Clinical trial NCT01035697: Inflammatory Cytokines Associated With Perinatal Brain Injury
Official title: A Study to Determine If Inflammatory Cytokines Are Associated With Perinatal Brain Injury and Long Term Neurodevelopmental Handicap or Death
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Cerebral Palsy
Keywords: NICHD Neonatal Research Network
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Prematurity
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)
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Centers for Disease Control and Prevention
name: National Center for Research Resources (NCRR)
First posted: 2009-12-21
Enrollment: 1067
Sex: ALL
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Infants 401-1,000 grams at birth of both genders and all racial/ethnic groups.

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.

Eligibility criteria: Inclusion Criteria:

* Infants 401-1,000 grams at birth

Exclusion Criteria:

* \>72 hours of age

Primary outcomes:
measure: Pro-cytokines increased and anti-inflammatory cytokines decreased
timeFrame: At birth and/or up to Day 3±1
Secondary outcomes:
measure: Type and severity of CP and other neurodevelopmental handicaps, the appearance of PVL, and neonatal mortality
timeFrame: 18-22 months corrected age
measure: 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)
timeFrame: At birth
measure: 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)
timeFrame: Up to Day of life 21
measure: 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
timeFrame: Up to Day of life 21
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Charlotte
country: United States
facility: Wake Forest University
state: North Carolina
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: Brown University, Women & Infants Hospital of Rhode Island
name: William Oh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University, Rainbow Babies & Children's Hospital
name: Michele C. Walsh, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Ronald N. Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Barbara J. Stoll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: James A. Lemons, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Abhik Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: David K. Stevenson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar A. Carlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Neil N. Finer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Edward F. Donovan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Shahnaz Duara, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Lu-Ann Papile, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Tennessee
name: Sheldon B. Korones, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center, Houston
name: Jon E. Tyson, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Abbot R. Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University
name: T. Michael O'Shea, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Richard A. Ehrenkranz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 death in extremely low birth weight infants. Pediatrics. 2009 Apr;123(4):1132-41. doi: 10.1542/peds.2008-0526.
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. Pediatr Res. 2010 Jan;67(1):77-82. doi: 10.1203/PDR.0b013e3181c0b16c.
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: 10.1203/PDR.0b013e3181d01a36.
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, Poindexter BB, Wright LL, Ambalavanan N, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines and neurodevelopmental outcomes in extremely low birth weight infants. J Pediatr. 2011 Dec;159(6):919-25.e3. doi: 10.1016/j.jpeds.2011.05.042. Epub 2011 Jul 27.