Subscribe to RSS
DOI: 10.1055/s-2006-924554
Georg Thieme Verlag KG Stuttgart · New York
Interleukin-10 High Producer Allele and Ultrasound-Defined Periventricular White Matter Abnormalities in Preterm Infants: A Preliminary Study
Publication History
Received: February 26, 2006
Accepted after Revision: August 8, 2006
Publication Date:
11 September 2006 (online)
![](https://www.thieme-connect.de/media/neuropediatrics/200603/lookinside/thumbnails/10.1055-s-2006-924554-1.jpg)
Abstract
Objectives: Inflammation plays a role in prematurity, in neonatal disorders of the brain, lung, eye, bowel, and in developmental disability among preterm infants. We initiated a pilot study in preterm children to determine the prevalence of single nucleotide polymorphisms (SNPs) in the infection/inflammation-associated genes for interleukin (IL)-10 (- 1082 G/A), IL-1β (+ 3953 C/T), tumor necrosis factor (TNF)-α (- 308 G/A) and toll-like receptor 4 (TLR-4) (Asp299Gly) and whether these SNPs affect the risk for neonatal disorders. Study Design: We genotyped 73 children ≥ 2 years of age whose gestational age at birth was < 32 weeks, and explored the associations between genotypes and neonatal disorders and developmental status at age 2 + years. Results: Infants homozygous for the high IL-10 producer - 1082 G‐allele (n = 15) were significantly less likely to develop ultrasound-defined periventricular echodensities. A non-significant, but prominent, risk reduction for bronchopulmonary dysplasia, high-grade retinopathy, cerebral palsy, and developmental delay at age 2 + years was present. Polymorphisms in the IL-1β, TNF-α, and TLR-4 genes were too infrequent in our pilot sample to allow for reasonable analysis. Conclusion: Infants homozygous for the IL-10 high producer - 1082 G allele might be at reduced risk for prematurity-associated disorders.
Key words
Infant - premature - brain - cytokine - polymorphism
References
- 1 An H, Nishimaki S, Ohyama M, Haruki A, Naruto T, Kobayashi N. et al . Interleukin-6, interleukin-8, and soluble tumor necrosis factor receptor-I in the cord blood as predictors of chronic lung disease in premature infants. Am J Obstet Gynecol. 2004; 191 1649-1654
- 2 Arbour N C, Lorenz E, Schutte B C, Zabner J, Kline J N, Jones M. et al . TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000; 25 187-191
- 3 Bancalari E, Claure N, Sosenko I RS. Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol. 2003; 8 63-71
- 4 Bos A F, Martijn A, Okken A, Prechtl H F. Quality of general movements in preterm infants with transient periventricular echodensities. Acta Paediatrica. 1998; 87 328-335
- 5 Chen C C, Huang C B, Chung M Y, Huang L T, Yang C Y. Periventricular echogenicity is related to delayed neurodevelopment of preterm infants. Am J Perinatol. 2004; 2 483-489
- 6 Dammann O, Leviton A. Duration of transient hyperechoic images of white matter in very-low-birth weight infants: a proposed classification. Dev Med Child Neurol. 1997; 39 2-5
- 7 Dammann O, Leviton A. Inflammatory brain damage in preterm newborns - dry numbers, wet lab, and causal inference. Early Hum Dev. 2004; 79 1-15
- 8 De Vries L S, Van Haastert I L, Rademaker K J, Koopman C, Groenendaal F. Ultrasound abnormalities preceding cerebral palsy in high-risk preterm infants. J Pediatr. 2004; 144 815-820
- 9 Dommergues M A, Patkai J, Renauld J C, Evrard P, Gressens P. Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium. Ann Neurol. 2000; 47 54-63
- 10 Erickson S J, Grauaug A, Gurrin L, Swaminathan M. Hypocarbia in the ventilated preterm infant and its effect on intraventricular haemorrhage and bronchopulmonary dysplasia. J Paediatr Child Health. 2002; 38 560-562
- 11 Fazzi E, Orcesi S, Caffi L, Ometto A, Rondini G, Telesca C. et al . Neurodevelopmental outcome at 5 - 7 years in preterm infants with periventricular leukomalacia. Neuropediatrics. 1994; 25 134-139
- 12 Frankenburg W K, Dodds J, Archer P, Shapiro H, Bresnick B. The Denver II: a major revision and restandardization of the Denver developmental screening test. Pediatrics. 1992; 89 91-97
- 13 Froen J F, Munkeby B H, Stray-Pedersen B, Saugstad O D. Interleukin-10 reverses acute detrimental effects of endotoxin-induced inflammation on perinatal cerebral hypoxia-ischemia. Brain Res. 2002; 942 87-94
- 14 Goepfert A R, Andrews W W, Carlo W, Ramsey P S, Cliver S P, Goldenberg R L. et al . Umbilical cord plasma interleukin-6 concentrations in preterm infants and risk of neonatal morbidity. Am J Obstet Gynecol. 2004; 191 1375-1381
- 15 Goldenberg R L, Hauth J C, Andrews W W. Intrauterine infection and preterm delivery. N Engl J Med. 2000; 342 1500-1507
- 16 Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005; 6 2-8
- 17 Gopel W, Kattner E, Seidenberg J, Kohlmann T, Segerer H, Moller J. The effect of the Val34Leu polymorphism in the factor XIII gene in infants with a birth weight below 1500 g. J Pediatr. 2002; 140 688-692
- 18 Hansen B M, Hoff B, Uldall P, Greisen G, Kamper J, Djernes B. et al . Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?. Acta Paediatr. 2004; 93 185-189
- 19 Harding D, Brull D, Humphries S E, Whitelaw A, Montgomery H, Marlow N. Variation in the interleukin-6 gene is associated with impaired cognitive development in children born prematurely: a preliminary study. Pediatr Res. 2005; 58 117-120
- 20 ICROP . An international classification of retinopathy of prematurity. Pediatrics. 1984; 74 127-133
- 21 Inder T E, Anderson N J, Spencer C, Wells S, Volpe J J. White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term. AJNR Am J Neuroradiol. 2003; 24 805-809
- 22 Jobe A H. Antenatal factors and the development of bronchopulmonary dysplasia. Semin Neonatol. 2003; 8 9-17
- 23 Jones C A, Cayabyab R G, Kwong K Y, Stotts C, Wong B, Hamdan H. et al . Undetectable interleukin (IL)-10 and persistent IL‐8 expression early in hyaline membrane disease: a possible developmental basis for the predisposition to chronic lung inflammation in preterm newborns. Pediatr Res. 1996; 39 966-975
- 24 Kerk J, Dordelmann M, Bartels D B, Brinkhaus M J, Dammann C EL, Dork T. et al . Multiplex measurement of cytokine/receptor gene polymorphisms and interaction between interleukin 10 (- 1082) genotype and chorioamnionitis in extreme preterm delivery. J Soc Gynecol Investig. 2006; 13 350
- 25 Kreuzer C, Urlesberger B, Maurer U, Muller W. (Transient periventricular echodensities [TPE] in preterm infants under 1500 gramms: an analysis of the outcome of the last 10 years). Klin Padiatr. 2003; 215 252-256
- 26 Kuban K C, Leviton A. Cerebral palsy. N Engl J Med. 1994; 330 188-195
- 27 Kwong K Y, Jones C A, Cayabyab R, Lecart C, Khuu N, Rhandhawa I. et al . The effects of IL‐10 on proinflammatory cytokine expression (IL-1beta and IL‐8) in hyaline membrane disease (HMD). Clin Immunol Immunopathol. 1998; 88 105-113
- 28 Lai F F, Tsou K Y. Transient periventricular echodensities and developmental outcome in preterm infants. Pediatr Neurol. 1999; 21 797-801
- 29 Leviton A, Paneth N, Reuss M L, Susser M, Allred E N, Dammann O. et al . Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Pediatric Research. 1999; 46 566-575
- 30 Lyng K, Munkeby B H, Saugstad O D, Stray-Pedersen B, Froen J F. Effect of interleukin-10 on newborn piglet brain following hypoxia-ischemia and endotoxin-induced inflammation. Biol Neonate. 2005; 87 207-216
- 31 Maalouf E F, Duggan P J, Counsell S J, Rutherford M A, Cowan F, Azzopardi D. et al . Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants. Pediatrics. 2001; 107 719-727
- 32 Mesples B, Plaisant F, Gressens P. Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice. Brain Res Dev Brain Res. 2003; 141 25-32
- 33 Moore K W, de Waal Malefyt R, Coffman R L, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Ann Rev Immunol. 2001; 19 683-765
- 34 Mormann M, Rieth H, Hua T D, Assohou C, Roupelieva M, Hu S L. et al . Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. Genes Immun. 2004; 5 246-255
- 35 Nelson K B, Dambrosia J M, Iovannisci D M, Cheng S, Grether J K, Lammer E. Genetic polymorphisms and cerebral palsy in very preterm infants. Pediatr Res. 2005; 57 494-499
- 36 Ogunyemi D, Murillo M, Jackson U, Hunter N, Alperson B. The relationship between placental histopathology findings and perinatal outcome in preterm infants. J Matern Fetal Neonatal Med. 2003; 13 102-109
- 37 O'Shea T M, Kothadia J M, Roberts D D, Dillard R G. Perinatal events and the risk of intraparenchymal echodensity in very-low-birth weight neonates. Paediatr Perinat Epidemiol. 1998; 12 408-421
- 38 Pinsky M R, Vincent J L, Deviere J, Alegre M, Kahn R J, Dupont E. Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest. 1993; 103 565-575
- 39 Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J. A TaqI polymorphism in the human interleukin-1 beta (IL‐1 beta) gene correlates with IL‐1 beta secretion in vitro. Eur J Clin Invest. 1992; 22 396-402
- 40 Resch B, Vollaard E, Maurer U, Haas J, Rosegger H, Muller W. Risk factors and determinants of neurodevelopmental outcome in cystic periventricular leucomalacia. Eur J Pediatr. 2000; 159 663-670
- 41 Rodts-Palenik S, Wyatt-Ashmead J, Pang Y, Thigpen B, Cai Z, Rhodes P. et al . Maternal infection-induced white matter injury is reduced by treatment with interleukin-10. Am J Obstet Gynecol. 2004; 191 1387-1392
- 42 Sonnander K. Early identification of children with developmental disabilities. Acta Paediatr Suppl. 2000; 89 17-23
- 43 Speer C P. Pre- and postnatal inflammatory mechanisms in chronic lung disease of preterm infants. Paediatr Respir Rev. 2004; 5 (Suppl A) S241-S244
- 44 Stoelhorst G M, Rijken M, Martens S E, van Zwieten P H, Feenstra J, Zwinderman A H. et al . Developmental outcome at 18 and 24 months of age in very preterm children: a cohort study from 1996 to 1997. Early Hum Dev. 2003; 72 83-95
- 45 Turner D M, Williams D M, Sankaran D, Lazarus M, Sinnott P J, Hutchinson I V. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997; 24 1-8
- 46 Vohr B R, Wright L L, Dusick A M, Perritt R, Poole W K, Tyson J E. et al . Center differences and outcomes of extremely low birth weight infants. Pediatrics. 2004; 113 781-789
- 47 Voigt M, Schneider K T, Jahrig K. [Analysis of a 1992 birth sample in Germany. 1: New percentile values of the body weight of newborn infants]. Geburtsh Frauenheilkd. 1996; 56 550-558
- 48 Wilson A G, Symons J A, McDowell T L, McDevitt H O, Duff G W. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997; 94 3195-3199
- 49 Wu Y W. Systematic review of chorioamnionitis and cerebral palsy. Mental Retardation and Developmental Disabilities Research Reviews. 2002; 8 25-29
- 50 Yanamandra K, Boggs P, Loggins J, Baier R J. Interleukin-10 - 1082 G/A polymorphism and risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants. Pediatr Pulmonol. 2005; 39 426-432
1 These two authors contributed equally
MD Michael Dördelmann
Department of Pediatric Pneumology and Neonatology
OE 6710
Hannover Medical School
30623 Hannover
Germany
Email: doerdelmann.michael@mh-hannover.de