coronavirus molecules with DNA

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

coronavirus molecules with DNA

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

While the paper is posted to the preprint server medRxiv and has not been peer-reviewed, it represents an early step towards establishing better surveillance of the COVID-19 pandemic.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

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

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

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

You can read the full preprint on medRxiv.

illustration of brain with stem cells

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

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

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

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


Learn more in this overview video.

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

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

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

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

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

MRI of the patient's head close-up

Early versus late MRI in newborn brain injury

MRI of the patient's head close-up

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

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

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

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

Read the full study in The Journal of Pediatrics.

structure of EGFR

Study suggests EGFR inhibition reverses alterations induced by hypoxia

structure of EGFR

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

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

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

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

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

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

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

Read the full article in iScience.

newborn

Predicting risk for infantile spasms after acute symptomatic neonatal seizures

newborn

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

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

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

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

Read the full study in Epilepsia.

Lee Beers

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

Lee Beers

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

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

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

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

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

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

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

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

Associations Between Resting State Functional Connectivity and Behavior in the Fetal Brain

Maternal anxiety affects the fetal brain

Associations Between Resting State Functional Connectivity and Behavior in the Fetal Brain

Anxiety in gestating mothers appears to affect the course of brain development in their fetuses, changing neural connectivity in the womb, a new study suggests.

Anxiety in gestating mothers appears to affect the course of brain development in their fetuses, changing neural connectivity in the womb, a new study by Children’s National Hospital researchers suggests. The findings, published Dec. 7, 2020, in JAMA Network Open, could help explain longstanding links between maternal anxiety and neurodevelopmental disorders in their children and suggests an urgent need for interventions to diagnose and decrease maternal stress.

Researchers have shown that stress, anxiety or depression in pregnant mothers is associated not only with poor obstetric outcomes but also social, emotional and behavioral problems in their children. Although the care environment after birth complicates the search for causes, postnatal imaging showing significant differences in brain anatomy has suggested that these problems may originate during gestation. However, direct evidence for this phenomenon has been lacking, says Catherine Limperopoulos, Ph.D., director of the Developing Brain Institute at Children’s National.

To help determine where these neurological changes might get their start, Dr. Limperopoulos, along with staff scientist Josepheen De Asis-Cruz, M.D., Ph.D., and their Children’s National colleagues used a technique called resting-state functional magnetic resonance imaging (rs-fMRI) to probe developing neural circuitry in fetuses at different stages of development in the late second and third trimester.

The researchers recruited 50 healthy pregnant volunteers from low-risk prenatal clinics in the Washington, D.C. area who were serving as healthy “control” volunteers in a larger study on fetal brain development in complex congenital heart disease. These study participants, spanning between 24 and 39 weeks in their pregnancies, each filled out widely used and validated questionnaires to screen for stress, anxiety and depression. Then, each underwent brain scans of their fetuses that showed connections between discrete areas that form circuits.

After analyzing rs-fMRI results for their fetuses, the researchers found that those with higher scores for either form of anxiety were more likely to carry fetuses with stronger connections between the brainstem and sensorimotor areas, areas important for arousal and sensorimotor skills, than with lower anxiety scores. At the same time, fetuses of pregnant women with higher anxiety were more likely to have weaker connections between the parieto-frontal and occipital association cortices, areas involved in executive and higher cognitive functions.

“These findings are pretty much in keeping with previous studies that show disturbances in connections reported in the years and decades after birth of children born to women with anxiety,” says Dr. De Asis-Cruz. “That suggests a form of altered fetal programming, where brain networks are changed by this elevated anxiety even before babies are born.”

Whether these effects during gestation themselves linger or are influenced by postnatal care is still unclear, adds Dr. Limperopoulos. Further studies will be necessary to follow children with these fetal differences in neural connectivity to determine whether these variations in neural circuitry development can predict future problems. In addition, it’s unknown whether easing maternal stress and anxiety can avoid or reverse these brain differences. Dr. Limperopoulos and her colleagues are currently studying whether interventions that reduce stress could alter the trajectory of fetal neural development.

In the meantime, she says, these findings emphasize the importance of making sure pregnant women have support for mental health issues, which helps ensure current and future health for both mothers and babies.

“Mental health problems remain taboo, especially in the peripartum period where the expectation is that this is a wonderful time in a woman’s life. Many pregnant mothers aren’t getting the support they need,” Dr. Limperopoulos says. “Changes at the systems level will be necessary to chip away at this critical public health problem and make sure that both mothers and babies thrive in the short and long term.”

Other Children’s National researchers who contributed to this study include Dhineshvikram Krishnamurthy, M.S., software engineer; Li Zhao, Ph.D., research faculty; Kushal Kapse, M.S., staff engineer; Gilbert Vezina, M.D., neuroradiologist; Nickie Andescavage, M.D., neonatologist; Jessica Quistorff, M.P.H., clinical research program lead; and Catherine Lopez, M.S., clinical research program coordinator.

This study was funded by R01 HL116585-01 from the National Heart, Lung, and Blood Institute and U54HD090257 from the Intellectual and Developmental Disabilities Research Center.

depressed mom holding baby

New grant to help establish maternal mental health telehealth program

depressed mom holding baby

Children’s National has received a $76,000 grant from the Health Resources & Services Administration (HRSA) which will allow a cross-functional team of neonatologists and psychologists to establish a parental mental telehealth program.

Worldwide about 10% of pregnant women and 13% of women who have just given birth experience a mental health disorder, primarily depression, according to the World Health Organization.

“This is a topic that is quickly garnering attention but remains extremely underfunded,” says Lamia Soghier, M.D., F.A.A.P., C.H.S.E., medical director of the Neonatal Intensive Care Unit (NICU) at Children’s National Hospital. “We tend to focus on the babies but don’t pay enough attention to the parents.”

Dr. Soghier’s focus has been on NICU parents who experience postpartum mood and anxiety disorders (PMADs), often due to their uniquely stressful experiences.

“We have been screening on a small scale for many years and have noticed a 33-45% rate of postpartum depression symptoms in our NICU families,” she says.

Maternal mental disorders are treatable with effective screening and interventions. Children’s National has received a $76,000 grant from the Health Resources & Services Administration (HRSA) which will allow a cross-functional team of neonatologists and psychologists to establish a parental mental telehealth program to expand screening and provide diagnosis, therapy and counseling to NICU parents who experience postpartum mood and anxiety disorders.

Dr. Soghier, along with Ololade ‘Lola’ Okito, M.D., neonatologist at Children’s National, and Erin Sadler, Psy.D., psychologist in the Division of Psychology and Behavioral Health at Children’s National, discuss the importance of this work.

Q: Tell us more about the program you’re establishing.

A: Dr. Soghier: This program will allow us to hire a licensed psychologist who will see families both in the NICU and through follow-up telehealth visits. It provides a one-stop shop for our families, which is particularly important during the COVID-19 pandemic. The grant will also allow us to develop an iPad loaner program to give loaner iPads to low income families who do not have access to a device or to reliable internet services so that they can receive therapy at home.

Dr. Sadler: We’ll be examining how the implementation of these services can increase accessibility and reduce barriers that prevent assessment and initiation of crucial mental health services for at-risk mothers. Our partnerships will be key. Mothers experiencing barriers to participating in care services in the NICU will also have access to an in-house, licensed psychologist through telehealth services within the comfort of their homes. Families experiencing problems accessing telehealth technology due to economic limits would get the loaner iPad. We’re meeting our families where they are in order to provide these critical services.

Q: Why is grant funding to important in this space?

A: Dr. Okito: Access to perinatal mental health services is limited at the local and national levels, particularly for vulnerable parents of infants admitted to the NICU. Little is known about the effect of interventions to address depression and anxiety among NICU parents, and this grant will allow us to contribute to this very important area of research.

Dr. Sadler: It is not enough to recognize the health disparities that exist amongst communities in our nation. It is imperative that we’re able to explore and examine solutions that can aid in enhancing the equity of care for children and adults alike. As Dr. Okito mentions, there is little to no research available that looks at the feasibility of the support programs we intended to put in place. We hope to create a viable model that could be used to help NICU families across the country.

Q: How is Children’s National uniquely positioned to do this work?

A: Dr. Soghier: Healthy moms and healthy dads equal happy babies. That’s why we will be taking care of the family as a whole. This is truly family-centered care and at the heart of what Children’s National is all about.

Dr. Sadler: The Children’s National NICU team has an established postpartum depression screening program. Through the piloted work, staff have identified notable barriers to universal screening, access to perinatal mental health support and the impact of PMADs on parent engagement in newborn care.  As a result, Children’s National is uniquely positioned to directly address such barriers and provide specialized care.

Q: What excites you about this work?

A: Dr. Sadler: As a specialist in perinatal and infant mental health, I look forward to being able to demonstrate the lasting impact maternal mental health services can provide for not only newborns and their families, but for care providers as well. I am excited to have additional opportunities to advocate for the integration of perinatal and infant mental health in non-traditional spaces.

Dr. Okito: I am most excited about the potential to expand universal depression screening among NICU parents. Having done this work for the past three years, I know there are limitations in screening because we’ve only been able to screen parents that are at the patient’s bedside. More screening will lead to more parents getting the referrals and services that they need.

Research & Innovation Campus

Boeing gives $5 million to support Research & Innovation Campus

Research & Innovation Campus

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus.

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus. The campus, now under construction, is being developed on nearly 12 acres of the former Walter Reed Army Medical Center. Children’s National will name the main auditorium in recognition of Boeing’s generosity.

“We are deeply grateful to Boeing for their support and commitment to improving the health and well-being of children in our community and around the globe,” said Kurt Newman, M.D., president and CEO of Children’s National “The Boeing Auditorium will help the Children’s National Research & Innovation campus become the destination for discussion about how to best address the next big healthcare challenges facing children and families.”

The one-of-a-kind pediatric hub will bring together public and private partners for unprecedented collaborations. It will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.

“Children’s National Hospital’s enduring mission of positively impacting the lives of our youngest community members is especially important today,” said Boeing President and CEO David Calhoun. “We’re honored to join other national and community partners to advance this work through the establishment of their Research & Innovation Campus.”

Children’s National Research & Innovation Campus partners currently include Johnson & Johnson Innovation – JLABS, Virginia Tech, the National Institutes of Health (NIH), Food & Drug Administration (FDA), U.S. Biomedical Advanced Research and Development Authority (BARDA), Cerner, Amazon Web Services, Microsoft, National Organization of Rare Diseases (NORD) and local government.

The 3,200 square-foot Boeing Auditorium will be the focal point of the state-of-the-art conference center on campus. Nationally renowned experts will convene with scientists, medical leaders and diplomats from around the world to foster collaborations that spur progress and disseminate findings.

Boeing’s $5 million commitment deepens its longstanding partnership with Children’s National. The company has donated nearly $2 million to support pediatric care and research at Children’s National through Chance for Life and the hospital’s annual Children’s Ball. During the coronavirus pandemic, Boeing fabricated and donated 2,000 face shields to help keep patients and frontline care providers at Children’s National safe.

Baby in the NICU

Quality improvement initiative reduces vancomycin use in NICU

Baby in the NICU

A quality improvement initiative in the Neonatal Intensive Care Unit (NICU) at Children’s National Hospital led to a significant reduction in treatment with intravenous vancomycin, an antibiotic used for resistant gram positive infections, which is often associated with acute kidney injury.

A quality improvement initiative in the Neonatal Intensive Care Unit (NICU) at Children’s National Hospital led to a significant reduction in treatment with intravenous vancomycin, an antibiotic used for resistant gram positive infections, which is often associated with acute kidney injury. The findings, published in the journal Pediatrics, show the initiative reduced vancomycin use in patients by 66%, and the NICU has sustained the reduction for more than a year.

Vancomycin is a broad-spectrum antibiotic often used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. It’s one of the most commonly prescribed antibiotics in NICUs, but its overuse poses an increased risk of morbidity. Benchmarking data showed that in 2017, vancomycin use at Children’s National Hospital was significantly higher than use at peer institutions, suggesting there was likely an opportunity to optimize use of this drug.

The intervention program was led by Rana Hamdy, M.D., M.S.C.E., M.P.H., an infectious diseases specialist at Children’s National, Lamia Soghier, M.D., medical unit director of the Children’s National NICU, and other team members from neonatologyinfectious diseases, pharmacy, nursing and quality improvement. The team accomplished the prescribing reduction by sequentially implementing a four-step approach involving interdisciplinary team building and provider education, pharmacist-initiated 48-hour time-outs, clinical pathway development and prospective audit with feedback.

“Our interdisciplinary quality improvement team was devoted to this project and implemented interventions that, early on, led not only to reduction in vancomycin use, but to better outcomes in our patients with fewer episodes of vancomycin-associated acute kidney injury,” said Dr. Hamdy. “This led to early buy-in from the prescribers, ultimately changing the culture of antibiotic prescribing in the NICU.”

Following the NICU’s intervention program to improve patient safety, vancomycin use in patients decreased from 112 days of therapy per 1,000 patient-days to 38 days of therapy per 1,000 patient-days. During the intervention program, the researchers noted that this was “the first work to show a significant change in vancomycin-associated acute kidney injury in neonates.”

Four key interventions were sequentially implemented to successfully achieve and sustain the reduction in vancomycin use. Intervention 1 was the development of an interdisciplinary and provider education team that addressed institutional antibiotic prescribing practices. Intervention 2, a pharmacist-initiated 48-hour time-out, involved clinical pharmacists identifying patients who have been on antibiotics for ≥ 48 hours and encouraged their providers to either discontinue vancomycin or to switch to a narrow-spectrum antibiotic. Intervention 3 consisted of the development of new clinical pathways including discontinuing vancomycin in infants at low risk for MRSA. Lastly, intervention 4, antimicrobial stewardship program (ASP) prospective audit and feedback, involved an ASP member reviewing all NICU vancomycin orders and issuing appropriate recommendations for NICU providers and pharmacists to be carried out within 24 hours.

This project was taken on as part of Children’s National Quality Improvement and Leadership Training (QuILT) course sponsored by the Quality & Safety Department. This notable work was highlighted in the 2019 annual Quality and Safety report and by the Magnet® program as an exemplary example of nursing-physician partnership working to improve patient care.

The associated article, “Reducing Vancomycin Use in a Level IV Neonatal Intensive Care Unit,” will be published July 1 in Pediatrics. The lead author is Dr. Rana Hamdy, an infectious diseases specialist and director of the Antimicrobial Stewardship Program. Twenty notable co-authors are also from Children’s National.

Annual Pediatric Device Innovation Symposium panelists

Accelerating pediatric device innovation through legislative processes and industry changes


Annual Pediatric Device Innovation Symposium panelists
While the way we deliver healthcare is changing rapidly, far too often the tools we use to treat children are stuck in the past.

Over the last decade, pediatric medical device innovation, particularly for the youngest, most fragile children, has made dismal progress. Of the Class 3 (high risk/high benefit) medical devices approved by FDA for pediatrics in the last 10 years, less than 4% are for ages 0-2 years old; and even less for neo-natal patients. Simply put, as medical devices advance, children are not seeing the benefit of innovation.

The 8th Annual Pediatric Device Innovation Symposium presented by Children’s National Hospital in conjunction with the National Capital Consortium for Pediatric Medical Devices (NCC-PDI) featured a keynote panel, “Pediatric Device Innovation: What’s Next?”, to examine the legislative and industry changes needed to speed up device innovation for kids.

One of the keynote panelists, and leading voices on this issue, is Children’s National Hospital president and CEO Kurt Newman, M.D. Dr. Newman, a former pediatric surgeon, knows firsthand that every day in our nation’s pediatric hospitals, surgeons are manipulating adult medical devices to create creative solutions for children’s bodies because it’s the only available option.

“Children need and deserve devices that are conceived and designed with their biology and future in mind,” says Dr. Newman. “While children may only make up a small percentage of our population – maybe 20 or 25% – they are 100% of our future.”

Dr. Kurt Newman in front of the capitol building

“Children need and deserve devices that are conceived and designed with their biology and future in mind,” says Children’s National Hospital president and CEO Kurt Newman, M.D. “While children may only make up a small percentage of our population – maybe 20 or 25% – they are 100% of our future.”

Dr. Newman also addressed the current barriers to pediatric device innovation, which ranges from limited pediatric clinical trials to a market size that’s not financially appealing.

“The truth is, the frontiers of pediatric medicine are really in the innovative treatments, devices, therapies, and cures awaiting us on the other side of research and development.,” says Dr. Newman.

Former CNN correspondent, Jeanne Meserve, moderated the 45-minute keynote panel discussion, asking questions about the challenges to pediatric innovation, what policy changes need to take place to see improvement in the field of pediatric device innovation, and how federal funding can assist in creating change.

Michelle McMurry-Heath, new CEO of DC-based Biotechnology Innovation Organization (BIO), who joined Dr. Newman on this keynote panel, agreed that more needs to be done in the pediatric space. Dr. McMurry-Heath believes the Food and Drug Administration (FDA) is a public health advocate at heart and that the Pediatric Device Consortia (PDC), which Children’s National Hospital is part of, is starting to make new advancements in pediatric innovation by giving FDA clearance to more start-up companies than we’ve seen in the past.

“The FDA is interested in is what improves the health outcomes for the people and innovation is a huge piece. This is an important part of their mission and it is starting to yield benefits,” says Dr. Michelle McMurry-Heath. “Innovation is a team sport – it’s not easy. It takes a village of expertise and collaboration to progress and projects like the Pediatric Device Consortia is an important piece in this puzzle.”

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

To date, NCC-PDI has mentored over 100 medical device sponsors to help advance their pediatric innovations, with seven devices having received either their FDA market clearance or CE marking.

Dr. McMurry-Heath also addressed the challenge of diseases that don’t exist in adults and posed the question, “How do you create a device for kids if it doesn’t exist in adults?” She cited the lack of market in pediatrics and the difficulty in bringing a device to market as problems that hinder innovation, which is why advocating for these devices is crucial to children’s healthcare everywhere.

“So much of our innovation comes from our small, innovative companies,” say Dr. McMurry-Heath. “For example, my company is working on a COVID-19 tracker now and 70% of the innovation is coming from our smallest biotech companies. It’s a race against time for these companies to bring their innovation to market in order to keep the lights on and pay their scientists; this dog-eat-dog world isn’t immediately obvious to outsiders.

Beyond advocating, Dr. Newman and Children’s National are developing the first-of-its-kind pediatric research and innovation campus, which is currently under construction at DC’s former Walter Reed Army Medical Center site.

“We secured 12 acres to create something that has never been done before and that’s a campus for innovation dedicated to children,” says Dr. Newman. “Our close proximity to federal research institutions and agencies enables the new Children’s National campus to leverage the rich ecosystem of public and private sectors to help bolster biohealth, medical device, and life science innovation.”

As Children’s National continues to champion ways to accelerate pediatric device development, one focus is the on-site incubator Johnson & Johnson Innovation – JLABS, which will help start-up companies strengthen their ideas by working with coaches, having access to mentors and learning how to interact with the FDA. This partnership also offers an audience for their device which could potentially lead to investments.

The Children’s National Research & Innovation Campus will create an ecosystem that can accelerate breakthroughs in pediatric healthcare discoveries and technologies: The new campus is currently under construction and expected to open in the first quarter of 2021.

Both panelists agreed they’d like to see more flexibility with regulators to work with innovators in order create more incentives for them to present their device, like the NCC-PDI “Make Your Medical Device Pitch for Kids!” Competition, which was recently held in September 2020. The six winners received up to $50,000 in FDA-funded grant awards in order to develop their device, eventually bring it to market in order to improve healthcare for kids.

NCC-PDI device competition

Medical device competition announces six winners to share in $250K

Judges award grants for pediatric medical devices that address cardiovascular, NICU, and orthopaedic and spine device innovations.

screenshot of pitch competition

“COVID-19-edition” of pediatric medical device competition announces winners

zika virus

The importance of following the Zika population long-term

zika virus

Invited commentary by Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in the Division of Prenatal Pediatrics at Children’s National Hospital, emphasizes importance of studying the Zika population long term.

A simple measuring tape could be the key to identifying which children could develop neurological and developmental abnormalities from Zika virus exposure during gestation. This is according to an invited commentary published July 7, 2020 in JAMA Network Open and written by Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in the Division of Prenatal Pediatrics at Children’s National Hospital.

Zika virus (ZIKV), first isolated in 1947 in the Zika Forest in Uganda, made headlines in 2015-2016 for causing a widespread epidemic that spread through parts of North and South America, several islands in the Pacific and parts of Southeast Asia. Although previously linked with no or mild symptoms, researchers discovered during this epidemic that Zika can cross from a pregnant woman to her gestating fetus, leading to a syndrome marked by microcephaly (decreased brain growth), abnormal neurologic tone, vision and hearing abnormalities and joint contractures.

“For the 90% to 95% of ZIKV-exposed infants who fortunately were not born with severe abnormalities at birth and were normocephalic, our hope was that these children would have normal neurodevelopmental outcomes,” Dr. Mulkey writes in the commentary. “Unfortunately, this has not been the case.”

Her commentary expands on a study in the same issue entitled “Association between exposure to antenatal Zika virus and anatomic and neurodevelopmental abnormalities in children” by Cranston et al. In this study, the researchers find that head circumference — a simple measure taken regularly at postnatal appointments in the U.S. — can provide insight into which children were most likely to develop neurologic abnormalities. Their findings show that 68% of those whose head circumference was in the “normal” range at birth developed neurologic problems. Those whose head circumference was at the upper end of this range were significantly less likely to have abnormalities than those at the lower end.

Just this single measurement offers considerable insight into the risk of developing neurologic problems after Zika exposure. However, notes Dr. Mulkey, head circumference growth trajectory is also key. Of the 162 infants whose heads were initially in the normocephalic range at birth, about 10.5% went on to develop microcephaly in the months after birth.

“Because early head growth trajectory is associated with cognitive outcomes in early childhood,” Dr. Mulkey writes, “following the head circumference percentile over time can enable recognition of a child with increased risk for poor outcome who could benefit from early intervention therapies.”

This simple assessment could be significantly augmented with neuroimaging, she adds. The study by Cranston et al., as well as others in the field, have shown that brain imaging often reveals problems in ZIKV-exposed children, such as calcifications and cerebral atrophy, even in those with normal head circumferences. This imaging doesn’t necessarily need to take place at birth, Dr. Mulkey says. Postnatal development of microcephaly, failure to thrive or developmental delay can all be triggers for imaging later on.

Together, Dr. Mulkey says, the study by Cranston et al. and others that focus on ZIKV-exposed children support the need for following these patients long term. Children exposed to ZIKV in the epidemic nearly five years ago are now approaching school age, a time fraught with more complicated cognitive and social demands. Through her own research at Children’s National’s Congenital Zika Virus Program and collaboration with colleagues in Colombia, Dr. Mulkey is following multiple cohorts of ZIKV exposed children as they grow. She recently published a study on neurological abnormalities in one of these cohorts in JAMA Pediatrics in January 2020.

“It’s really important to follow these children as long as possible so we’ll really know the outcomes of this virus,” Dr. Mulkey says.

US News Badges

Children’s National ranked a top 10 children’s hospital and No. 1 in newborn care nationally by U.S. News

US News Badges

Children’s National Hospital in Washington, D.C., was ranked No. 7 nationally in the U.S. News & World Report 2020-21 Best Children’s Hospitals annual rankings. This marks the fourth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide.

In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fourth year in a row.

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

“Our number one goal is to provide the best care possible to children. Being recognized by U.S. News as one of the best hospitals reflects the strength that comes from putting children and their families first, and we are truly honored,” says Kurt Newman, M.D., president and CEO of Children’s National Hospital.

“This year, the news is especially meaningful, because our teams — like those at hospitals across the country — faced enormous challenges and worked heroically through a global pandemic to deliver excellent care.”

“Even in the midst of a pandemic, children have healthcare needs ranging from routine vaccinations to life-saving surgery and chemotherapy,” said Ben Harder, managing editor and chief of Health Analysis at U.S. News. “The Best Children’s Hospitals rankings are designed to help parents find quality medical care for a sick child and inform families’ conversations with pediatricians.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

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

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

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

Vittorio Gallo and Mark Batshaw

Children’s National Research Institute releases annual report

Vittorio Gallo and Marc Batshaw

Children’s National Research Institute directors Vittorio Gallo, Ph.D., and Mark Batshaw, M.D.

The Children’s National Research Institute recently released its 2019-2020 academic annual report, titled 150 Years Stronger Through Discovery and Care to mark the hospital’s 150th birthday. Not only does the annual report give an overview of the institute’s research and education efforts, but it also gives a peek in to how the institute has mobilized to address the coronavirus pandemic.

“Our inaugural research program in 1947 began with a budget of less than $10,000 for the study of polio — a pressing health problem for Washington’s children at the time and a pandemic that many of us remember from our own childhoods,” says Vittorio Gallo, Ph.D., chief research officer at Children’s National Hospital and scientific director at Children’s National Research Institute. “Today, our research portfolio has grown to more than $75 million, and our 314 research faculty and their staff are dedicated to finding answers to many of the health challenges in childhood.”

Highlights from the Children’s National Research Institute annual report

  • In 2018, Children’s National began construction of its new Research & Innovation Campus (CNRIC) on 12 acres of land transferred by the U.S. Army as part of the decommissioning of the former Walter Reed Army Medical Center campus. In 2020, construction on the CNRIC will be complete, and in 2012, the Children’s National Research Institute will begin to transition to the campus.
  • In late 2019, a team of scientists led by Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, traveled to the Democratic Republic of Congo to collect samples from 60 individuals that will form the basis of a new reference genome data set. The researchers hope their project will generate better reference genome data for diverse populations, starting with those of Central African descent.
  • A gift of $5.7 million received by the Center for Translational Research’s director, Lisa Guay-Woodford, M.D., will reinforce close collaboration between research and clinical care to improve the care and treatment of children with polycystic kidney disease and other inherited renal disorders.
  • The Center for Neuroscience Research’s integration into the infrastructure of Children’s National Hospital has created a unique set of opportunities for scientists and clinicians to work together on pressing problems in children’s health.
  • Children’s National and the National Institute of Allergy and Infectious Diseases are tackling pediatric research across three main areas of mutual interest: primary immune deficiencies, food allergies and post-Lyme disease syndrome. Their shared goal is to conduct clinical and translational research that improves what we know about those conditions and how we care for children who have them.
  • An immunotherapy trial has allowed a little boy to be a kid again. In the two years since he received cellular immunotherapy, Matthew has shown no signs of a returning tumor — the longest span of time he’s been tumor-free since age 3.
  • In the past 6 years, the 104 device projects that came through the National Capital Consortium for Pediatric Device Innovation accelerator program raised $148,680,256 in follow-on funding.
  • Even though he’s watched more than 500 aspiring physicians pass through the Children’s National pediatric residency program, program director Dewesh Agrawal, M.D., still gets teary at every graduation.

Understanding and treating the novel coronavirus (COVID-19)

In a short period of time, Children’s National Research Institute has mobilized its scientists to address COVID-19, focusing on understanding the virus and advancing solutions to ameliorate the impact today and for future generations. Children’s National Research Institute Director Mark Batshaw, M.D., highlighted some of these efforts in the annual report:

  • Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, is looking at whether or not the microbiome of bacteria in the human nasal tract acts as a defensive shield against COVID-19.
  • Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research, and her team are seeing if they can “train” T cells to attack the invading coronavirus.
  • Sarah Mulkey, M.D., Ph.D., an investigator in the Center for Neuroscience Research and the Fetal Medicine Institute, is studying the effects of, and possible interventions for, coronavirus on the developing brain.

You can view the entire Children’s National Research Institute academic annual report online.

Vittorio Gallo

Special issue of “Neurochemical Research” honors Vittorio Gallo, Ph.D.

Vittorio Gallo

Investigators from around the world penned manuscripts that were assembled in a special issue of “Neurochemical Research” that honors Vittorio Gallo, Ph.D., for his leadership in the field of neural development and regeneration.

At a pivotal moment early in his career, Vittorio Gallo, Ph.D., was accepted to work with Professor Giulio Levi at the Institute for Cell Biology in Rome, a position that leveraged courses Gallo had taken in neurobiology and neurochemistry, and allowed him to work in the top research institute in Italy directed by the Nobel laureate, Professor Rita Levi-Montalcini.

For four years as a student and later as Levi’s collaborator, Gallo focused on amino acid neurotransmitters in the brain and mechanisms of glutamate and GABA release from nerve terminals. Those early years cemented a research focus on glutamate neurotransmission that would lead to a number of pivotal publications and research collaborations that have spanned decades.

Now, investigators from around the world who have worked most closely with Gallo penned tributes in the form of manuscripts that were assembled in a special issue of “Neurochemical Research” that honors Gallo “for his contributions to our understanding of glutamatergic and GABAergic transmission during brain development and to his leadership in the field of neural development and regeneration,” writes guest editor Arne Schousboe, of the University of Copenhagen in Denmark.

Dr. Gallo as a grad student

Vittorio Gallo, Ph.D. as a 21-year-old mustachioed graduate student.

“In spite of news headlines about competition in research and many of the negative things we hear about the research world, this shows that research is also able to create a community around us,” says Gallo, chief research officer at Children’s National Hospital and scientific director for the Children’s National Research Institute.

As just one example, he first met Schousboe 44 years ago when Gallo was a 21-year-old mustachioed graduate student.

“Research can really create a sense of community that we carry on from the time we are in training, nurture as we meet our colleagues at periodic conferences, and continue up to the present. Creating community is bi-directional: influencing people and being influenced by people. People were willing to contribute these 17 articles because they value me,” Gallo says. “This is a lot of work for the editor and the people who prepared papers for this special issue.”

In addition to Gallo publishing more than 140 peer-reviewed papers, 30 review articles and book chapters, Schousboe notes a number of Gallo’s accomplishments, including:

  • He helped to develop the cerebellar granule cell cultures as a model system to study how electrical activity and voltage-dependent calcium channels modulate granule neuron development and glutamate release.
  • He developed a biochemical/neuropharmacological assay to monitor the effects of GABA receptor modulators on the activity of GABA chloride channels in living neurons.
  • He and Maria Usowicz used patch-clamp recording and single channel analysis to demonstrate for the first time that astrocytes express glutamate-activated channels that display functional properties similar to neuronal counterparts.
  • He characterized one of the spliced isoforms of the AMPA receptor subunit gene Gria4 and demonstrated that this isoform was highly expressed in the cerebellum.
  • He and his Children’s National colleagues demonstrated that glutamate and GABA regulate oligodendrocyte progenitor cell proliferation and differentiation.
Purkinje cells

Purkinje cells are large neurons located in the cerebellum that are elaborately branched like interlocking tree limbs and represent the only source of output for the entire cerebellar cortex.

Even the image selected to grace the special issue’s cover continues the theme of continuity and leaving behind a legacy. That image of Purkinje cells was created by a young scientist who works in Gallo’s lab, Aaron Sathyanesan, Ph.D. Gallo began his career working on the cerebellum – a region of the brain important for motor control – and now studies with a team of scientists and clinician-scientists Purkinje cells’ role in locomotor adaptive behavior and how that is disrupted after neonatal brain injury.

“These cells are the main players in cerebellar circuitry,” Gallo says. “It’s a meaningful image because goes back to my roots as a graduate student and is also an image that someone produced in my lab early in his career. It’s very meaningful to me that Aaron agreed to provide this image for the cover of the special issue.”

preterm baby

Validating a better way to stratify BPD risk in vulnerable newborns

preterm baby

Factoring in the total number of days that extremely preterm infants require supplemental oxygen and tracking this metric for weeks longer than usual improves clinicians’ ability to predict respiratory outcomes according to bronchopulmonary dysplasia severity.

Factoring in the total number of days that extremely preterm infants require supplemental oxygen and tracking this metric for weeks longer than usual improves clinicians’ ability to predict respiratory outcomes according to bronchopulmonary dysplasia (BPD) severity, a research team led by Children’s National Hospital writes in Scientific Reports. What’s more, the researchers defined a brand-new category (level IV) for newborns who receive supplemental oxygen more than 120 days as a reliable way to predict which infants are at the highest risk of returning to the hospital due to respiratory distress after discharge.

About 1 in 10 U.S. infants is born preterm, before 37 weeks gestation, according to the Centers for Disease Control and Prevention. That includes extremely preterm infants who weigh about 1 lb. at birth. These very low birthweight newborns have paper thin skin, frail hearts and lungs that are not yet mature enough to deliver oxygen throughout the body as needed. Thanks to advances in neocritical care, an increasing number of them survive prematurity, and many develop BPD, a chronic lung disease characterized by abnormal development of the lungs and pulmonary vasculature.

“About half of the babies born prematurely will come back to the hospital within the first year of life with a respiratory infection. The key is identifying them and, potentially, preventing complications in this high-risk population,” says Gustavo Nino, M.D., a Children’s National pulmonologist and the study’s lead author.

For decades, the most common way to stratify BPD risk in these vulnerable newborns has been to see if they require supplemental oxygen at 36 weeks corrected gestational age.

“The problem with this classification is it doesn’t take into account the very premature babies who are on oxygen for much longer than other babies. So, we asked the question: Can we continue risk stratification beyond 36 weeks in order to identify a subset of babies who are at much higher risk of complications,” Dr. Nino says.

The longitudinal cohort study enrolled 188 infants born extremely preterm who were admitted to the neonatal intensive care unit (NICU) at Children’s National and tracked their data for at least 12 months after discharge. The team used a multidimensional approach that tracked duration of supplemental oxygen during the newborns’ NICU stay as well as scoring lung imaging as an independent marker of BPD severity. To validate the findings, these U.S.-born newborns were matched with 130 infants who were born preterm and hospitalized at two NICUs located in Bogotá, Colombia.

“Babies who are born very preterm and require oxygen beyond 120 days should have expanded ventilation of the lungs and cardiovascular pulmonary system before going home,” he notes. “We need to identify these newborns and optimize their management before they are discharged.”

And, the babies with level IV BPD risk need a different type of evaluation because the complications they experience – including pulmonary hypertension – place them at the highest risk of developing sleep apnea and severe respiratory infection, especially during the first year of life.

“The earlier we identify them, the better their outcome is likely to be,” Dr. Nino says. “We really need to change the risk stratification so we don’t call them all ‘severe’ and treat them the same when there is a subset of newborns who clearly are at a much higher risk for experiencing respiratory complications after hospital discharge.”

In addition to Dr. Nino, Children’s National study co-authors include Awais Mansoor, Ph.D., staff scientist at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI); Geovanny F. Perez, M.D., pediatric pulmonologist; Maria Arroyo, M.D., pulmonologist; Xilei Xu Chen, M.D., postdoctoral fellow; Jered Weinstock, pediatric pulmonary fellow; Kyle Salka, MS, research technician; Mariam Said, M.D., neonatologist, and Marius George Linguraru, DPhil, MA, MSc, SZI principal investigator and senior author. Additional co-authors include Ranniery Acuña-Cordero, Universidad Militar Nueva Granada, Bogotá, Colombia; and Monica P. Sossa-Briceño and Carlos E. Rodríguez-Martínez, both of Universidad Nacional de Colombia.

Funding for research described in this post was provided by the National Institutes of Health (NIH) under award Nos. HL145669, AI130502 and HL141237. In addition, the NIH has awarded Dr. Nino an RO1 grant to continue this research.

NICU evacuation training baby on a stretcher

Innovative NICU training lauded as ‘best article’ by national journal

NICU evacuation training baby on a stretcher

“Fires, tornadoes and other natural disasters are outside of our team’s control. But it is within our team’s control to train neonatal intensive care unit (NICU) staff to master this necessary skill,” says Lisa Zell, BSN, a clinical educator at Children’s National Hospital.

Research into how to create a robust emergency evacuation preparedness plan and continually train staff that was led by Zell was lauded by editors of The Journal of Perinatal & Neonatal Nursing. The journal named the study the “best article” for the neonatal section that the prestigious journal published in 2018-19.

“We all hope for the best no matter what the situation, but we also need to extensively plan for the worse,” says Billie Lou Short, M.D., chief of the division of neonatology at Children’s National. “I’m proud that Lisa Zell and co-authors received this much-deserved national recognition on behalf of the nation’s No. 1 NICU.”

Educators worked with a diverse group within Children’s National to design and implement periodic evacuation simulations.

In addition to Zell and Lamia Soghier, M.D., FAAP, CHSE, Children’s National NICU medical unit director, study co-authors include Carmen Blake, BSN; Dawn Brittingham, MSN; and Ann-Marie Brown, MSN.

Read more
View photos showing how disaster training occurs at Children’s National

newborn in incubator

A bronchopulmonary dysplasia primer to guide clinicians and researchers

newborn in incubator

Six months in the writing, the “Bronchopulmonary Dysplasia Primer” published recently by Nature Reviews will be the gold standard review on this topic for years to come.

The term bronchopulmonary dysplasia, or BPD, was first coined in 1967 to describe a chronic lung disease of preterm newborns after treatment with supplemental oxygen via mechanical ventilation in an effort to save their lives. Back then, infants had 50-50 odds of surviving.

In the intervening years, survival has improved and the characteristics of BPD have evolved. Now, BPD is the most common complication of preterm birth for infants born at fewer than 28 weeks’ gestation, as more and more newborns survive premature birth. Hence, the primer.

“The contributing authors are some of the biggest thinkers on this topic,” says Robin H. Steinhorn, M.D., senior vice president, Center for Hospital-Based Specialties, at Children’s National Hospital and author of the section about BPD diagnosis, screening and prevention. “This document will guide clinical education and investigators in the field of BPD. I anticipate this will be the definitive review article on the subject for the next several years.”

Gestational age and low birth weight remain the most potent predictors of BPD. Some 50,000 extremely low gestational age newborns are born each year in the U.S. About 35% will develop some degree of BPD, according to the primer authors.

These newborns are introduced to life outside the womb well before their lungs are ready. Indeed, the pulmonary surfactants needed for normal lung function – a complex mixture of phospholipids that reduce surface tension within the lungs – don’t differentiate until late in pregnancy. Infants who persistently need respiratory support after the 14th day of life are at the highest risk of being diagnosed with BPD at 36 weeks, the coauthors note.

A number of complicating factors can come into play, including maternal diet; fetal exposure to maternal smoking and infection; structural issues such as pre-eclampsia; acute injury from mechanical ventilation and supplemental oxygen; as well as the body’s halting efforts to repair injured, inflamed lung tissue.

“The good news is the number of the smallest and youngest preterm infants who survive extreme preterm birth has steadily increased. Neonatal intensive care units, like our award-winning NICU, now routinely care for babies born at 22 weeks’ gestation,” Dr. Steinhorn says.

Treatment strategies include:

  • Reducing exposure to intubation and ventilation.
  • Leveraging respiratory stimulants, like caffeine.
  • Postnatal steroid therapy.

“Children’s National Hospital is the only center in our immediate region that provides comprehensive care for infants and children with severe BPD,” Dr. Steinhorn adds. “As the population of vulnerable and fragile infants has grown, we have invested in the equipment and the personnel – including at the Hospital for Sick Children Pediatric Center (HSC) – to create a very safe and supportive environment that improves survival and quality of life.”

Some preterm infants spend their first 9 to 10 months of life at Children’s National, and their days are filled with concentrated physical, occupational and speech therapy, as well as music and play therapy to hasten their rehabilitation.

Once their medical condition stabilizes, they transition to HSC to focus more intently on rehabilitation.

“We see HSC as filling a very important role in their care. When our children graduate to HSC, they are going for ongoing care of their lung disease, but also their ongoing rehabilitation. At HSC, they focus on creating the most normal life that we can possibly create and, over time, that is a life free of ventilators and tracheostomy tubes.”

In addition to Dr. Steinhorn, BPD Primer co-authors include Bernard Thébaud, Children’s Hospital of Eastern Ontario; Kara N. Goss, University of Wisconsin-Madison; Matthew Laughon, The University of North Carolina at Chapel Hill; Jeffrey A. Whitsett and Alan H. Jobe, Cincinnati Children’s Hospital Medical Center; Steven H. Abman, Children’s Hospital Colorado;  Judy L. Aschner, Joseph M. Sanzari Children’s Hospital; Peter G. Davis, The Royal Women’s Hospital; Sharon A. McGrath- Morrow, Johns Hopkins University School of Medicine; and Roger F. Soll, University of Vermont.

Financial support for the research described in this post was provided by the National Institutes of Health under grant Nos. U01HL122642, U01HL134745, RO1HL68702, R01HL145679, U01HL12118-01 and K24 HL143283; the Australian National Health and Medical Research Council; the Canadian Institute for Health Research; Stem Cell Network and the Ontario Institute for Regenerative Medicine.