T Michael O'Shea1, Robert M Joseph2, Karl C K Kuban3, Elizabeth N Allred4, Janice Ware5, Taryn Coster5, Raina N Fichorova6, Olaf Dammann7, Alan Leviton4. 1. Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina. 2. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts. 3. Department of Pediatrics, Boston Medical Center, Boston, Massachusetts. 4. Department of Neurology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts. 5. Department of Medicine, Boston Children's Hospital, Boston, Massachusetts. 6. Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts. 7. 1] Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts [2] Perinatal Neuroepidemiology Unit, Hannover Medical School, Hannover, Germany.
Abstract
BACKGROUND: Extremely preterm birth is associated with subsequent behavioral problems. We hypothesized that perinatal systemic inflammation, a risk factor for cerebral white matter injury and cognitive impairment, is associated with behavior problems observed at 2 y. METHODS: In a cohort of 600 children born before 28 wk gestation, we measured 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14, and identified behavior problems using parent responses to the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5) at 2 y of age. A persistent or recurrent protein elevation was defined as a concentration in the highest quartile (for gestational age and postnatal age) on at least 2 d ~1 wk apart. Behavior problems were defined by CBCL/1.5-5 subscale scores at or above the 93 rd percentile. RESULTS: A single-day elevation of intercellular adhesion molecule-3 was associated with an increased risk of an attention problem, as were persistent or recurrent elevations of myeloperoxidase, interleukin-6, tumor necrosis factor-RI, interleukin-8, intercellular adhesion molecule-3, vascular endothelial growth factor-R1, and vascular endothelial growth factor-R2. These associations persisted among infants without white matter injury and cognitive impairment. CONCLUSION: Among children born extremely prematurely, recurrent, or persistent elevations of inflammation-related proteins in blood during in the first two postnatal weeks are associated with an attention problem at age 2 y.
BACKGROUND: Extremely preterm birth is associated with subsequent behavioral problems. We hypothesized that perinatal systemic inflammation, a risk factor for cerebral white matter injury and cognitive impairment, is associated with behavior problems observed at 2 y. METHODS: In a cohort of 600 children born before 28 wk gestation, we measured 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14, and identified behavior problems using parent responses to the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5) at 2 y of age. A persistent or recurrent protein elevation was defined as a concentration in the highest quartile (for gestational age and postnatal age) on at least 2 d ~1 wk apart. Behavior problems were defined by CBCL/1.5-5 subscale scores at or above the 93 rd percentile. RESULTS: A single-day elevation of intercellular adhesion molecule-3 was associated with an increased risk of an attention problem, as were persistent or recurrent elevations of myeloperoxidase, interleukin-6, tumor necrosis factor-RI, interleukin-8, intercellular adhesion molecule-3, vascular endothelial growth factor-R1, and vascular endothelial growth factor-R2. These associations persisted among infants without white matter injury and cognitive impairment. CONCLUSION: Among children born extremely prematurely, recurrent, or persistent elevations of inflammation-related proteins in blood during in the first two postnatal weeks are associated with an attention problem at age 2 y.
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