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

An Massaro

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

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

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

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

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

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

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

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

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

Pediatric Academic Societies 2019 Annual Meeting presentation

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

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

PICU room

How to help bereaved families

PICU room

To help clinicians provide better care to families after children die, Tessie W. October, M.D., MPH, and colleagues recently published an article on this topic in a special supplement to Pediatric Critical Care Medicine on death and dying.

Death and dying are always difficult topics to discuss at hospitals. They’re especially hard conversations when they occur within pediatric intensive care units (PICUs), says Tessie W. October, M.D., MPH, a critical care specialist at Children’s National.

“It’s almost easier to pretend that children don’t die in the ICU. But they do,” Dr. October says.

Tragically, some children do die in ICUs. However, even when pediatric patients die, Dr. October adds, the pediatric care team’s relationship with the bereaved family continues. Knowing how to help vulnerable families during these trying times and ensuring they have needed resources can be critical to lessening the health and social consequences of grief. To help clinicians provide better care to families after children die, Dr. October and colleagues recently published an article on this topic in a special supplement to Pediatric Critical Care Medicine on death and dying.

The multi-institutional research team performed a narrative literature review for this budding field. They pored through more than 75 papers to better understand the health outcomes of parents whose child died within a PICU and the different ways that hospitals help families cope with these tragedies.

The researchers found a range of detrimental health outcomes, from a significantly increased risk of parental death in the aftermath of a child’s death to higher rates of myocardial infarction, cancer and multiple sclerosis. Bereaved parents used more health care resources themselves, took more sick days and had more sleep problems than parents who weren’t bereaved.

Likewise, parents whose child died were at a high risk of experiencing mental health conditions including complicated grief, anxiety, depression and posttraumatic stress disorder. Divorce was eight times higher among bereaved parents compared with the general population, and financial crises were common after voluntary or involuntary unemployment.

Knowing which risks parents could face can help the care team respond better if a child dies, Dr. October explains. Their review highlighted simple ways to support families in the immediate aftermath of a child’s death and beyond, such as:

  • Giving parents the opportunity to spend time alone with the child’s body
  • Allowing friends, family and others to visit at the parents’ discretion and
  • Providing easy access to professional support, such as chaplains, social workers and grief coordinators.

Even simple acts such as closing doors and blinds to provide privacy can be helpful, Dr. October says.

An ongoing relationship with health care providers is also important for helping parents grieve, she adds. Children’s National is among hospitals across the country to set up meetings for parents and other family members within weeks of a child’s death. This gives parents a chance to ask questions about what happened in the confusing blur of the PICU and to gather resources for themselves and surviving siblings. Children’s National also provides ongoing support through periodic calls, sending sympathy cards, attending funeral services and in a special annual memorial during which surviving family members release butterflies.

“Our role doesn’t end when a child dies,” Dr. October says. “To help parents through bereavement, we need to maintain that strong connection.”

Another way to help bereaved families is to make sure they have adequate information, she adds, particularly about the confusing subject of brain death. In a different study recently published in Chest Journal, Dr. October and Children’s colleagues sought to understand which information the public typically accesses about this topic.

The team searched Google and YouTube using “brain dead” and “brain death” as search terms. They evaluated the top 10 results on both sites, assessing the accuracy of information using 2010 guidelines released by the American Academy of Neurology. They also assessed the reading level of websites and evaluated comments about the YouTube videos for content accuracy and tone.

They found that there was inaccurate information on four of the 10 websites, six of the 10 videos and within 80 percent of the YouTube comments. Most of these inaccuracies dealt with using terms like brain death, coma and persistent vegetative state interchangeably. “These conditions are very different and affect how we treat patients,” Dr. October says.

The average reading level of the websites was 12th grade, far too sophisticated for much of the public to comprehend, she adds. And the majority of comments on the YouTube videos were negative, often disparaging clinicians and deriding organ donation.

“It’s really important for providers to recognize that this is an emotionally laden topic, and a lot of times, families come to us with information that’s not always true,” she says. “That’s why it’s especially important for the field to respond with empathy and care.”

In addition to Dr. October, co-authors of the Pediatric Critical Care Medicine study include Karen Dryden-Palmer, R.N., MSN, Ph.D., The Hospital for Sick Children; Beverley Copnell, Ph.D., BAppSc, R.N., Monash University; and Senior Author Kathleen L. Meert, M.D., FCCM, Children’s Hospital of Michigan. Dr. October’s co-authors for the Chest Journal article include Lead Author, Amy H. Jones, M.D., and co-author Zoelle B. Dizon, BA, both of Children’s National.

ambulance

Accident or assault? Pediatric firearm injuries differ by age

ambulance

According to a retrospective, cross-sectional study led by Children’s researchers, younger kids are more likely to be shot by accident, and odds are higher that older youths are victims of an assault involving a firearm.

An increasing number of children are injured by firearms in the U.S. each year, but the reasons these injuries happen vary. According to a new retrospective, cross-sectional study led by Children’s researchers and presented at the American Academy of Pediatrics (AAP) 2018 National Conference & Exhibition, firearm injuries vary by the intent of the person discharging the weapon. Younger kids are more likely to be shot by accident, and odds are higher that older youths are victims of an assault involving a firearm. Efforts to protect children from firearm-related injuries should factor in these differences in intent as legislation and policies are drafted, the study team suggests.

Researchers led by Shilpa J. Patel, M.D., MPH, Children’s assistant professor of pediatrics and emergency medicine, reviewed data aggregated in the Nationwide Emergency Department Sample from 2009 to 2013 looking for emergency department visits to treat firearm-related injuries suffered by children and adolescents 21 and younger. They excluded emergency department visits for firearm-related injuries attributed to air, pellet, BB or paintball guns.

Firearm-related injuries are a leading cause of injury and death for U.S. children. Some 111,839 children and youth were treated in emergency departments for firearm-related injuries, or 22,367 per year when averaged over the five-year study period. Nearly 63 percent of these youths were injured by accident; 30.4 percent were victims of assault; 1.4 percent used a firearm to injure themselves. Of note:

  • 89.3 percent were male
  • Their mean age was 18 (67.3 percent 18 to 21; 27.9 percent 13 to 17; 4.8 percent younger than 12)
  • 1 percent were discharged from the emergency department
  • 30 percent had injuries grave enough to trigger hospital admission and
  • 1 percent died from their injuries.

“Children younger than 12 were more likely to be shot by accident. By contrast, we found that the odds of experiencing firearm-related injuries due to assault were higher for youths aged 18 to 21,” Dr. Patel says. “Physicians can play a powerful role in preventing pediatric firearm-related injuries by routinely screening for firearm access and speaking with families about safe firearm storage and violence prevention,” she adds.

Some 52.1 percent of children with firearm-related injuries lived with families whose median household incomes exceeded $56,486.

American Academy of Pediatrics National Conference & Exhibition presentation

  • “Emergency department visits for pediatric firearm-related injury: by intent of injury.”

Shilpa J. Patel, M.D., MPH, assistant professor of pediatrics and emergency medicine and lead author, Gia M. Badolato, MPH, senior clinical research data manager and study co-author, Kavita Parikh, M.D., MS, associate professor of pediatrics and study co-author, and Monika K. Goyal, M.D., MSCE, assistant division chief and director of Academic Affairs and Research in the Division of Emergency Medicine and study senior author, all of Children’s National Health System; and Sabah F. Iqbal, M.D., medical director, PM Pediatrics, study co-author.