Elevated Concentrations of Inflammation-Related Proteins in Postnatal Blood Predict Severe Developmental Delay at 2 Years of Age in Extremely Preterm Infants

被引:128
作者
O'Shea, T. Michael [1 ]
Allred, Elizabeth N. [2 ,3 ]
Kuban, Karl C. K. [4 ]
Dammann, Olaf
Paneth, Nigel [5 ]
Fichorova, Raina [2 ,6 ]
Hirtz, Deborah [7 ]
Leviton, Alan [2 ]
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, Winston Salem, NC 27157 USA
[2] Harvard Univ, Sch Med, Cambridge, MA 02138 USA
[3] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA
[4] Boston Med Ctr, Dept Pediat, Boston, MA USA
[5] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA
[6] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA
[7] NINDS, Bethesda, MD 20892 USA
关键词
WHITE-MATTER ABNORMALITIES; NECROTIZING ENTEROCOLITIS; CEREBRAL-PALSY; BRAIN-DAMAGE; CHILDREN; CHORIOAMNIONITIS; NEWBORNS; OUTCOMES; MARKERS; BIRTH;
D O I
10.1016/j.jpeds.2011.08.069
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Objective To evaluate the hypothesis that elevated levels of inflammation-related proteins in early postnatal blood predict impaired mental and motor development in extremely preterm infants. Study design We measured concentrations of 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14 from 939 infants born before 28 weeks gestation. An elevated level was defined as a concentration in the highest quartile for gestational age and day of blood collection. We identified impaired development at age 24 months using the Bayley Scales of Infant Development, Second Edition. The primary outcomes were scores on the Mental Scale or the Motor Scale of <55 (more than 3 SDs below the mean). Results For 17 of the 25 inflammation-related proteins, 1 or more statistically significant associations (P < .01) was found between an elevated blood level of the protein and a developmental impairment. Elevations on multiple days were more often associated with developmental impairment than were elevations present for only 1 day. The highest number of predictive elevations was found in day-14 blood. Conclusion In extremely preterm infants, elevated levels of inflammation-related proteins in blood collected on postnatal days 7 and 14, especially when sustained, are associated with impaired mental and motor development at age 2 years. (J Pediatr 2012; 160:395-401).
引用
收藏
页码:395 / 401
页数:7
相关论文
共 29 条
[1]  
Bayley N., 2006, Bayley scales of infant and toddler development, third edition: Administration manual, V3rd ed
[2]   Blood Protein Concentrations in the First Two Postnatal Weeks That Predict Bronchopulmonary Dysplasia Among Infants Born Before the 28th Week of Gestation [J].
Bose, Carl ;
Laughon, Matthew ;
Allred, Elizabeth N. ;
van Marter, Linda J. ;
O'Shea, T. Michael ;
Ehrenkranz, Richard A. ;
Fichorova, Raina ;
Leviton, Alan .
PEDIATRIC RESEARCH, 2011, 69 (04) :347-353
[3]   Inflammatory brain damage in preterm newborns - dry numbers, wet lab, and causal inferences [J].
Dammann, O ;
Leviton, A .
EARLY HUMAN DEVELOPMENT, 2004, 79 (01) :1-15
[4]   Brain damage in preterm newborns: Might enhancement of developmentally regulated endogenous protection open a door for prevention? [J].
Dammann, O ;
Leviton, A .
PEDIATRICS, 1999, 104 (03) :541-550
[5]   Cytokines and Perinatal Brain Damage [J].
Dammann, Olaf ;
O'Shea, T. Michael .
CLINICS IN PERINATOLOGY, 2008, 35 (04) :643-663
[6]   Interleukin-10 high producer allele and ultrasound-defined periventricular white matter abnormalities in preterm infants:: A preliminary study [J].
Doerdelmann, M. ;
Kerk, J. ;
Dressler, F. ;
Brinkhaus, M. -J. ;
Bartels, D. B. ;
Dammann, C. E. L. ;
Doerk, T. ;
Dammann, O. .
NEUROPEDIATRICS, 2006, 37 (03) :130-136
[7]   Circulating pro- and counterinflammatory cytokine levels and severity in necrotizing enterocolitis [J].
Edelson, MB ;
Bagwell, CE ;
Rozycki, HJ .
PEDIATRICS, 1999, 103 (04) :766-771
[8]   Lipopolysaccharide induces both a primary and a secondary phase of sensitization in the developing rat brain [J].
Eklind, S ;
Mallard, C ;
Arvidsson, P ;
Hagberg, H .
PEDIATRIC RESEARCH, 2005, 58 (01) :112-116
[9]   The clinical use of inflammatory markers during pregnancy [J].
Genc, Mehmet R. ;
Ford, Catherine E. .
CURRENT OPINION IN OBSTETRICS & GYNECOLOGY, 2010, 22 (02) :116-121
[10]   Inflammation at birth is associated with subnormal development in very preterm infants [J].
Hansen-Pupp, Ingrid ;
Hallin, Anne-Li ;
Hellstrom-Westas, Lena ;
Cilio, Corrado ;
Berg, Ann-Cathrine ;
Stjernqvist, Karin ;
Fellman, Vineta ;
Ley, David .
PEDIATRIC RESEARCH, 2008, 64 (02) :183-188