CHOC awarded $2.3-million grant to study how toxic stress and unpredictability in the early environment affects neurodevelopment

The state of California has awarded CHOC, in partnership with UC Irvine and Chapman University, a $2.3-million grant to screen patients for adverse childhood experiences (ACEs) and childhood unpredictability to assess how such high-stress events affect the brain and put kids at increased risk of later developing physical and mental illnesses.

In a novel aspect of the study, researchers also will determine if there are epigenetic markers on the DNA that predict whether any given child will be more adversely affected than another.

The team is among four awardees statewide that have been given a total of $9 million to assess which children are most vulnerable to the effects of ACEs and unpredictability in the home environment, and to design medical care to improve the outcomes for this particular group of patients – a model known as “precision medicine,” which eschews a one-therapy-fits-all approach to healthcare.

“The whole concept here is that kids who grow up in environments with frequent exposures to toxic levels of stress can have all kinds of internal things happen in their bodies related to prolonged or extensive stress hormone response – their brains can develop differently, and when they become adults, research has shown that they have a higher risk of developing medical conditions such as heart disease, asthma and cancer,  among other physical diseases, as well as mental disorders,” says Dr. Charles Golden, a co-investigator on the study and executive medical director of the CHOC Primary Care Network (PCN).

Dr. Charles Golden, executive medical director of the CHOC Primary Care Network (PCN)

The California Governor’s Office of Planning & Research, in partnership with the Office of the California Surgeon General, awarded the three-year research project as part of the California Initiative to Advance Precision Medicine (CIAPM). The other three recipients were Children’s Hospital Los Angeles, University of California, San Francisco, and Loma Linda University.

The CHOC-UCI-Chapman research project begins in July 2021, with screening expected to start in CHOC PCN clinics by November 2021. Lead principal investigator on the project is Dr. Tallie Baram, Bren Distinguished Professor and director of the Conte Center at UCI. The National Institute of Mental Health-funded Conte Center also addresses how early-life experiences influence the brain and contribute to mental illnesses.

Results of the study are expected by the end of 2024, says Laura Glynn, PhD, a Professor of Psychology and Associate Dean for Research at Chapman University and one of the principal investigators on the study.

CHOC’s PCN has been screening its Medi-Cal patient population for ACEs since February 2020, and expanded such screening – using a tool called PEARLS, for Pediatric ACEs and Related Life Events Screener – to all patients in November 2020, Dr. Golden says.

The 17-question PEARLS tool screens for such experiences as a parent being jailed, the prevalence of alcohol or drug abuse in the household, and whether the child has been a victim of violence in his or her neighborhood, in the community at large, or at school.

“This existing infrastructure at CHOC was a very important part of the application for this grant,” Glynn says.

The CHOC-UCI-Chapman study, “Using Precision Medicine to Tackle Impacts of Adverse and Unpredictable Experiences on Children’s Neurodevelopment,” will dig deeper than standard PEARLS screening.

The children will be asked an additional five questions to assess exposure to unpredictability in the social, emotional, and physical domains. Such questions are an attempt by researchers to develop an instrument that will predict this population of kids’ resilience to, or risk of developing, physical or mental illnesses. Children from low socioeconomic and racial/ethnic minority communities are at greater risk of exposure to ACEs.

“This study will involve looking at whether routine, or lack of routine, in a child’s life contribute as an ACE,” Dr. Golden explains. “In other words, do they eat dinner every night at 6 p.m., do they have a routine bedtime, do they have a stable household versus a family with no routine or little structure.”

Such factors of unpredictability potentially are amenable to intervention, Glynn notes.

Emerging evidence from experiments with rodents show that fragmented or unpredictable maternal signals influence the maturation of systems governing emotional and cognitive function in the developing brain. In preclinical work led by Dr. Baram, the group has shown that rats exhibited diminished memory function when exposed to unpredictable maternal signals early in life, as well as anhedonia (reduced ability to experience pleasure) beginning in adolescence.

Also, as part of the study, DNA swabs will be performed on a cohort of 120 children who experience high levels of ACEs to determine if genetic expression patterns indicate a vulnerability to chaos and unpredictability in their lives. The team also will be examining whether epigenetics – the process of how genes may be altered based on environmental events – may play a role in the development of ACE-related medical conditions.

“We think potentially we can look at these epigenetic profiles to predict neurodevelopmental outcomes,” Glynn says.

Dr. Michael Weiss, vice president of population health at CHOC and a primary investigator on the study, says such information may make it easier for doctors to identify a child who has a genetic predisposition to experiencing a bad outcome from being exposed to ACEs – thus leading to targeted interventions to kids who need them the most.

“This project is a great demonstration of a collaboration between CHOC and UCI and Chapman University involving primary care research,” Dr. Weiss says.

Other CHOC researchers who will participate in the research project are Dr. Dan Cooper, who treats kids with lung conditions at CHOC and who serves as director of UC Irvine’s Institute for Clinical & Translational Science; Dr. Candice Taylor Lucas, co-director of LEAD-ABC (Leadership Education to Advance Diversity–African, Black and Caribbean) at UCI/CHOC; Louis Ehwerhemuepa, PhD, a senior data scientist; and Dr. Mary Zupanc, co-medical director of the Neuroscience Institute.

CHOC leads first ED study on adverse childhood experiences and prevalence of food and housing insecurity

In the only known hospital research project of its kind in the United States, CHOC’s Emergency Department is leading a study on how food and housing insecurity impacts children’s health and environment.

The project, being conducted in collaboration with departments at UC Irvine and Chapman University, involves surveying 7,000 CHOC ED patients by September 2021, with results expected by the end of the year, says Dr. Theodore Heyming, medical director of emergency medicine at CHOC and chief architect of the effort.

Dr. Theodore Heyming, medical director of emergency medicine at CHOC

The study, which to date already has enrolled some 2,500 CHOC patients, will assess ACEs, also known as adverse childhood experiences. Most ACEs studies conducted to date by other hospitals have been limited to the primary care setting. Since July 2020, CHOC’s ED has been screening for ACEs with particular attention to the following three areas: abuse, neglect, and/or household challenges. 

“To my knowledge, we’re the only pediatric hospital that has this kind of health research project implemented in an emergency department,” Dr. Heyming says. And that makes sense, he adds.

“People don’t usually think of an emergency room as a primary care setting,” Dr. Heyming says. “However, the opposite actually is true. A lot of patients use the ER as their primary care. EDs also have the ability to potentially intervene on patients even to a greater extent than in the primary care setting, given the availability of experienced social workers.”

The potential benefits of the study, which involves questioning patients in more depth than standard ACEs screenings, are numerous, as detailed in an abstract that Dr. Heyming and his collaborators have submitted to the American Public Health Association (APHA), a Washington, D.C.-based organization for public health professionals.

For example, ED-based research has yet to investigate the extent to which neighborhood-level factors such as fast-food accessibility and a lack of healthy food options contribute to poor pediatric health outcomes.

The CHOC-led study aims to identify such neighborhood-level factors and generate valuable information that could be leveraged for public policy and advocacy efforts to improve pediatric health. That, in turn, could lead to a reduction of ED overutilization and associated healthcare costs.

Disadvantaged kids hit hardest

Food and housing insecurity disproportionately impact children in disadvantaged communities, studies show.

And children living in so-called “food swamps” — areas with an abundance of fast-food restaurants, pharmacies and discount stores that sell cheap but unhealthy food — as well as “food deserts,” areas that lack affordable food that is fresh and nutritious, are more at risk of obesity, diabetes and other adverse health conditions, as well as mental and behavioral issues and trauma, the paper explains.

The study of 7,000 CHOC ED patients comes on the heels of a smaller CHOC ED study on the prevalence of ACEs in patients that was conducted between July 2020 and February 2021. Twenty-four CHOC ED doctors were certified in state-run ACEs modules and 1,861 patients participated – the biggest cross-sectional survey that CHOC has done to date, according to Dr. Heyming.

About 20 percent of respondents in that smaller-scale survey reported at least one ACE or more — a percentage consistent with national numbers, Dr. Heyming says. In addition, the survey found that the prevalence of food insecurity among CHOC patients is about 15 percent. 

Now, in partnering with Chapman University and UCI, CHOC is digging deeper into the prevalence of food and housing insecurity with its study of 7,000 patients — and the potential neighborhood-level factors that contribute to such insecurity.

Dr. Jason Douglas, an assistant professor of public health at Chapman University, specializes in investigating social and environmental determinants of public health disparities that disproportionately impact the Black and Latinx communities. 

Dr. Douglas, who has extensive experience connecting social and environmental factors to public health disparities in Los Angeles County as well as Northern California, New York and Jamaica, will use data from the 7,000 survey respondents to analyze neighborhood-level factors that contribute to poor pediatric health.

“The goal is to identify factors that are affecting community health and well-being and inform public policies to improve health in underserved communities,” Dr. Douglas says. “To be able to identify adverse childhood experiences and food and housing security within the clinical context and use that data to garner a better understanding of how social and environmental factors may be exacerbating health disparities will allow us to develop a more holistic understanding of the deleterious impacts of these challenges on children’s lives.”

At UCI, Dr. Victor Cisneros, an emergency medicine clinical instructor and current research fellow in population health and social emergency medicine, will lead a team of investigators who will participate in follow-up phone calls with the CHOC ED survey respondents. The follow-up interviews will be conducted three and six weeks after respondents complete the survey.

“These follow-up interviews are important to assess if interventions given in the ED are effective, and if not, what barriers our patients are facing,” Dr. Cisneros says.

All CHOC ED patients up to 18 years of age and their parents or guardians qualify as potential participants in the survey, which is available in English and Spanish. The survey includes 16 questions that take about 5 to 10 minutes to complete on iPads provided by CHOC.

Patients identified as experiencing food and/or housing insecurity are directed to passive food and housing resource materials in the form of informational pamphlets and flyers.

“We’re going to potentially be able to leverage this data to help cities and the county to make informed policy changes,” Dr. Heyming says. 

“Obtaining this information will not only be great for Orange County,” he adds. “I think we’ll be able to point to the fact that pediatric EDs are a great place to conduct these screenings because there’s a high incidence of either adverse childhood experiences or food or housing insecurity.”

Dr. Heyming says pediatric EDs in the future would be able to provide patients more active resources such as gift and food cards.

Dr. Douglas says the study ideally will serve as a model for pediatric and other emergency departments across the country.

The bottom line, Dr. Cisneros says, is getting people resources they need – for example, food that restaurants now dispose of that can be “recycled.”

The ED, he says, is a perfect microcosm of the community.

“One of the beauties of this study,” Dr. Cisneros says, “is we’ll be able to identify people with housing and food insecurity and be able to refer these people to the appropriate tailored resources. In addition, we will be able to further quantify what obstacles our patients face both at the individual and community level.”

CHOC studies child maltreatment during COVID-19, adopts new tools to better recognize signs of abuse

With COVID-19 restrictions keeping more families at home, a critical question has emerged:

Are children suffering more physical and emotional maltreatment because they’re spending more time with parents who are dealing with extra stress in their lives?

A recently completed study by clinicians in the Julia and George Argyros Emergency Department at CHOC Hospital sheds some light on whether child abuse cases are rising because of stay-at-home orders. The study comes as CHOC ED personnel are using two new screening tools to help clinicians better recognize signs of abuse as well as victims of human sex trafficking.

COVID’s effect on child maltreatment

CHOC ED personnel studied whether the incidence of child maltreatment – which includes physical, sexual and emotional abuse, plus neglect – among patients being admitted to the emergency department has risen since the pandemic began in mid-March 2020.

They reviewed records of ED visits of patients up to 18 years old during a 3 ½-month period from March to July 2020 and reviewed the Child Protective Services database, then compared that period to the same time frame in 2019, 2018 and 2017.

Result: More reports of child mistreatment – 215 – were filed during the COVID-19 pandemic, compared to 204 during the same period in 2019, 199 in 2018 and 158 in 2017.

This is especially significant because CHOC’s ED has experienced a significantly lower ED patient census during the pandemic compared to pre-COVID days, says Dr. Mary Jane Piroutek, a CHOC ED attending physician.

Dr. Mary Jane Piroutek, CHOC ED attending physician

While sexual and physical abuse cases were down in the 3 ½-month period in 2020, cases of general neglect and medical neglect, as well as emotional abuse, were higher during COVID compared to the previous years.

Erika Jewell, manager of Case Management and Social Services at CHOC, put some of these numbers in context. In 2017, she reports, the rate of children in Orange County suffering abuse or neglect was 43.8 per 1,000, compared to 33.5 in 2012.

Of the 4,451 substantiated case of child abuse and neglect in Orange County in 2017, the vast majority – 3,204 – were cases of general neglect. Sexual abuse cases, in comparison, totaled 191.

“Our findings suggest the incidence of child neglect increased during the implementation of the stay-at-home guidelines,” says Dr. Piroutek, who spoke with Jewell and others on a panel on Research Day on Nov. 18, 2020.

Knowledge of such a trend, Dr. Piroutek explains, could help providers identify children at risk for maltreatment and, ultimately, provide an impetus to shape public policy and to improve the effectiveness with which resources are allocated to address the COVID-19 public health crisis.

Two new screening tools

Beginning in October 2019, the CHOC ED rolled out the first of two new screening tools aimed at making it easier for nurses and doctors to better identify patients at risk of abuse.

The first new screening tool being used in CHOC’s ED is TRAIN, for Timely Recognition of Abusive Injuries Collaborative. It is used to screen patients 6 months and younger.

The second screening tool, launched in July 2020, is CA-CDS, for Child Abuse – Clinical Decision Support. It is used to screen patients 11 years or younger. Components include a triage screen where nurses or doctors answer five questions, a pop-up computer alert that flags which patients may be at risk for physical abuse, a link to order sets and CHOC’s computerized suspected child abuse form.

With these two new tools, the CHOC ED estimates it can detect 50 percent more sentinel injuries than before. A sentinel injury is a seemingly trivial one that can be viewed as a “sentinel event” for much worse injuries in the future. Research shows that one-quarter of abused children had previous sentinel injuries.

The ED is collecting data through December 2021 to evaluate how well the new screening tools are helping healthcare workers detect cases of maltreatment, Dr. Piroutek says.

“It’s a more data-based and methodical approach; you have a computer that’s looking at data and flagging concerning patterns for you: ‘Hey, there’s something that might be abuse here,’” Dr. Piroutek explains.

The new screening tools will help CHOC better comply with treatment guidelines set forth by the American Academy of Pediatrics (AAP), Dr. Piroutek notes.

“CHOC is committed to research for the betterment of our patients and children,” Dr. Piroutek says. “With the implementation of these new screening tools I am confident we can provide the best care for our patients.”

Screening for human sex trafficking has also become an important part of CHOC nursing care.

Sheryl Riccardi, Emergency Department manager at CHOC, says a steering group of about 20 associates has been established to help healthcare workers better identify, intervene and advocate for these victims, many of whom are minors and most of whom come from the Unites States.

Santa Ana is the largest hub of human sex trafficking in the state, she notes. The ED has begun screening 12- to 18-year-olds – regardless of their chief complaint for possible further evaluation – if a child reports a complaint indicating a high risk of abuse, Riccardi says.

CHOC, she adds, recently became a partner with the Orange County Human Trafficking Task Force, a law enforcement-led coalition that is committed to combating all forms of human trafficking through the rescue and long-term support of victims, prosecution of offenders, training of fellow law enforcement professionals, community awareness and effective public/private partnerships.

According to Waymakers and the Salvation Army, in 2019 there were 415 identified victims of human trafficking in Orange County, with sex trafficking victims totaling 359. The other victims were trafficked for labor.

CHOC is determined to do what it can to find and help these victims.

“We’ve very passionate about this,” Riccardi says.

Learn more about how to identify child abuse.