Behavioral Sciences

Lenore Jarvis

Screening for postpartum depression in the emergency department

Lenore Jarvis

“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

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:

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 12th 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.

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., 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.

Preemie Baby

Brain food for preemies

Preemie Baby

Babies born prematurely – before 37 weeks of pregnancy – often have a lot of catching up to do. Not just in size. Preterm infants typically lag behind their term peers in a variety of areas as they grow up, including motor development, behavior and school performance.

New research suggests one way to combat this problem. The study, led by Children’s researchers and presented during the Pediatric Academic Societies 2018 annual meeting, suggests that the volume of carbohydrates, proteins, lipids and calories consumed by very vulnerable premature infants significantly contributes to increased brain volume and white matter development, even though additional research is needed to determine specific nutritional approaches that best support these infants’ developing brains.

During the final weeks of pregnancy, the fetal brain undergoes an unprecedented growth spurt, dramatically increasing in volume as well as structural complexity as the fetus approaches full term.

One in 10 infants born in the U.S. in 2016 was born before 37 weeks of gestation, according to the Centers for Disease Control and Prevention. Within this group, very low birthweight preemies are at significant risk for growth failure and neurocognitive impairment. Nutritional support in the neonatal intensive care unit (NICU) helps to encourage optimal brain development among preterm infants. However, their brain growth rates still lag behind those seen in full-term newborns.

“Few studies have investigated the impact of early macronutrient and caloric intake on microstructural brain development in vulnerable preterm infants,” says Katherine Ottolini, lead author of the Children’s-led study. “Advanced quantitative magnetic resonance imaging (MRI) techniques may help to fill that data gap in order to better direct targeted interventions to newborns who are most in need.”

The research team at Children’s National Health System enrolled 69 infants who were born younger than 32 gestational weeks and weighed less than 1,500 grams. The infants’ mean birth weight was 970 grams and their mean gestational age at birth was 27.6 weeks.

The newborns underwent MRI at their term-equivalent age, 40 weeks gestation. Parametric maps were generated for fractional anisotropy in regions of the cerebrum and cerebellum for diffusion tensor imaging analyses, which measures brain connectivity and white matter tract integrity. The research team also tracked nutritional data: Grams per kilogram of carbohydrates, proteins, lipids and overall caloric intake.

“We found a significantly negative association between fractional anisotropy and cumulative macronutrient/caloric intake,” says Catherine Limperopoulos, Ph.D., director of Children’s Developing Brain Research Laboratory and senior author of the research. “Curiously, we also find significantly negative association between macronutrient/caloric intake and regional brain volume in the cortical and deep gray matter, cerebellum and brainstem.”

Because the nutritional support does contribute to cerebral volumes and white matter microstructural development in very vulnerable newborns, Limperopoulos says the significant negative associations seen in this study may reflect the longer period of time these infants relied on nutritional support in the NICU.

In addition to Ottolini and Limperopoulos, study co-authors include Nickie Andescavage, M.D., Attending, Children’s Neonatal-Perinatal Medicine; and Kushal Kapse.

Dr. Jackson and colleagues with D.C. City Council

Shining a light on child abuse, how to prevent it and help kids recover

Dr. Jackson and colleagues with D.C. City Council

Dr. Jackson and colleagues from Children’s National Health System and the District’s Multidisciplinary Team join resolution sponsor Councilmember Vincent Gray and the D.C. City Council for the presentation of the Child Abuse Prevention Month Recognition Resolution of 2018.

In recognition of Child Abuse Prevention Month, Children’s National Health System joined the DC City Council on Tuesday, April 10, 2018, to present the Child Abuse Prevention Month Recognition Resolution of 2018. According to Councilmember Vincent Gray, who sponsored it, the unanimous resolution “recognizes all the community partners who work to prevent the tragedy of child abuse before it happens, and who keep the children of the District of Columbia as safe as we can.”

He mentioned the many years that the District of Columbia fell in the top five for child abuse victims per capita, and that, while the city still ranks highly, the number of victims per  1,000 children has declined significantly since 2009. He attributes this decline to the communities and agencies who work together to protect children and strengthen families.

Allison Jackson, M.D., MPH, chief of the Child and Adolescent Protection Center at Children’s National, expressed her sincere appreciation for all the people who care for and protect children.

“Every day we see the scores of children who have experienced maltreatment,” she says. “We are so thankful for the recognition of the small voices, and grateful to Councilman Gray and the other supportive councilmembers for helping us to remove the veil of secrecy that burdens so many children and families who have experienced child abuse.”

The Child and Adolescent Protection Center at Children’s National Health System was started in the mid-1970s to provide medical care, forensic medical evaluations by pediatric trained forensic professionals, and mental health treatment for children. Dr. Jackson notes that in the 1990s, the District established a multi-disciplinary team to implement the trauma-informed response framework across all agencies in the District addressing these issues.

She also cites that years of research into adverse childhood events have shown that childhood abuse, exploitation, and neglect has long term medical and brain health consequences that last throughout life and can shorten lives, as well.

However, that research also shows that trauma-informed care and interventions can reduce the exposure to maltreatment, and also reduce the long lasting impacts of maltreatment on a child.

“Child abuse can be prevented if we can all commit to promoting safe, stable and nurturing relationships for children and youth,” Dr. Jackson points out. “I encourage each of you to learn how to recognize child abuse and the appropriate response if you suspect it. Parenting is difficult, so support and encourage parents and caregivers.  Remember that ‘discipline’ means ‘to teach,’ so find constructive ways to teach children right from wrong. And SPEAK UP for children and families.”

The presentation occurs at 33:00 minutes of the 22nd Legislative Meeting of the D.C. City Council.

Vittorio Gallo

Perinatal brain injury headlines American Society for Neurochemistry

Vittorio Gallo

Dr. Gallo’s research could have major implications for overcoming the common behavioral and developmental challenges associated with premature birth.

Children’s National Chief Research Officer Vittorio Gallo, Ph.D., recently had the honor of presenting a presidential lecture at the 48th Annual Meeting of the American Society for Neurochemistry (ASN). The lecture focused on his lifelong investigations of the cellular and molecular mechanisms of white matter development and injury, including myelin and glial cells – which are involved in the brain’s response to injury.

Specifically, he outlined the underlying diffuse white matter injury observed in his lab’s pre-clinical model of perinatal hypoxia, and presented new, non-invasive interventions that promote functional recovery and attenuate developmental delay after perinatal injury in the model. Diffuse white matter injuries are the most frequently observed pattern of brain injury in contemporary cohorts of premature infants. Illuminating methods that might stimulate growth and repair of such injuries shows promise for potential noninvasive strategies that might mitigate the long-term behavioral abnormalities and developmental delay associated with premature birth.

Dr. Gallo’s work in developmental neuroscience has been seminal in deepening understanding of cerebral palsy and multiple sclerosis. During his tenure as center director, he transformed the Center for Neuroscience Research into one of the nation’s premier programs.

ASN gathers nearly 400 delegates from the neurochemistry sector each year, including bench and clinical scientists, principal investigators, graduate students and postdoctoral fellows all actively involved in research from North America and around the world.

Joseph Scafidi

Developing brains are impacted, but can recover, from molecularly targeted cancer drugs

Joseph Scafidi

“The plasticity of the developing brain does make it susceptible to treatments that alter its pathways,” says Joseph Scafidi, D. O., M.S. “Thankfully, that same plasticity means we have an opportunity to mitigate the damage from necessary and lifesaving treatments by providing the right support after the treatment is over.”

One of the latest developments in oncology treatments is the advancement of molecularly targeted therapeutic agents. These drugs can be used to specifically target and impact the signaling pathways that encourage tumor growth, and are also becoming a common go to for ophthalmologists to treat retinopathy of prematurity in neonates.

But in the developing brain of a child or adolescent, these pathways are also crucial to the growth and development of the brain and central nervous system.

“These drugs have been tested in vitro, or in tumor cells, or even in adult studies for efficacy, but there was no data on what happens when these pathways are inhibited during periods when their activation is also playing a key role in the development of cognitive and behavioral skills, as is the case in a growing child,” says Joseph Scafidi, D. O., M.S., a neuroscientist and pediatric neurologist who specializes in neonatology at Children’s National Health System.

As it turns out, when the drugs successfully inhibit tumor growth by suppressing receptors, they can also significantly impact the function of immature brains, specifically changing cognitive and behavioral functions that are associated with white matter and hippocampal development.

The results appeared in Cancer Research, and are the first to demonstrate the vulnerability of the developing brain when this class of drugs is administered. The pre-clinical study looked at the unique impacts of drugs including gefitinib (Iressa), sunitib malate (Sutent) and rapamycin (Sirolimus) that target specific pathways responsible for the rapid growth and development that occurs throughout childhood.

The agents alter signaling pathways in the developing brain, including decreasing the number of oligodendrocytes, which alters white matter growth. Additionally, the agents also impact the function of specific cells within the hippocampus related to learning and memory. When younger preclinical subjects were treated, impacts of exposure were more significant. Tests on the youngest pre-clinical subjects showed significantly diminished capacity to complete cognitive and behavioral tasks and somewhat older, e.g. adolescent, subjects showed somewhat fewer deficits. Adult subjects saw little or no deficit.

“The impacts on cognitive and behavioral function for the developing brain, though significant, are still less detrimental than the widespread impacts of chemotherapy on that young brain,” Dr. Scafidi notes. “Pediatric oncologists, neuro-oncologists and ophthalmologists should be aware of the potential impacts of using these molecularly targeted drugs in children, but should still consider them as a treatment option when necessary.”

The effects are reversible

Researchers also found measurable improvements in these impaired cognitive and behavioral functions when rehabilitation strategies such as environmental stimulation, cognitive therapy and physical activity were applied after drug exposure.

“The plasticity of the developing brain does make it susceptible to treatments that alter its pathways,” says Dr. Scafidi. “Thankfully, that same plasticity means we have an opportunity to mitigate the damage from necessary and lifesaving treatments by providing the right support after the treatment is over.”

Many major pediatric oncology centers, including the Center for Cancer and Blood Disorders at Children’s National, already incorporate rehabilitation strategies such as cognitive therapy and increased physical activity to help pediatric patients return to normal life following treatment. The results from this study suggest that these activities after treatment for pediatric brain tumors may play a vital role in improving recovery of brain cognitive and behavioral function in the pediatric population.

This research was funded by grants to Dr. Scafidi from the National Brain Tumor Society, Childhood Brain Tumor Foundation and the National Institutes of Health.

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.

Maureen Monaghan

Using text messages and telemedicine to improve diabetes self-management

Maureen Monaghan

Maureen Monaghan, Ph.D., C.D.E., clinical psychologist and certified diabetes educator in the Childhood and Adolescent Diabetes Program at Children’s National Health System, awarded nearly $1.6 million grant from American Diabetes Association.

Adolescents and young adults ages 17-22 with Type 1 diabetes are at high risk for negative health outcomes. If fact, some studies show that less than 20 percent of patients in this population meet targets for glycemic control, and visits to the Emergency Department for acute complications like diabetic ketoacidosis peak around the same age.

The American Diabetes Association (ADA) awarded Maureen Monaghan, Ph.D., C.D.E., clinical psychologist and certified diabetes educator in the Childhood and Adolescent Diabetes Program at Children’s National Health System, nearly $1.6 million to evaluate an innovative behavioral intervention to improve patient-provider communication, teach and help patients maintain self-care and self-advocacy skills and ultimately prepare young adults for transition into adult diabetes care, limiting the negative adverse outcomes that are commonly seen in adulthood.

Dr. Monaghan is the first psychologist funded through the ADA’s Pathway to Stop Diabetes program, which awards six annual research grants designed to spur breakthroughs in fundamental diabetes science, technology, diabetes care and potential cures. Dr. Monaghan received the Accelerator Award, given to diabetes researchers early in their careers, which will assist her in leading a behavioral science project titled, “Improving Health Communication During the Transition from Pediatric to Adult Diabetes Care.”

“Behavior is such a key component in diabetes care, and it’s wonderful that the American Diabetes Association is invested in promoting healthy behaviors,” says Dr. Monaghan. “I’m excited to address psychosocial complications of diabetes and take a closer look at how supporting positive health behavior during adolescence and young adulthood can lead to a reduction in medical complications down the road.”

During the five year study, Dr. Monaghan will recruit patients ages 17-22 and follow their care at Children’s National through their first visit with an adult endocrinologist. Her team will assess participants’ ability to communicate with providers, including their willingness to disclose diabetes-related concerns, share potentially risky behaviors like drinking alcohol and take proactive steps to monitor and regularly review glucose data.

“The period of transition from pediatric to adult diabetes care represents a particularly risky time. Patients are going through major life changes, such as starting new jobs, attending college, moving out of their parents’ homes and ultimately managing care more independently,” says Dr. Monaghan. “Behavioral intervention can be effective at any age, but we are hopeful that we can substantially help youth during this time of transition when they are losing many of their safety nets.”

Study leaders will help participants download glucose device management tools onto their smartphones and explain how to upload information from patients’ diabetes devices into the system. Participants will then learn how to review the data and quickly spot issues for intervention or follow-up with their health care provider.

Patients also will participate in behavioral telemedicine visits from the convenience of their own homes, and receive text messages giving them reminders about self-care and educational information, such as “Going out with your friends tonight? Make sure you check your glucose level before you drive.”

At the study’s conclusion, Dr. Monaghan anticipates seeing improvements in psychosocial indicators, mood and transition readiness, as well as improved diabetes self-management and engagement in adult medicine.

little girl holding a stuffed bear

Population Strategies for Children’s Health Summit

little girl holding a stuffed bear

Children’s National, with sponsorship from Cerner Corporation, is excited to announce the first Population Strategies for Children’s Health Summit on February 19 – 20, 2018 at The Westin in Washington, D.C. This is the first summit focused exclusively on comprehensive population health management approaches that can help children reach their highest levels of health and potential.

Join us in developing new ideas and best practices that engage millennial healthcare consumers and address challenges pediatric providers face in transitioning to value-based care. You’ll learn how population health management strategies can improve care quality for an entire pediatric population in a way that supports your health system’s bottom line.

Speakers at the summit will focus on topics such as:

  • Health policy
  • Care coordination
  • Physician engagement
  • Registries and risk stratification
  • Telehealth
  • Health disparities
  • Taking on risk

Get a sneak peek of the featured Millennial Panel discussion on February 20:

The current and future state of health care from a consumer’s perspective

Health care is a dynamic, constantly evolving entity. This three-person panel plus moderator takes on the consumer point of view to discuss what is and isn’t working in health care today. The panel consists of a pediatrician and mom of a child with Type 1 diabetes and a 15-year-old Type 1 diabetes patient. They’ll share their experiences and thoughts about how they believe health care will progress in the future.

For more information about the 2018 Population Strategies for Children’s Health Summit, please visit our website.

Lee Beers

Mental health screenings increase in practices with hands-on support

Lee Beers

A new study suggests many more pediatricians would make mental health screenings an integral part of a child’s annual checkup if they received training and support through a proven and powerful method used to improve health care processes and outcomes.

Results of the multidisciplinary study led by Children’s National Health System and published in Pediatrics, showed screening rates improved from one percent to 74 percent during the 15-month study. A total of 10 pediatric practices and 107 individual providers in the Washington, D.C., area voluntarily participated in the study.

“This study is an important first step towards early identification of children with mental health concerns,” says Lee S. Beers, M.D., the study’s lead author. “If you identify and treat children with mental health concerns earlier, you’re going to see better outcomes.”

In this country, approximately 13 percent of youth live with a serious mental illness, but only about 20 percent of them get the help they need, according to the D.C. Collaborative for Mental Health in Pediatric Primary Care. 

While many pediatricians agree that early mental health screenings are important, the researchers found that few providers were actually conducting them. In the past, primary care providers have cited a shortage of pediatric mental health providers, a lack of time, insufficient resources and lower reimbursements.

To address the lack of mental health screenings, researchers decided to test whether the Quality Improvement (QI) Learning Collaborative model, which was pioneered in the mid-1990s to scale and improve health care services, would help study participants integrate screenings into their practices.

The QI Learning Collaborative model takes a more hands-on approach than the typical “once and done” study, says Beers. Specifically, the participating primary care providers received periodic check-ins, ongoing support, monitoring and technical assistance. “We use rapid cycles of evaluation to see what’s working and what’s not working, and we keep going,” Beers says.

Dr. Beers is optimistic about how well the practices performed, adding the caveat that more information is needed about the burden it could place on already bustling pediatric practices. In addition, she says, “future research will be needed to determine whether identifying mental health issues also leads to improved access to care and outcomes for pediatric patients.”

Dr. Beers serves as medical director for Municipal and Regional Affairs at the Child Health Advocacy Institute (CHAI), part of Children’s National. CHAI is a founding member of the D.C. Healthy Communities Collaborative (DCHCC), which partnered on the study with the Georgetown University Medical Center and the Georgetown University Center for Child and Human Development.

Adolescent brain scan from obesity study

Imaging captures obesity’s impact on the adolescent brain

Adolescent brain scan from obesity study

For the first time, a team of researchers led by Chandan Vaidya, Ph.D., chair of the Department of Psychology at Georgetown University, has used functional magnetic resonance imaging (fMRI) to capture the brain function of a small population of adolescents with obesity, both before and after bariatric surgery.

Obesity affects the whole body, from more obvious physical impacts on bones and joints to more subtle, internal impacts on organs like the brain.

For the first time, a team of researchers has used functional magnetic resonance imaging (fMRI) to capture the brain function of a small population of adolescents with obesity, both before and after bariatric surgery. The goal is to better understand the neural changes that occur when an adolescent is obese, and determine the effectiveness of interventions, such as vertical sleeve gastrectomy, at improving brain function as weight is lost.

The study, published as the November Editors’ Choice in the journal Obesity, found that executive and reward-related brain functions of study participants with obesity improved following the surgical procedure and initial weight loss.

How bariatric surgery changes the teenage brain from Research Square on Vimeo.

“We’ve known for some time that severe obesity has negative consequences on some neurocognitive function areas for adults,” says Chandan Vaidya, Ph.D., chair of the Department of Psychology at Georgetown University and a senior author of the study. “But for the first time, we’ve captured fMRI evidence in young patients, and also shown that surgical intervention and the resulting weight loss can reverse some of those deficits.”

“For me, this early evidence makes a strong case that when kids are struggling with severe obesity, we need to consider surgical intervention as an option sooner in the process,” notes Evan Nadler, M.D., director of the Bariatric Surgery Program at Children’s National Health System, who also contributed to the study. “The question that remains is whether the neurocognitive function improves more if surgery, and thus weight loss, happens earlier – and is there a time factor that should help us determine when to perform a procedure that will maximize improvements?”

The preliminary study included 36 participants and was conducted using patients recruited from the Children’s National Bariatric Surgery program, one of the first children’s hospitals to achieve national accreditation by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program.

“We asked these questions because we know that in the kids we see, their behavioral, brain, and physical health are all very closely related to one another and have an impact on each other,” adds Eleanor Mackey, Ph.D., study senior author and co-principal investigator on the National Institute of Diabetes and Digestive and Kidney Diseases grant that funded the project. “We expected that as physical health improves, we might see corresponding improvements in brain and behavior such as cognitive and school performance.”

The study also pointed out some technical and practical challenges to studying this particular young population. Anyone with a BMI greater than 50 was not able to fit within the MR bore used in the study, preventing fMRI participation by those patients.

“In addition to future studies with a larger sample size, we’d like to see if there are neuroimaging markers of plasticity differences in a population with BMI greater than 50,” says Dr. Vaidya. “Does the severity of the obesity change how quickly the brain can adapt following surgery and weight loss?”

The abstract was selected by the journal’s editors as one that provides insights into preventing and treating obesity. It was featured at the Obesity Journal Symposium during Obesity Week 2017 in Washington, D.C., as part of the Obesity Week recognition, and a digital video abstract was also released about the findings.

Olanrewaju-Falusi

Improving health care for immigrant children

Olanrewaju-Falusi

Immigrant children may face multiple and complex challenges that underlie seemingly routine health concerns that bring them to clinic, says Olanrewaju Falusi, M.D., F.A.A.P.

Over the next 40 years, children of immigrant families will grow to represent one-third of residents of the United States. To help more pediatricians address the interplay between immigration and child health, a Children’s National Health System clinician helped to compile a set of case studies, resources and recommendations.

Olanrewaju Falusi, M.D., F.A.A.P., and a colleague explained these issues during their joint presentation, “Advancing health care quality for immigrant children,” during the 2017 American Academy of Pediatrics (AAP) national conference. The aim of the presentation and of their work is to help pediatricians understand the impact of immigration-related issues and unresolved immigration status on children’s mental health and well-being.

“As pediatricians, we are tasked with caring for the whole child. And, for immigrant children, there may be multiple and complex challenges that underlie seemingly routine health concerns that bring them to clinic,” says Dr. Falusi, associate medical director of municipal and regional affairs at the Child Health Advocacy Institute at Children’s National. “By more fully understanding immigrant children’s unique needs, we can help bolster their resiliency.”

Though refugees may be resettled anywhere, in fiscal year 2016 almost 7,400 unaccompanied children were released to sponsors in California, the highest of the states. In five states (California, Illinois, Massachusetts, New York, Washington state and the District of Columbia) immigration status has no bearing on a child accessing public health. Undocumented immigrants, however, are not eligible for subsidies that lower the price of health insurance. Nor can they access such federal entitlements as SNAP (formerly known as Food Stamps). Even something as basic as having a ride to a doctor’s appointment can be complicated since only one dozen states offer access to driver’s licenses regardless of immigration status.

Using the case of a child named “Pedro,” who feared deportation, Dr. Falusi and a colleague explained how immigration status impacts access to clinical care, discussed DACA, his parent’s undocumented status and explored how clinicians could support Pedro and his family.

In another scenario, Esperanza comes to clinic with her 3- and 6-year-old sons, who are afraid to leave her side. Since the family fled Honduras and settled in the United States, Esperanza worries about her older daughter’s behavioral problems in school.

“These are challenging mental health concerns to unravel because some families may be reluctant to reopen past traumas,” Dr. Falusi says. “During their flight from their home country, children can be victims of or witnesses to violence, including rape. They may have seen another person drown during a water crossing or die in arid deserts.”

Clinicians can begin such conversations simply by trying to understand why Esperanza and her children came to the United States in order to consider the range of options for appropriate clinical care, as well as possible legal services. Bridging from that more neutral starting point, the health care team could delve into her family’s experiences in Honduras. If Esperanza fears returning to Honduras, asylum may be an option if her fears are well-founded and the persecution is due to race, religion, nationality, political opinion or membership in a particular social group, Dr. Falusi says.  Additional options may include T visas and U visas for victims of certain crimes.

“We are all aware how little time there is during the clinical encounter to have such detailed conversations. Ideally, the clinician would serve as a trusted intermediary, helping the family connect with community resources in order to best address the unique social needs of immigrant children,” Dr. Falusi says.

Latina mother playing with her baby boy son on bed

Helping parents of babies leaving NICU cope

Latina mother playing with her baby boy son on bed

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

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

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

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

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

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

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

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

Kid being bullied

Reducing bullying the Finnish way – in the United States

Kid being bullied

Bullying is a pervasive problem for U.S. kids. Recent studies show that between one in four to one in three children have been bullied at school. About one in 10 are victimized regularly.

Research suggests that this isn’t just harmless “kids being kids” behavior, says Marissa Smith, Ph.D., a postdoctoral fellow in behavioral pain medicine at Children’s National Health System. Bullied children have a greater risk of experiencing overall negative academic outcomes, such as greater school avoidance, decreased classroom engagement and lower academic achievement than children who aren’t bullied. They also suffer emotionally, with more depression, anxiety and withdrawal, as well as suffering physically, reporting more headaches, stomachaches and sleep difficulties.

In response to these harmful consequences, researchers in Finland in 2009 developed the KiVa Anti-Bullying Program. This school-based program combats bullying through a series of teacher-led lessons provided to students throughout the academic year that aim to shift the entire school’s ethos.

Research in Finland demonstrating the success of KiVa has encouraged school systems around the world to pilot and evaluate the KiVa program in their schools. However, Smith cautions, differing school cultures could lead to differing results.

“Compared with Finland, teachers in the United States juggle many more competing demands on their time and, at times, have fewer resources and less institutional support in fulfilling those demands,” she explains. “Consequently, it’s not clear whether a program like KiVa would be as realistic here.”

To see how implementing KiVa might differ in an American setting, Smith and colleagues helped fourth- and fifth-grade teachers at nine elementary schools in one Delaware school district roll out the program to 1,409 students during the 2013 to 2014 school year. Each teacher completed a three-hour training course at the beginning of the year – already a drastic cut from the two full days of training that is standard in Finland – due to competing demands on American teachers’ professional development time.

Delaware teachers also completed questionnaires at the start of the year about variables that might affect how well they would be able to implement the program, such as their level of professional burnout, perceived principal support, self-efficacy at teaching and perceived feasibility and efficacy of KiVa. Students completed questionnaires at the beginning and end of the academic year that measured levels of victimization and bullying.

Once a month, teachers were to give their classes standard KiVa lessons. To track what they actually completed, teachers answered online questionnaires. They also met with a graduate student once monthly to learn tips about implementing the program.

Results published online Aug. 29, 2017 in Journal of School Psychology by Smith and co-authors showed that this program accomplished its goals of significantly reducing bullying and victimization by the end of the year. Precisely how successful these measures were hinged on what instructional “dose” of the program students received, Smith says. On average, teachers provided only half of the activities that were intended to be included in each lesson. They also gave an average of 7.8 KiVa lessons out of a possible total of 10.

When Smith and colleagues assessed which teacher variables correlated with a reduction in KiVa instruction, professional burnout had the highest impact. It’s hard to say what leads teachers to experience burnout; however, Smith explains, it might be an overall symptom of U.S. teaching culture.

“Teachers are highly regarded in Finland – at the same level as doctors – but U.S. teachers are not afforded nearly the same levels of respect,” she says. “Burnout here may speak to this lack of respect. Other factors that contributed to diminished KiVa instruction include lower levels of resources and institutional support, teachers’ own degree of emotional investment in the school and teachers’ perception they actually can accomplish the things they set out to do.”

Each of these differences, Smith adds, could contribute to KiVa not being as effective in the United States as it is in Finland.

One way to improve the success of this program in the United States, the study notes, might be to distill KiVa’s tenets to the bare minimum necessary to maintain positive outcomes, allowing more efficient lessons. Additionally, outsourcing lessons to guidance counselors or other school staff versed in social and emotional topics might ease teachers’ workloads.

“Schools in the United States differ significantly from those in Finland, where this program started,” she says. “Our results suggest that supporting U.S. teachers in ways that reduce burnout could lead to better implementation and less bullying – which could lead to real and lasting improvements to their students’ lives.”

Exchanging ideas

Exchanging ideas, best practices in China

Exchanging ideas

Physicians from the Children’s National delegation attended the Shanghai Pediatric Innovation Forum in June 2017. Pictured (left to right): Roberta DeBiasi, M.D., Michael Mintz, M.D., Robert Keating, M.D., Lawrence Jung, M.D., Peter Kim, M.D., and Sarah Birch, D.N.P., A.P.R.N.

In late June, a delegation of international pediatric experts from Children’s National Health System journeyed across the world to learn about the practice of pediatric medicine in China and to exchange ideas with colleagues there. Leaders from several of Children’s key specialties joined the delegation, including:

The group, led by Drs. Keating and Gaillard, traveled to China with Children’s Outreach Coordinator John Walsh, whose longtime connections and close familiarity with the pediatric medical community in Hangzhou and Shanghai made the collaboration possible. The team toured several of the largest children’s hospitals in country, including The Children’s Hospital of Zhejiang University School of Medicine in Hangzhou and Shanghai Children’s Medical Center, connecting with pediatric specialists there.

“Some of the most important parts of this trip were the opportunities to exchange ideas and solidify long term relationships that will allow us to work closely with our peers in China as they develop their pediatric programs. The potential is tremendous for unique collaborations between our teams and theirs for research and the development of clinical care improvements for children,” said Roger Packer, M.D., senior vice president of the Center for Neuroscience and Behavioral Health, who joined the delegation in Beijing.

A keynote lecture and more at the 3rd China International Forum on Pediatric Development

The delegation also was honored with an invitation to participate in the 3rd China International Forum on Pediatric Development. The forum is one of the largest pediatric focused meetings in the country and is led by all the major children’s hospitals in China, including those in Beijing and Shanghai. Close to 4,000 pediatricians attended the meeting, and presenters included esteemed international leaders in pediatric medicine from around the world.

Dr. Packer delivered one of the opening keynote lectures, entitled, “Translation of molecular advances into care: the challenge ahead for children’s hospitals.” His talk focused on the tremendous promise and significant challenges posed by the latest scientific advances, through the lens of a neurologist.

“Across the world, we are looking at the same challenges: How can we use scientific advances to find better outcomes? How can we financially support the new types of interventions made possible by these molecular biologics insights when they can cost millions of dollars for one patient?”

“There’s palpable excitement that these new developments will give us potential therapies we never dreamed about before, ways to reverse what we initially thought was irreversible brain damage, ways to prevent severe illnesses including brain tumors, but the issue is how to turn this promise into reality. That’s a worldwide issue, not simply a single country’s issue,” he continued.

He also flagged mental health and behavioral health as a crucial, universal challenge in need of addressing on both sides of the Pacific.

The Children’s National delegation, including Drs. DeBiasi, Song, Keating, Gaillard and Packer were also honored to share their insight in a series of specialty-specific breakout sessions at the Forum.

Overall, the long journey opened a dialogue between Children’s National and pediatric care providers in China, paving the way for future discussion about how to learn from each other and collaborate to enhance all institutions involved.

ECIN Briefing

Building resilient kids through healthy adults

ECIN Briefing

Mr. Lane, Dr. Hodgkinson, Dr. Biel, and Dr. Beers provided a briefing at the Washington, D.C., City Council in July about the Early Childhood Innovation Network, which takes evidence-based national models for early childhood mental health interventions and adds components designed to address Washington, D.C.’s unique needs.

Exposures to adverse childhood experiences are the single biggest predictor of outcomes for physical health, mental health, social functioning and academic achievement in children and into adulthood. There is evidence that negative experiences – such as poverty, housing insecurity, having a parent with untreated mental illness or actively engaged in substance abuse – have biological impacts on a child’s brain size and function.

Conversely, during the critical first few years of life, safe, stable and nurturing relationships from adult caregivers build healthy brains, even in the midst of adversity. Additionally, the ability of a child’s brain to absorb experience and to change means that early intervention to reduce exposure to or impact of these negative events can be particularly effective for young children. In a briefing for the Washington, D.C., City Council, leaders from the Early Childhood Innovation Network (ECIN) shared these facts and outlined how ECIN’s local collaborative of health, education and social service providers promotes resilient families and children through interventions designed to work best for each family.

“We are taking evidence-based practices from other places, and then personalizing them to our communities in D.C.,” says Lee Beers, M.D., co-director of the ECIN and the medical director for Municipal and Regional Affairs within the Child Health Advocacy Institute at Children’s National Health System. “We spent a lot of time seeking input and advice from primary care doctors, social services providers and community leaders, to make sure that we bring programs to clinics like the Children’s Health Center at Anacostia that are useful, sustainable and measurable for the children and families who live there.”

The network’s other co-director, Matthew G. Biel, M.D., chief of the Division of Child and Adolescent Psychiatry at MedStar Georgetown University Hospital continues, “We know that the best way to help these kids is by addressing challenges across generations – we can’t reach children without first helping the adults. In addition to evaluating for risk factors, we also need to screen for protective factors – how families can best buffer these young children from the toxic effects of adverse childhood experiences. Then, in a non-confrontational setting such as a routine primary care visit, we can provide them with additional tools to enhance those protective factors.”

A working example: HealthySteps D.C.

Drs. Beers and Biel cited the implementation of the HealthySteps program, an evidence-based intervention with a national network of over 100 pediatric and family practice sites across 15 states, locally in D.C. as one example of ECIN’s approach. The program, now underway at the Children’s Health Center at Anacostia and recently launched at the Children’s Health Center at THEARC, embeds specially trained HealthySteps specialists into the primary care team to provide parents and professionals with skills and tools that nurture healthy development in young children.

Nationwide, HealthySteps has been shown to have a significant impact on children, families and practices at relatively low cost, providing services within the primary care setting such as:

  • Early identification and access to effective interventions for development delays
  • Coaching on age-appropriate parent-child interactions and child social-emotional development
  • Support for parental depression, domestic violence, substance abuse, food, housing and other social determinants
  • Creating better integration between pediatric primary care and early childhood systems

ECIN’s D.C.-based version takes this successful national model and adds additional D.C. needs-based specific activities:

  • Each family is assigned a Family Champion who identifies and addresses specific resource needs, including mental health services, parent training, or support groups and basic needs such as insurance, housing or employment
  • HealthySteps specialists offer brief interventions within the primary care setting to address pressing needs such as maternal depression, grief and loss and child behavior management
  • HealthySteps specialists deliver specialized training to providers on child behavioral and developmental health

“Even in the short time since we implemented HealthySteps, we’re seeing significant impact around care coordination and case management for the families at our Children’s Health Center at Anacostia,” says Stacy Hodgkinson, Ph.D., a licensed clinical psychologist at Children’s National who serves as a HealthySteps specialist at the Children’s Health Center at Anacostia.

HealthySteps D.C. is the first of several initiatives under development by the Early Childhood Innovation Network. The group is also working together with additional community partners such as Educare, Martha’s Table, LIFT, and MedStar Washington Hospital Center to explore, implement and evaluate the effectiveness of programs in areas such as building social-emotional skills in young children, financial literacy and mental health support for mothers-to-be.

Community connections and coordination

“So many children with needs do not get connected to services, and the Early Childhood Innovation Network addresses this challenge. Even better, there has been a genuineness from ECIN to engaging community and earning buy-in for programs from the very beginning. They’ve made community leaders and parents an integral part of the network’s program design and implementation,” adds Ambrose Lane, Jr., chair and founder of the Health Alliance Network and chairman at the D.C. Department of Health Chronic Disease Citywide Collaborative.

Little girl eating

Daily tasks harder for girls with ASD

Little girl eating

Researchers found that girls with autism struggle with day-to-day functioning and independence skills more than boys.

Researchers at the Center for Autism Spectrum Disorders at Children’s National found something surprising in their recent study of executive function and adaptive skills. Girls, who often score well on direct assessments of communication skills, struggle more than boys with crucial tasks such as making a plan, getting organized and following through, as well as basic daily tasks like getting up and getting dressed, or making small talk.

“When parents were asked to rate a child’s day-to-day functioning, it turns out that girls were struggling more with these independence skills. This was surprising because in general, girls with ASD have better social and communication skills during direct assessments. The natural assumption would be that those communication and social skills would assist them to function more effectively in the world, but we found that this isn’t always the case,” says Allison Ratto, Ph.D., a psychologist in the Center for Autism Spectrum Disorders and one of the study’s authors. “Our goal was to look at real world skills, not just the diagnostic behaviors we use clinically to diagnose ASD, to understand how people are actually doing in their day to day lives.”

Conducted by a team within the Center for Autism Spectrum Disorders, the National Institute of Mental Health and The George Washington University, the study is the largest to date examining executive function and adaptive skills in women and girls with autism spectrum disorders (ASD).

The study collected parent-reported data from several rating scales of executive function and adaptive behavior, including the Behavior Rating Inventory of Executive Function, Parent Form (BRIEF) and the Vineland Adaptive Behavior Scales-II (VABS-II). The group included 79 females and 158 males meeting clinical criteria for autism spectrum disorders, ranging in ages from 7 to 18 years old. The groups were matched for intelligence, age and level of autism and ADHD symptoms.

Little is known about autism in females

The findings are part of a growing body of research focused on how ASD may affect females differently than males. The ratio of girls to boys with autism is approximately one to three. As a result of the larger numbers of males, existing data is predominantly focused on traits and challenges in that population. This is especially true in clinical trials, where enrollment is overwhelmingly male.

“Our understanding of autism is overwhelmingly based on males, similar to the situation faced by the medical community once confronted with heart disease research being predominantly male,” notes Lauren Kenworthy, Ph.D., director of the Center for Autism Spectrum Disorders and the study’s senior author. “We know how to identify signs, symptoms and treatments for autism in males, but we know very little about unique aspects of it in females.”

The historical lack of specific discovery around how autism presents in females may contribute to misdiagnosis or delay, and prevent implementation of necessary interventions. Such delays can have a major impact on outcomes, as recent research has demonstrated the critical importance of early diagnosis and intervention in ASD.

“Our focus in caring for children with autism is equipping all of them with strategies and skills to allow them to function and succeed in day-to-day living,” Dr. Kenworthy continues. “This study highlights that some common assumptions about the severity of challenges faced by girls with ASD may be wrong, and we may need to spend more time building the adaptive and executive function skills of these females if we want to help them thrive.”

“Enhancing our understanding of how biological differences change the presentation of autism in the long term is crucial to giving every person with ASD the tools they need to succeed in life,” she concludes.

Kazue Hashimoto Torii

A brain’s protector may also be its enemy

Kazue Hashimoto Torii

By looking back to the earliest moments of embryonic brain development, Kazue Hashimoto-Torii, Ph.D. and her collaborators sought to explain the molecular and cellular bases for complex congenital brain disorders that can result from exposure to harmful agents.

When the brain is exposed to an environmental stressor all is not immediately lost. Brain cells have mechanisms that protect them against the ravages of alcohol and other toxic substances. One of these is a protein the cells make, known as Heat Shock Factor 1 (Hsf1), which helps to shield them from damage. The fetal brain also can make Hsf1, which protects its particularly vulnerable cells from environmental stressors that pregnant mothers are exposed to during gestation.

However, a new study suggests that this system is not perfect. Research led by Children’s National Health System scientists suggests that when too much Hsf1 is produced, it actually can impair the brain during development. While this finding was made in a preclinical model, it raises questions about neural risks for human infants if their mothers drink alcohol in the first or second trimester of pregnancy.

When fetuses are chronically exposed to harmful agents such as alcohol, ethanol or methyl mercury in utero, the experience can negatively affect fetal brain development in unpredictable ways. Some fetal brains show little or no damage, while others suffer severe damage. By looking at the earliest moments of embryonic brain development, an international research team that includes five Children’s National authors sought to explain the molecular and cellular bases for complex congenital brain disorders that can result from exposure to such harmful agents.

“From a public health perspective, there is ongoing debate about whether there is any level of drinking by pregnant women that is ‘safe,’ ” says Kazue Hashimoto-Torii, Ph.D., principal investigator in the Center for Neuroscience Research at Children’s National and senior author of the paper published May 2 in Nature Communications. “We gave ethanol to pregnant preclinical models and found their offspring’s neural cells experienced widely differing responses to this environmental stress. It remains unclear which precise threshold of stress exposure represents the tipping point, transforming what should be a neuroprotective response into a damaging response. Even at lower levels of alcohol exposure, however, the risk for fetal neural cells is not zero,” Hashimoto-Torii adds.

The cerebral cortex – the thin outer layer of the cerebrum and cerebellum that enables the brain to process information – is particularly vulnerable to disturbances in the womb, the study authors write. To fend off insult, neural cells employ a number of self-preservation strategies, including launching the protective Hsf1-Heat shock protein (Hsp) signaling pathway that is used by a wide range of organisms, from single-cell microbes to humans. Developing fetuses activate Hsf1-Hsp signaling upon exposure to environmental stressors, some to no avail.

To help unravel the neurological mystery, the researchers used a method that allows a single molecule to fluoresce during stress exposure. They tapped specific environmental stressors, such as ethanol, hydrogen peroxide and methyl mercury – each of which are known to produce oxidative stress at defined concentrations. And, using an experimental model, they examined the Hsf1 activation pattern in the developing cerebral cortex by creating a marker, an encoding gene tagged with a type of fluorescent protein that makes it glow bright red.

“Our results suggest that heterogeneous events of abnormal brain development may occur probabilistically – which explains patterns of cortical malformations that vary with each individual, even when these individuals are exposed to similar levels of environmental stressors,” Hashimoto-Torii adds.

Among the more striking findings, neural cells with excessively high levels of Hsf1-Hsp activation due to ethanol exposure experience disruptions to normal development, with delayed migration by immature cortical neurons. For the fetal brain to develop normally, neurons need to migrate to precise places in the brain at just the right time to enable robust neural connections. When neurons fail to arrive at their destinations or get there too late, there can be gaps in the neural network, compromising efficient and effective communication across the brain’s various regions.

“Even a short period of Hsf1 overactivation during prenatal development causes critical neuronal migration deficiency. The severity of deficiency depends on the duration of Hsf1 overactivation,” Hashimoto-Torii says. “Expression patterns vary, however, across various tissues. Stochastic response within individual cells may be largely responsible for variability seen within tissue and organs.”

The research team found one bright spot: Cortical neurons that stalled due to lack of the microtubule-associated molecule Dcx were able to regain their ability to migrate properly when the gene was replenished after birth. A reduction in Hsf1 activity after birth, however, did not show the same ability to trigger the “reset” button on neural development.

“The finding suggests that genes other than microtubule-associated genes may play pivotal roles in ensuring that migrating neurons reach their assigned destinations in the brain at the right time – despite the added challenge of excessive Hsf1 activation,” according to Hashimoto-Torii.

Fetal Brain Cells

Tracking environmental stress damage in the brain

Fluorescence Reporter

A team led by Children’s National developed a fluorescence reporter system in an experimental model that can single out neurons that have survived prenatal damage but remain vulnerable after birth.

What’s known

When fetuses are exposed to environmental stressors, such as maternal smoking or alcohol consumption, radiation or too little oxygen, some of these cells can die. A portion of those that survive often have lingering damage and remain more susceptible to further environmental insults than healthy cells; however, researchers haven’t had a way to identify these weakened cells. This lack of knowledge has made it difficult to discover the mechanisms behind pathological brain development thought to arise from these very early environmental exposures, as well as ways to prevent or treat it.

What’s new

A team led by Kazue Hashimoto-Torii, Ph.D., a principal investigator in the Center for Neuroscience Research at Children’s National Health System, developed a marker that makes a protein known as Heat Shock Factor 1 glow red. This protein is produced in cells that become stressed through exposure to a variety of environmental insults. Gestation is a particularly vulnerable time for rapidly dividing nerve cells in the fetal brain. Tests showed that this marker worked not just on cells in petri dishes but also in an experimental model to detect brain cells that were damaged and remained vulnerable after exposure to a variety of different stressors. Tweaks to the system allowed the researchers to follow the progeny of cells that were affected by the initial stressor and track them as they divided and spread throughout the brain. By identifying which neurons are vulnerable, the study authors say, researchers eventually might be able to develop interventions that could slow or stop damage before symptoms arise.

Questions for future research

Q: How do different environmental insults damage brain cells during gestation?
Q: How does this damage translate into pathology in organisms as they mature?
Q: Do the progeny of damaged brain cells retain the same degree of damage as they divide and spread?
Q: Can this new detection system be used to find and track damage in other organs, such as the heart, eye and liver?

Source: Torii, M., S. Masanori, Y.W. Chang, S. Ishii, S.G. Waxman, J.D. Kocsis, P. Rakic and K. Hashimoto-Torii. “Detection of vulnerable neurons damaged by environmental insults in utero.” Published Dec. 22, 2016 by Proceedings of the National Academy of Sciences. doi: 10.1073/pnas.1620641114