Effect of Caffeine on Heart Rate Variability in Newborns

Effect of Caffeine for Apnoea Treatment on Heart Rate Variability in Newborns

The aim of this study was to evaluate the impact of caffeine treatment, given either orally or intravenously, on heart rate variability in newborns. In addition, the investigators sought for a potential association between caffeine treatment and vital functions.

Study Overview

• Status: Completed
• Conditions: Heart Rate Variability; Newborn; Caffeine; Apnoea of Newborn
• Intervention / Treatment: Diagnostic test: Electrocardiogram; Diagnostic test: Monitoring of vital functions; Drug: Caffeine Citrate 5 mg/kg

Detailed Description

At Neonatal Department of University Medical Centre Ljubljana caffeine is used to treat neonatal apnoea. It has known affects on central nervous and cardiovascular systems, but little is known about the impact of caffeine intake on heart rate variability (HRV) in newborns.

In this study, the investigators performed measurements on one sample of 25 newborns with apnoea who had been admitted to the Neonatal Department of University Medical Centre Ljubljana and treated with caffeine citrate. The treatment regimen consisted of caffeine citrate of a loading dose of 20 mg/kg of body mass, followed by a daily maintenance dose of 5 mg/kg after 24 hours. The investigators measured parameters of HRV in two situations: while the treatment with caffeine citrate was ongoing and after the treatment was withdrawn. The newborns served as controls. Electrical activity of the heart was measured with a Holter ECG while the newborn was sleeping in supine position, first without a bed tilt and afterwards with a 30° head-up tilt. Simultaneously was evaluated the alertness of the newborn and measured their physiological variables (the breathing frequency, the heart rate, the arterial oxygen saturation, and the body temperature).

All parents were given their written consent for their child to participate in the study.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• newborns with apnoea treated with caffeine citrate
• newborns whose parents have signed the informed consent form

Exclusion Criteria:

• severe perinatal hypoxia
• infection
• liver or renal insufficiency
• neurological disorders
• congenital anomalies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: On Caffeine, maintenance dose; During receiving maintenance dose of 5 mg/kg caffeine citrate (i.e. 2,5 mg/kg caffeine) in the form of solution, orally or intravenously, Holter electrocardiogram and vital functions were monitored for 40 minutes.	Diagnostic test: Electrocardiogram; Recording of the electrical activity of the heart during sleep; sleep phases were evaluated. The bed was initially in horizontal position and tilted for 30° head-up after 20 minutes of continuous tracing.; Other Names: Holter ECG; Diagnostic test: Monitoring of vital functions; Measuring of heart rate, breathing frequency, arterial oxygen saturation and body temperature while recording ECG.; Drug: Caffeine Citrate 5 mg/kg; Caffeine in the form of suspension was given to the newborns.
Experimental: Off caffeine; 100 hours after caffeine withdrawal Holter electrocardiogram and vital functions were monitored for 40 minutes.	Diagnostic test: Electrocardiogram; Recording of the electrical activity of the heart during sleep; sleep phases were evaluated. The bed was initially in horizontal position and tilted for 30° head-up after 20 minutes of continuous tracing.; Other Names: Holter ECG; Diagnostic test: Monitoring of vital functions; Measuring of heart rate, breathing frequency, arterial oxygen saturation and body temperature while recording ECG.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between caffeine treatment and total power (TP) spectrum of HRV	While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. TP (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.	During Procedure
Association between caffeine treatment and high frequency (HF) spectrum of HRV	While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. HF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.	During Procedure
Association between caffeine treatment and low frequency (LF) spectrum of HRV	While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. LF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.	During Procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between postmenstrual age and total power (TP) spectrum of HRV	While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. TP (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.	During Procedure
The correlation between postmenstrual age and high frequency (HF) spectrum of HRV	While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. HF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.	During Procedure
The correlation between postmenstrual age and low frequency (LF) spectrum of HRV	While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. LF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.	During Procedure
The effect of caffeine on heart rate	Heart rate (beats per minute) was obtained from the segments, recorded by ECG Holter and analysed by the Vision Premier Programme. The selected segments corresponded to the segments HRV parameters were obtained for each bed tilt. The values were compared across the two arms of the study.	During Procedure
The effect of caffeine on breathing frequency	Breathing frequency (breaths per minute) was determined manually by observing the chest movement. The measurement was performed three times while the newborn was sleeping for each bed tilt. The values were compared across the two arms of the study.	During Procedure
The effect of caffeine on arterial oxygen saturation	Arterial oxygen saturation (percent) was performed by a pulse oximeter attached to the right hand. The arterial oxygen saturation value was noted three times with the corresponding breathing frequency while the newborn was sleeping for each bed tilt. The values were compared across the two arms of the study.	During Procedure
The effect of caffeine on body temperature	Body temperature (degree Celsius) was measured by a frontal non-contact infrared thermometer three times for each bed tilt while the newborn was sleeping. The values were compared across the two arms of the study.	During Procedure

Collaborators and Investigators

• Sponsor: University of Ljubljana
• Investigators: Principal Investigator: Petja Fister, MD, PhD, University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Actual): July 31, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: March 20, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: autonomic nervous system; caffeine; newborn; heart rate variability; bed tilt
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Apnea; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine; Caffeine citrate
• Other Study ID Numbers: 0120-458/2016-3

Drug and device information, study documents

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