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Research will use precision medicine to identify biomarkers of early life stress
The Children’s Hospital of Los Angeles has received a $2 million grant from the State of California for research on precision medicine methods for screening children’s adverse childhood experiences.Three-year grant-part California Advances Precision Medicine Program-Announced by the Governor’s Office of Planning and Research in cooperation with the California Office of Surgeons.
Bad childhood experiences, also known as ACEs, are potentially traumatic events early in life, such as neglect, abuse, racism, witnessing violence, and financial hardship. These events can lead to toxic stress—a physiological response to severe adversity. ACE increases the risk of stunting, heart disease, cancer, diabetes, and mental illness in children.
The Los Angeles Children’s Hospital’s research aims to improve early screening of ACE by using precision medicine to identify specific biomarkers of early life stress. Nearly two-thirds of children in the United States have experienced ACE at least once, and 15% to 20% of children have experienced four or more times.
“Too many bad childhood experiences can lead to toxic stress in children, and many studies have shown that this may have life-long consequences for health challenges such as cardiovascular disease, obesity and mental illness,” said the lead principal investigator Pat Levitt, PhD, Chief Scientific Officer, Vice President and Director Saban Institute Chairman of Los Angeles Children’s Hospital and Simms/Mann Developmental Neurogenetics. “In order to improve the outcomes for these children, we need to identify those who are most at risk early, because early intervention will promote the best results.”
‘Red flag warning’
Currently, the only screening method for ACE involves questionnaire surveys of parents and caregivers. However, the screening rate in pediatric practice is usually low, and the questionnaire cannot determine which babies and children have toxic stress reactions.
The Los Angeles Children’s Hospital team will study a potential new screening method that combines a powerful questionnaire (Pediatric ACE Screening and Related Life Event Screening Tool (PEARLS)) with the development of a new type of laboratory test. The test measures potential interference in key cellular structures called mitochondria, which are responsible for generating energy for cells to function properly. Biomarkers measure mitochondrial balance load (MAL). The team aims to show that MAL measures are a “red flag warning” of toxic stress in infants.
Researchers from the Saban Institute and the Department of Pathology and Laboratory Medicine will develop and test three different new methods to measure infants’ MAL-this type of test will be used in children for the first time. A simple and painless oral swab will be used to collect the sample. In addition, mothers will complete questionnaires, including the PEARLS questionnaire, and researchers will assess the infant’s cognitive development and use new computerized methods to assess the interaction between mother and child and colleagues at the University of Southern California Viterbi School of Engineering.
Multidisciplinary cooperation brings together experts in precision medicine, clinical trial development and verification, pediatric health care, child development, infant mental health, the use of new measures to identify stress-related health risks, and health equity improvement research.
“We believe this multi-pronged approach will improve our understanding of mitochondrial stress associated with ACE and will ultimately lead to a cost-effective test that can be easily adopted by pediatricians across the state,” the joint investigator said Xiaowu Gai, PhD, Director of Bioinformatics Personalized Medicine Center At Los Angeles Children’s Hospital.
Challenging differences
The team’s goal is to recruit 300 mothers and infants from the Los Angeles Children’s Hospital/AltaMed Health Services general pediatric community clinic to participate in the study. The two-year partnership between Los Angeles Children’s Hospital and AltaMed brings pediatric expertise to the care of children in the local community. AltaMed is one of the largest federally qualified medical centers in the United States, providing care to families with insufficient medical services in Southern California.
Families who test positive for ACE will be referred to intervention services through the Los Angeles Children’s Hospital’s Behavioral Health Program, which specializes in family-centered infant mental health. Dr. Marianne Williams, Stein Tikun Olam Director of Infant Family Mental Health Project.
“The stress of early life is unevenly distributed,” said lead researcher Rajan Sonik, PhD, PhD, Master of Public Health, and research director of the AltaMed Health Equity Institute within the AltaMed Health Service. “Marginalized communities experience social and economic difficulties disproportionately, resulting in serious racial/ethnic differences. I look forward to working with Los Angeles Children’s Hospital and our community partners to challenge these differences, close the fairness gap, and take steps to improve A bright future is for all children and families.”
Nadine Burke-Harris, MD, MPH, FAAP, the first surgeon in California, set a bold goal of reducing ACE and toxic stress by half in a generation. In 2019, Dr. Burke-Harris shared these plans during a conference Special visit To the Los Angeles Children’s Hospital, she gave a speech in the Grand Tour of Pediatrics.
The Children’s Hospital of Los Angeles is one of four institutions that have chosen to receive grants under this initiative. A total of US$9 million in state funds will support proof-of-principle projects for the ACE patient population—all studies using precision medicine to improve access, care, and outcomes. These projects were selected from 39 applicants across the state and will begin in July.
Research collaborator
Other partners, collaborators and supporters include Alexander R. Judkins, MD, Alma Gharib, PhD, Hannah Perez, PsyD, Aime Ozuna, MPH, Jenny Kingsley, MD, MA and Suzanne Roberts, MD, Los Angeles Children’s Hospital; Gabriela Tovar , Juris Doctor, AltaMed Institute of Health Equity; Lauren Klein, MS, and Maja Mataric, PhD, USC Viterbi School of Engineering; Irene Martinez, MSW, Fiesta Educativa Inc.; Natalia Garcia, Pallas Nino Lorna Little, MSW, St. Anne’s; and Frances Nova of MSW, Cash Family Social Service Center.
About Los Angeles Children’s Hospital
Founded in 1901, Los Angeles Children’s Hospital is the highest-ranked children’s hospital in California, and ranked fifth in the United States on the prestigious U.S. News and World Report Best Children’s Hospital honor list. U.S. News ranks Los Angeles Children’s Hospital in all 10 professional categories. The hospital’s clinical care is led by doctors who are faculty members of the Keck School of Medicine at the University of Southern California, whose affiliation dates back to 1932. The hospital also runs the largest pediatric residency training program at an independent children’s hospital in the western United States. The Saban Institute of Children’s Hospital of Los Angeles is home to all basic, translational, clinical, and community research conducted at the hospital, enabling validated discoveries to reach patients quickly. Our mission: to create hope and build a healthier future.For more information, please follow us Facebook, Instagram, LinkedIn, YouTube with TwitterAnd visit our blog CHLA.org/blog.
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