Biomarkers Study in Infants With Prior Neonatal Brain Injury

Early Biomarkers Study for Prediction of Executive Dysfunction and Cognitive Outcomes Among Infants With Prior Neonatal Brain Injury

This research focuses on the long-term cognitive development of children, including healthy infants and those who had a perinatal brain injury. As part of this research study, children complete in-person games and assessments at UW-Madison University Hospital. Children will also take part in an EEG assessment. Parents will be asked to fill out questionnaires about their child's behavior and stress in the home.

Study Overview

• Status: Recruiting
• Conditions: Premature Birth; Healthy Participants; Perinatal Anoxic-ischemic Brain Injury; HIE - Hypoxic - Ischemic Encephalopathy

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Melisa Carrasco McCaul, MD, PhD; Phone Number: 608-577-2415; Email: carrascomccaul@neurology.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Recruiting
      • University of Wisconsin Madison University Hospital
      • Contact: Melisa Carrasco McCaul, MD, PhD; Phone Number: 608-577-2415; Email: carrascomccaul@neurology.wisc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Infants ages 6-24 months located across the United States and internationally. Must be able to travel to Madison, WI.

Description

Inclusion Criteria:

• Child-parent dyads will be recruited to the study.
• Children 3-24 months with and without a history of a perinatal brain injury (PBI) will be included in this study.

• Children with PBIs will include:

  • Children diagnosed during the neonatal period with hypoxic-ischemic encephalopathy,
  • Children born at a premature gestational age (born at less than 32 weeks gestational age).
  • Children diagnosed with cerebral palsy

• Healthy control participants meeting inclusion criteria will include:

  • healthy infants with no prior neurological (brain disorder) history
• For all parents: the only research inclusion criteria is to be the parent or legal guardian of a newborn with perinatal brain injury or healthy control participant.

Exclusion Criteria:

• Healthy infants to be included in the control group will not have:

  • a prior history of brain injury
  • a diagnosis of cerebral palsy
  • a history of a neurological disorder
  • prior admission to the Neonatal Intensive Care Unit (NICU)
• Children with chromosomal abnormalities, genetic syndromes and major congenital malformations will be excluded from both the patient groups and the control group.
• Parents will have no exclusionary criteria.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Children with perinatal brain injury; Children ages 6 months (may be enrolled prior to 6 months) - 18 months who are diagnosed with 1) hypoxic- ischemic encephalopathy, 2) cerebral palsy, and/or 3) were born premature at less than 28 weeks gestational age. (
Healthy Children; Children ages 6 months (may be enrolled prior to 6 months) - 18 months of age with no prior history of a brain and/or cardiac illness early in life.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant Attention Task (IAT) measured in seconds	A behavioral measure used with infants to assess attentional control and processing. Infants are presented with visual puppet stimuli four distinct "looks", and researchers record looking time, shifts in attention, or habituation patterns. More sustained attention in the early looks followed by habituation to the stimuli in the later looks often indicates better early attentional capacity. Total accumulated looking time to a stimulus in visual preference-type tasks commonly ranges from roughly 15-30+ seconds per trial, depending on the infant's age and the stimulus.	Assessed at the 6,12 and 18 month time-points
A not B Task	The A-not-B task is a developmental measure of object permanence, working memory, and inhibitory control in infants, requiring them to search for a hidden object after its location is changed. Performance is typically reported as the percentage of correct searches on B trials, with infants 8-9 months averaging 20-40% correct (range 0-100%), 10-11 months averaging 50-70%, and 12-month-olds reaching 75-90%, often near the maximum. Scores vary with delay length and task difficulty.	Assessed at the 6,12 and 18 month time points
EEG Power in Delta and Theta Bands	EEG data will be utilized to examine whether neural activity patterns are associated with later executive functioning outcomes. Specific EEG indices will be analyzed as predictors of executive functioning, with lower/higher executive functioning defined by performance on behavioral measures.	Assessed at the 6,12 and 18 month time points

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reilly Role Overload Questionnaire	In the Reilly Role Overload questionnaire, parents of child participants rate the frequency of feeling overwhelmed by role demands; item responses are summed to create a total role overload score. Total scores range from 13 to 65, with higher scores indicating greater perceived role overload due to excessive demands relative to time and energy.	Assessed at the 6,12 and 18 month time points
Confusion, Hubbub and Order Scale (CHAOS)	Parents and/or Caregivers rate items describing household noise, crowding, and routine; responses are summed to create a total CHAOS score. The CHAOS total score ranges from 15 to 60, with higher scores indicating a more chaotic, noisy, and disorganized home environment; scores below 25 typically reflect lower chaos, whereas scores above 35 suggest high household chaos.	Assessed at the 6,12 and 18 month time points
Parenting Daily Hassle (PDH) Scales: Intensity Score	A parent-report measure assessing the frequency and intensity of everyday parenting stressors (e.g., child demands, disruptions to routines); item ratings are summed or averaged to yield frequency and intensity scores. On the PDH Scale, intensity scores range from 0 to 100 with higher totals indicating more frequent and/or more stressful everyday parenting hassles.	Assessed at the 6, 12 and 18 month time points
Parenting Daily Hassle (PDH) Scales: Frequency Score	A parent-report measure assessing the frequency and intensity of everyday parenting stressors (e.g., child demands, disruptions to routines); item ratings are summed or averaged to yield frequency and intensity scores. On the PDH Scale, frequency scores range from 0 to 80 with higher totals indicating more frequent and/or more stressful everyday parenting hassles.	Assessed at the 6, 12 and 18 month time points
Parental Stress Scale	A questionnaire which measures stress and satisfaction associated with parenting; items are summed to create a total parental stress score. On the Parental Stress Scale, total scores range from 18 to 90, with higher scores indicating greater levels of parental stress and lower scores reflecting lower stress and more satisfaction in the parenting role.	Assessed at the 6, 12 and 18 month time points
Early Executive Function Questionnaire: EEFQ	A questionnaire is given to parents that assesses what executive functions children are exhibiting. More functions exhibited means further along in executive function development. The (EEFQ uses parent ratings on a 7-point scale for 31 items, with subscale and composite scores averaging between 1 and 7 - higher scores indicate stronger emerging executive function behaviors in infants and toddlers	Assessed at the 6, 12 and 18 month time points
Bayley Assessment	The Bayley is a cognitive and motor assessment conducted by an interventionalist to assess a child's development in these domains. The highest possible score on a subtest or subdomain is 19, and the lowest score is 1. Scores from 8-12 are considered average.	Assessed at the 6, 12 and 18 month time points

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Melisa Carrasco McCaul, MD, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Estimated): March 15, 2030
• Study Completion (Estimated): March 15, 2030

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth
• Other Study ID Numbers: 2021-1625; Protocol Version 11/22/2024 (Other Identifier: UW Madison); SMPH | NRL Neurology (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No