Catherine Limperopoulos Archives

Pioneering research center aims to revolutionize prenatal and neonatal health

February 29, 2024

Catherine Limperopoulos, Ph.D., was drawn to understanding the developing brain, examining how early adverse environments for a mother can impact the baby at birth and extend throughout its entire lifetime. She has widened her lens – and expanded her team – to create the new Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital.

“Despite the obvious connection between mothers and babies, we know that conventional medicine often addresses the two beings separately. We want to change that,” said Dr. Limperopoulos, who also directs the Developing Brain Institute. “Given the current trajectory of medicine toward precision care and advanced imaging, we thought this was the right moment to channel our talent and resources into understanding this delicate and highly dynamic relationship.”

Moving the field forward

Since its establishment in July 2023, the new research center has gained recognition through high-impact scientific publications, featuring noteworthy studies exploring the early phases of human development.

Dr. Limperopoulos has been at the forefront of groundbreaking research, directing attention to the consequences of maternal stress on the unborn baby and the placenta. In addition, under the guidance of Kevin Cook, Ph.D., investigators published a pivotal study on the correlation between pain experienced by premature infants in the Neonatal Intensive Care Unit and the associated risks of autism and developmental delays.

Another area of research has focused on understanding the impact of congenital heart disease (CHD) on prenatal brain development, given the altered blood flow to the brain caused by these conditions during this period of rapid development. Led by Josepheen De Asis-Cruz, M.D., Ph.D., a research team uncovered variations in the functional connectivity of the brains of infants with CHD. In parallel, Nickie Andescavage, M.D., and her team employed advanced imaging techniques to identify potential biomarkers in infants with CHD, holding promise for guiding improved diagnostics and postnatal care. Separately, she is investigating the impact of COVID-19 on fetal brain development.

In the months ahead, the team plans to concentrate its efforts on these areas and several others, including the impact of infectious disease, social determinants of health and protecting developing brains from the negative impacts of maternal stress, pre-eclampsia and other conditions prevalent among expectant mothers.

Assembling a team

Given its robust research plan and opportunities for collaboration, the center pulled together expertise from across the hospital’s faculty and has attracted new talent from across the country, including several prominent faculty members:

Daniel Licht, M.D., has joined Children’s National to build a noninvasive optical device research group to better care for children with CHD. Dr. Licht brings decades of experience in pediatric neurology, psychiatry and critical care and is recognized internationally for his expertise in neurodevelopmental outcomes in babies with CHD.
Katherine L. Wisner, M.S., M.D., has accumulated extensive knowledge on the impact of maternal stress on babies throughout her career, and her deep background in psychiatry made her a natural addition to the center. While Dr. Wisner conducts research into the urgent need to prioritize maternal mental health, she will also be treating mothers as part of the DC Mother-Baby Wellness Initiative — a novel program based at Children’s National that allows mothers to more seamlessly get care for themselves and participate in mother-infant play groups timed to align with their clinical appointments.
Catherine J. Stoodley, B.S., M.S., D.Phil., brings extensive research into the role of the cerebellum in cognitive development. Dr. Stoodley uses clinical studies, neuroimaging, neuromodulation and behavioral testing to investigate the functional anatomy of the part of the brain responsible for cognition.
Katherine M. Ottolini, M.D., attending neonatologist, is developing NICU THRIVE – a research program studying the effects of tailored nutrition on the developing newborn brain, including the impact of fortifying human milk with protein, fat and carbohydrates. With a grant from the Gerber Foundation, Dr. Ottolini is working to understand how personalized fortification for high-risk babies could help them grow.

Early accolades

The new center brings together award-winning talent. This includes Yao Wu, Ph.D., who recently earned the American Heart Association’s Outstanding Research in Pediatric Cardiology award for her groundbreaking work in CHD, particularly for her research on the role of altered placental function and neurodevelopmental outcomes in toddlers with CHD. Dr. Wu became the third Children’s National faculty member to earn the distinction, joining an honor roll that includes Dr. Limperopoulos and David Wessel, M.D., executive vice president and chief medical officer.

Interim Chief Academic Officer Catherine Bollard, M.D., M.B.Ch.B., said the cross-disciplinary collaboration now underway at the new center has the potential to make a dramatic impact on the field of neonatology and early child development. “This group epitomizes the Team Science approach that we work tirelessly to foster at Children’s National,” Dr. Bollard said. “Given their energetic start, we know these scientists and physicians are poised to tackle some of the toughest questions in maternal-fetal medicine and beyond, which will improve outcomes for our most fragile patients.”

Drs. Catherine Limperopoulos, Yao Wu and David Wessel

AHA’s Outstanding Research Award: Three generations of pediatric cardiac excellence

December 13, 2023

Catherine Limperopoulos, Ph.D., Yao Wu, Ph.D., and David Wessel, M.D.

Children’s National Hospital is celebrating a remarkable milestone as three of its faculty members have been honored over 15 years with the American Heart Association’s Outstanding Research in Pediatric Cardiology Award. Yao Wu, Ph.D., became the latest researcher to earn the accolade for her groundbreaking work into congenital heart disease (CHD).

A research faculty member with the newly established Center for Prenatal, Neonatal & Maternal Health Research, Dr. Wu received the award specifically for her studies on the role of altered placental function, measured by advanced in utero imaging, and neurodevelopmental outcomes in toddlers with CHD.

Honored at the association’s annual meeting in Philadelphia, Dr. Wu returned to Children’s National to warm congratulations from her colleagues who had previously won the award: David Wessel, M.D., executive vice president and chief medical officer, and Catherine Limperopoulos, Ph.D., director of the new center.

“I am thrilled to pass the baton to one of our own,” Dr. Limperopoulos said. “Dr. Wu’s recognition speaks to the outstanding and innovative research happening at Children’s National among junior faculty who are focusing on advancing our understanding of congenital heart disease and its long-term neurodevelopmental outcomes.”

Why we’re excited

The prestigious award represents more than individual accomplishments; it symbolizes three generations of mentorship and collaboration at the hospital. In 2007, Dr. Wessel joined Children’s National to enhance the care of newborns across specialty services by expanding programs and research, with a focus on critically ill newborns with heart disease. He recruited and mentored Dr. Limperopoulos in 2010, who became one of his research partners and creator of the hospital’s Center for Prenatal, Neonatal & Maternal Health Research. Dr. Limperopoulos, in turn, recruited and mentored Dr. Wu, providing her with the tools to conduct advanced imaging on in-utero brains and placentas, as well as the development of children with CHD.

“Each one of us is in different phases of our careers, yet we are connected by our deep interest in advancing cardiac care for critically ill newborns,” Dr. Wessel said. “In this collaborative environment, we learn from each other to improve entire lifetimes for our patients.”

Dr. Wu said she believes in sharing scientific developments for the advancement of the entire medical community. “It was an honor to be chosen to join this esteemed club, which has a relentless focus on improving health outcomes,” she said.

Children’s National leads the way

The award winners shared five collaborations published in leading journals to contribute to the ongoing dialogue in the field and the innovative work happening at Children’s National:

Painful NICU procedures change neurological development in preterm babies

December 12, 2023

Premature infants exposed to pain while in the Neonatal Intensive Care Unit (NICU) are at greater risk for motor delays, language deficits and autism, even in the absence of structural brain injuries, according to findings from the new Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital.

The research sheds light on the potential outcomes of routine medical interventions – such as heel pricks, venipunctures and IV placements – and correlates these skin breaks to changes in neurological connectivity in the preterm infants’ brains. Published in BMC Medicine, the work provides valuable insights about the far-reaching impact of early medical care.

“We know that premature babies are often exposed to repeated medical interventions, light, sound and other stimuli that they would not experience in utero, and we wanted to better understand the long-term effect,” said Kevin Cook, Ph.D., research faculty at the new center and an expert in fetal and neonatal neurology. “Through this study, we can see that early and repeated exposure to pain appears to alter brain development and put children at risk for poor neurodevelopmental outcomes.”

The big picture

Globally, nearly 1 in 10 babies is born preterm, and the Children’s National team was particularly interested in the experience of those born “very” and “extremely” preterm, which is considered any delivery earlier than 32 and 28 weeks of gestation, respectively. While rates of prematurity have been relatively stable, survival rates of these babies have increased remarkably in recent decades, thanks to improved interventions and therapies for preterm infants. Yet neurodevelopmental challenges among these children persist, with noteworthy risks of autism and other neurological deficits.

At Children’s National, researchers are working to understand the mechanism behind those challenges. Given that the late second trimester and the third trimester are critical periods for brain development, the team wanted to study the effects of exposing babies to the world outside the womb early.

The fine print

Dr. Cook and his colleagues collected resting-state functional MRI (fMRI) scans from 148 infants born at least four weeks prematurely, along with 99 infants born full term. The fMRI scans, uniquely suited for studying the resting state of the brain in non-responsive infants, revealed significant hyperconnectivity within the cerebellum, which coordinates muscle activity, and the limbic and paralimbic regions, which govern emotions, motivation and cognitive functions.

Notably, the hyperconnectivity correlated with the number of skin break procedures, including heel pricks, venipunctures and IV placements. When the children returned for developmental evaluations at 18 months, the skin breaks were strongly associated with an increased risk of autism and lower motor and language scores. The toddlers identified at risk for autism had an average of 118 skin breaks, which is significantly more than the average of 65 skin breaks in those who were not at risk.

What’s ahead

Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal & Maternal Health Research, said the findings have important implications for understanding how painful NICU procedures can impact long-term outcomes and how physicians conceptualize the risks of care given to preterm babies. She and her team at the center recommend further research into managing pain in premature babies, especially given the limits of current options and the known risk of opioids.

“With this foundational study, we should consider ways to improve pain management for preterm infants and methods to better weigh the interventions used on these incredibly vulnerable patients,” Dr. Limperopoulos said. “Saving their lives is certainly the priority, and the quality of that life should also be forefront of our minds.”

Babies with congenital heart disease display disrupted brain function before birth

November 1, 2023

In their study, the team at Children’s National Hospital found that specific brain regions become especially vulnerable to injury around 24 weeks of pregnancy when developing babies begin to have high energy demands and rapid neurovascular changes.

For the first time, researchers have found that babies born with congenital heart disease (CHD) have alterations to the emerging functional connectivity of their brains in utero. The changes are related to the subtype of their CHD and their oxygen status before they have lifesaving surgery to treat their cardiac malformation, according to new findings published in the American Heart Association’s Circulation Research.

In their study, the team at Children’s National Hospital found that specific brain regions become especially vulnerable to injury around 24 weeks of pregnancy when developing babies begin to have high energy demands and rapid neurovascular changes. That leaves certain parts of the brain, including the brainstem, more susceptible to injury from cardiac complications and poor circulation.

“We used a special type of magnetic resonance imaging to safely study the brains of these unborn babies, and we found that they have weakened connectivity in the deep grey structures, which are responsible for sensation, movement, alertness and other core functions,” said Josepheen De Asis-Cruz, M.D., Ph.D., assistant professor at the Developing Brain Institute at Children’s National and an author of the study. “This offers an important clue in utero to the type of care the babies will eventually need when they are born.”

The big picture

In the past decade, the survival rate for fetuses with CHD has greatly improved. About 80% of cases – even some of the most high-risk heart defects – can be successfully treated or palliated with surgery and survive. Yet Dr. Cruz said researchers are finding that the rates of poor neurodevelopmental outcomes are about the same. That’s why she and her colleagues are looking at what precisely may be injuring the brains of these newborns prior to surgery, offering a possible roadmap to interventions.

The fine print

The research team studied 107 healthy, low-risk pregnancies and 75 pregnancies known to be complicated by CHD. They used functional connectivity magnetic resonance imaging (fcMRI) to examine the emerging connections of the brains of unborn babies, given fcMRI’s unique ability to query the brain in a resting state when a patient is unable to respond to tasks. They also studied the oxygen saturation levels of the babies after they were born and then mapped all of this information to the type of CHD that they were diagnosed with.

“Our findings indicate that the compromised connectivity in the brains of CHD patients before delivery is linked to hypoxia after birth,” Cruz said. “There were important differences in the low- and high-risk CHD groups. Babies born with transposition of the great arteries or hypoplastic left heart syndrome – two of the most high-risk diagnoses – have notable changes in their brain function, which could someday be used as biomarkers to guide their care.”

What’s ahead

Researchers at Children’s National are working together, using a variety of modalities, to move toward precision imaging in utero to help predict a child’s neurodevelopmental outcomes. The ultimate goal: better interventions sooner.

“This work is foundational. As we fine-tune more techniques to identify babies at risk, we can understand how environmental, genetic and epigenetic factors impact brain development and guide care decisions,” said Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal & Maternal Health Research and a senior author of the paper. “We can imagine a day where we can offer pregnant mothers highly detailed and personalized information about their unborn baby, and individualized interventions that lead to healthier lifetimes.”

Imaging reveals altered brain chemistry of babies with CHD

October 9, 2023

Researchers at Children’s National Hospital used magnetic resonance spectroscopy to find new biomarkers that reveal how congenital heart disease (CHD) changes an unborn baby’s brain chemistry, providing early clues that could someday guide treatment decisions for babies facing lifelong health challenges.

Published in the Journal of the American College of Cardiology, the findings detail the ways that heart defects disrupt metabolic processes in the developing brain, especially during the third trimester of pregnancy when babies grow exponentially.

“Over the past decade, our team has been at the forefront of developing safe and sophisticated ways to measure and monitor fetal brain health in the womb,” said Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal and Maternal Health Research at Children’s National. “By tapping into the power of advanced imaging, we were able to measure certain maturational components of the brain to find early biomarkers for newborns who are going to struggle immediately after birth.”

The fine print

In one of the largest cohorts of CHD patients assembled to date, researchers at Children’s National studied the developing brains of 221 healthy unborn babies and 112 with CHD using magnetic resonance spectroscopy, a noninvasive diagnostic test that can examine chemical changes in the brain. They found:

Those with CHD had higher levels of choline and lower levels of N-Acetyl aspartate-to-choline ratios compared to healthy babies, potentially representing disrupted brain development.
Babies with more complex CHD also had higher levels of cerebral lactate compared to babies with two ventricle CHD. Lactate, in particular, is a worrying signal of oxygen deprivation.

Specifically, elevated lactate levels were notably increased in babies with two types of heart defects: transposition of the great arteries, a birth defect in which the two main arteries carrying blood from the heart are switched in position, and single ventricle CHD, a birth defect causing one chamber to be smaller, underdeveloped or missing a valve. These critical heart defects generally require babies to undergo heart surgery not long after birth. The elevated lactate levels also were associated with an increased risk of death, highlighting the urgency needed for timely and effective interventions.

The research suggests that this type of imaging can provide a roadmap for further investigation and hope that medicine will someday be able to better plan for the care of these children immediately after their delivery. “With important clues about how a fetus is growing and developing, we can provide better care to help these children not only survive, but thrive, in the newborn period and beyond,” said Nickie Andescavage, M.D., Children’s National neonatologist and first author on the paper.

The big picture

CHD is the most common birth defect in the United States, affecting about 1% of all children born or roughly 40,000 babies each year. While these defects can be fatal, babies who survive are known to be at significantly higher risk of lifelong neurological deficits, including lower cognitive function, poor social interaction, inattention and impulsivity. The impact can also be felt in other organ systems because their hearts did not pump blood efficiently to support development.

Yet researchers are only beginning to pinpoint the biomarkers that can provide information about which babies are going to struggle most and require higher levels of care. The National Institutes of Health (NIH) and the District of Columbia Intellectual and Developmental Disabilities Research Center supported the research at Children’s National to improve this understanding.

“For many years we have known that the brains of children with severe heart problems do not always develop normally, but new research shows that abnormal function occurs already in the fetus,” said Kathleen N. Fenton, M.D., M.S., chief of the Advanced Technologies and Surgery Branch in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). “Understanding how the development and function of the brain is already different before a baby with a heart defect is born will help us to intervene with personal treatment as early as possible, perhaps even prenatally, and improve outcomes.”

Note: This research and content are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The NIH provided support for this research through NHLBI grant R01HL116585 and the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant P50HD105328.

Pandemic stress reshapes the placentas of expectant moms

May 10, 2023

Elevated maternal stress during the COVID-19 pandemic changed the structure, texture and other qualities of the placenta in pregnant mothers.

Elevated maternal stress during the COVID-19 pandemic changed the structure, texture and other qualities of the placenta in pregnant mothers – a critical connection between mothers and their unborn babies – according to new research from the Developing Brain Institute at Children’s National Hospital.

Published in Scientific Reports, the findings spotlight the underappreciated link between the mental health of pregnant mothers and the health of the placenta – a critical organ that develops during pregnancy to nourish and protect babies. The long-term neurodevelopmental impact on their children is under investigation.

“During the pandemic, mothers were exposed to a litany of negative stressors including social distancing, fear of dying, financial insecurity and more,” said Catherine Limperopoulos, Ph.D., chief and director of the Developing Brain Institute, which led the research. “We now know that this vital organ was changed for many mothers, and it’s essential that we continue to investigate the impact this may have had on children who were born during this global public health crisis.”

The big picture

Dr. Limperopoulos’s team compared magnetic resonance imaging (MRI) of 165 women who were pregnant before March 2020 to 63 women who became pregnant during the pandemic. Those pregnant during the pandemic were not knowingly exposed to COVID-19, and they collectively scored significantly higher on questionnaires measuring stress and depression. They were recruited at Children’s National as part of a clinical trial aimed at reducing pregnant women’s elevated stress levels during the pandemic.

The placenta is a temporary organ that grows during pregnancy to provide oxygen, nutrients and immunological protection to babies, and its health is vital to the well-being of the developing fetus. The data showed key changes in how the placenta grew and developed among women pregnant during the pandemic, especially when compared to placental growth and development among women who were pregnant before the pandemic. Changes in placental development also were associated with the infant’s birth weight at delivery. Importantly, these changes seem to be connected to maternal stress and depression symptoms.

Taken as a whole, the findings suggest that the disturbances measured on placental development in the womb may influence the placenta’s ability to support fetal health and wellness. “We are continuing to follow up on these mother-baby dyads to determine the long-term functional significance of these placental changes in utero,” Dr. Limperopoulos said.

Studies have shown that the placenta adapts to negative changes in the maternal environment and mental health status, and disruptions in placental function impact infant brain development and children’s neurobehavior and temperament.

The patient benefit

Dr. Limperopoulos’s research studying childbirth amid the pandemic builds on her extensive work investigating the impact of maternal stress on unborn children, including its adverse effect on brain structure and biochemistry. She’s also working on treatments and interventions to better support new families. Her program, DC Mother-Baby Wellness, brings together community partners to provide wrap-around care to expectant and new moms with elevated scores for stress, anxiety and depression.

“When identified early, maternal stress is a modifiable risk factor that can be treated with psychotherapy, social support and other personalized, evidence-based interventions,” Dr. Limperopoulos said. “We look forward to continued research in this area to better understand the mechanisms behind these biological changes and the needs of mothers and children who are born during pandemics, natural disasters and other significantly stressful events.”

DC Mother Baby Wellness marks 1,000-referral milestone

April 19, 2023

Launched 18 months ago, the city-wide DC MBW program brings together prenatal care providers, pediatricians, community-based organizations and birthing hospitals to provide essential services to mothers and babies at high risk for adverse health outcomes.

Launched 18 months ago, the city-wide DC MBW program brings together prenatal care providers, pediatricians, community-based organizations and birthing hospitals to provide essential services to mothers and babies at high risk for adverse health outcomes. Using evidence-based screening and evaluation tools, the program provides timely and targeted resources – including mental health care for mothers, developmental screening and treatment for newborns and other support – to ensure that families with the most acute social and medical needs have access to culturally relevant resources.

“Healthy moms are the foundation of healthy families and communities,” says Catherine Limperopoulos, Ph.D., the program’s director and director of the Developing Brain Institute at Children’s National. “Perinatal mood and anxiety disorders are among the most common complications of pregnancy. By offering thoughtful, individualized mental health resources – in English and Spanish – we are improving outcomes for local families facing some of the most complex and challenging health needs.”

Dr. Limperopoulos has done extensive research on the profound, negative effects of expectant mothers’ stress on their unborn children. Using advanced fetal MRI technology, her published research continues to show that stress, anxiety or depression in pregnant mothers alters babies’ brain development. These mental health challenges are associated with poor obstetric outcomes and social, emotional and behavioral problems in children.

The DC MBW 1,000-referral milestone comes as Dr. Limperopoulos expands her research role at Children’s National with the creation of a new Center for Prenatal, Neonatal & Maternal Health Research that she will lead. Opened in April, the center will be a research hub for maternal health and prevalent pediatric disorders that may be present in the earliest stages of life.

At DC MBW, Dr. Limperopoulos and her team serve mostly women of color with complex social needs that drive their anxiety, stress, depression and other mental health concerns. More than a third of the mothers referred to the wellness program are experiencing housing insecurity at intake – a number that climbs to more than 75% during their pregnancy and first year postpartum. About 30% of referred women are experiencing food insecurity. One in four are experiencing intimate partner violence, and 10% report contemplating suicide.

Dr. Limperopoulos says the team’s data indicate expectant mothers’ symptoms of depression drop dramatically within as few as six weeks of engagement with the wellness program’s services. These mothers are supported during pregnancy and beyond, as they check in with their providers during primary care visits at various Children’s National locations, participate in interactive, evidence-based play to boost child development and attend prenatal group classes that start this spring.

“It is not an overstatement to say that this program has saved lives,” says Siobhan Burke, M.D., director of Obstetrics and Gynecology at Unity Health Care. “There are so many initiatives and programs that focus on screening for depression in pregnancy, but DC MBW is actually doing the work and getting patients the treatments that they want and need. The team has designed a program that focuses on removing barriers. Whether that’s things like transportation, insurance status or language barriers, they find a way to help.”

The Centers for Disease Control and Prevention reports that the U.S maternal death rate continues to climb locally and nationally. The rates for Black mothers are significantly higher than for white and Latina mothers, making early intervention and wrap-around healthcare services even more vital to reverse this sobering trend.

The DC MBW program was underwritten by a $36 million investment from the A. James & Alice B. Clark Foundation and has hired more than a dozen full-time experts who provide care coordination, psychotherapy and patient referrals to a range of community resources. Most often, patients are referred by providers at Unity Health Care, the George Washington University Hospital, MedStar Washington Hospital Center and other leading prenatal care practices in the city.

“I credit our team’s tireless efforts for achieving this milestone so quickly. I have witnessed firsthand the dedication, time and boundless energy that they have devoted to each and every one of these people, walking side by side with them on their journey toward wellness,” Dr. Limperopoulos says. “Our research clearly supports the need for the care and resources we provide through the DC Mother-Baby Wellness initiative. Through our existing referral collaborative, we look forward to welcoming even more patients to this city-wide network as we welcome their babies into the world.”

New research center focuses on origins of prenatal and neonatal disease

March 21, 2023

Children’s National Hospital researchers will develop new diagnostic tools and precision medicine for unborn children, babies and young children at the hospital’s newly established Center for Prenatal, Neonatal & Maternal Health Research.

The investment comes as research continues to show the importance of high-quality, evidence-based care at this crucial stage of pediatric development, especially for underserved families. The center is the sixth organization to join the Children’s National Research Institute.

What we hope to discover

“We know that many chronic diseases that crop up during adulthood have their footprint in the womb,” said center Director Catherine Limperopoulos, Ph.D. “While this concept has been around for years, our new center will provide a unique opportunity to study such research questions as the role of prenatal stressors on long-term outcomes. And we’ll be able to provide interventions earlier, improving mothers’ outcomes sooner. This benefits the mom, the fetus, the child and has implications for the next generation.”

Limperopoulos’s research will continue the hospital’s longstanding investment in improving the understanding, prevention and treatment of childhood diseases. The center will foster collaborations throughout the hospital by teaming with experts in neuroscience, oncology, genetics and other disciplines that are vital for safeguarding the health of mothers and their babies, even before they’re born.

The big picture

“We know that many chronic diseases that crop up during adulthood have their footprint in the womb,” said center Director Catherine Limperopoulos, Ph.D. “While this concept has been around for years, our new center will provide a unique opportunity to study such research questions as the role of prenatal stressors on long-term outcomes.

Limperopoulos will also continue to serve as the director of the Children’s National Developing Brain Institute, which focuses on the brain in utero, after birth and throughout preschool. Her research is paving the way toward understanding how maternal stress impacts fetal brain development and helping to advance perinatal mental health while addressing racial disparities in access to care. The center will also partner with clinical leaders throughout Children’s National and community partners to expand existing efforts, such as the DC Mother-Baby Wellness Initiative, an innovative program that Limperopoulos leads.

“The care of mothers and their young children will change dramatically in the next decade, and the breadth of our research has the power to lead the way in harnessing medical advancements to nurture healthier families,” Limperopoulos said. “Imagine a day when we can identify in utero a biomarker for a disorder such as sickle cell disease and prevent the disease from taking hold with a novel therapy. This is the vision for the groundbreaking research that will happen at the new center.”

Lee Beers, M.D., and Catherine Limperopoulos, Ph.D., named A. James & Alice B. Clark Distinguished Professors

October 11, 2022

Lee Beers, M.D., and Catherine Limperopoulos, Ph.D., have been named A. James & Alice B. Clark Distinguished Professors by Children’s National Hospital.

Children’s National Hospital named Lee Savio Beers, M.D., as the A. James & Alice B. Clark Distinguished Professor of Early Childhood Intervention and Advocacy. She serves as the medical director for Community Health and Advocacy at Children’s National.

Children’s National Hospital also named Catherine Limperopoulos, Ph.D., as the A. James & Alice B. Clark Distinguished Professor of Maternal-Infant Health. She serves as chief and director of the Developing Brain Institute and director of Research for the Prenatal Pediatrics Institute at Children’s National.

About the award

Drs. Beers and Limperopoulos join a distinguished group of 42 Children’s National physicians and scientists who hold an endowed chair. Professorships support groundbreaking work on behalf of children and their families. They foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect each recipient’s achievements and a donor’s forethought to advance and sustain knowledge.

Dr. Beers has spent her life dedicated to bringing together the diverse voices of pediatricians, children and families to improve the health of all children. She previously served as the 2021 president of the American Academy of Pediatrics. She currently oversees the Child Health Advocacy Institute’s Community Mental Health CORE (Collaboration, Outreach, Research and Equity). It includes initiatives such as the Early Childhood Innovation Network and serves as a catalyst to elevate the standard of mental health care for every young person in Washington, D.C. Dr. Beers’ clinical and research interests include the integration of mental health and pediatric primary care, the impact of adversity and stress on child well-being and advocacy education.

Dr. Limperopoulos is at the forefront of clinical research and translational efforts focused on accelerating screening, diagnosing, treating and preventing prenatal onset brain disorders to improve child health and well-being for life. Her research seeks to understand the impact of an adverse intra- and extra-uterine environment on the developing brain and its long-term neurodevelopmental repercussions. She is founder and director of the District of Columbia Perinatal Consortium. It brings together regional stakeholders in obstetrics, psychiatry, pediatrics and the community to determine the optimal delivery of screening and low-cost interventions aimed at reducing health disparities experienced by women in under-resourced Washington, D.C., communities.

Drs. Beers and Limperopoulos are champions in their respective and rapidly growing fields. Together, they are blazing new trails for young children and their families. Their important work through the Clark Parent & Child Network is improving the lives of children in our community today while advancing knowledge to inspire the next generation of leaders.

The A. James & Alice B. Clark Foundation, through their vision and generosity, are ensuring that

Drs. Beers and Limperopoulos and future holders of these distinguished professorships will launch bold, new initiatives to rapidly advance the fields of early childhood development and maternal-infant health, elevate the hospital’s leadership and improve the lifetimes of young children.

About the donors

The Clark Foundation supports the work of organizations with strong leadership and values that reflect those of its founder, A. James Clark. Its mission is to ensure that these organizations have the resources they need to grow and support their communities today and in the future. Mr. Clark founded Clark Construction Group, which transformed the landscape of Washington, D.C., with its many projects, including Children’s National Hospital’s main campus. Mr. Clark was dedicated to giving back to the communities where he lived and worked. This includes longstanding support for Children’s National through strategic investments in genetic medicine, early childhood development, family resiliency and child mental health.

“The A. James & Alice B. Clark Foundation’s investments at Children’s National have created the foundation of one of the most significant philanthropic partnerships in our hospital’s history. Its most recent investment in the Clark Parent & Child Network, led by Drs. Beers and Limperopoulos, gives young families in Washington, D.C., greater access to vital mental health care and community resources. The Network is advancing our mission to build a healthy foundation for all kids so they can grow up stronger. The two new Clark Distinguished Professorships held by Drs. Beers and Limperopoulos will advance this vital work far into the future. We are proud to carry forward the legacy of Mr. Clark and the Clark family through these distinguished chairs.” –Kurt Newman, M.D., President & CEO, Children’s National Hospital

Pandemic-related stressors in pregnant women affect fetal brain development

May 26, 2022

Dr. Catherine Limperopoulos walking with a mom.

Prolonged levels of stress and depression during the COVID-19 pandemic contributed to altering key features of fetal brain development — even if the mother was not infected by the virus. This is what a study published in Communications Medicine suggests after following more than 200 pregnant women. The study, led by Children’s National Hospital experts, emphasized the need for more scientific inquiry to shed light on the long-term neurodevelopmental consequences of their findings and COVID-19 exposures on fetal brain development.

“Understanding how contemporary stressors may influence fetal brain development during pregnancy has major implications for basic science and informing public policy initiatives,” said Catherine Limperopoulos, Ph.D., chief and director of the Developing Brain Institute at Children’s National and senior author of the study. “With this work, we are able to show there’s a problem, it’s happening prenatally, and we can use this model to start exploring how we can reduce stress in moms and support unborn babies.”

To better understand the effects of environmental exposures on the fetus during pregnancy, further confirmation of the team’s latest findings is needed by ruling out other possibilities, such as maternal nutrition, financial security and genetic factors.

The psychosocial impact of COVID-19 on fetal brain development remains vastly understudied. The neurologic underpinnings of fetal development that turn into psycho-behavioral disorders later in life, including bipolar disorder, mood disorder or anxiety disorder, remain complex and difficult to explain.

Among the 202 participants from the Washington D.C. metropolitan area, 137 were part of the pre-pandemic cohort and 65 were part of the pandemic cohort.

Through advanced MRI imaging techniques and reconstruction of high-resolution 3D brain models, the researchers found a reduction of fetal white matter, hippocampal and cerebellar volumes and delayed brain gyrification in COVID-19 pandemic-era pregnancies. Validated maternal stress, anxiety and depression scales were also used to compare the scores between the two cohorts.

This study builds upon previous work from the Developing Brain Institute led by Limperopoulos, which discovered that anxiety in pregnant women appears to affect the brain development of their babies. Her team also found that maternal mental health, even in high socioeconomic status, alters the structure and biochemistry of the developing fetal brain, emphasizing the importance of mental health support for pregnant women.

“We’re looking at modifiable conditions,” said Limperopoulos. “What’s clear is the next frontier is intervening early to see how we can prevent or reduce stress in the mom’s current setting.”

Stress during pregnancy may hinder cognitive development

April 29, 2022

This is the first study to shed light on an important link between altered in-utero fetal brain development and the long-term cognitive development consequences for fetuses exposed to high levels of toxic stress during pregnancy.

Women’s elevated anxiety, depression and stress during pregnancy altered key features of the fetal brain, which subsequently decreased their offspring’s cognitive development at 18 months. These changes also increased internalizing and dysregulation behaviors, according to a new study by Children’s National Hospital published in JAMA Network Open. Researchers followed a cohort of 97 pregnant women and their babies. The findings further suggest that persistent psychological distress after the baby is born may influence the parent-child interaction and infant self-regulation.

This is the first study to shed light on an important link between altered in-utero fetal brain development and the long-term cognitive development consequences for fetuses exposed to high levels of toxic stress during pregnancy. While in the womb, the researchers observed changes in the sulcal depth and left hippocampal volume, which could explain the neurodevelopment issues seen after birth. Once they grow into toddlers, these children may experience persistent social-emotional problems and have difficulty establishing positive relationships with others, including their mothers. To further confirm this, future studies with a larger sample size that reflect more regions and populations are needed.

“By identifying the pregnant women with elevated levels of psychological distress, clinicians could recognize those babies who are at risk for later neurodevelopmental impairment and might benefit from early, targeted interventions,” said Catherine Limperopoulos, Ph.D., chief and director of the Developing Brain Institute at Children’s National and senior author of the study.

Regardless of their socioeconomic status, about one of every four pregnant women suffers from stress-related symptoms, the most common pregnancy complication. The relationship between altered fetal brain development, prenatal maternal psychological distress and long-term neurodevelopmental outcomes remain unknown. Studying in utero fetal brain development poses challenges due to fetal and maternal movements, imaging technology, signal-to-noise ratio issues and changes in brain growth.

All pregnant participants were healthy, most had some level of education and were employed. To quantify prenatal maternal stress, anxiety and depression, the researchers used validated self-reported questionnaires. Fetal brain volumes and cortical folding were measured from three-dimensional reconstructed images derived from MRI scans. Fetal brain creatine and choline were quantified using proton magnetic resonance spectroscopy. The 18-month child neurodevelopment was measured using validated scales and assessments.

This study builds upon previous work from the Developing Brain Institute led by Limperopoulos, which discovered that anxiety in pregnant women appears to affect the brain development of their babies. Her team also found that maternal mental health, even for women with high socioeconomic status, alters the structure and biochemistry of the developing fetal brain. The growing evidence underscores the importance of mental health support for pregnant women.

“We’re looking at shifting the health care paradigm and adopting these changes more broadly to better support moms,” said Limperopoulos. “What’s clear is early interventions could help moms reduce their stress, which can positively impact their symptoms and thereby their baby long after birth.”

Children’s National awarded $4.2 million to lead maternal mental health research programs

April 5, 2021

Mothers and their babies often experience stress, depression and anxiety, which impacts the infant’s brain development.

Children’s National Hospital announces a $4.2 million funding award from the Patient-Centered Outcomes Research Institute (PCORI) to support maternal mental health research. The Developing Brain Institute at Children’s National will lead a new program that seeks to advance perinatal mental health and well-being while addressing racial disparities in access to resources that could boost positive health outcomes for women with few opportunities.

Mothers and their babies often experience stress, depression and anxiety, which impacts the infant’s brain development. Maternal psychological distress is more pronounced among low-income mothers — a health disparity that was exacerbated during the COVID-19 pandemic.

“The new fund will support many scientific research portfolios, including our project that will ensure pregnant women in D.C. get the care they need and deserve,” said Catherine Limperopoulos, Ph.D., director of The Developing Brain Institute at Children’s National and co-principal investigator of the project.

“I’m honored to be working alongside Dr. Limperopoulos and our partners. Collectively, our team aims to meet the needs of African American pregnant and postpartum women and their families during this important transition in their lives by providing services to address social determinants of health and prevent and treat maternal distress,” said Huynh-Nhu Le, Ph.D., the co-principal investigator of the project and professor in the Clinical Psychology program, part of the department of Psychological and Brain Sciences at George Washington University.

Cognitive-behavioral intervention, patient navigation and peer support, such tailored strategies developed in the program will provide effective mental health screening and care for 1,000 mothers living in Washington D.C. that is responsive to their cultural, social, environmental, behavioral and medical needs. The participants will access the resources either online or in-person, depending on the type of assistance that fits their lifestyle.

“I am overjoyed that PCORI has provided this essential funding, giving life to our project. The research done here will have a grand effect! Our goals are ambitious: To dissect all aspects of maternal health, beyond just mental health, literally creating a detailed timeline of events a mother can anticipate experiencing from pregnancy, at delivery and postpartum,” said Shanae Bond, one of the women whose firsthand experience giving birth in D.C. informed the study design. “With the maternal health crisis we are currently facing, it’s imperative to gain this type of insight to not only support mothers but to learn how they wish to be supported and how to best improve the care they receive – based on how it impacts, improves (or impairs) their lives,” said Bond.

The multidisciplinary group includes doctors, midwives, psychologists, advisors, community leaders and four prenatal care centers, MedStar Washington Hospital Center, Howard University, The George Washington University and Unity Health Care.

“Our initiative brings together obstetrics, pediatrics, and mental health care in an integrated care model. This collaboration brings early identification and immediate care coordination to its rightful place at the center of care,” said Loral Patchen, Ph.D., CNM, vice chair, Innovation and Community Programs at MedStar Washington Hospital Center. “The prenatal period offers an opportunity for us to support emotional healing, build coping strategies, and offer a safe space for people to prepare for the complex transitions that accompany childbearing. Offering services prior to delivery optimizes opportunity for strong parent-infant attachment and mitigates potential disruptions.”

Kristin L. Atkins, M.D., FACOG, assistant professor in the Obstetrics and Gynecology Department at Howard University College of Medicine, mentioned that Howard University is honored to partner with Children’s National Hospital. “The new program will help discover more about prenatal care interventions related to maternal mental health and how they may impact fetal and pediatric brain development,” said Dr. Atkins. “We are just discovering the impact of long-standing stress on health and well-being, and this starts in utero.”

To Jennifer Keller, M.D., MPH, FACOG, associate professor at The George Washington University School of Medicine & Health Sciences, this project is essential. “The events of the last year have had a profound impact on families in this city,” said Dr. Keller. “This project begins at a time of critical mental health needs for pregnant people in D.C.”

Siobhan Burke, M.D., director of OB/GYN at Unity Health Care, is also thrilled to be part of this partnership. “We all know underlying stressors such as financial difficulties, housing instability and systemic racism can impact health, but it’s important to find out what these things do to the developing fetus and to explore strategies to make lives better,” said Dr. Burke.

In 2020, Children’s National established The Clark Parent & Child Network funded by a $36 million investment from the A. James & Alice B. Clark Foundation. The Clark Network aims to provide families with greater access to mental health care and community resources. New projects like the D.C. mother-infant behavioral wellness program underwritten by PCORI funding will become natural extensions of this essential work.

“This project was selected for PCORI funding not only for its scientific merit and commitment to engaging patients and other stakeholders, but also for its potential to fill an important gap in our health knowledge and give people information to help them weigh the effectiveness of their care options,” said PCORI Executive Director Nakela L. Cook, M.D., M.P.H.. “We look forward to following the study’s progress and working with Children’s National Hospital to share the results.”

This $4.2 million PCORI funding has been approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.

Low parental socioeconomic status alters brain development in unborn babies

March 29, 2021

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.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation

Maternal mental health alters structure and biochemistry of developing fetal brain

January 30, 2020

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. 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

Stressful pregnancies can leave fingerprint on fetal brain

January 13, 2020

“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.

Novel approach to detect fetal growth restriction

October 28, 2019

Morphometric and textural analyses of magnetic resonance imaging can point out subtle architectural deviations associated with fetal growth restriction during the second half of pregnancy, a first-time finding that has the promise to lead to earlier intervention.

Morphometric and textural analyses of magnetic resonance imaging (MRI) can point out subtle architectural deviations that are associated with fetal growth restriction (FGR) during the second half of pregnancy. The first-time finding hints at the potential to spot otherwise hidden placental woes earlier and intervene in a more timely fashion, a research team led by Children’s National Hospital faculty reports in Pediatric Research.

“We found reduced placental size, as expected, but also determined that the textural metrics are accelerated in FGR when factoring in gestational age, suggesting premature placental aging in FGR,” says Nickie Andescavage, M.D., a neonatologist at Children’s National and the study’s lead author. “While morphometric and textural features can discriminate placental differences between FGR cases with and without Doppler abnormalities, the pattern of affected features differs between these sub-groups. Of note, placental insufficiency with abnormal Doppler findings have significant differences in the signal-intensity metrics, perhaps related to differences of water content within the placenta.”

The placenta, an organ shared by the pregnant woman and the developing fetus, delivers oxygen and nutrients to the developing fetus and ferries away waste products. Placental insufficiency is characterized by a placenta that develops poorly or is damaged, impairing blood flow, and can result in still birth or death shortly after birth. Surviving infants may be born preterm or suffer early brain injury; later in life, they may experience cardiovascular, metabolic or neuropsychiatric problems.

Because there are no available tools to help clinicians identify small but critical changes in placental architecture during pregnancy, placental insufficiency often is found after some damage is already done. Typically, it is discovered when FGR is diagnosed, when a fetus weighs less than 9 of 10 fetuses of the same gestational age.

“There is a growing appreciation for the prenatal origin of some neuropsychiatric disorders that manifest years to decades later. Those nine months of gestation very much define the breath of who we later become as adults,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National and the study’s senior author. “By identifying better biomarkers of fetal distress at an earlier stage in pregnancy and refining our imaging toolkit to detect them, we set the stage to be able to intervene earlier and improve children’s overall outcomes.”

The research team studied 32 healthy pregnancies and compared them with 34 pregnancies complicated by FGR. These women underwent up to two MRIs between 20 weeks to 40 weeks gestation. They also had abdominal circumference, fetal head circumference and fetal femur length measured as well as fetal weight estimated.

In pregnancies complicated by FGR, placentas were smaller, thinner and shorter than uncomplicated pregnancies and had decreased placental volume. Ten of 13 textural and morphometric features that differed between the two groups were associated with absolute birth weight.

“Interestingly, when FGR is diagnosed in the second trimester, placental volume, elongation and thickness are significantly reduced compared with healthy pregnancies, whereas the late-onset of FGR only affects placental volume,” Limperopoulos adds. “We believe with early-onset FGR there is a more significant reduction in the developing placental units that is detected by gross measures of size and shape. By the third trimester, the overall shape of the placenta seems to have been well defined so that primarily volume is affected in late-onset FGR.”

In addition to Dr. Andescavage and Limperopoulos, study co-authors include Sonia Dahdouh, Sayali Yewale, Dorothy Bulas, M.D., chief of the Division of Diagnostic Imaging and Radiology, and Biostatistician, Marni Jacobs, Ph.D., MPH, all of Children’s National; Sara Iqbal, of MedStar Washington Hospital Center; and Ahmet Baschat, of Johns Hopkins Center for Fetal Therapy.

Financial support for research described in this post was provided by the National Institutes of Health under award number 1U54HD090257, R01-HL116585, UL1TR000075 and KL2TR000076, and the Clinical-Translational Science Institute-Children’s National.

Tag Archive for: Catherine Limperopoulos

Moving the field forward

Assembling a team

Early accolades

Why we’re excited

Children’s National leads the way

The big picture

The fine print

What’s ahead

The big picture

The fine print

What’s ahead

The fine print

The big picture

The big picture

What we hope to discover

The big picture

About the award

About the donors