Neonatology News Archives

Exclusive breastfeeding lowers odds of some schoolchildren having eczema

February 25, 2019

Breastfeeding Mom

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

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

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

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

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

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

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

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

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

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

New model mimics persistent interneuron loss seen in prematurity

February 19, 2019

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

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

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

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

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

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

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

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

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

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

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

Neurodevelopmental disorders: Developing medical treatments

February 13, 2019

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

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

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

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

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

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

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

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

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

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

Children’s perinatal hypoxia research lauded

January 29, 2019

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

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

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

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

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

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

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

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

Getting micro-preemie growth trends on track

January 23, 2019

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

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

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

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

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

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

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

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

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

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

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

Institute for Healthcare Improvement 2018 Scientific Symposium presentation

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

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

Fighting perinatal mood and anxiety disorders on multiple levels

January 16, 2019

new mom with baby

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

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

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

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

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

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

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

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

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

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

Breakthrough device objectively measures pain type, intensity and drug effects

January 10, 2019

Clinical Research Assistant Kevin Jackson uses AlgometRx Platform Technology on Sarah Taylor’s eyes to measure her degree of pain. Children’s National is testing an experimental device that aims to measure pain according to how pupils react to certain stimuli. (AP Photo/Manuel Balce Ceneta)

Pediatric anesthesiologist Julia C. Finkel, M.D., of Children’s National Health System, gazed into the eyes of a newborn patient determined to find a better way to measure the effectiveness of pain treatment on one so tiny and unable to verbalize. Then she realized the answer was staring back at her.

Armed with the knowledge that pain and analgesic drugs produce an involuntary response from the pupil, Dr. Finkel developed AlgometRx, a first-of-its-kind handheld device that measures a patient’s pupillary response and, using proprietary algorithms, provides a diagnostic measurement of pain intensity, pain type and, after treatment is administered, monitors efficacy. Her initial goal was to improve the care of premature infants. She now has a device that can be used with children of any age and adults.

“Pain is very complex and it is currently the only vital sign that is not objectively measured,” says Dr. Finkel, who has more than 25 years of experience as a pain specialist. “The systematic problem we are facing today is that healthcare providers prescribe pain medicine based on subjective self-reporting, which can often be inaccurate, rather than based on an objective measure of pain type and intensity.” To illustrate her point, Dr. Finkel continues, “A clinician would never prescribe blood pressure medicine without first taking a patient’s blood pressure.”

The current standard of care for measuring pain is the 0-to-10 pain scale, which is based on subjective, observational and self-reporting techniques. Patients indicate their level of pain, with zero being no pain and ten being highest or most severe pain. This subjective system increases the likelihood of inaccuracy, with the problem being most acute with pediatric and non-verbal patients. Moreover, Dr. Finkel points out that subjective pain scores cannot be standardized, heightening the potential for misdiagnosis, over-treatment or under-treatment.

Dr. Finkel, who serves as director of Research and Development for Pain Medicine at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, says that a key step in addressing the opioid crisis is providing physicians with objective, real-time data on a patient’s pain level and type, to safely prescribe the right drug and dosage or an alternate treatment.,

She notes that opioids are prescribed for patients who report high pain scores and are sometimes prescribed in cases where they are not appropriate. Dr. Finkel points to the example of sciatica, a neuropathic pain sensation felt in the lower back, legs and buttocks. Sciatica pain is carried by touch fibers that do not have opioid receptors, which makes opioids an inappropriate choice for treating that type of pain.

A pain biomarker could rapidly advance both clinical practice and pain research, Dr. Finkel adds. For clinicians, the power to identify the type and magnitude of a patient’s nociception (detection of pain stimuli) would provide a much-needed scientific foundation for approaching pain treatment. Nociception could be monitored through the course of treatment so that dosing is targeted and personalized to ensure patients receive adequate pain relief while reducing side effects.

“A validated measure to show whether or not an opioid is indicated for a given patient could ease the health care system’s transition from overreliance on opioids to a more comprehensive and less harmful approach to pain management,” says Dr. Finkel.

She also notes that objective pain measurement can provide much needed help in validating complementary approaches to pain management, such as acupuncture, physical therapy, virtual reality and other non-pharmacological interventions.

Dr. Finkel’s technology, called AlgometRx, has been selected by the U.S. Food and Drug Administration (FDA) to participate in its “Innovation Challenge: Devices to Prevent and Treat Opioid Use Disorder.” She is also the recipient of Small Business Innovation Research (SBIR) grant from the National Institute on Drug Abuse.

How does diet during pregnancy impact allergies in offspring?

December 17, 2018

A small percentage of women said they consumed fewer allergens during pregnancy to stave off food allergies in their newborns, according to preliminary research Karen Robbins, M.D., presented during the American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting.

Pregnant women routinely swear off alcohol and tobacco to boost their chances of having a healthy baby. What about common food allergens like nuts and milk?

There are scant data that describe how often pregnant women deliberately stop eating a specific food item in order to prevent future food allergies in their newborns. As a first step toward addressing this data gap, a research team led by Karen Robbins, M.D., an allergist at Children’s National Health System, pored through a longitudinal study conducted by the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention.

About 4,900 pregnant women completed the Infant Feeding Practices Study II prenatal questionnaire from May 2005 to June 2007. The study tracked 2,000 pregnant women from the third trimester of pregnancy and their infants through the first year of life. A small percentage of women said they had consumed fewer allergens during pregnancy to stave off food allergies in their newborns, according to a poster Dr. Robbins presented during the American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting. While their numbers were small, most of these women reported giving up major allergens like nuts, milk or eggs during pregnancy, including:

144 (2.9 percent) reported restricting their diet in some way to prevent future food allergies in their offspring
84 women (1.7 percent) ate fewer nuts
15 women (.3 percent) ate fewer eggs and
2 women (.04 percent) ate/drank consumed less dairy/milk.

“At the time the survey was conducted, few pregnant women in this large data set said they gave up certain foods with the express aim of avoiding a food allergy in their babies,” Dr. Robbins says. “However, mothers who had an older child with a food allergy or who had food allergies themselves had significantly higher odds of trying this food avoidance strategy.”

Despite the diet changes, infants born to these expectant mothers were twice as likely to experience problems with food at age 4 months – though not at age 9 months or 12 months. And these infants were no more likely to be diagnosed with a food allergy.

According to the FDA, millions of Americans suffer a food allergy each year. Reactions can range from mild to life-threatening and can begin soon after eating a problematic food item or an ingredient from that food. Among the most common allergenic foods are milk, eggs, fish, shellfish, tree nuts, peanuts, wheat and soybeans.

“We really need to know more about how often targeted food avoidance occurs among U.S. pregnant women who have a family history of food allergies,” Dr. Robbins adds. “We hope to learn what factors into these women’s decision-making as well as why many of them settled on food avoidance as a potential strategy to try to prevent food allergy in their infants.”

American College of Asthma Allergy and Immunology 2018 Annual Scientific Meeting presentation

“Prenatal food allergen avoidance practices for food allergy prevention.”

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

MRI and ultrasound imaging detect the spectrum of Zika’s impact

December 7, 2018

“A combination of prenatal MRI and US was able to detect Zika-related brain abnormalities during pregnancy, giving families timely information to prepare for the potential complex care needs of these infants,” says Sarah B. Mulkey, M.D., Ph.D.

Worldwide, thousands of babies have been born to mothers who were infected during pregnancy with Zika, a virus associated with neurological deficits, impaired vision and neurodevelopmental disabilities, among other birth defects. These birth defects are sometimes severe, causing lifelong disability. But they’re also relatively rare compared with the overall rates of infection.

Predicting how many Zika-exposed babies would experience neurological birth defects has been challenging.

However, an international study led by Children’s faculty suggests that ultrasound (US) imaging performed during pregnancy and after childbirth revealed most Zika-related brain abnormalities experienced by infants exposed to the Zika virus during pregnancy, according to a prospective cohort study published online Nov. 26, 2018, in JAMA Pediatrics. Some Zika-exposed infants whose imaging had been normal during pregnancy had mild brain abnormalities detected by US and magnetic resonance imaging (MRI) after they were born.

“A combination of prenatal MRI and US was able to detect Zika-related brain abnormalities during pregnancy, giving families timely information to prepare for the potential complex care needs of these infants,” says Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist at Children’s National Health System and the study’s lead author. “In our study, we detected mild brain abnormalities on postnatal neuroimaging for babies whose imaging was normal during pregnancy. Therefore, it is important for clinicians to continue to monitor brain development for Zika-exposed infants after birth.”

As of Nov. 20 2018, nearly 2,500 pregnant women in the U.S. had laboratory confirmed Zika infection, and about 2,400 of them had given birth, according to the Centers for Disease Control and Prevention (CDC). While more than 100 U.S. infants were born with Zika-associated birth defects, the vast majority of Zika-exposed U.S. infants were apparently normal at birth. The sequential neuroimaging study Dr. Mulkey leads seeks to determine the spectrum of brain findings in infants exposed to Zika in the womb using both US and MRI before and after birth.

The international research team enrolled 82 women in the study from June 15, 2016, through June 27, 2017. All of the women had been exposed to Zika during pregnancy; all but one experienced clinical symptoms by a mean gestational age of 8.2 weeks. Eighty of those women lived in or near Barranquilla, Colombia, and were exposed to Zika there. Two U.S. study participants were exposed to the primarily mosquito-borne illness during travel to Zika hot zones.

All women received fetal MRIs and US during the second and/or third trimester of pregnancy. After their infants were born, the children received brain MRI and cranial US. Blood samples from both mothers and babies were tested for Zika using polymerase chain reaction and serology.

Fetal MRI was able to discern Zika-related brain damage as early as 18 weeks gestation and picked up significant fetal brain abnormalities not fully appreciated in US imaging. In one case, the US remained normal while fetal MRI alone detected brain abnormalities. Three fetuses (4 percent) had severe fetal brain abnormalities consistent with Zika infection, including:

Two cases of heterotopias and malformations in cortical development, and
One case of parietal encephalocele, Chiari II malformation and microcephaly.

Seventy-five infants were born at term. One pregnancy was terminated at 23 weeks gestation due to the gravity of the fetal brain abnormalities. One fetus with normal imaging died during pregnancy. One newborn who was born with significant fetal brain abnormalities died at age 3 days.

Cranial US and brain MRI was performed on the majority of infants whose prenatal imaging had been normal. Seven of 53 (13 percent) Zika-exposed infants had mild brain abnormalities detected by MRI after birth. In contrast, postnatal cranial US was better at detecting changes of lenticulostriate vasculopathy, cysts within the brain’s choroid plexus (cells that produce cerebrospinal fluid), germinolytic/subependymal cysts and/or calcifications, which were seen in 21 of 57 (37 percent) infants.

“Sequential neuroimaging revealed that the majority of Zika-exposed fetuses had normal brain development. Tragically, in a small number of pregnancies, Zika-related brain abnormalities were quite severe,” Dr. Mulkey adds. “Our data support the CDC’s recommendation that cranial US be performed after Zika-exposed babies are born. In addition, there is clearly a need to follow these babies over time to gauge whether the brain anomalies we see in imaging affects language, motor and social skills.”

Companion editorial: Revealing the effects of Zika

In addition to Dr. Mulkey, study co-authors include Dorothy I. Bulas, M.D., Gilbert Vezina, M.D., Margarita Arroyave-Wessel, MPH, Stephanie Russo, B.S, Youssef A. Kousa, D.O, Ph.D., Roberta L. DeBiasi, M.D., MS, Senior Author Adré J. du Plessis, M.B.Ch.B., MPH, all of Children’s National; Christopher Swisher, BS, Georgetown University and Caitlin Cristante, BS, Loyola University, both of whose contributions included research performed at Children’s National; Yamil Fourzali, M.D., Armando Morales, M.D., both of Sabbag Radiologos; Liliana Encinales, M.D., Allied Research Society; Nelly Pacheco, Bacteriologa, Bio-Nep; Robert S. Lanciotti, Ph.D., Arbovirus Diseases Branch, Centers for Disease Control and Prevention; and Carlos Cure, M.D., BIOMELAB.

Research reported in this news release was supported by the IKARIA fund.

A growing list of factors that impact CKD severity for kids

November 20, 2018

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments.

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease (CKD) for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments, according to an invited commentary published in the November 2018 edition of American Journal of Kidney Diseases.

Clinicians caring for “these vulnerable children should be mindful of these multiple competing and compounding issues as treatment options are being considered along the continuum from CKD to kidney failure to transplantation,” writes Marva Moxey-Mims, M.D., chief of the Division of Nephrology at Children’s National Health System.

The supplemental article was informed by lessons learned from The Chronic Kidney Disease in Children (CKiD) longitudinal study and conversations that occurred during the Frank M. Norfleet Forum for Advancement of Health, “African Americans and Kidney Disease in the 21^st Century.”

African American children represent 23 percent of the overall population of kids with CKD in the CKiD study. While acquired kidney diseases can get their start during childhood when the diseases betray few symptoms, the full impact of illness may not be felt until adulthood. A number of factors can uniquely affect children of African descent, heightening risk for some kids who already are predisposed to suffering more severe symptoms. These include:

Preterm birth. African American children make up 36 percent of patients in CKiD with glomerular disease, which tends to have faster progression to end-stage renal disease. These diseases impair kidney function by weakening glomeruli, which impairs the kidneys’ ability to clean blood. Patients with a high-risk apolipoprotein L1 (APOL1) genotype already are at higher risk for focal segmental glomerulosclerosis (FSGS) and CKD. Researchers hypothesize that preterm birth may represent “a second hit that facilitates the development of glomerular damage resulting from the high-risk genotype.” According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, e.g., prior to 37 weeks gestation.
APOL1 genotype. Compared with children who had a low-risk genotype and FSGS, children with a high-risk genotype had higher rates of uncontrolled hypertension, left ventricular hypertrophy, elevated C-reactive protein levels and obesity.
Human immunodeficiency viral (HIV) status. About 65 percent of U.S. children with HIV-1/AIDS are African American. In a recent nested case-control study of children infected with HIV in the womb, infants with high-risk APOL1 genotypes were 3.5 times more likely to develop CKD with viral infection serving as “a likely second hit.”
Access to kidney transplant. African American adults experience a faster transition to end-stage renal disease and are less likely to receive kidney transplants. African American children with CKD from nonglomerular diseases begin renal replacement therapy 1.6 years earlier than children of other races, after adjusting for socioeconomic status. Their wait for dialysis therapy was 37.5 percent shorter. However, these African American children waited 53.7 percent longer for transplants. Although donor blood types, genetic characteristics and other biological factors each play contributing roles, “these findings may reflect sociocultural and institutional differences not captured by socioeconomic status,” Dr. Moxey-Mims writes.

To alleviate future health care disparities, she suggests that additional research explore the impact of expanding services to pregnant women to lower their chances of giving birth prematurely; early childhood interventions to help boost children’s educational outcomes, future job prospects and income levels; expanded studies about the impact of environmental toxicities on prenatal and postnatal development; and heightened surveillance of preterm infants as they grow older to spot signs of kidney disease earlier to slow or prevent disease progression.

“Clinicians can now begin to take into account genetics, socioeconomic status and the impact of the built environment, rather than blaming people and assuming that their behavior alone brought on kidney disease,” Dr. Moxey-Mims adds. “Smoking, not eating properly and not exercising can certainly make people vulnerable to disease. However, there are so many factors that go into developing a disease that patients cannot control: You don’t control to whom you’re born, where you live or available resources where you live. These research projects will be useful to help us really get to the bottom of which factors we can impact and which things can’t we prevent but can strive to mitigate.”

The article covered in this post is part of a supplement that arose from the Frank M. Norfleet Forum for Advancement of Health: African Americans and Kidney Disease in the 21st Century, held March 24, 2017, in Memphis, Tennessee. The Forum and the publication of this supplement were funded by the Frank M. Norfleet Forum for Advancement of Health, the Community Foundation of Greater Memphis and the University of Tennessee Health Science Center.

Boosting parental resilience in the NICU

November 20, 2018

Preliminary findings from an ongoing cross-sectional study presented during the American Academy of Pediatrics 2018 National Conference & Exhibition suggests a strong relationship between resilience and the presence of social support, which may help parents to better contend with psychological distress related to their preterm infant being in the NICU.

Resilience is the remarkable ability of some people to bounce back and overcome stress, trauma and adversity. Being resilient is especially important for parents whose babies are born prematurely – a condition that predisposes these children to numerous health risks both immediately and far into the future and that often triggers a stay in the neonatal intensive care unit (NICU). According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. infants was born preterm in 2016.

Parents of these vulnerable newborns who feel less resilient may experience more symptoms of psychological distress, including depression and anxiety. However, preliminary findings from an ongoing cross-sectional study presented during the American Academy of Pediatrics (AAP) National Conference & Exhibition suggests a strong relationship between resilience and the presence of social support, which may help parents to better contend with psychological distress related to their preterm infant being in the NICU.

“Oftentimes, parenting a child in the NICU can be a time of crisis for families,” says Ololade A. Okito, M.D., FAAP, a Neonatal-Perinatal Medicine Fellow at Children’s National Health System who presented the preliminary study results during the 2018 AAP conference. “Studies have indicated a relationship between higher resilience and a reduction in psychological stress in other groups of people. However, it was unclear whether that finding also applies to parents of infants in the NICU.”

Because parental psychological distress can impact the quality of parent-child interactions, the Children’s research team wants to evaluate the relationship between resilience and psychological distress in these parents and to gauge whether activities that parents themselves direct, like the skin-to-skin contact that accompanies kangaroo care, helps to bolster resiliency.

So far, they have analyzed data from 30 parents of preterm infants in the NICU and used a number of validated instruments to assess parental resilience, depressive symptoms, anxiety, NICU-related stress and perceived social support, including:

The Connor-Davidson Resilience Scale
Edinburgh Postnatal Depression Scale
State-Trait Anxiety Inventory Form
Parental Stressor Scale: Neonatal Intensive Care Unit and
The Multidimensional Scale of Perceived Social Support.

The infants were born at a mean gestational age of 29.2 weeks. When their newborns were 2 weeks old:

44 percent of parents (16 of 30) reported higher resilience
37 percent of parents (11 of 30) screened positive for having elevated symptoms of depression and
33 percent of parents had elevated anxiety.

“These early findings appear to support a relationship between low parental resilience scores and higher scores for depression, anxiety and NICU-related stress. These same parents were less likely to participate in kangaroo care and had lower social support. By contrast, parents who had more social support – including receiving support from family, friends and significant others – had higher resilience scores,” says Lamia Soghier, M.D., FAAP, CHSE, Medical Unit Director of Children’s Neonatal Intensive Care Unit and senior study author.

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. The research team hopes to complete study enrollment in early 2019.

American Academy of Pediatrics National Conference & Exhibition presentation

“Parental resilience and psychological distress in the neonatal intensive care unit (PARENT) study.”

Ololade A. Okito, M.D., FAAP, Neonatal-Perinatal Medicine Fellow and presenting author; Yvonne Yui, M.D.; Nicole Herrera, MPH, Children’s Research Institute; Randi Streisand, Ph.D., Chief, Division of Psychology and Behavioral Health; Carrie Tully, Ph.D.; Karen Fratantoni, M.D., MPH, Medical Director of the Complex Care Program; and Senior Author, Lamia Soghier, M.D., FAAP, CHSE, Medical Unit Director, Neonatal Intensive Care Unit; all of Children’s National Health System.

Making the case for a comprehensive national registry for pediatric CKD

October 22, 2018

“It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD.,” says Marva Moxey-Mims, M.D. “A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

Even though chronic kidney disease (CKD) is a global epidemic that imperils cardiovascular health, impairs quality of life and heightens mortality, very little is known about how CKD uniquely impacts children and how kids may be spared from its more devastating effects.

That makes a study published in the November 2018 issue of the American Journal of Kidney Diseases all the more notable because it represents the largest population-based study of CKD prevalence in a nationally representative cohort of adolescents aged 12 to 18, Sun-Young Ahn, M.D., and Marva Moxey-Mims, M.D., of Children’s National Health System, write in a companion editorial published online Oct. 18, 2018.

In their invited commentary, “Chronic kidney disease in children: the importance of a national epidemiological study,” Drs. Ahn and Moxey-Mims point out that pediatric CKD can contribute to growth failure, developmental and neurocognitive defects and impaired cardiovascular health.

“Children who require renal-replacement therapy suffer mortality rates that are 30 times higher than children who don’t have end-stage renal disease,” adds Dr. Moxey-Mims, chief of the Division of Nephrology at Children’s National. “It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD. A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

At its early stages, pediatric CKD usually has few symptoms, and clinicians around the world lack validated biomarkers to spot the disease early, before it may become irreversible.

While national mass urine screening programs in Japan, Taiwan and Korea have demonstrated success in early detection of CKD, which enabled successful interventions, such an approach is not cost-effective for the U.S., Drs. Ahn and Moxey-Mims write.

According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, prior to 37 weeks gestation. Because of that trend, the commentators advocate for “a concerted national effort” to track preterm and low birth weight newborns. (These infants are presumed to have lower nephron endowment, which increases their risk for developing end-stage kidney disease.)

“We need a comprehensive, national registry just for pediatric CKD, a database that represents the entire U.S. population that we could query to glean new insights about what improves kids’ lifespan and quality of life. With a large database of anonymized pediatric patient records we could, for example, assess the effectiveness of specific therapeutic interventions, such as angiotensin-converting enzyme inhibitors, in improving care and slowing CKD progression in kids,” Dr. Moxey-Mims adds.

Natella Yurievna Rakhmanina named to regional HIV planning commission

September 13, 2018

Natella Rakhamania

Natella Yurievna Rakhmanina, M.D., Ph.D., FAAP, AAHIVS, director of Ryan White HIV Services at Children’s National Health System, was appointed a commissioner to the Washington, D.C., Regional Planning Commission on Health and HIV.

Dr. Rakhmanina will be among the District of Columbia board and commission appointees honored during a swearing-in ceremony on Sept. 17, 2018, at the Walter Washington Convention Center.

Looking back over the last decade, she says the District has made impressive progress in lowering the prevalence rate of human immunodeficiency virus (HIV), which in 2002 had 1,686 per 100,000 District residents diagnosed with AIDS.

“It was really high. I was stunned coming to clinic and seeing a large number of kids and adolescents in care and many suffering significant complications, as our treatment options were limited at the time,” she says.

Since that time, DC Health has made “incredible investments” and adopted innovative approaches, such as name-based reporting of HIV and a Red Carpet program, to ensure newly diagnosed people are quickly linked with care. As a proud partner of DC Health’s HIV/AIDS, Hepatitis, STD and TB Administration, Children’s National launched a campaign in 2009 to universally test adolescents for HIV in two pediatric emergency departments (ED), she says.

“All teenagers aged 13 and older who arrive for any medical diagnosis are offered an oral HIV test. Children’s National ED-based HIV screening program alone has tested 30,000 children at both of our emergency departments,” she says. “We’re still not at our goal. However, the prevalence of HIV had dropped to 1.9 percent in the latest department of health analysis. We are doing better. We have much fewer people dying from AIDS. We are diagnosing earlier.”

What’s more, trends in mother-to-child transmission, a major route of transmission for pediatric HIV, also have improved in D.C.

“In 2006, our maternal HIV transmission rates were among the highest in the nation. But, in 2013, 2014 and 2015 there were zero cases. We have seen some setbacks recently, however. In 2016, there were three perinatally acquired cases and four in 2017, but these cases came out of the larger Metropolitan D.C. area,” she explains. “Every perinatally transmitted case for us is a red star. We work very closely with the regional departments of health. We really want to get back to zero cases of maternal transmission in the region.”

The regional planning commission meets several times per year to decide how to distribute federal funding in Washington and the Metropolitan D.C. area to support HIV prevention, diagnosis, treatment and care.

“My voice on the council is to make sure I speak up for services for mothers, children and adolescents,” Dr. Rakhmanina says. “The biggest challenge of HIV care remains treating children. There’s a good selection of medicines for adults, but not all are suited for kids. Young children in particular can’t be given one pill once a day. Really young children can’t swallow a pill. Using a liquid formulation, which kids prefer, may mean opening three different bottles twice daily and swallowing a liquid that often doesn’t taste good.”

Adolescents diagnosed with HIV also find medication adherence challenging, she says.

“At that age, they face a lot of challenges to self-acceptance and disease management, in part, because it’s not a physical disability. A young person with HIV may not feel anything,” she says. “They struggle with staying on daily medications. Many of them tell us they don’t want to think about HIV and face stigma.”

Another ongoing challenge is ensuring moms living with HIV remain on medicines after they’ve given birth.

“They’re tremendously committed to continuing treatment while pregnant: Treatment means their babies are born free of HIV,” she says. “That is a great success. Once the baby is born, many times the women bring their babies to be tested, but the woman’s own health becomes less of a priority. We see a drop in adherence once they have the baby.”

By serving on the commission, Dr. Rakhmanina aims to push to extend Children’s commitment to excellence beyond its walls.

Perinatal hypoxia associated with long-term cerebellar learning deficits and Purkinje cell misfiring

August 20, 2018

The type of hypoxia that occurs with preterm birth is associated with locomotor miscoordination and long-term cerebellar learning deficits but can be partially alleviated with an off-the-shelf medicine, according to a study using a preclinical model.

Oxygen deprivation associated with preterm birth leaves telltale signs on the brains of newborns in the form of alterations to cerebellar white matter at the cellular and the physiological levels. Now, an experimental model of this chronic hypoxia reveals that those cellular alterations have behavioral consequences.

Chronic sublethal hypoxia is associated with locomotor miscoordination and long-term cerebellar learning deficits in a clinically relevant model of neonatal brain injury, according to a study led by Children’s National Health System researchers published online Aug. 13, 2018, by Nature Communications. Using high-tech optical and physiological methods that allow researchers to turn neurons on and off and an advanced behavioral tool, the research team finds that Purkinje cells fire significantly less often after injury due to perinatal hypoxia. However, an off-the-shelf medicine now used to treat epilepsy enables those specialized brain cells to regain their ability to fire, improving locomotor performance.

Step out of the car onto the pavement, hop up to the level of the curb, stride to the entrance, and climb a flight of stairs. Or, play a round of tennis. The cerebellum coordinates such locomotor performance and muscle memory, guiding people of all ages as they adapt to a changing environment.

“Most of us successfully coordinate our movements to navigate the three-dimensional spaces we encounter daily,” says Vittorio Gallo, Ph.D., Children’s Chief Research Officer and the study’s senior author. “After children start walking, they also have to learn how to navigate the environment and the spaces around them.”

These essential tasks, Gallo says, are coordinated by Purkinje cells, large neurons located in the cerebellum that are elaborately branched like interlocking tree limbs and represent the only source of output for the entire cerebellar cortex. The rate of development of the fetal cerebellum dramatically increases at a time during pregnancy that often coincides with preterm birth, which can delay or disrupt normal brain development.

“It’s almost like a short circuit. Purkinje cells play a very crucial role, and when the frequency of their firing is diminished by injury the whole output of this brain region is impaired,” Gallo says. “For a family of a child who has this type of impaired neural development, if we understand the nature of this disrupted circuitry and can better quantify it, in terms of locomotor performance, then we can develop new therapeutic approaches.”

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

The research team leveraged a fully automated, computerized apparatus that looks like a ladder placed on a flat surface, encased in glass, with a darkened box at either end. Both the hypoxic and control groups had training sessions during which they learned how to traverse the horizontal ladder, coaxed out of the darkened room by a gentle puff of air and a light cue. Challenge sessions tested their adaptive cerebellar locomotor learning skills. The pads they strode across were pressure-sensitive and analyzed individual stepping patterns to predict how long it should take each to complete the course.

During challenge sessions, obstacles were presented in the course, announced by an audible tone. If learning was normal, then the response to the tone paired with the obstacle would be a quick adjustment of movement, without breaking stride, says Aaron Sathyanesan, Ph.D., co-lead author. Experimental models exposed to perinatal hypoxia showed significant deficits in associating that tone with the obstacle.

“With the control group, we saw fewer missteps during any given trial,” Sathyanesan says. “And, when they got really comfortable, they took longer steps. With the hypoxic group, it took them longer to learn the course. They made a significantly higher number of missteps from day one. By the end of the training period, they could walk along all of the default rungs, but it took them longer to learn how to do so.”

Purkinje cells fire two different kinds of spikes. Simple spikes are a form of constant activity as rhythmic and automatic as a heartbeat. Complex spikes, by contrast, occur less frequently. Sathyanesan and co-authors say that some of the deficits that they observed were due to a reduction in the frequency of simple spiking.

Two weeks after experiencing hypoxia, the hypoxic group’s locomotor performance remained significantly worse than the control group, and delays in learning could still be seen five weeks after hypoxia.

Gamma-aminobutyric acid (GABA), a neurotransmitter, excites immature neurons before and shortly after birth but soon afterward switches to having an inhibitory effect within in the cerebellum, Sathyanesan says. The research team hypothesizes that reduced levels of excitatory GABA during early development leads to long-term motor problems. Using an off-the-shelf drug to increase GABA levels immediately after hypoxia dramatically improved locomotor performance.

“Treating experimental models with tiagabine after hypoxic injury elevates GABA levels, partially restoring Purkinje cells’ ability to fire,” Gallo says. “We now know that restoring GABA levels during this specific window of time has a beneficial effect. However, our approach was not specifically targeted to Purkinje cells. We elevated GABA everywhere in the brain. With more targeted and selective administration to Purkinje cells, we want to gauge whether tiagabine has a more powerful effect on normalizing firing frequency.”

In addition to Gallo and Sathyanesan, Children’s co-authors include Co-Lead Author, Srikanya Kundu, Ph.D., and Joseph Abbah, B.Pharm., Ph.D., both of Children’s Center for Neuroscience Research.

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

Making weight: Ensuring that micro preemies gain pounds and inches

August 13, 2018

Tory Peitz, R.N., (left) and Victoria Catalano, RDN, LD, CNSC, CLC, (right) Pediatric Dietitian Specialist in the Neonatal Intensive Care Unit at Children’s National Health System, measure the length of a micro preemie who weighed 1.5 pounds at birth.

A quality-improvement project to standardize feeding practices for micro preemies – preterm infants born months before their due date – helped to boost their weight and nearly quadrupled the frequency of lactation consultations ordered in the neonatal intensive care unit (NICU), a multidisciplinary team from Children’s National Health System finds.

According to the Centers for Disease Control and Prevention, about 1 in 10 infants in 2016 was preterm, born prior to completing 37 gestational weeks of pregnancy. Micro preemies are the tiniest infants in that group, weighing less than 1,500 grams and born well before their brain, lungs and organs like the liver are fully developed.

As staff reviewed charts for very low birth weight preterm infants admitted to Children’s NICU, they found dramatic variation in nutritional practices among clinicians and a mean decline in delta weight Z-scores, a more sensitive way to monitor infants’ weight gain along growth percentiles for their gestational age. A multidisciplinary team that included dietitians, nurses, neonatologists, a lactation consultant and a quality-improvement leader evaluated nutrition practices and determined key drivers for improving nutrition status.

“We tested a variety of strategies, including standardizing feeding practices; maximizing intended delivery of feeds; tracking adequacy of calorie, protein and micronutrient intake; and maximizing use of the mother’s own breast milk,” says Michelande Ridoré, MS, a Children’s NICU quality-improvement lead who will present the group’s findings during the Virginia Neonatal Nutrition Association conference this fall. “We took nothing for granted: We reeducated everyone in the NICU about the importance of the standardized feeding protocol. We shared information about whether infants were attaining growth targets during daily rounds. And we used an infographic to help nursing moms increase the available supply of breastmilk,” Ridoré says.

On top of other challenges, very low birth weight preterm infants are born very lean, with minimal muscle. During the third trimester, pregnant women pass on a host of essential nutrients and proteins to help satisfy the needs of the fetus’ developing muscles, bones and brain. “Because preterm infants miss out on that period in utero, we add fortification to provide preemies with extra protein, phosphorus, calcium and zinc they otherwise would have received from mom in the womb,” says Victoria Catalano, RDN, LD, CNSC, CLC, a pediatric clinical dietitian in Children’s NICU and study co-author. Babies’ linear growth is closely related to neurocognitive development, Catalano says. A dedicated R.N. is assigned to length boards for Children’s highest-risk newborns to ensure consistency in measurements.

Infants who were admitted within the first seven days of life and weighed less than 1,500 grams were included in the study. At the beginning of the quality-improvement project, the infants’ mean delta Z-score for weight was -1.8. By December 2018, that had improved to -1.3. And the number of lactation consultation ordered weekly increased from 1.1 to four.

“We saw marked improvement in micro preemies’ nutritional status as we reduced the degree of variation in nutrition practices,” says Mary Revenis, M.D., NICU medical lead on nutrition and senior author for the research. “Our goal was to increase mean delta Z-scores even more. To that end, we will continue to test other key drivers for improved weight gain, including zinc supplementation, updating infants’ growth trajectories in the electronic medical record and advocating for expanded use of birth mothers’ breast milk,” Dr. Revenis says.

In addition to Ridoré, Catalano and Dr. Revenis, study co-authors include Caitlin Forsythe MS, BSN, RNC-NIC, lead author; Rebecca Vander Veer RD, LD, CNSC, CLC, pediatric dietitian specialist; Erin Fauer RDN, LD, CNSC, CLC, pediatric dietitian specialist; Judith Campbell, RN, IBCLC, NICU lactation consultant; Eresha Bluth MHA; Anna Penn M.D., Ph.D., neonatalogist; and Lamia Soghier M.D., Med., NICU medical unit director.

Safeguarding fetal brain health in pregnancies complicated by CHD

August 1, 2018

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

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

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

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

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

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

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

The ‘secret sauce’ for high-performing NICUs

July 19, 2018

Quoting the literature, Lamia Soghier, M.D., Children’s NICU medical unit director, and Billie Lou Short, M.D., chief of Children’s Division of Neonatology, write that hospitals with strong performance-improvement programs share eight critical factors in common.

Leaders of neonatal intensive care units (NICUs) across the nation share the same play books as they strive to provide safe, high-quality medical and surgical care for vulnerable newborns. A growing number of quality collaborations share best practices and evidence-based guidelines across the nation in the hopes of replicating quality and safety success stories while minimizing harms.

Still, NICUs that use similar interventions in similar fashions often do not achieve identical results.

“This unexplained variability in outcomes between NICUs begs the question: What is the secret sauce? Why do some NICUs consistently outshine others in spite of the application of the same ‘potentially best practices,’ ” the leaders of Children’s award-winning NICU ask in an editorial published online July 12, 2018, by Archives of Disease in Childhood (ADC) – Fetal & Neonatal edition.

Quoting the literature, Lamia Soghier, M.D., Children’s NICU medical unit director, and Billie Lou Short, M.D., chief of Children’s Division of Neonatology, write that hospitals with strong performance-improvement programs share eight critical factors in common:

Strong performance-improvement leadership at the administrative and executive levels
Boards of Trustees who are actively involved and provide continuity in vision regardless of changes in senior hospital leadership
An effective oversight structure that avoids duplicating efforts
Expert performance-improvement staff who are trained in quality and safety and able to carry out projects successfully
Physicians who are involved and held accountable
Staff who are actively involved
Effective use of data in decision-making
Effective communication strategies for all stakeholders

The “‘secret sauce’ may lie in establishing systems that promote the culture of quality and safety rather than waiting for a reduction in morbidity,” write Drs. Soghier and Short.

For the second year running, Children’s neonatology division ranked No. 1 among NICUs ranked by U.S. News & World Report. Despite challenges inherent in being a “busy level IV NICU in a free-standing children’s hospital with a rapidly growing capacity, higher levels of complex patients, [the] presence of trainees on rounds and routine 3:1 and 2:1 staffing models,” Children’s NICU has continued to have the lowest rates of such objective quality measures as central line-associated bloodstream infections and unintended extubations, they write.

“We attribute our success to direct involvement of all levels of leadership in our unit in [performance improvement] PI initiatives, a dedicated local PI team, quality trained medical unit director, engagement of front-line staff in PI, the presence of local subject-matter experts, multidisciplinary diverse team both within the NICU and with other departments that bring an array of experiences and opinions and a supportive data infrastructure through local information technology, and use of the Children’s Hospital Neonatal Database that allows benchmarking to other non-delivery NICUs, Drs. Soghier and Short write. “Our team finds motivation in solving local issues routine in our work, and leadership prioritises these issues and promotes engagement of front-line staff.”

The commentary was a companion to “Using a Composite Morbidity Score and Cultural Survey to Explore Characteristics of High Proficiency Neonatal Intensive Care Units,” also published by ADC Fetal & Neonatal.

Screening for postpartum depression in the emergency department

June 29, 2018

“Some of these women had no idea how common postpartum depression was,” says Lenore Jarvis, M.D., M.Ed. “They thought they were crazy and felt alone and were bad moms.”

It’s a scenario that Children’s emergency medicine specialist Lenore Jarvis, M.D., M.Ed., has seen countless times: A mother brings her infant to the emergency department (ED) in the middle of the night with a chief complaint of the baby being fussy. Nothing she does can stop the incessant crying, she tells the triage nurse. When doctors examine the baby, they don’t see anything wrong. Often, this finding is reassuring. But, despite their best efforts to comfort her, the mother isn’t reassured and leaves the hospital feeling anxious and overwhelmed.

After these encounters, Dr. Jarvis wondered: Might the mother be the actual patient?

Postpartum depression (PPD) is the most common complication of childbirth, Dr. Jarvis explains, occurring in up to 20 percent of all mothers, and may be higher (up to 50 percent) in low-income and immigrant women. Far beyond simple “baby blues,” the mood disorder can have significant implications for the mother, her baby and the entire family. It can hinder mother-child bonding and lead to early discontinuation of breastfeeding, delayed immunizations, and child abuse and neglect. The associated effects on early brain development might cause cognitive and developmental delays for the infant and, later in life, can manifest as emotional and behavioral problems. PPD can disrupt relationships between parents. And suicide is the top cause of postpartum death.

Mothers are supposed to be screened routinely for PPD at postpartum visits with their maternal or pediatric health care providers. In addition, several medical professional societies – including the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists – now recommend screening for PPD in the prenatal and postnatal periods and during routine well-child visits in the outpatient setting. But these screenings often don’t happen, Dr. Jarvis says, either because doctors aren’t following the recommendations or parents aren’t attending these visits due to barriers to health care access or other problems.

One way to sidestep these challenges, she says, is to provide PPD screening in the emergency setting.

“The ED becomes the safety net for people who are not routinely accessing regular checkups for themselves and their children,” Dr. Jarvis says. “If a mother is having an acute crisis in the middle of the night and feeling anxious and depressed, they often come to the emergency department for help.”

Dr. Jarvis and colleagues launched a pilot study in the Children’s ED to screen for PPD. For eight months beginning June 2015, the researchers invited English- and Spanish-speaking mothers who arrived at the ED with infants 6 months old or younger with complaints that didn’t necessitate immediate emergency care to take a short questionnaire on a computer tablet. This questionnaire included the Edinburgh Postnatal Depression Scale, a well-validated tool to screen for PPD, along with basic sociodemographic questions and queries about risk factors that other studies previously identified for PPD.

Just over half agreed to participate. When Dr. Jarvis and colleagues analyzed the results from these 209 mothers, they found that 27 percent scored positive for PPD, more than the average from previous estimates. Fourteen of those mothers reported having suicidal thoughts. Surprisingly, nearly half of participants reported that they’d never been screened previously for PPD, despite standing recommendations for routine screenings at mother and baby care visits, the research team writes in findings published online May 5, 2018, in Pediatric Emergency Care.

Based on the screening results, the researchers implemented a range of interventions. All mothers who participated in the study received an informational booklet from the March of Dimes on PPD. If mothers scored positive, they also received a local PPD resource handout and were offered a consultation with a social worker. Those with a strongly positive score were required to receive a social worker consultation and were given the option of “warm-line” support to PPD community partners, a facilitated connection to providers who offer individual or group therapy or home visits, or to a psychiatrist who might prescribe medication. Mothers with suicidal thoughts were assessed by a physician and assisted by crisis intervention services, if needed.

When the researchers followed up with mothers who screened positive one month later, an overwhelming majority said that screening in the ED was important and that the resources they were given had been key for finding help. Many commented that even the screening process seemed like a helpful intervention.

“Some of these women had no idea how common PPD was. They thought they were crazy and felt alone and were bad moms,” Dr. Jarvis says. “For someone to even ask about PPD made these women aware that this exists, and it’s something people care about.”

Many thanked her and colleagues for the follow-up call, she adds, saying that it felt good to be cared for and checked on weeks later. “It goes to show that putting support systems in place for these new mothers is very important,” she says.

Dr. Jarvis and ED colleagues are currently collaborating with social workers, neonatology and other Children’s National Health System care partners to start screening mothers in the neonatal intensive care unit (NICU) and ED for PPD. They plan to compare results generated by this universal screening to those in their study. These findings will help researchers better understand the prevalence of PPD in mothers with higher triage acuity levels and how general rates of PPD for mothers in the ED and NICU compare with those generated in past studies based on well-child checks. Eventually, she says, they would like to study whether the interventions they prescribed affected the known consequences of PPD, such as breastfeeding, timely immunization rates and behavior outcomes.

“With appropriate care and resources,” Dr. Jarvis adds, “we’re hoping to improve the lives of these women and their families.”

In addition to Dr. Jarvis, the lead study author, Children’s co-authors include Kristen A. Breslin, M.D., M.P.H.; Gia M. Badolato, M.P.H.; James M. Chamberlain, M.D.; and Monika K. Goyal, M.D., MSCE, the study’s senior author.

Making the grade: Children’s National is nation’s Top 5 children’s hospital

June 26, 2018

Children’s National rose in rankings to become the nation’s Top 5 children’s hospital according to the 2018-19 Best Children’s Hospitals Honor Roll released June 26, 2018, by U.S. News & World Report. Additionally, for the second straight year, Children’s Neonatology division led by Billie Lou Short, M.D., ranked No. 1 among 50 neonatal intensive care units ranked across the nation.

Children’s National also ranked in the Top 10 in six additional services:

Neurology and Neurosurgery (No. 5), led by Roger Packer, M.D., and Robert Keating, M.D.
Nephrology (No.6), led by Marva Moxey-Mims, M.D., FASN
Cancer (No. 7), led by Jeffrey Dome, M.D., Ph.D.
Orthopedics (No. 8), led by Matthew Oetgen, M.D.
Pulmonary (No. 9), led by Anastassios Koumbourlis, M.D., M.P.H., and
Diabetes and Endocrinology (a tie for No. 10), led by Fran Cogen, M.D., acting division co-chief

For the eighth year running, Children’s National ranked in all 10 specialty services, which underscores its unwavering commitment to excellence, continuous quality improvement and unmatched pediatric expertise throughout the organization.

“It’s a distinct honor for Children’s physicians, nurses and employees to be recognized as the nation’s Top 5 pediatric hospital. Children’s National provides the nation’s best care for kids and our dedicated physicians, neonatologists, surgeons, neuroscientists and other specialists, nurses and other clinical support teams are the reason why,” says Kurt Newman, M.D., Children’s President and CEO. “All of the Children’s staff is committed to ensuring that our kids and families enjoy the very best health outcomes today and for the rest of their lives.”

The excellence of Children’s care is made possible by our research insights and clinical innovations. In addition to being named to the U.S. News Honor Roll, a distinction awarded to just 10 children’s centers around the nation, Children’s National is a two-time Magnet^® designated hospital for excellence in nursing and is a Leapfrog Group Top Hospital. Children’s ranks seventh among pediatric hospitals in funding from the National Institutes of Health, with a combined $40 million in direct and indirect funding, and transfers the latest research insights from the bench to patients’ bedsides.

“The 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver exceptional care across a range of specialties and deserve to be highlighted,” says Ben Harder, chief of health analysis at U.S. News. “Day after day, these hospitals provide state-of-the-art medical expertise to children with complex conditions. Their U.S. News’ rankings reflect their commitment to providing high-quality care.”

The 12^th annual rankings recognize the top 50 pediatric facilities across the U.S. in 10 pediatric specialties: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology. Hospitals received points for being ranked in a specialty, and higher-ranking hospitals receive more points. The Best Children’s Hospitals Honor Roll recognizes the 10 hospitals that received the most points overall.

This year’s rankings will be published in the U.S. News & World Report’s “Best Hospitals 2019” guidebook, available for purchase in late September.

Keeping an eye on autonomic function for infants with HIE

June 8, 2018

“By including heart rate variability measurements and other markers of autonomic function in our current predictive armamentarium,” says An Massaro, M.D., “we may be able to offer new hope for infants with HIE.”

In about two to three in every 1,000 full-term births, babies develop a neurological condition called hypoxic ischemic encephalopathy (HIE) when their brains receive insufficient oxygen. HIE can be a devastating condition, leading to severe developmental or cognitive delays or motor impairments that become more evident as the child grows older. Despite improvements in care – including therapeutic hypothermia, a whole-body cooling method administered shortly after birth that can slow brain damage – about half of children with this condition die from neurological complications by age 2.

Finding ways to identify children with the most severe HIE could help researchers focus their efforts and provide even more intense neuroprotective care, explains An Massaro, M.D., a neonatologist at Children’s National Health System. But thus far, it’s been unclear which symptoms reflect the extent of HIE-induced brain damage.

That’s why Dr. Massaro and colleagues embarked on a study published in the May 2018 issue of Journal of Pediatrics. The team sought to determine whether dysfunction of the autonomic nervous system (ANS) – the auto-pilot part of the nervous system responsible for unconscious bodily functions, such as breathing and digestion – reflected in routine care events can be used as a marker for brain injury severity.

The researchers collected data from 25 infants who were treated for HIE with therapeutic hypothermia at Children’s National. Thanks to multi-modal monitoring, these babies’ medical records hold a treasure trove of information, explains Rathinaswamy B. Govindan, Ph.D., a staff scientist in Children’s Advanced Physiological Signals Processing Lab.

In addition to including continuous heart rate tracings and blood pressure readings that are standard for many infants in the neonatal intensive care unit (NICU), they also recorded cerebral near infrared spectroscopy, a monitor that measures brain tissue oxygen levels. The investigators performed detailed analyses to evaluate how these monitor readings change in response to a variety of routine care events, such as diaper changes, heel sticks, endotracheal tube manipulations and pupil examinations.

The researchers stratified these infants based on how dysfunctional their ANS behaved by using heart rate variability as a marker: The fewer natural fluctuations in heart rate, the more damaged their ANS was thought to be. And they also used non-invasive brain magnetic resonance imaging (MRI) to determine brain damage. They then compared this information with the babies’ physiological responses during each care event.

Their findings show that infants with impaired ANS, based on depressed heart rate variability before the care event, had significantly different responses to these care events compared with babies with intact ANS.

For stimulating interventions, such as diaper changes and heel sticks, both heart rate and blood pressure increased in babies with intact ANS but decreased in babies with impaired ones.
Shining a light in their pupils led to an expected decreased heart rate with stable blood pressure in ANS-intact infants, but in ANS-impaired infants, there was no responsive change in heart rate and, additionally, a decrease in blood pressure was observed.
Responses were similar between the two groups during breathing tube manipulations, except for a slight increase in heart rate a few minutes later in the ANS-impaired group.

These results, Govindan explains, suggest that a real-time, continuous way to assess ANS function may offer insights into the expected physiological response for a given infant during routine NICU care.

“This is exactly the type of additional information that intensivists need to pinpoint infants who may benefit from additional neuroprotective support,” he says. “Right now, it is standard practice to monitor brain activity continuously using electroencephalogram and to check the status of the brain using MRI to assess the response to therapeutic cooling. Neither of these assessments can be readily used by neonatologists at the bedside in real-time to make clinical decisions.”

Assessing ANS function in real-time can help guide neuroprotective care in high-risk newborns by providing insight into the evolving nature of brain damage in these infants, Dr. Massaro adds.

Beyond simply serving as a biomarker into brain injury, poor ANS function also could contribute to the development of secondary injury in newborns with HIE by stymieing the normal changes in heart rate and blood pressure that help oxygenate and heal injured brains. The researchers found that the cumulative duration of autonomic impairment was significantly correlated with the severity of brain injury visible by MRI in this group of infants.

“By including heart rate variability measurements and other markers of autonomic function in our current predictive armamentarium,” says Dr. Massaro, “we may be able to offer new hope for infants with HIE.”

In addition to Dr. Massaro, the Senior Author, study co-authors include Lead Author, Heather Campbell, M.D.; Rathinaswamy B. Govindan, Ph.D., Children’s Advanced Physiological Signals Processing Lab; Srinivas Kota, Ph.D.; Tareq Al-Shargabi, M.S.; Marina Metzler, B.S.; Nickie Andescavage, M.D., Children’s neonatalogist; Taeun Chang, M.D., Children’s neonatal and fetal neurologist; L. Gilbert Vezina, M.D., attending in Children’s Division of Diagnostic Imaging and Radiology; and Adré J. du Plessis, M.B.Ch.B., M.P.H., chief of Children’s Division of Fetal and Transitional Medicine.

This research was supported by the Clinical and Translational Science Institute at Children’s National under awards UL1TR000075 and 1KL2RR031987-01 and the Intellectual and Developmental Disabilities Research Consortium within the National Institutes of Health under award P30HD040677.