Neonatology

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.

covers of books edited by Children's National faculty

We wrote the book

Children’s National Hospital is proud to have a number of faculty members who literally wrote the books on pediatric cardiology, neonatology, neurology and pulmonology. These texts, edited by experts Gil Wernovsky, M.D., Gordon Avery, M.D., Ricardo Munoz, M.D., Anastassios Koumbourlis, M.D., MPH, Robert Keating, M.D. and Roger Packer, M.D., have become the definitive references for medical students everywhere.

Through these books, generations of children worldwide will benefit from the expertise at Children’s National:

  • Anderson’s Pediatric Cardiology. Wernovsky, G., Anderson, R.H., Kumar, K., Mussatto, K.A., Redington, A.N., Tweddell, J.S., Tretter, J.T. (Eds.). (2019). Philadelphia, PA: Elsevier Publishing.
  • Avery’s Neonatology: Pathophysiology and Management of the Newborn. MacDonald, M.G., and Seshia, M.M.K. (Eds.) (2015). Philadelphia, PA: Lippincott Williams & Wilkins.
  • Critical Care of Children with Heart Disease: Basic Medical and Surgical Concepts. Munoz, R.A., More, V.O., da Cruz, E.M., Vetterly, C.G., da Silva, J.P. (Eds.). (2010) London, UK: Springer-Verlag London Ltd.
  • Diagnostic Tests in Pediatric Pulmonology. Davis, S.D., Koumbourlis, A.C., and Eber, E. (Eds.). (2015) London, UK: Springer-Verlag London Ltd.
  • Pulmonary Complications of Non-Pulmonary Pediatric Koumbourlis, A.C., and Nevin, M. (Eds.). (2018) London, UK: Springer-Verlag London Ltd.
  • Tumors of the Pediatric Central Nervous system. Keating, R.F., Goodrich, J.T., and Packer, R.J. (Eds.). (2013) New York, NY: Thieme Medical Publishers.

covers of books edited by Children's National faculty

2019 pitch competition

Pediatric medical device pitch competition deadline extended

2019 pitch competition

Pediatric innovators pitch for up to $250,000 in FDA-funded grant awards.

The National Capital Consortium for Pediatric Device Innovation (NCC-PDI) announced today that the application deadline for its annual “Make Your Medical Device Pitch for Kids!” competition is extended one week to Feb. 22 at midnight EST. Innovators and startup companies with devices in the pediatric cardiovascular, orthopedic and spine, or NICU sectors are invited to apply for a share of up to $250,000 in FDA-funded awards and access to a newly created NCC-PDI pediatric device accelerator program led by MedTech Innovator. Submissions are being accepted now.

Up to 30 companies will be selected for the first round of competition scheduled for March 23, 2020 at the University of Maryland, College Park. Up to 10 finalists chosen from that event will compete for up to $250,000 in grant awards in Toronto, Canada on October 4. Finalists also receive a spot in the MedTech Innovator 2020 Accelerator – Pediatric Track, which provides a customized curriculum and in-depth mentorship.  Finalists will be announced in May, 2020.

This is the ninth competition in seven years hosted by NCC-PDI, one of five FDA Pediatric Device Consortia Grant Program members supporting the development and commercialization of pediatric medical devices. NCC-PDI is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital and the A. James Clark School of Engineering at the University of Maryland. Additional consortium members include accelerators Medtech Innovator, BioHealth Innovation and design firm partner Archimedic.

“This year’s competition focuses on three medical device areas of critical need for pediatric patients, so we want to give innovators as much time as possible to prepare their submissions,” said Kolaleh Eskandanian, Ph.D., MBA, PMP, vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI . “Our goal is to support devices that will improve care for children by helping them advance on the pathway to commercialization. We have seen how this competition can provide significant momentum for pediatric innovations, so we want to encourage as much participation as possible.”

To date, NCC-PDI has mentored over 100 medical device sponsors to help advance their pediatric innovations, notes Eskandanian, with six devices having received either their FDA market clearance or CE marking. Along with the positive exposure of presenting at this competition, she notes that the success of NCC-PDI’s portfolio companies is attributed to funding, mentorship, support from partners and facilitated interactions between device innovators and potential investors.

Eskandanian notes that enhancing access to resources for pediatric innovators is one aim of the Children’s National Research & Innovation Campus, a first-of-its-kind campus focused on pediatric healthcare innovation, currently under development on the former Walter Reed Army Medical Center campus in Washington, D.C. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on site accelerator Johnson & Johnson Innovation – JLABS, the campus will create a rich ecosystem of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization. Opening is scheduled for December 2020.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation

Maternal mental health alters structure and biochemistry of developing fetal brain

Even when pregnant women have uncomplicated pregnancies and high socioeconomic status, when they experience elevated anxiety, stress or depression these prenatal stressors can alter the structure of the developing fetal brain and disrupt its biochemistry, according to Children’s National Hospital research published online Jan. 29, 2020, in JAMA Network Open.

The Children’s National research findings “have enormous scientific, clinical and public health implications,” Charles A. Nelson III, Ph.D.,  Boston Children’s Hospital, writes in a companion editorial.

“Previously we found that 65% of pregnant women who received a diagnosis of fetal congenital heart disease had elevated levels of stress. It’s concerning but not surprising that pregnant women who wonder if their baby will need open heart surgery would feel stress,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s senior author. “In this latest study, we ran the same panel of questionnaires and were surprised to find a high proportion of otherwise healthy pregnant women whose unborn babies are doing well also report high levels of stress.”

Anxiety and depression are the most common mental health problems during pregnancy. To learn more about the implications for the developing fetal brain, the Children’s National research team recruited 119 healthy volunteers with low-risk pregnancies from obstetric clinics in Washington, D.C., from Jan. 1, 2016, to April 17, 2019. The women’s mean age was 34.4 years old. All were high school graduates, 83% were college graduates, and 84% reported professional employment.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation. Segmentation results of total brain (orange), cortical gray matter (green), white matter (blue), deep gray matter (brown), brainstem (yellow), cerebellum (light blue), left hippocampus (purple) and right hippocampus (red) on a 3-Dimensional reconstructed T2-weighted MR image of a fetus at 26.4 gestational weeks. The hippocampus plays a central role in memory and behavioral inhibition and contains high concentrations of corticosteroid receptors and, thus, this brain region is sensitive to stress. Credit: JAMA Network Open.

The team performed 193 fetal brain magnetic resonance imaging (MRI) sessions between 24-40 weeks gestation and measured the volume of the total fetal brain as well as the cortical gray matter, white matter, deep gray matter, cerebellum, brainstem and hippocampus volumes. On the same day as their MRI visit, the pregnant women completed validated questionnaires to measure maternal stress, anxiety and depression, answering questions such as “how do you feel right now,” “how do you generally feel” as well as the degree of stressful feelings they experienced the month prior.

Of the pregnant women in the study:

  • 27% tested positive for stress
  • 26% tested positive for anxiety
  • 11% tested positive for depression
  • Maternal anxiety and stress were associated with increased fetal cortical gyrification
  • Elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain
  • Maternal stress scores decreased with increasing gestational age, while anxiety and depression did not

“We report for the first time that maternal psychological distress may be associated with increased fetal local gyrification index in the frontal and temporal lobes,” says Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author. “We also found an association with left fetal hippocampal volume, with maternal psychological distress selectively stunting the left hippocampal volumetric growth more than the right. And elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain,” Wu adds.

Late in pregnancy – at the time these women were recruited into the cohort study – the fetal brain grows exponentially and key metabolite levels also rise. Creatine facilitates recycling of adenosine triphosphate, the cell’s energy currency. Typically, levels of this metabolite rise, denoting rapid changes and higher cellular maturation; creatine also is known to support cognitive function. Choline levels also typically rise, marking cell membrane turnover as new cells are generated and support memory, mental focus and concentration.

“These women were healthy, and of high socioeconomic status and educational level, leading us to conclude that the prevalence of prenatal maternal psychological distress may be underestimated,” Limperopoulos adds. “While stress is an everyday reality for most of us, this is different because elevated stress during pregnancy can alter fetal brain programming. Our findings underscore the critical need to universally screen all pregnant women for prenatal psychological distress, even young mothers whose pregnancies wouldn’t otherwise raise red flags.”

In addition to Limperopoulos and Wu, Children’s National study co-authors include Yuan-Chiao Lu, Ph.D., research associate; Marni Jacobs, Ph.D., biostatistician; Subechhya Pradhan, Ph.D., research faculty; Kushal Kapse, MS, staff engineer; Li Zhao, Ph.D., research faculty; Nickie Niforatos-Andescavage, M.D., neonatologist; Gilbert Vezina, M.D., director of the neuroradiology program; and Adré  J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Research coordinators Catherine Lopez, MS, Kathryn Lee Bannantine, BSN, and Jessica Lynn Quistorff, MPH, assisted with subject recruitment.

Financial support for the research described in this post was provided by the National Institutes of Health under grant No. RO1 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.

Journal Reference:
Yao Wu, Yuan-Chiao Lu, Marni Jacobs, Subechhya Pradhan, Kushal Kapse, Li Zhao, Nickie Niforatos-Andescavage, Gilbert Vezina, Adré J. du Plessis, Catherine Limperopoulos. “Association of prenatal maternal psychological distress with fetal brain growth, metabolism and cortical maturation,” JAMA Network Open, 3(1): e1919940, 2020

Marc Levitt

Premier pediatric colorectal program opens doors at Children’s National

Marc Levitt

“With the broad range of expertise at Children’s National, including the nation’s best NICU, I’m confident that colorectal patients will get better, integrated care faster and more effectively here than anywhere else in the world,” says Marc Levitt, M.D.

World-renowned surgeon opens first program for care and treatment of colorectal conditions in the mid-Atlantic.

A new, highly-specialized surgical program at Children’s National Hospital is expected to draw patients from around the world. The colorectal surgery program is the first in the mid-Atlantic region to fully integrate surgery, urology, gynecology and gastroenterology into one cohesive program for children. The program is led by Marc Levitt, M.D., an internationally recognized expert in the surgical care and treatment of pediatric colorectal disorders who has performed over 10,000 surgeries to address a wide spectrum of problems involving the colon and rectum – more than any other full time practicing pediatric surgeon in the world.

“In the 25 years that I’ve been passionate about helping children with colorectal and pelvic conditions, I’ve learned that collaborative and integrated programs are the best way to care for them,” says Dr. Levitt. “With the broad range of expertise at Children’s National, including the nation’s best NICU, I’m confident that colorectal patients will get better, integrated care faster and more effectively here than anywhere else in the world.”

The program provides diagnosis and treatment for every type of colorectal disorder occurring in infants, children and adolescents, from the most common to the most complex. Every necessary specialty is integrated into the program in one convenient location to provide seamless care for all colon and rectum conditions, with particular expertise in:

  • Anorectal malformations
  • Cloacal malformations
  • Chronic constipation and fecal incontinence
  • Fecal and urinary incontinence related to spinal conditions such as spina bifida
  • Hirschsprung disease
  • Motility disorders

“Every child receives a customized treatment plan to address his or her unique needs,” Dr. Levitt says about the program. “Additionally, our surgeons often combine complex procedures across specialties to reduce the number of surgeries a child requires. It isn’t unusual for us to include urology, gynecology, and gastroenterology teams in the operating room alongside the colorectal surgeons so multiple issues can be addressed in a single procedure – we know that when possible, fewer surgeries is always better for the child.”

Dr. Levitt has cared for children from 50 states and 76 countries. He is the founder of Colorectal Team Overseas (CTO), a group of international providers who travel to the developing world to provide care for patients and teaching of their physicians and nurses. He co-founded the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC), an organization of collaborating colorectal centers across the globe.

“We’re absolutely thrilled to welcome Marc Levitt and launch the comprehensive colorectal program under his expert leadership,” adds Anthony Sandler, M.D., surgeon-in-chief and vice president of the Joseph E. Robert, Jr., Center for Surgical Care at Children’s National. “There are few in the world who can provide the expertise and leadership in colorectal diagnoses and treatment that Marc brings with him to Children’s. Many children and families from the region and from around the world will benefit from his expertise and from the program in general.”

Pediatric device competition

Premier annual pediatric medical device competition now accepting submissions

Pediatric device competition

Pediatric innovators pitch for grant awards and participation in a special accelerator program.

The official call for submissions is underway for the premiere annual pediatric medical device competition, sponsored by National Capital Consortium for Pediatric Device Innovation (NCC-PDI). The competition is led by Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital, the A. James Clark School of Engineering at the University of Maryland and non-profit accelerator MedTech Innovator. The three organizations are all an integral part of the FDA-funded NCC-PDI, which aims to facilitate the development, production and distribution of pediatric medical devices. Additional NCC-PDI members include accelerator BioHealth Innovation and design firm Archimedic.

The competition focuses on pediatric devices in three areas of critical need: cardiovascular, orthopedic and spine, and neonatal intensive care (NICU) and is now accepting applications. Contestants will pitch for a share of up to $250K in grant awards and the opportunity to participate in the MedTech Innovator 2020 Accelerator – Pediatric Track.

The first stage of competition will be held on March 23 at the University of Maryland and will include up to 30 companies selected from all submissions received. Up to 10 finalists selected from that event will move on to the “Make Your Medical Device Pitch for Kids!” finals on October 4, 2020 in Toronto, Canada. Finalists from the March qualifying round will be notified in May, 2020.

“While there is a great need for pediatric devices in many specialty areas, the development and commercialization process is very challenging because of the small market size and dynamic characteristics of the patient population,” says Kolaleh Eskandanian, Ph.D., MBA, PMP, vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “To provide pediatric innovators with greater support in meeting these unique challenges, we must go beyond grant funding, which is why we are collaborating with MedTech Innovator to offer an accelerator program with a pediatric track.”

To date, NCC-PDI has mentored over 100 medical device sponsors to help advance their pediatric innovations, notes Eskandanian, with six devices having received either their FDA market clearance or CE marking. She says the success of NCC-PDI’s portfolio companies is attributed to funding, mentorship, support from partners, facilitated interactions between device innovators and potential investors, and being discovered during their presentations at the signature “Make Your Medical Device Pitch for Kids!” competitions.

While advancements have been made in some pediatric specialties, there is still a critical need for novel devices in cardiovascular, orthopedic and spine, and NICU areas. On average over the past decade, only 24 percent of life-saving medical devices approved by FDA – those that go through PMA and HDE regulatory pathways – have an indication for pediatric use. Of those, most are designated for children age 12 or older. “Devices designed specifically for the younger pediatric population are vitally needed and, at this early stage of the intervention, can significantly improve developmental outcomes for a child,” Eskandanian said.

For more information and to apply for the upcoming NCC-PDI pitch competition, visit https://medtechinnovator.org/pediatricapply/.

Enhancing access to resources for pediatric innovators is also one of the aims of the Children’s National Research and Innovation Campus, a first-of-its-kind focused on pediatric healthcare innovation, currently under development on the former Walter Reed Army Medical Center campus in Washington, D.C. and opening in December, 2020. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on site accelerator Johnson and Johnson Innovation – JLABS, the campus will create a rich ecosystem of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization.

NOTE: The deadline for submissions has been extended to February 22 at midnight EST.

Catherine Limperopoulos

Stressful pregnancies can leave fingerprint on fetal brain

Catherine Limperopoulos

“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author.

When a diagnosis of fetal congenital heart disease causes pregnant moms to test positive for stress, anxiety and depression, powerful imaging can detect impaired development in key fetal brain regions, according to Children’s National Hospital research published online Jan. 13, 2020, in JAMA Pediatrics.

While additional research is needed, the Children’s National study authors say their unprecedented findings underscore the need for universal screening for psychological distress as a routine part of prenatal care and taking other steps to support stressed-out pregnant women and safeguard their newborns’ developing brains.

“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author. “Equally concerning is how prevalent psychological distress is among pregnant women generally. We report for the first time that this challenging prenatal environment impairs regions of the fetal brain that play a major role in learning, memory, coordination, and social and behavioral development, making it all the more important for us to identify these women early during pregnancy to intervene,” Limperopoulos adds.

Congenital heart disease (CHD), structural problems with the heart, is the most common birth defect. Still, it remains unclear how exposure to maternal stress impacts brain development in fetuses with CHD.

The multidisciplinary study team enrolled 48 women whose unborn fetuses had been diagnosed with CHD and 92 healthy women with uncomplicated pregnancies. Using validated screening tools, they found:

  • 65% of pregnant women expecting a baby with CHD tested positive for stress
  • 27% of women with uncomplicated pregnancies tested positive for stress
  • 44% of pregnant women expecting a baby with CHD tested positive for anxiety
  • 26% of women with uncomplicated pregnancies tested positive for anxiety
  • 29% of pregnant women expecting a baby with CHD tested positive for depression and
  • 9% women with uncomplicated pregnancies tested positive for depression

All told, they performed 223 fetal magnetic resonance imaging sessions for these 140 fetuses between 21 and 40 weeks of gestation. They measured brain volume in cubic centimeters for the total brain as well as volumetric measurements for key regions such as the cerebrum, cerebellum, brainstem, and left and right hippocampus.

Maternal stress and anxiety in the second trimester were associated with smaller left hippocampi and smaller cerebellums only in pregnancies affected by fetal CHD. What’s more, specific regions — the hippocampus head and body and the left cerebellar lobe – were more susceptible to stunted growth. The hippocampus is key to memory and learning, while the cerebellum controls motor coordination and plays a role in social and behavioral development.

The hippocampus is a brain structure that is known to be very sensitive to stress. The timing of the CHD diagnosis may have occurred at a particularly vulnerable time for the developing fetal cerebellum, which grows faster than any other brain structure in the second half of gestation, particularly in the third trimester.

“None of these women had been screened for prenatal depression or anxiety. None of them were taking medications. And none of them had received mental health interventions. In the group of women contending with fetal CHD, 81% had attended college and 75% had professional educations, so this does not appear to be an issue of insufficient resources,” Limperopoulos adds. “It’s critical that we routinely to do these screenings and provide pregnant women with access to interventions to lower their stress levels. Working with our community partners, Children’s National is doing just that to help reduce toxic prenatal stress for both the health of the mother and for the future newborns. We hope this becomes standard practice elsewhere.”

Adds Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author: “Our next goal is exploring effective prenatal cognitive behavioral interventions to reduce psychological distress felt by pregnant women and improve neurodevelopment in babies with CHD.”

In addition to Limperopoulos and Wu , Children’s National study co-authors include Kushal Kapse, MS, staff engineer; Marni Jacobs, Ph.D., biostatistician; Nickie Niforatos-Andescavage, M.D., neonatologist; Mary T. Donofrio, M.D., director, Fetal Heart Program; Anita Krishnan, M.D., associate director, echocardiography; Gilbert Vezina, M.D., director, Neuroradiology Program; David Wessel, M.D., Executive Vice President and Chief Medical Officer; and Adré  J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Jessica Lynn Quistorff, MPH, Catherine Lopez, MS, and Kathryn Lee Bannantine, BSN, assisted with subject recruitment and study coordination.

Financial support for the research described in this post was provided by the National Institutes of Health under grant No. R01 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.

newborn baby

Directly measuring function in tiny hearts

newborn baby

The amount of blood the heart pumps in one minute can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates the first clinical study of direct cardiac output measurement in newborns.

The amount of blood that the heart pumps in one minute (cardiac output) can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates a paper published online Dec. 17, 2019 in the Journal of Pediatrics and Neonatal Medicine. The research, conducted by Children’s National Hospital faculty, is believed to be the first clinical study of direct cardiac output measurement in newborns.

Right now, cardiac output is measured indirectly in the nation’s neonatal intensive care units (NICU) using newborns’ blood pressure, heart rate, urine output and other indirect measures. However, these techniques can produce imprecise readings in children. And the field lacks a feasible “gold standard” to measure cardiac output in newborns.

The COstatus monitor already uses ultrasound dilution – the expected decrease in the velocity of blood when saline is injected, producing a dilution curve. A Children’s National research team used ultrasound dilution in their small pilot study to gauge the feasibility of directly measuring cardiac output in newborns.

“Infants who stand to benefit most from directly monitoring cardiac hemodynamics are often so sick they already have central venous access,” says Khodayar Rais-Bahrami, M.D., an attending neonatologist at Children’s National and the study’s senior author. “Using the COstatus monitor in these children would enable the clinical team to personalize care based on the newborn’s current hemodynamic status, while introducing minimal fluid during measurements,” Dr. Rais-Bahrami adds.

COstatus monitor

The COstatus Monitor uses an extracorporeal loop attached to arterial and venous lines to measure cardiac output using ultrasound dilution. The research team injected 1mL/kg of body temperature saline into the loop and performed up to two measurement sessions daily.

The research team recruited 12 newborns younger than 2 weeks old who already had central venous and arterial access. The venous line of the arteriovenous AV loop is connected to the umbilical venous catheter while the COstatus monitor’s arterial line is connected to the umbilical arterial catheter. During measurement sessions, two injections of solution are injected into the venous loop, allowing for two measures of cardiac output, cardiac index, active circulating volume index, central blood volume index and systemic vascular resistance index.

Infants enrolled in the pilot study underwent up to two measurement sessions per day for up to four days, for a total of 54 cardiac hemodynamic measurements. The newborns ranged from 720 to 3,740 grams in weight and 24 to 41.3 weeks in gestational age.

The infants’ mean cardiac output was 0.43L/min and increased with gestational age. By contrast, the mean cardiac index was 197mL/kg/min and changed little with infants’ increasing maturity – either by gestational age or postnatal age. Two of the study participants were undergoing therapeutic cooling for hypoxic-ischemic encephalopathy and had their measurements taken during cooling and after rewarming.

“Although this study size is small, it demonstrates that this minimally invasive technique can safely be used in newborns to directly measure cardiac hemodynamics,” says Simranjeet S. Sran, M.D., a Children’s National neonatalogist and the study’s lead author. “This technology may allow for more precise and personalized care of critically ill newborns in a range of disease states – real-world utility in NICUs that serve some of the youngest and sickest newborns,” Dr. Sran adds.

The research team notes that direct measurement by ultrasound dilution revealed a stark increase in cardiac index as infants undergoing therapeutic hypothermia were rewarmed, raising questions about whether indirect measures using other technology, such as echocardiography, underestimate hypothermia’s effect on hemodynamics.

In addition to Drs. Rais-Bahrami and Sran, Mariam Said, M.D., also a Children’s National neonatalogist, was a study co-author.

sleeping baby

False negatives: Delayed Zika effects in babies who appeared normal at birth

sleeping baby

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants.

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants, according to a cohort study published online Jan. 6, 2020, in JAMA Pediatrics.

“These infants had no evidence of Zika deficits or microcephaly at birth. Neurodevelopmental deficits, including declines in mobility and social cognition, emerged in their first year of life even as their head circumference remained normal,” says Sarah B. Mulkey, M.D. Ph.D., a fetal/neonatal neurologist at Children’s National Hospital and the study’s first author. “About one-third of these newborns who underwent postnatal head ultrasound had nonspecific imaging results, which we believe are the first published results finding a link between subtle brain injuries and impaired neuromotor development in Zika-exposed children.”

The multi-institutional research group led by Children’s National enrolled pregnant women in Atlántico Department, which hugs the Caribbean coast of Colombia, who had been exposed to Zika, and performed a series of fetal magnetic resonance images (MRI) and ultrasounds as their pregnancies progressed.

Even though their mothers had laboratory-confirmed Zika infections, 77 out of 82 of their offspring were born with no sign of congenital Zika syndrome, a constellation of birth defects that includes severe brain abnormalities, eye problems and congenital contractures, and 70 underwent additional testing of neurodevelopment during infancy. These apparently normal newborns were born between Aug. 1, 2016, and Nov. 30, 2017, at the height of the Zika epidemic, and had normal head circumference.

When they were 4 to 8 months or 9 to 18 months of age, the infants’ neurodevelopment was evaluated using two validated tools, the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (a 50-item test of such skills as self-care, mobility, communication and social cognition) and the Alberta Infant Motor Scale (a motor examination of infants in prone, supine, sitting and standing positions). Some infants were assessed during each time point.

Women participating in the study were highly motivated, with 91% following up with appointments, even if it meant traveling hours by bus. In addition to Children’s National faculty traveling to Colombia to train staff how to administer the screening instruments, videotaped assessments, MRIs and ultrasounds were read, analyzed and scored at Children’s National. According to the study team, the U.S. scoring of Alberta Infant Motor Scale tests administered in Colombia is also unprecedented for a research study and offers the potential of remote scoring of infants’ motor skill maturity in regions of the world where pediatric specialists, like child neurologists, are lacking.

“Normally, neurodevelopment in infants and toddlers continues for years, building a sturdy neural network that they later use to carry out complex neurologic and cognitive functions as children enter school,” Dr. Mulkey adds. “Our findings underscore the recommendations by the Centers for Disease Control and Prevention (CDC) that all infants exposed to Zika in the womb undergo long-term follow-up, providing an opportunity to intervene earlier.”

An accompanying editorial by CDC staffers concurs, saying the study reported “intriguing data” that add “to the growing evidence of the need for long-term follow-up for all children with Zika virus exposure in utero to ensure they receive the recommended clinical evaluations even when no structural defects are identified at birth.”

In addition to Dr. Mulkey, study co-authors include Margarita Arroyave-Wessel, MPH, Dorothy I. Bulas, M.D., chief of Diagnostic Imaging and Radiology, JiJi Jiang, MS, Stephanie Russo, BS, Robert McCarter, ScD, research section head, design and biostatistics,  Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, and co-Senior Author, Roberta L. DeBiasi, MD, MS, chief of the Division of Pediatric Infectious Diseases, all of Children’s National; Colleen Peyton, PT, DPT, of Northwestern University; Yamil Fourzali, M.D., of Sabbag Radiologos, Barranquilla, Colombia; Michael E. Msall, M.D., of University of Chicago Comer Children’s Hospital; and co-Senior Author, Carlos Cure, M.D., BIOMELab, Barranquilla, Colombia.

Funding for the research described in this post was provided by the Thrasher Research Fund, the National Institutes of Health under award Nos. UL1TR001876 and KL2TR001877, and the Leadership Education in Neurodevelopmental and Related Disorders Training Program under grant HRSA/MCHB T73 MC11047.