Neonatology

preterm brain scans

Early lipids boost brain growth for vulnerable micro-preemies

preterm brain scans

Segmentation of a preterm brain T2-weighted MRI image at 30 gestational weeks [green=cortical grey matter; blue=white matter; grey=deep grey matter; cyan=lateral ventricle; purple=cerebellum; orange=brainstem; red=hippocampus; yellow=cerebrospinal fluid].

Dietary lipids, already an important source of energy for tiny preemies, also provide a much-needed brain boost by significantly increasing global brain volume as well as increasing volume in regions involved in motor activities and memory, according to research presented during the Pediatric Academic Societies 2019 Annual Meeting.

“Compared with macronutrients like carbohydrates and proteins, lipid intake during the first month of life is associated with increased overall and regional brain volume for micro-preemies,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National and senior author. “Using non-invasive magnetic resonance imaging, we see increased volume in the cerebellum by 2 weeks of age. And at four weeks of life, lipids increase total brain volume and boost regional brain volume in the cerebellum, amygdala-hippocampus and brainstem.”

The cerebellum is involved in virtually all physical movement and enables coordination and balance. The amygdala processes and stores short-term memories. The hippocampus manages emotion and mood. And the brainstem acts like a router, passing messages from the brain to the rest of the body, as well as enabling essential functions like breathing, a steady heart rate and swallowing.

According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. babies is born preterm, or before 37 weeks gestation. Regions of the brain that play vital roles in complex cognitive and motor activities experience exponential growth late in pregnancy, making the developing brains of preterm infants particularly vulnerable to injury and impaired growth.

Children’s research faculty examined the impact of lipid intake in the first month of life on brain volumes for very low birth weight infants, who weighed 1,500 grams or less at birth. These micro-preemies are especially vulnerable to growth failure and neurocognitive impairment after birth.

The team enrolled 68 micro-preemies who were 32 weeks gestational age and younger when they were admitted to Children’s neonatal intensive care unit during their first week of life. They measured cumulative macronutrients – carbohydrates, proteins, lipids and calories – consumed by these newborns at 2 and 4 weeks of life. Over years, Limperopoulos’ lab has amassed a large database of babies who were born full-term; this data provides unprecedented insights into normal brain development and will help to advance understanding of brain development in high-risk preterm infants.

“Even after controlling for average weight gain and other health conditions, lipid intake was positively associated with cerebellar and brainstem volumes in very low birthweight preterm infants,” adds Katherine M. Ottolini, the study’s lead author.

According to Limperopoulos, Children’s future research will examine the optimal timing and volume of lipids to boost neurodevelopment for micro-preemies.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Early lipid intake improves brain growth in premature infants.”
    • Saturday, April 27, 2019, 1:15-2:30 p.m. (EST)

Katherine M. Ottolini, lead author; Nickie Andescavage, M.D., Attending, Neonatal-Perinatal Medicine and co-author; Kushal Kapse, research and development staff engineer and co-author; and Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain and senior author, all of Children’s National.

newborn in incubator

In HIE lower heart rate variability signals stressed newborns

newborn in incubator

In newborns with hypoxic-ischemic encephalopathy (HIE), lower heart rate variability correlates with autonomic manifestations of stress shortly after birth, underscoring the value of this biomarker, according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Tethered to an array of machines that keep their bodies nourished, warm and alive, newborns with health issues can’t speak. But Children’s research teams are tapping into what the machinery itself says, looking for insights into which vulnerable infants are most in need of earlier intervention.

Heart rate variability – or the variation between heartbeats – is a sign of health. Our autonomic nervous system constantly sends signals to adjust our heart rate under normal conditions. We can measure heart rate variability non-invasively, providing a way to detect potential problems with the autonomic nervous system as a sensitive marker of health in critically ill newborns,” says An N. Massaro, M.D., co-Director of Research for the Division of Neonatology at Children’s National, and the study’s senior author. “We’re looking for validated markers of brain injury in babies with HIE, and our study helps to support heart rate variability as one such valuable physiological biomarker.”

In most newborns, the autonomic nervous system reliably and automatically receives information about the body and the outside world and, in response, controls essential functions like blood pressure, body temperature, how quickly the baby breathes and how rapidly the newborn’s heart beats. The sympathetic part stimulates body processes, while the parasympathetic part inhibits body processes. When the nervous system’s internal auto-pilot falters, babies can suffer.

The Children’s team enrolled infants with HIE in the prospective, observational study. (HIE is brain damage that occurs with full-term babies who experience insufficient blood and oxygen flow to the brain around the time they are born.) Fifteen percent had severe encephalopathy. Mean age of babies in the observational study was 38.9 weeks gestation. Their median Apgar score at five minutes was 3; the 0-9 Apgar range indicates how ready newborns are for the rigors of life outside the womb.

The team analyzed heart rate variability metrics for three time periods:

  • The first 24 to 27 hours of life
  • The first three hours after babies undergoing therapeutic cooling were rewarmed and
  • The first three hours after babies’ body temperature had returned to normal.

They correlated the relationship between heart rate variability for 68 infants during at least one of these time periods with the stress z-score from the NICU Network Neurobehavioral Scale. The scale is a standardized assessment of newborn’s neurobehavioral integrity. The stress summary score indicates a newborn’s overall stress response, and six test items specifically relate to autonomic function.

“Alpha exponent and root mean square in short timescales, root mean square in long timescales, as well as low and high frequency powers positively correlated with stress scores and, even after adjusting for covariates, remained independently associated at 24 hours,” says Allie Townsend, the study’s lead author.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Heart rate variability (HRV) measures of autonomic nervous system (ANS) function relates to neonatal neurobehavioral manifestations of stress in newborn with hypoxic-ischemic encephalopathy (HIE).”
    • Monday, April 29, 2019, 5:45 p.m. (EST)

Allie Townsend, lead author; Rathinaswamy B. Govindan, Ph.D., staff scientist, Advanced Physiological Signals Processing Lab and co-author; Penny Glass, Ph.D., director, Child Development Program and co-author; Judy Brown, co-author; Tareq Al-Shargabi, M.S., co-author; Taeun Chang, M.D., director, Neonatal Neurology and Neonatal Neurocritical Care Program and co-author; Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine and co-author; An N. Massaro, M.D., co-Director of Research for the Division of Neonatology and senior author, all of Children’s National.

Claire Marie Vacher

Placental function linked to brain injuries associated with autism

Claire Marie Vacher

“We saw long-term cerebellar white matter alterations in male experimental models, and behavioral testing revealed social impairments and increased repetitive behaviors, two hallmark features of ASD,” says Claire-Marie Vacher, Ph.D., lead study author.

Allopregnanolone (ALLO), a hormone made by the placenta late in pregnancy, is such a potent neurosteroid that disrupting its steady supply to the developing fetus can leave it vulnerable to brain injuries associated with autism spectrum disorder (ASD), according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

In order to more effectively treat vulnerable babies, the Children’s research team first had to tease out what goes wrong in the careful choreography that is pregnancy. According to the Centers for Disease Control and Prevention, about 1 in 10 babies is born preterm, before 37 weeks of gestation. Premature birth is a major risk factor for ASD.

The placenta is an essential and understudied organ that is shared by the developing fetus and the pregnant mother, delivering oxygen, glucose and nutrients and ferrying out waste products. The placenta also delivers ALLO, a progesterone derivative, needed to ready the developing fetal brain for life outside the womb.

ALLO ramps up late in gestation. When babies are born prematurely, their supply of ALLO stops abruptly. That occurs at the same time the cerebellum – a brain region essential for motor coordination, posture, balance and social cognition– typically undergoes a dramatic growth spurt.

“Our experimental model demonstrates that losing placental ALLO alters cerebellar development, including white matter development,” says Anna Penn, M.D., Ph.D., a neonatologist in the divisions of Neonatology and Fetal Medicine, and a developmental neuroscientist at Children’s National. “Cerebellar white matter development occurs primarily after babies are born, so connecting a change in placental function during pregnancy with lingering impacts on later brain development is a particularly striking result.”

The research team created a novel experimental model in which the gene encoding the enzyme responsible for producing ALLO is deleted in the placenta. They compared these preclinical models with a control group and performed whole brain imaging and RNAseq gene expression analyses for both groups.

“We saw long-term cerebellar white matter alterations in male experimental models, and behavioral testing revealed social impairments and increased repetitive behaviors, two hallmark features of ASD,” says Claire-Marie Vacher, Ph.D., lead study author. “These male-specific outcomes parallel the increased risk of brain injury and ASD we see in human babies born prematurely.”

ALLO binds to specific GABA receptors, which control most inhibitory signaling in the nervous system.

“Our findings provide a new way to frame poor placental function: Subtle but significant changes in utero may set in motion neurodevelopmental disorders that children experience later in life,” adds Dr. Penn, the study’s senior author. “Future directions for our research could include identifying new targets in the placenta or brain that could be amenable to hormone supplementation, opening the potential for earlier treatment for high-risk fetuses.”

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Placental allopregnanolone loss alters postnatal cerebellar development and function.”
    • Sunday, April 28, 2019, 5:15 p.m. to 5:30 p.m. (EST)

Claire-Marie Vacher, Ph.D., lead author; Jackie Salzbank, co-author; Helene Lacaille, co-author; Dana Bakalar, co-author; Jiaqi O’Reilly, co-author; and Anna Penn, M.D., Ph.D., a neonatologist in the divisions of Neonatology and Fetal Medicine, developmental neuroscientist and senior study author.

Catherine Limperopoulos

Breastfeeding boosts metabolites important for brain growth

Catherine Limperopoulos

“Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites that may play a critical role for growth and explain what makes breastfeeding beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D.

Micro-preemies who primarily consume breast milk have significantly higher levels of metabolites important for brain growth and development, according to sophisticated imaging conducted by an interdisciplinary research team at Children’s National.

“Our previous research established that vulnerable preterm infants who are fed breast milk early in life have improved brain growth and neurodevelopmental outcomes. It was unclear what makes breastfeeding so beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National. “Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites essential for growth and answer that lingering question.”

According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. infants is born preterm. The Children’s research team presented their findings during the Pediatric Academic Societies 2019 Annual Meeting.

The research-clinicians enrolled babies who were very low birthweight (less than 1,500 grams) and 32 weeks gestational age or younger at birth when they were admitted to Children’s neonatal intensive care unit in the first week of life. The team gathered data from the right frontal white matter and the cerebellum – a brain region that enables people to maintain balance and proper muscle coordination and that supports high-order cognitive functions.

Each chemical has its own a unique spectral fingerprint. The team generated light signatures for key metabolites and calculated the quantity of each metabolite. Of note:

  • Cerebral white matter spectra showed significantly greater levels of inositol (a molecule similar to glucose) for babies fed breast milk, compared with babies fed formula.
  • Cerebellar spectra had significantly greater creatine levels for breastfed babies compared with infants fed formula.
  • And the percentage of days infants were fed breast milk was associated with significantly greater levels of both creatine and choline, a water soluble nutrient.

“Key metabolite levels ramp up during the times babies’ brains experience exponential growth,” says Katherine M. Ottolini, the study’s lead author. “Creatine facilitates recycling of ATP, the cell’s energy currency. Seeing greater quantities of this metabolite denotes more rapid changes and higher cellular maturation. Choline is a marker of cell membrane turnover; when new cells are generated, we see choline levels rise.”

Already, Children’s National leverages an array of imaging options that describe normal brain growth, which makes it easier to spot when fetal or neonatal brain development goes awry, enabling earlier intervention and more effective treatment. “Proton magnetic resonance spectroscopy may serve as an important additional tool to advance our understanding of how breastfeeding boosts neurodevelopment for preterm infants,” Limperopoulos adds.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Improved cerebral and cerebellar metabolism in breast milk-fed VLBW infants.”
    • Monday, April 29, 2019, 3:30–3:45 p.m. (EST)

Katherine M. Ottolini, lead author; Nickie Andescavage, M.D., Attending, Neonatal-Perinatal Medicine and co-author; Kushal Kapse, research and development staff engineer and co-author; Sudeepta Basu, M.D., neonatologist and co-author; and Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain and senior author, all of Children’s National.

An-Massaro

Looking for ‘help’ signals in the blood of newborns with HIE

An Massaro

“This data support our hypothesis that a panel of biomarkers – not a one-time test for a single biomarker – is needed to adequately determine the risk and timing of brain injury for babies with HIE,” says An N. Massaro, M.D.

Measuring a number of biomarkers over time that are produced as the body responds to inflammation and injury may help to pinpoint newborns who are more vulnerable to suffering lasting brain injury due to disrupted oxygen delivery and blood flow, according to research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Hypoxic-ischemic encephalopathy (HIE) happens when blood and oxygen flow are disrupted around the time of birth and is a serious birth complication for full-term infants. To lessen the chance of these newborns suffering permanent brain injury, affected infants undergo therapeutic cooling, which temporarily lowers their body temperatures.

“Several candidate blood biomarkers have been investigated in HIE but we still don’t have one in clinical use.  We need to understand how these markers change over time before we can use them to direct care in patients,” says An N. Massaro, M.D., co-director of the Neonatal Neurocritical Care Program at Children’s National and the study’s senior author. “The newborns’ bodies sent out different ‘help’ signals that we detected in their bloodstream, and the markers had strikingly different time courses. A panel of plasma biomarkers has the potential to help us identify infants most in need of additional interventions, and to help us understand the most optimal timing for those interventions.”

Past research has keyed in on inflammatory cytokines and Tau protein as potential biomarkers of brain injury for infants with HIE who are undergoing therapeutic cooling. The research team led by Children’s faculty wanted to gauge which time periods to measure such biomarkers circulating in newborns’ bloodstreams. They enrolled 85 infants with moderate or severe HIE and tapped unused blood specimens that had been collected as cooling began, as well as 12, 24, 72 and 96 hours later. The infants’ mean gestational age was 38.7 weeks, their mean birth weight was about 7 pounds (3.2 kilograms), and 19% had severe brain disease (encephalopathy).

Cytokines – chemicals like Interleukin (IL) 6, 8 and 10 that regulate how the body responds to infection, inflammation and trauma – peaked in the first 24 hours of cooling for most of the newborns. However, the highest measure of Tau protein for the majority of newborns was during or after the baby’s temperature was restored to normal.

“After adjusting for clinical severity of encephalopathy and five-minute Apgar scores, IL-6, IL-8 and IL-10 predicted adverse outcomes, like severe brain injury or death, as therapeutic hypothermia began. By contrast, Tau protein measurements predicted adverse outcomes during and after the infants were rewarmed,” Dr. Massaro says.

IL-6 and IL-8 proteins are pro-inflammatory cytokines while IL-10 is considered anti-inflammatory.  These chemicals are released as a part of the immune response to brain injury. Tau proteins are abundant in nerve cells and stabilize microtubules.

“This data support our hypothesis that a panel of biomarkers – not a one-time test for a single biomarker – is needed to adequately determine the risk and timing of brain injury for babies with HIE,” she adds.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Serial plasma biomarkers of brain injury in infants with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH).”
    • Saturday, April 27, 2019, 6 p.m. (EST)

Meaghan McGowan, lead author; Alexandra C. O’Kane, co-author; Gilbert Vezina, M.D.,  director, Neuroradiology Program and co-author; Tae Chang, M.D., director, Neonatal Neurology Program and co-author; and An N. Massaro, M.D., co-director of the Neonatal Neurocritical Care Program and senior author; all of Children’s National; and co-author Allen Everett, of Johns Hopkins School of Medicine.

Ololade Okito

Parents of older, healthier newborns with less social support less resilient

Ololade Okito

“We know that having a child hospitalized in the NICU can be a high-stress time for families,” says Ololade Okito, M.D., lead author of the cross-sectional study. “The good news is that as parental resiliency scores rise, we see a correlation with fewer symptoms of depression and anxiety.

Parents of older, healthier newborns who had less social support were less resilient during their child’s hospitalization in the neonatal intensive care unit (NICU), a finding that correlates with more symptoms of depression and anxiety, according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Resiliency is the natural born, yet adaptable ability of people to bounce back in the face of significant adversity. Published research indicates that higher resilience is associated with reduced psychological distress, but the phenomenon had not been studied extensively in parents of children hospitalized in a NICU.

“We know that having a child hospitalized in the NICU can be a high-stress time for families,” says Ololade Okito, M.D., lead author of the cross-sectional study. “The good news is that as parental resiliency scores rise, we see a correlation with fewer symptoms of depression and anxiety. Parents who feel they have good family support also have higher resilience scores.”

The project is an offshoot of a larger study examining the impact of peer mentoring by other NICU parents who have experienced the same emotional rollercoaster ride as their tiny infants sometimes thrived and other times struggled.

The research team enrolled 35 parents whose newborns were 34 weeks gestation and younger and administered a battery of validated surveys, including:

Forty percent of these parents had high resilience scores; parents whose infants were a mean of 27.3 gestational weeks and who had more severe health challenges reported higher resilience. Another 40% of these parents had elevated depressive symptoms, while 31% screened positive for anxiety. Parental distress impairs the quality of parent-child interactions and long-term child development, the research team writes.

“Higher NICU-related stress correlates with greater symptoms of depression and anxiety in parents,” says Lamia Soghier, M.D., MEd, medical director of Children’s neonatal intensive care unit and the study’s senior author. “Specifically targeting interventions to these parents may help to improve their resilience, decrease the stress of parenting a child in the NICU and give these kids a healthier start to life.”

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Parental resilience and psychological distress in the neonatal intensive care unit (PARENT) study”
    • Tuesday, April 30, 2019, 7:30 a.m. (EST)

Ololade Okito, M.D., lead author; Yvonne Yui, M.D., co-author; Nicole Herrera, MPH, co-author; Randi Streisand, Ph.D., chief, Division of Psychology and Behavioral Health, and co-author; Carrie Tully, Ph.D., clinical psychologist and co-author; Karen Fratantoni, M.D., MPH, medical director, Complex Care Program, and co-author; and Lamia Soghier, M.D., MEd, medical unit director, neonatal intensive care unit, and senior author; all of Children’s National.

DNA Molecule

Decoding cellular signals linked to hypospadias

DNA Molecule

“By advancing our understanding of the genetic causes and the anatomic differences among patients, the real goal of this research is to generate knowledge that will allow us to take better care of children with hypospadias,” Daniel Casella, M.D. says.

Daniel Casella, M.D., a urologist at Children’s National, was honored with an AUA Mid-Atlantic Section William D. Steers, M.D. Award, which provides two years of dedicated research funding that he will use to better understand the genetic causes for hypospadias.

With over 7,000 new cases a year in the U.S., hypospadias is a common birth defect that occurs when the urethra, the tube that transports urine out of the body, does not form completely in males.

Dr. Casella has identified a unique subset of cells in the developing urethra that have stopped dividing but remain metabolically active and are thought to represent a novel signaling center. He likens them to doing the work of a construction foreman. “If you’re constructing a building, you need to make sure that everyone follows the blueprints.  We believe that these developmentally senescent cells are sending important signals that define how the urethra is formed,” he says.

His project also will help to standardize the characterization of hypospadias. Hypospadias is classically associated with a downward bend to the penis, a urethra that does not extend to the head of the penis and incomplete formation of the foreskin. Still, there is significant variability among patients’ anatomy and to date, no standardized method for documenting hypospadias anatomy.

“Some surgeons take measurements in the operating room, but without a standardized classification system, there is no definitive way to compare measurements among providers or standardize diagnoses from measurements that every surgeon makes,” he adds. “What one surgeon may call ‘distal’ may be called ‘midshaft’ by another.” (With distal hypospadias, the urethra opening is near the penis head; with midshaft hypospadias, the urethra opening occurs along the penis shaft.)

“By advancing our understanding of the genetic causes and the anatomic differences among patients, the real goal of this research is to generate knowledge that will allow us to take better care of children with hypospadias,” he says.

Parents worry about lingering social stigma, since some boys with hypospadias are unable to urinate while standing, and in older children the condition can be associated with difficulties having sex. Surgical correction of hypospadias traditionally is performed when children are between 6 months to 1 year old.

When reviewing treatment options with family, “discussing the surgery and postoperative care is straight forward. The hard part of our discussion is not having good answers to questions about long-term outcomes,” he says.

Dr. Casella’s study hopes to build the framework to enable that basic research to be done.

“Say we wanted to do a study to see how patients are doing 15-20 years after their surgery.  If we go to their charts now, often we can’t accurately describe their anatomy prior to surgery.  By establishing uniform measurement baselines, we can accurately track long-term outcomes since we’ll know what condition that child started with and where they ended up,” he says.

Dr. Casella’s research project will be conducted at Children’s National under the mentorship of Eric Vilain, M.D., Ph.D., an international expert in sex and genitalia development; Dolores J. Lamb, Ph.D., HCLD, an established leader in urology based at Weill Cornell Medicine; and Marius George Linguraru, DPhil, MA, MSc, an expert in image processing and artificial intelligence.

Mark Batshaw

40 years, 8 editions: Writing “Children With Disabilities”

Mark Batshaw

Forty years ago, Mark L. Batshaw, M.D., almost singlehandedly wrote a 23-chapter first edition that ran about 300 pages. Now Dr. Batshaw’s tome, “Children With Disabilities,” is in its eighth edition, and this new volume is almost 1,000 pages, with 42 chapters, two co-editors and over 35 authors from Children’s National.

Back in 1978, Mark L. Batshaw, M.D., was a junior faculty member at John’s Hopkins University School of Medicine. In the evenings he taught a course in the university’s School of Education  titled “The Medical and Physical Aspects of the Handicapped Child,” for Master’s level special education students. Because no textbook at that time focused on that specific topic, Batshaw developed his own slide set.

“At the end of the first year of teaching the course my students said ‘You really ought to consider writing a text book based on your slides to help us move forward,’ ” Dr. Batshaw recalls. The father of three carved out time by writing on weekends and at night, cutting back on sleep.

His first goal was to create a textbook that would serve as a curriculum for a series of courses that would be taught at universities to specialists who work with children with disabilities, including social workers, physical and occupational therapists, speech and language pathologists, special education teachers, nurses, doctors and dentists.

“I wanted to cover the whole range of disabilities and divided the book initially into a series of sections, including embryology, to help students understand what can go wrong in fetal development to lead to a developmental disability; and chapters on each developmental disability, including autism, attention-deficit/hyperactivity disorder (ADHD), cerebral palsy, learning disabilities and traumatic brain injury,” he says. “The third section was devoted to available treatments, including occupational and physical therapy, speech language therapy, nutrition and medications. The final section focused on outcomes.”

His second aim was for the book to serve as a reference text for professionals in the field. The 33-year-old contacted a brand-new new publisher, Paul H. Brookes Publishing Co., that focused on special education. “They took a chance on me, and I took a chance on them,” he says.

Forty years ago, he almost singlehandedly produced a 23-chapter first edition that ran about 300 pages. Now Dr. Batshaw’s tome is in its eighth edition, and this new volume is almost 1,000 pages. And, rather than being its sole author, Dr. Batshaw enlisted two co-editors and at least five dozen authors who contributed specialty expertise in genetic counseling, social work, physical and occupational therapy, medicine and nursing. His daughter, Elissa, a special education teacher and school psychologist, authored a chapter about special education services, and his son, Drew, an executive at a start-up company, contributed autobiographical letters about the effect ADHD has had on his life.

The book, “Children With Disabilities,” also includes:

  • A glossary of medical terms so that as the reader reviews patient reports they can easily look up an unfamiliar term
  • An appendix on commonly used drugs to treat children with disabilities in order to look up the medicine by name and see the range of doses
  • An appendix devoted to different syndromes children might have
  • A reference section with organizations and foundations that help children with disabilities
  • A web site with sections designed for students and other content designed for teachers with thought questions to guide practical use of information in each chapter and more than 450 customizable PowerPoint slides for download
  • Call-out boxes for interdisciplinary team members, such as genetic counselors, explaining the roles they serve and their educational background, and
  • Excerpts of recent research articles.

“The students say they don’t sell the book. Usually when students have a textbook, they try to sell it second hand after the course ends,” explains Dr. Batshaw, now Executive Vice President, Physician-in-Chief and Chief Academic Officer at Children’s National. “Instead, students keep it and use it as a practical reference as they become professionals in their field. It has had the impact I had hoped for both as a textbook and a reference book: They say they refer to it when they have patients with a particular disorder they’re not used to treating to read up on it.”

Now a bestseller, there are more than 200,000 copies in print, including Portuguese and Ukrainian translations. “It didn’t start that way. It grew organically,” he says.

In addition to Dr. Batshaw, Children’s contributors to “Children With Disabilities” include Nicholas Ah Mew, M.D., pediatric geneticist; Nickie N. Andescavage, M.D., neonatologist; Mackenzie E. Brown, D.O., fellow in Pediatric Rehabilitation Medicine; Justin M. Burton, M.D., chief, Division of Pediatric Rehabilitation Medicine; Gabrielle Sky Cardwell, BA, clinical research assistant; Catherine Larsen Coley, PT, DPT, PCS, physical therapist; Laurie S. Conklin, M.D., pediatric gastroenterologist; Denice Cora-Bramble, M.D., MBA, executive vice president and chief medical officer; Heather de Beaufort, M.D., pediatric ophthalmologist; Dewi Frances T. Depositario-Cabacar, M.D., pediatric neurologist; Lina Diaz-Calderon, M.D., fellow in Pediatric Gastroenterology; Olanrewaju O. Falusi, M.D., associate medical director of municipal and regional affairs, Child Health Advocacy Institute; Melissa Fleming, M.D., pediatric rehabilitation specialist; William Davis Gaillard, M.D., chief Division of Epilepsy, Neurophysiology and Critical Care; Satvika Garg, Ph.D., occupational therapist; Virginia C. Gebus, R.N., MSN, APN, CNSC, nutritionist; Monika K. Goyal, M.D., MSCE, assistant chief, Division of Emergency Medicine; Andrea Gropman, M.D., chief, Division of Neurodevelopmental Pediatrics and Neurogenetics, geneticist and Neurodevelopmental pediatrician; Mary A. Hadley, BS, senior executive assistant; Susan Keller, MLS., MS-HIT, research librarian; Lauren Kenworthy, Ph.D., director, Center for Autism Spectrum Disorders; Monisha S. Kisling, MS, CGC, genetic counselor; Eyby Leon, M.D., pediatric geneticist; Erin MacLeod, Ph.D., RD, LD, director, Metabolic Nutrition; Margaret B. Menzel, MS, CGC, genetic counselor; Shogo John Miyagi, Ph.D., PharmD, BCPPS, Pediatric Clinical Pharmacology fellow; Mitali Y. Patel, DDS, program director, Pediatric Dentistry; Deborah Potvin, Ph.D., neuropsychologist; Cara E. Pugliese, Ph.D., clinical psychologist; Khodayar Rais-Bahrami, M.D., neonatologist and director, Neonatal-Perinatal Medicine Fellowship Program; Allison B. Ratto, Ph.D., clinical psychologist; Adelaide S. Robb, M.D., chief, Division of Psychiatry and Behavioral Sciences; Joseph Scafidi, D.O., neonatal neurologist; Erik Scheifele, D.M.D., chief, Division of Oral Health; Rhonda L. Schonberg, MS, CGC, genetic counselor; Billie Lou Short, M.D., chief, Division of Neonatology; Kara L. Simpson, MS, CGC, genetic counselor; Anupama Rao Tate, D.M.D., MPH, pediatric dentist; Lisa Tuchman, M.D., chief, Division of Adolescent and Young Adult Medicine; Johannes N. van den Anker, M.D., Ph.D., FCP, chief, Division of Clinical Pharmacology, Vice Chair of Experimental Therapeutics; Miriam Weiss, CPNP-PC, nurse practitioner; and Tesfaye Getaneh Zelleke, M.D., pediatric neurologist.

Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents:
Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students:
Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty:
Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students:
Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents:
Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students:
Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty:
Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff:
Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents:
Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students:
Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty:
Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff:
Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents:
Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students:
Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Beth Tarini

Getting to know SPR’s future President, Beth Tarini, M.D., MS

Beth Tarini

Quick. Name four pillar pediatric organizations on the vanguard of advancing pediatric research.

Most researchers and clinicians can rattle off the names of the Academic Pediatric Association, the American Academy of Pediatrics and the American Pediatric Society. But that fourth one, the Society for Pediatric Research (SPR), is a little trickier. While many know SPR, a lot of research-clinicians simply do not.

Over the next few years, Beth A. Tarini, M.D., MS, will make it her personal mission to ensure that more pediatric researchers get to know SPR and are so excited about the organization that they become active members. In May 2019 Dr. Tarini becomes Vice President of the society that aims to stitch together an international network of interdisciplinary researchers to improve kids’ health. Four-year SPR leadership terms begin with Vice President before transitioning to President-Elect, President and Past-President, each for one year.

Dr. Tarini says she looks forward to working with other SPR leaders to find ways to build more productive, collaborative professional networks among faculty, especially emerging junior faculty. “Facilitating ways to network for research and professional reasons across pediatric research is vital – albeit easier said than done. I have been told I’m a connector, so I hope to leverage that skill in this new role,” says Dr. Tarini, associate director for Children’s Center for Translational Research.

“I’m delighted that Dr. Tarini was elected to this leadership position, and I am impressed by her vision of improving SPR’s outreach efforts,” says Mark Batshaw, M.D., Executive Vice President, Chief Academic Officer and Physician-in-Chief at Children’s National. “Her goal of engaging potential members in networking through a variety of ways – face-to-face as well as leveraging digital platforms like Twitter, Facebook and LinkedIn – and her focus on engaging junior faculty will help strengthen SPR membership in the near term and long term.”

Dr. Tarini adds: “Success to me would be leaving after four years with more faculty – especially junior faculty – approaching membership in SPR with the knowledge and enthusiasm that they bring to membership in other pediatric societies.”

SPR requires that its members not simply conduct research, but move the needle in their chosen discipline. In her research, Dr. Tarini has focused on ensuring that population-based newborn screening programs function efficiently and effectively with fewer hiccups at any place along the process.

Thanks to a heel stick to draw blood, an oxygen measurement, and a hearing test, U.S. babies are screened for select inherited health conditions, expediting treatment for infants and reducing the chances they’ll experience long-term health consequences.

“The complexity of this program that is able to test nearly all 4 million babies in the U.S. each year is nothing short of astounding. You have to know the child is born – anywhere in the state – and then between 24 and 48 hours of birth you have to do testing onsite, obtain a specific type of blood sample, send the blood sample to an off-site lab quickly, test the sample, find the child if the test is out of range, get the child evaluated and tested for the condition, then send them for treatment. Given the time pressures as well as the coordination of numerous people and organizations, the fact that this happens routinely is amazing. And like any complex process, there is always room for improvement,” she says.

Dr. Tarini’s research efforts have focused on those process improvements.

As just one example, the Advisory Committee on Heritable Disorders in Newborns and Children, a federal advisory committee on which she serves, was discussing how to eliminate delays in specimen processing to provide speedier results to families. One possible solution floated was to open labs all seven days, rather than just five days a week. Dr. Tarini advocated for partnering with health care engineers who could help model ways to make the specimen transport process more efficient, just like airlines and mail delivery services. A more efficient and effective solution was to match the specimen pick-up and delivery times more closely with the lab’s operational times – which maximizes lab resources and shortens wait times for parents.

Conceptual modeling comes so easily for her that she often leaps out of her seat mid-sentence, underscoring a point by jotting thoughts on a white board, doing it so often that her pens have run dry.

“It’s like a bus schedule: You want to find a bus that not only takes you to your destination but gets you there on time,” she says.

Dr. Tarini’s current observational study looks for opportunities to improve how parents in Minnesota and Iowa are given out-of-range newborn screening test results – especially false positives – and how that experience might shake their confidence in their child’s health as well as heighten their own stress level.

“After a false positive test result, are there parents who walk away from newborn screening with lingering stress about their child’s health? Can we predict who those parents might be and help them?” she asks.

Among the challenges is the newborn screening occurs so quickly after delivery that some emotionally and physically exhausted parents may not remember it was done. Then they get a call from the state with ominous results. Another challenge is standardizing communication approaches across dozens of birthing centers and hospitals.

“We know parents are concerned after receiving a false positive result, and some worry their infant remains vulnerable,” she says. “Can we change how we communicate – not just what we say, but how we say it – to alleviate those concerns?”

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. She has contributed to myriad published works, including:

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.

Dr. Kurt Newman in front of the capitol building

Kurt Newman, M.D., shares journey as a pediatric surgeon in TEDx Talk

Kurt Newman, M.D., president and chief executive officer of Children’s National, shares his poignant journey as a pediatric surgeon, offering a new perspective for approaching the most chronic and debilitating health conditions. In this independently-organized TEDx event, Dr. Newman also shares his passion for Children’s National and the need to increase pediatric innovations in medicine.

Robin Steinhorn in the NICU

Coming together as a team for the good of the baby

Robin Steinhorn in the NICU

Children’s National has a new program to care for children who have severe bronchopulmonary dysplasia, a serious complication of preterm birth.

Around the 1-year-old’s crib is a tight circle of smiling adults, and at the foot of his bed is a menagerie of plush animals, each a different color and texture and shape to spark his curiosity and sharpen his intellect.

Gone are the days a newborn with extremely complex medical needs like Elijah would transfer from the neonatal intensive care unit (NICU) to the pediatric intensive care unit and transition through a couple of other hospital units by the time he was discharged. Gone are the days when he’d see a variety of new physician faces at every stop. And gone are the days he’d be confined to his room, divorced from the sights and sounds and scents of the outside world, stimulation that helps little baby’s neural networks grow stronger.

Children’s National has a new program designed to meet the unique needs of children like Elijah who have severe bronchopulmonary dysplasia (BPD), a common complication of preterm birth.

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D. Dr. Steinhorn is senior vice president of the Center for Hospital-Based Specialties and one of Children’s multidisciplinary team members who visited Elijah’s bed twice weekly during his lengthy hospitalization and who continues to see him regularly during outpatient visits.

“The pulmonologist, the neonatologist, the respiratory therapist, the physical therapist, the dietitian, the cardiologist – we all come as a team to work together for the good of the baby,” Dr. Steinhorn adds. “We stick with these babies through thick and thin. We will stick with that baby with this team and this location until they are ready to go home – and beyond.”

BPD, a serious lung condition, mostly affects extremely low birthweight preterm babies whose lungs were designed to continue developing inside the womb until the pregnancy reaches full term. Often born months before their due dates, these extremely vulnerable newborns have immature organs, including the lungs, which are not ready for the task of breathing air. Children’s program targets infants who experience respiratory failure from BPD. The respiratory support required for these infants ranges from oxygen delivered through a nasal cannula to mechanical ventilators.

Robin Steinhorn and Colleague

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D.

About 1 percent of all preterm births are extremely low birthweight, or less than 1,500 grams. Within that group, up to 40 percent will develop BPD. While they represent a small percentage of overall births, these very sick babies need comprehensive, focused care for the first few years of their lives. And some infants with severe BPD also have pulmonary hypertension which, at Children’s National, is co-managed by cardiology and pulmonary specialists.

Children’s BPD team not only focuses on the child’s survival and medical care, they focus on the neurodevelopmental and social care that a baby needs to thrive. From enhanced nutrition to occupational and physical therapy to a regular sleep cycle, the goal is to help these babies achieve their full potential.

“These babies are at tremendous risk for long-term developmental issues. Everything we do is geared to alleviate that,” adds John T. Berger III, M.D., director of Children’s Pulmonary Hypertension Program.

“Our NICU care is more focused, comprehensive and consistent,” agrees Mariam Said, M.D., a neonatologist on the team. “We’re also optimizing the timing of care and diagnostic testing that will directly impact health outcomes.”

Leaving no detail overlooked, the team also ensures that infants have age-appropriate developmental stimuli, like toys, and push for early mobility by getting children up and out of bed and into a chair or riding in a wagon.

“The standard approach is to keep the baby in a room with limited physical or occupational therapy and a lack of appropriate stimulation,” says Geovanny Perez, M.D., a pulmonologist on the team. “A normal baby interacts with their environment inside the home and outside the home. We aim to mimic that within the hospital environment.”

Dr. Steinhorn, who had long dreamed of creating this comprehensive team care approach adds that “it’s been so gratifying to see it adopted and embraced so quickly by Children’s NICU caregivers.”

toddler nursing

Newborns with suspected food allergies breastfed significantly longer

toddler nursing

Mothers whose newborns had suspected food allergies reported breastfeeding them significantly longer than women whose infants had no adverse reactions after food exposure, according to preliminary research led by Karen A. Robbins, M.D., and presented during the American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting.

According to the Centers for Disease Control and Prevention (CDC), food allergies affect 4 to 6 percent of U.S. children, making such allergies a growing public health concern. Researchers are attempting to learn more about the interplay between food allergies and what, when and how children eat to inform allergy-prevention efforts. Little is known about the association between perceived food allergies, intolerance or hypersensitivity among babies eating their first bites of solid food and how long they’re breastfed.

Dr. Robbins and colleagues analyzed data gathered through a longitudinal study led by the Food and Drug Administration (FDA) and the CDC from 2005 to 2007. The Infant Feeding Practices Study II tracked diet and feeding practices of about 2,000 women late in their pregnancies and followed their babies’ diets through the first year of life.

Some 2,586 breastfeeding mothers in the study completed surveys when their infants were 4, 9 and 12 months old. The women were asked whether there were problems caused by food, such as an allergic reaction, sensitivity or intolerance. The majority of these infants (84.6 percent) had no suspected allergic reaction to either food they ate on their own or to food they were exposed to via breastmilk. The mothers reported that nearly 11 percent of infants reacted to something they ate; 2.4 percent reacted to food products they were exposed to via breastmilk; and 2.4 percent reacted to both food they consumed directly or were exposed to via breastfeeding. They also found:

  • Infants with suspected food allergies after exposure to food their mothers ate were breastfed a mean of 45.8 weeks.
  • Infants with food intolerance after both exposure to food their mother consumed and food they ate themselves were breastfed a mean of 40.2 weeks.

That contrasts with infants with no concern for food reactions, who were breastfed a mean of 32 weeks.

“Breastfeeding a newborn for the first few months of life helps their developing immune system become more robust, may affect the microbiome, and could influence or prevent development of allergy later in life,” says Dr. Robbins, an allergist at Children’s National Health System and lead author of the research. “However, mothers’ perceptions of their newborns’ adverse reactions to food appears to factor into how long they breastfeed.”

One potential concern is that extended breastfeeding can impact solid food introduction practices.

“Gradually transitioning to solid food gives infants an opportunity to sample an array of foods, nibble by nibble, including food allergens like peanut and eggs. We know from previously published research that introducing high-risk babies to a food allergen like peanuts early in life appropriately primes their immune system and dramatically decreases how often these children actually develop peanut allergies,” Dr. Robbins adds. “The relationship between breastfeeding and allergy development is complex, so understanding mothers’ practices is important. We also do not know how often these early reactions result in true food allergy, compared with transient food intolerance.”

American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting presentation

  • “Perceived food allergy, sensitivity or intolerance and its impact on breastfeeding practices.”

Monday, Feb. 25, 2019, 9:45-10:45 a.m. (PST)

Karen A. Robbins M.D., lead author; Marni Jacobs, Ph.D., co-author; Ashley Ramos Ph.D., co-author; Daniel V. DiGiacomo, M.D., co-author; Katherine M. Balas BS, co-author; and Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program and senior author.

Breastfeeding Mom

Exclusive breastfeeding lowers odds of some schoolchildren having eczema

Breastfeeding Mom

Children exclusively breastfed for the first three months of life had significantly lower odds of having eczema at age 6 compared with peers who were not breastfed or were breastfed for less time, according to preliminary research presented during the American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting.

Eczema is a chronic condition characterized by extremely itchy skin that, when scratched, becomes inflamed and covered with blisters that crack easily. While genes and the environment are implicated in this inflammatory disease, many questions remain unanswered, such as how best to prevent it. According to the Centers for Disease Control and Prevention (CDC), breastfed infants have reduced risks for developing many chronic conditions, including asthma and obesity.

“The evidence that being exclusively breastfed protects children from developing eczema later in life remains mixed,” says Katherine M. Balas, BS, BA, a clinical research assistant at Children’s National and the study’s lead author. “Our research team is trying to help fill that data gap.”

Balas and colleagues tapped data collected in Infant Feeding Practices Study II, a longitudinal study co-led by the CDC and the Food and Drug Administration (FDA) from 2005 to 2007, as well as the agencies’ 2012 follow-up examination of that study cohort. This study first tracked the diets of about 2,000 pregnant women from their third trimester and examined feeding practices through their babies’ first year of life. Their follow-up inquiry looked at the health, development and dietary patterns for 1,520 of these children at 6 years of age.

About 300 of the children had been diagnosed with eczema at some point in their lives, and 58.5 percent of the 6-year-olds had eczema at the time of the CDC/FDA Year Six Follow-Up. Children with higher socioeconomic status or a family history of food allergies had higher odds of being diagnosed with eczema.

“Children who were exclusively breastfed for three months or longer were significantly less likely (adjusted odds ratio: 0.477) to have continued eczema at age 6, compared with peers who were never breastfed or who were breastfed for less than three months,” Balas adds. “While exclusive breastfeeding may not prevent kids from getting eczema, it may protect them from experiencing extended flare-ups.”

American Academy of Allergy, Asthma & Immunology 2019 Annual Meeting presentation

  • “Exclusive breastfeeding in infancy and eczema diagnosis at 6 years of age.”

Sunday, Feb. 24, 2019, 9:45 a.m. (PST)

Katherine M. Balas BS, BA, lead author; Karen A. Robbins M.D., co-author; Marni Jacobs, Ph.D., co-author; Ashley Ramos Ph.D., co-author; Daniel V. DiGiacomo, M.D., co-author; and Linda Herbert, Ph.D., director of Children’s Division of Allergy and Immunology’s psychosocial clinical program and senior author.

Dr. Anna Penn uses a microscope

New model mimics persistent interneuron loss seen in prematurity

Dr. Anna Penn uses a microscope

Children’s research-clinicians created a novel preclinical model that mimics the persistent interneuron loss seen in preterm human infants, identifying interneuron subtypes that could become future therapeutic targets to prevent or lessen neurodevelopmental risks.

Research-clinicians at Children’s National Health System have created a novel preclinical model that mimics the persistent interneuron loss seen in preterm human infants, identifying interneuron subtypes that could become future therapeutic targets to prevent or lessen neurodevelopmental risks, the team reports Jan. 31, 2019, in eNeuro. The open access journal for Society for Neuroscience recognized the team’s paper as its “featured” article.

In the prefrontal cortex (PFC) of infants born preterm, there are decreased somatostatin and calbindin interneurons seen in upper cortical layers in infants who survived for a few months after preterm birth. This neuronal damage was mimicked in an experimental model of preterm brain injury in the PFC, but only when the newborn experimental models had first experienced a combination of prenatal maternal immune activation and postnatal chronic sublethal hypoxia. Neither neuronal insult on its own produced the pattern of interneuron loss in the upper cortical layers observed in humans, the research team finds.

“These combined insults lead to long-term neurobehavioral deficits that mimic what we see in human infants who are born extremely preterm,” says Anna Penn, M.D., Ph.D., a neonatologist in the Division of Neonatology and the Fetal Medicine Institute and a developmental neuroscientist at Children’s National Health System, and senior study author. “Future success in preventing neuronal damage in newborns relies on having accurate experimental models of preterm brain injury and well-defined outcome measures that can be examined in young infants and experimental models of the same developmental stage.”

According to the Centers for Disease Control and Prevention 1 in 10 infants is born preterm, before the 37th week of pregnancy. Many of these preterm births result from infection or inflammation in utero. After delivery, many infants experience other health challenges, like respiratory failure. These multi-hits can exacerbate brain damage.

Prematurity is associated with significantly increased risk of neurobehavioral pathologies, including autism spectrum disorder and schizophrenia. In both psychiatric disorders, the prefrontal cortex inhibitory circuit is disrupted due to alterations of gamma-aminobutyric acid (GABA) interneurons in a brain region involved in working memory and social cognition.

Cortical interneurons are created and migrate late in pregnancy and early infancy. That timing leaves them particularly vulnerable to insults, such as preterm birth.

In order to investigate the effects of perinatal insults on GABAergic interneuron development, the Children’s research team, led by Helene Lacaille, Ph.D., in Dr. Penn’s laboratory, subjected the new preterm encephalopathy experimental model to a battery of neurobehavioral tests, including working memory, cognitive flexibility and social cognition.

“This translational study, which examined the prefrontal cortex in age-matched term and preterm babies supports our hypothesis that specific cellular alterations seen in preterm encephalopathy can be linked with a heightened risk of children experiencing neuropsychiatric disorders later in life,” Dr. Penn adds. “Specific interneuron subtypes may provide specific therapeutic targets for medicines that hold the promise of preventing or lessening these neurodevelopmental risks.”

In addition to Dr. Penn and Lead Author Lacaille, Children’s co-authors include Claire-Marie Vacher; Dana Bakalar, Jiaqi J. O’Reilly and Jacquelyn Salzbank, all of Children’s Center for Neuroscience Research.

Financial support for research described in this post was provided by the National Institutes of Health under award R01HD092593, District of Columbia Intellectual Developmental Disabilities Research Center under award U54HD090257, Cerebral Palsy Alliance Research Foundation, Children’s National Board of Visitors, Children’s Research Institute and Fetal Medicine Institute.

Vittorio Gallo

Neurodevelopmental disorders: Developing medical treatments

Vittorio Gallo

Vittorio Gallo, Ph.D., Chief Research Officer, participates in the world’s largest general scientific gathering, leading panelists in a timely conversation about progress made so far with neurodevelopmental disorders and challenges that lie ahead.

The human brain is the body’s operating system. Imagine if rogue code worked its way into its hardware and software, delaying some processes, disrupting others, wreaking general havoc.

Neurodevelopmental disorders are like that errant code. They can occur early in life and impact brain development for the rest of the person’s life. Not only can fundamental brain development go awry, processes that refine the brain also can become abnormal, creating a double neural hit.  Adding to those complications, children with neurodevelopmental disorders like autism spectrum disorder (ASD) and Fragile X syndrome often contend with multiple, overlapping cognitive impairments and learning disabilities.

The multiple layers of complexities for these disorders can make developing effective medical treatments particularly challenging, says Vittorio Gallo, Ph.D., Chief Research Officer at Children’s National Health System and recipient of a coveted Senator Jacob Javits Award in the Neurosciences.

During the Feb. 16, 2019, “Neurodevelopmental Disorders: Developing Medical Treatments” symposium, Gallo will guide esteemed panelists in a timely conversation about progress made so far and challenges that lie ahead during the AAAS Annual Meeting in Washington, the world’s largest general scientific gathering.

“This is a very important symposium; we’re going to put all of the open questions on the table,” says Gallo. “We’re going to present a snapshot of where the field is right now: We’ve made incredible advances in developmental neuroscience, neonatology, neurology, diagnostic imaging and other related fields. The essential building blocks are in place. Where are we now in developing therapeutics for these complex disorders?”

For select disorders, many genes have been identified, and each new gene has the potential to become a target for improved therapies. However, for other neurodevelopmental disorders, like ASD, an array of new genes continue to be discovered, leaving an unfinished picture of which genetic networks are of most importance.

Gallo says the assembled experts also plan to explore major research questions that remain unanswered as well as how to learn from past experiences to make future studies more powerful and insightful.

“One topic up for discussion will be new preclinical models that have the potential to help in identifying specific mechanisms that cause these disorders. A combination of genetic, biological, psychosocial and environmental risk factors are being combined in these preclinical models,” Gallo says.

“Our studies of the future need to move beyond describing and observing in order to transform into studies that establish causality between the aberrant developmental processes and these constellations of neurodevelopmental disorders.”

Study authors Aaron Sathyanesan, Ph.D., Joseph Abbah, B.Pharm., Ph.D., Srikanya Kundu, Ph.D. and Vittorio Gallo, Ph.D.

Children’s perinatal hypoxia research lauded

Study authors Aaron Sathyanesan, Ph.D., Joseph Abbah, B.Pharm., Ph.D., Srikanya Kundu, Ph.D. and Vittorio Gallo, Ph.D.

Study authors Aaron Sathyanesan, Ph.D., Joseph Abbah, B.Pharm., Ph.D., Srikanya Kundu, Ph.D. and Vittorio Gallo, Ph.D.

Chronic sublethal hypoxia is associated with locomotor miscoordination and long-term cerebellar learning deficits in a clinically relevant model of neonatal brain injury, according to a study led by Children’s National Health System researchers published by Nature Communications. Using high-tech optical and physiological methods that allow researchers to turn neurons on and off and an advanced behavioral tool, the research team found that Purkinje cells fire significantly less often after injury due to perinatal hypoxia.

The research team leveraged a fully automated, computerized apparatus – an Erasmus Ladder – to test experimental models’ adaptive cerebellar locomotor learning skills, tracking their missteps as well as how long it took the models to learn the course.

The research project, led by Aaron Sathyanesan, Ph.D., a Children’s postdoctoral research fellow, was honored with a F1000 primevery good rating.” The Children’s research team used both quantitative behavior tests and electrophysiological assays, “a valuable and objective platform for functional assessment of targeted therapeutics in neurological disorders,” according to the recommendation on a digital forum in which the world’s leading scientists and clinicians highlight the best articles published in the field.

Calling the Erasmus Ladder an “elegant” behavioral system, Richard Lu, Ph.D., and Kalen Berry write that the Children’s National Health System research team “revealed locomotor behavior and cerebellar learning deficits, and further utilized multielectrode recording/optogenetics approaches to define critical pathophysiological features, such as defects in Purkinje cell firing after neonatal brain injury.”

Lu, Beatrice C. Lampkin Endowed Chair in Cancer Epigenetics, and Berry, an associate faculty member in the Cancer and Blood Diseases Institute, both at Cincinnati Children’s, note that the Children’s results “suggest that GABA signaling may represent a potential therapeutic target for hypoxia-related neonatal brain injury that, if provided at the correct time during development post-injury, could offer lifelong improvements.”

In addition to Sathyanesan, Children’s co-authors include Co-Lead Author, Srikanya Kundu, Ph.D., and Joseph Abbah, both of Children’s Center for Neuroscience Research, and Vittorio Gallo, Ph.D., Children’s Chief Research Officer and the study’s senior author.

Research covered in this story was supported by the Intellectual and Developmental Disability Research Center under award number U54HD090257.

Preemie Baby

Getting micro-preemie growth trends on track

Preemie Baby

According to Children’s research presented during the Institute for Healthcare Improvement 2018 Scientific Symposium, standardizing feeding practices – including the timing for fortifying breast milk and formula with essential elements like zinc and protein – improves growth trends for the tiniest preterm infants.

About 1 in 10 infants is born before 37 weeks gestation. These premature babies have a variety of increased health risks, including deadly infections and poor lung function.

Emerging research suggests that getting their length and weight back on track could help. According to Children’s research presented during the Institute for Healthcare Improvement 2018 Scientific Symposium, standardizing feeding practices – including the timing for fortifying breast milk and formula with essential elements like zinc and protein – improves growth trends for the tiniest preterm infants.

The quality-improvement project at Children’s National Health System targeted very low birth weight infants, who weigh less than 3.3 pounds (1,500 grams) at birth. These fragile infants are born well before their internal organs, lungs, brain or their digestive systems have fully developed and are at high risk for ongoing nutritional challenges, health conditions like necrotizing enterocolitis (NEC) and overall poor development.

The research team measured progress by tracking the micro-preemies’ mean delta weight Z-score for weight gain, which measures nutritional status.

“In this cohort, mean delta weight Z-scores improved by 43 percent, rising from -1.8 to the goal of -1.0, when we employed an array of interventions. We saw the greatest improvement, 64 percent, among preterm infants who had been born between 26 to 28 weeks gestation,” says Michelande Ridoré, MS, Children’s NICU quality-improvement program lead who presented the group’s preliminary findings. “It’s very encouraging to see improved growth trends just six months after introducing these targeted interventions and to maintain these improvements for 16 months.”

Within Children’s neonatal intensive care unit (NICU), micro-preemies live in an environment that mimics the womb, with dimmed lighting and warmed incubators covered by blankets to muffle extraneous noise. The multidisciplinary team relied on a number of interventions to improve micro-preemies’ long-term nutritional outcomes, including:

  • Reducing variations in how individual NICU health care providers approach feeding practices
  • Fortifying breast milk (and formula when breast milk was not available), which helps these extra lean newborns add muscle and strengthen bones
  • Early initiation of nutrition that passes through the intestine (enteral feeds)
  • Re-educating all members of the infants’ care teams about the importance of standardized feeding and
  • Providing a decision aid about feeding intolerance.

Dietitians were included in the daily rounds, during which the multidisciplinary team discusses each infant’s care plan at their room, and used traffic light colors to describe how micro-preemies were progressing with their nutritional goals. It’s common for these newborns to lose weight in the first few days of life.

  • Infants in the “green” zone had regained their birth weight by day 14 of life and possible interventions included adjusting how many calories and protein they consumed daily to reflect their new weight.
  • Infants in the “yellow” zone between day 15 to 18 of life remained lighter than what they weighed at birth and were trending toward lower delta Z-scores. In addition to assessing the infant’s risk factors, the team could increase calories consumed per day and add fortification, among other possible interventions.
  • Infants in the “red” zone remained below their birth weight after day 19 of life and recorded depressed delta Z-scores. These infants saw the most intensive interventions, which could include conversations with the neonatologist and R.N. to discuss strategies to reverse the infant’s failure to grow.

Future research will explore how the nutritional interventions impact newborns with NEC, a condition characterized by death of tissue in the intestine. These infants face significant challenges gaining length and weight.

Institute for Healthcare Improvement 2018 Scientific Symposium presentation

  • “Improved growth of very low birthweight infants in the neonatal intensive care unit.”

Caitlin Forsythe, MS, BSN, RNC-NIC, NICU clinical program coordinator, Neonatology, and lead author; Michelande Ridoré, MS, NICU quality-improvement program lead; Victoria Catalano Snelgrove, RDN, LD, CNSC, CLC, pediatric clinical dietitian; Rebecca Vander Veer, RD, LD, CNSC, CLC, pediatric clinical dietitian; Erin Fauer, RDN, LD, CNSC, CLC, pediatric clinical dietitian; Judith Campbell, RNC, IBCLC, NICU lactation consultant; Eresha Bluth, MHA, project administrator; Anna Penn, M.D., Ph.D., neonatologist; Lamia Soghier, M.D., MEd, Medical Unit Director, Neonatal Intensive Care Unit; and Mary Revenis, M.D., NICU medical lead on nutrition and senior author; all of Children’s National Health System.

new mom with baby

Fighting perinatal mood and anxiety disorders on multiple levels

new mom with baby

Over the past several decades, it’s become increasingly recognized that perinatal mood and anxiety disorders (PMADs), including postpartum depression, are more than just “baby blues.” They’re the most common complication of childbirth in the U.S., affecting about 14 percent of women in their lifetimes and up to 50 percent in some specific populations. PMADs can lead to a variety of adverse outcomes for both mothers and their babies, including poor breastfeeding rates, poor maternal-infant bonding, lower infant immunization rates and maternal suicides that account for up to 20 percent of postpartum deaths.

But while it’s obvious that PMADs are a significant problem, finding a way to solve this issue is far from clear. In a policy statement published December 2018 in the journal Pediatrics, the American Academy of Pediatrics recommends that pediatric medical homes coordinate more effectively with prenatal providers to ensure PMAD screening occurs for new mothers at well-child checkups throughout the first several weeks and months of infancy and use community resources and referrals to ensure women suffering with these disorders receive follow-up treatment.

To help solve the huge issue of PMADs requires a more comprehensive approach, suggests Lenore Jarvis, M.D., MEd, an emergency medicine specialist at Children’s National Health System. A poster that Dr. Jarvis and colleagues from Children’s Perinatal Mental Health Taskforce recently presented at the American Academy of Pediatrics 2018 National Convention and Exhibit in Orlando, Florida, details the integrated care to help women with PMADs that originated at Children’s National and is being offered at several levels, including individual, interpersonal, organizational, community and policy. The poster was ranked best in its section for the Council on Early Childhood.

At the base level of care for mothers with possible PMADs, Dr. Jarvis says, are the one-on-one screenings that take place in primary care clinics. Currently, all five of Children’s primary care clinics screen for mental health concerns at annual visits. At the 2-week, 1-, 2-, 4- and 6-month visits, mothers are screened for PMADs using the Edinburgh Postnatal Depression Scale, a validated tool that’s long been used to gauge the risk of postpartum depression. In addition, recent studies at Children’s neonatal intensive care unit (NICU) and emergency department (ED) suggest that performing PMAD screenings in these settings as well could help catch even more women with these disorders: About 45 percent of parents had a positive screen for depression at NICU discharge, and about 27 percent of recent mothers had positive screens for PMADs in the ED.

To further these efforts, Children’s National recently started a Perinatal Mental Health Taskforce to promote multidisciplinary collaboration and open communication with providers among multiple hospital divisions. This taskforce is working together to apply lessons learned from screening in primary care, the NICU and the ED to discuss best practices and develop hospital-wide recommendations. They’re also sharing their experiences with hospitals across the country to help them develop best practices for helping women with PMADs at their own institutions.

Furthering its commitment to PMAD screening, Children’s National leadership set a goal of increasing screening in primary care by 15 percent for fiscal year 2018 – then exceeded it. Children’s National is also helping women with PMADs far outside the hospital’s walls by developing a PMAD screening toolkit for other providers in Washington and across the country and by connecting with community partners through the DC Collaborative for Mental Health in Pediatric Primary Care. In April 2019, the hospital will host a regional perinatal mental health conference that not only will include its own staff but also staff from other local hospitals and other providers who care for new mothers, including midwives, social workers, psychologists, community health workers and doulas.

Finally, on a federal level, Dr. Jarvis and colleagues are part of efforts to obtain additional resources for PMAD screening, referral and treatment. They successfully advocated for Congress to fully fund the Screening and Treatment for Maternal Depression program, part of the 21st Century Cures Act. And locally, they provided testimony to help establish a task force to address PMADs in Washington.

Together, Dr. Jarvis says, these efforts are making a difference for women with PMADs and their families.

“All this work demonstrates that you can take a problem that is very personal, this individual experience with PMADS, and work together with a multidisciplinary team in collaboration to really have an impact and promote change across the board,” she adds.

In addition to Dr. Jarvis, the lead author, Children’s co-authors include Penelope Theodorou, MPH; Sarah Barclay Hoffman, MPP, Program Manager, Child Health Advocacy Institute; Melissa Long, M.D.; Lamia Soghier M.D., MEd, NICU Medical Unit Director; Karen Fratantoni M.D., MPH; and Senior Author Lee Beers, M.D., Medical Director, Municipal and Regional Affairs, Child Health Advocacy Institute.