Inflammatory Cytokines Associated With Perinatal Brain Injury

Completed

• Conditions: Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Infant, Newborn; Cerebral Palsy

• Registration Number: NCT01035697
• Lead Sponsor: 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.

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 Timeline

• Study Start: 1999-07
• Primary Completion: 2002-07
• Study Completion: 2004-05
• Study First Submitted: 2009-12-17
• Study First Submitted QC: 2009-12-17
• Study First Posted: 2009-12-21
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-20
• Last Update Posted: 2019-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1067

Inclusion Criteria

• Infants 401-1,000 grams at birth

Exclusion Criteria

• >72 hours of age

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Pro-cytokines increased and anti-inflammatory cytokines decreased	At birth and/or up to Day 3±1

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (18)

University of Tennessee; 🇺🇸 Memphis, Tennessee, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of New Mexico; 🇺🇸 Albuquerque, New Mexico, United States

Wake Forest University; 🇺🇸 Charlotte, North Carolina, United States

Brown University, Women & Infants Hospital of Rhode Island; 🇺🇸 Providence, Rhode Island, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

University of California at San Diego; 🇺🇸 San Diego, California, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

RTI International; 🇺🇸 Durham, North Carolina, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Case Western Reserve University, Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Cincinnati Children's Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of Texas Southwestern Medical Center at Dallas; 🇺🇸 Dallas, Texas, United States

University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States