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pregnant woman getting a checkup

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

pregnant woman getting a checkup

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.

 

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.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation

Maternal mental health alters structure and biochemistry of developing fetal brain

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

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

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

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

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

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

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

Of the pregnant women in the study:

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

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

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

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

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

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

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

Catherine Limperopoulos

Stressful pregnancies can leave fingerprint on fetal brain

Catherine Limperopoulos

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.