Transitional Cerebrovascular Reactivity in Very Preterm Infants

Clinical Determinants of Cerebrovascular Reactivity in Very Preterm Infants During the Transitional Period

The transitional period, defined as the first 72 hours after preterm birth, is often characterized by a significant hemodynamic instability and may also be associated with an impairment of cerebral autoregulation, with relevant clinical implications. The moving correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx, has been previously proposed as a marker of cerebrovascular reactivity and provides an indirect estimation of cerebral autoregulation in preterm infants.

This study aims to evaluate whether different antenatal, perinatal and postnatal factors may influence cerebrovascular reactivity in very preterm infants during the transitional period.

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Cerebral Autoregulation; Premature Infant Disease
• Intervention / Treatment: Device: Near Infrared Spectroscopy monitoring; Device: Electrical velocimetry and pulse oximetry

Detailed Description

The transitional period, defined as the first 72 hours after preterm birth, is often characterized by a significant hemodynamic instability and may also be associated with an impairment of cerebral autoregulation, with relevant clinical implications. The moving correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx, has been previously proposed as a marker of cerebrovascular reactivity and provides an indirect estimation of cerebral autoregulation in preterm infants.

This prospective observational study aims to evaluate whether different antenatal, perinatal, and postnatal factors may influence cerebrovascular reactivity in very preterm infants during the transitional period.

Infants <32 weeks' gestation are enrolled within 12h from birth. A simultaneous monitoring of cerebral oxygenation (CrSO2) by near-infrared spectroscopy and of heart rate (HR) by pulse oximetry and electrical velocimetry is performed continuously over the first 72h.

The moving correlation coefficient between CrSO2 and HR is calculated using the ICM+ software (Cambridge Enterprise Ltd) using 5-min, 30-point epochs. Time periods with evidence of major artefacts, or with a missing data proportion >50% are excluded from this calculation. Positive TOHRx values will be interpreted as markers of impaired autoregulation.

A screening echocardiogram is routinely performed at the time of enrollment and repeated 6-12 hourly in the presence of a patent ductus arteriosus (PDA) or 12-24 hourly if there is no evidence of PDA. Based on echocardiographic features, the ductal status is classified as follows: no evidence of PDA, restrictive PDA (restrictive shunt pattern and left atrium to aortic root ratio [LA:Ao] ratio <1.5), hemodynamically significant PDA (pulsatile shunt pattern, LA:Ao ratio ≥1.5 or presence of reversed end-diastolic flow either in the descending aorta or in the anterior cerebral artery).

A concomitant cerebral ultrasound scan, aimed at evaluating brain parenchyma and the occurrence of prematurity-related complications, such as intraventricular hemorrhage, is also performed.

During the study period, the following antenatal and neonatal data are tracked down on a specific case report form: gestational age (GA); birth weight (BW); non-invasive blood pressure; antenatal steroids (complete course vs. incomplete course or not given); evidence of reversed end-diastolic flow at antenatal umbilical Doppler (uREDF) (present vs. absent); ventilatory status over the first 72 hours of life (mechanical ventilation, continuous positive airway pressure [CPAP], nasal cannulas or self-ventilating in air [SVIA]); surfactant administration; development of IVH over the first 72 hours of life; ongoing inotropes (dopamine, dobutamine or both).

The correlation between antenatal, perinatal, and postnatal clinical variables and TOHRx is going to be evaluated using generalized linear mixed models or generalized estimating equations.

• Study Type: Observational
• Enrollment (Actual): 72

Contacts and Locations

Study Locations

• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Sant'Orsola-Malpighi University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 days (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Preterm infants <32 weeks' gestation during the transitional period (0-72 hours of life)

Description

Inclusion Criteria:

• gestational age <32 weeks' gestation

Exclusion Criteria:

• major congenital malformations
• congenital heart disease

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between TOHRx and gestational age	Correlation between TOHRx and gestational age	0-72 hours
Correlation between TOHRx and antenatal steroids administration	Correlation between TOHRx and antenatal steroids administration (full course vs. incomplete course or not given)	0-72 hours
Correlation between TOHRx and antenatal Doppler status	Correlation between TOHRx and antenatal Doppler status (normal or abnormal)	0-72 hours
Correlation between TOHRx and ductal status	Correlation between TOHRx and ductal status (hemodynamically significant, restrictive or closed)	0-72 hours
Correlation between TOHRx and respiratory support	Correlation between TOHRx and respiratory support modality (mechanical ventilation, CPAP, nasal cannulas or self-ventilating in air)	0-72 hours
Correlation between TOHRx and inotropes	Correlation between TOHRx and inotropes administration (dopamine; dobutamine; dopamine and dobutamine)	0-72 hours

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Luigi Corvaglia, MD, S. Orsola-Malpighi University Hospital, Bologna, Italy

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): July 3, 2021

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: preterm infants; cerebral autoregulation; cerebrovascular reactivity; transitional period
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Premature Birth
• Other Study ID Numbers: NEO-TOHRx

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