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Safeguarding fetal brain health in pregnancies complicated by CHD

Pregnant-Mom

During the last few weeks of pregnancy, certain regions of the fetal brain experience exponential growth but also are more vulnerable to injury during that high-growth period.

Yao Wu, a research postdoctoral fellow in the Developing Brain Research Laboratory at Children’s National Health System, has received a Thrasher Research Fund early career award to expand knowledge about regions of the fetal brain that are vulnerable to injury from congenital heart disease (CHD) during pregnancy.

CHD, the most common birth defect, can have lasting effects, including overall health issues; difficulty achieving milestones such as crawling, walking or running; and missed days at daycare or school, according to the Centers for Disease Control and Prevention. Brain injury is a major complication for infants born with CHD. Catherine Limperopoulos, Ph.D., director of Children’s brain imaging lab, was the first to provide in vivo evidence that fetal brain growth and metabolism in the third trimester of pregnancy is impaired within the womb.

“It remains unclear which specific regions of the fetal brain are more vulnerable to these insults in utero,” Limperopoulos says. “We first need to identify early brain abnormalities attributed to CHD and understand their impact on infants’ later behavioral and cognitive development in order to better counsel parents and effectively intervene during the prenatal period to safeguard brain health.”

During the last few weeks of pregnancy, certain regions of the fetal brain experience exponential growth but also are more vulnerable to injury during that high-growth period. The grant, $26,749 over two years, will underwrite “Brain Development in Fetuses With Congenital Heart Disease,” research that enables Wu to utilize quantitative, non-invasive magnetic resonance imaging (MRI) to compare fetal brain development in pregnancies complicated by CHD with brain development in healthy fetuses of the same gestational age.Wu will leverage quantitative, in vivo 3-D volumetric MRI to compare overall fetal and neonatal brain growth as well as growth in key regions including cortical grey matter, white matter, deep grey matter, lateral ventricles, external cerebrospinal fluid, cerebellum, brain stem, amygdala and the hippocampus.

The research is an offshoot of a prospective study funded by the National Institutes of Health that uses advanced imaging techniques to record brain growth in 50 fetuses in pregnancies complicated by CHD who need open heart surgery and 50 healthy fetuses. MRI studies are conducted during the second trimester (24 to 28 weeks gestational age), third trimester (33 to 37 weeks gestational age) and shortly after birth but before surgery. In addition, fetal and neonatal MRI measurements will be correlated with validated scales that measure infants’ and toddlers’ overall development, behavior and social/emotional maturity.

“I am humbled to be selected for this prestigious award,” Wu says. “The findings from our ongoing work could be instrumental in identifying strategies for clinicians and care teams managing high-risk pregnancies to optimize fetal brain development and infants’ overall quality of life.”

Neonatal baby

Thrasher to fund Children’s project

Neonatal baby

The Thrasher Research Fund will fund a Children’s National Health System project, “Defining a new parameter for post-hemorrhagic ventricular dilation in premature infants,” as part of its Early Career Award Program, an initiative designed to support the successful training and mentoring of the next generation of pediatric researchers.

The proposal was submitted by Rawad Obeid, M.D., a neonatal neurology clinical research fellow at Children’s National who will serve as the project’s principal investigator. The competition for one-year Thrasher Research Fund awards is highly competitive with just two dozen granted across the nation. Research clinicians at Children’s National received two awards this funding cycle, with another awarded to support a neurologic outcomes study about Zika-affected pregnancies led by Fetal-Neonatal Neurologist Sarah B. Mulkey, M.D., Ph.D.

“Preterm infants born earlier than the 29th gestational week are at high risk for developing cerebral palsy and other brain injuries,” Dr. Obeid says. “Infants with intraventricular hemorrhage (IVH) followed by hydrocephalus (post-hemorrhagic hydrocephalus) face the highest risks of such brain injuries.”

Dr. Obeid hypothesizes that measuring distinct frontal and temporal horn ratio trajectories in extremely premature infants with and without IVH will help to definitively characterize post-hemorrhagic ventricular dilation (PHVD). Right now, experts disagree about the degree of PHVD that should trigger treatment to avoid life-long impairment.

He will be mentored by Anna A. Penn, M.D., Ph.D., Director, Translational Research for Hospital-Based Services & Board of Visitors Cerebral Palsy Prevention Program; Taeun Chang, M.D., Director of the Neonatal Neurology Program within the Division of Neurophysiology, Epilepsy & Critical Care; and Dorothy Bulas, M.D., F.A.C.R., F.A.I.U.M., F.S.R.U., Vice Chief of Academic Affairs.

In the award nomination letter, Dr. Penn noted that in “clinical settings and in the laboratory, I have supervised many trainees, but a trainee like Dr. Obeid is rare. He has pursued his research interests with great commitment. Before coming to Children’s National, he already had multiple job offers, but chose further training to enhance his research skills. While I have worked with many accomplished students, residents and fellows, Dr. Obeid stands out not only for his strong clinical skills, but also for his eagerness to learn and his dedication to both his patients and his research.”

 

Thrasher Research Fund supports Zika virus neurologic outcomes study

The Thrasher Research Fund will fund a Children’s National project, “Neurologic Outcomes of Apparently Normal Newborns From Zika Virus-Positive Pregnancies,” as part of its Early Career Award Program, an initiative designed to support the successful training and mentoring of the next generation of pediatric researchers.

The project was submitted by Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist who is a member of the Congenital Zika Virus Program at Children’s National. During the award period, Dr. Mulkey will be mentored by Adre du Plessis, M.B.Ch.B., director of the Fetal Medicine Institute, and Roberta L. DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases. Drs. du Plessis and DeBiasi co-direct the multidisciplinary Zika program, one of the nation’s first.

In the award letter, the fund mentioned Children’s institutional support for Dr. Mulkey, as demonstrated by the mentors’ letter of support, as “an important consideration throughout the funding process.”