Inflammatory Cytokines Associated With Perinatal Brain Injury (Cytokines)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01035697
Recruitment Status : Completed
First Posted : December 21, 2009
Last Update Posted : September 26, 2017
Centers for Disease Control and Prevention
National Center for Research Resources (NCRR)
Information provided by:
NICHD Neonatal Research Network

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
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 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 : July 1999
Actual Primary Completion Date : July 2002
Actual Study Completion Date : May 2004

Primary Outcome Measures :
  1. Pro-cytokines increased and anti-inflammatory cytokines decreased [ Time Frame: At birth and/or up to Day 3±1 ]

Secondary Outcome Measures :
  1. Type and severity of CP and other neurodevelopmental handicaps, the appearance of PVL, and neonatal mortality [ Time Frame: 18-22 months corrected age ]
  2. 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) [ Time Frame: At birth ]
  3. 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) [ Time Frame: Up to Day of life 21 ]
  4. 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 [ Time Frame: Up to Day of life 21 ]

Biospecimen Retention:   Samples With DNA
Whole blood spots collected on filter paper.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   up to 72 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Infants 401-1,000 grams at birth of both genders and all racial/ethnic groups.

Inclusion Criteria:

  • Infants 401-1,000 grams at birth

Exclusion Criteria:

  • >72 hours of age

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01035697

United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35249-7335
United States, California
Stanford University
Palo Alto, California, United States, 94304
University of California at San Diego
San Diego, California, United States, 92103-8774
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, North Carolina
Wake Forest University
Charlotte, North Carolina, United States, 27157
RTI International
Durham, North Carolina, United States, 27705
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
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)
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

Additional Information:
Publications of Results:

Responsible Party: Waldemar A. Carlo, MD, Lead Principal Investigator, University of Alabama at Birmingham Identifier: NCT01035697     History of Changes
Other Study ID Numbers: NICHD-NRN-0022
U10HD027853 ( U.S. NIH Grant/Contract )
M01RR008084 ( U.S. NIH Grant/Contract )
U10HD040492 ( U.S. NIH Grant/Contract )
M01RR000030 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
M01RR000039 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
M01RR000750 ( U.S. NIH Grant/Contract )
U10HD021364 ( U.S. NIH Grant/Contract )
M01RR000080 ( U.S. NIH Grant/Contract )
U01HD036790 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
M01RR000070 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
M01RR000032 ( U.S. NIH Grant/Contract )
U10HD040461 ( U.S. NIH Grant/Contract )
U10HD021397 ( U.S. NIH Grant/Contract )
M01RR016587 ( U.S. NIH Grant/Contract )
U10HD027881 ( U.S. NIH Grant/Contract )
M01RR000997 ( U.S. NIH Grant/Contract )
U10HD021415 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
M01RR000633 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD040498 ( U.S. NIH Grant/Contract )
M01RR007122 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
M01RR006022 ( U.S. NIH Grant/Contract )
First Posted: December 21, 2009    Key Record Dates
Last Update Posted: September 26, 2017
Last Verified: September 2017

Keywords provided by NICHD Neonatal Research Network:
NICHD Neonatal Research Network
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Pro-inflammatory cytokines
Anti-inflammatory cytokines
Interleukin-1 (IL-1β)
Interleukin-2 (IL-2)
Interleukin-3 (IL-3)
Interleukin-8 (IL-8)
Interleukin-9 (IL-9)
Tumor necrosis factor-α (TNF-α)
Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES)

Additional relevant MeSH terms:
Brain Injuries
Cerebral Palsy
Birth Weight
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Brain Damage, Chronic
Body Weight
Signs and Symptoms