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

NCT05767385 | Recruiting Phase 2

• 2 other identifiers: IRB_00145850U24HL135691
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Congenital Heart Disease in Children; Hypoxia; Neurodevelopmental Disorders; Complex Congenital Heart Disease

Keywords

Congenital Heart Disease; Maternal Fetal; Neonatal Neurodevelopment

Outcome Measures

Primary Outcomes (2)

• Pre-operative Neonatal Network Neurobehavioral Scale (NNNS) attention scores

  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

  The fetal middle cerebral artery (MCA) pulsatility index (PI)

  <= 30 days of life

Study Arms (1)

Single Arm

EXPERIMENTAL

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; Procedure: Neonatal Neurobehavioral Scale

Interventions

Single Arm PROCEDURE

* 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.

Single Arm

Neonatal Neurobehavioral Scale PROCEDURE

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.

Single Arm

Eligibility Criteria

• Age: 0 Years - 52 Years
• Gender Eligibility Details: Pregnant females with fetus diagnosis congenital heart disease.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Utah: lead
• Primary Children's Hospital: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

University of California San Francisco

San Francisco, California, 94143, United States

NOT YET RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

NOT YET RECRUITING

Maine Medical Center

Scarborough, Maine, 04074, United States

NOT YET RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

NOT YET RECRUITING

University of Utah

Salt Lake City, Utah, 84132, United States

RECRUITING

Related Publications (19)

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  PMID: 21881507 BACKGROUND

• McQuillen PS, Miller SP. Congenital heart disease and brain development. Ann N Y Acad Sci. 2010 Jan;1184:68-86. doi: 10.1111/j.1749-6632.2009.05116.x.

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• Limperopoulos C, Tworetzky W, McElhinney DB, Newburger JW, Brown DW, Robertson RL Jr, Guizard N, McGrath E, Geva J, Annese D, Dunbar-Masterson C, Trainor B, Laussen PC, du Plessis AJ. Brain volume and metabolism in fetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy. Circulation. 2010 Jan 5;121(1):26-33. doi: 10.1161/CIRCULATIONAHA.109.865568. Epub 2009 Dec 21.

  PMID: 20026783 BACKGROUND

• Peyvandi S, Xu D, Wang Y, Hogan W, Moon-Grady A, Barkovich AJ, Glenn O, McQuillen P, Liu J. Fetal Cerebral Oxygenation Is Impaired in Congenital Heart Disease and Shows Variable Response to Maternal Hyperoxia. J Am Heart Assoc. 2021 Jan 5;10(1):e018777. doi: 10.1161/JAHA.120.018777. Epub 2020 Dec 21.

  PMID: 33345557 BACKGROUND

• Dimitropoulos A, McQuillen PS, Sethi V, Moosa A, Chau V, Xu D, Brant R, Azakie A, Campbell A, Barkovich AJ, Poskitt KJ, Miller SP. Brain injury and development in newborns with critical congenital heart disease. Neurology. 2013 Jul 16;81(3):241-8. doi: 10.1212/WNL.0b013e31829bfdcf. Epub 2013 Jun 14.

  PMID: 23771484 BACKGROUND

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  PMID: 28421173 BACKGROUND

• Oros D, Figueras F, Cruz-Martinez R, Padilla N, Meler E, Hernandez-Andrade E, Gratacos E. Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol. 2010 Apr;35(4):456-61. doi: 10.1002/uog.7588.

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• Hogan WJ, Moon-Grady AJ, Zhao Y, Cresalia NM, Nawaytou H, Quezada E, Brook M, McQuillen P, Peyvandi S. Fetal cerebrovascular response to maternal hyperoxygenation in congenital heart disease: effect of cardiac physiology. Ultrasound Obstet Gynecol. 2021 May;57(5):769-775. doi: 10.1002/uog.22024. Epub 2021 Apr 13.

  PMID: 32202689 BACKGROUND

• Donofrio MT, Bremer YA, Schieken RM, Gennings C, Morton LD, Eidem BW, Cetta F, Falkensammer CB, Huhta JC, Kleinman CS. Autoregulation of cerebral blood flow in fetuses with congenital heart disease: the brain sparing effect. Pediatr Cardiol. 2003 Sep-Oct;24(5):436-43. doi: 10.1007/s00246-002-0404-0.

  PMID: 14627309 BACKGROUND

• Williams IA, Tarullo AR, Grieve PG, Wilpers A, Vignola EF, Myers MM, Fifer WP. Fetal cerebrovascular resistance and neonatal EEG predict 18-month neurodevelopmental outcome in infants with congenital heart disease. Ultrasound Obstet Gynecol. 2012 Sep;40(3):304-9. doi: 10.1002/uog.11144. Epub 2012 Aug 2.

  PMID: 22351034 BACKGROUND

• Hahn E, Szwast A, Cnota J 2nd, Levine JC, Fifer CG, Jaeggi E, Andrews H, Williams IA. Association between fetal growth, cerebral blood flow and neurodevelopmental outcome in univentricular fetuses. Ultrasound Obstet Gynecol. 2016 Apr;47(4):460-5. doi: 10.1002/uog.14881. Epub 2016 Feb 18.

  PMID: 25900850 BACKGROUND

• Szwast A, Putt M, Gaynor JW, Licht DJ, Rychik J. Cerebrovascular response to maternal hyperoxygenation in fetuses with hypoplastic left heart syndrome depends on gestational age and baseline cerebrovascular resistance. Ultrasound Obstet Gynecol. 2018 Oct;52(4):473-478. doi: 10.1002/uog.18919. Epub 2018 Sep 3.

  PMID: 28976608 BACKGROUND

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• Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC. Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: a randomized study. Circulation. 1998 Jan 27;97(3):257-62. doi: 10.1161/01.cir.97.3.257.

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• Hogan WJ, Winter S, Pinto NM, Weng C, Sheng X, Conradt E, Wood J, Puchalski MD, Tani LY, Miller TA. Neurobehavioral evaluation of neonates with congenital heart disease: a cohort study. Dev Med Child Neurol. 2018 Dec;60(12):1225-1231. doi: 10.1111/dmcn.13912. Epub 2018 May 10.

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• Gakenheimer-Smith L, Glotzbach K, Ou Z, Presson AP, Puchalski M, Jones C, Lambert L, Delgado-Corcoran C, Eckhauser A, Miller T. The Impact of Neurobehavior on Feeding Outcomes in Neonates with Congenital Heart Disease. J Pediatr. 2019 Nov;214:71-78.e2. doi: 10.1016/j.jpeds.2019.06.047. Epub 2019 Aug 8.

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• Ebbing C, Rasmussen S, Kiserud T. Middle cerebral artery blood flow velocities and pulsatility index and the cerebroplacental pulsatility ratio: longitudinal reference ranges and terms for serial measurements. Ultrasound Obstet Gynecol. 2007 Sep;30(3):287-96. doi: 10.1002/uog.4088.

  PMID: 17721916 BACKGROUND

• Williams IA, Fifer C, Jaeggi E, Levine JC, Michelfelder EC, Szwast AL. The association of fetal cerebrovascular resistance with early neurodevelopment in single ventricle congenital heart disease. Am Heart J. 2013 Apr;165(4):544-550.e1. doi: 10.1016/j.ahj.2012.11.013. Epub 2013 Feb 13.

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MeSH Terms

Conditions

Hypoxia; Neurodevelopmental Disorders; Heart Defects, Congenital

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Whitnee Hogan, MD

CONTACT

801-213-3599; whitnee.hogan@hsc.utah.edu

Lisa M. Hansen, BA

CONTACT

801-587-9104; lisa.hansen@hsc.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Assistant Professor

Model Details: Interventional Research Design

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 14, 2023
• Study Start: December 17, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)