI is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital and the A. James Clark School of Engineering at the University of Maryland, with support from partners MedTech Innovator,  BioHealth Innovation and design firm Archimedic.

A pediatric accelerator program, powered by MedTech Innovator, is the consortium’s latest addition to a network of resources and experts that NCC-PDI provides in support of pediatric innovators. All five of this year’s competition finalists had an opportunity to participate in the year-long accelerator program.

Eskandanian adds that supporting the progress of pediatric innovators is a key focus of the new Children’s National Research & Innovation Campus, a one-of-its-kind ecosystem that drives discoveries that save and improve the lives of children. On a nearly 12-acre portion of the former, historic Walter Reed Army Medical Center in Northwest Washington, D.C., Children’s National has combined its strengths with those of public and private partners, including industry, universities, federal agencies, start-up companies and academic medical centers, the campus provides a rich environment of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization.

Drs. Katie Donnelly, Panagiotis Kratimenos, Rana Hamdy, Shayna Coburn and Brynn Marks

Five Children’s National Hospital faculty named to Society for Pediatric Research

Drs. Katie Donnelly, Panagiotis Kratimenos, Rana Hamdy, Shayna Coburn and Brynn Marks

The Society for Pediatric Research (SPR) announced five new members from Children’s National Hospital: Drs. Rana Hamdy, Panagiotis Kratimenos, Brynn Marks, Shayna Coburn and Katie Donnelly.

The Society for Pediatric Research (SPR) announced five new members from Children’s National Hospital. Established in 1929, SPR’s mission is to create a multi-disciplinary network of diverse researchers to improve child health.

Membership in SPR is a recognized honor in academic pediatrics. It requires nomination by academic peers and leaders as well as recognition of one’s role as an independent, productive child health researcher.

“I am so proud of our faculty and all that they have accomplished. I am thrilled that they have been recognized for their achievements,” said Beth A. Tarini, M.D., M.S., SPR president and associate director for the Center for Translational Research at Children’s National Hospital.

SPR 2021 active new members from Children’s National are:

    • Katie Donnelly, M.D., M.P.H., attending physician in the Emergency Department at Children’s National Hospital. She is the medical director for Safe Kids DC, an organization dedicated to preventing accidental injuries in children in Washington DC. Her personal research interest is in preventing firearm injuries in children and she is a member of Safer through Advocacy, Firearm Education and Research (SAFER), a multidisciplinary team dedicated to firearm injury prevention at Children’s National. She is also the medical director of the newly founded hospital-based violence intervention program at Children’s National and an associate professor of pediatrics and emergency medicine at The George Washington University.“To be recognized by my peers as a researcher with a significant contribution to our field is very validating. It also opens a world of potential collaborations with excellent scientists, which is very exciting!” said Dr. Donnelly. “I am grateful for the immense support offered to me by the Division of Emergency Medicine to complete the research I am passionate about, especially my mentor Monika Goyal.”
    • Panagiotis Kratimenos, M.D., Ph.D., newborn intensivist and neuroscientist at Children’s National. He studies mechanisms of brain injury in the neonate, intending to prevent its sequelae later in life. Dr. Kratimenos’ interest lies in identifying therapies to prevent or improve neurodevelopmental disabilities of sick newborns caused by prematurity and perinatal insults.“Being a member of SPR is a deep honor for me. SPR has always been a ‘mentorship home’ for me since I was a trainee and a member of the SPR junior section,” said Dr. Kratimenos. “A membership in the SPR allows us to access a very diverse, outstanding team of pediatric academicians and researchers who support the development of physician-scientists, honors excellence through prestigious grants and awards, and advocates for children at any level either locally, nationally, or internationally.”
    • Rana Hamdy, M.D., M.P.H., M.S.C.E., pediatric infectious diseases physician at Children’s National and Director of the Antimicrobial Stewardship Program. She is an assistant professor of pediatrics at George Washington University School of Medicine and Health Sciences. Her area of expertise focuses on the prevention and treatment of antimicrobial resistant infections and the promotion of good antimicrobial stewardship in inpatient and outpatient settings.“It’s an honor to be joining the Society for Pediatric Research and becoming part of this distinguished multidisciplinary network of pediatric researchers,” said Dr. Hamdy. “I look forward to the opportunity to meet and work with SPR members, make connections for future collaborations, as well as encourage trainees to pursue pediatric research through the opportunities that SPR offers.”
    • Shayna Coburn, Ph.D., director of Psychosocial Services in the Celiac Disease Program at Children’s National. She is a licensed psychologist specializing in coping and interpersonal relationships in chronic illness treatment, particularly for conditions involving specialized diets. She holds an appointment as assistant professor of psychiatry and behavioral sciences at The George Washington University School of Medicine and Health Sciences. Her work has focused on promoting effective doctor-patient communication, reducing healthcare disparities and supporting successful adherence across the developmental span of childhood and adolescence. She currently has a Career Development Award from National Institute of Diabetes and Digestive and Kidney Diseases to refine and test a group intervention designed to improve self-management and quality of life in teens with celiac disease.
      “I hope that my background as a psychologist researcher will help diversify SPR. As an SPR member, I hope to encourage more opportunities for training, awards, and other programs that would be inclusive of clinician researchers who may not hold a traditional medical degree,” said Dr. Coburn.
    • Brynn Marks, M.D., M.S.-H.P.Ed., endocrinologist at Children’s National. As a clinical and translational scientist her goal is to use unique personal experiences and training to optimize both patient and provider knowledge of and behaviors surrounding diabetes technologies thereby realizing the potential of diabetes technologies improve the lives and clinical outcomes of all people living with diabetes. Her experiences as a person living with Type 1 diabetes have undoubtedly shaped her clinical and research interests in diabetes management and medical education.
      “It is an honor to be accepted for membership in the Society for Pediatric Research,” said Dr. Marks.  “Being nominated and recognized by peers in this interprofessional pediatric research community will allow me networking and growth opportunities as I continue to advance my research career.”
Neuronal network with electrical activity

Neonatal hypoxia-ischemia causes damage to the cholinergic system

Neuronal network with electrical activity

Study suggests permanent injury to the cholinergic system after neonatal hypoxia-ischemia is responsible for the poor executive functions and difficulties in learning and memory.

Newborn babies who go through periods of low oxygen — also known as hypoxic-ischemic encephalopathy — during their first hours of life often experience difficulties in learning, memory and executive functions later on. Even when treated with therapeutic hypothermia, memory deficits and executive functions remain severely affected. These functions are linked to a neurotransmitter network called the cholinergic system.

“Complications from hypoxic-ischemic brain injury contribute to one-quarter of neonatal deaths worldwide and cause significant long-term neurological morbidity,” explains Panagiotis Kratimenos, M.D., Ph.D., neonatologist at Children’s National Hospital and Assistant Professor of Pediatrics at the George Washington University School of Medicine and Health Sciences.

In a study published in the Journal of Comparative Neurology led by Frances Northington, M.D., co-director of Neurosciences Intensive Care Nursery at Johns Hopkins and Professor of Pediatrics at Johns Hopkins University School of Medicine, with contributions from Dr. Kratimenos, the authors found significant injury to the neurons of the cholinergic systems in specific parts of the brain after exposure to low oxygen and restricted blood flow. These areas included the ipsilateral medial septal nucleus (MSN), the ipsilateral nucleus basalis of Meynert (nbM) and striatum. Within the injured part of the cortex at the site of injury, acetylcholine — the neurotransmitter found in cholinergic systems — was abnormally overactivated.

The authors hypothesize that permanent injury to the cholinergic system after neonatal hypoxia-ischemia is responsible for the poor executive functions and difficulties in learning and memory.

“Because cholinergic systems can easily be manipulated pharmacologically with already established treatments that have been used in other areas of medicine, they could be a good a target for therapeutic interventions for neonates with hypoxic-ischemic encephalopathy,” says Dr. Kratimenos.

Read the full article in the Journal of Comparative Neurology.

Maria Susana Rueda Altez

Maria Susana Rueda Altez, M.D., to lead as Junior Section President-Elect

Maria Susana Rueda Altez

Maria Susana Rueda Altez, M.D., junior section president-elect for the Society for Pediatric Research (SPR).

Maria Susana Rueda Altez, M.D., was selected as junior section president-elect for the Society for Pediatric Research (SPR). During her tenure, Dr. Rueda Altez will ensure more trainees benefit from networking opportunities and leverage her online communications experience to increase awareness, membership and participation in SPR among students, residents and fellows.

The president of the junior section is a fellow who is elected by other junior member peers and is in-charge of managing and enhancing the junior section, by participating in SPR council meetings, promoting membership among trainees and reinforcing the pipeline from junior to active members.

“I am so honored, not only as a Peruvian physician, but as an international medical graduate (IMG), to have been elected for this position,” said Dr. Rueda Altez. “As an IMG, there are special challenges to conducting research, so I plan to raise awareness and provide support to my fellow IMG junior members.”

To Beth A. Tarini, M.D., M.S., SPR president and associate director for the Center for Translational Research at Children’s National Hospital, it is an honor for the hospital to have representatives in the roles of SPR president and SPR junior section president-elect simultaneously.

Dr. Rueda Altez added that there is an urgent need for increased funding in pediatric research, especially for minority and health disparities research. Through her participation in SPR, she will also have the opportunity to advocate for increases in child health research funding.

“I encourage all the trainees and junior faculty in our institution to join the SPR junior section,” said Dr. Rueda Altez. “It provides wonderful resources for career development and guidance, grant writing courses and invaluable mentorship.”

Her research interest is newborn infections, and her overall goal is to reduce the unnecessary use of antibiotics in this population.

“I am currently working on a quality improvement project to reduce the number of days NICU infants are exposed to antibiotics,” said Dr. Rueda Altez. “I have developed a project to ascertain the utility of microbial cell-free DNA next generation sequencing, a novel microbiologic diagnostic tool, for the diagnosis of neonatal infections.”

Dr. Rueda Altez’s work on neonatal sepsis will help scientists better distinguish between neonates who do and don’t have serious bacterial infections.

“Right now, when in doubt we tend to treat it as bacterial infections, which can lead to unnecessary medical treatment and worsen resistance to antibiotics,” said Tarini.

Dr. Rueda Altez also serves as an independent reviewer of investigational manuscripts for The Journal of Pediatrics and Pediatrics and guest editor for The Journal of Pediatrics. Her passion for the peer-review process also shows in her long list of published research.

Dr. Tarini also foresees multiple research trends in the next five years that might appear in peer-reviewed publications.

“We have so much to tackle in child health research, both ongoing and new challenges,” said Dr. Tarini.  “Some issues that come to mind are the mental health crisis in children and teens, continuing to make strides on treating and preventing childhood obesity, the effect of poverty on children’s health, and the pandemic’s effect on all of these issues and its direct effect on health outcomes.”

x-ray of human skull

Researchers awarded $3.5 million to study brain and cranium development in children

x-ray of human skull

Currently, studies on typical brain and cranium development are limited. One reason for this is that imaging techniques are optimized to best visualize either bone or soft tissue, but not both.

With prevalence of developmental disorders on the rise, the need to understand brain development has never been more critical. Development of the brain is strongly influenced by the cranium, but this relationship has not been adequately studied because of limitations in imaging technology. Now, researchers from Children’s Hospital Los Angeles and Children’s National Hospital are working together to develop techniques that will provide greater insight into this relationship. Their studies will be funded by The National Institute of Dental and Craniofacial Research, which has awarded them $3.5 million.

Natasha Leporé, Ph.D., of Children’s Hospital Los Angeles, studies methods to interpret brain imaging data. “There’s a lot of interaction between the skull and the brain,” she says, “and we want to better understand how they grow together.”

Currently, studies on typical brain and cranium development are limited. One reason for this is that imaging techniques are optimized to best visualize either bone or soft tissue, but not both.

The brain — mostly composed of water, protein and fat — doesn’t show up well on computerized tomography (CT) scans, which use X-ray images. In addition, radiation exposure limits the amount of CT scan data available in children. On the other hand, magnetic resonance imaging (MRI) scans are excellent for brain images but are not optimal for surrounding bone.

This presents researchers with a dilemma if they want to see the brain and the skull together in one image. Fortunately, research barriers like these are often overcome by collaboration.

Leporé will work with Marius George Linguraru, D.Phil, M.A., MS.c., principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital.

Linguraru works on a set of tools for cranial phenotyping, using existing CT images from typically developing children. In their collaboration, Leporé and Linguraru will extend the tools to MRI scans, allowing the team to analyze the brain and cranium simultaneously. The pair has received a $3.5 million award over 5 years.

“The tools we develop together will help us to better understand the healthy growth of children,” says Linguraru. “We will have the ability to analyze the joint cranial and brain development from large medical image datasets of pediatric patients.”

This, the team says, will be invaluable to the medical community.

“These tools will help clinicians to better assess, diagnose and plan treatment for infants with cranial deformities,” says Linguraru.

Collaborations like this allow expertise to be shared across specialties, ultimately benefiting children in need. Exceptional pediatric care is a result of teamwork; not only doctors, nurses and clinical staff, but also biomedical research, which arms clinicians with the information they depend on.

“We need to have a clear idea of what is expected in normal development,” says Leporé. “This allows doctors to detect and better understand differences in development.”

Other members of the research team include: Vidya Rajagopalan, Ph.D.; Marvin Nelson, M.D.; Alexis Johns, Ph.D.; Niharika Gajawelli, Ph.D. (from Children’s Hospital Los Angeles and University of Southern California); Robert Keating, M.D. (Children’s National Hospital); Yalin Wang, Ph.D. (Arizona State University); Antonio Porras, Ph.D. (University of Colorado); Sean Deoni, Ph.D. (Rhode Island Hospital and Brown University).

A version of this story appeared on the Children’s Hospital Los Angeles newsroom.

Bear Institute PACK logo

Winners of the first annual Bear Institute PACK Event

Bear Institute PACK logo

On August 26, 2021, the Bear Institute, along with Children’s National Hospital and Cerner Corporation, hosted the first annual Bear Institute PACK (Pediatric Accelerator Challenge for Kids). Bear Institute PACK is a start-up competition aimed to address the gap in digital health innovation funding dedicated to children.

“Children are a unique population that requires different health solutions than those designed for adults, which address their unique needs,” says Dr. Lu de Souza, Vice President and Chief Medical Officer, Cerner Corporation. “With Bear Institute PACK, we hope to increase focus and delivery of digital health innovations for kids. Bear Institute PACK brings together the pediatric health care community, including pediatric health care providers and hospital administrators from across the country to identify top start-up digital applications that best serve children.”

This year’s start-up participants competed across four innovation tracks, including rare disease, telemedicine, remote patient monitoring and patient education. Student teams competed in a separate student track. Bear Institute PACK consists of three rounds of judging: an initial review of applications from the Bear Institute PACK team, judging from participating pediatric healthcare providers and administrators and review from an expert panel of judges during finalist start-ups’ live pitches.

The start-ups competed for a rich prize pool, including cash prizes totaling over $100,000, on-site pilots and software development support. Winners were selected in each of the event’s four innovation tracks, as well as an additional two student team winners. This year winners are:

  • In the rare disease track, first place winner, Bloom Standard, Inc., with its solution Automated Ultrasound Wrap that screen infants and children for serious lung and cardiac conditions, and second place winner, Mira Medical LLC, with its solution Bear Growth: A Three-Dimensional Pediatric Growth Modeling App.
  • In the telehealth track, Keriton, Inc., with its solution Keriton Kare, a healthcare SaaS platform built to improve outcomes for neonatal and pediatric patients.
  • In the remote patient monitoring track, Sonavi Labs, with its solution Feelix, a platform that features proprietary hardware embedded with clinically validated diagnostic software capable of detecting respiratory diseases.
  • In the patient education track, Smileyscope, with its comprehensive virtual reality (VR) platform to help support patients with procedural pain management, drug-free anxiety care, education, and guided relaxation.
  • Student team first place winner, CASP Technologies, with its solution Operation Serenity, which allows pediatric patients to prepare for and understand their simulated surgery to reduce anxiety and second place winner, Ankle Rehab, with its solution Foot Joystick for Children with Cerebral Palsy meant to improve mobility.

More information on this year’s winners can be found on the Bear Institute PACK website.

“This year’s Bear Institute PACK had a lot of start-ups and student team participants with very impressive innovation solutions for kids. Selecting a single winner in each innovation track was a tough decision, and it was encouraging to see all the work being done to bring these solutions to market,” says Matt MacVey, Vice President and Chief Information Officer, Children’s National Hospital. “Thank you to everyone who participated and helped make the inaugural Bear Institute PACK a success! We hope to make next year even bigger as we continue to strive to close the gap in funding for children’s digital health innovation.”

More information on next year’s event will be forthcoming on the Bear Institute PACK website.

Could whole-exome sequencing become a standard part of state newborn screening?

smiling baby boy

There are concerns about implementing whole-exome sequencing since it takes away the child’s right to decide if they want to know — or not — about their specific inherited disease.

It is still premature to standardize an innovative methodology known as whole-exome sequencing (WES) as part of state newborn screening programs, argues Beth A. Tarini, M.D., M.S., associate director for the Center of Translational Research at Children’s National Hospital, in a new editorial published in JAMA Pediatrics.

About 4 million infants are born annually in the United States. Newborn screening is a mandatory state-run public health program that screens infants for inherited diseases in the first days of life so they can receive treatment before irreversible damage occurs. Several of these screening tests are done on blood drawn from an infant’s heel.

WES holds the potential to screen infants for thousands of disorders and traits, including those that appear in adulthood. But there are concerns about implementing WES since it takes away the child’s right to decide if they want to know — or not — about their specific inherited disease. There is also the unknown effect that it could have on their ability to obtain health insurance.

“As caretakers for their children, parents have the challenge of deciding what kind of information, including genetic, will be valuable for their child,” says Dr. Tarini. “As a society, we have the responsibility of deciding where the healthcare dollars get the best return – especially when it comes to children. We need to start that conversation for universal genomic sequencing of newborns sooner rather than later.”

The Pereira et al. study, appearing in the new edition of JAMA Pediatrics and referenced in Dr. Tarini’s editorial, is the first to demonstrate no significant harm in the initial 10 months of life after performing WES under the best conditions of access to resources and a controlled environment.

While the Pereira et al. study has limited data on the effects of WES on families from underrepresented backgrounds, Dr. Tarini notes that it does provide a critical first step in this area of pediatric genomic research and for policy decision-making about the widespread implementation of WES in newborns.

“Moving forward, the U.S. will have to make a collective decision about the value of WES for newborns,” says Dr. Tarini. That value calculus cannot be made without consideration of the general state of healthcare for infants. As she points out, “This is not an easy question to answer in a country whose infant mortality ranks 34th according to the Organization for Economic Co-operation and Development (OECD).”

Dr. Tarini’s research identifies ways to optimize the delivery of genetic services to families and children, particularly newborn screening. She has also chaired state newborn screening committees and served on several federal newborn screening committees.

morphine vial and needle

Replacing morphine with methadone in the NICU

morphine vial and needle

A synthetic analgesic drug, known as methadone, may serve as a better alternative for newborns in the neonatal intensive care unit (NICU) suffering from opioid withdrawal syndrome, according to a commentary published in Pediatric Research.

A synthetic analgesic drug, known as methadone, may serve as a better alternative for newborns in the neonatal intensive care unit (NICU) suffering from opioid withdrawal syndrome, according to a commentary published in Pediatric Research. Some existing literature suggests that methadone may also address painful stimuli that hinders neurodevelopment throughout adulthood, added Johannes van den Anker, M.D., Ph.D., division chief of Clinical Pharmacology at Children’s National Hospital.

The commentary was selected as the Editor’s Focus in Pediatric Research for the June editionsignaling the scientific community as noteworthy to further explore methadone’s potential as an alternative for pharmacologic treatments instead of morphine.

“It is important to define the pharmacokinetics and pharmacodynamics of methadone to treat pain in neonates in intensive care before replacing morphine with methadone. Pre-clinical research shows that the use of methadone might have fewer side effects than morphine,” said Dr. van den Anker. “If this is also the case in the human neonate, then a shift from morphine to methadone might be beneficial. However, first, we need to define what the safe and effective dose of methadone will be for this purpose.”

While there is a need to better understand how newborns and preemies metabolize methadone, there is existing knowledge that this drug minimizes pain. The commentary, too, raises the question for clinicians to possibly consider methadone as a better option to avoid long-term negative neurodevelopmental consequences — such as hypersensitivity to re-injury in later life — usually associated with pain.

The current but limited data out there still provides “exciting and stimulating” information about the possible use of methadone for the treatment of neonatal pain in the NICU, according to Dr. van den Anker. He believes that, in the future, methadone could also serve as mechanism-based analgesia in newborns experiencing pain.

“There needs to be a collaboration between neonatal medicine specialists, pharmacometricians and developmental pharmacologists to assure not only the generation of evidence-based data to determine these optimal dosing regimens, but also to facilitate the implementation of this new knowledge into daily clinical care in neonatal intensive care units across the globe,” added Dr. van den Anker.

US News badges

For fifth year in a row, Children’s National Hospital nationally ranked a top 10 children’s hospital

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll 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 fifth year in a row.

For the eleventh straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“It is always spectacular to be named one of the nation’s best children’s hospitals, but this year more than ever,” says Kurt Newman, M.D., president and CEO of Children’s National. “Every member of our organization helped us achieve this level of excellence, and they did it while sacrificing so much in order to help our country respond to and recover from the COVID-19 pandemic.”

“When choosing a hospital for a sick child, many parents want specialized expertise, convenience and caring medical professionals,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings have always highlighted hospitals that excel in specialized care. As the pandemic continues to affect travel, finding high-quality care close to home has never been more important.”

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:

The other three specialties ranked among the top 50 were cardiology and heart surgerygastroenterology and gastro-intestinal surgery, and urology.

PAS Logo

Children’s National participants share their expertise at PAS meeting

PAS Logo

The 2021 Pediatric Academic Societies (PAS) Virtual meeting hosted live-streamed events, on-demand sessions with live Q+A, a virtual exhibit hall, poster presentations and networking events that attracted pediatricians and healthcare providers worldwide. Among the physician-scientists, there were over 20 Children’s National Hospital-affiliated participants at this year’s meeting, adding to the conversation of pediatric research in specialty and sub-specialty areas.

Children’s National experts covered a range of topics, including heart disease, neurology, abnormal glycemia in newborns and antibiotic use in hospitalized children.

The “Neurological Implications of Abnormal Glycemia in Neonatal Encephalopathy and Prematurity” was a hot topic symposium presented by a panel of experts, including Sudeepta Basu, M.B.B.S., M.S., neonatologist at Children’s National.

The experts addressed the importance of recognizing early blood glucose disturbances in newborns with encephalopathy following birth asphyxia and its likely impact on brain injury and long-term outcomes. Although whole body cooling for newborns with encephalopathy after birth asphyxia is now standard of care in most advanced centers like Children’s National, many newborns still die or have neurological impairments. Dr. Basu emphasized on the need of continued advances in newer therapies and optimizing intensive care support for these vulnerable newborns immediately after birth. Dr. Basu’s presentation focused on the association of not only low blood glucose (hypoglycemia) but also high blood glucose (hyperglycemia) with abnormal motor, visual and intellectual outcomes in surviving newborns.

“Recognizing the problem is the first step for further advancement,” Dr. Basu said. “The scientific community needs to recognize the importance of early glucose status as an early marker for disease severity and risk of brain injury.” To sum up, Dr. Basu drew attention to recent newborn resuscitation guidelines from the International Liaison Committee on Resuscitation (ILCOR), which recommends close monitoring of blood glucose levels and optimizing supportive care to maintain it within normal range. Dedicated clinical trials are the need of the hour to guide what are “normal” glucose levels in newborns with encephalopathy and what treatment options are most beneficial.

Rana F. Hamdy, M.D., M.P.H., M.S.C.E., director of the Children’s National Antimicrobial Stewardship Program, delved into the increased number of children receiving care for acute conditions – like acute respiratory tract infections – from urgent care centers and direct-to-consumer (DTC) telemedicine companies during her session “Implementing Antibiotic Stewardship in Telemedicine and Urgent Care Settings.”

Telemedicine, in this case, refers to DTC telemedicine companies—not to be confused with the telemedicine established with primary care providers, like the services provided by Children’s National.

There has been little research focused on promoting good antibiotic stewardship in urgent care settings that tend to overprescribe antibiotics compared to a primary care setting. In addition to her work focusing on improving antimicrobial use within Children’s National, Dr. Hamdy has led collaborative quality improvement work nationally in both the pediatric urgent care and DTC telemedicine settings.

“What we’ve learned from our work with the DTC telemedicine setting is that leadership commitment coming from the company is a necessary core element,” Dr. Hamdy said. “There may be unique opportunities in the telemedicine setting to employ the home-grown computer systems for antimicrobial stewardship interventions, for example, incorporating clinical decision support or feedback reports into the electronic health record systems or displaying a commitment letter in the virtual waiting room.”

In the urgent care setting, Dr. Hamdy’s team recruited approximately 150 pediatric urgent care providers to participate in the national quality improvement initiative. Communication training modules for pediatric urgent care providers with scripted language for target infectious conditions — acute otitis media, pharyngitis and otitis media with effusion — were among the successful intervention approaches that led to improved appropriate antibiotic prescribing practices, according to her team’s findings.

“Understanding the prescribing practices in the urgent care setting is important to knowing where and how to focus on target conditions and to be able to support with education and resources,” Dr. Hamdy said. “And understanding the perceived barriers to judicious antibiotic prescribing can help to identify the highest yield interventions.”

This also reflects the approach taken by the outpatient antibiotic stewardship team at the Children’s National Goldberg Center, led by Ariella Slovin, M.D., primary care pediatrics provider at Children’s National Hospital. Dr. Slovin’s oral abstract entitled “Antibiotic Prescribing Via Telemedicine in the Time of COVID-19,” examined the effect that a shift to telemedicine due to the COVID-19 pandemic had on antibiotic use for acute respiratory tract infections. Overall, her team found a decrease in the proportion of acute respiratory tract infections prescribed antibiotics and concluded that the shift to telemedicine did not adversely affect judicious antibiotic prescribing for acute respiratory tract infections.

Other participants from Children’s National included: Taeun Chang, M.D.; Yuan-Chiao Lu, Ph.D.; Chidiogo Anyigbo, M.D., M.P.H.; Panagiotis Kratimenos, M.D.; Sudeepta Basu, M.B.B.S., M.S.; Ashraf Harahsheh, M.D., F.A.C.C., F.A.A.P.; Rana F. Hamdy, M.D., M.P.H., M.S.C.E.; John Idso, M.D.; Michael Shoykhet, M.D., Ph.D.; Monika Goyal, M.D.; Ioannis Koutroulis, M.D., Ph.D., M.B.A.; Josepheen De Asis-Cruz, M.D., Ph.D.; Asad Bandealy, M.D., M.P.H.; Priti Bhansali, M.D.; Sabah Iqbal, M.D.; Kavita Parikh, M.D.; Shilpa Patel, M.D.; Cara Lichtenstein, M.D.

To view the PAS phase I mini session list and the various areas of expertise at Children’s National, visit: https://innovationdistrict.childrensnational.org/childrens-national-hospital-at-the-2021-pediatric-academic-societies-meeting/

The PAS virtual conference phase II starts on Monday, May 10 and it goes through Friday, June 4. Those interested in attending may still register for phase II here: http://2021.pas-meeting.org/registration/

Purkinje cell

Premature birth disrupts Purkinje cell function, resulting in locomotor learning deficits

Purkinje cell

Children’s National Hospital researchers explored how preterm birth disrupts Purkinje cell function, resulting in locomotor learning deficits.

As the care of preterm babies continues to improve, neonatologists face new challenges to ensure babies are protected from injury during critical development of the cerebellum during birth and immediately after birth. How does this early injury affect locomotor function, and to what extent are clinicians able to protect the brain of preterm babies?

A new peer-reviewed study by Aaron Sathyanesan, Ph.D., Panagiotis Kratimenos, M.D., Ph.D., and Vittorio Gallo, Ph.D., published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), explores exactly what neural circuitry of the cerebellum is affected due to complications that occur around the time of birth causing these learning deficits, and finds a specific type of neurons — Purkinje cells — to play a central role.

Up until now, there has been a sparsity of techniques available to measure neuronal activity during locomotor learning tasks that engage the cerebellum. To surmount this challenge, Children’s National used a multidisciplinary approach, bringing together a team of neuroscientists with neonatologists who leveraged their joint expertise to devise a novel and unique way to measure real-time Purkinje cell activity in a pre-clinical model with clinical relevance to humans.

Researchers measured neural circuit function by pairing GCaMP6f fiber photometry, used to measure neuronal activity in the brain of a free moving subject, with an ErasmusLadder, in which it needs to travel from point A to point B on a horizontal ladder with touch-sensitive rungs that register the type and length of steps. By introducing a sudden obstacle to movement, researchers observed how the subject coped and learned accordingly to avoid this obstacle. By playing a high-pitch tone just before the obstacle was introduced, researchers were able to measure how quickly the subjects were able to anticipate the obstacle and adjust their steps accordingly. Subjects with neonatal brain injury and normal models were run through a series of learning trials while simultaneously monitoring brain activity. In this way, the team was able to quantify cerebellum-dependent locomotor learning and adaptive behavior, unlocking a functional and mechanistic understanding of behavioral pathology that was previously unseen in this field.

In addition to showing that normal Purkinje cells are highly active during movement on the ErasmusLadder, the team explored the question of whether Purkinje cells of injured pre-clinical models were generally non-responsive to any kind of stimuli. They found that while Purkinje cells in injured subjects responded to puffs of air, which generally cue the subject to start moving on the ErasmusLadder, dysfunction in these cells was specific to the period of adaptive learning. Lastly, through chemogenetic inhibition, which specifically silences neonatal Purkinje cell activity, the team was able to mimic the effects of perinatal cerebellar injury, further solidifying the role of these cells in learning deficits.

The study results have implications for clinical practice. As the care of premature babies continues to improve, neonatologists face new challenges to ensure that babies not only survive but thrive. They need to find ways to prevent against the lifelong impacts that preterm birth would otherwise have on the cerebellum and developing brain.

Read the full press release here.

Read the full journal article here.

coronavirus molecules with DNA

Novel SARS-CoV-2 spike variant found in a newborn in Washington, D.C.

coronavirus molecules with DNA

Researchers at Children’s National Hospital found a new SARS-CoV-2 spike variant in a neonatal patient, according to a study that genetically sequenced the virus in 27 pediatric patients. The newborn presented with a viral load of 50,000 times more particles than the average patient, which led to identifying the N679S spike protein variant — the earliest known sample of this coronavirus lineage in the U.S. mid-Atlantic region.

While the paper is posted to the preprint server medRxiv and has not been peer-reviewed, it represents an early step towards establishing better surveillance of the COVID-19 pandemic. The new variant helps understand the process of viral adaptation, potentially informing treatment development and vaccine design for any viral variants in the future.

All genomes change and evolve. Additional viral variants are expected to emerge as more patients are infected. The data analysis recognized eight other cases in Washington, D.C., with the N679S variant, pointing toward a European origin due to the genetic similarity between of SARS-CoV-2 strains in the U.S. and United Kingdom.

“We need to sequence more cases to identify variants and stay ahead of the virus,” said Drew Michael, Ph.D., molecular geneticist at Children’s National and senior author of the study. “The United States sequences a tiny fraction of all cases, and because we are not sequencing enough, we are not aware of the variants in SARS-CoV-2 that may be spreading in our community.”

“Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak,” was published on the preprint server medRxiv. Additional authors include Jonathan LoTempio, Erik Billings, Kyah Draper, Christal Ralph, Mahdi Moshgriz, Nhat Duong, Jennifer Dien Bard, Xiaowu Gai, David Wessel, M.D., Roberta L. DeBiasi, M.D., M.S., Joseph M. Campos, Ph.D., Eric Vilain, M.D., Ph.D. and Meghan Delaney, D.O., M.P.H.

You can read the full preprint on medRxiv.

illustration of brain with stem cells

Innovative phase 1 trial to protect brains of infants with CHD during and after surgery

A novel phase 1 trial looking at how best to optimize brain development of babies with congenital heart disease (CHD) is currently underway at Children’s National Hospital.

Children with CHD sometimes demonstrate delay in the development of cognitive and motor skills. This can be a result of multiple factors including altered prenatal oxygen delivery, brain blood flow and genetic factors associated with surgery including exposure to cardiopulmonary bypass, also known as the heart lung machine.

This phase 1 trial is the first to deliver mesenchymal stromal cells from bone marrow manufactured in a lab (BM-MSC) into infants already undergoing cardiac surgery via cardiopulmonary bypass. The hypothesis is that by directly infusing the MSCs into the blood flow to the brain, more MSCs quickly and efficiently reach the subventricular zone and other areas of the brain that are prone to inflammation. The trial is open to eligible patients ages newborn to six months of age.


Learn more in this overview video.

The trial is part of a $2.5 million, three-year grant from the National Institutes of Health (NIH) led by Richard Jonas, M.D.Catherine Bollard, M.B.Ch.B., M.D., and Nobuyuki Ishibashi, M.D.. The project involves collaboration between the Prenatal Cardiology program of Children’s National Heart Institute, the Center for Cancer and Immunology Research, the Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

“NIH supported studies in our laboratory have shown that MSC therapy may be extremely helpful in improving brain development in animal models after cardiac surgery,” says Dr. Ishibashi. “MSC infusion can help reduce inflammation including prolonged microglia activation that can occur during surgery that involves the heart lung machine.”

Staff from the Cellular Therapy Laboratory, led by director Patrick Hanley, Ph.D., manufactured the BM-MSC at the Center for Cancer and Immunology Research, led by Dr. Bollard.

The phase 1 safety study will set the stage for a phase 2 effectiveness trial of this highly innovative MSC treatment aimed at reducing brain damage, minimizing neurodevelopmental disabilities and improving the postoperative course in children with CHD. The resulting improvement in developmental outcome and lessened behavioral impairment will be of enormous benefit to individuals with CHD.

For more information about this new treatment, contact the clinical research team: Gil Wernovsky, M.D., Shriprasad Deshpande, M.D., Maria Fortiz.

MRI of the patient's head close-up

Early versus late MRI in newborn brain injury

MRI of the patient's head close-up

A single magnetic resonance imaging (MRI) performed in the first week after birth is adequate to assess brain injury and offer prognostic information in newborn infants with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia, according to a new study published in The Journal of Pediatrics.

A collaborative team of neonatology, neurology and neuroradiology experts from Children’s National Hospital that included Gilbert Vezina, M.D., Taeun Chang, M.D., and An N. Massaro, M.D., came together to evaluate the agreement in brain injury findings between early and late MRI in newborn infants with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. The team then compared the ability of early versus late MRI to predict early neurodevelopmental outcomes.

This was a prospective longitudinal study of 49 patients with HIE who underwent therapeutic hypothermia and had MRI performed at both <7 and ≥7 days of age. MRIs were reviewed by an experienced neuroradiologist and assigned brain injury severity scores according to established systems. Scores for early and late MRIs were assessed for agreement using the kappa statistic. The ability of early and late MRI scores to predict death or developmental delay at 15-30 months of age was assessed by logistic regression analyses.

The results of the study found agreement between the early and late MRI was substantial to near perfect (k>0.75, p<0.001) across MRI scoring systems. In cases of discrepant scoring, early MRI was more likely to identify severe injury when compared with late MRI. Early MRI scores were more consistently predictive of adverse outcomes compared with late MRI.

Read the full study in The Journal of Pediatrics.

structure of EGFR

Study suggests EGFR inhibition reverses alterations induced by hypoxia

structure of EGFR

The study suggests that specific molecular responses modulated by EGFR (seen here) may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

Hypoxic (HX) encephalopathy is a major cause of death and neurodevelopmental disability in newborns. While it is known that decreased oxygen and energy failure in the brain lead to neuronal cell death, the cellular and molecular mechanisms of HX-induced neuronal and glial cell damage are still largely undefined.

Panagiotis Kratimenos, M.D., and colleagues from the Center for Neuroscience Research at the Children’s National Research Institute, discovered increased expression of activated-epidermal growth factor receptor (EGFR) in affected cortical areas of neonates with HX and decided to further investigate the functional role of EGFR-related signaling pathways in the cellular and molecular changes induced by HX in the cerebral cortex.

The researchers found that HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation and reversed HX-induced astrogliosis.

The researchers also performed, for the first time, high-throughput transcriptomic analysis of the cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in brain injury. Their results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

This study defines many new exciting avenues of scientific exploration to further elucidate the beneficial impact of EGFR blockade on perinatal brain injury at the cellular and molecular levels. This analysis could potentially result in the identification of new therapeutic targets associated with EGFR signaling in the developing mammalian brain that are linked with specific long-term abnormalities caused by perinatal brain injury.

Children’s National researchers who contributed to this study include Panagiotis Kratimenos, M.D., Ioannis Koutroulis, M.D., Ph.D., M.B.A., Susan Knoblach, Ph.D., Payal Banerjee, Surajit Bhattacharya, Ph.D., Maria Almira-Suarez, M.D., and Vittorio Gallo, Ph.D.

Read the full article in iScience.

newborn

Predicting risk for infantile spasms after acute symptomatic neonatal seizures

newborn

Infantile spasms (IS) is a severe epilepsy in early childhood. Early treatment of IS provides the best chance of seizure remission and favorable developmental outcome.

Taeun Chang, M.D., director of the Neonatal Neurology and Neurocritical Care Program at Children’s National Hospital, participated in a study with other national pediatric experts which aimed to develop a prediction rule to accurately predict which neonates with acute symptomatic seizures will develop IS.

The group of researchers found that multiple potential predictors were associated with IS, including Apgar scores, EEG features, seizure characteristics, MRI abnormalities and clinical status at hospital discharge. The final model born from this work included three risk factors: (a) severely abnormal EEG or ≥3 days with seizures recorded on EEG, (b) deep gray or brainstem injury on MRI and (c) abnormal tone on discharge exam.

The significance of these findings is that IS risk after acute symptomatic neonatal seizures can be stratified using commonly available clinical data. No child without risk factors, vs >50% of those with all three factors, developed IS. This risk prediction rule may be valuable for clinical counseling as well as for selecting participants for clinical trials to prevent post‐neonatal epilepsy. This tailored approach may lead to earlier diagnosis and treatment and improve outcomes for a devastating early life epilepsy.

Read the full study in Epilepsia.

Lee Beers

Lee Beers, M.D., F.A.A.P, begins term as AAP president

Lee Beers

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
  • Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
  • Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.