Tag Archive for: neonatal

brain scan of newborn

New study finds prenatal opioid exposure linked to smaller newborn brain volumes

brain scans of newbornA new study out of the Center for Prenatal, Neonatal & Maternal Health Research, directed by Catherine Limperopoulos, PhD, led by Yao Wu, PhD and Stephanie Merhar, MD, MS, out of Cincinnati Children’s Hospital Medical Center, sought answers to the question: “Do brain volumes differ in opioid-exposed vs. unexposed newborns?” In one of the largest studies of this kind, researchers found that prenatal exposure to opioids is associated with smaller brain volumes in newborns. These findings from the landmark Outcomes of Babies with Opioid Exposure (OBOE) study build on, reinforce smaller studies, and achieve a better understanding of the impacts of prenatal opioid exposure (POE).

Dive Deeper

The Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT-NOW)’s OBOE study is a multi-site observational study of newborns with prenatal opioid exposure and a control group of unexposed newborns from four different sites in the United States – Case Western Reserve University, Cincinnati Children’s Hospital Medical Center, University of Alabama at Birmingham, and Children’s Hospital of Philadelphia.

In a study involving 173 newborns who were exposed to opioids during pregnancy and 96 newborns not exposed to opioids prenatally showed smaller brain sizes in several key areas. Specifically, these exposed babies had smaller total brain volumes, as shown through MRI, as well as reduced volumes in important parts of the brain, including the cortex (outer layer of the brain), deep gray matter (areas that control movement and emotions), white matter (which helps transmit signals in the brain), cerebellum (responsible for coordination and movement), brainstem (controls basic functions like breathing), and the amygdala (involved in emotions and memory).

Further details showed that newborns exposed to medication for opioid use disorder (MOUD) during pregnancy with methadone, had smaller white matter volumes, while those exposed to MOUD with buprenorphine had smaller volumes specifically in the right amygdala. Additionally, newborns who were exposed to opioids plus additional substances such as THC and gabapentin had smaller volumes in even more brain areas compared to those who were only exposed to opioids.

What’s Next

The OBOE study sets the groundwork for further research into the long-term impact of opioid exposure during pregnancy. Additional work is necessary to expand on these findings and how they relate to functions in childhood – including exploring the way these reduced brain volumes may impact cognitive, behavioral, and motor impairments. The study raises important questions about how current guidelines for MOUD during pregnancy – specifically with methadone and buprenorphine – might evolve considering these findings. This study highlights the need for further research to assess the long-term effects of MOUD regimens on both maternal and infant outcomes.

This significant study underscores the importance of multi-disciplinary collaboration in opioid exposure research, effective regulation, and policy interventions – involving healthcare providers, researchers, policymakers, and affected families – to best mitigate the consequences and improve the health outcomes of children affected by prenatal opioid exposure.

You can read the full study, Antenatal Opioid Exposure and Global and Regional Brain Volumes in Newborns, and its companion editorial, Following the Developing Brain Affected by Opioid Exposure, in the Journal of the American Medical Association.

Additional authors from Children’s National include Kushal Kapse, BS, MS, and Josepheen De Asis-Cruz, MD, PhD. Other authors include Carla M. Bann, PhD, Jamie E. Newman, PhD4, Nicole Mack, MS, Sara B. De Mauro, MD, MSCE, Namasivayam Ambalavanan, MD, Jonathan M. Davis, MD, Scott A. Lorch, MD, MSCE5, Deanne Wilson-Costello, MD, Brenda B. Poindexter, MD and Myriam Peralta-Carcelen, MD.

Visitors from the UAE at Children's National Hospital.

New philanthropic support from the United Arab Emirates furthers research breakthroughs and care

Visitors from the UAE at Children's National Hospital.

His Highness Sheikh Mohamed bin Zayed Al Nahyan, President of the United Arab Emirates (right) visited Children’s National in September 2024.

Continuing a 30-year partnership that has yielded 82 U.S. patents and countless medical breakthroughs for kids and their families, the Government of the United Arab Emirates (UAE) has strengthened its transformational commitment to Children’s National Hospital with a new $35 million donation focused on prenatal, neonatal and maternal health.

The announcement of the new gift comes after a recent visit to the hospital by His Highness Sheikh Mohamed bin Zayed Al Nahyan, President of the United Arab Emirates (UAE), who met with Emirati families and patients receiving care at Children’s National Hospital.

The investment is the latest chapter of a longstanding philanthropic partnership between the UAE and Children’s National. Each year, more than 100 Emirati families travel to Children’s National for advanced pediatric care and life-saving treatments.

This latest investment will bolster various strategic health initiatives, including within the hospital’s Center for Prenatal, Neonatal & Maternal Health Research and the Zickler Family Prenatal Pediatrics Institute.

Researchers in the Center for Prenatal, Neonatal & Maternal Health Research are focused on the role of perinatal factors — including maternal stress, anxiety and depression — on the developing brain of the child. Studies also are revealing the impact of congenital anomalies such as heart disease and acquired conditions such as maternal infection with COVID-19 or Zika virus. New approaches to prenatal and postnatal care promise to optimize long-term outcomes of many hospitalized babies.

“Children in the Washington, D.C., area and across the world benefit greatly from the breakthroughs that have emerged from the incredible decades-long partnership between the UAE and Children’s National,” said Michelle Riley-Brown, President and CEO of Children’s National. “I am deeply grateful for the UAE’s most recent gift. The contribution will positively impact children and families and support the teams of researchers and specialists who dedicate their lives to developing innovative medical care.”

Key milestones

The UAE helped to establish the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National in 2009. Today, the Sheikh Zayed Institute (SZI) has grown into a world-class, self-sustaining research center receiving more than 80% of its funding from grants and outside sources.

This platform for invention is advancing autonomous, robotic surgery. The institute’s researchers believe pediatric surgical outcomes will improve if the precision and delicacy of a robot are incorporated into procedures such as gallbladder removal. SZI is also propelling the use of artificial intelligence to improve pediatric medicine and expand health equity. One example is a deep learning algorithm that uses hand-held ultrasounds to detect early signs of rheumatic heart disease, which kills nearly 400,000 people worldwide each year.

“The lives and health of countless children and families in the Washington area, in the UAE and around the world have been transformed by our partnership,” said Yousef Al Otaiba, the UAE Ambassador to the United States. “Our continued support promises even more breakthrough innovations in pediatric medicine.”

The UAE also supported the opening of the Children’s National Research & Innovation Campus through a 2019 commitment. The campus represents the first pediatric innovation hub of its kind, where scientists, inventors, caregivers, patients’ families and health authorities come together to advance pediatric health.

The Children’s National Rare Disease Institute and Center for Genetic Medicine Research are two of the teams housed at the campus. Together, they are pioneering care for children in the Washington region and abroad as an international referral site for rare disorders. Two examples of their research endeavors include: next-generation genomic testing to better understand how differences in genetic material can affect human health and identifying biochemical analytes.

The UAE opened a medical office in Washington, D.C., in 1991. Since then, thousands of Emirati patients have visited Children’s National for life-changing care for conditions such as congenital heart disease, neurological disorders and cancer. The hospital is currently treating 40 Emirati patients.

“Having our child treated at Children’s National means accessing specialized pediatric care from a renowned institution dedicated to children’s health,” said Hamad Alnuaimi, an Emirati father of a Children’s National patient. “It provides us with confidence and reassurance that our son is receiving the best possible medical attention from experts who understand and prioritize the unique needs of children. For the UAE to have a strong relationship with Children’s National signifies a valuable connection that enhances pediatric healthcare in our country. This partnership allows us to benefit from advanced treatments, medical innovations, and expertise that might otherwise be inaccessible. It represents a commitment to improving the health and well-being of children through international collaboration.”

Vittorio Gallo

Special issue of “Neurochemical Research” honors Vittorio Gallo, Ph.D.

Vittorio Gallo

Investigators from around the world penned manuscripts that were assembled in a special issue of “Neurochemical Research” that honors Vittorio Gallo, Ph.D., for his leadership in the field of neural development and regeneration.

At a pivotal moment early in his career, Vittorio Gallo, Ph.D., was accepted to work with Professor Giulio Levi at the Institute for Cell Biology in Rome, a position that leveraged courses Gallo had taken in neurobiology and neurochemistry, and allowed him to work in the top research institute in Italy directed by the Nobel laureate, Professor Rita Levi-Montalcini.

For four years as a student and later as Levi’s collaborator, Gallo focused on amino acid neurotransmitters in the brain and mechanisms of glutamate and GABA release from nerve terminals. Those early years cemented a research focus on glutamate neurotransmission that would lead to a number of pivotal publications and research collaborations that have spanned decades.

Now, investigators from around the world who have worked most closely with Gallo penned tributes in the form of manuscripts that were assembled in a special issue of “Neurochemical Research” that honors Gallo “for his contributions to our understanding of glutamatergic and GABAergic transmission during brain development and to his leadership in the field of neural development and regeneration,” writes guest editor Arne Schousboe, of the University of Copenhagen in Denmark.

Dr. Gallo as a grad student

Vittorio Gallo, Ph.D. as a 21-year-old mustachioed graduate student.

“In spite of news headlines about competition in research and many of the negative things we hear about the research world, this shows that research is also able to create a community around us,” says Gallo, chief research officer at Children’s National Hospital and scientific director for the Children’s National Research Institute.

As just one example, he first met Schousboe 44 years ago when Gallo was a 21-year-old mustachioed graduate student.

“Research can really create a sense of community that we carry on from the time we are in training, nurture as we meet our colleagues at periodic conferences, and continue up to the present. Creating community is bi-directional: influencing people and being influenced by people. People were willing to contribute these 17 articles because they value me,” Gallo says. “This is a lot of work for the editor and the people who prepared papers for this special issue.”

In addition to Gallo publishing more than 140 peer-reviewed papers, 30 review articles and book chapters, Schousboe notes a number of Gallo’s accomplishments, including:

  • He helped to develop the cerebellar granule cell cultures as a model system to study how electrical activity and voltage-dependent calcium channels modulate granule neuron development and glutamate release.
  • He developed a biochemical/neuropharmacological assay to monitor the effects of GABA receptor modulators on the activity of GABA chloride channels in living neurons.
  • He and Maria Usowicz used patch-clamp recording and single channel analysis to demonstrate for the first time that astrocytes express glutamate-activated channels that display functional properties similar to neuronal counterparts.
  • He characterized one of the spliced isoforms of the AMPA receptor subunit gene Gria4 and demonstrated that this isoform was highly expressed in the cerebellum.
  • He and his Children’s National colleagues demonstrated that glutamate and GABA regulate oligodendrocyte progenitor cell proliferation and differentiation.
Purkinje cells

Purkinje cells are large neurons located in the cerebellum that are elaborately branched like interlocking tree limbs and represent the only source of output for the entire cerebellar cortex.

Even the image selected to grace the special issue’s cover continues the theme of continuity and leaving behind a legacy. That image of Purkinje cells was created by a young scientist who works in Gallo’s lab, Aaron Sathyanesan, Ph.D. Gallo began his career working on the cerebellum – a region of the brain important for motor control – and now studies with a team of scientists and clinician-scientists Purkinje cells’ role in locomotor adaptive behavior and how that is disrupted after neonatal brain injury.

“These cells are the main players in cerebellar circuitry,” Gallo says. “It’s a meaningful image because goes back to my roots as a graduate student and is also an image that someone produced in my lab early in his career. It’s very meaningful to me that Aaron agreed to provide this image for the cover of the special issue.”

sleeping baby

False negatives: Delayed Zika effects in babies who appeared normal at birth

sleeping baby

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants.

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants, according to a cohort study published online Jan. 6, 2020, in JAMA Pediatrics.

“These infants had no evidence of Zika deficits or microcephaly at birth. Neurodevelopmental deficits, including declines in mobility and social cognition, emerged in their first year of life even as their head circumference remained normal,” says Sarah B. Mulkey, M.D. Ph.D., a fetal/neonatal neurologist at Children’s National Hospital and the study’s first author. “About one-third of these newborns who underwent postnatal head ultrasound had nonspecific imaging results, which we believe are the first published results finding a link between subtle brain injuries and impaired neuromotor development in Zika-exposed children.”

The multi-institutional research group led by Children’s National enrolled pregnant women in Atlántico Department, which hugs the Caribbean coast of Colombia, who had been exposed to Zika, and performed a series of fetal magnetic resonance images (MRI) and ultrasounds as their pregnancies progressed.

Even though their mothers had laboratory-confirmed Zika infections, 77 out of 82 of their offspring were born with no sign of congenital Zika syndrome, a constellation of birth defects that includes severe brain abnormalities, eye problems and congenital contractures, and 70 underwent additional testing of neurodevelopment during infancy. These apparently normal newborns were born between Aug. 1, 2016, and Nov. 30, 2017, at the height of the Zika epidemic, and had normal head circumference.

When they were 4 to 8 months or 9 to 18 months of age, the infants’ neurodevelopment was evaluated using two validated tools, the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (a 50-item test of such skills as self-care, mobility, communication and social cognition) and the Alberta Infant Motor Scale (a motor examination of infants in prone, supine, sitting and standing positions). Some infants were assessed during each time point.

Women participating in the study were highly motivated, with 91% following up with appointments, even if it meant traveling hours by bus. In addition to Children’s National faculty traveling to Colombia to train staff how to administer the screening instruments, videotaped assessments, MRIs and ultrasounds were read, analyzed and scored at Children’s National. According to the study team, the U.S. scoring of Alberta Infant Motor Scale tests administered in Colombia is also unprecedented for a research study and offers the potential of remote scoring of infants’ motor skill maturity in regions of the world where pediatric specialists, like child neurologists, are lacking.

“Normally, neurodevelopment in infants and toddlers continues for years, building a sturdy neural network that they later use to carry out complex neurologic and cognitive functions as children enter school,” Dr. Mulkey adds. “Our findings underscore the recommendations by the Centers for Disease Control and Prevention (CDC) that all infants exposed to Zika in the womb undergo long-term follow-up, providing an opportunity to intervene earlier.”

An accompanying editorial by CDC staffers concurs, saying the study reported “intriguing data” that add “to the growing evidence of the need for long-term follow-up for all children with Zika virus exposure in utero to ensure they receive the recommended clinical evaluations even when no structural defects are identified at birth.”

In addition to Dr. Mulkey, study co-authors include Margarita Arroyave-Wessel, MPH, Dorothy I. Bulas, M.D., chief of Diagnostic Imaging and Radiology, JiJi Jiang, MS, Stephanie Russo, BS, Robert McCarter, ScD, research section head, design and biostatistics,  Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, and co-Senior Author, Roberta L. DeBiasi, MD, MS, chief of the Division of Pediatric Infectious Diseases, all of Children’s National; Colleen Peyton, PT, DPT, of Northwestern University; Yamil Fourzali, M.D., of Sabbag Radiologos, Barranquilla, Colombia; Michael E. Msall, M.D., of University of Chicago Comer Children’s Hospital; and co-Senior Author, Carlos Cure, M.D., BIOMELab, Barranquilla, Colombia.

Funding for the research described in this post was provided by the Thrasher Research Fund, the National Institutes of Health under award Nos. UL1TR001876 and KL2TR001877, and the Leadership Education in Neurodevelopmental and Related Disorders Training Program under grant HRSA/MCHB T73 MC11047.

Neonatology employees at Children's National

2019 at a glance: Neonatology at Children’s National

Infographic of Neonatology at Children's National
Nickie Andescavage

To understand the preterm brain, start with the fetal brain

Nickie Andescavage

“My best advice to future clinician-scientists is to stay curious and open-minded; I doubt I could have predicted my current research interest or described the path between the study of early oligodendrocyte maturation to in vivo placental development, but each experience along the way – both academic and clinical – has led me to where I am today,” Nickie Andescavage, M.D., writes.

Too often, medical institutions erect an artificial boundary between caring for the developing fetus inside the womb and caring for the newborn whose critical brain development continues outside the womb.

“To improve neonatal outcomes, we must transform our current clinical paradigms to begin treatment in the intrauterine period and continue care through the perinatal transition through strong collaborations with obstetricians and fetal-medicine specialists,” writes Nickie Andescavage, M.D., an attending in Neonatal-Perinatal Medicine at Children’s National.

Dr. Andescavage’s commentary was published online March 25, 2019, in Pediatrics Research and accompanies recently published Children’s research about differences in placental development in the setting of placental insufficiency. Her commentary is part of a new effort by Nature Publishing Group to spotlight research contributions from early career investigators.

The placenta, an organ shared by a pregnant woman and the developing fetus, plays a critical but underappreciated role in the infant’s overall health. Under the mentorship of Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain, and Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, Dr. Andescavage works with interdisciplinary research teams at Children’s National to help expand that evidence base.

While attending Cornell University as an undergraduate, Dr. Andescavage had an early interest in neuroscience and neurobehavior. As she continued her education by attending medical school at Columbia University, she corroborated an early instinct to work in pediatrics.

It wasn’t until the New Jersey native began pediatric residency at Children’s National that those complementary interests coalesced into a focus on brain autoregulation and autonomic function in full-term and preterm infants and imaging the brains of both groups. In normal, healthy babies the autonomic nervous system regulates heart rate, blood pressure, digestion, breathing and other involuntary activities. When these essential controls go awry, babies can struggle to survive and thrive.

“My best advice to future clinician-scientists is to stay curious and open-minded; I doubt I could have predicted my current research interest or described the path between the study of early oligodendrocyte maturation to in vivo placental development, but each experience along the way – both academic and clinical – has led me to where I am today,” Dr. Andescavage writes in the commentary.