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Kindergarten Readiness Assessment Scores after Having Early-childhood Respiratory failure (KRASHER)

Award Number: R21HD119353
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/03/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Kindergarten Readiness Assessment Scores after Having Early-childhood Respiratory failure (KRASHER) - Up to 40% of pediatric intensive care unit (PICU) patients acquire new morbidities during critical illness. Research into their exact rates, mechanisms and treatments is hampered by difficulty in getting PICU survivors to undergo in-person testing years later. Our innovative approach is to use the results of standardized school testing as an objective, practical PICU outcome measure. We are uniquely positioned to do this because we have “kindergarten readiness assessment” (KRA) scores from 14 local school districts available in our Child and Household Integrated Longitudinal Data” (CHILD) system, which integrates data from administrative agencies across our county. Our overall hypothesis is that benzodiazepine sedatives are a modifiable risk factor for poor long-term PICU outcomes. Most PICU patients on invasive mechanical ventilation (IMV) receive these drugs for days to weeks. The impact of these prolonged exposures on the developing brain is unknown, but exposure to general anesthetics – which work through the same receptors in the brain – early in life for even a few hours is associated with decreased school performance. We published a pilot study of KRA scores of children who received sedation while on IMV at age <3yo. These PICU survivors (n=32) had lower rates of “on-track” KRA scores (22% vs 64%, p<0.001) and 17-point lower total scores (p<0.001) versus controls matched on pertinent socio-economic, demographic and birth data. Now that we have established proof-of-concept for our approach, we will study a larger cohort in order to achieve: Aim 1a) Confirm that PICU survivors who received sedation during early life IMV have unfavorable KRA scores compared to matched controls. Based on our pilot, we estimate retrospectively identifying 2000 PICU survivors who received IMV with sedation at age <3yo in either of the two local PICUs, of whom 400 will have KRA scores in CHILD. We hypothesize that PICU survivors’ KRA scores will be lower than propensity score-matched controls from CHILD. Aim 1b) Determine if cumulative benzodiazepine exposure is associated with unfavorable KRA scores. We hypothesize that, among PICU survivors with KRA data available, total benzodiazepine dosage in the PICU will be associated with worse KRA scores in a multivariable model including confounders. Aim 2) Leverage machine learning (ML) to construct a prediction model that identifies PICU survivors at high risk of having KRA scores below the “on track” level. We hypothesize that an ML-based model that integrates data on sedation exposure and patient-specific factors will identify children at increased risk of unfavorable KRA scores. The proposed project will thus 1) confirm that sedation during early life IMV in the PICU is associated with unfavorable cognitive outcomes at school entry, 2) further the evidence supporting that benzodiazepines are a modifiable risk factor for poor outcomes, and 3) provide a novel tool to identify PICU survivors most at-risk for unfavorable school performance. These findings may have immediate clinical impact, and are needed to plan subsequent larger trials designed to improve cognitive function at age 6yo.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $472,336 )
2026	2026	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Child Health and Human Development Extramural Research	000	1	9/3/2026	NEW	$472,336
														Subtotal = $472,336

Grand Total All Awards = $472,336

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Kindergarten Readiness Assessment Scores after Having Early-childhood Respiratory failure (KRASHER)

Award Number: R21HD119353

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/03/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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