Assessment of Autonomic Nervous Regulation During Postnatal Period in Newborns

Assessment of Autonomic Nervous System Regulatory Mechanisms During Postnatal Period in Newborns

The project aims to assess the regulatory mechanisms of autonomic nervous system using noninvasive methods in newborns during postnatal adaptation period. Evaluated parameters will include complex analysis of electrodermal activity as a parameter reflecting sympathetic cholinergic system and indices of heart rate variability reflecting the activity of parasympathetic cardiac regulation. The project is focused on the neuro-psycho-physiological characteristics of physiological adaptation in early postnatal age and the effect of non-pharmacological pain relieving.

Study Overview

• Status: Active, not recruiting
• Conditions: Infant, Newborn
• Intervention / Treatment: Procedure: Pain stimulus; Dietary supplement: Non-pharmacological pain relief

• Study Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

Study Locations

• Slovakia
  • Martin, Slovakia, 03601
    • Jessenius Medical Faculty, Comenius University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 4 days (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy term newborns with physiological postnatal adaptation born in University Hospital in Martin (Slovakia).

Description

Inclusion Criteria:

• healthy term newborns
• physiological postnatal adaptation
• signed parental informed consent

Exclusion Criteria:

• preterm delivery
• impaired postnatal adaptation
• perinatal infection
• congenital diseases and genetic anomalies
• hypoglycemia
• hyperbilirubinemia requiring phototherapy treatment

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control group; Healthy term newborns without pain relief during pain stimulus (intramuscular K vitamin administration and heel lancing for blood spot examination).	Procedure: Pain stimulus; Pain stimulus - intramuscular K vitamin administration, heel lancing = standard healthcare procedure
Sucrose group; Healthy term newborns with oral application of sucrose during pain stimulus (intramuscular K vitamin administration and heel lancing for blood spot examination).	Procedure: Pain stimulus; Pain stimulus - intramuscular K vitamin administration, heel lancing = standard healthcare procedure; Dietary supplement: Non-pharmacological pain relief; Administration of sucrose/mother milk during pain stimulus
Mother milk group; Healthy term newborns with oral application of mother milk during pain stimulus (intramuscular K vitamin administration and heel lancing for blood spot examination).	Procedure: Pain stimulus; Pain stimulus - intramuscular K vitamin administration, heel lancing = standard healthcare procedure; Dietary supplement: Non-pharmacological pain relief; Administration of sucrose/mother milk during pain stimulus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics of parasympathetic (vagal) heart regulation in newborns in relation to nociception	The study of cardiac vagal regulation of heart rate in relation to nociceptive stimulus using conventional linear and novel nonlinear analysis of heart rate variability (HRV) by special software (Kubios HRV, University of Eastern Finland, Kuopio, Finland). Continual recordings of RR intervals will be recorded using Polar V800 (Polar, Finland). HRV indices: linear (time domain - mean square of successive differences (MSSD); spectral domain - low frequency power (LF), high frequency power (HF), total spectral power (TP); non-linear (symbolic dynamics - 0V%, 2LV%, entropy).	within the first 4 days of postnatal life
Characteristics of sympathetic activity in newborns in relation to nociception	The study of sympathetic cholinergic system indexed by electrodermal activity (EDA) using linear and novel nonlinear parameters characterizing complex sympathetic behavior in relation to nociceptive stimulus. Continual EDA recording associated with peripheral temperature monitoring will be performed using device BioInfinity, Thought Technology Ltd., Canada. EDA indices: linear - SCA (skin conductance amplitude), frequency of NS-EDR (nonspecific electrodermal responses), nonlinear - SIE (symbolic information entropy), and ApEn (approximate entropy).	within the first 4 days of postnatal life
Autonomic (parasympathetic) reactivity in response to non-pharmacological pain relief in newborns	The study of autonomic nervous system complex regulatory mechanisms included in the reactivity - test: stress stimulus (painful intervention) with non-pharmacological pain relieving and recovery phase using HRV quantitative and qualitative analysis. 1st group (control group, n=25) without pain relief; 2nd group (n=25) with oral application of sucrose during nociception stimulus; 3rd group (n=25) with oral application of mother milk during nociceptive stimulus.	within the first 4 days of postnatal life - during and after pain stimulus
Autonomic (sympathetic) reactivity in response to non-pharmacological pain relief in newborns	The study of autonomic nervous system complex regulatory mechanisms included in the reactivity - test: stress stimulus (painful intervention) with non-pharmacological pain relieving and recovery phase using EDA quantitative and qualitative analysis. 1st group (control group, n=25) without pain relief; 2nd group (n=25) with oral application of sucrose during nociception stimulus; 3rd group (n=25) with oral application of mother milk during nociceptive stimulus.	within the first 4 days of postnatal life - during and after pain stimulus
Pain quality assessment in newborns: Neonatal Facial Coding System (NFCS) scaling system	Assessment of the pain quality during painful intervention in newborns associated with muscular application of K vitamin after birth and heel lancing (blood spot) on 3rd postnatal day (standard neonatal care) according to Neonatal Facial Coding System (NFCS). NFCS: visual monitoring of newborn's face during pain stimulus for the presence of 9 specific facial actions: brow bulge, eye squeeze, naso - labial furrow, open lips, stretch mouth (horizontal/vertical), lip purse, taut tongue, chin quiver. Scale range: 0 - 9 points; (0 = no pain; 9 = maximal pain presentation).	within the first 4 days of postnatal life - during pain stimulus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Developmental aspect of parasympathetic regulatory mechanisms in early postnatal period	Assessment of the developmental aspect of cardiac vagal regulation indexed by HRV indices in relation to postnatal age (measures of HRV: early after birth; 24 hours of life; 3rd - 4th day of life).	early after birth; 24 hours of life; 3rd - 4th day of life
Developmental aspect of sympathetic regulatory mechanisms in early postnatal period	Assessment of the developmental aspect of sympathetic cholinergic regulation indexed by EDA complex analysis in relation to postnatal age (early after birth; 24 hours of life; 3rd - 4th day of life).	early after birth; 24 hours of life; 3rd - 4th day of life
Maternal clinical parameters effect on the neonatal autonomic (sympathetic) nervous system regulation	Study of the selected maternal clinical parameters [age (years), weight gain during pregnancy (kilograms), heart rate (beats per minute), systolic and diastolic blood pressure (millimeters of mercury) before delivery] in the interaction with sympathetic regulatory mechanisms - indexed by EDA.	prior to delivery + retrospective data
Maternal clinical parameters effect on the neonatal autonomic (parasympathetic) nervous system regulation	Study of the selected maternal clinical parameters [age (years), weight gain during pregnancy (kilograms), heart rate (beats per minute), systolic and diastolic blood pressure (millimeters of mercury) before delivery] in the interaction with parasympathetic regulatory mechanisms - indexed by HRV.	prior to delivery + retrospective data
Delivery mode effect on autonomic (sympathetic) nervous system regulation	Study of the effect of delivery mode on the function and maturation of autonomic (sympathetic) nervous regulatory mechanisms - indexed by EDA.	at the time of delivery
Delivery mode effect on autonomic (parasympathetic) nervous system regulation	Study of the effect of delivery mode on the function and maturation of autonomic (parasympathetic) nervous regulatory mechanisms - indexed by HRV.	at the time of delivery
Blood pressure in relation to autonomic (sympathetic) nervous system regulation	Study of the relation between physiological parameters - blood pressure (systolic, mean, diastolic - in millimeters of mercury) and sympathetic regulatory mechanisms - indexed by EDA.	within the first 4 days of postnatal life
Blood pressure in relation to autonomic (parasympathetic) nervous system regulation	Study of the relation between physiological parameters - blood pressure (systolic, mean, diastolic - in millimeters of mercury) and parasympathetic regulatory mechanisms - indexed by HRV.	within the first 4 days of postnatal life
Blood oxygen saturation in relation to autonomic (sympathetic) nervous system regulation	Study of the relation between physiological parameters - blood oxygen saturation (in percentage) and sympathetic regulatory mechanisms - indexed by EDA.	within the first 4 days of postnatal life
Blood oxygen saturation in relation to autonomic (parasympathetic) nervous system regulation	Study of the relation between physiological parameters - blood oxygen saturation (in percentage) and parasympathetic regulatory mechanisms - indexed by HRV.	within the first 4 days of postnatal life
Selected laboratory parameters in relation to autonomic (sympathetic) nervous system regulation	Study of the effect of selected laboratory parameters [glycaemia (millimoles per liter), lactate (millimoles per liter), bilirubin (micromoles per liter)] on the sympathetic regulatory mechanisms - indexed by EDA.	immediately after birth + on 3rd - 4th postnatal day
Selected laboratory parameters in relation to autonomic (parasympathetic) nervous system regulation	Study of the effect of selected laboratory parameters [glycaemia (millimoles per liter), lactate (millimoles per liter), bilirubin (micromoles per liter)] on the parasympathetic regulatory mechanisms - indexed by HRV.	immediately after birth + on 3rd - 4th postnatal day
Acid - base parameters in relation to autonomic (sympathetic) nervous system regulation	Study of the effect of acid - base parameters [pH, pCO2 (kilopascals), base excess (millimoles per liler)] acquired immediately after birth on the sympathetic regulatory mechanisms - indexed by EDA.	immediately after birth + on 3rd - 4th postnatal day
Acid - base parameters in relation to autonomic (parasympathetic) nervous system regulation	Study of the effect of acid - base parameters [pH, pCO2 (kilopascals), base excess (millimoles per liler)] acquired immediately after birth on the parasympathetic regulatory mechanisms - indexed by HRV.	immediately after birth + on 3rd - 4th postnatal day
Role of psychosocial factors in autonomic (sympathetic) nervous system regulation	Study of the effect of psychosocial factors (bonding, breastfeeding) on the sympathetic regulatory mechanisms - indexed by EDA.	immediately after birth + within the first 4 days of postnatal life
Role of psychosocial factors in autonomic (parasympathetic) nervous system regulation	Study of the effect of psychosocial factors (bonding, breastfeeding) on the parasympathetic regulatory mechanisms - indexed by HRV.	immediately after birth + within the first 4 days of postnatal life
Role of umbilical cord clamping in autonomic (sympathetic) nervous system regulation	Study of the effect of immediate vs. delayed cord clamping on sympathetic regulatory mechanisms - indexed by EDA.	at the time of delivery
Role of umbilical cord clamping in autonomic (parasympathetic) nervous system regulation	Study of the effect of immediate vs. delayed cord clamping on parasympathetic regulatory mechanisms - indexed by HRV.	at the time of delivery

Collaborators and Investigators

• Sponsor: Comenius University
• Investigators: Study Director: Mirko Zibolen, Prof, MD, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2019
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: January 3, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: EK69/2018

Drug and device information, study documents

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