Tag Archive for: Nickie Andescavage

brain scans

Fetal MRI study reveals links between neighborhood disadvantages and brain development

brain scans

New research from the Developing Brain Institute used fetal MRI to explore how neighborhood environments may influence brain development before birth.

New research from scientists at Children’s National Hospital suggests that the environments families live in may begin shaping brain development even before a baby is born. In a study published in the journal Cerebral Cortex, researchers from the Developing Brain Institute used fetal MRI to examine how neighborhood conditions are associated with brain growth during pregnancy.

The findings suggest that factors linked to neighborhood disadvantage may influence the trajectory of brain development in utero, particularly in regions involved in emotion, memory and stress regulation.

Mechanics of the study

Neighborhood conditions are known to affect health outcomes across the lifespan. Children growing up in disadvantaged communities face higher risks for a range of health and developmental challenges. But researchers have long wondered when these effects first begin. To explore this question, investigators studied 199 healthy pregnancies in the Washington, D.C., region. Using advanced fetal MRI imaging, the team analyzed 298 brain scans collected between 18 and 39 weeks of gestation.

Researchers then compared patterns of fetal brain growth with neighborhood-level measures from the CDC’s Social Vulnerability Index. This index reflects factors such as income, education, housing conditions and access to transportation. The goal was to understand whether broader community conditions are associated with differences in early brain development.

What the study found

The study found that higher levels of neighborhood disadvantage were associated with differences in fetal brain development over the course of pregnancy. Early in gestation, fetuses from more disadvantaged neighborhoods showed slightly larger total brain volumes. As pregnancy progressed, however, the pattern shifted. By the end of gestation, those same fetuses tended to show smaller overall brain volumes and differences in subcortical brain structures.

Many of the strongest effects were seen in limbic regions, which help regulate emotions, stress responses and memory. “These findings suggest that the developmental pathways linking neighborhood conditions and brain development may begin earlier than previously understood,” the authors wrote. The results align with previous research in children and adolescents showing that socioeconomic environments can influence brain structure and connectivity.

What this means

Because fetuses do not directly interact with their neighborhoods, the researchers believe the association likely occurs through maternal experiences during pregnancy. One possible pathway is maternal stress, which has been linked to hormonal changes that can affect fetal brain development. Other potential contributors include environmental exposures, nutrition and access to health resources. While the study cannot determine which factors drive the relationship, it highlights how broader community conditions may influence development before birth.

What’s Next

The research provides new insight into how social environments intersect with early brain development. Understanding when these differences emerge may help guide future public health strategies aimed at supporting families during pregnancy. “Our findings emphasize the importance of considering the communities mothers live in during pregnancy,” the authors wrote. By identifying when developmental trajectories begin to diverge, scientists hope to better understand where early interventions may have the greatest impact.

Read the full study “Prenatal experience of greater neighborhood disadvantage is associated with altered fetal volumetric brain growth in utero” in Cerebral Cortex here.

Authors from Children’s National include Kevin M. Cook, PhD; Josepheen De Asis-Cruz, PhD; Kushal Kapse; Kelsey Christoffel, MD; Caitlin McDermott; Nickie Andescavage, MD; and Catherine Limperopoulos, PhD.

mom wearing mask and holding baby

New insights into early brain development following in-utero COVID-19 exposure

mom wearing mask and holding baby

New research from Children’s National links in-utero COVID-19 exposure to subtle differences in newborn brain development and cognitive and emotional outcomes at age two.

Researchers studying prenatal exposure to SARS-CoV-2 found that it was linked to measurable differences in newborn brain structure and, by age two, lower cognitive scores and higher internalizing behaviors.

Led by the Developing Brain Institute at Children’s National Hospital, a new study in Brain, Behavior, and Immunity followed mother-baby pairs in the Washington, D.C., region and compared infants exposed to SARS-CoV-2 during pregnancy (2020–2022) with a normative pre-pandemic cohort (2016–2019). Researchers used newborn brain MRI scans and standardized toddler developmental assessments to better understand what in-utero exposure may mean as children grow.

The big picture

During past viral outbreaks, prenatal infections have been linked with later neurodevelopmental and mental health risks. The COVID-19 pandemic raised similar concerns, but the longer-term effects of in-utero exposure are still coming into focus.

In this study, researchers prospectively enrolled 142 mother baby pairs: 103 from a pre-pandemic cohort and 39 with confirmed maternal SARS-CoV-2 infection during pregnancy. Infants underwent quantitative brain MRI scans at about two weeks old during natural sleep and without sedation. When children were about 2 years old, they were assessed by trained pediatric developmental psychologists using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), alongside parent-reported social-emotional and behavioral measures using the Infant-Toddler Social and Emotional Assessment (ITSEA).

The newborn MRI findings showed that prenatal SARS-CoV-2 exposure was associated with differences in regional brain volumes, including cortical gray matter, subcortical gray matter, cerebral white matter and the left hippocampus, compared to infants from healthy pregnancies.

“At the newborn stage, we’re seeing differences in how specific brain regions are developing after in-utero exposure,” said Nickie Andescavage, MD, neonatologist at Children’s National and a senior author on the study. “Brain imaging allows us to detect these changes very early, before behavioral differences are visible.”

Two-year follow-up

At age two, toddlers exposed to SARS-CoV-2 in utero scored lower on cognitive measures and social-emotional measures compared with children in the pre-pandemic cohort. They also had higher scores on the internalizing domain of the ITSEA, a reflection of early anxiety symptoms.

The research team used mediation analyses to explore how early brain differences might relate to later outcomes. Their results suggest that differences in newborn cortical gray matter volumes statistically accounted for part of the association between prenatal exposure and lower toddler cognitive scores. In turn, lower cognitive scores statistically mediated part of the association between prenatal exposure and higher internalizing behaviors.

“Our goal was not just to identify differences, but to understand how early brain development after SARS-CoV-2 exposure might relate to later learning and behavioral outcomes,” said Susan Weiner, PhD, lead author of the study and a researcher at Children’s National. “These findings suggest that early changes in brain structure may help explain why we see differences in cognition and emotional development at toddler age.”

Why this matters for families and clinicians

For families, one of the hardest parts of the pandemic has been uncertainty about what it might mean for children born during that period. Most children exposed to SARS-CoV-2 in utero will not have severe developmental problems, and this study does not suggest outcomes are predetermined. But it does add to growing evidence that prenatal exposure may be associated with subtle differences that can be detected early.

The findings reinforce the importance of routine developmental screening and follow-up, especially for children born during the COVID era. Pediatric developmental surveillance is already a standard part of well-child care, and early identification of concerns can connect families with supportive services when they are most effective.

“The most important message is not alarm,” Andescavage said. “It’s awareness and follow-up. Early monitoring helps ensure children get support if and when they need it.”

What’s next

The authors note several limitations. The exposed cohort was relatively small, and the study population had high overall education levels, which may limit how broadly the findings apply across populations. The study also compared a pandemic cohort to a pre-pandemic cohort, making it difficult to fully separate the effects of viral exposure from broader pandemic-related stressors, even though maternal stress and anxiety were assessed.

Larger and more diverse longitudinal studies are now needed to determine whether these early differences persist, change or diminish as children reach school age and to identify factors that may protect or promote healthy development.

For now, the takeaway is practical and actionable: Children born during the COVID era, including those exposed to SARS-CoV-2 in utero, benefit from consistent developmental screening, and families should feel empowered to raise concerns early.

Read the full open access study, “The COVID generation: the neurodevelopmental consequences of in-utero COVID-19 exposure,” in Brain, Behavior, and Immunity. Additional authors from Children’s National include Yao Wu, PhD,  Jacob Jenhao Cheng, PhD, Melissa O’Connell Ligget, PhD, Cassianna McCants, PsyD, Esther Adegbulugbe, MS, Anna Mears, Diedtra Henderson and Catherine Limperopoulos, PhD.

stressed pregnant woman

Pandemic stress in pregnant mothers may affect anxiety regions of babies’ brains

stressed pregnant woman

The research from Children’s National Hospital provides mounting evidence that children of the pandemic, even those far too young to understand it, need ongoing assessments of developmental or mental health support later in life.

A critical part of the brain linked to risks for anxiety later in life – the left amygdala – was significantly smaller by volume in babies of mothers who reported stress during the COVID-19 pandemic, according to a new manuscript published in JAMA Network Open.

The right hippocampus, which governs spatial, visual and verbal memories, and the white matter were also reduced in children whose mothers reported stress.

The research from Children’s National Hospital provides mounting evidence that children of the pandemic, even those far too young to understand it, need ongoing assessments of developmental or mental health support later in life.

“Looking ahead, we want to use this information – and studies with similar findings – to empower pregnant mothers to request support to mitigate their stress, especially in the event of another global health crisis,” said Nickie Andescavage, M.D., a neonatologist and principal investigator at the Center for Prenatal, Neonatal & Maternal Health Research. “We also want to make sure babies born during COVID-19 get the services that they need in life if they develop anxiety or other mental health disorders.”

The fine print

Researchers at the center used magnetic resonance imaging (MRI) to compare the brains of 103 babies born between 2014 and 2019 prior to the pandemic to 59 born between 2020 and 2022. Mothers who had COVID-19 or other complications in their pregnancies were excluded. The babies underwent MRI imaging while in utero and again soon after delivery.

The mothers were evaluated for stress and anxiety, using the Spielberger State-Train Anxiety Inventory and other evidence-based scoring measures. Pre-pandemic, 21% of mothers reported elevated symptoms of anxiety; in the pandemic cohort, that number jumped to nearly 62%.

Their babies’ brains were also changed, as regions widely understood to control emotion and anxiety displayed smaller volumes on MRI imaging. Given the global impact of the pandemic and universal reports of mental distress worldwide, the potential impact of these findings may impact an entire generation of children born during the pandemic. The team is just beginning to unravel the medical significance.

What’s next

Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal & Maternal Health Research, said understanding the impact of stress is vital in supporting the healthy development of young children. Current studies are underway at her center to tease apart the role of stress in prenatal development and examine its long-term impact on development, including cognition, behavior and mental health.

“We all know that being pregnant can be quite stressful, and there are certain times of collective stress that can provide us windows to understand how the body and mind manage it,” Dr. Limperopoulos said. “At our center, we care deeply about the health of mothers and babies, and our researchers plan to continue investigating the role of stress in development to continue building data to show that mental health must be a greater priority.”

This study – “Prenatal maternal psychological distress during the COVID-19 pandemic and newborn brain development” – was supported by the National Institutes of Health, the Intellectual and Developmental Disabilities Research Center, and the A. James & Alice B. Clark Foundation. You can read the full study in JAMA Network Open.

Newborn baby in a crib

Pioneering research center aims to revolutionize prenatal and neonatal health

  • Katherine Wisner
  • Catherine Stoodley
  • Katherine Ottolini
PreviousNext
123

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:

  • 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.”

pregnant woman talking to doctor

Prenatal COVID exposure associated with changes in newborn brain

pregnant woman talking to doctor

The team found differences in the brains of both infants whose mothers were infected with COVID while pregnant, as well as those born to mothers who did not test positive for the virus.

Babies born during the COVID-19 pandemic have differences in the size of certain structures in the brain, compared to infants born before the pandemic, according to a new study led by researchers at Children’s National Hospital.

The team found differences in the brains of both infants whose mothers were infected with COVID while pregnant, as well as those born to mothers who did not test positive for the virus, according to the study published in Cerebral Cortex.

The findings suggest that exposure to the coronavirus and being pregnant during the pandemic could play a role in shaping infant brain development, said Nickie Andescavage, M.D., the first author of the paper and associate chief for the Developing Brain Institute at Children’s National.

The fine print

The study’s authors looked at three groups of infants: 108 born before the pandemic; 47 exposed to COVID before birth; and 55 unexposed infants. In all cases, researchers performed magnetic resonance imaging (MRI) scans of the newborns’ brains during the first few weeks of life. The MRI scans, which are non-invasive and do not expose patients to radiation, provided 3D images of the brain, allowing doctors to calculate the volume of different areas.

Researchers found several differences in the brains of babies exposed to COVID. They had larger volumes of the gray matter that makes up the brain’s outermost layer, compared to the two other groups. In contrast, an inner area of the brain, known as deep gray matter, was smaller than in unexposed babies. These are areas that contain large numbers of neurons that generate and process signals throughout the brain. “Their brains formed differently if they were exposed to COVID,” said Dr. Andescavage, adding that “those exposed to COVID had unique signatures” in the brain.

Doctors also measured the depths of the folds in the babies’ brains – a way to determine how the brain is maturing during early development. Babies born to mothers who had COVID in pregnancy had deeper grooves in the frontal lobe, while babies born during the pandemic – even without being exposed to COVID – had increased folds and grooves throughout the brain, compared to babies born before the pandemic. “There was something about being born during the pandemic that changed how the brain developed,” Dr. Andescavage said.

What’s ahead

The study authors can’t fully explain what caused the differences in brain development in these babies, Dr. Andescavage said. But other studies have linked maternal stress and depression to changes in the newborn brain. In a future study, Dr. Andescavage and her colleagues will examine the relationship between infant brain development and how stress and anxiety during the pandemic may have played a role in early development.

Because the babies in the study were just a few weeks old, researchers don’t know if their altered brain development will affect how they learn or behave. Researchers plan to follow the children until age 6, allowing them to observe whether pandemic-era babies hit key developmental milestones on time, such as walking, talking, holding a crayon and learning the alphabet.

Researchers have been worried about the effect of COVID on the fetus since the beginning of the pandemic. Studies show that babies exposed to COVID in the womb may experience developmental impacts, and research is underway to better understand long-term outcomes.

Although the coronavirus rarely crosses the placenta to infect the fetus directly, there are other ways maternal infection can influence the developing baby. Dr. Andescavage said inflammation is one potential harm to a developing baby. In addition, if a pregnant woman becomes so sick that the levels of oxygen in her blood fall significantly, that can deprive the fetus of oxygen, she added.

In recent decades, studies of large populations have found that maternal infections with influenza and other viruses increased the risk of serious problems in children even years later, including autism, attention deficit hyperactivity disorder and schizophrenia, although the reasons behind the association are not well understood. Technology may allow doctors to answer a number of questions about COVID and the infant brain.

“With advanced imaging and MRI, we’re in a position now to be able to understand how the babies are developing in ways we never previously could,” Dr. Andescavage said. “That will better allow us to identify the exposures that may be harmful, and at what times babies may be especially vulnerable, to better position us to promote maternal wellness. This, in turn, helps infant wellness.”

Catherine Limperopoulos

Imaging reveals altered brain chemistry of babies with CHD

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.

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.

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

Maternal anxiety affects the fetal brain

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

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

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

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

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

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

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

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

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

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

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

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

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

doctor checking pregnant woman's belly

Novel approach to detect fetal growth restriction

doctor checking pregnant woman's belly

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.