Neurophysiologic Maturation Index for Moderate and Late Preterm Infants

Study Overview
=================
Brief Summary
-----------------
Moderate and late preterm infants contribute to significant neonatal intensive care unit health care resource utilization because of their sheer numbers. Determinants of the length of hospitalization (LOH) in this population are understudied. Gestational age (GA) is used most commonly as a predictor for LOH but there are many limitations including inaccurate dating and morbidities of prematurity which at least partly related to neurophysiological immaturity. The latter can be assessed by amplitude integrated electroencephalogram (aEEG, a simplified 5 lead EEG), and possibly by heart rate variability (HRV) and respiratory variability (RV). All 3 are non-invasive tests that can be done at the bedside. Our study hypothesis is to determine if neurophysiologic maturation as assessed by aEEG, HRV and RV within 24-96 hours following birth improves the correlation between gestational age and length of hospitalization compared to gestational age alone.

Official Title
-----------------
Neurophysiologic Maturation Index: NEMO Project for Moderate and Late Preterm Infants

Conditions
-----------------
Neurophysiologic Maturation

Intervention / Treatment
-----------------
* Other: Amplitude integrated electroencephalogram, Cardiorespiratory signal acquisition


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Gestational age of either 320-326 weeks or 340-346 weeks by Obstetric criteria (presence of a sure LMP or sonogram performed in the first trimester, or agreement between LMP and a sonogram performed between the first trimester and 20 weeks) Admitted to a NICU of a participating institution Post-natal age less than 96 hours Exclusion Criteria: Major congenital anomaly/genetic anomaly Growth restriction (birth weight < 10%, Fenton growth curves) Unsure obstetric dating (e.g., absence of a sure LMP without a sonogram, earliest sonogram performed after 20 weeks without a sure LMP, or discrepancy between LMP and sonogram) Exposure to medications within the preceding 12 hrs which may affect CNS function (e.g., fentanyl, morphine, midazolam) Neonatal seizures Neonatal abstinence syndrome secondary to in-utero exposure to narcotics, methadone etc, or at high risk for development of abstinence Hypoxia-ischemia defined as the combination of fetal acidemia (cord gas or blood gas within 1 hour of birth: pH ≤ 7.15 or BE ≥ -10mEq/L), need for resuscitation at birth (PPV ± chest compressions or medications), and evidence of encephalopathy (Stage 1, 2 or 3 Sarnat). Stage 1 encephalopathy will be defined based on the level of consciousness which is characterized by a hyper-alert state, apparent alertness, and irritability. In the absence of a cord or early post-natal blood gas, there must be a history of a perinatal event which may have compromised oxygenation or blood flow to the fetus. Infants who are expected to be on mechanical (via an endotracheal tube) or high frequency ventilation for the first 96 hours after birth. Inability to obtain the informed consent

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 4 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Late Preterm Infants (LPT)<br>34 weeks and 0-6 days gestational age | Other: Amplitude integrated electroencephalogram, Cardiorespiratory signal acquisition<br> <br> |
| Moderate preterm infants (MPT)<br>32 weeks and 0-6 days gestational age | Other: Amplitude integrated electroencephalogram, Cardiorespiratory signal acquisition<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnitude of variance, R square | linear regression model: LOH = intercept + b1GA + b2aEEG + b3HRV + b4RV + error term; b1 - b4 represents the weight of each variable to explain the variance of the equation (R2), GA is gestational age, aEEG is amplitude integrated EEG, HRV is heart rate variability, RV is respiratory variability, LOH is length of hospital stay | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amplitude integrated electroencephalogram (aEEG) | number of cycles/hour, the lower border voltage, the span voltage or the percent of the tracing which is discontinuous | participants will be followed for the duration of hospital stay, an expected average of 5 weeks | 
| Heart rate variability (HRV) | standard deviation of the R-R interval, sample asymmetry and sample entropy | participants will be followed for the duration of hospital stay, an expected average of 5 weeks | 
| Respiratory variability (RV) | instantaneous respiratory effort, phase between ribcage and abdomen, amplitude of the signal, pause metrics and movement artifact metrics | participants will be followed for the duration of hospital stay, an expected average of 5 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amplitude integrated electroencephalogram, Heart rate variability, Respiratory rate variability, Preterm Infants, Length of Hospital Stay