banner year

2017: A banner year for innovation at Children’s National

banner year

In 2017, clinicians and research faculty working at Children’s National Health System published more than 850 research articles about a wide array of topics. A multidisciplinary Children’s Research Institute review group selected the top 10 articles for the calendar year considering, among other factors, work published in high-impact academic journals.

“This year’s honorees showcase how our multidisciplinary institutes serve as vehicles to bring together Children’s specialists in cross-cutting research and clinical collaborations,” says Mark L. Batshaw, M.D., Physician-in-Chief and Chief Academic Officer at Children’s National. “We’re honored that the National Institutes of Health and other funders have provided millions in awards that help to ensure that these important research projects continue.”

The published papers explain research that includes using imaging to describe the topography of the developing brains of infants with congenital heart disease, how high levels of iron may contribute to neural tube defects and using an incisionless surgery method to successfully treat osteoid osteoma. The top 10 Children’s papers:

Read the complete list.

Dr. Batshaw’s announcement comes on the eve of Research and Education Week 2018 at Children’s National, a weeklong event that begins April 16, 2018. This year’s theme, “Diversity powers innovation,” underscores the cross-cutting nature of Children’s research that aims to transform pediatric care.

As pediatric use of iNO increased, mortality rates dropped


iNO, a colorless odorless gas, is used to treat hypoxic respiratory failure in infants born full-term and near term.

Use of inhaled nitric oxide (iNO) among pediatric patients has increased since 2005 and, during a 10-year time period, mortality rates dropped modestly as the therapeutic approach was applied to a broader range of health ailments, according to an observational analysis presented Feb. 26, 2018, during the 47th Critical Care Congress.

iNO, a colorless odorless gas, is used to treat hypoxic respiratory failure in infants born full-term and near term and also has become an important therapy for acute respiratory distress syndrome and pulmonary hypertension in newborns.

Jonathan Chan, M.D., a Children’s National Health System critical care fellow, analyzed de-identified data from patient visits from January 2005 to December 2015 at 47 children’s hospitals around the nation. Dr. Chan included 18,343 patients in the analysis. Among the findings:

  • As a group, the children had an overall mortality rate of 22.7 percent. The mortality rate dropped from 29.1 percent in 2005 to 21.2 percent in 2015.
  • The median adjusted cost per admission was an estimated $158,740 ($5,846 per patient day).

“This large observational study indicates that the use of iNO grew from 2005 to 2015,” Dr. Chan says. “While hospital stays grew longer during the study period, we saw a decrease in mortality of 0.01 percent per year.”

The highest number of admissions with iNO use included:

Dr. Chan notes that because this is a retrospective observational analysis, the study’s findings should be interpreted as exploratory.

“Off-label use of iNO continues to increase among pediatric patients. And an increasing proportion of admissions are for specialty areas other than neonatal care,” he adds. “Increasing off-label use of iNO is associated with decreased mortality. But it also is associated with an increased length of stay, higher hospital costs and more units of iNO administered.”

47th Critical Care Congress presentation

Monday, Feb. 26, 2018

baby in arms

Breast-feeding, anesthesia and analgesics: What’s safe?

baby in arms

Breast-feeding is safe even just after moms have woken from anesthesia or while they take most pain medications, says Sarah Reece-Stremtan, M.D., lead author of an expanded protocol about the topic.

Moms can safely continue breast-feeding even just after waking from anesthesia and while taking most pain medications, according to a newly expanded clinical guidance, “Clinical Protocol No. 15: Analgesia and Anesthesia for the Breastfeeding Mother,” from the Academy of Breastfeeding Medicine (ABM).

In general, mothers who are beyond the postpartum stage do not need to avoid breast-feeding or to pump and discard breast milk while taking analgesics or receiving local or general anesthesia. The protocol was published in the journal Breastfeeding Medicine.

Sarah Reece-Stremtan, M.D., an anesthesiologist and acute pain medicine specialist at Children’s National Health System, co-chairs ABM’s protocol committee and is the lead author of the expanded protocol. A specialist in the intersection of anesthesia, pain medicine and breast-feeding medicine, Dr. Reece-Stremtan led the drafting of the recommendations.

“The key recommendation in this protocol is after waking up from anesthesia, most moms can breast-feed right away,” says Dr. Reece-Stremtan. “The standard thinking has been ‘pump and dump’ – discarding the breast milk for 24 hours after anesthesia. As an outdated practice, it is not evidence-based and is potentially harmful for babies. The evidence shows that this breast milk is safe.”

The authors’ main note of caution relates to opioids: “The most concerning class of medications used for anesthesia and analgesia in breast-feeding mothers is opioids, as these medications transfer into breast milk,” they write. “Judicious use of opioids for short periods is likely to be safe for most breast-feeding mothers and infants.”

The protocol recommendations cover pain medications, brief procedures, regional and general anesthesia and perioperative considerations. They provide more granular detail about specific anesthesia and analgesic agents.

For each recommendation, the protocol notes the strength or weakness of the evidence base. The authors note there is little rigorous information in the scientific literature about anesthesia or procedural sedation in breast-feeding mothers.

“For obvious reasons, it is unethical to conduct randomized, controlled clinical trials for this area, so we rely on expert opinion and on observational studies that do exist,” says Dr. Reece-Stremtan.

The protocol is intended to be relevant to a broad range of medical fields, from anesthesiology to general pediatrics, and to help any physician who may care for a new mother.

For instance, it includes a perioperative plan with suggestions that surgeons or physicians can share with their patients to make things easier for a breast-feeding mom who needs local or general anesthesia – and safer for their babies. “It’s important to acknowledge that medication isn’t the only or even the most important thing,” says Dr. Reece-Stremtan. Tips to aid breast-feeding can ease the minds of mothers and their physicians alike.

Dr. Reece-Stremtan has long been interested in breast-feeding and has seen a need for more education about where her areas of expertise, pediatric anesthesia and pain medicine, intersect. Few physicians specialize in this area, so she often gives talks to other clinicians on the topic.

“I know that most anesthesiologists do not encounter this scenario often, so many have questions about the impact of anesthesia agents on breast-feeding,” says Dr. Reece-Stremtan. “Likewise, general pediatricians, neonatal specialists and other health professionals who care for moms and newborns may have limited knowledge about the safety of pain medicine or anesthesia for breast-feeding infants.”

In developing this new set of recommendations, ABM’s protocol committee aimed to provide practical clinical guidance for two scenarios: Postpartum, and moms and babies who are past that stage. The committee divided a previous ABM protocol into these two areas and expanded them to offer clinicians more complete guidance that is clinically relevant yet concise. Dr. Reece-Stremtan attributes this expansion to a growing appreciation of the importance of breast-feeding to both individual and public health. She is helping to finalize ABM’s new birth-postpartum protocol on anesthesia and analgesics, which will be published in early 2018.

To build on these protocols, Dr. Reece-Stremtan is helping the Academy develop a set of free patient education materials that will inform mothers about the use of pain medications or the need for anesthesia while breast-feeding, so they can feel at ease that they are doing the best thing for their baby’s health.

newborn in incubator

Tracking oxygen saturation with vital signs to identify vulnerable preemies



What’s known

Critically ill infants in neonatal intensive care units (NICU) require constant monitoring of their vital signs. Invasive methods, such as using umbilical arterial catheters to check blood pressure, are the gold standard but pose significant health risks. Low-risk noninvasive monitoring, such as continuous cardiorespiratory monitors, can measure heart rate, respiratory rate and blood oxygenation. A noninvasive technique called near-infrared spectroscopy (NIRS) can gauge how well tissues, including the brain, are oxygenated. While NIRS long has been used to monitor oxygenation in conditions in which blood flow is altered, such as bleeding in the brain, how NIRS values relate to other vital sign measures in NICU babies was unknown.

What’s new

A research team led by Khodayar Rais-Bahrami, M.D., a neonatologist at Children’s National Health System, investigated this question in 27 babies admitted to Children’s NICU. The researchers separated these subjects into two groups: Low birth weight (LBW, less than 1.5 kg or 3.3 pounds) and moderate birth weight (MBW, more than 1.5 kg). Then, they looked for correlations between information extracted from NIRS, such as tissue oxygenation (specific tissue oxygen saturation, StO2) and the balance between oxygen supply and consumption (fractional tissue oxygen extraction, FTOE), and various vital signs. They found that StO2 increased with blood pressure for LBW babies but decreased with blood pressure for MBW babies. Brain and body FTOE in LBW babies decreased with blood pressure. In babies with abnormal brain scans, brain StO2 increased with blood pressure and brain FTOE decreased with blood pressure. Together, the researchers suggest, these measures could give a more complete picture of critically ill babies’ health.

Questions for future research

Q: Can NIRS data be used as a surrogate for other forms of monitoring?

Q: How could NIRS data help health care professionals intervene to improve the health of critically ill infants in the NICU?

Source: Significant correlation between regional tissue oxygen saturation and vital signs of critically ill infants.” B. Massa-Buck, V. Amendola, R. McCloskey and K. Rais-Bahrami. Published by Frontiers in Pediatrics Dec. 21, 2017.


MRI opens new understanding of fetal growth restriction


Quantitative MRI can identify placental dysfunction complicated by fetal growth restriction earlier, creating the possibility for earlier intervention to minimize harm to the developing fetus.

A team of researchers has found that quantitative magnetic resonance imaging (MRI) can identify pregnancies where placental dysfunction results in fetal growth restriction (FGR), creating the possibility for earlier FGR detection and intervention to augment placental function and thus minimize harm to the fetal brain.

The study, published online in the Journal of Perinatology, reports for the first time that in vivo placental volume is tied to global and regional fetal brain volumes.

Placental insufficiency is a known risk factor for impaired fetal growth and neurodevelopment. It may cause the fetus to receive inadequate oxygen and nutrients, making it difficult to grow and thrive. The earlier placental insufficiency occurs in a pregnancy, the more serious it can be. But detecting a failing placenta before the fetus is harmed has been difficult.

One additional challenge is that a fetus may be small because the placenta is not providing adequate nourishment. Or the fetus simply may be genetically predisposed to be smaller. Being able to tell the difference early can have a lifelong impact on a baby. Infants affected by FGR can experience behavioral problems, learning difficulties, memory and attention deficits, and psychiatric issues as the child grows into adolescence and adulthood.

“Our study proved that MRI can more accurately determine which pregnancies are at greater risk for impaired fetal health or compromised placenta function,” says Nickie Andescavage, M.D., the study’s lead author and a specialist in neonatology and neonatal neurology and neonatal critical care at Children’s National Health System. “The earlier we can identify these pregnancies, the more thoughtful we can be in managing care.”

Dr. Andescavage’s research focus has been how fetal growth affects labor, delivery and postnatal complications.


“Our study proved that MRI can more accurately determine which pregnancies are at greater risk for impaired fetal health or compromised placenta function,” says Nickie Andescavage, M.D., the study’s lead author.

“We don’t have a good understanding of why FGR happens, but we do know it’s hard to identify during pregnancy because often there are no signs,” says Dr. Andescavage. “Even when detected, it’s hard to follow. But if we’re aware of it, we can better address important questions, like when to deliver an at-risk fetus.”

In the study, the team measured placental and fetal brain growth in healthy, uncomplicated pregnancies and in pregnancies complicated by FGR. A total of 114 women participated, undergoing ultrasound, Doppler ultrasound and MRI imaging to measure placental volume and fetal brain volume.

An ultrasound test is often what detects FGR, but the measurements generated by ultrasound can be non-specific. In addition, reproducibility issues with 3D sonography limit its use as a standalone tool for placental assessment. Once FGR is detected via ultrasound, this study showed that complementary MRI provides more accurate structural measures of the fetal brain, as well as more detail and insight into placental growth and function.

“Our team has studied FGR for a few years, using imaging to see that’s happening with the fetus in real time,” says Dr. Andescavage. “The relationship of placental volume and fetal brain development had not been previously studied in utero.”

In pregnancies complicated by FGR, MRI showed markedly decreased placental and brain volumes. The team observed significantly smaller placental, total brain, cerebral and cerebellar volumes in these cases than in the healthy controls. The relationship between increasing placental volume and increasing total brain volume was similar in FGR and in normal pregnancies. However, the study authors write “the overall volumes were smaller and thus shifted downward in pregnancies with FGR.”

In addition, FGR-complicated pregnancies that also showed abnormalities in Doppler ultrasound imaging had even smaller placental, cerebral and cerebellar volumes than pregnancies complicated by FGR that did not have aberrations in Doppler imaging.

Since this study showed that quantitative fetal MRI can accurately detect decreased placental and brain volumes when FGR is present, Dr. Andescavage believes this imaging technique may give doctors important new insights into the timing and possibly the mechanisms of brain injury in FGR.  “Different pathways can lead to FGR. With this assessment strategy, we could potentially elucidate those,” she adds.

Using quantitative MRI to identify early deviations from normal growth may create opportunities for future interventions to protect the developing fetal brain. New treatments on the horizon promise to address placental health. MRI could be used to investigate these potential therapies in utero. When those therapies become available, it could allow doctors to monitor treatment effects in utero.

Study co-authors include Adré J. du Plessis, M.B.Ch.B., M.P.H., Director of Children’s Fetal Medicine Institute; Marina Metzler; Dorothy Bulas, M.D., FACR, FAIUM, FSRU, Chief of Children’s Division of Diagnostic Imaging and Radiology; L. Gilbert Vezina, M.D., Director of Children’s Neuroradiology Program; Marni Jacobs; Catherine Limperopoulos, Ph.D., Director of Children’s Developing Brain Research Laboratory and study senior author; Sabah N. Iqbal, MedStar Washington Hospital Center; and Ahmet Alexander Baschat, Johns Hopkins Center for Fetal Therapy.

Research reported in this post was supported by the Canadian Institutes of Health Research, MOP-81116; the National Institutes of Health under award numbers UL1TR000075 and KL2TR000076; and the Clinical and Translational Science Institute at Children’s National.

Neonatal baby

Multidisciplinary experts help CDC’s Zika research

“We are very excited about this next phase in our Zika research,” says Roberta L. DeBiasi, M.D., M.S. “It is a natural extension of our earlier participation as subject matter experts assisting as the CDC developed and published guidelines to inform the care of Zika-exposed and Zika-infected infants across the nation and U.S. territories.”

The Centers for Disease Control and Prevention (CDC) is funding three multidisciplinary experts from the Congenital Zika Virus Program at Children’s National Health System to collaborate on two of the CDC’s longitudinal Zika research projects in Colombia, South America.

“Zika en embarazadas y niños en Colombia” (ZEN) is a research study jointly designed by Colombia’s Instituto Nacional de Salud (INS) and the CDC to evaluate the association between Zika virus infection and adverse maternal, fetal and infant health outcomes. The study is following a large cohort of Colombian women from the first trimester of pregnancy, their male partners and their infants.

Under the six-month contract, Roberta L. DeBiasi, M.D., M.S., Sarah B. Mulkey, M.D., Ph.D., and Cara Biddle, M.D., M.P.H., will serve as consultants for the ZEN study providing expertise in pediatric infectious diseases, neurology, neurodevelopment and coordination of the complex care needs of Zika-affected infants.

The federal funding will underwrite the consultants’ work effort, as well as travel to the CDC’s headquarters in Atlanta and to research sites in Colombia. To that end, Drs. DeBiasi, Mulkey and Biddle participated in a December 2017 kickoff meeting, joining ZEN team leaders based in the U.S. at the CDC, as well as the INS in Colombia, with whom they will conduct research and collaborate academically.


Cara Biddle, M.D., M.P.H., and Sarah B. Mulkey, M.D., Ph.D., also will serve as consultants for the ZEN study.

“We are very excited about this next phase in our Zika research,” says Dr. DeBiasi, chief of the Division of Pediatric Infectious Diseases and co-director of the Children’s Zika program. “It is a natural extension of our earlier participation as subject matter experts assisting as the CDC developed and published guidelines to inform the care of Zika-exposed and Zika-infected infants across the nation and U.S. territories.”

Children’s National is leading its own longitudinal studies in Colombia that explore such questions as whether Zika-exposed infants whose neuroimaging appears normal when they are born experience any longer-term neurological issues and the role of genetics in neurologic injury following congenital Zika virus exposure and infection.

Carlos Ferreira Lopez

Researchers discover new gene variant for inherited amino acid-elevating disease

Carlos Ferreira Lopez

What’s known

Hypermethioninemia is a rare condition that causes elevated levels of methionine, an essential amino acid in humans. This condition stems from genetic variations inherited from one or both parents. Some forms of hypermethioninemia are recessive, meaning that two copies of defective genes are necessary to cause this disease. Other forms are dominant, meaning that only one copy can cause hypermethioninemia. Recessive forms of the disease tend to have more serious consequences, causing elevated methionine levels throughout life and leading to changes in the brain’s white matter visible on magnetic resonance imaging that can cause neurological problems. The dominant forms are generally thought to be largely benign and require minimal follow-up.

What’s new

A research team led by Carlos R. Ferreira, M.D., a medical geneticist at Children’s National Health System, discovered a new gene variant that had not been associated with hypermethioinemia previously when an infant who had tested positive for elevated methionine on newborn blood-spot screening came in for a follow-up evaluation. While the majority of dominant hypermethioninemia are caused by a genetic mutation known as MAT1A p.Arg264His, the child didn’t have this or any of the common recessive hypermethioninemia mutations. Genetic testing showed that she carried a different mutation to the MAT1A gene known as p.Ala259Val, of which she carried only a single copy. The child fit the typical profile of having the dominant form of the disease, with methionine levels gradually declining over time. Testing of her mother showed that she carried the same gene variant, with few consequences other than a hepatitis-like illness as a child. Because liver disease can accompany dominant hypermethioninemia, the infant’s doctors will continue periodic follow-up to ensure she remains healthy.

Questions for future research

Q: Besides the potential for harmful liver effects, does dominant hypermethioninemia have other negative consequences?

Q: How common is this gene variant, and are certain people at more risk for carrying it?

Source: Confirmation that MAT1A p.Ala259Val mutation causes autosomal dominant hypermethioninemia. Muriello, M.J., S. Viall, T. Bottiglieri, K. Cusmano-Ozog and C. R. Ferreira. Published by Molecular Genetics and Metabolism Reports December 2017.

Volumetric imaging of upper airways

Preemies’ narrowed upper airways may explain higher OSA risk

Volumetric imaging of upper airways

The airway structures of interest to the Children’s National research team included the nasopharynx (labeled red), oropharynx (labeled purple), hypopharynx (labeled green), adenoids (labeled yellow) and tonsils (labeled blue). The team displayed the volumetric imaging in three perpendicular planes and a three-dimensional model.
Credit: A. Smitthimedhin, et al, Clinical Imaging.

Infants born preterm have significantly lower nasopharyngeal and oropharyngeal volumes, compared with newborn peers carried to full term, and those lower airway volumes are independent of the infants’ gender, ethnicity or weight, according to a study published online Dec. 16, 2017 in Clinical Imaging.

According to the Centers for Disease Control and Prevention, 1 in 10 babies born in the United States is preterm, or born prior to the 37th gestational week. Premature birth leaves these children more susceptible to disordered breathing while sleeping, including obstructive sleep apnea (OSA), an ailment characterized by increased upper-airway resistance that narrows airways.

“In addition to finding some airway volumes were smaller in preterm infants, our results indicated both sets of newborns had similar hypopharyngeal volumes. This suggests that risk factors that lead to OSA are confined to the uppermost airway and do not appear to be explained by enlarged adenoids and tonsils,” says Anilawan Smitthimedhin, a Children’s National Health System radiology research fellow at the time the study was performed and lead author of the paper.

In order to diagnose OSA, clinicians now use bronchoscopy, but the method has limitations, including the need to insert a lighted instrument into the airway, which can affect pressure and resistance within the airway.

The Children’s National research team theorized that magnetic resonance imaging (MRI) could offer a non-invasive way to evaluate the upper airway, determine its anatomy and dynamic function, while shielding infants from radiation exposure that can accompany other imaging techniques.

They enrolled 96 infants who had undergone brain MRIs as part of an unrelated study about neonatal brain development. The newborns had a range of medical conditions, including suspected hypoxic ischemic encephalopathy, cardiac disease and seizures/movement disorders.

Forty-nine of the infants were born preterm; at the time of the MRI, their corrected mean gestational age was 38.4 weeks. Forty-seven of the newborns were born full term; they received MRIs at 1.7 weeks of age. The airway structures of interest included the nasopharynx (the upper part of the pharynx), oropharynx (located at the back of the mouth behind the oral cavity), hypopharynx (the entrance into the esophagus), adenoids and tonsils. The team displayed the volumetric imaging in three perpendicular planes and a three-dimensional model.

“Nasopharyngeal volume of full-term infants was 495.6 mm, compared with 221.1 mm in preterm infants. Oropharyngeal volume of full-term infants was 313.6 mm, compared with 179.3 mm in preterm infants,” Smitthimedhin says.

Aided by volumetric 3D data that more accurately measures airway and lymphoid tissue, the team proposes to study a larger group of infants to determine whether narrowing of the uppermost airways predisposes very young children to experiencing OSA later in life.

“Ultimately, our goal is to incorporate dedicated, dynamic MR imaging of the airway while children sleep, which would provide real-time, detailed information about the changes associated with sleep. This innovation holds the promise of leading to more accurate, non-invasive diagnosis of OSA in infants,” says Dorothy Bulas, M.D., chief of Diagnostic Imaging and Radiology at Children’s National.

Children’s National study co-authors include Radiologist Matthew Whitehead, M.D.; University of Maryland student Mahya Bigdeli; Pulmonologist Gustavo Nino, M.D.; Pulmonologist Geovanny Perez, M.D,; and Hansel Otero, who was at Children’s National when the research work was performed but now works at Children’s Hospital of Philadelphia.

the cerebral blood flow (CBF) maps, corresponding anatomical image aligned to the CBF map, and the regions of interest examined

Tracking preemies’ blood flow to monitor brain maturation

Blood is the conduit through which our cells receive much of what they need to grow and thrive. The nutrients and oxygen that cells require are transported by this liquid messenger. Getting adequate blood flow is especially important during the rapid growth of gestation and early childhood – particularly for the brain, the weight of which roughly triples during the last 13 weeks of a typical pregnancy. Any disruption to blood flow during this time could dramatically affect the development of this critical organ.

Now, a new study by Children’s National Health System researchers finds that blood flow to key regions of very premature infants’ brains is altered, providing an early warning sign of disturbed brain maturation well before such injury is visible on conventional imaging. The prospective, observational study was published online Dec. 4, 2017 by The Journal of Pediatrics.

“During the third trimester of pregnancy, the fetal brain undergoes an unprecedented growth spurt. To power that growth, cerebral blood flow increases and delivers the extra oxygen and nutrients needed to nurture normal brain development,” says Catherine Limperopoulos, Ph.D., director of the Developing Brain Research Laboratory at Children’s National and senior author of the study. “In full-term pregnancies, these critical brain structures mature inside the protective womb where the fetus can hear the mother and her heartbeat, which stimulates additional brain maturation. For infants born preterm, however, this essential maturation process happens in settings often stripped of such stimuli.”

The challenge: How to capture what goes right or wrong in the developing brains of these very fragile newborns? The researchers relied on arterial spin labeling (ASL) magnetic resonance (MR) imaging, a noninvasive technique that labels the water portion of blood to map how blood flows through infants’ brains in order to describe which regions do or do not receive adequate blood supply. The imaging work can be done without a contrast agent since water from arterial blood itself illuminates the path traveled by cerebral blood.

“In our study, very preterm infants had greater absolute cortical cerebral blood flow compared with full-term infants. Within regions, however, the insula (a region critical to experiencing emotion), anterior cingulate cortex (a region involved in cognitive processes) and auditory cortex (a region involved in processing sound) for preterm infants received a significantly decreased volume of blood, compared with full-term infants. For preterm infants, parenchymal brain injury and the need for cardiac vasopressor support both were correlated with decreased regional CBF,” Limperopoulos adds.

The team studied 98 preterm infants who were born June 2012 to December 2015, were younger than 32 gestational weeks at birth and who weighed less than 1,500 grams. They matched those preemies by gestational age with 104 infants who had been carried to term. The brain MRIs were performed as the infants slept.

Blood flows where it is needed most with areas of the brain that are used more heavily commandeering more oxygen and nutrients. Thus, during brain development, CBF is a good indicator of functional brain maturation since brain areas that are the most metabolically active need more blood.

the cerebral blood flow (CBF) maps, corresponding anatomical image aligned to the CBF map, and the regions of interest examined

This figure represents the cerebral blood flow (CBF) maps, corresponding anatomical image aligned to the CBF map, and the regions of interest examined. The scale indicates the quantitative value of the CBF map and is expressed in mL/100g/min. The data are from a preterm infant scanned at term age without evidence of brain injury. The insula (see black arrows in panel ‘D’) may be particularly vulnerable to the added stresses of the preterm infant’s life outside the womb.
Credit: M. Bouyssi-Kobar, et al., The Journal of Pediatrics.

“The ongoing maturation of the newborn’s brain can be seen in the distribution pattern of cerebral blood flow, with the greatest volume of blood traveling to the brainstem and deep grey matter,” says Marine Bouyssi-Kobar, M.S., the study’s lead author. “Because of the sharp resolution provided by ASL-MR images, our study finds that in addition to the brainstem and deep grey matter, the insula and the areas of the brain responsible for sensory and motor functions are also among the most oxygenated regions. This underscores the critical importance of these brain regions in early brain development. In preterm infants, the insula may be particularly vulnerable to the added stresses of life outside the womb.”

Of note, compromised regional brain structures in adults are implicated in multiple neurodevelopmental disorders. “Altered development of the insula and anterior cingulate cortex in newborns may represent early warning signs of preterm infants at greater risk for long-term neurodevelopmental impairments,” Limperopoulos says.

Research reported in this post was supported by the Canadian Institutes of Health Research, MOP-81116; the SickKids Foundation, XG 06-069; and the National Institutes of Health under award number R01 HL116585-01.

Human Rhinovirus

When a common cold may trigger early supportive care

Human Rhinovirus

A new study led by Children’s National Health System shows that in infants who were born severely premature, human rhinovirus infections appear to trigger airway hyper-reactivity, which leads to wheezing, hyperinflation and more severe respiratory disease.

Human rhinovirus (HRV), the culprit behind most colds, is the leading cause of hospitalization for premature babies. However, in very preterm children, exactly how HRV causes severe respiratory disease – and which patients may need more intensive observation and treatment – is less well understood.

A new study led by Children’s National Health System research-clinicians showed in children who were born severely premature, HRV infections seem to trigger an airway hyper-reactivity (AHR) type of disease, which leads to wheezing and air-trapping (hyperinflation) and more severe respiratory disease. This, in turn, increases the risk for hospitalization.

The study, published online Oct. 21, 2017 in Pediatrics and Neonatology, found that other signs of respiratory distress, such as low arterial blood oxygen or rapid shallow breathing, were no more common in severely premature children (less than 32 weeks of gestational age) than in kids born preterm or full-term. The findings have implications for administering supportive care sooner or more intensively for severely premature children than for other infants.

“When it comes to how they respond to such infections, severely premature children are quite different,” says Geovanny Perez, M.D., a specialist in pulmonary medicine at Children’s National and lead study author. “We’ve known they are more susceptible to human rhinovirus infection and have more severe disease. However, our study findings suggest that severely premature kids have an ‘asthma’ type of clinical picture and perhaps should be treated differently.”

The study team sought to identify clinical phenotypes of HRV infections in young children hospitalized for such infections. The team theorized that severely premature babies would respond differently to these infections and that their response might resemble symptoms experienced by patients with asthma.

“For a number of years, our team has studied responses to viruses and prematurity, especially HRV and asthma,” Dr. Perez says. “We know that premature babies have an immune response to HRV from the epithelial cells, similar to that seen in older patients with asthma. But we wanted to address a gap in the research to better understand which children may need closer monitoring and more supportive care during their first HRV infection.”

Geovanny Perez

“When it comes to how they respond to such infections, severely premature children are quite different,” says Geovanny Perez, M.D. “We’ve known they are more susceptible to human rhinovirus infection and have more severe disease. However, our study findings suggest that severely premature kids have an ‘asthma’ type of clinical picture and perhaps should be treated differently.”

In a retrospective cross-sectional analysis, the study looked at 205 children aged 3 years or younger who were hospitalized at Children’s National in 2014 with confirmed HRV infections. Of these, 71 percent were born full-term (more than 37 gestational weeks), 10 percent were preterm (32 to 37 gestational weeks) and 19 percent were severely premature (less than 32 gestational weeks).

Dr. Perez and his team developed a special respiratory distress scoring system based on physical findings in the children’s electronic medical records to assess the degree of lower-airway obstruction or AHR (as occurs in asthma) and of parenchymal lung disease. The physical findings included:

  • Wheezing;
  • Subcostal retraction (a sign of air-trapping/hyperinflation of the lungs), as can occur in pneumonia;
  • Reduced oxygen levels (hypoxemia); and
  • Increased respiratory rate (tachypnea).

The research team assigned each case an overall score. The severely premature children had worse overall scores – and significantly worse scores for AHR and hyperinflated lungs relative to children born late preterm or full-term.

“What surprised us, though, in this study was that the phenotypical characterization using individual parameters for parenchymal lung disease, such as hypoxemia or tachypnea, were not different in severe preterm children and preterm or full term,” says Dr. Perez. “On the other hand, our study found that severely preterm children had a lower airway obstruction phenotype associated with retractions and wheezing. Moreover there was a ‘dose effect’ of prematurity: Children who were born more premature had a higher risk of wheezing and retractions.”

Among the implications of this study, Dr. Perez sees the potential to use phenotypical (clinical markers, such as retractions and wheezing) and biological biomarkers to better personalize patients’ treatments. Dr. Perez and his team have identified biological biomarkers in nasal secretions of children with rhinovirus infection that they plan to combine with clinical biomarkers to identify which patients with viral infections will benefit from early supportive care, chronic treatments or long-term monitoring.

Dr. Perez says further research in this area should pursue a number of paths, including:

  • A longitudinal study to elucidate which children will benefit from asthma-like treatment, such as bronchodilators or corticosteroids;
  • A study of biomarkers, including microRNAs and other inflammatory molecules; or
  • Alternatively, a longitudinal study exploring the mechanism by which wheezing develops, perhaps looking at first and subsequent rhinovirus infections in babies born at different gestational ages.
Dorothy Bulas

Congratulations to Dorothy Bulas, M.D. – 2017 RSNA Outstanding Educator recipient

Dorothy Bulas

Dorothy Bulas, M.D., section head of ultrasound and fetal imaging at Children’s National Health System, was honored with the RSNA 2017 Outstanding Educator award at the Radiological Society of North America’s (RSNA) Annual Meeting, held November 26 – December 1 in Chicago, Illinois.

The winner of the award is selected annually by the RSNA Board of Directors based on the awardee’s significant contributions and long-term commitment – 15 years or more – to radiologic education.

“In addition to being a talented clinician and an accomplished researcher, Dr. Bulas is an extraordinary teacher who has made tireless contributions to the educational programs of RSNA,” said RSNA President Richard L. Ehman, M.D. “For more than three decades, she has been a passionate and effective advocate for improving pediatric radiology worldwide – especially in poorly served countries – by participating in educational outreach.”

newborn in incubator

Working to reduce brain injury in newborns

A new study from Children’s National Health System and Drexel University College of Medicine has identified a promising treatment to reduce or prevent brain injury in newborns who have suffered hypoxia-ischemia.

Research-clinicians at Children’s National Health System and Drexel University College of Medicine led the first study to identify a promising treatment to reduce or prevent brain injury in newborns who have suffered hypoxia-ischemia, a serious complication in which restricted blood flow deprives the brain of oxygen.

Consequences of brain injury resulting from oxygen deprivation affect the entire lifespan and range from mild (learning disabilities) to severe (inability to breathe, walk, talk or see). This complication can occur during or before birth due to maternal/placental problems, such as placental abruption or cord prolapse, or due to fetal/newborn issues, such as asphyxia due to labor difficulties, infection, fetal-maternal bleeding or twin-to-twin transfusion.

Published in Neonatology on Oct. 13, 2017, the study evaluated newborn experimental models exposed to hypoxia-ischemia. The experimental models were given standard cooling therapy (therapeutic hypothermia) alone and in combination with a selective Src kinase inhibitor, PP2, that blocks a regulatory enzyme of apoptosis (cell death), which intensifies as a result of hypoxia-ischemia. The Food and Drug Administration has approved a Src kinase inhibitor as an oncology treatment. This study is the first to test the benefits of blocking this enzyme in reducing the neurological damage caused by brain hypoxia-ischemia.

“In hypoxia-ischemia, CaM kinase is over-activated, but hypothermia has been shown to decrease this enzyme’s activation. We theorized that a Src kinase inhibitor, in addition to hypothermia, would further attenuate the activation of CaM kinase IV and that the result might be less brain damage,” explains Panagiotis Kratimenos, M.D., Ph.D., the study’s lead author, and a specialist in neonatology and neonatal neurocritical care at Children’s National. “From this study, we were pleased that this seems to be the case.”

The research team assessed neuropathology, adenosine triphosphate and phosphocreatine  concentrations as well as CaM kinase IV activity. The CaM kinase IV activity in cerebral tissue was 2,002 (plus or minus 729) with normal oxygen levels and in normal temperatures, 4,104 (plus or minus 542) in hypoxia with hypothermia treatment, and 2,165 (plus or minus 415) in hypoxia with hypothermia treatment combined with PP2 administration.

The authors conclude that hypothermia alone attenuated the over-activation of CaM kinase IV and improved neuropathology after hypoxia. However, the combination of hypothermia with Src kinase inhibition following hypoxia further attenuated the increased activation of CaM kinase IV, compared with hypothermia alone in the newborn experimental model brain.

Currently, the only treatment for hypoxia-ischemia is therapeutic hypothermia. Starting in the first six hours of life, doctors in the neonatal intensive care unit lower a baby’s temperature by about 3 degrees Celsius for three days. This therapy is proven to reduce neural defects by up to 30 percent, yet many infants still have poor outcomes even after the therapeutic cooling treatment.

“In oxygen deprivation of the brain, the pathways leading to cell death are over-activated, including the nuclear enzyme CaM kinase IV. We sought to intervene in this pathway to reduce the heightened cell death, which leads to brain damage,” explains Dr. Kratimenos, an assistant professor of pediatrics at The George Washington University School of Medicine and Health Sciences whose research focus is neonatal encephalopathy and therapeutic hypothermia.

To continue preclinical research into this approach, Dr. Kratimenos envisions studying the effect of other types of small molecule inhibitors to target the apoptotic cascade, perhaps in multiple doses, eliminating the potential side effects, and determining the best dose and duration of treatment.

“If confirmed by further studies, this approach─in combination with cooling─may help to further attenuate neurological damage that babies suffer after experiencing hypoxia-ischemia,” says Dr. Kratimenos.

The study co-authors include Ioannis Koutroulis, M.D., Ph.D., a faculty member in Children’s Division of Emergency Medicine; and Amit Jain, M.D.; Shadi Malaeb, M.D.; and the world-renowned neonatologist and pioneer in bioenergetics of the brain, Maria Delivoria-Papadopoulos, M.D., all of the Drexel University College of Medicine.


Continuous EEG monitoring better predicts HIE outcomes


“What we were trying to determine with this study is whether evaluating the pattern of evolution of the aEEG as a whole provides more information compared with looking at snapshots in time,” explains the study’s senior author An N. Massaro, M.D.

For newborns who experience a serious complication that deprives their brain of oxygen, continuously monitoring brain activity and examining how the electrical signals evolve may be a more reliable way to identify infants most at risk for brain injury, compared with doing evaluations at discreet intervals, according to a prospective cohort study led by Children’s National Health System research-clinicians.

Amplitude-integrated electroencephalogram (aEEG) is a bedside tool that permits clinicians to monitor the complex electrical activity of the child’s brain over time. It’s a positive sign when an aEEG shows babies beginning to sleep and wake normally by the time they are 3 days old. Conversely, severely abnormal aEEG readings in the first days of life predict poor outcomes.

The Children’s team used aEEG with infants born with hypoxic-ischemic encephalopathy (HIE), one of the most severe complications that can affect full-term infants. During pregnancy, birth or shortly after birth, a hypoxic-ischemic event can occur that impedes blood flow and oxygen delivery to the brain, resulting in destruction of brain tissue. Cooling (therapeutic hypothermia) is now standard for newborns with HIE in order to stave off life-long consequences, but deaths and neurodevelopmental disability still can occur.

“We know whole-body cooling – or lowering the body’s temperature by about 3 degrees Celsius – can help vulnerable newborns survive and can protect their brains from suffering profound injuries,” says An N. Massaro, M.D., a Children’s National neonatologist and senior author of the study published online Sept. 28, 2017 in American Journal of Perinatology.  “What we were trying to determine with this study is whether evaluating the pattern of evolution of the aEEG as a whole provides more information compared with looking at snapshots in time.”

Eighty infants undergoing therapeutic cooling who met the inclusion criteria were enrolled in the five-year study, one of the largest such studies to date. The babies weighed more than 1,800 grams and were older than 35 weeks’ gestational age at birth, and either needed prolonged resuscitation after birth or had low APGAR scores – a measure of how well newborns fare outside the womb. Continuous recordings of EEG data occurred from the time of admission up to 12 hours after the infants’ temperatures were raised to normal and aEEG tracings were calculated.

After the therapeutic cooling blankets were removed, the infants underwent at least one magnetic resonance imaging (MRI) scan prior to discharge. During the routine follow-up check at about 18 months of age, the HIE survivors’ cognitive and motor skills were assessed using validated instruments.

Fifty-six of the infants in the study had favorable outcomes. Twenty-four infants had adverse outcomes, including 15 with severe brain injury detected by MRI and nine infants who died. These children had lower APGAR scores at five minutes, and were more likely to have severe HIE and to have experienced more frequent seizures.

“Infants whose aEEG abnormalities do not improve were at increased risk: Infants who do not reach a discontinuous background pattern by 15.5 hours of life, achieve cycling by 45.5 hours after birth and who fail to achieve continuous normal voltage by 78 hours after birth are most at risk for adverse outcomes,” Dr. Massaro says. “In addition to defining worrisome trends, we found that overall assessment of continuous aEEG readings through the course of hypothermia treatment provide the most meaningful predictive power. This means we can speak with families at the bedside with more confidence about their child’s outcomes after the infant undergoes cooling therapy.”

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Roberta DeBiasi and Sarah Mulkey

Children’s National experts contribute to new Zika guidelines

Roberta DeBiasi and Sarah Mulkey

Roberta DeBiasi, M.D., M. S., and Sarah B. Mulkey, M.D., Ph.D., members of Children’s multidisciplinary Congenital Zika Virus Program, were among the experts invited to participate in a forum held in Atlanta at CDC headquarters in late August to formulate new Zika recommendations.

The Centers for Disease Control and Prevention (CDC) on Oct. 19, 2017 updated guidelines for evaluation of women, fetuses and infants exposed to the Zika virus during pregnancy. Although only women with symptoms will now be routinely tested, asymptomatic and symptomatic infants born to these women will still be tested for the Zika virus using blood and urine tests.

Infants who appear normal, whose mothers either had negative Zika results or who had not undergone testing, will not undergo Zika testing. These infants still will undergo a standard evaluation, including a detailed physical exam, hearing screen and routine developmental assessments. The revised Zika guidance includes input from practitioners on the front lines of the Zika epidemic, including Children’s National Health System clinicians.

“These changes in the recommendations for Zika testing should not be interpreted as Zika infection risks subsiding for pregnant women and their infants in the United States. It’s simply an acknowledgement of the limitations of current testing methods – which must occur within a narrow window after Zika exposure – and the poor predictive value of Zika testing right now,” says Roberta L. DeBiasi, M.D., M.S., chief of Children’s Division of Pediatric Infectious Diseases. Dr. DeBiasi and Sarah B. Mulkey, M.D., Ph.D., members of Children’s multidisciplinary Congenital Zika Virus Program, were among the experts invited to participate in the Zika forum held in Atlanta at CDC headquarters in late August to formulate the recommendations.

While all infants will receive a standard evaluation, expanded evaluations that include an ophthalmologic assessment, more detailed hearing evaluation and ultrasound of the newborn’s head will be reserved for infants born to mothers confirmed to be Zika positive or Zika probable, or for infants born with abnormalities potentially consistent with congenital Zika syndrome, regardless of maternal status.

The majority of U.S. infants who have been exposed to Zika in the womb appeared normal at birth, according to CDC registries. Now, the next wave of these normal-appearing babies will receive standard evaluations when they are born, including a newborn hearing screening. At each well-child visit, these infants will receive:

  • A comprehensive physical examination
  • An age-appropriate vision screening
  • Developmental monitoring and screening using validated tools

“This is a natural evolution in the diagnosis and screening strategy now that the peak of the first wave of Zika transmission appears to be over,” Dr. DeBiasi says. “While we continue to evaluate new possible cases of Zika infection among pregnant women in our practice, a sizable proportion of Children’s cases are Zika-exposed infants whose physical exam and neuroimaging appeared normal at birth. Through ongoing monitoring, we hope to learn more about these children’s long-term neurodevelopment outcomes.”

NICU Nurse Manager receives the 2017 Richard Hader Visionary Leader Award

Maureen Maurano accepts the 2017 Richard Hader Visionary Leader Award at the Nursing Management Congress 2017.

Maureen Maurano accepts the 2017 Richard Hader Visionary Leader Award at the Nursing Management Congress 2017.

Maureen Maurano, NICU Nurse Manager at Children’s National Health System, was honored as the winner of the 2017 Richard Hader Visionary Leader Award at the Nursing Management Congress 2017 held October 2-6, 2017 in Las Vegas, Nevada. The annual award recognizes excellence in nursing leadership and awards a nurse leader who views nursing as both an art and a science by promoting caring and competence as the link between science and humanity.

The winner of the award is nominated by a colleague and is entered into the competition after the Nursing Management journal’s editorial board has received a 2,000 word manuscript detailing the nominee’s accomplishment in the planning, development, implementation and evaluation of a sustainable change in the work environment or clinical practice that has resulted in a positive outcome. The editorial board selects the winner based on the manuscript’s readability, originality, and evidence of credibility. The winning manuscript will be featured in the January 2018 issue of Nursing Management.

“I am truly honored to have accepted this Visionary Leadership Award, however, this could not have been achieved without our amazing leadership and nursing team,” says  Maurano. “It is truly a team effort that empowers our success on a daily basis in providing the most innovative and world-class care for our patients at Children’s.”

Vice President of Nursing and Chief Nursing Officer, Linda Talley says, “Maureen is an outstanding nurse leader who exemplifies our core values – commitment, compassion and connection – through her engagement of others, creating a positive work environment and driving change that has a positive influence on the professional practice of nursing.  We are very proud of her and the recognition she has so deservedly earned.”

With a crowd of over 2,000 medical professionals, Maurano accepted her award as a leader of excellence representing the U.S. News and World Report #1 NICU for babies. Congratulations again Maureen for receiving this great honor!

Sarah Mulkey

Fetal MRI plus ultrasound assess Zika-related brain changes

Sarah Mulkey

Magnetic resonance imaging and ultrasound provide complementary data needed to assess ongoing changes to the brains of fetuses exposed to Zika in utero, says Sarah B. Mulkey, M.D., Ph.D.

For Zika-affected pregnancies, fetal magnetic resonance imaging (MRI) used in addition to standard ultrasound (US) imaging can better assess potential brain abnormalities in utero, according to research presented by Children’s National Health System during IDWeek 2017. In cases of abnormal brain structure, fetal MRI can reveal more extensive areas of damage to the developing brain than is seen with US.

“MRI and US provide complementary data needed to assess ongoing changes to the brains of fetuses exposed to Zika in utero,” says Sarah B. Mulkey, M.D., Ph.D., a fetal/neonatal neurologist at Children’s National Health System and lead author of the research paper. “In addition, our study found that relying on ultrasound alone would have given one mother the false assurance that her fetus’ brain was developing normally while the sharper MRI clearly pointed to brain abnormalities.”

As of Sept. 13, the Centers for Disease Control and Prevention (CDC) reported that 1,901 U.S. women were exposed to Zika at some point during their pregnancies but their infants appeared normal at birth. Another 98 U.S. women, however, gave birth to infants with Zika-related birth defects.  And eight more women had pregnancy losses with Zika-related birth defects, according to CDC registries.

The longitudinal neuroimaging study led by Children’s National enrolled 48 pregnant women exposed to the Zika virus in the first or second trimester whose infection was confirmed by reverse transcription polymerase chain reaction, which detects Zika viral fragments shortly after exposure, and/or Immunoglobulin M testing, which reveals antibodies the body produces to neutralize the virus. Forty-six of the study volunteers live in Barranquilla, Colombia, where Zika infection is endemic. Two women live in the Washington region and were exposed to Zika during travel elsewhere.

All of the women underwent at least one diagnostic imaging session while pregnant, receiving an initial MRI or US at 25.1 weeks’ gestational age. Thirty-six women underwent a second MRI/US imaging pair at roughly 31 weeks’ gestation. Children’s National radiologists read every image.

Three of 48 pregnancies, or 6 percent, were marked by abnormal fetal MRIs:

  • One fetus had heterotopias (clumps of grey matter located at the wrong place) and abnormal cortical indent (a deformation at the outer layer of the cerebrum, a brain region involved in consciousness). The US taken at the same gestational age for this fetus showed its brain was developing normally.
  • Another fetus had parietal encephalocele (an uncommon skull defect) and Chiari malformation Type II (a life-threatening structural defect at the base of the skull and the cerebellum, the part of the brain that controls balance). The US for this fetus also detected these brain abnormalities.
  • The third fetus had a thin corpus callosum (bundle of nerves that connects the brain’s left and right hemispheres), an abnormally developed brain stem, temporal cysts, subependymal heterotopias and general cerebral/cerebellar atrophy. This fetal US showed significant ventriculomegaly (fluid-filled structures in the brain that are too large) and a fetal head circumference that decreased sharply from the 32nd to 36th gestational week, a hallmark of microcephaly.

After they were born, infants underwent a follow-up MRI without sedation and US. For nine infants, these ultrasounds revealed cysts in the choroid plexus (cells that produce cerebrospinal fluid) or germinal matrix (the source for neurons and glial cells that migrate during brain development). And one infant’s US after birth showed lenticulostriate vasculopathy (brain lesions).

“Because a number of factors can trigger brain abnormalities, further studies are needed to determine whether the cystic changes to these infants’ brains are attributable to Zika exposure in the womb or whether some other insult caused these troubling results,” Dr. Mulkey says.

What Children’s has learned about congenital Zika infection

Roberta DeBiasi

Roberta DeBiasi, M.D., M.S., outlined lessons learned during a pediatric virology workshop at IDWeek2017, one of three such Zika presentations led by Children’s National research-clinicians during this year’s meeting of pediatric infectious disease specialists.

The Congenital Zika Virus Program at Children’s National Health System provides a range of advanced testing and services for exposed and infected fetuses and newborns. Data that the program has gathered in evaluating and managing Zika-affected pregnancies and births may offer instructive insights to other centers developing similar programs.

The program evaluated 36 pregnant women and their fetuses from January 2016 through May 2017. Another 14 women and their infants were referred to the Zika program for postnatal consultations during that time.

“As the days grow shorter and temperatures drop, we continue to receive referrals to our Zika program, and this is a testament to the critical need it fulfills in the greater metropolitan D.C. region,” says Roberta L. DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases and co-leader of the program. “Our multidisciplinary team now has consulted on 90 dyads (mothers and their Zika-affected fetuses/infants). The lessons we learned about when and how these women were infected and how their offspring were affected by Zika may be instructive to institutions considering launching their own programs.”

Dr. DeBiasi outlined lessons learned during a pediatric virology workshop at IDWeek2017, one of three such Zika presentations led by Children’s National research-clinicians during this year’s meeting of pediatric infectious disease specialists.

“The Zika virus continues to circulate in dozens of nations, from Angola to the U.S. Virgin Islands. Clinicians considering a strategic approach to managing pregnancies complicated by Zika may consider enlisting an array of specialists to attend to infants’ complex care needs, including experts in fetal imaging, pediatric infectious disease, physical therapists, audiologists, ophthalmologists and radiologists skilled at reading serial magnetic resonance images as well as ultrasounds,” Dr. DeBiasi says. “At Children’s we have a devoted Zika hotline to triage patient and family concerns. We provide detailed instructions for referring institutions explaining protocols before and after childbirth, and we provide continuing education for health care professionals.”

Of the 36 pregnant women possibly exposed to Zika during pregnancy seen in the program’s first year, 32 lived in the United States and traveled to countries where Zika virus was circulating. Two women had partners who traveled to Zika hot zones. And two moved to the Washington region from places where Zika is endemic. Including the postnatal cases, 89 percent of patients had been bitten by Zika-tainted mosquitoes, while 48 percent of women could have been exposed to Zika via sex with an infected partner.

Twenty percent of the women were exposed before conception; 46 percent were exposed to Zika in the first trimester of pregnancy; 26 percent were exposed in the second trimester; and 8 percent were exposed in the final trimester. In only six of 50 cases (12 percent) did the Zika-infected individual experience symptoms.

Zika infection can be confirmed by detecting viral fragments but only if the test occurs shortly after infection. Twenty-four of the 50 women (nearly 50 percent) arrived for a Zika consultation outside that 12-week testing window. Eleven women (22 percent) had confirmed Zika infection and another 28 percent tested positive for the broader family of flavivirus infections that includes Zika. Another detection method picks up antibodies that the body produces to neutralize Zika virus. For seven women (14 percent), Zika infection was ruled out by either testing method.

“Tragically, four fetuses had severe Zika-related birth defects,” Dr. DeBiasi says. “Due to the gravity of those abnormalities, two pregnancies were not carried to term. The third pregnancy was carried to term, but the infant died immediately after birth. The fourth pregnancy was carried to term, but that infant survived less than one year.”

Catherine Limperopoulous

Brain impairment in newborns with CHD prior to surgery

Catherine Limperopoulous

Children’s National researchers led by Catherine Limperopoulos, Ph.D., demonstrate for the first time that the brains of high-risk infants show signs of functional impairment before they undergo corrective cardiac surgery.

Newborns with congenital heart disease (CHD) requiring open-heart surgery face a higher risk for neurodevelopmental disabilities, yet prior studies had not examined whether functional brain connectivity is altered in these infants before surgery.

Findings from a Children’s National Health System study of this question suggest the presence of brain dysfunction early in the lives of infants with CHD that may be associated with neurodevelopmental impairments years later.

Using a novel imaging technique, Children’s National researchers demonstrated for the first time that the brains of these high-risk infants already show signs of functional impairment even before they undergo corrective open heart surgery. Looking at the newborns’ entire brain topography, the team found intact global organization – efficient and effective small world networks – yet reduced functional connectivity between key brain regions.

“A robust neural network is critical for neurons to travel to their intended destinations and for the body to carry out nerve cells’ instructions. In this study, we found the density of connections among rich club nodes was diminished, and there was reduced connectivity between critical brain hubs,” says Catherine Limperopoulos, Ph.D., director of the Developing Brain Research Laboratory at Children’s National and senior author of the study published online Sept. 28, 2017 in NeuroImage: Clinical. “CHD disrupts how oxygenated blood flows throughout the body, including to the brain. Despite disturbed hemodynamics, infants with CHD still are able to efficiently transfer neural information among neighboring areas of the brain and across distant regions.”

The research team led by Josepheen De Asis-Cruz, M.D., Ph.D., compared whole brain functional connectivity in 82 healthy, full-term newborns and 30 newborns with CHD prior to corrective heart surgery. Conventional imaging had detected no brain injuries in either group. The team used resting state functional connectivity magnetic resonance imaging (rs-fcMRI), a imaging technique that characterizes fluctuating blood oxygen level dependent signals from different regions of the brain, to map the effect of CHD on newborns’ developing brains.

The newborns with CHD had lower birth weights and lower APGAR scores (a gauge of how well brand-new babies fare outside the womb) at one and five minutes after birth. Before the scan, the infants were fed, wrapped snugly in warm blankets, securely positioned using vacuum pillows, and their ears were protected with ear plugs and ear muffs.

While the infants with CHD had intact global network topology, a close examination of specific brain regions revealed functional disturbances in a subnetwork of nodes in newborns with cardiac disease. The subcortical regions were involved in most of those affected connections. The team also found weaker functional connectivity between right and left thalamus (the region that processes and transmits sensory information) and between the right thalamus and the left supplementary motor area (the section of the cerebral cortex that helps to control movement). The regions with reduced functional connectivity depicted by rs-fcMRI match up with regional brain anomalies described in imaging studies powered by conventional MRI and diffusion tensor imaging.

“Global network organization is preserved, despite CHD, and small world brain networks in newborns show a remarkable ability to withstand brain injury early in life,” Limperopoulos adds. “These intact, efficient small world networks bode well for targeting early therapy and rehabilitative interventions to lower the newborns’ risk of developing long-term neurological deficits that can contribute to problems with executive function, motor function, learning and social behavior.”

mom and baby

Improving NICU discharge for families and staff

mom and baby

The day of discharge from a neonatal intensive care unit (NICU) can be overwhelming for families and for hospital staff. A Children’s National Health System team found that beginning discharge education early, communicating in ways attuned to families’ needs and using a classroom setting to teach hands-on skills for newborn care can improve parents’ experience during the discharge process, according to a study presented at the 2017 American Academy of Pediatrics (AAP) national conference.

“So much innovation in our NICU comes from listening to parents,” says Michelande Ridoré, M.S., program lead in Children’s Division of Neonatology. “Beyond caring for the child, we also care for the family, and input from parents helps improve our processes and improve parents’ readiness to care for their child when a NICU baby is ready to go home.”

With discharge, the first hint of a problem in the NICU came from lagging Press Ganey scores, measures of families’ satisfaction with their overall hospital experience. Parents whose very sick infants had round-the-clock care felt overwhelmed by the array of skills they needed to learn to replicate that care at home. NICU staff determined the root cause of the problem and, using the Institute for Healthcare Improvement’s Model for Improvement, former NICU parents, nurse educators, family support specialists and quality improvement managers crafted strategies to ameliorate them.

Already, Children’s NICU parents can “room in,” sleeping in their child’s room overnight as discharge nears in order to practice caring for a child with complex care needs. Children’s goal was to increase the number of discharge education sessions so that 90 percent of parents would receive discharge guidance more than 24 hours before their newborn was released from the NICU. The sessions included such staples as how to bathe and feed newborns who often were intubated; the benefits of skin-to-skin contact that characterizes kangaroo care; the child’s diagnosis and immunization status; optimal placement while sleeping; a hearing test and a car seat test, among other information.

“When we speak with parents, they said ‘I had no idea my car seat expired. I had no idea I needed to stay for a car seat test. You had an x, y and z list for me to take my child home. Now, I’ve interacted with someone who told me about that check list and how important it is,’ ” Ridoré says.

Many parents received the one-hour sessions in a classroom setting. On the door to their child’s room, they received alerts indicating whether they had completed courses. Beside the bed was a poster to help track progress toward discharge goals.

According to the study authors, the initiative boosted the number of parents who received discharge training in the 24 hours prior to discharge by 27 percent, a figure that grew over time to a 36 percent boost in such timely communication. Satisfaction scores improved and, in interviews, NICU staff said the process improvements streamlined how much time it takes to prepare families for discharge.

“Preparing parents for discharge in a classroom setting was a successful way to increase the number of families who receive this education before their child prepares to leave the NICU,” Ridoré says. “Families and nurses are happy. In the next phase of this research, we will quantify improvements in satisfaction and further refine pre-discharge training sessions.”

Latina mother playing with her baby boy son on bed

Helping parents of babies leaving NICU cope

Latina mother playing with her baby boy son on bed

A study team from Children’s National tried to determine factors closely associated with poor emotional function in order to identify at-risk parents most in need of mental health support.

Nearly half of parents reported depressive symptoms, anxiety and stress when their infants were discharged from the neonatal intensive care unit (NICU), and parents who were the most anxious were the most depressed. A Children’s National Health System team presented these research findings during the 2017 American Academy of Pediatrics (AAP) national conference.

Because their infants’ lives hang in the balance, NICU parents are at particular risk for poor emotional function, including mood disorders, anxiety and distress. Children’s National Neonatologist Lamia Soghier, M.D., and the study team tried to determine factors closely associated with poor emotional function in order to identify at-risk parents most in need of mental health support.

The study team enrolled 300 parents and infants in a randomized controlled clinical trial that explored the impact of providing peer-to-peer support to parents after their newborns are discharged from the NICU. The researchers relied on a 10-item tool to assess depressive symptoms and a 46-question tool to describe the degree of parental stress. They used regression and partial correlation to characterize the relationship between depressive symptoms, stress, gender and educational status with such factors as the infant’s gestational age at birth, birth weight and length of stay.

Some 58 percent of the infants in the study were male; 58 percent weighed less than 2,500 grams at birth; and the average length of stay for 54 percent of infants was less than two weeks. Eighty-nine percent of parents who completed the surveys were mothers; 44 percent were African American; and 45 percent reported having attained at least a college degree. Forty-three percent were first-time parents.

About 45 percent of NICU parents had elevated Center for Epidemiological Studies Depression Scale (CES-D) scores.

“The baby’s gender, gestational age at birth and length of NICU stay were associated with the parents having more pronounced depressive symptoms,” Dr. Soghier says. “Paradoxically, parents whose newborns were close to full-term at delivery had 6.6-fold increased odds of having elevated CES-D scores compared with parents of preemies born prior to 28 weeks’ gestation. Stress levels were higher in mothers compared with fathers, but older parents had lower levels of stress than younger parents.”

Dr. Soghier says the results presented at AAP are an interim analysis. The longer-term PCORI-funded study continues and explores the impact of providing peer support for parents after NICU discharge.