for people ages 3 months to 11 years (full criteria)
Healthy Volunteers
healthy people welcome
at Oakland, California
study started
estimated completion
Principal Investigator
by Dayna Long, MDNeeta Thakur, MD
Photo of Neeta Thakur
Neeta Thakur



Stressful and traumatic experiences in childhood (Adverse Childhood Events, or ACEs) have been associated with poor health outcomes that extend into adulthood. When stress is sustained or severe in the absence of an adequate buffer, the stress response can become dysregulated--a state referred to as toxic stress. Some professional organizations have advocated for ACEs screening to be part of routine medical care. To date, however, no ACEs screening tool has been validated for use with children. Intervening early at critical points in the life course has the potential to allow a child to avoid the negative consequences of these adverse events. The proposed study has three overarching aims: (1) Examine the relationship between ACEs, stress biomarkers, and symptoms in children and caregivers over time; (2) Validate an ACEs screening in a pediatric health care setting; and (3) Test whether providing primary care-based preventive interventions for children with or at risk for toxic stress can lead to detectable changes in biomarkers, behavior, or health outcomes for children and/or caregivers.


The study first aims to validate a pediatric ACEs screening tool. The creation of a scientifically validated, standard screening tool is a crucial step that will facilitate widespread screening for ACEs in clinical pediatric settings. Subject participants will be randomized to either a control group or to an ACEs screening group. For the ACEs screening group, participants will be further randomized to 2 different formats for screening: (1) identified screening in which each individual item is endorsed or (2) de-identified screening in which only a total composite score is known. Universal screening has limited utility in the absence of effective long-term interventions, and to date there are limited evidence-based interventions for the physiological and physical health consequences of toxic stress. This study will provide all families with ACEs-specific anticipatory guidance. Families with one or more ACEs will then be randomized to one of two interventions: Care Coordination or a Resiliency Clinic. Both of these interventions will specifically address ACEs-related needs, and will be evaluated based on mental and physical health outcomes as well as biomarker profiles before and after the intervention. Care coordination will be based on the Family Information & Navigation Desk (FIND) Program model as implemented at UCSF Benioff Children's Hospital Oakland. The overarching goal of care-coordination is to routinely identify a family's basic social needs, in this case based on ACEs screener results, and then connect the family to appropriate community resources. This model moves beyond a focus on biomedical and risk-behavior explanations of health to understand the root causes of health inequities and provides a preventive approach to population health. The goal is to target the social and environmental factors that profoundly impact health. The Resiliency Clinic will be an innovative monthly, mindfulness-based, caregiver-child group intervention focused on understanding toxic stress, and the development of self-regulation and co-regulation skills in caregivers and children identified as exposed to ACEs. The curriculum is based on existing models of mindfulness intervention and the structure of the caregiver-child group will be based upon 30 years of experience at UCSF Benioff Children's Hospital Oakland's Early Intervention Services, with group collaboration from pediatric medical providers, developmental and behavioral specialists, and mental health specialists. The entire research project will be anchored by the collection of bio-specimens on each child. The normal stress response to acute life events induces several physiological responses that aid in adaptation and survival. Chronic exposure to adversity may result in a disruption of these normal stress pathways and is known as the toxic stress response (TSR). Several pathways have been suggested and include inflammatory and non-inflammatory mechanisms (disrupted neuroendocrine and/or autonomic nervous system functioning), epigenetic modification, and alteration of the body's microbiome. These pathways are sensitive to individual differences and adaptation mechanisms and aberrations in any of these pathways may negatively affect disease outcomes. An increased understanding of the multiple pathways of stress may unveil causal mechanisms that can lead to novel clinical interventions and allow for better targeting of these interventions. The biomarkers selected for this proposal are representative of the hypothesized pathways to disease and were selected based on relevance, clinical availability, and novelty. The collection of bio-specimens on all patients enrolled in the study will deepen our understanding of the correlations between ACEs, stress physiology and health outcomes. It will ground all aspects of this project in the underlying bio-chemical and genetic links between adversity and health outcomes. Biomarkers may help evaluate the concurrent validity of the pediatric ACEs screening tool and may offer insight on the pathways to poor health outcomes as a result of exposure to ACEs. Evaluating biomarker patterns and health outcomes in relation to ACE scores may allow for the establishment of a meaningful threshold for a clinical cut-point to the ACE score. Measuring biomarkers and therefore stress physiology before and after interventions may lead to more targeted and appropriate referrals and treatment modalities. Ultimately, this study will help advance ACE screening in the pediatric clinic setting, offer families and providers further direction in choosing ACEs-related interventions, provide insight into the underlying biochemical patterns associated with adverse childhood experiences, and lay a strong foundation for future work elucidating the specific underlying mechanisms causing childhood adversity to lead to poor mental and physical health outcomes.


Fibrinogen Abnormality Telomere Length, Mean Leukocyte Atopic Acute Infection Inflammatory Response Self-regulation Adverse Childhood Experiences Trauma Social Determinants of Health Child Mental Health Resiliency Primary Care Universal screening Congenital Abnormalities Care Coordination Resiliency Clinic


You can join if…

Open to people ages 3 months to 11 years

  • English and Spanish-speaking
  • Patients receiving a well visit at Primary Care.
  • Parents/primary caregivers of the children above, ages 18 and over, who are also legal guardians capable of consent.

You CAN'T join if...

  • Children who are dependents of the court
  • Caregiver active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with full participation in the study
  • Child or caregiver serious illness (mental or physical; requiring systemic treatment and/or hospitalization) or significant developmental disability that would interfere with full participation in the study
  • Inability or unwillingness of subject or legal guardian/representative to give written informed consent.


  • UCSF Benioff Children's Hospital Oakland
    Oakland California 94609 United States

Lead Scientists at UCSF

  • Dayna Long, MD
    Authored (or co-authored) 11 research publications.
  • Neeta Thakur, MD
    Dr. Neeta Thakur is a pulmonary and critical care physician at UCSF who examines the role of social and environmental stressors on asthma and COPD in vulnerable populations. Better definitions of the mechanism of how social and environmental stressors impact asthma and COPD will allow for the development of targeted interventions and therapies to improve related outcomes in vulnerable populations.


in progress, not accepting new patients
Start Date
Completion Date
UCSF Benioff Children's Hospital Oakland
Study Type
Last Updated