Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior

June 18, 2025 updated by: Whitnee Hogan, MD (Assistant Professor), University of Utah

Determine 1) the impact of abnormal fetal cerebrovascular physiology with neurodevelopmental delay (ND) outcomes and 2) how this relationship is modified by patient and environmental factors such as chronic congenital heart disease (CCHD) lesion, maternal-fetal environment, and social determinants of heath (SDOH) in a diverse population using a multicenter design.

Pregnant women will be approached during one of their fetal cardiology clinic visits.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Aim 1:

Determine the association of baseline cerebrovascular resistance and reactivity and pre-operative neurobehavior in neonates with complex congenital heart disease (CCHD).

Exposures: The baseline middle cerebral artery pulsatility index (MCA-PI) and change in MCA-PI.

Analyses: Our principal analyses for Aim 1 will use separate linear regression models to relate the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) attention score to 1) the baseline MCA-PI while controlling for maternal age, infant sex, race/ethnicity, and SDOH measures (maternal education, socioeconomic status (SES), insurance status), and clinical site, and 2) the change in MCA-PI adjusted for baseline MCA-PI while controlling for the same set of covariates. If the NNNS attention score distribution is skewed, we will consider transformations so that model residual plots achieve approximate normality. The covariates in the above regression analyses exclude factors that may potentially lie on the causal pathway from the MCA-PI to the attention score to avoid risk of over adjustment. In secondary analyses, 2 regression analyses will be repeated after additional adjustment for the maternal-fetal environment indicator(s), CCHD category, and age at NNNS evaluation. As a secondary analysis, we will evaluate the interaction between baseline MCA-PI and change in MCA-PI. For this analysis, we will consider dichotomizing baseline MCA-PI to facilitate interpretation of the interaction effect.

Aim 2:

Determine the impact of patient and environmental factors on cerebrovascular resistance and reactivity Exposures: Patient factors including CCHD category, indicators of the maternal-fetal environment, and SDOH

Analysis: The primary analysis for Aim 2 will investigate the joint relationship of the MCA-PI with SDOH measures and the maternal-fetal comorbidity indicator while accounting for the CCHD category (defined as Left sided obstructive lesion, Right sided obstructive lesion, Dextro-Transposition of the Great Arteries, and Other). We will apply multiple linear regression to relate the MCA-PI to the SDOH measures and a maternal-fetal comorbidity indicator for the presence of any of maternal hypertension, diabetes, pre-eclampsia, eclampsia, and abruption, prematurity, and small for gestational age. The CCHD category will also be a covariate in the regression model. Additional exploratory regression analyses will include pairwise interaction terms between the maternal-fetal comorbidity indicator(s) with the SDOH measures to assess if the association of the maternal-fetal environment indicator(s) with the MCA-PI varies across the different levels of the SDOH measures. We will perform a separate multiple regression with the change in the MCA-PI as the outcome and with the baseline MCA-PI as an additional covariate.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
    • District of Columbia
      • Washington, DC, District of Columbia, United States, 20010
    • Maine
      • Scarborough, Maine, United States, 04074
    • Utah
      • Salt Lake City, Utah, United States, 84132
      • Salt Lake City, Utah, United States, 84113
        • Not yet recruiting
        • Primary Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 52 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pregnant women 18 years of age and over with a singleton fetus with known or suspected congenital heart disease anticipated to need intervention or surgery within 30 days of birth.

Exclusion Criteria:

  • Known fetal chromosomal or genetic abnormalities
  • Multiple gestation pregnancy
  • Fetal extra-cardiac anomalies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm
Maternal Hyperoxia (MH) will be administered to pregnant patients after their standard of care fetal echocardiogram has been performed at their scheduled fetal cardiology visit at ³28 weeks gestation. The evaluation at ³28 weeks was chosen since gestational age impacts both the cardiovascular and cerebrovascular response to MH.31 The evaluation will extend the duration of the visit by approximately 30 minutes but additional evaluations or visits for the study will not be required.
Procedure: Single Arm
  • Phase 1- Baseline: A fetal echocardiogram will be performed as part of routine standard clinical care.
  • Phase 2- MH: The participant will be placed on 8 litres of 100% FiO2 (inspired oxygen fraction) via a non-rebreather face mask for 10 minutes. After 10 minutes, additional images will be obtained. MH will be discontinued after additional imaging is complete.
  • Phase 3- Recovery: After at least 5 minutes of discontinuation of MH, additional images will be obtained to ensure any changes have returned back to baseline.
Procedure: Neonatal Neurobehavioral Scale
Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) evaluation: All neonates with CHD expected to undergo neonatal cardiac intervention or surgery have pre-operative NNNS assessment as PCH as standard of care. The NNNS takes approximately 30 minutes to complete. It is administered by a licensed physical, speech, or occupational therapist who has completed training and additional certification. The NNNS therapist will be blinded to the results of the fetal echocardiogram and MCA-PI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pre-operative Neonatal Network Neurobehavioral Scale (NNNS) attention scores
Time Frame: <=30 days of life
The NeoNatal Neurobehavioral Scale (NNNS-II) examines the neurobehavioral organization, neurological reflexes, motor development - active and passive tone, and signs of stress and withdrawal of the at-risk and drug-exposed infant
<=30 days of life
Baseline MCA-PI and change in MCA-PI with Maternal Hyperoxia
Time Frame: <= 30 days of life
The fetal middle cerebral artery (MCA) pulsatility index (PI)
<= 30 days of life

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Primary Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 17, 2021

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

March 1, 2023

First Submitted That Met QC Criteria

March 1, 2023

First Posted (Actual)

March 14, 2023

Study Record Updates

Last Update Posted (Estimated)

June 25, 2025

Last Update Submitted That Met QC Criteria

June 18, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB_00145850
  • U24HL135691 (U.S. NIH Grant/Contract)

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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