Public Health

distressed woman holding baby

When depression lingers after the NICU

distressed woman holding baby

Roughly half a million babies end up in the neonatal intensive care unit (NICU) each year in the U.S., often sending their parents on a wild emotional rollercoaster. Like other new parents, many parents feel symptoms of depression when their child leaves the NICU. For the majority, these depressive symptoms lift over time. But for others, depression can persist, affecting their well-being and relationships, including those with their new babies.

Thus far, it’s been unclear which parents are at a higher risk for this lasting depression. However, a new study led by Children’s researchers and presented at the Pediatric Academic Societies 2018 annual meeting suggests that parents whose depression lingers six months after their child’s NICU discharge tend to share certain demographic characteristics: They’re younger, have less education and care for more than one child.

“Using a validated screening tool, we found that 40 percent of parents in our analyses were positive for depression at the time their newborn was discharged from the NICU,” says Karen Fratantoni, M.D., M.P.H., a Children’s pediatrician and the lead study author. “It’s reassuring that, for many parents, these depressive symptoms ease over time. However for a select group of parents, depression symptoms persisted six months after discharge. Our findings help to ensure that we target mental health screening and services to these more vulnerable parents,” Dr. Fratantoni adds.

The study is an offshoot from “Giving Parents Support (GPS) after NICU discharge,” a large, randomized clinical trial exploring whether providing peer-to-peer parental support after NICU discharge improves babies’ overall health as well as their parents’ mental health.

Mothers of preterm and full-term infants who are hospitalized in NICUs are at risk for peripartum mood disorders, including postpartum depression. The Children’s research team sought to determine how many parents of NICU graduates experience depression and which characteristics are shared by parents with elevated depression scores.

They included 125 parents who had enrolled in the GPS clinical trial in their exploratory analyses and assessed depressive symptoms using a 10-item, validated screening tool, the Center for Epidemiological Studies Depression Scale (CES-D). Eighty-four percent of the parents were women. Nearly 61 percent of their infants were male and were born at a median gestational age of 37.7 weeks and mean birth weight of 2,565 grams. The median length of time these newborns remained in the NICU was 18 days.

When the newborns were discharged, 50 parents (40 percent) had elevated CES-D scores. By six months after discharge, that number dropped to 17 parents (14 percent).Their mean age ranged from 26.5 to 30.6 years old.

“Parents of NICU graduates who are young, have less education and are caring for other children are at higher risk for persistent symptoms of depression,” says Dr. Fratantoni. “We know that peripartum mood disorders can persist for one year or more after childbirth so these findings will help us to better match mental health care services to parents who are most in need.”

An American College of Obstetricians and Gynecologists’ committee opinion issued May 2018 calls for all women to have contact with a maternal care provider within the first three weeks postpartum and to undergo a comprehensive postpartum visit no later than 12 weeks after birth that includes screening for postpartum depression and anxiety using a validated instrument.

Study co-authors include Lisa Tuchman, M.D., MPH, chief, Children’s Adolescent and Young Adult Medicine Division; Randi Streisand, Ph.D., Children’s interim chief of Psychology and Behavioral Health; Nicole S. Herrera; Katherine Kritikos and Lamia Soghier, M.D., Children’s neonatologist.

Presidnet's Award for Innovation in Research

President’s Award highlights innovative work by early-career researchers

Presidnet's Award for Innovation in Research

As part of Research and Education Week 2018, two Presidential awardees were recognized for their research contributions, Catherine “Katie” Forster, M.D., M.S., and Nathan Anthony Smith, Ph.D.

Catherine “Katie” Forster, M.D., M.S., and Nathan Anthony Smith, Ph.D., received the President’s Award for Innovation in Research honoring their respective research efforts to explore an understudied part of the microbiome and to shed light on an underappreciated player in nerve cell communication.

Drs. Forster and Smith received their awards April 19, 2018, the penultimate day of Research and Education Week 2018, an annual celebration of the excellence in research, education, innovation and scholarship that takes place at Children’s National Health System. This year marks the fifth time the President’s Award honor has been bestowed to Children’s faculty.

Dr. Forster’s work focuses on preventing pediatric urinary tract infections (UTIs). Frequently, children diagnosed with illnesses like spina bifida have difficulty urinating on their own, and they often develop UTIs. These repeated infections are frequently treated with antibiotics which, in turn, can lead to the child developing antibiotic-resistant organisms.

“The majority of the time if you culture these children, you’ll grow something. In a healthy child, that culture would indicate a UTI,” Dr. Forster says. “Children with neurogenic bladder, however, may test positive for bacteria that simply look suspect but are not causing infection. Ultimately, we’re looking for better ways to diagnose UTI at the point of care to better personalize antibiotic treatment and limit prescriptions for children who do not truly need them.”

Powered by new sequencing techniques, a research group that includes Dr. Forster discovered that the human bladder hosts a significant microbiome, a diverse bacterial community unique to the bladder. Dr. Forster’s research will continue to characterize that microbiome to determine how that bacterial community evolves over time and whether those changes are predictable enough to intervene and prevent UTIs.

“Which genes are upregulated in Escherichia coli and the epithelium, and which genes are upregulated by both in response to each other? That can help us understand whether genes being upregulated are pathogenic,” she adds. “It’s a novel and exciting research area with significant public health implications.”

Smith’s work focuses on the role of astrocytes, specialized star-shaped glial cells, in modulating synaptic plasticity via norepinephrine. Conventional thinking describes astrocytes as support cells but, according to Smith, astrocytes are turning out to be more instrumental.

Norepinephrine, a neurotransmitter that plays an essential role in attention and focus, is released by a process known as volume transmission, which is a widespread release of a neurotransmitter at once, says Smith, a principal investigator in Children’s Center for Neuroscience Research. Astrocytes, which outnumber neurons in the brain, are strategically and anatomically located to receive this diffuse input and translate it into action to modulate neural networks.

“We hypothesize that astrocytes are integral, functional partners with norepinephrine in modulating cortical networks,” Smith adds. “Since astrocytes and norepinephrine have been implicated in many central nervous system functions, including learning and attention, it is critical to define mechanistically how astrocytes and norepinephrine work together to influence neural networks. This knowledge also will be important for the development of novel therapeutics to treat diseases such as attention deficit hyperactivity disorder and epilepsy.”

Monika Goyal

Monika Goyal M.D., M.S.C.E., consultant on $5M NIH grant to reduce pediatric firearm injuries

Monika Goyal

Monika Goyal M.D., M.S.C.E., director of research in Children’s Division of Emergency Medicine and Trauma Services, has been named a consultant on a new $5 million National Institutes of Health research grant that represents the agency’s largest funding commitment in more than two decades to reduce pediatric firearm injuries.

“I am honored that Children’s National Health System is among the 12 universities and health systems around the nation selected to work collaboratively to identify solutions to lower pediatric deaths and injuries due to firearms,” Dr. Goyal says. “This grant will expand the nation’s research capacity on this important subject area and will power the next wave of research to inform policy at the state and national level.”

Dr. Goyal is a member of Children’s firearms research work group which has published or presented at academic meetings on topics that include efforts to reduce pediatric firearm-related injuries and the pivotal role pediatricians can play in reducing the burden of firearm-related injuries among children.

Faculty from Ann & Robert H. Lurie Children’s Hospital of Chicago/Northwestern University, Arizona State University, Brown University, Children’s National Health System, Columbia University, Harvard University, Medical College of Wisconsin, Michigan State University, University of Colorado, University of Michigan, University of Pennsylvania and University of Washington make up the Firearm-Safety Among Children & Teens Consortium (FACTS). The initiative is co-led by Rebecca Cunningham, M.D., and Marc Zimmerman, Ph.D., of the University of Michigan.

In addition to tapping the expertise of scientists and researchers who specialize in criminal justice, emergency medicine, pediatrics, psychology, public health and trauma surgery, FACTS will include a stakeholder group that includes teachers, parent groups, gun owners, firearm safety trainers and law enforcement partners.

The five-year grant will produce a number of deliverables, including:

  • A research agenda for the field of pediatric firearm injury
  • Generating preliminary data through five small pilot projects that focus on topics such as the epidemiology of pediatric firearm injuries and prevention of firearm injuries
  • A data archive on childhood firearm injury
  • Training for the next generation of researchers, including postdoctoral trainees and graduate students

Financial support for this research was provided by the National Institute of Child Health & Human Development under award number R24HD087149.

Gustavo Nino

New method may facilitate childhood respiratory research

Gustavo Nino

“The use of CRC is a potentially powerful translational approach to shed light on the molecular mechanisms that control airway epithelial immune responses in infants and young children. This novel approach enables us to study the origins of respiratory disease and its chronic progression through childhood and beyond,” observes Gustavo Nino, M.D., a Children’s pulmonologist and study senior author.

A new method perfected by a team at Children’s National Health System may help expand research into pulmonary conditions experienced by infants and children, an understudied but clinically important age group. The study describing the new technique was published in the December 2017 print edition of Pediatric Allergy and Immunology.

Using conditionally reprogrammed cells (CRCs), a technique that enables indefinite proliferation of cells in the lab, the team was able to produce cell cultures that have a number of advantages over standard cultures and that may make it easier and more efficient to conduct research into pediatric respiratory immune responses.

The epithelial cells that line human airways are crucial in controlling immune responses to viruses, allergens and other environmental factors. The function and dysfunction of these airway epithelial cells (AECs) play a key role in asthma, cystic fibrosis and other pulmonary conditions, many of which begin in early life.

To generate enough of these cells for research, scientists culture AECs from primary nasal and bronchial cell samples. Cells derived from adults have fueled research leading to new therapies and the discovery of key biomarkers. But little comparable research has been conducted in infants. Airway sampling in premature infants has not been reported, likely to due to airway size limitations and underlying comorbidities. Similarly, sampling in infants is limited by the need for bronchoscopy and sedation.

“A major barrier has been the lack of a good system to culture epithelial cells, since airway sampling in infants and children is a challenge,” says co-lead author, Geovanny F. Perez, M.D., co-director of Children’s Severe Bronchopulmonary Dysplasia Program. “We needed a better way to culture cells in this age group.”

While primary AECs do not survive long in the lab, that hurdle was recently overcome by a process that generates CRCs from the primary AECs of adults, making it possible to quickly generate cell cultures from specimens.

In this study, the Children’s team adapted that approach, producing CRCs from primary AECs of neonates and infants. The CRC induction successfully enabled AEC cultures from infants born prematurely and from bronchial specimens of young children.

Geovanny Perez

“A major barrier has been the lack of a good system to culture epithelial cells, since airway sampling in infants and children is a challenge,” says co-lead author, Geovanny F. Perez, M.D., co-director of Children’s Severe Bronchopulmonary Dysplasia Program. “We needed a better way to culture cells in this age group.”

“We found that the CRCs have longer cell life and greater proliferation ability than standard cultures of epithelial cells. They preserved their original characteristics even after multiple experiments. And, they presented an innate immune response similar to that seen in primary human epithelial cells during viral respiratory responses in children,” says Dr. Perez.

“The use of CRC is a potentially powerful translational approach to shed light on the molecular mechanisms that control airway epithelial immune responses in infants and young children. This novel approach enables us to study the origins of respiratory disease and its chronic progression through childhood and beyond,” observes Gustavo Nino, M.D., a Children’s pulmonologist and study senior author.

The authors note that further studies are needed to define more precisely the differences and similarities in the immune responses of CRC and non-CRC derived from primary AEC. However, they conclude that CRC represents a new, effective method to study AEC innate immune responses in infants.

In addition to Drs. Perez and Nino, Children’s Center for Genetic Medicine Research co-authors include Co-Lead Author S. Wolf; Lana Mukharesh; Natalia Isaza Brando, M.D.; Diego Preciado, M.D., Ph.D.; Robert J. Freishtat, M.D., M.P.H.; Dinesh Pillai, M.D.; and M. C. Rose.

Financial support for this research was provided by the National Institute of Allergy and Infectious Diseases under grant number R21AI130502; Eunice Kennedy Shriver National Institute of Child Health and Human Development under grant number HD001399; National Heart, Lung and Blood Institute under grant number HL090020; and National Center for Advancing Translational Sciences under grant number UL1TR000075.

Adora Lin

Funding will help uncover immune system differences that trigger food allergies

Adora Lin

“When it comes to food allergies, we really don’t know how they develop. We don’t know how to best differentiate between a child who can safely eat a potential allergen, like peanuts, compared with a child who cannot safely eat peanuts.” says Adora A. Lin, M.D., Ph.D.

Adora A. Lin, M.D., Ph.D., an attending physician in Children’s department of Allergy and Immunology, was awarded $240,000 to improve understanding of how children’s immune systems tolerate or react to certain food allergens – sometimes triggering a cascade of side effects that can be fatal.

The three-year American Academy of Allergy, Asthma & Immunology (AAAAI) Foundation award will underwrite Dr. Lin’s ongoing research into the regulation of the antibody Immunoglobulin E (IgE), which plays a pivotal role in these allergic responses.

“Our immune system maintains a delicate balance, working just enough to ward off potential invaders and pathogens, but not so much that it triggers problems of its own making,” Dr. Lin says. “When it comes to food allergies, we really don’t know how they develop. We don’t know how to best differentiate between a child who can safely eat a potential allergen, like peanuts, compared with a child who cannot safely eat peanuts.”

Food allergies have become a growing problem and affect about 1 in 13 U.S. children, or about two per classroom. Food items such as eggs, milk, peanuts, tree nuts, soy and wheat trigger allergic reactions that can include itching, swelling, hives and difficulty breathing. As children’s immune systems react to exposure to such allergens, their B-cells produce IgE antibodies.

Apart from avoiding these foods and carrying rescue medications, which must be used immediately after accidental exposure, there is no way to treat food allergies effectively. That makes it essential to better understand how the immune system works in order to innovate new and better food allergy treatments and diagnostics.

Dr. Lin’s work involves isolating immune cells from blood samples, culturing them and stimulating an immune response to known food allergy triggers. B-cells make IgE, but additional clarity is needed about what turns on the “make IgE” signal as well as which signals indicate it’s time to stop making IgE. Ultimately, the aim is to identify biomarkers that are akin to the “check engine” light that illuminates to warn of a potential problem long before a car stalls in traffic.

“I’m very excited about this funding,” Dr. Lin adds. “Our field has done an exceptional job with clinical work to help children with food allergies. This award recognizes the importance of the mechanistic side of the equation. I’m excited to help make that contribution to the research.”

As it stands now, blood tests are sensitive to food-related IgE, but are not specific. Only 30 to 55 percent of children who have IgE to common food allergens have an allergic reaction after eating the food, which means that 45 to 70 percent are merely sensitized and could tolerate eating the food. Current tests cannot distinguish between sensitized and allergic children.

“Our hope is to identify biomarkers that would serve as the ‘check engine’ light that tell us in advance which child’s immune system will react strongly to that food. Right now, there is no way to tell. This project will help uncover those differences,” she says.

Dr. Lin was one of three recipients of the AAAAI Foundation’s faculty development award, which was presented during a March 3, 2018, award ceremony held during the organization’s business meeting.

ER Nurse

An unexpected discovery in a central line

ER Nurse

About a year and a half ago, a 6-year-old boy arrived at Children’s Emergency Department after accidently removing his own gastrointestinal feeding tube. He wasn’t a stranger to Children’s National Health System: This young patient had spent plenty of time at the hospital since birth. Diagnosed in infancy with an intestinal pseudo-obstruction, a rare condition in which his bowels acted as if there were a blockage even though one was not present, parts of his intestine died and had been removed through multiple surgeries.

Because of this issue and associated health problems, at 4 years old he had a central line placed in a large vein that leads to his heart. That replaced other central lines placed in his neck earlier after those repeatedly broke. This latest central line in his chest als0 had frequent breaks. It also had become infected with multidrug-resistant Klebsiella bacteria two years before he was treated at Children’s National for inadvertently removing his feeding tube.

On that day, he seemed otherwise well. His exam was relatively unremarkable, except for a small leak in his central line and a slight fever. Those findings triggered cultures taken both from blood flowing through his central line and the surrounding skin.

“No one expected him to grow anything from these cultures, especially from a child who looked so healthy,” explains Madan Kumar, a fellow in Children’s division of Pediatric Infectious Disease and a member of the child’s care team. But a mold grew prolifically. Further investigation from a sample sent to the National Institutes of Health showed that it was a relatively new species known as Mucor velutinosus.

Because such an infection had never been reported in a child whose immune system wasn’t extremely compromised from cancer, Kumar and team decided to publish a case report. The study appeared online Jan. 24, 2018, in the Journal of the Pediatric Infectious Diseases Society.

Kumar notes that this patient faced myriad challenges. Not only did he have a central line, but the line also had numerous problems, necessitating fixes that could increase the chance of infection. Additionally, because of his intestinal issues, he had a chronic problem with malabsorption of nutrients. Patients with this issue often are treated liberally with antibiotics. Although this intervention can kill “bad” bacteria that can cause an infection, they also knock out “good” bacteria that keep other microorganisms – like fungi – in check. On top of all of this, the patient was receiving a nutrient-rich formula in his central line to boost his caloric intake, yet another factor associated with infections.

Patients who develop this specific fungal infection are overwhelmingly adults who are immunocompromised, Kumar explains, including those with diabetes, transplant recipients, patients with cancer and those who have abnormally low concentrations of immune cells called neutrophils in their blood. The only children who tend to get this infection are preterm infants of very low birth weight who haven’t yet developed a robust immune response.

Because there was only one other published case report about a child with M. velutinosus – a 1-year-old with brain cancer who had undergone a bone marrow transplant – Kumar notes that he and colleagues were at a loss as to how best to treat their patient. “There’s a paucity of literature on what to do in a case like this,” he says.

Fortunately, the treatment they selected was successful. As soon as the cultures came back positive for this mold, the patient went on a three-week course of an antifungal drug known as amphotericin B. Surgeons also removed his infected central line and placed a new one. These efforts cured the patient’s infection and prevented it from spreading and potentially causing the multi-organ failure associated with these types of infections.

This case taught Kumar and colleagues quite a bit – knowledge that they wanted to share by publishing the case report. For example, it reinforces the importance of central line care. It also highlights the value of thoroughly investigating potential problems in a patient with risk factors, even one who appears otherwise healthy.

Finally, Kumar adds, the case emphasizes the importance of good antibiotic stewardship, which can help prevent patients from developing sometimes deadly secondary infections like this one. “This is not an organism that you see growing in a 6-year-old very often,” he says. “The fact that we saw it here speaks to the need to be judicious with broad-spectrum antibiotics so that we have a number of therapeutic options should we see unusual cases like this one.”

STAT Madness

Voters select Children’s National innovation as runner-up in national competition

STAT Madness

Facial recognition technology developed and tested by researchers with the Sheikh Zayed Institute for Pediatric Surgical Innovation and Rare Disease Institute at Children’s National was the runner-up in this year’s STAT Madness 2018 competition.

Facial recognition technology developed and tested by researchers with the Sheikh Zayed Institute for Pediatric Surgical Innovation and Rare Disease Institute at Children’s National was the runner up in this year’s STAT Madness 2018 competition. Garnering more than 33,000 overall votes in the bracket-style battle that highlights the best biomedical advances, the Children’s National entry survived five rounds and made it to the championship before falling short of East Carolina University’s overall vote count.

Children’s entry demonstrates the potential widespread utility of digital dysmorphology technology to diverse populations with genetic conditions. The tool enables doctors and clinicians to identify children with genetic conditions earlier by simply taking the child’s photo with a smartphone and having it entered into a global database for computer analyses.

The researchers partnered with the National Institutes of Health National Human Genome Research Institute and clinicians from 20 different countries to acquire pictures from local doctors for the study. Using the facial analysis technology, they compared groups of Caucasians, Africans, Asians and Latin Americans with Down syndrome, 22q11.2 deletion syndrome (also called DiGeorge syndrome) and Noonan syndrome to those without it. Based on more than 125 individual facial features, they were able to correctly identify patients with the condition from each ethnic group with more than a 93 percent accuracy rate. Missed diagnoses of genetic conditions can negatively impact quality of life and lead to premature death.

Children’s National also was among four “Editor’s Pick” finalists, entries that span a diverse range of scientific disciplines. Journalists at the digital publication STAT pored through published journal articles for 64 submissions in the single-elimination contest to honor a select group of entries that were the most creative, novel, and most likely to benefit the biomedical field and the general public.

Each year, 1 million children are born worldwide with a genetic condition that requires immediate attention. Because many of these children experience serious medical complications and go on to suffer from intellectual disability, it is critical that doctors accurately diagnose genetic syndromes as early as possible.

“For years, research groups have viewed facial recognition technology as a potent tool to aid genetic diagnosis. Our project is unique because it offers the expertise of a virtual geneticist to general health care providers located anywhere in the world,” says Marius George Linguraru, D.Phil., M.A., M.S., a Sheikh Zayed Institute for Pediatric Surgical Innovation principal investigator who invented the technology. “Right now, children born in under-resourced regions of the U.S. or the world can wait years to receive an accurate diagnosis due to the lack of specialized genetic expertise in that region.”

In addition to providing patient-specific benefits, Marshall Summar, M.D., director of Children’s Rare Disease Institute that partners in the facial recognition technology research, says the project offers a wider societal benefit.

“Right now, parents can endure a seemingly endless odyssey as they struggle to understand why their child is different from peers,” says Dr. Summar. “A timely genetic diagnosis can dispel that uncertainty and replace it with knowledge that can speed patient triage and deliver timely medical interventions.”

chromosome

X-linked genes help explain why boys of all ages face higher respiratory risk

chromosome

A multi-institution research team that includes Children’s National Health System attempted to characterize gender-based epigenomic signatures in the human airway early in children’s lives with a special attention to defining DNA methylation patterns of the X chromosome.

Human airways already demonstrate gender-based differences in DNA methylation signatures at birth, providing an early hint of which infants may be predisposed to develop respiratory disorders like asthma later in life, a research team reports in a paper published online April 3, 2018, in Scientific Reports.

It’s clear that boys and young men are more likely to develop neonatal respiratory distress syndrome, bronchopulmonary dysplasia, viral bronchiolitis, pneumonia, croup and childhood asthma. Unlike boys, girls have an additional copy of the X chromosome, which is enriched with immune-related genes, some of which play key roles in the development of respiratory conditions. Methylation prevents excessive gene activity in X-linked genes, however much remains unknown about how this process influences infants’ risk of developing airway diseases.

A multi-institution research team that includes Children’s National Health System attempted to characterize gender-based epigenomic signatures in the human airway early in children’s lives with a special attention to defining DNA methylation patterns of the X chromosome.

“It’s clear as we round in the neonatal intensive care unit that baby boys remain hospitalized longer than girls and that respiratory ailments are quite common. Our work provides new insights about gender differences in airway disease risk that are pre-determined by genetics,” says Gustavo Nino, M.D., a Children’s pulmonologist and the study’s senior author.

“Characterizing early airway methylation signatures holds the promise of clarifying the nature of gender-based disparities in respiratory disorders and could usher in more personalized diagnostic and therapeutic approaches.”

The research team enrolled 12 newborns and infants in the study and obtained their nasal wash samples. Six of the infants were born preterm, and six were born full term. The researchers developed a robust gender classification algorithm to generate DNA methylation signals. The machine learning algorithm identified X-linked genes with significant differences in methylation patterns in boys, compared with girls.

As a comparison group, they retrieved pediatric nasal airway epithelial cultures from a study that looked at genomic DNA methylation patterns and gene expression in 36 children with persistent atopic asthma compared with 36 heathy children.

The team went on to classify X-linked genes that had significant gender-based X methylation and those genes whose X methylation was variable.

“These results confirm that the X chromosome contains crucial information about gender-related genetic differences in different airway tissues,” Dr. Nino says. “More detailed knowledge of the genetic basis for gender differences in the respiratory system may help to predict, prevent and treat respiratory disorders that can affect patients over their entire lifetimes.”

In addition to Dr. Nino, study co-authors include Lead Author Cesar L. Nino, bioinformatics scientist, Pontificia Universidad Javeriana; Geovanny F. Perez, M.D., co-director of Children’s Severe Bronchopulmonary Dysplasia Program; Natalia Isaza Brando, M.D., Children’s neonatology attending; Maria J. Gutierrez, Johns Hopkins University School of Medicine; and Jose L. Gomez, Yale University School of Medicine.

Financial support for this research was provided by the National Institutes of Health under award numbers AI130502-01A1, HL090020, HL125474-03, HD001399, UL1TR000075 and KL2TR000076.

Sarah Mulkey

MRI finds novel brain defects in Zika-exposed newborns

Sarah Mulkey

“Imaging is constantly helping us make new discoveries with this virus, and in these two cases we found things that had not been previously described,” says Sarah Mulkey, M.D., Ph.D.

Magnetic resonance imaging (MRI) has identified two brain abnormalities never before reported in newborns with prenatal exposure to the Zika virus. Children’s National Health System researchers reported these findings from a study of more than 70 fetuses or newborns with Zika exposure in utero. The study was published in the January 2018 edition of Pediatric Neurology.

The two novel defects – cranial nerve enhancement and cerebral infarction – may join the growing list of neurological findings associated with congenital Zika infection.

“Imaging is constantly helping us make new discoveries with this virus, and in these two cases we found things that had not been previously described,” says Sarah Mulkey, M.D., Ph.D., the study’s lead author and a fetal-neonatal neurologist at Children’s National. Dr. Mulkey works in Children’s Congenital Zika Virus Program, one of the nation’s first comprehensive, dedicated Zika programs.

The research team recommends that postnatal brain MRI be considered in addition to ultrasound for newborns exposed to Zika in utero. “Brain MRI can be performed in the newborn often without sedation and provides an opportunity to look for brain abnormalities we might not catch otherwise – or might not detect until much later,” says Dr. Mulkey.

Birth defects are seen in 6 to 11 percent of pregnancies affected by Zika, and some of the neurological complications in infants are not apparent until well after birth.

Of the two infants in which the new abnormalities were observed, both had normal head size at birth. Neither had smaller-than-normal head size (microcephaly), one of the more severe effects associated with congenital Zika syndrome.

One infant had a normal neurological evaluation at 2 days of age. However, a brain MRI conducted the following day, using gadolinium contrast due to concern of infection, showed enhancement of multiple cranial nerves. “Nerve root enhancement is very rare in a newborn and had not been described with Zika before,” Dr. Mulkey says. “Yet, there was no neurological deficit that we could identify by physical exam.”

The research team acknowledges that the clinical significance of this finding is not yet known.

In the second patient, brain MRI conducted without contrast at 16 days of age revealed a small area consistent with chronic infarction (ischemic stroke) that likely occurred during the third trimester.

“We followed the mother throughout her pregnancy, and both MRI and ultrasound imaging were normal at 28 weeks gestation,” Dr. Mulkey says. “A postnatal ultrasound was also normal, but the postnatal MRI showed a stroke that had occurred at least one month prior to the MRI and after the last fetal study.”

She adds: “This is the first published report of fetal stroke associated with Zika infection, and it may add to our knowledge of what can occur with congenital Zika infection.”

Unlike most congenital infections, Zika virus does not appear to cause viral-induced placental inflammation, which can lead to fetal stroke. So, the authors say they cannot be sure that congenital Zika contributed to the infarct in this case. However, they write, “Given the relatively low incidence of perinatal ischemic infarct and the lack of other maternal- or birth-related risk factors for this patient, Zika infection is considered a possible etiology.”

In both patients, neonatal brain MRI identified subclinical findings that had not previously been described as part of congenital Zika syndrome. As the body of evidence about the Zika virus has grown, the spectrum of associated brain abnormalities has expanded to include considerably more findings than isolated microcephaly.

Data gathered in 2017 from the Centers for Disease Control and Prevention’s Zika pregnancy and infant registry indicates that 25 percent of eligible U.S. infants receive recommended postnatal imaging. Dr. Mulkey said this represents many possible missed opportunities for earlier identification of brain abnormalities.

“Brain MRI should be considered in all newborns exposed to Zika virus in utero, even in the presence of normal birth head circumference, normal cranial ultrasound and normal fetal imaging,” she says. “In both of these patients, the changes we observed were not evident on cranial ultrasound or on fetal MRI and fetal ultrasound.”

In addition to Dr. Mulkey, Children’s co-authors include L. Gilbert Vezina, M.D., Neuroradiology Program director; Dorothy I. Bulas, M.D., chief of Diagnostic Imaging and Radiology; Zarir Khademian, M.D., radiologist; Anna Blask, M.D., radiologist; Youssef A. Kousa, M.S., D.O., Ph.D., child neurology fellow; Lindsay Pesacreta, FNP; Adré  J. du Plessis, M.B.Ch.B., M.P.H., Fetal Medicine Institute director; and Roberta L. DeBiasi, M.D., M.S., senior author and Pediatric Infectious Disease division chief; and Caitlin Cristante, B.S.

Financial support for this research was provided by the Thrasher Research Fund.

Jennifer Porter

Jennifer L. Porter receives the 2018 National Minority Quality Forum 40 under 40 Award for Leaders in Minority Health

Jennifer Porter

Jennifer L. Porter, MPH, MCHES, 2018 NMQF 40 Under 40 Award Winner.

Jennifer L. Porter, government affairs specialist in the Child Health Advocacy Institute, has been selected as one of the 2018 National Minority Quality Forum 40 leaders under 40 in minority health for her achievements in advocacy and research on behalf of Children’s National Health System. The 2018 National Minority Quality Forum Leadership Summit on Health Disparities and Spring Health Braintrust will be held in Washington, D.C on April 16-17, 2018.

After receiving hundreds of applications from health care professionals across the country, 40 individuals were chosen to represent the next generation of thought leaders working to reduce health disparities and decrease health inequality for minority communities.

This award acknowledges Jennifer’s approach to bringing fresh ideas to help those suffering from poor access to quality health care and focuses on a wide range of adolescent sexual issues including: economic influences of medical adherence for HIV positive adolescents, structural barriers, HIV prevention for youth and pregnancy prevention outcomes.

Throughout her career, Mrs. Porter has been a tireless health advocate and has held a number of volunteer leadership positions in local, regional and national community service organizations. She currently serves as a commissioner for the District of Columbia Commission for Women; the National Health Policy Conference Advisory Committee and serves on the National Policy Advisory Group for Girls, Inc.

“When it comes down to advocacy, this award validates the importance of these types of roles where you never see the work behind the scenes,” says Porter. “Whether it’s research or advocacy, my mission is to make a positive impact on the changing health care landscape and to tell these people’s story with dignity and context.”

Along with U.S. Rep. John Lewis, Rep. Maxine Waters and Merck CEO Kenneth Frazier, Porter will accept her award during the leadership summit on April 16-17, 2018 in Washington, D.C. Congratulations again Jennifer for receiving this award!

Lawrence D'Angelo

Being a young parent while also HIV positive

Lawrence D'Angelo

“We realize that at some point in time, these patients will have to transition their care to an adult setting, and they will confront a different kind of health system,” says Lawrence D’Angelo, M.D., M.P.H. “We want to make sure all of their providers will be able to help them advocate for themselves and for their children.”

By the time the human immunodeficiency virus (HIV) – the virus that causes AIDS – first came to the public consciousness in the 1980s, it was clear that infected pregnant mothers readily pass it to their babies. For those infected babies to eventually have their own children was inconceivable then, says Lawrence J. D’Angelo, M.D., M.P.H., adolescent medicine specialist at Children’s National Health System. Before the advent of antiretroviral therapy, AIDS was universally fatal.

Now, about 22 percent of young adults with HIV have lived with this disease their entire lives. And like many people this age, they’re exploring romantic relationships, sex and – for some – parenthood. This unexpected turn of events, Dr. D’Angelo explains, has left many health care providers unprepared.

“We never expected that these individuals would live to reach early adulthood, so we certainly didn’t expect them to be involved in parenting,” he says. “We have no real knowledge of what to expect from them or how best to support them because we don’t understand what they’re going through.”

To learn more about these young parents living with perinatally acquired HIV (PHIV), Dr. D’Angelo worked with Cynthia Fair, professor of human services studies and public health studies coordinator at Elon University. The two conducted a qualitative assessment of parents with PHIV. After recruiting 17 individuals who fit this description directly from Dr. D’Angelo’s practice, interviewers on the research team sat down with study participants to have a conversation about what it was like to parent while also being HIV positive. They asked standard questions, such as: What do you think makes a good parent? And, describe your relationship with your parents or caregivers. How does this relate, if at all, to your views on parenthood?

The team then transcribed these interviews and fed the text into a qualitative analysis program. With the aid of this software, and their own manual analysis, the researchers found several themes emerge from the conversations.

About 90 percent of the interviews focused on challenges universal to nearly every parent: Worries about a baby taking a bottle or sleeping through the night, struggles with discipline, concerns about money. “For the most part, these are young parents with a chronic illness just trying to be good parents,” says Fair, lead author of the study published Nov. 1, 2017 in AIDS Patient Care and STDs.

However, she adds, HIV inserts an added layer of complexity. Many of the parents said they felt deprived of the opportunity to enjoy lives as long and healthy as their peers. Consequently, having a child carried a sense of pressure to accomplish more in life for their children and to leave a positive legacy. Some worried that their own HIV status would stigmatize their children and that people outside their families would automatically assume their children were HIV positive when they weren’t.

All but one parent in the study had a child who was HIV negative, but even those children require regular testing to make sure they maintain that status. Parents with infants prescribed preventive protocols spoke about the exhaustion of having to deliver prophylactic medicines around the clock. The sole parent in the study with an HIV-positive child was separated from the baby’s father; she talked about the stress of not knowing whether her baby was receiving the necessary medicines to stay healthy when the child wasn’t with her.

These young parents also spoke with interviewers about the role their own pediatric care providers played in helping them make the transition to parenthood. For example, social workers on one study participant’s care team stepped in when she had nowhere to live, finding her an appropriate shelter. Another talked about how her desire to be a good parent was strongly influenced by the care she was given by her medical providers growing up. Many of the study participants had lost one or both parents to HIV or had absentee parents due to incarceration or other causes, says Fair, making their relationships with their medical team one of the few constants they could count on.

That’s why helping care providers develop a deep understanding of the perspectives of PHIV parents is even more important, particularly as these individuals move from pediatric to adult care settings, says Dr. D’Angelo, the study’s senior author and director of the Youth Pride and Burgess Clinics at Children’s National.

“We realize that at some point in time, these patients will have to transition their care to an adult setting, and they will confront a different kind of health system,” he says. “We want to make sure all of their providers will be able to help them advocate for themselves and for their children.”

Millenial Panel at Population Strategies for Childrens Health Summit

Population health and value based care discussed at the Population Strategies for Children’s Health Summit

With sponsorship from Cerner Corporation, Children’s National held the first Population Strategies for Children’s Health (PSCH) event on February 19 – 20, 2018 at The Westin City Center in Washington, D.C. Speakers and attendees gathered from around the country to discuss pediatric population health and the transition to value based care.

PSCH opened with an insightful presentation from Ellen-Marie Whelan Ph.D., CRNP, FAAN, chief population health officer at the CMS Center for Medicaid and CHIP Services. Her presentation, “Medicaid Transformation to Value Based Care,” explored an incentivized health care delivery system reform that will result in better care, smarter spending and healthier people.

Sean Gleeson, M.D., M.B.A., president of Partners for Kids at Nationwide Children’s Hospital, spoke about the mechanics of Partners for Kids and the population health strategies they choose to implement. These strategies require an entire enterprise to be engaged and they must be an intentional component of each healthcare organization. Dr. Gleeson put it simply that population health turns healthcare “right side up” by tying financial incentives to positive value outcomes versus upside down when health organizations make more money when kids are sicker.

A presentation from William Feaster, M.D., M.B.A., chief medical information officer at CHOC Children’s Hospital, and Brian Jacobs, M.D., vice president, chief medical information officer and chief information officer at Children’s National Health System, delved into implementing condition-specific pediatric registries. They highlighted that it’s necessary to integrate registries and workflows into the daily work of clinicians and make them actionable to encourage engagement.

Another highlight of the conference was the millennial panel “The Current and Future State of Health Care from a Consumer’s Perspective.” The panel consisted of Janice Bitetti, a physician and mother of a 10-year-old with Type 1 diabetes; Jonathan Morris, a 15-year-old Type 1 Diabetes patient at Children’s National; and moderator Emily Webber, M.D., FAAP, chief medical information officer at Riley Children’s Hospital. Panel participants shared their take on the current state of Type 1 diabetes care, and the way millennials interact with healthcare. Both Jonathan and Janice agreed that the intensive nature of Type 1 diabetes care puts many families who don’t have the time, resources and initiative that they do in a very difficult place.

Other speakers throughout the two day event explored topics including population health strategies to reduce child health disparities, the role of telehealth in population health, care coordination and coaching to health, and technology in population health.

Millenial Panel at Population Strategies for Childrens Health Summit

Brian Jacobs, M.D. introduces the Millennial Panel at the Population Strategies for Children’s Health Summit.

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.

foods rich in folate

An ironclad way to prevent neural tube defects? Not yet

foods rich in folate

Researchers have known for decades that folate, a vitamin enriched in dark, leafy vegetables; fruit; nuts; and other food sources, plays a key role in preventing neural tube defects.

Every year, about 3,000 pregnancies in the U.S. are affected by neural tube defects (NTDs) –  birth defects of the brain, spine and spinal cord. These include anencephaly, in which a major part of the brain, skull and scalp is missing; and spina bifida, in which the backbone and membranes around the spinal cord don’t close properly during fetal development. These structural birth defects can have devastating effects: In the best cases, they might lead to mild but lifelong disability; in the worst cases, babies don’t survive.

Researchers have known for decades that folate, a vitamin enriched in dark, leafy vegetables; fruit; nuts; and other food sources, plays a key role in preventing NTDs. To help get more folate into pregnant women’s diets, wheat flour in the U.S. and many other countries is often fortified with folic acid, a synthetic version of this vitamin, as part of an intervention credited with significantly reducing the incidence of NTDs.

But folic acid supplementation isn’t enough, says Irene E. Zohn, Ph.D., a principal investigator at the Center for Neuroscience Research at Children’s National Health System who studies how genes and the environment interact during development. A significant number of NTDs still occur, suggesting that other approaches – potentially, other nutrients in the maternal diet – might provide further protection.

That’s why Zohn and colleagues decided to investigate iron. Iron deficiency is one of the most common micronutrient deficiencies in women of childbearing age, Zohn explains. Additionally, iron and folate deficiencies often overlap and signal overall poor maternal diets.

The idea that iron deficiency might play a role in NTDs came from studies by Zohn and colleagues of the flatiron mutant line of experimental models. This experimental model line has a mutation in a gene that transports iron across cell membranes, including the cells that supply embryos with this critical micronutrient.

To determine if NTDs develop in these mutant experimental models because of reduced iron transport, the researchers devised a simple experiment: They took female adult experimental models with the mutation and separated them into four groups. For several weeks, one group ate a diet that was high in folic acid. Another group ate a diet high in iron. The third group ate a diet high in both folic acid and iron. The fourth group ate standard chow. All of these experimental models then became pregnant with embryos that harbored the flatiron mutation, and the researchers assessed the offspring for the presence of NTDs.

Irene Zohn

“We were hoping that iron supplements would be the next folic acid, but it did not turn out that way,” says Irene E. Zohn, Ph.D. “Even though our results demonstrate that iron is important for proper neural tube development, giving extra iron definitely has its downsides.”

As they reported in Birth Defects Research, the dietary interventions successfully increased iron stores: Experimental model mothers whose diets were supplemented with iron, folic acid or both had increased concentrations of these micronutrients in their blood.

The dietary interventions also affected their offspring. While about 80 percent of flatiron mutant embryos fed a standard diet during pregnancy had NTDs, feeding a diet high in iron prevented NTDs in half of the offspring. This lower rate was similar in the offspring of mothers fed a diet high in both folic acid and iron, but not for those whose mothers ate just a diet high in folic acid. Those embryos had NTD rates as high as those who ate just the standard chow, suggesting that low iron was the cause of the high rates, not low folic acid.

Together, Zohn says, these experiments show that iron plays an important role in the development of the neural tube and that deficits in iron might cause some cases of NTDs. However, she notes, reducing NTDs isn’t nearly as simple as supplementing pregnant women’s diets with iron. In the same study, the researchers found that when they gave normal experimental models that didn’t have the flatiron mutation concentrated iron supplements – amounts akin to what doctors might prescribe for human patients with very severe iron-deficiency anemia – folate stores dropped.

That’s because these two micronutrients interact in the body with similar sites for absorption and storage in the intestines and liver, Zohn explains. At either the intestines or liver or at both locations, an iron overload might interfere with the body’s ability to absorb or use folate.

At this point, she says, giving high doses of iron routinely during pregnancy doesn’t look like a feasible way to prevent NTDs.

“We were hoping that iron supplements would be the next folic acid, but it did not turn out that way,” Zohn says. “Even though our results demonstrate that iron is important for proper neural tube development, giving extra iron definitely has its downsides.”

Zohn’s team plans to continue to investigate the role of iron, as well as the role of other micronutrients that might influence neural tube development.

Zohn’s coauthors include Bethany A. Stokes, The George Washington University, and Julia A. Sabatino, Children’s National.

Research reported in this story was supported by a grant from the Board of Visitors, Eunice Kennedy Shriver National Institute of Child Health & Human Development under award number R21-HD076202, the National Center for Research Resources under award number UL1RR031988, Children’s Research Institute and the National Institutes of Health under grant P30HD040677.

Janelle Vaughns

Few prescribing options exist for obese kids

Janelle Vaughns

“We are making progress in expanding the number of medicines with pediatric labeling, but we need to do more concerning providing dosing guidelines for children with obesity,” says Janelle D. Vaughns, M.D., director of bariatric anesthesia at Children’s National and the lead study author.

Despite years of study and numerous public health interventions, overweight and obesity continue to grow in the U.S. Currently, more than two-thirds of adults have these issues, according to data from the Centers for Disease Control and Prevention. Children and adolescents also are being affected at an increasing rate: About one in five is obese. Obesity and overweight have been linked with a bevy of health problems, including Type 2 diabetes, high blood pressure, coronary heart disease and stroke.

Additionally, because obesity increases the percentage of fat tissue in relation to lean tissue and enlarges kidney size, it can affect how readily the body takes up, metabolizes and excretes medicines.

This latter issue can be particularly problematic in children, a population for whom relatively few drug studies exist. Now, a study team that includes Children’s National Health System researchers suggests that, despite the U.S. Congress providing incentives to drug manufacturers to encourage the study of medications in children, few approved drugs include safe dosing information for obese kids.

The study, performed in conjunction with the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research, surveyed pediatric medical and clinical pharmacology reviews under the FDA Amendments Act of 2007 and the FDA Safety and Innovation Act of 2012. The researchers used search terms related to weight and size to determine the current incorporation of obesity as a covariate in pediatric drug development.

Of the 89 product labels identified, none provided dosing information related to obesity. The effect of body mass index on drug pharmacokinetics was mentioned in only four labels, according to the study “Obesity and Pediatric Drug Development,” published online Jan. 19, 2018, in The Journal of Clinical Pharmacology.

“We are making progress in expanding the number of medicines with pediatric labeling, but we need to do more concerning providing dosing guidelines for children with obesity,” says Janelle D. Vaughns, M.D., director of bariatric anesthesia at Children’s National and the lead study author. “Moving forward, regulators, clinicians and the pharmaceutical industry should consider enrolling more obese patients in pediatric clinical trials to facilitate the safe and effective use of the next generation of medicines by obese children and adolescents.”

Study co-authors include Children’s Gastroenterologist Laurie Conklin, M.D., and Children’s Division Chief of Clinical Pharmacology Johannes N. van den Anker, M.D., Ph.D.; Ying Long, Pharm.D., University of Southern California; Panli Zheng, Pharm.D., University of North Carolina at Chapel Hill; Fahim Faruque, Pharm.D., University of Maryland; and Dionna Green, M.D., and Gilbert Burckart, Pharm.D., both of the FDA.

Research reported in this news release was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award number 5T32HD087969.

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.

Love is in the air and, for parasites, inside our bodies

Michael H. Hsieh

As featured in a PBS video, schistosome worms form lifelong bonds and females produce thousands of eggs daily only when they live inside human hosts, says Michael H. Hsieh, M.D., Ph.D.

“Love is in the air, the sea, the earth and all over and inside our bodies,” the PBS Valentine’s Day-themed video begins. As the public television station notes, what humans consider romance can look vastly different for creatures big and small, including serenading mice, spiders who wrap their gifts in silk and necking giraffes.

The “spooning” parasites segment of the video is where viewers see research conducted by Michael H. Hsieh, M.D., Ph.D., director of the Clinic for Adolescent and Adult PedIatric OnseT UroLogy at Children’s National Health System, and video filmed in his lab.

Schistosomiasis, a chronic infection with schistosome worms, is a distinctly one-sided love affair. As shown in Dr. Hsieh’s video clips, the male worm is shorter and fatter and equipped with a groove, a love canal where the longer, thinner female lodges, enabling the pair to mate for decades. This lifelong bond and the thousands of eggs it produces daily can only occur when the worms are inside the human host, Dr. Hsieh says.

While the video stresses Valentine’s Day romance, there are few rosy outcomes for humans who are the subject of the schistosome worms’ attention.

“Heavily and chronically infected individuals can have lots of problems,” Dr. Hsieh says. “This is a stunting and wasting health condition that prevents people from reaching their growth potential, impairs their academic performance and leaves them sapped of the energy needed to exercise or work. It truly perpetuates a cycle of poverty, particularly for affected children.”

Even the potential bright spot in this sobering story, the ability of the body’s immune system to fend off the parasitic worms, is only partly good news.

Schistosome worms have co-evolved with their human hosts, learning to take advantage of human vulnerabilities. Take the immune system. If it kicks too far into overdrive in trying to wall off the eggs from the rest of the body, it can interfere with organ function and trigger liver failure, kidney failure and early onset of bladder cancer, he says.

However, Dr. Hsieh and other schistosomiasis researchers are working on ways to positively harness the human immune response to schistosome worms, including developing diagnostics, drugs and vaccines. He says he and his colleagues would “love” to eliminate schistosomiasis as a global scourge.

Kavita Parikh

Discharge strategies to prevent asthma readmissions

“Improving how we care for children who are hospitalized with asthma includes preparing them for a successful return home with the best tools to manage their illness and prevent a future hospital visit,” says Kavita Parikh, M.D., M.S.H.S.

Readmission rates at three months for kids hospitalized for acute asthma dropped when families received comprehensive education prior to discharge, the only single component of discharge bundles that was strongly associated with lowered readmissions, finds a multicenter retrospective cohort study published online Feb. 1, 2018, in The Journal of Pediatrics.

According to the Centers for Disease Control and Prevention, asthma is the most common chronic lung disease of childhood, affecting roughly 6 million U.S. children. Hospitalization for asthma accounts for $1.5 billion in annual hospital charges and represents almost one-third of childhood asthma costs.

Children who are hospitalized for asthma have a roughly 20 percent chance of returning to the hospital in the next year, and individual hospital readmission rates can range from 5.7 percent to 9.1 percent at three months, writes the study team. While the National Institutes of Health (NIH) has published evidence-based guidelines for discharge planning, there is no single, standardized asthma discharge process used across all pediatric hospitals in the U.S. that impacts 30-day readmission rates.

“Improving how we care for children who are hospitalized with asthma includes preparing them for a successful return home with the best tools to manage their illness and prevent a future hospital visit,” says Kavita Parikh, M.D., M.S.H.S., an associate professor of pediatrics at Children’s National Health System and lead study author. “Our study underscores the importance of increasing the intensity of select discharge components. For example, ensuring that children hospitalized for asthma receive asthma medication at discharge along with comprehensive education and environmental mitigation may reduce asthma readmissions.”

The study team analyzed records from a national sample of tertiary care children’s hospitals, looking at hospitalizations of 5- to 17-year-olds for acute asthma exacerbation during the 2015 calendar year. They characterized how frequently hospitals used 13 separate asthma discharge components by distributing an electronic survey to quality leaders. Forty-five of 49 hospitals (92 percent) completed the survey.

The 45 hospitals recorded a median of 349 asthma discharges per year and had a median adjusted readmission rate of 2.6 percent at 30 days and a 6.6 percent median adjusted readmission rate at three months. The most commonly used discharge components employed for children with asthma were having a dedicated person providing education (76 percent), providing a spacer at discharge (67 percent) and communicating with a primary medical doctor (58 percent).

Discharge components that were trending toward reduced readmission rates at three months include:

  • Comprehensive asthma education, including having dedicated asthma educators
  • Medications and devices provided to patients at discharge, such as spacers, beta-agonists, controller medication and oral steroids
  • Communication and scheduled appointments with a primary medical doctor
  • Post-discharge activities, including home visits and referrals for environmental mitigation programs.

“In addition to being aligned with NIH asthma recommendations, connecting the family with a primary care provider after discharge helps to improve patients’ timely access to care if symptoms recur when they return home,” Dr. Parikh adds. “Bundling these discharge components may offer multiple opportunities to educate patients and families and to employ a range of communication styles such as didactic, visual and interactive.”

Study co-authors include Matt Hall, Ph.D., Children’s Hospital Association; Chén C. Kenyon, M.D., M.S.H.P., The Children’s Hospital of Philadelphia; Ronald J. Teufel II, M.D., M.S.C.R., Medical University of South Carolina; Grant M. Mussman, M.D., M.H.S.A. and Samir S. Shah, M.D., M.S.C.E., Cincinnati Children’s Hospital Medical Center; Amanda Montalbano, M.D., M.P.H., Children’s Mercy; Jessica Gold, M.D., M.S., Lucile Packard Children’s Hospital Stanford; James W. Antoon, M.D., Children’s Hospital; Anupama Subramony, M.D., Cohen Children’s Medical Center; Vineeta Mittal, M.D., M.B.A. and Rustin B. Morse, M.D., Children’s Health; and Karen M. Wilson, M.D., M.P.H., Icahn School of Medicine at Mount Sinai.

Research reported in this post was supported by the Agency for Healthcare Research and Quality, K08HS024554.

Dr. Kurt Newman in front of the capitol building

Leading conversations about what’s right for children

Dr. Kurt Newman in front of the capitol building

“Who speaks for children?” That’s a question Children’s National President and CEO Kurt Newman, M.D., often asks when he talks to groups around the country. As he sees it, children’s hospitals and their pediatric specialists should follow two main principles: Speak out to our nation’s policy leaders, local government officials and other business leaders about what’s right for the most vulnerable among us, namely our children; and listen to parents, helping them find their voices when it comes to health care decisions.

Pediatric specialists have a unique opportunity to serve as the voice for children and families who are so often lost in state and federal health care policy debates. As the children’s hospital located in the nation’s capital, Children’s National has leveraged both its expertise and close proximity to key decision makers to engage in a dialogue about issues vital to the health and well-being of kids.

Amplifying the CHIP call to action

In a perfect example of politics getting in the way of doing the right thing for children, it took almost four months for Congress to extend funding for the Children’s Health Insurance Plan (CHIP), which provides health coverage for nearly 9 million children of working families in the United States. CHIP often supports the patients with the most medically complex needs – and is pivotal to their care at Children’s National and hospitals around the country.

During the agonizing wait for the extension, Dr. Newman, as well as countless Children’s National pediatricians and government affairs leaders, spent hours encouraging, asking and telling policymakers at every level of government about the importance of investing more in children, not less.

He stresses that it’s not just the right thing to do, it’s a wise investment. Spending dollars on children for prevention, early detection and education means that we have a healthier workforce, military and national community. It’s less expensive to treat mental and behavioral health problems, asthma and diabetes early on, before they become chronic issues.

The steady drumbeat from Children’s National supported national advocacy urging Congress to protect health insurance for the millions of children who rely on CHIP for all their health care needs.

The restored measure makes a world of difference for working families, but additional advocacy is needed as Congress continues to seek agreement on a long-term budget and other important legislation, some of which could have tremendous impacts on children’s health.

Leading a conversation about the needs of military families with terminally ill children

Concurrent care for terminally ill children – where lifesaving treatments such as chemotherapy and physical rehabilitation can take place alongside comfort measures and palliative care like 24-hour nursing – is covered by most insurance programs, including CHIP and Medicaid. However, until recently, military families covered under Tricare with such desperately ill children were forced to choose coverage for one OR the other.

Children’s National brought this challenge to its coalition partners at Tricare for Kids after watching several military families forced to make an agonizing decision between comfort and treatment. The coalition, a collection of military advocacy groups, children’s hospitals and other advocates, then fought hard to add a landmark provision to the National Defense Authorization Act allowing military families concurrent care coverage for their children. Implementing Tricare adjustments that deviate from Medicare provisions has been extremely difficult and politically fraught in the past, but when advocates and lawmakers focused on doing what’s right for kids, there was little to no Capitol Hill opposition and the change was easily passed in both the House and Senate.

In addition to advocacy, every day, a children’s hospital should help parents find their voices as active, empowered and engaged team members when it comes to caring for a sick child.

“It is crucial for a child’s care team to include his or her parents – the people who know them best,” Dr. Newman recently wrote. “I want every parent to feel comfortable being a true champion for their children at the pediatrician’s office or the hospital in the same way they champion them on the playing field or in the classroom.”

“That’s why I wrote the book Healing Children,” he says during book talks and interviews. “If parents knew what I knew, they’d make sure the doctors and nurses caring for their kids were experts in treating children. These stories show the power of pediatric specialty medicine, illustrate why parents should think ahead about how best to demand the care they deserve when something bad happens and show why we should always listen to parents’ concerns.”

Children and their families are at the center of every decision made at Children’s National, from day-to-day care planning to large scale business initiatives. When focusing on doing what’s right for them, everyone – the children, their families, the community AND the healthcare organization – benefits.

Human Rhinovirus

Finding the root cause of bronchiolitis symptoms

Human Rhinovirus

A new study shows that steroids might work for rhinovirus but not for respiratory syncytial virus.

Every winter, doctors’ offices and hospital emergency rooms fill with children who have bronchiolitis, an inflammation of the small airways in the lung. It’s responsible for about 130,000 admissions each year. Sometimes these young patients have symptoms reminiscent of a bad cold with a fever, cough and runny nose. Other times, bronchiolitis causes breathing troubles so severe that these children end up in the intensive care unit.

“The reality is that we don’t have anything to treat these patients aside from supportive care, such as intravenous fluids or respiratory support,” says Robert J. Freishtat, M.D., M.P.H., chief of emergency medicine at Children’s National Health System. “That’s really unacceptable because some kids get very, very sick.”

Several years ago, Dr. Freishtat says a clinical trial tested using steroids as a potential treatment for bronchiolitis. The thinking was that these drugs might reduce the inflammation that’s a hallmark of this condition. However, he says, the results weren’t a slam-dunk for steroids: The drugs didn’t seem to improve outcomes any better than a placebo.

But the trial had a critical flaw, he explains. Rather than having one homogenous cause, bronchiolitis is an umbrella term for a set of symptoms that can be caused by a number of different viruses. The most common ones are respiratory syncytial virus (RSV) and rhinovirus, the latter itself being an assortment of more than 100 different but related viruses. By treating bronchiolitis as a single disease, Dr. Freishtat says researchers might be ignoring the subtleties of each virus that influence whether a particular medication is useful.

“By treating all bronchiolitis patients with a single agent, we could be comparing apples with oranges,” he says. “The treatment may be completely different depending on the underlying cause.”

To test this idea, Dr. Freishtat and colleagues examined nasal secretions from 32 infants who had been hospitalized with bronchiolitis from 2011 to 2014 at 17 medical centers across the country that participate in a consortium called the 35th Multicenter Airway Research Collaboration. In half of these patients, lab tests confirmed that their bronchiolitis was caused by RSV; in the other half, the cause was rhinovirus.

From these nasal secretions, the researchers extracted nucleic acids called microRNAs. These molecules regulate the effects of different genes through a variety of different mechanisms, usually resulting in the effects of target genes being silenced. A single microRNA typically targets multiple genes by affecting messenger RNA, a molecule that’s key for producing proteins.

Comparing results between patients with RSV or rhinovirus, the researchers found 386 microRNAs that differed in concentration. Using bioinformatic software, they traced these microRNAs to thousands of messenger RNAs, looking for any interesting clues to important mechanisms of illness that might vary between the two viruses.

Their findings eventually turned up important differences between the two viruses in the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway, a protein cascade that’s intimately involved in the inflammatory response and is a target for many types of steroids. Rhinovirus appears to upregulate the expression of many members of this protein family, driving cells to make more of them, and downregulate inhibitors of this cascade. On the other hand, RSV didn’t seem to have much of an effect on this critical pathway.

To see if these effects translated into cells making more inflammatory molecules in this pathway, the researchers searched for various members of this protein cascade in the nasal secretions. They found an increase in two, known as RelA and NFkB2.

Based on these findings, published online Jan. 17, 2018, in Pediatric Research, steroids might work for rhinovirus but not for RSV, notes Dr. Freishtat the study’s senior author.

“We’re pretty close to saying that you’d need to conduct a clinical trial with respect to the virus, rather than the symptoms, to measure any effect from a given drug,” he says.

Future clinical trials might test the arsenal of currently available medicines to see if any has an effect on bronchiolitis caused by either of these two viruses. Further research into the mechanisms of each type of illness also might turn up new targets that researchers could develop new medicines to hit.

“Instead of determining the disease based on symptoms,” he says, “we can eventually treat the root cause.”

Study co-authors include Kohei Hasegawa, study lead author, and Carlos A. Camargo Jr., Massachusetts General Hospital; Marcos Pérez-Losada, The George Washington University School of Medicine and Health Sciences; Claire E. Hoptay, Samuel Epstein and Stephen J. Teach, M.D., M.P.H., Children’s National; Jonathan M. Mansbach, Boston Children’s Hospital; and Pedro A. Piedra, Baylor College of Medicine.