Elevated blood levels of inflammation-related proteins are associated with an attention problem at age 24 mo in extremely preterm infants

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 similar to 1 wk apart. Behavior problems were defined by CBCL/1.5-5 subscale scores at or above the 93rd 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.