Julia Finkel

Two Children’s National spin-outs join Johnson & Johnson–JLABS

Julia Finkel

AlgometRx, which joins JPOD @ Philadelphia, was founded by Julia Finkel, M.D., pediatric anesthesiologist and director of Pain Medicine and Research at Children’s Sheikh Zayed Institute.

AlgometRx and Adipomics, two companies that spun out of innovations discovered at Children’s National Health System, have been selected by Johnson & Johnson Innovation – JLABS to join JPOD @ Philadelphia and JPOD @ Boston, respectively.

JLABS is a global network of no-strings-attached incubators for innovative companies from across the pharmaceutical, medical device, consumer and health technology sectors. Start-up companies are free to pursue their own research priorities independently, with access to state-of-the-art facilities to develop new drugs, medical devices, precision diagnostics and health technologies for people around the world.

Both companies got their start at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National. The Institute focuses on research and innovation that can improve health for children everywhere.

AlgometRx, which joins JPOD @ Philadelphia, was founded by Julia Finkel, M.D., pediatric anesthesiologist and director of Pain Medicine and Research at Children’s Sheikh Zayed Institute. The AlgometRx device is a first-of-its-kind platform technology that aims to objectively measure pain intensity, type and drug effects in real time by capturing a digital image of a patient’s pupillary light response and applying a series of proprietary algorithms to various characteristics.

AlgometRx is designed to provide an objective pain measurement that aims to help physicians select the correct analgesic class of drug and dosage. By optimizing pain assessment, drug selection and drug management, AlgometRx aims to impact the opioid epidemic and the monitoring and management of Opioid Use Disorder.

Robert Freishtat and Evan Nadler

Adipomics, which joins JPOD @ Boston, was co-founded by Robert Freishtat, M.D., M.P.H., senior investigator in the Center for Genetic Medicine of the Children’s Research Institute and chief of the Division of Emergency Medicine at Children’s National, and pediatric surgeon Evan P. Nadler, M.D., co-director of the Obesity Program and director of the Bariatric Surgery Program at Children’s National.

Adipomics, which joins JPOD @ Boston, was co-founded by pediatric surgeon Evan P. Nadler, M.D., co-director of the Obesity Program and director of the Bariatric Surgery Program at Children’s National, and Robert Freishtat, M.D., M.P.H., senior investigator in the Center for Genetic Medicine of the Children’s Research Institute and chief of the Division of Emergency Medicine at Children’s National. Adipomics was founded with the aim to address the global epidemic of obesity-related diseases including Type 2 diabetes and cardiovascular diseases. World health experts predict that one billion people worldwide will be obese by 2030.

Drs. Nadler and Freishtat discovered that exosomes released from fat cells (adipocytes) carry genetic material that can mediate various diseases related to obesity. Through their research, they developed a proprietary method that aims to detect how obesity affects an individual patient’s metabolism before the onset of overt disease. Adipomics aims to create the first non-invasive, “anticipatory medicine” diagnostic that detects risk for obesity-related diseases prior to the onset of clinical signs or even biochemical abnormalities. If successful, this predictive methodology would enable treatment much earlier in the disease process, which is likely to improve effectiveness.

A recent news release from Children’s National provides more details on these innovations.

As organizations that share a commitment to improving the pace of healthcare innovation, Children’s National and Johnson & Johnson Innovation – JLABS also recently announced their collaboration to launch JLABS @ Washington, DC,  a 32,000-square foot facility to be located at the new Children’s National Research & Innovation Campus in Washington, D.C. The JLABS @ Washington, DC will have the capacity to house up to 50 pharmaceutical, medical device, consumer and health technology companies that are aiming to advance the development of new drugs, medical devices, precision diagnostics and health technologies, including applications in pediatrics. The campus is located on a 12-acre portion of the former Walter Reed Army Medical Center campus in the nation’s capital and is slated to open in 2020, coinciding with the 150th Anniversary of Children’s National Health System.

Test tube with DNA

“Liquid biopsies” could track diffuse midline gliomas

Test tube with DNA

A multi-institutional team led by researchers at Children’s National in Washington, D.C., developed and tested “liquid biopsy,” a measure of circulating tumor DNA in patients’ cerebrospinal fluid and blood plasma. They show that quantifying the amount of circulating tumor DNA possessing key mutations characteristic of diffuse midline gliomas could reliably predict the tumors’ response to radiotherapy.

Diffuse midline gliomas are rare, diagnosed in fewer than 800 Americans every year, the majority of whom are children. These cancers arise in the cellular “glue” that holds the brain and spinal cord’s neurons together, grow swiftly and have no cure. About half of patients with these cancers, including diffuse intrinsic pontine glioma, die within one year of diagnosis.

Clinical trials are increasingly investigating new treatments that could offer hope for patients and their families. Yet, thus far, there have been few ways to track the progression of these conditions, offering little insight on whether a treatment is hitting its intended goal.

To solve this problem, a multi-institutional team led by researchers at Children’s National in Washington, D.C., developed and tested “liquid biopsy,” a measure of circulating tumor DNA in patients’ cerebrospinal fluid and blood plasma. They show that quantifying the amount of circulating tumor DNA possessing key mutations characteristic of these cancers could reliably predict the tumors’ response to radiotherapy. The scientists published their results online Oct. 15, 2018, in Clinical Cancer Research.

“We heard from our clinician colleagues that many kids were coming in and their magnetic resonance imaging (MRI) suggested a particular type of tumor. But it was always problematic to identify the tumor’s molecular subtype,” says Javad Nazarian, Ph.D., MSC, a principal investigator in Children’s Center for Genetic Medicine Research. “Our colleagues wanted a more accurate measure than MRI to find the molecular subtype. That raised the question of whether we could actually look at their blood to determine the tumor subtype.”

Children’s liquid biopsy, which remains at the research phase, starts with a simple blood draw using the same type of needle as is used when people donate blood. When patients with brain tumors provide blood for other laboratory testing, a portion of it is used for the DNA detective work. Just as a criminal leaves behind fingerprints, tumors shed telltale clues in the blood. The team at Children’s National searches for the histone 3K27M (H3K27M), a mutation associated with worse clinical outcomes.

“With liquid biopsy, we were able to detect a few copies of tumor DNA that were hiding behind a million copies of healthy DNA,” Nazarian says. “The blood draw and liquid biopsy complement the MRI. The MRI gives the brain tumor’s ZIP code. Liquid biopsy gives you the demographics within that ZIP code.”

Working with collaborators around the nation, Children’s National continues to refine the technology to improve its accuracy.

Even though this research technique is in its infancy, the rapid, cheap and sensitive technology already is being used by people around the globe.

“People around the world are sending blood to us, looking for this particular mutation, H3K27M,” says Lindsay B. Kilburn, M.D., a neurooncologist, principal investigator at Children’s National for the Pacific Pediatric Neuro-Oncology Consortium, and study co-author. “In many countries or centers children to not have access to teams experienced in taking a biopsy of tumors in the brainstem, they can perform a simple blood draw and have that blood processed and analyzed by us. In only a few days, we can provide important molecular information on the tumor subtype previously only available to patients who had undergone a tumor biopsy.”

With that DNA finding, physicians can make more educated therapeutic decisions, including prescribing medications that could not have been given previously, Nazarian adds.

In addition to Nazarian and Dr. Kilburn, study co-authors include Eshini Panditharatna, Madhuri Kambhampati, Heather Gordish-Dressman, Ph.D., Suresh N. Magge, M.D., John S. Myseros, M.D., Eugene I. Hwang, M.D., and Roger J. Packer, M.D., all of Children’s National; Mariam S. Aboian, Nalin Gupta, Soonmee Cha, Michael Prados and Co-Senior Author Sabine Mueller, all of University of California, San Francisco; Cassie Kline, UCSF Benioff Children’s Hospital;  John R. Crawford, UC San Diego; Katherine E. Warren, National Cancer Institute; Winnie S. Liang and Michael E. Berens, Translational Genomics Research Institute; and Adam C. Resnick, Children’s Hospital of Philadelphia.

Financial support for the research described in the report was provided by the V Foundation for Cancer Research, Goldwin Foundation, Pediatric Brain Tumor Foundation, Smashing Walnuts Foundation, The Gabriella Miller Kids First Data Resource Center, Zickler Family Foundation, Clinical and Translational Science Institute at Children’s National under award 5UL1TR001876-03, Piedmont Community Foundation, Musella Foundation for Brain Tumor Research, Mathew Larson Foundation, The Lilabean Foundation for Pediatric Brain Cancer Research, The Childhood Brain Tumor Foundation, the National Institutes of Health and American Society of Neuroradiology.

ID-KD vaccine induced T-cell cytotoxicity

Fighting lethal cancer with a one-two punch

The immune system is the ultimate yin and yang, explains Anthony D. Sandler, M.D., senior vice president and surgeon-in-chief of the Joseph E. Robert Jr. Center for Surgical Care at Children’s National in Washington, D.C. With an ineffective immune system, infections such as the flu or diarrheal illness can run unchecked, causing devastating destruction. But on the other hand, excess immune activity leads to autoimmune diseases, such as lupus or multiple sclerosis. Thus, the immune system has “checks and balances” to stay controlled.

Cancer takes advantage of “the checks and balances,” harnessing the natural brakes that the immune system puts in place to avoid overactivity. As the cancer advances, molecular signals from tumor cells themselves turn on these natural checkpoints, allowing cancers to evade immune attack.

Several years ago, a breakthrough in pharmaceutical science led to a new class of drugs called checkpoint inhibitors. These medicines take those proverbial brakes off the immune system, allowing it to vigorously attack malignancies. However, Dr. Sandler says, these drugs have not worked uniformly and in some cancers, they barely work at all against the cancer.

One of these non-responders is high risk neuroblastoma, a common solid tumor found outside the skull in children. About 800 U.S. children are diagnosed with this cancer every year. And kids who have the high-risk form of neuroblastoma have poor prognoses, regardless of which treatments doctors use.

However, new research could lead to promising ways to fight high-risk neuroblastoma by enabling the immune system to recognize these tumors and spark an immune response. Dr. Sandler and colleagues recently reported on these results in the Jan. 29, 2018, PLOS Medicine using an experimental model of the disease.

The researchers created this model by injecting the preclinical models with cancer cells from an experimental version of neuroblastoma. The researchers then waited several days for the tumors to grow. Samples of these tumors showed that they expressed a protein on their cell surfaces known as PD-L1, a protein that is also expressed in many other types of human cancers to evade immune system detection.

To thwart this protective feature, the researchers made a cancer vaccine by removing cells from the experimental model’s tumors and selectively turning off a gene known as Id2. Then, they irradiated them, a treatment that made these cells visible to the immune system but blocked the cells from dividing to avoid new tumors from developing.

They delivered these cells back to the experimental models, along with two different checkpoint inhibitor drugs – antibodies for proteins known as CLTA-4 and PD-L1 – over the course of three treatments, delivered every three days. Although most checkpoint inhibitors are administered over months to years, this treatment was short-term for the experimental models, Dr. Sandler explains. The preclinical models were completely finished with cancer treatment after just three doses.

Over the next few weeks, the researchers witnessed an astounding turnaround: While experimental models that hadn’t received any treatment uniformly died within 20 days, those that received the combined vaccine and checkpoint inhibitors were all cured of their disease. Furthermore, when the researchers challenged these preclinical models with new cancer cells six months later, no new tumors developed. In essence, Dr. Sandler says, the preclinical models had become immune to neuroblastoma.

Further studies on human patient tumors suggest that this could prove to be a promising treatment for children with high-risk neuroblastoma. The patient samples examined show that while tumors with a low risk profile are typically infiltrated with numerous immune cells, tumors that are high-risk are generally barren of immune cells. That means they’re unlikely to respond to checkpoint inhibiting drugs alone, which require a significant immune presence in the tumor microenvironment. However, Dr. Sandler says, activating an immune response with a custom-made vaccine from tumor cells could spur the immune response necessary to make these stubborn cancers respond to checkpoint inhibitors.

Dr. Sandler cautions that the exact vaccine treatment used in the study won’t be feasible for people. The protocol to make the tumor cells immunogenic is cumbersome and may not be applicable to gene targeting in human patients. However, he and his team are currently working on developing more feasible methods for crafting cancer vaccines for kids. They also have discovered a new immune checkpoint molecule that could make this approach even more effective.

“By letting immune cells do all the work we may eventually be able to provide hope for patients where there was little before,” Dr. Sandler says.

In addition to Dr. Sandler, study co-authors include Priya Srinivasan, Xiaofang Wu, Mousumi Basu and Christopher Rossi, all of the Joseph E. Robert Jr. Center for Surgical Care and The Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI), at Children’s National in Washington, D.C.

Financial support for research described in this post was provided by the EVAN Foundation, the Catherine Blair foundation, the Michael Sandler Research Fund and SZI.

ID-KD vaccine induced T-cell cytotoxicity

Mechanism of Id2kd Neuro2a vaccination combined with α-CTLA-4 and α-PD-L1 immunotherapy in a neuroblastoma model. During a vaccine priming phase, CTLA-4 blockade enhances activation and proliferation of T-cells that express programmed cell death 1 (PD1) and migrate to the tumor. Programmed cell death-ligand 1 (PD-L1) is up-regulated on the tumor cells, inducing adaptive resistance. Blocking PD-L1 allows for enhanced cytotoxic effector function of the CD8+ tumor-infiltrating lymphocytes. Artist: Olivia Abbate

Dr. Natasha Shur shares “Genetics and Telemedicine: Extending Our Reach” at the Future of Pediatrics CME

Virtual visits: A new house call for rare disease treatment

Dr. Natasha Shur shares “Genetics and Telemedicine: Extending Our Reach” at the Future of Pediatrics CME

Natasha Shur, M.D., an attending clinical geneticist at Children’s National Health System, shares “Genetics and Telemedicine: Extending Our Reach” at the Future of Pediatrics CME symposium in Bethesda, Maryland, on June 20.

“For the first time it wasn’t autism, autism, autism,” Shannon Chin says after learning the reason her newborn daughter, Sariyah, who turned 3 in August, couldn’t feed like normal infants was due to a tiny deletion of chromosome 22. This atypical deletion, a variation of a genetic condition known as 22q11.2 deletion syndrome, left Sariyah unable to suck and obtain nourishment as an infant. She was born premature and relied on assisted feeding tubes, inserted through her nose, to help her grow.

At 22-weeks-old, Sariyah received the diagnosis, which affects 1 in 4,000 children born each year. Sariyah’s genetic tests encouraged Chin to follow up with a nagging question: What if her two sons, Rueben and Caleb, both of whom were diagnosed with autism spectrum disorder (ASD), had something else?

Debra Regier, M.D., a medical geneticist at Children’s National Health System, encouraged Chin to follow up with a genetic test to answer these questions and to confirm 22q11.2 deletion syndrome symptoms she observed in Rueben.

A microarray analysis recently revealed Rueben, 17, has atypical  22q11.2 deletion syndrome. Caleb, 5, took the test and has developmental delay and ASD, which is more likely to occur in children with 22q11.2 deletion syndrome. He tested negative for the same deletion as his siblings. Additional tests are underway.

As Chin juggles complex care for her children, she realizes the partial deletion of chromosome 22 presents differently in every child. Sariyah and Rueben share short stature; they fit into tiny clothes. That’s where the phenotypical clues stop. They don’t have a cleft palate or dysmorphic facial features, distinctive of typical cases of 22q11.2 deletion syndrome. Sariyah has physical symptoms. Her intestines merged together, which gastrointestinal surgery fixed. Rueben experiences behavioral and neurological symptoms, including picky eating, aggression and uncontrolled body movements, which led the Chin family to Dr. Regier. Sariyah, Rueben and Caleb all have neurodevelopmental delays that impact their speech and development.

Coordinating multiple visits with geneticists, specialists, surgeons, genetic counselors and pediatricians, while navigating insurance, is a lot for any parent, but especially for those, like Chin, who have special considerations. Her children are non-verbal, so she pays close attention to their physical cues. Simplifying this process is one reason why Natasha Shur, M.D., a medical geneticist at Children’s National, introduced virtual visits to her patients, including Rueben, who had challenges with in-person visits. She thought: How can we make medical care easier for patients and families?

In January, Dr. Shur expanded virtual visits into a pilot program for 50 to 60 patients, including Sariyah and Caleb, with the support of a grant from the Health Resources and Services Administration (HRSA), the division of telemedicine at Children’s National and the Rare Disease Institute (RDI), the medical home to thousands of pediatric patients living with rare or genetic conditions. This program lets patients with concern for or already diagnosed genetic conditions in Maryland, the District of Columbia and Virginia, where Dr. Shur is licensed to practice medicine, test out virtual visits. Patients can download the HIPAA-compliant app or click through a secure link on a digital device to connect with Dr. Shur or a pediatric subspecialist.

Dr. Shur shares the preliminary findings of a new virtual visits pilot program,

Dr. Shur shares the preliminary findings of a virtual visits pilot program, which 50-60 local patients have tested in conjunction with in-person visits as a flexible way to manage medical care for genetic conditions.

On June 20, Dr. Shur shared a presentation about the program, “Genetics and Telemedicine: Extending Our Reach,” with pediatricians attending the Children’s National Future of Pediatrics continuing medical education (CME) symposium in Bethesda, Maryland.

Instead of a formal pilot program launch and end date with data, Dr. Shur mentions she conducts quality improvement assessments with each patient. She asks what they like about virtual visits. Do they feel comfortable with the software and technology? What types of visits do they prefer to do at home? What works best at the hospital? Do they want to keep using this program?

For Chin and most participants, the answer is yes. These families appreciate saving time, mileage, and being in close access to pediatric subspecialists from the comfort of home.

Parents can conference call from separate locations and share screens with the doctors, which works well if one parent is at work and another is at home – or if they live apart. Children can maintain their normal routine, such as finishing breakfast, homework, playing or staying in bed if they don’t feel well, though it is important to see the child in the virtual visit.

Families can obtain virtual assessments about urgent conditions without taking time off from work or school. Currently, only 10 to 30% of virtual visit patients with concerns about genetic conditions need an in-person, follow-up appointment. Fortunately, many conditions are less urgent than thought at the time of referral. Dr. Shur and specialists also benefit from observing children in their natural environment.

At the symposium, Dr. Shur translates this into clinical terms: reduced no-show visits, the ability to schedule shorter, more flexible visits, the ability to quickly and accurately diagnose conditions and provide care, and the ability to keep children with compromised immune function out of public areas, including waiting rooms. She discussed building rapport with patients, almost all of whom like these flexible care models.

“The idea is that we’re trying to understand what is best done using virtual technology and what is better for those in-person connections. More detailed physical exams take place in person. There are some cases where eye-to-eye contact and sitting in the exam room together is important,” says Dr. Shur. “Virtual visits should never replace in-person care. It’s just a forward way of thinking about: How do we use our time best?”

Case study 1: Saving families time and miles

Dr. Shur notes that for some patients, distance is a deciding factor for scheduling care. One mother’s five-hour round-trip commute to the children’s hospital, without traffic, is now five minutes. As an air-traffic controller, her schedule changes. She values the flexibility of the new program. To connect with Dr. Shur, she logs into the app on her computer or smart phone and brings her 2-year-old son into the video. He has cardiofaciocutaneous syndrome (CFC), a condition that affects 200 to 300 people in the world. As a result of a MAP2K1 gene variant, one of four genes – BRAF, MAP2K1, MAP2K2 and KRAS – associated with CFC, he experiences feeding problems, reflux, constipation and developmental delays.

By scheduling more frequent, but shorter check-ins, Dr. Shur assesses how he responds to treatment and makes recommendations to the mother in real time, such as trying prune juice for digestive health. They talk about rearranging feeding measurements and intervals, including his 2 a.m. dose of a peptide formula, which the mom blends at home to support her son’s growth. This modification equates to more sleep for everyone.

If follow-up tests, such as an X-ray or a blood test are needed, Dr. Shur coordinates these exams with the family at the hospital or at a nearby medical center. Depending on the condition, Dr. Shur may refer the family to an ophthalmologist, cardiologist, neurologist or learning and development specialist.

As a parent, Dr. Shur appreciates the direct approach virtual visits deliver.

“As a mom, if I’m taking my child to the doctor for two hours, I want to know why I’m there,” Dr. Shur says. “What are all the options?”

Case study 2: Observing children at home

Chin, who was also featured in Dr. Shur’s CME presentation, appreciates virtual visits for their convenience and efficiency, but her favorite feature is letting doctors observe her children at home.

“Children act differently outside the home,” says Chin.

For example, instead of describing Rueben’s rapid, rhythmic arm movements, a flinging of the arms, Chin showed neurologists at a scheduled virtual home visit. For Marc DiFazio, M.D., a pediatric neurologist, it was evident that Reuben had a movement disorder commonly seen in children with ASD, which is responsive to medication. In five minutes, her son had a diagnosis. The involuntarily movement wasn’t a behavioral issue, as previously thought, but a movement disorder.

“The regular in-person visit has a beautiful role and it’s very important, but virtual visits bring a different focus,” says Dr. Shur. “We get to see what the child’s life is like, what the home setting is like and what their schedule is like. How can we make their day-to-day life easier?”

Phenylketonuria (PKU), a rare condition that prevents the body from breaking down phenylalanine (Phe), an amino acid in protein, is another condition that pairs well with virtual visits. PKU affects 1 in 10,000 to 15,000 newborns in the U.S. People with PKU often require medication, food-based formulas and a protein-restricted diet to help their body process or regulate Phe.

If a patient with PKU connects through a virtual visit, they (or their parents) can open the refrigerator, talk about low-protein foods, discuss potential barriers to following a low-Phe diet, show the team new supplements or over-the-counter medications they are taking, discuss reactions to new therapies and, for adults, discuss an injectable drug recently approved by the FDA that has side effects but may ultimately allow them to follow a regular diet. These observations may not warrant a traditional trip to the doctor but are important for geneticists and patients to discuss. The goal of these visits is to identify and work around potential health barriers, while preventing adverse health outcomes.

To support this model, a 60-minute in-person visit scheduled every six months to a year can be broken into 15-minute video appointments at more frequent intervals. The result, based on the same amount of clinical time, is a targeted and detailed assessment to support personalized treatment and to help the patient adapt to a low-Phe meal plan.

During the video call, Dr. Shur and the team may prescribe a different medication, order a diagnostic procedure or schedule a follow-up appointment, if necessary. Depending on the situation, the patient will still likely come in for in-person annual visits.

Program assessment: Evaluating visits for each patient

Despite the popularity of virtual visits, Dr. Shur mentions this program isn’t a good fit for everyone – depending on a patient’s preferences. There are also limitations to consider. If a parent is hesitant to try this platform or if the comprehensive physical examination is the first key step, they should schedule in-person visits. The goal is to give parents who are requesting or curious about virtual visits a chance to try the platform. Having a secure area, preferably a private space at home, is important. A Wi-Fi connection and a digital device are required, which may create barriers for some patients.

However, Dr. Shur finds the program can alleviate hurdles – such as transportation challenges. One patient lives two hours away and couldn’t make it in for routine medical visits due to car problems. Now she makes every virtual appointment. For the first time in her life, she can manage medical care for herself and for her children.

Most insurance companies Dr. Shur works with cover virtual visits. The key is to have the virtual connection, or video, so Dr. Shur can still physically see the patient. Otherwise, the visit doesn’t count. A grant from CareFirst covers the costs of visits for patients who are using Medicaid or who don’t have medical insurance.

Parallel trends are happening across the country and for other conditions. Officials at the Federal Communications Commission (FCC) are reviewing a three-year pilot to expand the use of connected care services, like virtual visits, for low-income Americans living in rural areas. The Rural Health Care Program, funded by the FCC, supports hospitals that implement telehealth programs.

The American Academy of Pediatrics (AAP) released a statement in 2015 about telemedicine technologies, noting that if these technologies are applied in a synergistic model under one health care system or are guided by a family doctor, they can transform pediatric health care.

The key is to avoid a fragmented virtual health system.

The AAP applauds virtual connections that support collaborations among pediatric physicians, subspecialists and surgeons, reduce travel burdens for families, alleviate physician shortages, improve the efficiency of health care and enhance the quality of care and quality of life for children with special health care needs.

Planning for the future, investing in physician-patient partnerships

A poster at the Future of Pediatrics conference

The American Academy of Pediatrics supports telemedicine technologies that enhance the quality of care and the quality of life for children with special health care needs.

“The feedback has been phenomenal,” Dr. Shur says about the future of virtual visits for genetics. “Virtual visits will never replace in-person visits. They will be used in conjunction with in-person visits to maximize care.”

Dr. Regier and Jamie Frasier, M.D., Ph.D., medical geneticists at Children’s National, are introducing virtual visits to their patients, and many providers plan to do so as the program expands.

Sarah Viall, PPCNP, a nurse practitioner and newborn screening specialist, works with Dr. Shur and the geneticists during some visits to explain non-urgent newborn screening results to parents through virtual connections. Some parents find it’s easier to dial in during lunch or while they are together at home.

To improve education for patients and families, the education and technology committees at the RDI – led by geneticists and genetic counselors in partnership with the Clinical and Translational Science Institute at Children’s National – launched a new smartphone app called BearGenes. Families can watch 15 videos about genetics on the pin-protected app or view them online. The interactive guide serves as a gene glossary for terms patients may hear in a clinical setting. Topics range from genetics 101, describing how DNA is encrypted in the body through four letters – A, T, C and G – to different types of genetic tests, such as whole exome sequencing, to look for differences in the spelling of genes, which the genetic counselors explain are genetic mutations.

“As we unite patients with virtual health platforms and new forms of technology, we want to see what works and what doesn’t. We want their feedback,” Dr. Shur reemphasizes. “Virtual visits are a dynamic process. These visits only work through patient partnership and feedback.”

As Chin navigates atypical 22q11.2 deletion syndrome and ASD, she continues to appreciate the virtual waiting room and the ease of access virtual visits provides.

Sharing screens during virtual visits enables Chin to examine and better understand her children’s abdomen and kidney sonograms, cardiology reports and hearing exams. It forces everyone in the visit to focus on one topic or image at a time, strengthening the connection.

Chin still has questions about her children’s DNA, but she’s getting close to having more answers. She’s eager to see Caleb’s genetic test results and to work with Hillary Porter, M.S., CGC, the family’s genetic counselor, to interpret the data.

“We’re all learning together,” Dr. Shur says about the new pilot program, which applies to genomics at large.

As research about 22q11.2 deletion syndrome advances, geneticists, pediatric subspecialists and pediatricians are unifying efforts to work as one diagnostic and treatment team. Virtual visits enable faster consultations and can shorten diagnostic odysseys, some of which may take up to five years for children with rare disorders.

Attendees at the Future of Pediatrics conference

Nearly 400 pediatricians attend the Children’s National Future of Pediatrics CME symposium to learn about the future of pediatrics and about ways to work together as a diagnostic and treatment team.

For Chin, by better understanding how a tiny fragment of a missing chromosome may influence her children’s growth and development, she is already making long-term plans and coordinating multidisciplinary medical treatment for each child.

She hopes that by sharing her story and knowledge about 22q11.2 deletion syndrome, she can help other parents navigate similar situations. Heradvice to parents is to follow up on lingering questions by bringing them up with your medical team.

Chin is optimistic and happy she did. She’s grateful for the virtual visits program, which simplifies complex care for her family. And she’s still waiting, but she hopes to learn more about her middle child’s DNA, unraveling another medical mystery.

Read more about the virtual visits pilot program at Becker’s Hospital Review and listen to an interview with Dr. Shur and Shannon Chin on WTOP.

illustration of brain showing cerebellum

Focusing on the “little brain” to rescue cognition

illustration of brain showing cerebellum

Research faculty at Children’s National in Washington, D.C., with colleagues recently published a review article in Nature Reviews Neuroscience that covers the latest research about how abnormal development of the cerebellum leads to a variety of neurodevelopmental disorders.

Cerebellum translates as “little brain” in Latin. This piece of anatomy – that appears almost separate from the rest of the brain, tucked under the two cerebral hemispheres – long has been known to play a pivotal role in voluntary motor functions, such as walking or reaching for objects, as well as involuntary ones, such as maintaining posture.

But more recently, says Aaron Sathyanesan, Ph.D., a postdoctoral research fellow at the Children’s Research Institute, the research arm of Children’s National  in Washington, D.C., researchers have discovered that the cerebellum is also critically important for a variety of non-motor functions, including cognition and emotion.

Sathyanesan, who studies this brain region in the laboratory of Vittorio Gallo, Ph.D., Chief Research Officer at Children’s National and scientific director of the Children’s Research Institute, recently published a review article with colleagues in Nature Reviews Neuroscience covering the latest research about how altered development of the cerebellum contributes to a variety of neurodevelopmental disorders.

These disorders, he explains, are marked by problems in the nervous system that arise while it’s maturing, leading to effects on emotion, learning ability, self-control, or memory, or any combination of these. They include diagnoses as diverse as intellectual disability, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder and Down syndrome.

“One reason why the cerebellum might be critically involved in each of these disorders,” Sathyanesan says, “is because its developmental trajectory takes so long.”

Unlike other brain structures, which have relatively short windows of development spanning weeks or months, the principal cells of the cerebellum – known as Purkinje cells – start to differentiate from stem cell precursors at the beginning of the seventh gestational week, with new cells continuing to appear until babies are nearly one year old.  In contrast, cells in the neocortex, a part of the brain involved in higher-order brain functions such as cognition, sensory perception and language is mostly finished forming while fetuses are still gestating in the womb.

This long window for maturation allows the cerebellum to make connections with other regions throughout the brain, such as extensive connections with the cerebral cortex, the outer layer of the cerebrum that plays a key role in perception, attention, awareness, thought, memory, language and consciousness. It also allows ample time for things to go wrong.

“Together,” Sathyanesan says, “these two characteristics are at the root of the cerebellum’s involvement in a host of neurodevelopmental disorders.”

For example, the review article notes, researchers have discovered both structural and functional abnormalities in the cerebellums of patients with ASD. Functional magnetic resonance imaging (MRI), an imaging technique that measures activity in different parts of the brain, suggests that significant differences exist between connectivity between the cerebellum and cortex in people with ASD compared with neurotypical individuals. Differences in cerebellar connectivity are also evident in resting-state functional connectivity MRI, an imaging technique that measures brain activity in subjects when they are not performing a specific task. Some of these differences appear to involve patterns of overconnectivity to different brain regions, explains Sathyanesan; other differences suggest that the cerebellums of patients with ASD don’t have enough connections to other brain regions.

These findings could clarify research from Children’s National and elsewhere that has shown that babies born prematurely often sustain cerebellar injuries due to multiple hits, including a lack of oxygen supplied by infants’ immature lungs, he adds. Besides having a sibling with ASD, premature birth is the most prevalent risk factor for an ASD diagnosis.

The review also notes that researchers have discovered structural changes in the cerebellums of patients with Down syndrome, who tend to have smaller cerebellar volumes than neurotypical individuals. Experimental models of this trisomy recapitulate this difference, along with abnormal connectivity to the cerebral cortex and other brain regions.

Although the cerebellum is a pivotal contributor toward these conditions, Sathyanesan says, learning more about this brain region helps make it an important target for treating these neurodevelopmental disorders. For example, he says, researchers are investigating whether problems with the cerebellum and abnormal connectivity could be lessened through a non-invasive form of brain stimulation called transcranial direct current stimulation or an invasive one known as deep brain stimulation. Similarly, a variety of existing pharmaceuticals or new ones in development could modify the cerebellum’s biochemistry and, consequently, its function.

“If we can rescue the cerebellum’s normal activity in these disorders, we may be able to alleviate the problems with cognition that pervade them all,” he says.

In addition to Sathyanesan and Senior Author Gallo, Children’s National study co-authors include Joseph Scafidi, D.O., neonatal neurologist; Joy Zhou and Roy V. Sillitoe, Baylor College of Medicine; and Detlef H. Heck, of University of Tennessee Health Science Center.

Financial support for research described in this post was provided by the National Institute of Neurological Disorders and Stroke under grant numbers 5R01NS099461, R01NS089664, R01NS100874, R01NS105138 and R37NS109478; the Hamill Foundation; the Baylor College of Medicine Intellectual and Developmental Disabilities Research Center under grant number U54HD083092; the University of Tennessee Health Science Center (UTHSC) Neuroscience Institute; the UTHSC Cornet Award; the National Institute of Mental Health under grant number R01MH112143; and the District of Columbia Intellectual and Developmental Disabilities Research Center under grant number U54 HD090257.

baby cardioilogy patient

Researchers receive $2.5M grant to optimize brain development in babies with CHD

baby cardioilogy patient

Children’s National Health System researchers Richard Jonas, M.D., Catherine Bollard, M.B.Ch.B., M.D., and Nobuyuki Ishibashi, M.D., have been awarded a $2.5 million, three-year grant from the National Institutes of Health (NIH) to conduct a single-center clinical trial at Children’s National. The study will involve collaboration between the 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.

The goal of the study will be to optimize brain development in babies with congenital heart disease (CHD) who 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 the heart lung machine.

The award will be used to complete three specific aims of a Phase 1 safety study as described in the NIH grant:

  • Aim 1: To determine the safety and feasibility of delivering allogeneic bone marrow derived mesenchymal stromal cell (BM-MSC) during heart surgery in young infants less than 3 months of age using the heart lung machine. The optimal safe dose will be determined.
  • Aim 2: To determine the impact of MSC infusion on brain structure using advanced neuroimaging and neurodevelopmental outcomes.
  • Aim 3: To determine differences in postoperative inflammatory and patho-physiological variables after MSC delivery in the infant with CHD.

“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.”

In addition the researchers’ studies have demonstrated that cell-based intervention can promote white matter regeneration through progenitor cells, restoring the neurogenic potential of the brain’s own stem cells that are highly important in early brain development.

The Phase 1 clinical trial is being implemented in two stages beginning with planning, regulatory documentation, training and product development. During the execution phase, the trial will focus on patient enrollment. 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 Advanced Pediatric Brain Imaging Laboratory, led by Catherine Limperopoulos, Ph.D., will perform MR imaging.

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.

INSAR 2019 logo

Autism’s heterogeneity on display at INSAR 2019

INSAR 2019 logo

At the INSAR Annual Meeting, presentations from around the world share a common goal: finding better ways to support and care for people with autism.

There are countless aspects of autism spectrum disorder (ASD) to study, as evidenced by the 1,800-plus abstracts accepted at the 2019 International Society for Autism Research’s (INSAR) annual meeting. Presentations from investigators around the world ranged from pre-clinical studies of the genetic and biological underpinnings to community-based studies of diagnosis, assessment and treatment.

Along that broad spectrum of autism research, the work at Children’s National emphasizes better understanding of the clinical implications and community experiences of autism, with a particular focus on:

  • How well diagnostic and assessment tools capture the many differences between subpopulations of children with autism, whether based on sex/gender identity, cultural background or age
  • Understanding what children and adolescents with autism, and their parents, really need to help them thrive, and how to target supports to their unique needs
  • Finding the best ways to deliver vital information to autistic youth and their families in clear and accessible ways.

Researchers from Children’s Center for Autism Spectrum Disorders (CASD) presented nearly 20 scientific panels, oral presentations and posters at INSAR highlighting their most recent findings in these areas.

In addition to their own research, the CASD team attended sessions from INSAR’s global community of researchers, clinicians, and others with vested interest in the study of ASD. Lauren Kenworthy, Ph.D., CASD’s director, shared some of her key takeaways from the meeting with the ASD-focused publication Spectrum.

“At many levels of analyses, we are learning that a diagnostic label may not always be the best construct for identifying, treating or probing the biology underlying a person’s problems,” she said. “The keynote by Jason Lerch, professor at Oxford University, for example, was an elegant synthesis of imaging and genetic findings that made a strong case for the importance of exploring subtypes within autism and across developmental and psychiatric problems.”

“We also received another powerful reminder of our field’s complex heterogeneity,” Dr. Kenworthy noted. “Katherine Gotham, assistant professor at Vanderbilt University, was able to divide groups of autistic individuals in a study according to different criteria than the study’s initial design and effectively erase what appeared to be clear, statistically significant differences between typically developing and autistic participants. Her presentation demonstrated once more the importance of looking deeply at our data from many angles before drawing conclusions based on study outcomes.”

These studies, both at Children’s and elsewhere, all share one common theme: the importance of asking these questions and exploring the answers, with the goal of finding better ways to support and care for the millions of people around the world with autism and their families, no matter what autism looks like for them.

CASD presentations at INSAR 2019

Panel presentation: Clinical Presentation of ASD and Access to Care Among Girls

Allison Ratto, Ph.D., chaired a panel focused on the differences in performance on standard diagnostic tools based on the sex of autistic youth. The panel included presentations such as:

  • Sex Differences in Youth with ASD: Language Phenotype and Relation to Autism Behaviors from the ACE GENDAAR Network, presented by Sara Jane Webb of the University of Washington
  • Social Strengths of Autistic Girls: Sex Differences in Clinician-Rated and Parent-Reported Autistic Traits, presented by Dr. Ratto
  • Gender and Psychiatric Symptoms among Youth with ASD and ADHD, Alyssa Verbalis, Ph.D.
  • Evidence for Undertreatment of ADHD in Girls with ASD in the National Survey of Children’s Health, Kelly Register-Brown, M.D., MSc.

Oral and poster presentations

Oral session: Comparing Online and in-Person Parent Trainings to Support Executive Function and Self-Regulation: Feasibility, Acceptability, and Outcomes, presented by Lauren Kenworthy, Ph.D.

Poster sessions:

  • Executive Function and School-Based Interventions
    • Self-Report and Parent-Report Reveal Similar Patterns of Executive Function Problems in Autistic Adolescents, presented by Rachael Clinton and Charlotte Jeppsen
    • What Services Are Families of Children with Executive Function Challenges Getting? What Do Parents Say They Want?
    • A Mixed Methods Approach to Evaluation of Student Acceptability of the School-Based Interventions Unstuck and on Target and Parents and Teachers Supporting Students
    • A New Way to Help Parents? Exploring the Impact of School-Based Interventions on Parenting Outcomes
    • Executive Function and Academic Achievement in Autism Spectrum Disorder
    • Development of an Interactive, E-Learning Tool to Support Parent Implementation of an Executive Function Intervention
    • The Moderating Effects of Implementation Factors on Improvement in Classroom Behaviors in Unstuck and on Target and Contingency Behavior Management
  • Youth with ASD making the transition to adulthood
    • Preliminary Outcomes of a New Executive Function Treatment for Transition-Age Youth with ASD, presented by Cara Pugliese, Ph.D.
    • Self-determination in transition-aged individuals with autism spectrum disorder.
  • ASD population subgroups, including gender and ethnically diverse:
    • Parent-Teacher Discrepancy in Ratings of Executive Functioning in Black and White Children with ASD, presented by Serene Habayeb
    • Capturing the Autistic Experience: Self-Advocates Develop Self-Assessment Tools to Inform Autism Diagnosis and Validate Neuroimaging Findings across the Gender Spectrum
    • Comparing Parent-Report of Non-Intellectually Disabled Asian-American Youth with ASD and ADHD to Their White Peers
    • Autistic Traits in Transgender Youth: Dysphoria, Stigma, and Barriers to Care
    • Higher Rates of Gender Diversity in Children with ASD Based on Self-Report, Not Parent Report
Children's National employs 45 pediatric neurologists and 6 pediatric neurosurgeons.

Neuroscience at Children’s National

The Children’s National Division of Neurology and Neurosurgery is consistently recognized by U.S. News & World Report as one of the top neurology programs in the nation.

Children’s National ranked No. 6 overall and No. 1 for newborn care by U.S. News

Children’s National in Washington, D.C., is the nation’s No. 6 children’s hospital and, for the third year in a row, its neonatology program is No.1 among all children’s hospitals providing newborn intensive care, according to the U.S. News Best Children’s Hospitals annual rankings for 2019-20.

This is also the third year in a row that Children’s National has been in the top 10 of these national rankings. It is the ninth straight year it has ranked in all 10 specialty services, with five specialty service areas ranked among the top 10.

“I’m proud that our rankings continue to cement our standing as among the best children’s hospitals in the nation,” says Kurt Newman, M.D., President and CEO for Children’s National. “In addition to these service lines, today’s recognition honors countless specialists and support staff who provide unparalleled, multidisciplinary patient care. Quality care is a function of every team member performing their role well, so I credit every member of the Children’s National team for this continued high performance.”

The annual rankings recognize the nation’s top 50 pediatric facilities based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

“The top 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver outstanding care across a range of specialties and deserve to be nationally recognized,” says Ben Harder, chief of health analysis at U.S. News. “According to our analysis, these Honor Roll hospitals provide state-of-the-art medical expertise to children with rare or complex conditions. Their rankings reflect U.S. News’ assessment of their commitment to providing high-quality, compassionate care to young patients and their families day in and day out.”

The bulk of the score for each specialty is based on quality and outcomes data. The process also includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with challenging conditions.

Below are links to the five specialty services that U.S. News ranked in the top 10 nationally:

The other five specialties ranked among the top 50 were cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastro-intestinal surgery, orthopedics, and urology.

Pediatric Neurology Update Attendees

Pediatric neurologists get a primer on the state of ASD research and care

Pediatric Neurology Update Attendees

Neurologists who attended the 2019 Pediatric Neurology Update received a broad look at autism spectrum disorders, ranging from biology to clinical care and advocacy.

Autism spectrum disorders (ASD) took center stage for the afternoon sessions of the annual Pediatric Neurology Update in April. The meeting, hosted by the Center for Neuroscience and Behavioral Medicine at Children’s National Health System, brings together 150-plus pediatric neurologists each year to discuss critical research and clinical care of pediatric neurological conditions.

Led by the Center for Autism Spectrum Disorders Director Lauren Kenworthy, Ph.D., the afternoon’s slate of presentations sought to give broad perspective of the current state of ASD research and treatment best practices.

“We know that the brain is different in autism, but many times we continue to define autism by behavioral traits,” Dr. Kenworthy told the crowd in her introduction. “Sitting between the brain and behavior often is cognition – how do you understand your world and interpret it?”

The afternoon’s presentations were organized to provide the audience with a clear picture of many facets of ASD research and treatment. Highlights included:

  • Joshua Corbin, Ph.D., director of the Center for Neuroscience Research, offered “New Insights into the Neurobiologic Underpinnings of Autism,” which mapped out some of the biological mechanisms of autism.
  • Adelaide Robb, M.D., and Dr. Kenworthy presented current clinical care outlines, with Dr. Robb focusing on pharmacological therapies and Dr. Kenworthy sharing successful strategies to improve executive functioning and day to day task management for school-aged children.

Attendees also received a taste of two current “hot topics” in autism research and care:

  • Kevin Pelphrey, Ph.D., presented recent findings on “Gender Differences in Autism Spectrum Disorders: Girls with Autism” calling attention to the fact that the current diagnostic standards may not capture some female-associated phenotypes of ASD.
  • Julia Bascom of the Autistic Self Advocacy Network brought the autistic person’s point of view to the table via her presentation: “Autism: Society and Government Challenges and Solutions,” which focused on her organization’s efforts to improve inclusivity in advocacy and research, which she sums up as, “Nothing about us without us.”

The session concluded with a real-world focused “Autism-Friendly Hospital Roundtable,” of six panelists from the clinical, advocacy, community and technology fields, who are all involved in hands-on practices to improve medical experiences for autistic children and adults.

  • CASD’s Yetta Myrick talked about her work to engage families of autistic children in discussions of research and clinical care programs, including the start of CASD’s first-ever Stakeholder Advisory Board.
  • Julia Bascom talked about some of the less-often discussed challenges for many autistic people who seek medical services.
  • Kathleen Atmore, Psy.D., and Eileen Walters, MSN, RN, CPN, provided an overview of Beyond the Spectrum, the clinical service at Children’s National that coaches providers and families in techniques to reduce the stress of routine medical visits for patients with autism and other developmental disabilities.
  • Amy Kratchman, director of the LEND Family Collaboration at Children’s Hospital of Philadelphia, talked about some of the autism-friendly strategies underway at her institution.
  • Michael O’Neil, JD, MBA, founder and CEO of the GetWell Network, Inc., previewed how GetWell and Children’s National are partnering on a new tool that harnesses app technology to bring better information to autistic children and their families after a new autism diagnosis.
  • Vijay Ravindran, CEO and co-founder at Floreo, demonstrated how it might be possible to reduce stress and create a calm peaceful autism-friendly environment even in the busiest of waiting rooms, by allowing the patient to escape via virtual reality.

The roundtable showcased how Children’s National and other health care institutions are using evidence-based strategies to improve medical care experiences for autistic people and their families. Ideally any provider, including pediatric neurologists, who cares for people from the autism community, can incorporate any or all of these strategies as a way to meet the unique needs of this patient population.

The content was so timely and relevant to the audience that many attendees stayed past the official end of the meeting to continue discussing best practices with the panelists and each other.

John Schreiber

New study to raise profile of SCN8A-related disorders

John Schreiber

“The Cute Syndrome Foundation reached out because children with this disorder are dying. They were hoping to find a way to make more people, especially medical professionals, aware of this disorder and treatment recommendations,” said John Schreiber, M.D.

Children’s National Health System is proud to share that they have launched into a 6-month pilot research program to evaluate and improve education and access to care for SCN8A-related epilepsy. Due to advances in genetic testing, more patients with SCN8A mutations and other rare genetic epilepsies are being discovered all the time.

The research for the pilot program is being led by John Schreiber, M.D., assistant professor of neurology and pediatrics and director of the epilepsy genetics program at Children National. Dr. Schreiber will help to develop a more focused effort to provide families and clinicians with the Clinician Information and Reference Guide that was created by The Cute Syndrome Foundation. The goal of the information is to provide families and clinicians with a guide to remove barriers to access expert care.

“The Cute Syndrome Foundation reached out because children with this disorder are dying. They were hoping to find a way to make more people, especially medical professionals, aware of this disorder and treatment recommendations,” said Dr. Schreiber. “We’re at a critical point of collecting information as patients from around the world are looking at Children’s National as a leader to combat this type of disorder.”

As the first study of its kind in a rare genetic epilepsy, the pilot will provide the opportunity for future interventions that will help elevate the profile of SCN8A-related disorders, improve overall patient outcomes and facilitate collaborative partnerships that focus on research and on supporting positive outcomes for patients.

To help uncover barriers to accessing expert advice, the SCN8A survey was given out to over 200 health care professionals at Children’s National 2019 Pediatric Neurology Update meeting. Specifically, the study will help doctors at Children’s National increase provider knowledge of SN8A-related disorders, improve utilization of appropriate anti-seizure therapies and may ultimately end up reducing mortality.

Children’s National received a gift of $15,397 to establish the SCN8A Education and Research Fund, which will support research within the Comprehensive Pediatric Epilepsy Program to evaluate access to and increase awareness of SCN8A epileptic encephalopathy and treatment recommendation from experts in the field. The funds will be used for personnel, technology and material costs associated with the research.

preterm brain scans

Early lipids in micropreemies’ diets can boost brain growth

preterm brain scans

Segmentation of a preterm brain T2-weighted MRI image at 30 gestational weeks [green=cortical grey matter; blue=white matter; grey=deep grey matter; cyan=lateral ventricle; purple=cerebellum; orange=brainstem; red=hippocampus; yellow=cerebrospinal fluid].

Dietary lipids, already an important source of energy for tiny preemies, also provide a much-needed brain boost by significantly increasing global brain volume as well as increasing volume in regions involved in motor activities and memory, according to research presented during the Pediatric Academic Societies 2019 Annual Meeting.

“Compared with macronutrients like carbohydrates and proteins, lipid intake during the first month of life is associated with increased overall and regional brain volume for micro-preemies,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National and senior author. “Using non-invasive magnetic resonance imaging, we see increased volume in the cerebellum by 2 weeks of age. And at four weeks of life, lipids increase total brain volume and boost regional brain volume in the cerebellum, amygdala-hippocampus and brainstem.”

The cerebellum is involved in virtually all physical movement and enables coordination and balance. The amygdala processes and stores short-term memories. The hippocampus manages emotion and mood. And the brainstem acts like a router, passing messages from the brain to the rest of the body, as well as enabling essential functions like breathing, a steady heart rate and swallowing.

According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. babies is born preterm, or before 37 weeks gestation. Regions of the brain that play vital roles in complex cognitive and motor activities experience exponential growth late in pregnancy, making the developing brains of preterm infants particularly vulnerable to injury and impaired growth.

Children’s research faculty examined the impact of lipid intake in the first month of life on brain volumes for very low birth weight infants, who weighed 1,500 grams or less at birth. These micro-preemies are especially vulnerable to growth failure and neurocognitive impairment after birth.

The team enrolled 68 micro-preemies who were 32 weeks gestational age and younger when they were admitted to Children’s neonatal intensive care unit during their first week of life. They measured cumulative macronutrients – carbohydrates, proteins, lipids and calories – consumed by these newborns at 2 and 4 weeks of life. Over years, Limperopoulos’ lab has amassed a large database of babies who were born full-term; this data provides unprecedented insights into normal brain development and will help to advance understanding of brain development in high-risk preterm infants.

“Even after controlling for average weight gain and other health conditions, lipid intake was positively associated with cerebellar and brainstem volumes in very low birthweight preterm infants,” adds Katherine M. Ottolini, the study’s lead author.

According to Limperopoulos, Children’s future research will examine the optimal timing and volume of lipids to boost neurodevelopment for micro-preemies.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Early lipid intake improves brain growth in premature infants.”
    • Saturday, April 27, 2019, 1:15-2:30 p.m. (EST)

Katherine M. Ottolini, lead author; Nickie Andescavage, M.D., Attending, Neonatal-Perinatal Medicine and co-author; Kushal Kapse, research and development staff engineer and co-author; and Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain and senior author, all of Children’s National.

newborn in incubator

In HIE lower heart rate variability signals stressed newborns

newborn in incubator

In newborns with hypoxic-ischemic encephalopathy (HIE), lower heart rate variability correlates with autonomic manifestations of stress shortly after birth, underscoring the value of this biomarker, according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Tethered to an array of machines that keep their bodies nourished, warm and alive, newborns with health issues can’t speak. But Children’s research teams are tapping into what the machinery itself says, looking for insights into which vulnerable infants are most in need of earlier intervention.

Heart rate variability – or the variation between heartbeats – is a sign of health. Our autonomic nervous system constantly sends signals to adjust our heart rate under normal conditions. We can measure heart rate variability non-invasively, providing a way to detect potential problems with the autonomic nervous system as a sensitive marker of health in critically ill newborns,” says An N. Massaro, M.D., co-Director of Research for the Division of Neonatology at Children’s National, and the study’s senior author. “We’re looking for validated markers of brain injury in babies with HIE, and our study helps to support heart rate variability as one such valuable physiological biomarker.”

In most newborns, the autonomic nervous system reliably and automatically receives information about the body and the outside world and, in response, controls essential functions like blood pressure, body temperature, how quickly the baby breathes and how rapidly the newborn’s heart beats. The sympathetic part stimulates body processes, while the parasympathetic part inhibits body processes. When the nervous system’s internal auto-pilot falters, babies can suffer.

The Children’s team enrolled infants with HIE in the prospective, observational study. (HIE is brain damage that occurs with full-term babies who experience insufficient blood and oxygen flow to the brain around the time they are born.) Fifteen percent had severe encephalopathy. Mean age of babies in the observational study was 38.9 weeks gestation. Their median Apgar score at five minutes was 3; the 0-9 Apgar range indicates how ready newborns are for the rigors of life outside the womb.

The team analyzed heart rate variability metrics for three time periods:

  • The first 24 to 27 hours of life
  • The first three hours after babies undergoing therapeutic cooling were rewarmed and
  • The first three hours after babies’ body temperature had returned to normal.

They correlated the relationship between heart rate variability for 68 infants during at least one of these time periods with the stress z-score from the NICU Network Neurobehavioral Scale. The scale is a standardized assessment of newborn’s neurobehavioral integrity. The stress summary score indicates a newborn’s overall stress response, and six test items specifically relate to autonomic function.

“Alpha exponent and root mean square in short timescales, root mean square in long timescales, as well as low and high frequency powers positively correlated with stress scores and, even after adjusting for covariates, remained independently associated at 24 hours,” says Allie Townsend, the study’s lead author.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Heart rate variability (HRV) measures of autonomic nervous system (ANS) function relates to neonatal neurobehavioral manifestations of stress in newborn with hypoxic-ischemic encephalopathy (HIE).”
    • Monday, April 29, 2019, 5:45 p.m. (EST)

Allie Townsend, lead author; Rathinaswamy B. Govindan, Ph.D., staff scientist, Advanced Physiological Signals Processing Lab and co-author; Penny Glass, Ph.D., director, Child Development Program and co-author; Judy Brown, co-author; Tareq Al-Shargabi, M.S., co-author; Taeun Chang, M.D., director, Neonatal Neurology and Neonatal Neurocritical Care Program and co-author; Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine and co-author; An N. Massaro, M.D., co-Director of Research for the Division of Neonatology and senior author, all of Children’s National.

Claire Marie Vacher

Placental function linked to brain injuries associated with autism

Claire Marie Vacher

“We saw long-term cerebellar white matter alterations in male experimental models, and behavioral testing revealed social impairments and increased repetitive behaviors, two hallmark features of ASD,” says Claire-Marie Vacher, Ph.D., lead study author.

Allopregnanolone (ALLO), a hormone made by the placenta late in pregnancy, is such a potent neurosteroid that disrupting its steady supply to the developing fetus can leave it vulnerable to brain injuries associated with autism spectrum disorder (ASD), according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

In order to more effectively treat vulnerable babies, the Children’s research team first had to tease out what goes wrong in the careful choreography that is pregnancy. According to the Centers for Disease Control and Prevention, about 1 in 10 babies is born preterm, before 37 weeks of gestation. Premature birth is a major risk factor for ASD.

The placenta is an essential and understudied organ that is shared by the developing fetus and the pregnant mother, delivering oxygen, glucose and nutrients and ferrying out waste products. The placenta also delivers ALLO, a progesterone derivative, needed to ready the developing fetal brain for life outside the womb.

ALLO ramps up late in gestation. When babies are born prematurely, their supply of ALLO stops abruptly. That occurs at the same time the cerebellum – a brain region essential for motor coordination, posture, balance and social cognition– typically undergoes a dramatic growth spurt.

“Our experimental model demonstrates that losing placental ALLO alters cerebellar development, including white matter development,” says Anna Penn, M.D., Ph.D., a neonatologist in the divisions of Neonatology and Fetal Medicine, and a developmental neuroscientist at Children’s National. “Cerebellar white matter development occurs primarily after babies are born, so connecting a change in placental function during pregnancy with lingering impacts on later brain development is a particularly striking result.”

The research team created a novel experimental model in which the gene encoding the enzyme responsible for producing ALLO is deleted in the placenta. They compared these preclinical models with a control group and performed whole brain imaging and RNAseq gene expression analyses for both groups.

“We saw long-term cerebellar white matter alterations in male experimental models, and behavioral testing revealed social impairments and increased repetitive behaviors, two hallmark features of ASD,” says Claire-Marie Vacher, Ph.D., lead study author. “These male-specific outcomes parallel the increased risk of brain injury and ASD we see in human babies born prematurely.”

ALLO binds to specific GABA receptors, which control most inhibitory signaling in the nervous system.

“Our findings provide a new way to frame poor placental function: Subtle but significant changes in utero may set in motion neurodevelopmental disorders that children experience later in life,” adds Dr. Penn, the study’s senior author. “Future directions for our research could include identifying new targets in the placenta or brain that could be amenable to hormone supplementation, opening the potential for earlier treatment for high-risk fetuses.”

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Placental allopregnanolone loss alters postnatal cerebellar development and function.”
    • Sunday, April 28, 2019, 5:15 p.m. to 5:30 p.m. (EST)

Claire-Marie Vacher, Ph.D., lead author; Jackie Salzbank, co-author; Helene Lacaille, co-author; Dana Bakalar, co-author; Jiaqi O’Reilly, co-author; and Anna Penn, M.D., Ph.D., a neonatologist in the divisions of Neonatology and Fetal Medicine, developmental neuroscientist and senior study author.

Katie Donnelly

Firearm injuries disproportionately affect African American kids in DC Wards 7 and 8

Katie Donnelly

“Because the majority of patients in our analyses were injured through accidental shootings, this particular risk factor can help to inform policy makers about possible interventions to prevent future firearm injury, disability and death,” says Katie Donnelly, M.D.

Firearm injuries disproportionately impact African American young men living in Washington’s Wards 7 and 8 compared with other city wards, with nearly one-quarter of injuries suffered in the injured child’s home or at a friend’s home, according to a hot spot analysis presented during the Pediatric Academic Societies 2019 Annual Meeting.

“We analyzed the addresses where youths were injured by firearms over a nearly 12-year period and found that about 60 percent of these shootings occurred in Ward 7 or Ward 8, lower socioeconomic neighborhoods when compared with Washington’s six other Wards,” says Monika K. Goyal, M.D., MSCE, assistant chief of Children’s Division of Emergency Medicine and Trauma Services and the study’s senior author. “This granular detail will help to target resources and interventions to more effectively reduce firearm-related injury and death.”

In the retrospective, cross-sectional study, the Children’s research team looked at all children aged 18 and younger who were treated at Children’s National for firearm-related injuries from Jan. 1, 2006, to May 31, 2017. During that time, 122 children injured by firearms in Washington were treated at Children’s National, the only Level 1 pediatric trauma center in the nation’s Capitol:

  • Nearly 64 percent of these firearm-related injuries were accidental
  • The patients’ mean age was 12.9 years old
  • More than 94 percent of patients were African American and
  • Nearly 74 percent were male.

Of all injuries suffered by children, injuries due to firearms carry the highest mortality rates, the study authors write. About 3 percent of patients in Children’s study died from their firearm-related injuries. Among surviving youth:

  • Patients had a mean Injury Severity Score of 5.8. (The score for a “major trauma” is greater than 15.)
  • 54 percent required hospitalization, with a mean hospitalization of three days
  • Nearly 28 percent required surgery, with 14.8 percent transferred directly from the emergency department to the operating room and
  • Nearly 16 percent were admitted to the intensive care unit.

“Regrettably, firearm injuries remain a major public health hazard for our nation’s children and young adults,” adds Katie Donnelly, M.D., emergency medicine specialist and the study’s lead author. “Because the majority of patients in our analyses were injured through accidental shootings, this particular risk factor can help to inform policy makers about possible interventions to prevent future firearm injury, disability and death.”

Pediatric Academic Societies 2019 Annual Meeting poster presentatio

  • “Pediatric firearm-related injuries and outcomes in the District of Columbia.”
    • Monday, April 29, 2019, 5:45 p.m. to 7:30 p.m. (EST)

Katie Donnelly, M.D., emergency medicine specialist and lead author; Shilpa J. Patel, M.D., MPH, emergency medicine specialist and co-author; Gia M. Badolato, co-author; James Jackson, co-author; and Monika K. Goyal, M.D., MSCE, assistant chief of Children’s Division of Emergency Medicine and Trauma Services and senior author.

Other Children’s research related to firearms presented during PAS 2019 includes:

April 27, 8 a.m.: “Protect kids, not guns: What pediatric providers can do to improve firearm safety.” Gabriella Azzarone, Asad Bandealy, M.D.; Priti Bhansali, M.D.; Eric Fleegler; Monika K. Goyal, M.D., MSCE;  Alex Hogan; Sabah Iqbal; Kavita Parikh, M.D.; Shilpa J. Patel, M.D., MPH; Noe Romo; and Alyssa Silver.

April 29, 5:45 p.m.: “Emergency department visits for pediatric firearm-related injury: By intent of injury.” Shilpa J. Patel, M.D., MPH; Gia M. Badolato; Kavita Parikh, M.D.; Sabah Iqbal; and Monika K. Goyal, M.D., MSCE.

April 29, 5:45 p.m.: “Assessing the intentionality of pediatric firearm injuries using ICD codes.” Katie Donnelly, M.D.; Gia M. Badolato; James Chamberlain, M.D.; and Monika K. Goyal, M.D., MSCE.

April 30, 9:45 a.m.: “Defining a research agenda for the field of pediatric firearm injury prevention.” Libby Alpern; Patrick Carter; Rebecca Cunningham, Monika K. Goyal, M.D., MSCE; Fred Rivara; and Eric Sigel.

Catherine Limperopoulos

Breastfeeding boosts metabolites important for brain growth

Catherine Limperopoulos

“Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites that may play a critical role for growth and explain what makes breastfeeding beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D.

Micro-preemies who primarily consume breast milk have significantly higher levels of metabolites important for brain growth and development, according to sophisticated imaging conducted by an interdisciplinary research team at Children’s National.

“Our previous research established that vulnerable preterm infants who are fed breast milk early in life have improved brain growth and neurodevelopmental outcomes. It was unclear what makes breastfeeding so beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National. “Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites essential for growth and answer that lingering question.”

According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. infants is born preterm. The Children’s research team presented their findings during the Pediatric Academic Societies 2019 Annual Meeting.

The research-clinicians enrolled babies who were very low birthweight (less than 1,500 grams) and 32 weeks gestational age or younger at birth when they were admitted to Children’s neonatal intensive care unit in the first week of life. The team gathered data from the right frontal white matter and the cerebellum – a brain region that enables people to maintain balance and proper muscle coordination and that supports high-order cognitive functions.

Each chemical has its own a unique spectral fingerprint. The team generated light signatures for key metabolites and calculated the quantity of each metabolite. Of note:

  • Cerebral white matter spectra showed significantly greater levels of inositol (a molecule similar to glucose) for babies fed breast milk, compared with babies fed formula.
  • Cerebellar spectra had significantly greater creatine levels for breastfed babies compared with infants fed formula.
  • And the percentage of days infants were fed breast milk was associated with significantly greater levels of both creatine and choline, a water soluble nutrient.

“Key metabolite levels ramp up during the times babies’ brains experience exponential growth,” says Katherine M. Ottolini, the study’s lead author. “Creatine facilitates recycling of ATP, the cell’s energy currency. Seeing greater quantities of this metabolite denotes more rapid changes and higher cellular maturation. Choline is a marker of cell membrane turnover; when new cells are generated, we see choline levels rise.”

Already, Children’s National leverages an array of imaging options that describe normal brain growth, which makes it easier to spot when fetal or neonatal brain development goes awry, enabling earlier intervention and more effective treatment. “Proton magnetic resonance spectroscopy may serve as an important additional tool to advance our understanding of how breastfeeding boosts neurodevelopment for preterm infants,” Limperopoulos adds.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Improved cerebral and cerebellar metabolism in breast milk-fed VLBW infants.”
    • Monday, April 29, 2019, 3:30–3:45 p.m. (EST)

Katherine M. Ottolini, lead author; Nickie Andescavage, M.D., Attending, Neonatal-Perinatal Medicine and co-author; Kushal Kapse, research and development staff engineer and co-author; Sudeepta Basu, M.D., neonatologist and co-author; and Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain and senior author, all of Children’s National.

An-Massaro

Looking for ‘help’ signals in the blood of newborns with HIE

An Massaro

“This data support our hypothesis that a panel of biomarkers – not a one-time test for a single biomarker – is needed to adequately determine the risk and timing of brain injury for babies with HIE,” says An N. Massaro, M.D.

Measuring a number of biomarkers over time that are produced as the body responds to inflammation and injury may help to pinpoint newborns who are more vulnerable to suffering lasting brain injury due to disrupted oxygen delivery and blood flow, according to research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Hypoxic-ischemic encephalopathy (HIE) happens when blood and oxygen flow are disrupted around the time of birth and is a serious birth complication for full-term infants. To lessen the chance of these newborns suffering permanent brain injury, affected infants undergo therapeutic cooling, which temporarily lowers their body temperatures.

“Several candidate blood biomarkers have been investigated in HIE but we still don’t have one in clinical use.  We need to understand how these markers change over time before we can use them to direct care in patients,” says An N. Massaro, M.D., co-director of the Neonatal Neurocritical Care Program at Children’s National and the study’s senior author. “The newborns’ bodies sent out different ‘help’ signals that we detected in their bloodstream, and the markers had strikingly different time courses. A panel of plasma biomarkers has the potential to help us identify infants most in need of additional interventions, and to help us understand the most optimal timing for those interventions.”

Past research has keyed in on inflammatory cytokines and Tau protein as potential biomarkers of brain injury for infants with HIE who are undergoing therapeutic cooling. The research team led by Children’s faculty wanted to gauge which time periods to measure such biomarkers circulating in newborns’ bloodstreams. They enrolled 85 infants with moderate or severe HIE and tapped unused blood specimens that had been collected as cooling began, as well as 12, 24, 72 and 96 hours later. The infants’ mean gestational age was 38.7 weeks, their mean birth weight was about 7 pounds (3.2 kilograms), and 19% had severe brain disease (encephalopathy).

Cytokines – chemicals like Interleukin (IL) 6, 8 and 10 that regulate how the body responds to infection, inflammation and trauma – peaked in the first 24 hours of cooling for most of the newborns. However, the highest measure of Tau protein for the majority of newborns was during or after the baby’s temperature was restored to normal.

“After adjusting for clinical severity of encephalopathy and five-minute Apgar scores, IL-6, IL-8 and IL-10 predicted adverse outcomes, like severe brain injury or death, as therapeutic hypothermia began. By contrast, Tau protein measurements predicted adverse outcomes during and after the infants were rewarmed,” Dr. Massaro says.

IL-6 and IL-8 proteins are pro-inflammatory cytokines while IL-10 is considered anti-inflammatory.  These chemicals are released as a part of the immune response to brain injury. Tau proteins are abundant in nerve cells and stabilize microtubules.

“This data support our hypothesis that a panel of biomarkers – not a one-time test for a single biomarker – is needed to adequately determine the risk and timing of brain injury for babies with HIE,” she adds.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Serial plasma biomarkers of brain injury in infants with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH).”
    • Saturday, April 27, 2019, 6 p.m. (EST)

Meaghan McGowan, lead author; Alexandra C. O’Kane, co-author; Gilbert Vezina, M.D.,  director, Neuroradiology Program and co-author; Tae Chang, M.D., director, Neonatal Neurology Program and co-author; and An N. Massaro, M.D., co-director of the Neonatal Neurocritical Care Program and senior author; all of Children’s National; and co-author Allen Everett, of Johns Hopkins School of Medicine.

Ololade Okito

Parents of older, healthier newborns with less social support less resilient

Ololade Okito

“We know that having a child hospitalized in the NICU can be a high-stress time for families,” says Ololade Okito, M.D., lead author of the cross-sectional study. “The good news is that as parental resiliency scores rise, we see a correlation with fewer symptoms of depression and anxiety.

Parents of older, healthier newborns who had less social support were less resilient during their child’s hospitalization in the neonatal intensive care unit (NICU), a finding that correlates with more symptoms of depression and anxiety, according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Resiliency is the natural born, yet adaptable ability of people to bounce back in the face of significant adversity. Published research indicates that higher resilience is associated with reduced psychological distress, but the phenomenon had not been studied extensively in parents of children hospitalized in a NICU.

“We know that having a child hospitalized in the NICU can be a high-stress time for families,” says Ololade Okito, M.D., lead author of the cross-sectional study. “The good news is that as parental resiliency scores rise, we see a correlation with fewer symptoms of depression and anxiety. Parents who feel they have good family support also have higher resilience scores.”

The project is an offshoot of a larger study examining the impact of peer mentoring by other NICU parents who have experienced the same emotional rollercoaster ride as their tiny infants sometimes thrived and other times struggled.

The research team enrolled 35 parents whose newborns were 34 weeks gestation and younger and administered a battery of validated surveys, including:

Forty percent of these parents had high resilience scores; parents whose infants were a mean of 27.3 gestational weeks and who had more severe health challenges reported higher resilience. Another 40% of these parents had elevated depressive symptoms, while 31% screened positive for anxiety. Parental distress impairs the quality of parent-child interactions and long-term child development, the research team writes.

“Higher NICU-related stress correlates with greater symptoms of depression and anxiety in parents,” says Lamia Soghier, M.D., MEd, medical director of Children’s neonatal intensive care unit and the study’s senior author. “Specifically targeting interventions to these parents may help to improve their resilience, decrease the stress of parenting a child in the NICU and give these kids a healthier start to life.”

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Parental resilience and psychological distress in the neonatal intensive care unit (PARENT) study”
    • Tuesday, April 30, 2019, 7:30 a.m. (EST)

Ololade Okito, M.D., lead author; Yvonne Yui, M.D., co-author; Nicole Herrera, MPH, co-author; Randi Streisand, Ph.D., chief, Division of Psychology and Behavioral Health, and co-author; Carrie Tully, Ph.D., clinical psychologist and co-author; Karen Fratantoni, M.D., MPH, medical director, Complex Care Program, and co-author; and Lamia Soghier, M.D., MEd, medical unit director, neonatal intensive care unit, and senior author; all of Children’s National.

Mark Batshaw

40 years, 8 editions: Writing “Children With Disabilities”

Mark Batshaw

Forty years ago, Mark L. Batshaw, M.D., almost singlehandedly wrote a 23-chapter first edition that ran about 300 pages. Now Dr. Batshaw’s tome, “Children With Disabilities,” is in its eighth edition, and this new volume is almost 1,000 pages, with 42 chapters, two co-editors and over 35 authors from Children’s National.

Back in 1978, Mark L. Batshaw, M.D., was a junior faculty member at John’s Hopkins University School of Medicine. In the evenings he taught a course in the university’s School of Education  titled “The Medical and Physical Aspects of the Handicapped Child,” for Master’s level special education students. Because no textbook at that time focused on that specific topic, Batshaw developed his own slide set.

“At the end of the first year of teaching the course my students said ‘You really ought to consider writing a text book based on your slides to help us move forward,’ ” Dr. Batshaw recalls. The father of three carved out time by writing on weekends and at night, cutting back on sleep.

His first goal was to create a textbook that would serve as a curriculum for a series of courses that would be taught at universities to specialists who work with children with disabilities, including social workers, physical and occupational therapists, speech and language pathologists, special education teachers, nurses, doctors and dentists.

“I wanted to cover the whole range of disabilities and divided the book initially into a series of sections, including embryology, to help students understand what can go wrong in fetal development to lead to a developmental disability; and chapters on each developmental disability, including autism, attention-deficit/hyperactivity disorder (ADHD), cerebral palsy, learning disabilities and traumatic brain injury,” he says. “The third section was devoted to available treatments, including occupational and physical therapy, speech language therapy, nutrition and medications. The final section focused on outcomes.”

His second aim was for the book to serve as a reference text for professionals in the field. The 33-year-old contacted a brand-new new publisher, Paul H. Brookes Publishing Co., that focused on special education. “They took a chance on me, and I took a chance on them,” he says.

Forty years ago, he almost singlehandedly produced a 23-chapter first edition that ran about 300 pages. Now Dr. Batshaw’s tome is in its eighth edition, and this new volume is almost 1,000 pages. And, rather than being its sole author, Dr. Batshaw enlisted two co-editors and at least five dozen authors who contributed specialty expertise in genetic counseling, social work, physical and occupational therapy, medicine and nursing. His daughter, Elissa, a special education teacher and school psychologist, authored a chapter about special education services, and his son, Drew, an executive at a start-up company, contributed autobiographical letters about the effect ADHD has had on his life.

The book, “Children With Disabilities,” also includes:

  • A glossary of medical terms so that as the reader reviews patient reports they can easily look up an unfamiliar term
  • An appendix on commonly used drugs to treat children with disabilities in order to look up the medicine by name and see the range of doses
  • An appendix devoted to different syndromes children might have
  • A reference section with organizations and foundations that help children with disabilities
  • A web site with sections designed for students and other content designed for teachers with thought questions to guide practical use of information in each chapter and more than 450 customizable PowerPoint slides for download
  • Call-out boxes for interdisciplinary team members, such as genetic counselors, explaining the roles they serve and their educational background, and
  • Excerpts of recent research articles.

“The students say they don’t sell the book. Usually when students have a textbook, they try to sell it second hand after the course ends,” explains Dr. Batshaw, now Executive Vice President, Physician-in-Chief and Chief Academic Officer at Children’s National. “Instead, students keep it and use it as a practical reference as they become professionals in their field. It has had the impact I had hoped for both as a textbook and a reference book: They say they refer to it when they have patients with a particular disorder they’re not used to treating to read up on it.”

Now a bestseller, there are more than 200,000 copies in print, including Portuguese and Ukrainian translations. “It didn’t start that way. It grew organically,” he says.

In addition to Dr. Batshaw, Children’s contributors to “Children With Disabilities” include Nicholas Ah Mew, M.D., pediatric geneticist; Nickie N. Andescavage, M.D., neonatologist; Mackenzie E. Brown, D.O., fellow in Pediatric Rehabilitation Medicine; Justin M. Burton, M.D., chief, Division of Pediatric Rehabilitation Medicine; Gabrielle Sky Cardwell, BA, clinical research assistant; Catherine Larsen Coley, PT, DPT, PCS, physical therapist; Laurie S. Conklin, M.D., pediatric gastroenterologist; Denice Cora-Bramble, M.D., MBA, executive vice president and chief medical officer; Heather de Beaufort, M.D., pediatric ophthalmologist; Dewi Frances T. Depositario-Cabacar, M.D., pediatric neurologist; Lina Diaz-Calderon, M.D., fellow in Pediatric Gastroenterology; Olanrewaju O. Falusi, M.D., associate medical director of municipal and regional affairs, Child Health Advocacy Institute; Melissa Fleming, M.D., pediatric rehabilitation specialist; William Davis Gaillard, M.D., chief Division of Epilepsy, Neurophysiology and Critical Care; Satvika Garg, Ph.D., occupational therapist; Virginia C. Gebus, R.N., MSN, APN, CNSC, nutritionist; Monika K. Goyal, M.D., MSCE, assistant chief, Division of Emergency Medicine; Andrea Gropman, M.D., chief, Division of Neurodevelopmental Pediatrics and Neurogenetics, geneticist and Neurodevelopmental pediatrician; Mary A. Hadley, BS, senior executive assistant; Susan Keller, MLS., MS-HIT, research librarian; Lauren Kenworthy, Ph.D., director, Center for Autism Spectrum Disorders; Monisha S. Kisling, MS, CGC, genetic counselor; Eyby Leon, M.D., pediatric geneticist; Erin MacLeod, Ph.D., RD, LD, director, Metabolic Nutrition; Margaret B. Menzel, MS, CGC, genetic counselor; Shogo John Miyagi, Ph.D., PharmD, BCPPS, Pediatric Clinical Pharmacology fellow; Mitali Y. Patel, DDS, program director, Pediatric Dentistry; Deborah Potvin, Ph.D., neuropsychologist; Cara E. Pugliese, Ph.D., clinical psychologist; Khodayar Rais-Bahrami, M.D., neonatologist and director, Neonatal-Perinatal Medicine Fellowship Program; Allison B. Ratto, Ph.D., clinical psychologist; Adelaide S. Robb, M.D., chief, Division of Psychiatry and Behavioral Sciences; Joseph Scafidi, D.O., neonatal neurologist; Erik Scheifele, D.M.D., chief, Division of Oral Health; Rhonda L. Schonberg, MS, CGC, genetic counselor; Billie Lou Short, M.D., chief, Division of Neonatology; Kara L. Simpson, MS, CGC, genetic counselor; Anupama Rao Tate, D.M.D., MPH, pediatric dentist; Lisa Tuchman, M.D., MPH, chief, Division of Adolescent and Young Adult Medicine; Johannes N. van den Anker, M.D., Ph.D., FCP, chief, Division of Clinical Pharmacology, Vice Chair of Experimental Therapeutics; Miriam Weiss, CPNP-PC, nurse practitioner; and Tesfaye Getaneh Zelleke, M.D., pediatric neurologist.

Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents:
Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students:
Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty:
Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students:
Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents:
Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students:
Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty:
Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff:
Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents:
Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students:
Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty:
Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff:
Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents:
Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students:
Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.