Inflammatory Cytokines Associated With Perinatal Brain Injury

Sponsor

NICHD Neonatal Research Network (Other)

Overall Status

Completed

CT.gov ID

NCT01035697

Collaborator

Centers for Disease Control and Prevention (U.S. Fed), National Center for Research Resources (NCRR) (NIH)

1,067

Enrollment

Locations

Duration (Months)

59.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This observational study assessed whether measurements of certain pro-inflammatory and anti-inflammatory cytokines in the blood (either singly or in combination) at birth and/or up to day of life 21 can predict cerebral palsy at 18-22 months corrected age.

Condition or Disease	Intervention/Treatment	Phase
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Cerebral Palsy

Detailed Description

Inflammatory cytokines [interleukin-1 (IL-1β), IL-8, IL-9, tumor necrosis factor-α (TNF-α), and RANTES] but not anti-inflammatory cytokines released during the perinatal period have been associated with the development of periventricular leukomalacia (PVL) and cerebral palsy (CP) in near term and term infants. However, because blood samples were obtained on any day between day 1 and 18, these data cannot distinguish between prenatal and postnatal effects on neurological outcome. Furthermore, very low birth weight infants who are at the highest risk have not been studies.

The goal of this study was to measure pro-inflammatory and anti-inflammatory cytokine levels at various times in the perinatal period (at birth up to day of life 21), since they may be elevated at different points in the disease process. Blood samples (whole blood spots, dried on filter paper) were obtained on day 1 within 4 hours after birth, and on days 3, 7, 14, and 21. Neurodevelopmental assessments were conducted at 18-22 months corrected age.

Study Design

Study Type:

Observational

Actual Enrollment :

1067 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Study to Determine If Inflammatory Cytokines Are Associated With Perinatal Brain Injury and Long Term Neurodevelopmental Handicap or Death

Study Start Date :

Jul 1, 1999

Actual Primary Completion Date :

Jul 1, 2002

Actual Study Completion Date :

May 1, 2004

Outcome Measures

Primary Outcome Measures

Pro-cytokines increased and anti-inflammatory cytokines decreased [At birth and/or up to Day 3±1]

Secondary Outcome Measures

Type and severity of CP and other neurodevelopmental handicaps, the appearance of PVL, and neonatal mortality [18-22 months corrected age]
Abnormal pro-inflammatory and anti-inflammatory cytokines at birth are associated with prenatal insults (e.g., chorioamnionitis, occult intrauterine infection, early-onset neonatal sepsis, perinatal asphyxia, early death) [At birth]
Abnormal postnatal cytokine levels associated with postnatal insults (e.g., postnatal intraventricular hemorrhage, late-onset neonatal sepsis, bronchopulmonary dysplasia, chronic lung disease, and/or necrotizing enterocolitis) [Up to Day of life 21]
Pro-inflammatory cytokine elevations at the time of a workup for possible sepsis occur in infants with a positive bacterial blood culture and those with negative blood cultures who are treated with a full course of antibiotics [Up to Day of life 21]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 72 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Infants 401-1,000 grams at birth

Exclusion Criteria:

72 hours of age

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35249-7335
2	Stanford University	Palo Alto	California	United States	94304
3	University of California at San Diego	San Diego	California	United States	92103-8774
4	Yale University	New Haven	Connecticut	United States	06504
5	University of Miami	Miami	Florida	United States	33136
6	Emory University	Atlanta	Georgia	United States	30303
7	Indiana University	Indianapolis	Indiana	United States	46202
8	Wayne State University	Detroit	Michigan	United States	48201
9	University of New Mexico	Albuquerque	New Mexico	United States	87131
10	Wake Forest University	Charlotte	North Carolina	United States	27157
11	RTI International	Durham	North Carolina	United States	27705
12	Duke University	Durham	North Carolina	United States	27710
13	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States	45267
14	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
15	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
16	University of Tennessee	Memphis	Tennessee	United States	38163
17	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
18	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

NICHD Neonatal Research Network
Centers for Disease Control and Prevention
National Center for Research Resources (NCRR)

Investigators

Principal Investigator: William Oh, MD, Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Michele C. Walsh, MD MS, Case Western Reserve University, Rainbow Babies & Children's Hospital
Principal Investigator: Ronald N. Goldberg, MD, Duke University
Principal Investigator: Barbara J. Stoll, MD, Emory University
Principal Investigator: James A. Lemons, MD, Indiana University
Principal Investigator: Abhik Das, PhD, RTI International
Principal Investigator: David K. Stevenson, MD, Stanford University
Principal Investigator: Waldemar A. Carlo, MD, University of Alabama at Birmingham
Principal Investigator: Neil N. Finer, MD, University of California, San Diego
Principal Investigator: Edward F. Donovan, MD, Children's Hospital Medical Center, Cincinnati
Principal Investigator: Shahnaz Duara, MD, University of Miami
Principal Investigator: Lu-Ann Papile, MD, University of New Mexico
Principal Investigator: Sheldon B. Korones, MD, University of Tennessee
Principal Investigator: Jon E. Tyson, MD MPH, The University of Texas Health Science Center, Houston
Principal Investigator: Abbot R. Laptook, MD, University of Texas
Principal Investigator: T. Michael O'Shea, MD MPH, Wake Forest University
Principal Investigator: Seetha Shankaran, MD, Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD, Yale University