Neurophysiologic Maturation Index for Moderate and Late Preterm Infants (NEMO Project)

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

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.

Study Overview

• Status: Unknown
• Conditions: Neurophysiologic Maturation
• Intervention / Treatment: Other: Amplitude integrated electroencephalogram, Cardiorespiratory signal acquisition

• Study Type: Observational
• Enrollment (Anticipated): 171

Contacts and Locations

• Study Contact: Name: Birju A Shah, MD, MPH; Phone Number: 48016 401-274-1122; Email: Birju_Shah@Brown.edu
• Study Contact Backup: Name: Abbot Laptook, MD; Phone Number: 47421 401-274-1122; Email: ALaptook@wihri.org

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • Recruiting
      • McGill University Health Center
      • Contact: Guilherme Sant' Anna, MD; Phone Number: 23489 1-514-412-4400; Email: guilherme.santanna@mcgill.ca
      • Principal Investigator: Guilherme Sant'Anna, MD
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Not yet recruiting
      • Wayne State University
      • Contact: Sanjay Chawla, MD; Phone Number: 313-745-5638; Email: schawla@dmc.org
      • Principal Investigator: Sanjay Chawla, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Recruiting
      • Brown University - Women and Infants Hospital of Rhode Island NICU
      • Contact: Birju A Shah, MD, MPH; Phone Number: 48016 401-274-1122; Email: Birju_Shah@Brown.edu
      • Contact: Abbot Laptook, MD; Phone Number: 47421 401-274-1122; Email: ALaptook@wihri.org
      • Principal Investigator: Birju A Shah, MD, MPH
      • Principal Investigator: Abbot Laptook, MD
      • Sub-Investigator: Martin Keszler, MD
      • Sub-Investigator: Richard Tucker, BA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Neonatal intensive care unit Newborn nursery

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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

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

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: Wayne State University; McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Birju A Shah, MD, MPH, Brown University - Women and Infants Hospital of Rhode Island; Principal Investigator: Abbot Laptook, MD, Brown University - Women and Infants Hospital of Rhode Island

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): March 1, 2016

Study Registration Dates

• First Submitted: May 17, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 5, 2014

Study Record Updates

• Last Update Posted (Estimate): June 5, 2014
• Last Update Submitted That Met QC Criteria: June 2, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Heart rate variability; Preterm Infants; Length of Hospital Stay; Amplitude integrated electroencephalogram; Respiratory rate variability
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 13-0052