Inflammatory Cytokines Associated With Perinatal Brain Injury

Cerebral Palsy Clinical Trial

— Cytokines  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01035697
• Other study ID #: NICHD-NRN-0022
• Secondary ID: U10HD027853M01RR
• Status: Completed
• Start date: July 1999
• Est. completion date: May 2004

Study information

• Verified date: March 2019
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1067
• Est. completion date: May 2004
• Est. primary completion date: July 2002
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 72 Hours

Eligibility

Inclusion Criteria:

• Infants 401-1,000 grams at birth

Exclusion Criteria:

• >72 hours of age

Related Conditions & MeSH terms

• Birth Weight
• Brain Injuries
• Cerebral Palsy
• Infant, Low Birth Weight
• Infant, Newborn
• Infant, Premature
• Infant, Small for Gestational Age

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Wake Forest University	Charlotte	North Carolina
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Tennessee	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of California at San Diego	San Diego	California

Sponsors (3)

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

Country where clinical trial is conducted

United States, 

References & Publications (4)

Ambalavanan N, Carlo WA, D'Angio CT, McDonald SA, Das A, Schendel D, Thorsen P, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with bronchopulmonary dysplasia or — View Citation

Carlo WA, McDonald SA, Tyson JE, Stoll BJ, Ehrenkranz RA, Shankaran S, Goldberg RN, Das A, Schendel D, Thorsen P, Skogstrand K, Hougaard DM, Oh W, Laptook AR, Duara S, Fanaroff AA, Donovan EF, Korones SB, Stevenson DK, Papile LA, Finer NN, O'Shea TM, Poin — View Citation

Natarajan G, Shankaran S, McDonald SA, DAS A, Stoll BJ, Higgins RD, Thorsen P, Skogstrand K, Hougaard DM, Carlo WA; NICHD neonatal research network. Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants. — View Citation

Sood BG, Madan A, Saha S, Schendel D, Thorsen P, Skogstrand K, Hougaard D, Shankaran S, Carlo W; NICHD neonatal research network. Perinatal systemic inflammatory response syndrome and retinopathy of prematurity. Pediatr Res. 2010 Apr;67(4):394-400. doi: 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pro-cytokines increased and anti-inflammatory cytokines decreased		At birth and/or up to Day 3±1
Secondary	Type and severity of CP and other neurodevelopmental handicaps, the appearance of PVL, and neonatal mortality		18-22 months corrected age
Secondary	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
Secondary	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
Secondary	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

External Links

•   NICHD Neonatal Research Network