Neurology & Neurosurgery

boy with a chromosomal developmental disability.

NIH award will support intellectual and developmental disabilities research at Children’s National

boy with a chromosomal developmental disability.

Children’s National Hospital announces a $7 million award from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to support the DC Intellectual and Developmental Disabilities Research Center (DC-IDDRC).

Children’s National Hospital announces a $7 million award from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to support the DC Intellectual and Developmental Disabilities Research Center (DC-IDDRC). Through this award, the DC-IDDRC will enhance the recruitment and training of investigators, generate innovation and promote transdisciplinary research to facilitate the development, implementation and dissemination of new diagnostic and therapeutic advances for the care of individuals with intellectual and developmental disabilities.

The DC-IDDRC, led by Children’s National in partnership with George Washington University, Howard University and Georgetown University, is one of only 14 IDDRCs in the United States funded by NICHD. This long standing NICHD program supports researchers whose goals are to advance understanding of a variety of conditions and topics related to intellectual and developmental disabilities.

“Children’s National cares for one of the largest cohorts of children with developmental disabilities in the U.S. — which uniquely positions us to lead the way in both care and research of developmental disabilities in young children,” said Vittorio Gallo, Ph.D., interim chief academic officer and interim director of the Children’s National Research Institute, and principal investigator for the DC-IDDRC.

The research strategy for this period will address three key areas: neural development and neurodevelopmental disorders, fetal and neonatal brain injury and genetic disorders by leveraging the core facilities and core innovation — including the Genomics and Bioinformatics Core, Cell and Tissue Microscopy Core, Neuroimaging Core, Clinical Translational Core and Neurobehavioral Evaluation Core.

“In spite of tremendous advances in our understanding of how abnormalities in brain development cause neurodevelopmental disorders and developmental disabilities, integrated knowledge in all these areas of research is still lacking. In particular, it is still unknown how specific genetic defects and cellular abnormalities result in behavioral phenotypes,” said Gallo.

One in six children suffers from a chronic, complex neurodevelopmental disability — conditions such as intellectual disability, learning disability, attention deficit hyperactivity disorder, autism spectrum disorder, cerebral palsy and Down syndrome. For 20 years, the DC-IDDRC has been a home for researchers from different specialties and different institutions to discover new therapies and treatments for children with these types of neurodevelopmental disabilities.

“The DC-IDDRC promises to be a great vehicle to spawn new research and collaborative networks for D.C. area investigators,” said Chandan Vaidya, Ph.D., vice provost for faculty and professor at Georgetown University. “We will be examining whether a behavioral intervention to enhance self-regulation in adolescents with Autism changes how they learn and use computational modeling to understand learning strategy and identify associated changes in the brain using functional magnetic resonance imaging.”

The robust relationships and spirit of cooperation built over two decades of collaboration have laid a strong groundwork for the establishment of the expansive post-doctoral training program and continuous growth of the research programs within the DC-IDDRC. Gallo continues his efforts in expanding access to these programs and building a sustainable pipeline of young scholars from diverse backgrounds. The partnership between Children’s National and Howard University continues to play a crucial role in these goals.

The DC-IDDRC continues to work toward translating research findings into novel approaches and personalized treatments for people with developmental disabilities and their caregivers. This work will be amplified when the DC-IDDRC moves into the expanded facility at the Children’s National Research & Innovation Campus, which houses startup incubator programs and other support for device innovation.

3d illustration of blood cells, plasmodium causing malaria disease

International projects spearheaded by Children’s National Neurology leaders

NIH approves grant for clinical trial on pediatric cerebral malaria in Malawi

3d illustration of blood cells, plasmodium causing malaria disease

Cerebral malaria, when patients lapse into coma after developing a malaria infection, is the most severe neurological complication of infection with Plasmodium falciparum.

The National Institutes of Health (NIH) approved a $5.8 million grant for a Phase I/IIa randomized clinical trial of 6-diazo-5-oxo-L-norleucine (DON), a new medication for pediatric cerebral malaria. Douglas Postels, M.D., neurologist at Children’s National Hospital, will serve as the trial’s principal investigator. The clinical trial will enroll participants in Blantyre, Malawi.

More than 400,000 people die each year from malaria. Cerebral malaria, when patients lapse into coma after developing a malaria infection, is the most severe neurological complication of infection with Plasmodium falciparum. Many children who survive are left suffering from neurological complications because of the disease, leaving some unable to walk, see or go to school. Dr. Postels and others are seeking to initiate this clinical trial with the primary goal to save lives and improve the quality of life for children who survive the disease.

“The purpose of this study is to see if DON is safe in the Malawian population,” Dr. Postels said, noting that adult participants will be enrolled in the first year and children subsequently. “Once the medication has proven to be safe, our intention is to expand this research elsewhere in Africa allowing us to enroll more children and evaluate whether DON decreases the likelihood of death or neurological disability in pediatric cerebral malaria.”

DON was originally tested 50 years ago as an anti-cancer agent but was recently repurposed by the National Institute of Allergy and Infectious Diseases (NIAID) for pediatric cerebral malaria. The current clinical trial is a collaborative project with the NIAID scientists who performed the pre-clinical testing with DON.

“There are currently no adjunctive treatments, used in combination with intravenous anti-malarial medications, that decrease death or disability in pediatric cerebral malaria,” Dr. Postels said. “Our hope is that DON will be the “magic bullet” that helps these critically ill children.”

Improving access to epilepsy care in Ethiopia

Over the next three years, Tesfaye Zelleke, M.D., neurophysiologist at Children’s National Hospital, the Comprehensive Pediatric Epilepsy Program team and the Children’s National Global Health Initiative will create a sustainable program to reduce the epilepsy treatment gap in Ethiopia in collaboration with the Ethiopian Ministry of Health.

In a three-tier approach, the program is looking to help children in the country benefit from the increased access to the treatment and care for epilepsy, the most common neurologic disorder affecting about 1% of the population.

Ethiopia is one of the poorest countries in Africa with very limited access to epilepsy care — there are a handful of pediatric neurologists for a population of over 120 million. Only few referral hospitals have neurology clinics and those clinics are largely concentrated in Addis Ababa, the capital city. Improving access to epilepsy care in resource poor countries like Ethiopia would require utilizing non-neurologist providers, a task-shifting model.

“In the first year, we will focus on creating an epilepsy center of excellence, training of trainers (local non-neurologist providers), create treatment guidelines for epilepsy, and produce health education material for families and public,” said Dr. Zelleke. “In the subsequent years, we plan to expand to other areas outside of Addis Ababa — the Ethiopian capital — and collaborate with epilepsy advocacy groups to continue to increase access to care.”

After the three years, Dr. Zelleke and the team have envisioned working closely with the country’s Ministry of Health to further the impact of the project at a national level.

fetus in utero

Loss of placental hormone linked to brain and social behavior changes

fetus in uteroPreterm birth has been shown to increase the risk of autism spectrum disorders and other developmental problems, particularly in males. The more premature a baby is, the greater the risk of either motor or cognitive deficits. What does the preterm baby lose that is so critical to long-term outcomes?

A new pre-clinical study suggests that one factor may be the loss of a placental hormone that the developing brain would normally see in the second half of pregnancy.

The study is the first to provide direct evidence that loss of a placental hormone alters long-term brain development.

In the study, researchers in the laboratory of Anna Penn, M.D., Ph.D., now at Columbia University Vagelos College of Physicians and Surgeons and previously at Children’s National Hospital in Washington, D.C., found that reducing amounts of a single hormone, called allopregnanolone (ALLO), in the placenta caused brain and behavior changes in male offspring that resemble changes seen in some people with autism spectrum disorder.

The study also found that both brain structure and behavioral changes in the subjects could be prevented with a single injection of ALLO in late pregnancy.

“Our study provides new and intriguing insights into how the loss of placental hormones—which happens in preterm birth or if the placenta stops working well during pregnancy—can lead to long-term structural changes in the brain that increase the risk for autism or other neuropsychiatric disorders,” says lead author Claire-Marie Vacher, Ph.D., assistant professor of neonatal sciences in the Department of Pediatrics at Columbia University’s Vagelos College of Physicians and Surgeons. “What’s encouraging is that these disorders may be preventable if diagnosed and treated early.”

The study was published online August 16 in the journal Nature Neuroscience.

The placenta is an organ that provides the fetus with oxygen and nutrients and removes waste products. It also produces hormones, including high levels of ALLO in late pregnancy that may influence brain development. Penn, now the L. Stanley James Associate Professor of Pediatrics at Columbia University Vagelos College of Physicians and Surgeons and chief of neonatology at Columbia and New York-Presbyterian Morgan Stanley Children’s Hospital, coined the term “neuroplacentology” to describe this new field of research connecting placental function to brain development.

About one in 10 infants is born prematurely (and is thus deprived of normal levels of ALLO and other hormones), and many more pregnancies have poor placental function.

For this study, the researchers created a pre-clinical model in which they were able to selectively decrease the production of ALLO during pregnancy so that some developing pups were exposed to sufficient placental ALLO while others were not. Although male and female fetuses were both subjected to ALLO deficiency, only male subjects showed autism-like behaviors after birth. Working with collaborators in Washington, D.C., France, and Canada, the Penn laboratory analyzed brain development and long-term behavioral outcomes in the offspring.

ALLO reduction led to cerebellum changes, autism-like behaviors

The male subjects that lacked placental ALLO had structural changes in the cerebellum, a brain region that coordinates movement and has been linked to autism, while their littermates did not.

“In particular, we observed thickening of the myelin sheaths, the lipid coating that protects nerve fibers and speeds up neural signaling,” Vacher says. The same type of thickening is also known to occur transiently in the cerebellum of some boys with autism.

The degree of myelin thickening in juvenile male subjects correlated with abnormal behavior, the researchers also found. The more the sheath was thickened (as measured by myelin protein levels), the more the male subjects exhibited autism-like behaviors, such as decreased sociability and repetitive activities.

“Our experimental model demonstrates that losing placental ALLO alters cerebellar development, including white matter development. Cerebellar white matter development occurs primarily after birth, so connecting a change in placental function during pregnancy with lingering impacts on later brain development is a particularly striking result,” says Penn.

“The findings provide a new way to understand poor placental function. Subtle but important changes during pregnancy or after delivery may set in motion neurodevelopmental disorders that children experience later in life.”

Similarities with human tissue

To determine if similar changes occur in infants, the researchers also examined post-mortem cerebellar tissues from preterm and full-term infants who had died soon after birth. Analysis of these human tissues showed similar changes in brain proteins when cerebellum from male babies born preterm were compared to male full-term babies.

“This study is an important first step in understanding how placental hormones may contribute to specific human neurobehavioral outcomes. We look forward to continuing our collaboration with Dr. Penn and her team to help define how cerebellar neurons and glia respond to environmental factors, including placental function, that can compromise the developing brain,” says study co-author Vittorio Gallo, Ph.D., interim chief academic officer at Children’s National Hospital and interim director of the Children’s National Research Institute.

Hormone injection reduced autism symptoms

ALLO’s therapeutic potential was then tested in the preclinical model.

Male offspring of the pre-clinical model given a single injection of ALLO in late pregnancy had fewer autism-like behaviors, the researchers found. Similar results were seen after an injection of muscimol, a drug that enhances the function of GABA receptors—the same receptors that respond to ALLO. Myelin protein levels in the developing cerebellum also normalized with the treatment.

“Identifying when key hormone levels are abnormal, and figuring out how and when to adjust these levels, provides an opportunity to intervene,” Penn says. “Performing additional studies with our pre-clinical model, and measuring hormone levels in moms and babies, may lead to earlier treatment to reduce or prevent long-term cognitive and behavioral impairments in high-risk fetuses and newborns.”

A version of this story appeared on the Columbia University newsroom.

The study is titled “Placental endocrine function shapes cerebellar development and social behavior.” The other contributors: Helene Lacaille (Columbia), Jiaqi J. O’Reilly (Columbia), Jacquelyn Salzbank (Columbia), Dana Bakalar (National Institutes of Health, Bethesda, MD), Sonia Sebaoui (Children’s National Hospital, Washington, DC), Philippe Liere (University Paris Saclay, Le Kremlin‐Bicêtre Cedex, France), Cheryl Clarkson-Paredes (George Washington University, Washington, DC), Toru Sasaki (Children’s National Hospital), Aaron Sathyanesan (Children’s National Hospital), Panagiotis Kratimenos (Children’s National Hospital), Jacob Ellegood (Hospital for Sick Children, Toronto, ON), Jason Lerch (Hospital for Sick Children and University of Oxford, John Radcliffe Hospital, Oxford, UK), Yuka Imamura (Pennsylvania State University College of Medicine, PA), Anastas Popratiloff (George Washington University), Kazue Hashimoto-Torii (Children’s National Hospital and George Washington University), and Michael Schumacher (University Paris Saclay).

Yuan Zhu

Yuan Zhu, Ph.D., receives Outstanding Scientist Award

Yuan Zhu

The George Washington University (GW) Cancer Center recently announced the selection of the 2021 GW Cancer Center Awards, recognizing excellence in research, mentorship and early career contributions.

The GW Cancer Center Outstanding Scientist Award was presented to Yuan Zhu, Ph.D., professor of pediatrics at the GW School of Medicine and Health Sciences (SMHS) and Children’s National Hospital. The award is presented to faculty members who make a noteworthy contribution in the areas of basic science, clinical science, translational science or population science.

In his nomination, Dr. Zhu was cited for his contributions to the understanding of the mechanisms underlying the development of tumors and altered brain development arising in the setting of the inherited condition neurofibromatosis type 1 (NF1). “Throughout his career, Dr. Zhu has had a remarkable consistency of focus in his scholarly work, where he has sought to advance new molecular and mechanistic insights to understand the biological basis of NF1 and the cancers arising in individuals affected by this genetic disease.”

You can find a full list of award winners here.

Hands holding letters that spell autism

Gene associated with autism affects social interactions differently in males and females

Hands holding letters that spell autism

The loss function of a gene associated with autism spectrum disorder (ASD), Foxp2, impacts brain circuits that control olfactory processing, social interaction, mating, aggressive and parental behaviors in a pre-clinical model. Sex differences were most notable in females with low social interaction and higher aggression behavior compared to males, suggesting ASD-like behavior in females, according to the study published in Frontiers in Behavioral Neuroscience.

ASD affects social communication and behavior in approximately 1 in 68 people, many of the symptoms appear in the first two years of life, and the disorder is mostly seen in males. Recent studies suggest that FOXP2 mutations have been implicated in a subset of individuals with ASD.

“Our work provides insights into how this gene may function mechanistically to control social interactions in both males and females,” said Joshua Corbin, Ph.D., principal investigator at Children’s National Hospital and senior author. “Foxp2 is an autism susceptibility gene, thus potentially revealing insights into the neurobiological underpinnings of deficits in social communication in neurodevelopmental disorders.”

Dopamine (DA) also plays a role in motivation and reward-seeking behavior. Herrero et al. further found that patterns of Foxp2+ cell activation in the amygdala, a structure involved in social motivation, differed in females and males in response to DA, with greater activation in females. Although how this ties together with the function of Foxp2 in social behavior remains to be elucidated, this finding suggests an intriguing link between this important neuropeptide and Foxp2 function.

FOXP2 mutations in humans are associated with disorders affecting speech and language. The scientific community has extensively studied the Foxp2 gene in other brain regions, most notably those involved in language production, such as the cerebral cortex and basal ganglia (striatum). Still, little is known regarding the function of Foxp2 in male or female social behavior, which has a large amygdala component.

“Rational interventions for human disorders and diseases relies on an understanding of the underlying biology of these conditions,” said Corbin. “Our work presents an important step toward elucidating the genetic pathways required for neurotypical social behavior.”

To better understand the role that Foxp2 plays in the amygdala-linked social behaviors, the researchers used a comprehensive panel of behavioral tests in male and female subjects. The research team relied on visual observation and video recordings to collect and score the behavioral data, work that was conducted as part of Children’s National NIH funded DC-IDDRC.

The set of behavioral tests included a “social interaction assay” that utilized a 3-chamber device, an “olfactory habituation and discrimination assay,” which pooled several odors with a cotton swab and a “maternal aggression assay” that measured aggressive encounters of a lactating female to a male intruder.

The researchers also compared the ex vivo tissue samples of female and male subjects to assess protein changes in the amygdala that might affect the activation of DA pathways.

blood glucose monitoring system

Patterns of continuous glucose monitoring use in young children after T1D diagnosis

blood glucose monitoring system

The findings suggest that, when clinically appropriate, continuous glucose monitoring initiation near or at the time of diagnosis benefits glycemic outcomes in young children when followed by sustained use.

Continuous glucose monitoring (CGM) is a blood glucose monitoring device worn on the body that is linked to positive glycemic outcomes in people with Type 1 diabetes (T1D). However, very little research has examined CGM use and glycemic outcomes in young children, particularly those newly diagnosed with T1D.

A new Diabetes Technology and Therapeutics study led by Randi Streisand, Ph.D., C.D.C.E.S., Chief of Psychology and Behavioral Health at Children’s National Hospital, and others identified four meaningful trajectories of CGM use among young children across 18-months post-T1D diagnosis: those who “always” used CGM; those who got on CGM later but stayed on it (“late/stable”); those who used CGM inconsistently; and those who “never” used CGM. The investigators conducted a study of 157 parents of young children (1-6 years) newly diagnosed with T1D who enrolled in a behavioral intervention.

Importantly, the authors found that those with private insurance were more likely than those with only public insurance to be in the “always” and “late/stable” groups (as opposed to the “never” group). Those in the “always” and “late/stable” groups also had better glycemic outcomes than those in the “never group” at 18-months post-T1D diagnosis.

“This research highlights that insurance type can be a barrier to accessing CGM,” Dr. Streisand noted. “Further, this is one of the first studies, among newly diagnosed young children, to show that CGM initiation at diagnosis or near diagnosis followed by sustained use is associated with better glycemic outcomes compared to never initiating CGM, supporting findings from other studies conducted with older youth.”

The findings inform clinical care with patients as it suggests that, when clinically appropriate, CGM initiation near or at the time of diagnosis benefits glycemic outcomes in young children when followed by sustained use. This is the only study to examine patterns of CGM use among 1-6-year-old children newly diagnosed with T1D over the first 18-months post-diagnosis.

“It was exciting to find differences in glycemic outcomes based on CGM initiation and use in this unique population,” Dr. Streisand said. However, the authors concluded that, given the health benefits of CGM, further exploration of barriers to CGM access and use among some families is needed.

In addition to Dr. Streisand, other Children’s National co-authors include Brynn Marks, M.D., M.S. HPEd.; Carrie Tully, Ph.D.Maureen Monaghan, Ph.D., C.D.E. , and Christine Wang, Ph.D.

Miriam Bornhorst

Miriam Bornhorst, M.D., receives DOD New Investigator Award

Miriam Bornhorst

Miriam Bornhorst, M.D., clinical director of the Gilbert Neurofibromatosis Institute at Children’s National Hospital, received the Department of Defense’s Neurofibromatosis Research Program New Investigator Award.

This award, which is funded by the U.S. Department of Defense, has granted $450,000 in funds which Dr. Bornhorst hopes to use towards a study for patients with Neurofibromatosis Type 1 (NF1).

“There is very little known about metabolism in NF1, but we know that abnormalities in metabolism can not only affect a person’s overall health, but may also influence how tumors develop and grow,” Dr. Bornhorst explained.

Patients with NF1 can have defining clinical features related to growth and energy metabolism, such as short stature, low weight and decreased bone mineral density, findings that are more prominent in patients with high plexiform neurofibroma (a nerve sheath tumor) burden. The mechanism for this metabolic phenotype and its association with plexiform neurofibromas is not currently understood.

Preliminary data and the work of others suggest that the MAPK pathway may play a role in metabolism and Mek-inhibitor (MEKi) treatment, which decreases activity of the MAPK pathway and promotes weight gain in patients with NF1. Dr. Bornhorst’s study will be the first to explore global metabolism in NF1, determine which metabolic pathways are most active in plexiform neurofibromas and define how metabolomic signatures change during MEKi treatment.

“These findings will improve management and may lead to novel treatment options for patients with NF1,” she said. “It is my hope that the grant funding received for my study will not only allow me to generate data that will answer questions about metabolism in NF1, but foster interest in this topic so there are more opportunities for researchers in the future.”

The NFRP was initiated in 1996 to provide support for research of exceptional scientific merit that promotes the understanding, diagnosis, and treatment of neurofibromatosis (NF) including NF type 1 (NF1) and type 2 (NF2) and schwannomatosis. Since it was first offered, 346 new Investigator Award applications have been received and only 79 have been recommended for funding – with Children’s National receiving one in the latest grant cycle. The Gilbert Family Neurofibromatosis Institute at Children’s National is one of the world’s largest programs and the longest standing program in the United States.

Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

neurons

Recommendations for the treatment of pediatric NMDAR antibody encephalitis

neurons

NMDA receptor antibody encephalitis (NMDARE) is one of the most common autoimmune encephalitides characterized by a recognizable constellation of neurologic and psychiatric features alongside positive NMDAR antibodies.

In a new study published in Neuroimmunology and Neuroinflammation, authors, including Elizabeth Wells, M.D., vice president of Neuroscience and Behavioral Medicine Center at Children’s National Hospital, created a consensus recommendation for the treatment of pediatric NMDARE, which was pragmatic and relevant to a global community and could serve as a practical decision support tool for the clinician confronted with this rare and challenging condition.

The authors conclude that their recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients.

Read the full article in Neuroimmunology and Neuroinflammation.

boy with autism blowing bubbles

Autistic youth self-reporting critical to understanding of executive function challenges

boy with autism blowing bubbles

Young people with autism are distinctly aware of their own challenges in areas such as flexibility, working memory and inhibition—abilities known collectively as “executive function,” according to the first study to measure and compare self-reports in these areas to more traditional reporting from parents.

Young people with autism are distinctly aware of their own challenges in areas such as flexibility, working memory and inhibition — abilities known collectively as “executive function,” according to the first study to measure and compare self-reports in these areas to more traditional reporting from parents. The study appears in the Journal Autism.

While autism research has started to focus on incorporating the experiences of autistic people themselves through self-reporting and greater inclusion in the design and execution of related research, this is the first time that a study has definitively captured self-reports of executive functions directly from young people with autism.

The study, which included 197 autistic youth, found that while both youth and their parents are in basic agreement about which areas of executive functioning that individual youth struggle with most, parents tended to report higher levels of impairment than the youth reported themselves. Executive function is related to a person’s ability to complete tasks such as adjusting to change, making a plan, getting organized and following through, as well as basic daily tasks like getting up and getting dressed or making small talk.

“While parents are reporting on outwardly observed behaviors in the context of home/community, for example, youth are reporting on their inner experiences across many contexts,” said Lauren Kenworthy, Ph.D., first author on the study and director of the Center for Autism Spectrum Disorders at Children’s National Hospital. “Our findings support the idea that autistic youth may be drawing their conclusions from different environmental data and cognitive frameworks than their parents, which adds a new dimension to our understanding of executive function in people with autism.”

The data are especially compelling because youth and parent reports of executive function were gathered on parallel measures with consistent items and factor structure, allowing for a true one-to-one comparison between youth and parent reporting.

“These kids are very aware of the areas where they struggle,” Dr. Kenworthy said. “And the findings from this study further elevate the importance of making sure that assessments of executive function take into account the perspective of the youth themselves, which can provide powerful insights into the interventions that they may benefit from the most.”

The study also compared reports from autistic youth to reports from both neurotypical youth and those with attention deficit hyperactivity disorder (ADHD), another condition where executive functioning skills can be challenged. There were distinct differences between all three groups—and the challenges profiled by youth with autism and those with ADHD were distinct from each other. For example, autistic youth reported greater challenges with flexibility, emotional control and self-monitoring than those with ADHD, who reported greater struggles with working memory.

The authors noted that future studies should include more performance-based measures, as well as larger numbers of females and people with intellectual disabilities to better understand how self-reporting can play a role in understanding and helping these specific groups. Additionally, developing new measures that capture the inner experience of autism by engaging autistic people in their creation could provide deeper insight into how young people with autism experience the world and how interventions designed to assist them are working (or not).

“These data provide clear evidence of the executive functioning challenges actually experienced by autistic youth as well as the primary role inflexibility plays in the lives of these young people,” the authors concluded. “This additional perspective and context for the experiences of these executive functioning challenges are of high clinical value and complement more frequently gathered assessments in ways never captured before.”

schematic of Mueller polarimetric imaging

Novel technique improved nerve visualization in head and neck surgery

In a pre-clinical model, researchers from Children’s National Hospital found that the Mueller polarimetric imaging, a novel technique that improves image contrast, may help identify nerves from other surrounding tissues during neck and head surgical procedures, avoiding accidental nerve damage.

“This technology holds great promise for the possibility of a truly noninvasive imaging approach and may help improve surgical outcomes by potentially reducing inadvertent, ill effects of nerve injuries in head and neck surgery,” said Bo Ning, Ph.D., R&D engineer at Children’s National and lead author of the study.

This pre-clinical study presents the first application of a full-field polarimetric imaging technique in vivo during head and neck surgery to highlight the vagus nerve (VN) and a branch that supplies all the intrinsic muscles to the larynx, known as recurrent laryngeal nerve (RLN).

“Unlike conventional nerve identification devices, this technique is noninvasive and less interruptive to intact tissues without disrupting surgical workflows,” said Ning et al. “Since the technique has an easy mechanism and promising performance in our study, this novel method holds great potential for real-time, noninvasive, and convenient nerve visualization.”

While some promising methods use polarimetric imaging for tissue characterizations, the current literature is still limited to ex vivo conditions due to the system complications and prolonged acquisition speeds.

“Recently, the industry released a new polarimetric camera, which is compact and allows fast and high-definition polarimetric imaging through simple snapshots. Enlightened by this technical advance, we have developed a practical polarimetric imaging method,” said Ning, who also develops compact and practical imaging systems for surgical innovation, including 3D, fluorescent, laser speckle and hyperspectral techniques. “It allows fast polarimetric analysis and can acquire birefringence maps over the whole field of view within 100 milliseconds, which provides an appropriate speed for directly surgical use.”

The new approach proofs that the concept is feasible to set up in live subjects during head and neck surgery, which can also be easily adapted for other surgeries. Among the seven subjects, the VNs and RLNs were successfully differentiated from arteries and other surrounding tissues.

Additional co-authors from Children’s National include Itai Katz, Ph.D., M.S., R&D staff engineer III; Anthony D. Sandler, M.D., Senior Vice President and Surgeon-in-Chief; Richard Jaepyeong Cha, Ph.D., research faculty assistant professor.

schematic of Mueller polarimetric imaging

Researchers at Children’s National used a novel technique that improves image contrast, which may help improve surgical outcomes.

Dr. Wells with patient

Elizabeth Wells, M.D., named Vice President of the Neuroscience and Behavioral Medicine Center

Dr. Wells with patient

Elizabeth Wells, M.D., Vice President of the Neuroscience and Behavioral Medicine Center, interacting with patient.

Elizabeth Ann Molloy Wells, M.D., MHS, has been appointed to the role of Vice President of the Neuroscience and Behavioral Medicine Center at Children’s National Hospital. This new role has been created to further the growth of the Center, broaden and deepen the leadership structure and allow Children’s National to continue to deliver the highest level of care, education, safety and scholarship for our patients and families. “I joined Children’s National 15 years ago as a pediatric neurology resident because I thought it was the best place to train and develop in academic neurology, and I am so honored to serve as the Neuroscience Center Vice-President” said Dr. Wells.

Dr. Wells is a graduate of Harvard University and the George Washington University School of Medicine and Health Sciences. She holds a master’s in Health Science from the NIH-Duke Clinical Research Training Program. Dr. Wells completed her pediatrics and neurology training at Children’s National and has been on staff as a pediatric neurologist within the Brain Tumor Institute and the Division of Neurology for the past 10 years. In addition to caring for children with neurologic effects from cancer, Dr. Wells developed the multidisciplinary program in pediatric neuro-immunology. She serves on numerous national committees and receives national and international referrals for children with neuro-inflammatory disorders. She is a principal investigator for translational research studies and serves in a leadership role for the Clinical and Translational Science Institute and the District of Columbia Intellectual and Developmental Disabilities Research Center.  Dr. Wells has been director of Inpatient Neurology and the Neuroscience Medical Unit since 2015 and was elected president of the medical staff in July 2020.

During her time at Children’s National, Dr. Wells has become known for her communication skills, team building and tireless commitment to excellence. She will expand the Neuroscience Center’s work on quality and safety, medical informatics, diversity and inclusion and patient experience.  “I am especially excited to promote growth and visibility for developing and expanding Neuroscience programs. Doing so will enable us to serve more kids and spread knowledge and expertise for children affected by brain disorders and injuries. I also look forward to fostering our culture of teamwork” said Dr. Wells. “There is a sense of urgency in the Neuroscience and Behavioral Medicine Center to rapidly translate discoveries into answers for children and families, better treatments and tools to support strong and healthy lives.”

US News badges

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

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll list, which ranks the top 10 children’s hospitals nationwide. In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fifth year in a row.

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

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

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

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

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

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

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

blue and pink chalk transgender symbol

New study looks at potential predictors of mental health in transgender adolescents

blue and pink chalk transgender symbol

Autism and autism-related traits, common in transgender populations, are associated with greater mental health burden in transgender adolescents, according to a new study published in the Journal of Clinical Child and Adolescent Psychology.

Autism and autism-related traits, common in transgender populations, are associated with greater mental health burden in transgender adolescents, according to a new study published in the Journal of Clinical Child and Adolescent Psychology.

The study, led by John Strang, Psy.D., director of the Gender and Autism Program (GAP) at Children’s National Hospital, found that autistic transgender adolescents experienced significantly greater emotional distress compared to both autistic cisgender and non-autistic transgender adolescents.

The research team notes that given the mental health risks transgender youth often face, characterization of attributes that predispose certain gender-diverse youth to mental health challenges may be useful in clinical settings. For example, this information may be helpful in screening transgender young people to identify those who may benefit from specific supports, such as accommodations for organization and planning skills (executive function skills) which are needed to navigate the multiple steps of gender transition.

“To date, the primary focus of transgender youth mental health research has been environmental drivers of wellbeing and distress. Specifically, rejection and stigma are established predictors of poorer mental health in transgender adolescents,” Dr. Strang said. “This current study takes a new direction by examining cognitive and neurodevelopmental factors as additional potential predictors of emotional distress in transgender youth.”

In addition to well-established LGBT stigma-related predictors of transgender youth mental health challenges, this study found cognitive and autism-related factors associated with increased transgender youth distress. Specifically, problems with executive function and the impact of executive function problems on a young person navigating their gender transition were associated with greater suicidality. Social symptoms of autism and executive function problems impacting gender transition were associated with greater emotional internalizing symptoms.

More than 90 adolescents ages 13 through 21 were part of the study. Participants were evenly divided between autistic-transgender, autistic-cisgender and non-autistic-transgender groups. Thirteen transgender adolescents were found to be at the margin of autism spectrum disorder (ASD) diagnosis and included within a larger “broad-ASD” grouping for analyses. To evaluate the groups psychologically and neuropsychologically, the study included comprehensive gold-standard assessment of autism and autistic symptoms for all participants as well as evaluation of mental health, IQ, gender dysphoria, LGBT-related perceived stigma, executive function planning skills, and executive function-related barriers to achieving gender transition.

Children’s National GAP is the first clinical and research initiative founded to address the needs of the many transgender youth who are autistic, or more broadly, neurodiverse. Findings from this current study and the growing body of research on co-occurring autism and gender diversity help inform the GAP’s evaluation and support programs for neurodiverse gender diverse youth.

Roger Packer

All about neurology: Upcoming conferences led by Roger Packer, M.D.

Roger Packer

Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, will speak at a series of symposiums in the next couple of months.

Most recently, he presented on pediatric brain tumor trials at a webinar hosted by the American Brain Tumor Association titled “Clinical Trials – Paving the Way Forward.” In case you missed it, you can watch it here.

For details on more upcoming presentations, see below:

On Friday, May 14, Dr. Packer will speak at the Cure Search for Children’s Cancer’s ‘Blurred Lines: Therapeutic vs. Research-only Biopsies,’ a session highlighting technologies, including liquid biopsies and single-cell sequencing, that have the potential to allow researchers to collect more data while decreasing the amount of tissue needed from solid tumor biopsies.

On Friday, May 28, he will give a virtual keynote address at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology during their “Pediatric oncology, hematology and immunology in 21st century: From research to clinical practice” online presentation. Dr. Packer will co-chair the session on central nervous system tumors and present on “CNS tumors: Major advances in neuro-oncology in last 10 years.”

And at the 50th Golden Anniversary Meeting of the Child Neurology Society, taking place September 29 to October 2, Dr. Packer will lead a symposium on new therapies for childhood medulloblastoma — the most common malignant brain tumor in children. Here, he will receive a recognition during the society’s annual gala honoring the “Founders of Child Neurology,” for his contribution in a new book in which Dr. Packer has a chapter outlining the history of child neurologists in the field of pediatric neuro-oncology.

PAS Logo

Children’s National participants share their expertise at PAS meeting

PAS Logo

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Magnetic resonance angiography (MRI) of vessel in the brain

A new framework helps guide safe pediatric diagnostic cerebral angiography

Magnetic resonance angiography (MRI) of vessel in the brain

Although many practitioners perform cerebral angiograms in children, these practitioners have varying levels of prior neuroangiography training and experience.

The Society of Neurointerventional Surgery (SNIS) Pediatric Committee published practice guidelines for pediatric diagnostic cerebral angiography (DCA) in a recent report. Monica Pearl, M.D., director of Neurointerventional Radiology Program at Children’s National Hospital, and other experts developed a framework within the report to ensure that DCA is performed safely in children. The findings detailed specific procedural considerations as well as peri-procedural evaluation and care.

“Diagnostic cerebral angiography has a low complication rate and maintaining this safety profile in children is an expectation for all practitioners performing this procedure,” Dr. Pearl said. “This is predicated on supplementing prior training and experience with a sustained, consistent volume of pediatric cases while paying special attention to the important nuances described in the findings.”

Although many practitioners perform cerebral angiograms in children, these practitioners have varying levels of prior neuroangiography training and experience. Dr. Pearl and experts suggest that a consistent volume of pediatric cases, modifications in device sizes, medication dosing, radiation protocols and technique are necessary to maintain the expected favorable safety profile. The recommendations also include referral to a higher-volume pediatric center or practitioner for those operators who infrequently perform cerebral angiography in children.

“Patient families and referring providers should seek practitioners with ample pediatric neuroangiography experience,” Dr. Pearl advised. “We provide this level of care and experience here at Children’s National.”

As the senior author for this paper, Dr. Pearl led this effort and shaped the task force recommendations providing critical input based on her current and prior pediatric neuroangiography experience. She and her team continue to serve as the leading advocates for the safety of cerebral neuroangiography procedures in children.

Blood Clot or thrombus

Endovascular therapy for acute stroke in children

Blood Clot or thrombus

Endovascular therapies for acute childhood stroke remain controversial and little evidence exists to determine the minimum age and size cut-off for thrombectomy in children. In a recent study published in the Journal of NeuroInterventional Surgery, Monica S. Pearl, M.D., director of Neurointerventional Radiology Program at Children’s National Hospital, and other experts found an increasing number of reports suggesting the feasibility of thrombectomy in at least some children by experienced operators.

When compared with adults, technical modifications may be necessary in children owing to differences in vessel sizes, tolerance of blood loss, safety of contrast and radiation exposure, and differing stroke etiologies. Dr. Pearl and experts reviewed critical considerations for neurologists and neurointerventionalists when treating pediatric stroke with endovascular therapies.

Additional study authors from Children’s National include: Dana Harrar, M.D., Ph.D., and Carlos Castillo Pinto, M.D., F.A.A.P.

Read the full study in the Journal of NeuroInterventional Surgery.

Neuronal network with electrical activity

New robotic platform at Children’s National aids adult epilepsy patient

Neuronal network with electrical activity

Epilepsy specialists at Children’s National Hospital are working collaboratively with their colleagues at George Washington University Hospital (GWU) to deliver advanced epilepsy surgical care to some adult patients by using cutting-edge surgical technologies available at Children’s National.

Epilepsy specialists at Children’s National Hospital are working collaboratively with their colleagues at George Washington University Hospital (GWU) to deliver advanced epilepsy surgical care to some adult patients by using cutting-edge surgical technologies available at Children’s National.

The need for this collaboration has risen because of the availability and experience of the Children’s National team in minimally invasive epilepsy surgery techniques, which require the use of advanced neurosurgical robots and laser ablation technologies. Children’s National has been a leader in this area of advanced epilepsy care.

Years after being diagnosed with epilepsy, an adult patient was referred to Children’s National Hospital for epilepsy surgery, where doctors have been using a robot-assisted stereotactic system called ROSA ONE Brain.

Doctors were having difficulties locating the origin of the seizures. The brain MRI did not show any abnormalities. Using stereo electroencephalography (SEEG) assisted by the robot, the joint Children’s National and GWU team were able to confirm the origin of the seizures.

“In this procedure we use a robot to implant a number of wires into specific areas of the brain where we suspect the seizures could be coming from,” said Chima Oluigbo, M.D., pediatric epilepsy neurosurgeon at Children’s National.

Children’s National is one of the few centers to have this technology available and has been using it since 2016. Up to date, Children’s National has done over 40 SEEG cases where doctors deal with more complicated cases with patients who have seizures and it is hard to pinpoint the seizure’s origin in the brain.

“The surgical procedures performed in adults are what we perform in children,” said William D. Gaillard, M.D., chief of the Divisions of Child Neurology, Epilepsy and Neurophysiology at Children’s National. Children’s National is one of the oldest pediatric epilepsy surgery centers in the country.

“The wires are 1.1 mm in diameter and the technology allows us to place these wires in the brain in such a way that it avoids hurting the patient while being able to conduct the procedure repeatedly and precisely,” Dr. Oluigbo added.

The risk with placing wires in brain is that there are many blood vessels. Doctors must be precise because if there is any mistake it can cause one of the vessels to bleed and thus, cause a stroke. Using robotic placement of SEEG wires minimizes these risks.

Once they identified where the seizures came from, Dr. Oluigbo and the epilepsy team scheduled a second surgery using laser ablation to destroy the area causing the seizures.

First, the robot scanned the patient’s brain (just like an iPhone scans the face, enabling ID recognition) while combining the brain MRI scan. Then, the doctors used a laser beam to heat the tissue area that needed to be removed by the absorbed laser energy and evaporated the target.

“It is a one-time procedure that has few side effects, such as less bleeding and less risk of infection with shorter recovery time at the hospital,” Dr. Gaillard said. “It is a little safer than other procedures and more cost-effective.”

Following the procedure, the patient was discharged back to the care of their adult GWU epileptologist, with whom the team at Children’s National worked closely with while caring for the patient. “It is wonderful to be in a position to partner with our adult-care hospitals to provide a full spectrum of care for patients, even those that have graduated from pediatric care,” concluded Dr. Oluigbo.

Sickle-Cell-Blood-Cells

Treating neurocognitive difficulties in children with sickle cell disease

Sickle-Cell-Blood-Cells

An adaptive cognitive training program could help treat attention and working memory difficulties in children with sickle cell disease (SCD), a new study published in the of Journal of Pediatric Psychology shows.

An adaptive cognitive training program could help treat attention and working memory difficulties in children with sickle cell disease (SCD), a new study published in the of Journal of Pediatric Psychology shows.

These neurocognitive difficulties have practical implications for the 100,000 individuals in the U.S. with SCD, as 20-40% of youth with SCD repeat a grade in school and fewer than half of adults with SCD are employed. Interventions to prevent and treat neurocognitive difficulties caused by SCD have the potential to significantly improve academic outcomes, vocational attainment and quality of life.

The study, led by Steven Hardy, Ph.D., director of Psychology and Patient Care Services at the Center for Cancer and Blood Disorders at Children’s National Hospital, examined a promising approach using an adaptive cognitive training program (known as Cogmed Working Memory Training) that patients complete at home on an iPad.

Using a randomized controlled trial design, children were asked to complete Cogmed training sessions 3 to 5 times per week for about 30 minutes at a time until they completed 25 sessions. The Cogmed program involves game-like working memory exercises that adapt to the user’s performance, gradually becoming more challenging over time as performance improves. The team found that patients with sickle cell disease (SCD) who completed the cognitive training intervention showed significant improvement in visual working memory compared to a waitlist group that used Cogmed after the waiting period. Treatment effects were especially notable for patients who completed a training “dose” of 10 sessions.

“Patients who completed at least 10 cognitive training sessions showed improved visual working memory, verbal short-term memory and math fluency,” Dr. Hardy said.

SCD increases risk for neurocognitive difficulties because of cerebrovascular complications (such as overt strokes and silent cerebral infarcts) and underlying disease characteristics (such as chronic anemia). Neurocognitive effects of SCD most commonly involve problems with attention, working memory and other executive functions.

“This study demonstrates that digital working memory training is an effective approach to treating neurocognitive deficits in youth with sickle cell disease,” Dr. Hardy added. “We also found that benefits of the training extend to tasks that involve short-term verbal memory and math performance when patients are able to stick with the program and complete at least 10 training sessions. These benefits could have a real impact on daily living, making it easier to remember and follow directions in school and at home, organize tasks or solve math problems that require remembering information for short periods of time.”

To date, there have been few efforts to test interventions that address the neurocognitive issues experienced by many individuals with SCD. These findings show that abilities are modifiable and that a non-pharmacological treatment exists.

The Comprehensive Sickle Cell Disease Program at Children’s National is a leader in pediatric SCD research and clinical innovation. This study was funded by a grant from the Doris Duke Charitable Foundation, which was the only Innovations in Clinical Research Award ever awarded to a psychologist (out of 31 grants totaling over $15 million), since the award established a focus on sickle cell disease in 2009.

doctor examining pregnant woman

Low parental socioeconomic status alters brain development in unborn babies

doctor examining pregnant woman

A first-of-its-kind study with 144 pregnant women finds that socioeconomic status (SES) has an impact in the womb, altering several key regions in the developing fetal brain as well as cortical features.

Maternal socioeconomic status impacts babies even before birth, emphasizing the need for policy interventions to support the wellbeing of pregnant women, according to newly published research from Children’s National Hospital.

A first-of-its-kind study with 144 pregnant women finds that socioeconomic status (SES) has an impact in the womb, altering several key regions in the developing fetal brain as well as cortical features. Parental occupation and education levels encompassing populations with lower SES hinder early brain development, potentially affecting neural, social-emotional and cognitive function later in the infant’s life.

Having a clear understanding of early brain development can also help policymakers identify intervention approaches such as educational assistance and occupational training to support and optimize the well-being of people with low SES since they face multiple psychological and physical stressors that can influence childhood brain development, Lu et al. note in the study published in JAMA Network Open.

“While there has been extensive research about the interplay between socioeconomic status and brain development, until now little has been known about the exact time when brain development is altered in people at high-risk for poor developmental outcomes,” said Catherine Limperopoulos, Ph.D., director of the Developing Brain Institute and senior author. “There are many reasons why these children can be vulnerable, including high rates of maternal prenatal depression and anxiety. Later in life, these children may experience conduct disorders and impaired neurocognitive functions needed to acquire knowledge, which is the base to thrive in school, work or life.”

The findings suggest that fetuses carried by women with low socioeconomic backgrounds had decreased regional brain growth and accelerated brain gyrification and surface folding patterns on the brain. This observation in lower SES populations may in part be explained by elevated parental stress and may be associated with neuropsychiatric disorders and mental illness later in life.

In contrast, fetuses carried by women with higher education levels, occupation and SES scores showed an increased white matter, cerebellar and brainstem volume during the prenatal period, and lower gyrification index and sulcal depth in the parietal, temporal and occipital lobes of the brain. These critical prenatal brain growth and development processes lay the foundation for normal brain function, which ready the infant for life outside the womb, enabling them to attain key developmental milestones after birth, including walking, talking, learning and social skills.

There is also a knowledge gap in the association between socioeconomic status and fetal cortical folding — when the brain undergoes structural changes to create sulcal and gyral regions. The study’s findings of accelerated gyrification in low SES adds to the scientific record, helping inform future research, Limperopoulos added.

The Children’s National research team gathered data from 144 healthy women at 24 to 40 weeks gestation with uncomplicated pregnancies. To establish the parameters for socioeconomic status, which included occupation and education in lieu of family income, parents completed a questionnaire at the time of each brain magnetic resonance imaging (MRI) visit. The researchers used MRI to measure fetal brain volumes, including cortical gray matter, white matter, deep gray matter, cerebellum and brain stem. Out of the 144 participants, the scientists scanned 40 brain fetuses twice during the pregnancy, and the rest were scanned once. The 3-dimensional computational brain models among healthy fetuses helped determine fetal brain cortical folding.

Potential proximal risk factors like maternal distress were also measured in the study using a questionnaire accounting for 60% of the participants but, according to the limited data available, there was no significant association with low and high socioeconomic status nor brain volume and cortical features.

Authors in the study from Children’s National include: Yuan-Chiao Lu, Ph.D., Kushal Kapse, M.S., Nicole Andersen, B.A., Jessica Quistorff, M.P.H., Catherine Lopez, M.S., Andrea Fry, B.S., Jenhao Cheng, Ph.D., Nickie Andescavage, M.D., Yao Wu, Ph.D., Kristina Espinosa, Psy.D., Gilbert Vezina, M.D., Adre du Plessis, M.D., and Catherine Limperopoulos, Ph.D.