Intrauterine Infektion und das Gehirn Frühgeborener - Dimensionen der Ätiologieforschung

 

 Buy Article Permissions and Reprints

Zusammenfassung

Die Ätiologie perinataler Hirnschäden ist vielfältig und komplex. In den vergangenen Jahrzehnten sind in diesem Forschungsbereich zahlreiche neue Erkenntnisse erarbeitet worden. In diesem Artikel diskutiere ich sieben Dimensionen der Ätiologieforschung: (1) Hypoxie-Ischämie vs Inflammation; (2) „klassische” vs „remote” intrauterine Infektion; (3) fokale vs diffuse Schäden in der weißen Substanz; (4) maternale vs fetale Inflammationsreaktion; (5) klinische vs experimentelle Daten; (6) bakterielle vs virale Infektion; und (7) Früh- vs Termingeburt. Aus perinatal neuroepidemiologischer Perspektive bleibt trotz der offensichtlich komplexen Forschungslage zu hoffen, dass es zeitnah zu einem regen Austausch zwischen Geburtshelfern, Neonatologen und Neuropädiatern und der gemeinsamen Planung einer perinatal neuroprotektiven Strategie kommen möge.

Abstract

Perinatal brain damage has a diverse and complex aetiology. Over the past decades, much progress has been made in this research field. In this article, I offer a discussion of seven dimensions of aetiological perinatal brain damage research: (1) hypoxia-ischaemia vs. inflammation; (2) „classic” vs. „remote” intrauterine infection; (3) focal vs. diffuse white matter damage; (4) maternal vs. foetal inflammatory response; (5) clinical vs. experimental data; (6) bacterial vs. viral infection; and (7) preterm vs. term delivery. Despite these complexities, it is hoped that obstetricians, neonatologists, and neuropaediatricians will agree on a perinatal neuroprotective strategy in the near future.

Literatur

• 1 Banker B Q, Larroche J C. Periventricular leukomalacia of infancy.  Arch Neurol. 1962;  7 386-410
  CrossrefPubMedGoogle Scholar
• 2 Leviton A, Gilles F H. An epidemiologic study of perinatal telencephalic leucoencephalopathy in an autopsy population.  J Neurol Sci. 1973;  18(1) 53-66
  CrossrefPubMedGoogle Scholar
• 3 Leviton A, Gilles F, Neff R, Yaney P. Multivariate analysis of risk of perinatal telencephalic leucoencephalopathy.  Am J Epidemiol. 1976;  104(6) 621-6
  PubMedGoogle Scholar
• 4 Gilles F H, Murphy S F. Perinatal telencephalic leucoencephalopathy.  J Neurol Neurosurg Psychiatry. 1969;  32 404-13
  PubMedGoogle Scholar
• 5 Levene M I, Wigglesworth J S, Dubowitz V. Cerebral structure and intraventricular haemorrhage in the neonate: a real-time ultrasound study.  Arch Dis Child. 1981;  56(6) 416-24
  PubMedGoogle Scholar
• 6 De Vries L S, Groenendaal F. Neuroimaging in the preterm infant.  Ment Retard Dev Disabil Res Rev. 2002;  8 273-80
  CrossrefPubMedGoogle Scholar
• 7 O'Shea T M, Counsell S J, Bartels D B, Dammann O. Magnetic resonance and ultrasound brain imaging in preterm newborns.  Early Hum Dev. 2005;  81(3) 263-71
  CrossrefPubMedGoogle Scholar
• 8 Rees S, Inder T. Fetal and neonatal origins of altered brain development.  Early Hum Dev. 2005;  81(9) 753-61
  CrossrefPubMedGoogle Scholar
• 9 Levine S. Anoxic-ischemic encephalopathy in rats.  Am J Pathol. 1960;  36 1-17
  PubMedGoogle Scholar
• 10 Levy D E, Brierley J B, Silverman D G, Plum F. Brief hypoxia-ischemia initially damages cerebral neurons.  Arch Neurol. 1975;  32(7) 450-6
  PubMedGoogle Scholar
• 11 Rice J Ed, Vannucci R C, Brierley J B. The influence of immaturity on hypoxic-ischemic brain damage in the rat.  Ann Neurol. 1981;  9(2) 131-41
  CrossrefPubMedGoogle Scholar
• 12 Hagberg H, Bona E, Gilland E, Puka-Sundvall M. Hypoxia-ischaemia model in the 7-day-old rat: possibilities and shortcomings.  Acta Paediatr Suppl. 1997;  422 85-8
  PubMedGoogle Scholar
• 13 Fellman V, Raivio K O. Reperfusion injury as the mechanism of brain damage after perinatal asphyxia.  Pediatr Res. 1997;  41 599-606
  PubMedGoogle Scholar
• 14 Rothman K J. Causes.  Am J Epidemiol. 1976;  104 87-92
  PubMedGoogle Scholar
• 15 Dammann O, Leviton A. Perinatal brain damage causation (submitted). 
  Google Scholar
• 16 Leviton A. Single-cause attribution.  Dev Med Child Neurol. 1987;  29(6) 805-7
  PubMedGoogle Scholar
• 17 Volpe J J. Brain injury in the premature infant-current concepts of pathogenesis and prevention.  Biology of the Neonate. 1992;  62(4) 231-42
  PubMedGoogle Scholar
• 18 De Reuck J, Chattha A S, Richardson E PJ. Pathogenesis and evolution of periventricular leukomalacia in infancy.  Arch Neurol. 1972;  27 229-36
  PubMedGoogle Scholar
• 19 Lou H C, Lassen N A, Friis-Hansen B. Impaired autoregulation of cerebral blood flow in the distressed newborn infant.  J Pediatr. 1979;  94 118-21
  PubMedGoogle Scholar
• 20 Kuban K C, Gilles F H. Human telencephalic angiogenesis.  Ann Neurol. 1985;  17(6) 539-48
  CrossrefPubMedGoogle Scholar
• 21 Nelson M D, Jr., Gonzalez-Gomez I, Gilles F H. Dyke Award. The search for human telencephalic ventriculofugal arteries.  AJNR Am J Neuroradiol. 1991;  12(2) 215-22
  PubMedGoogle Scholar
• 22 Gilles F H. Telencephalic angiogenesis: a review.  Dev Med Child Neurol Suppl. 2001;  86 3-5
  PubMedGoogle Scholar
• 23 Tyszczuk L, Meek J, Elwell C, Wyatt J S. Cerebral blood flow is independent of mean arterial blood pressure in preterm infants undergoing intensive care.  Pediatrics. 1998;  102 337-41
  CrossrefPubMedGoogle Scholar
• 24 Okumura A, Toyota N, Hayakawa F. et al . Cerebral hemodynamics during early neonatal period in preterm infants with periventricular leukomalacia.  Brain Dev. 2002;  24(7) 693-7
  CrossrefPubMedGoogle Scholar
• 25 Dammann O, Leviton A. Brain damage in preterm newborns: might enhancement of developmentally-regulated endogenous protection open a door for prevention?.  Pediatrics. 1999;  104(3) 541-50
  CrossrefPubMedGoogle Scholar
• 26 Leviton A. Preterm birth and cerebral palsy: is tumor necrosis factor the missing link?.  Dev Med Child Neurol. 1993;  35(6) 553-8
  PubMedGoogle Scholar
• 27 Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn.  Pediatr Res. 1997;  42(1) 1-8
  CrossrefPubMedGoogle Scholar
• 28 Dammann O, Leviton A. Inflammatory brain damage in preterm newborns - dry numbers, wet lab, and causal inference.  Early Hum Dev. 2004;  79(1) 1-15
  CrossrefPubMedGoogle Scholar
• 29 Dammann O, Leviton A. Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant.  Semin Pediatr Neurol. 1998;  5(3) 190-201
  PubMedGoogle Scholar
• 30 Counsell S J, Rutherford M A, Cowan F M, Edwards A D. Magnetic resonance imaging of preterm brain injury.  Arch Dis Child Fetal Neonatal Ed. 2003;  88(4) F269-74
  CrossrefPubMedGoogle Scholar
• 31 Leviton A, Paneth N. White matter damage in preterm newborns - an epidemiologic perspective.  Early Hum Dev. 1990;  24(1) 1-22
  CrossrefPubMedGoogle Scholar
• 32 Papile L A, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm.  J Pediatr. 1978;  92(4) 529-34
  CrossrefPubMedGoogle Scholar
• 33 Paneth N. Classifying brain damage in preterms.  J Pediatr. 1999;  134(5) 527-9
  PubMedGoogle Scholar
• 34 Deeg K H, Staudt F, von Rohden L. Klassifikation der intrakraniellen Blutungen des Frühgeborenen.  Ultraschall Med. 1999;  20(4) 165-70
  Article in Thieme ConnectPubMedGoogle Scholar
• 35 Kuban K C, Allred E N, Dammann O ,. et al . Topography of cerebral white-matter disease of prematurity studied prospectively in 1607 very-low-birthweight infants.  J Child Neurol. 2001;  16(6) 401-8
  PubMedGoogle Scholar
• 36 Maalouf E F, Duggan P J, Counsell S J,. et al . Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants.  Pediatrics. 2001;  107(4) 719-27
  CrossrefPubMedGoogle Scholar
• 37 Counsell S J, Allsop J M, Harrison M C. et al . Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality.  Pediatrics. 2003;  112(1 Pt 1) 1-7
  CrossrefPubMedGoogle Scholar
• 38 Duggan P J, Maalouf E F, Watts T L,. et al . Intrauterine T-cell activation and increased proinflammatory cytokine concentrations in preterm infants with cerebral lesions.  Lancet. 2001;  358(9294) 1699-700
  CrossrefPubMedGoogle Scholar
• 39 Romero R, Mazor M. Infection and preterm labor.  Clin Obstet Gynecol. 1988;  31(3) 553-84
  CrossrefPubMedGoogle Scholar
• 40 Redline R W, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns.  Pediatr Dev Pathol. 2003;  6(5) 435-48
  CrossrefPubMedGoogle Scholar
• 41 Romero R, Gomez R, Ghezzi F. et al . A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition.  Am J Obstet Gynecol. 1998;  179(1) 186-93
  CrossrefPubMedGoogle Scholar
• 42 Wu Y W. Systematic review of chorioamnionitis and cerebral palsy.  Mental Retardation and Developmental Disabilities Research Reviews. 2002;  8 25-9
  CrossrefPubMedGoogle Scholar
• 43 Leviton A, Paneth N, Reuss M L,. et al . Maternal infection, fetal inflammatory response, and brain damage in very low birthweight infants.  Pediatric Research. 1999;  46(5) 566-75
  CrossrefPubMedGoogle Scholar
• 44 Redline R W, Wilson-Costello D, Borawski E, Fanaroff A A, Hack M. Placental lesions associated with neurologic impairment and cerebral palsy in very-low-birth-weight infants.  Arch Pathol Lab Med. 1998;  122 1091-8
  PubMedGoogle Scholar
• 45 Yoon B H, Romero R, Park J S. et al . Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years.  Am J Obstet Gynecol. 2000;  182 675-81
  CrossrefPubMedGoogle Scholar
• 46 Hagberg H, Peebles D, Mallard C. Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults.  Ment Retard Dev Disabil Res Rev. 2002;  8(1) 30-8
  CrossrefPubMedGoogle Scholar
• 47 Hagberg H, Dammann O, Mallard C, Leviton A. Preconditioning and the developing brain.  Seminars in Perinatology. 2004;  28 389-95
  CrossrefPubMedGoogle Scholar
• 48 Eklind S, Mallard C, Leverin A L. et al . Bacterial endotoxin sensitizes the immature brain to hypoxic-ischaemic injury.  Eur J Neurosci. 2001;  13(6) 1101-6
  PubMedGoogle Scholar
• 49 Goldenberg R L, Hauth J C, Andrews W W. Intrauterine infection and preterm delivery.  N Engl J Med. 2000;  342(20) 1500-7
  CrossrefPubMedGoogle Scholar
• 50 Romero R, Espinoza J, Chaiworapongsa T, Kalache K. Infection and prematurity and the role of preventive strategies.  Semin Neonatol. 2002;  7(4) 259-74
  PubMedGoogle Scholar
• 51 Brown A S, Begg M D, Gravenstein S. et al . Serologic evidence of prenatal influenza in the etiology of schizophrenia.  Arch Gen Psychiatry. 2004;  61(8) 774-80
  CrossrefPubMedGoogle Scholar
• 52 Dammann O, Leviton A. Is some white matter damage in preterm neonates induced by a human pestivirus?.  Arch Dis Child Fetal Neonatal Ed. 1998;  78(3) F230-1
  PubMedGoogle Scholar
• 53 Dammann O, Hori A, Szentiks C, Hewicker-Trautwein M. Absence of pestivirus antigen in brains with white matter damage. Dev Med Child Neurol (in press)
  Google Scholar
• 54 Grether J K, Nelson K B. Maternal infection and cerebral palsy in infants of normal birth weight.  JAMA. 1997;  278(3) 207-11
  CrossrefPubMedGoogle Scholar
• 55 Nelson K B, Dambrosia J M, Grether J K, Phillips T M. Neonatal cytokines and coagulation factors in children with cerebral palsy.  Ann Neurol. 1998;  44(4) 665-75
  Google Scholar
• 56 Shalak L F, Laptook A R, Jafri H S, Ramilo O, Perlman J M. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants.  Pediatrics. 2002;  110(4) 673-80
  CrossrefPubMedGoogle Scholar
• 57 Wu Y W, Escobar G J, Grether J K, Croen L A, Greene J D, Newman T B. Chorioamnionitis and cerebral palsy in term and near-term infants.  Jama. 2003;  290(20) 2677-84
  CrossrefPubMedGoogle Scholar
• 58 Bartha A I, Foster-Barber A, Miller S P. et al . Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome.  Pediatr Res. 2004;  56(6) 960-6
  Google Scholar
• 59 Willoughby R E, Jr., Nelson K B. Chorioamnionitis and brain injury.  Clin Perinatol. 2002;  29(4) 603-21
  PubMedGoogle Scholar
• 60 Grether J K, Nelson K B, Walsh E, Willoughby R E, Redline R W. Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants.  Arch Pediatr Adolesc Med. 2003;  157(1) 26-32
  CrossrefPubMedGoogle Scholar
• 61 Nelson K B, Grether J K, Dambrosia J M,. et al . Neonatal cytokines and cerebral palsy in very preterm infants.  Pediatr Res. 2003;  53(4) 600-7
  CrossrefPubMedGoogle Scholar
• 62 Hagberg H. No correlation between cerebral palsy and cytokines in postnatal blood of preterms.  Pediatr Res. 2003;  53(4) 544-5
  CrossrefPubMedGoogle Scholar
• 63 Mittendorf R, Dammann O, Lee K S. Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor.  J Perinatol. 2006;  26(1) 57-63
  CrossrefPubMedGoogle Scholar
• 64 Crowther C A, Hiller J E, Doyle L W, Haslam R R. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial.  Jama. 2003;  290(20) 2669-76
  CrossrefPubMedGoogle Scholar
• 65 Nelson K B, Grether J K. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants?.  Pediatrics. 1995;  95(2) 263-9
  PubMedGoogle Scholar
• 66 Leviton A, Paneth N, Susser M. et al . Maternal receipt of magnesium sulfate does not seem to reduce the risk of neonatal white matter damage.  Pediatrics. 1997;  99(4) E2
  PubMedGoogle Scholar
• 67 Dammann O, Dammann C EL, Leviton A. Magnesiumsulfat und Zerebralparese bei Frühgeborenen.  Geburtsh Frauenheilk. 1997;  57 670-4
  PubMedGoogle Scholar

Prof. Olaf Dammann

Perinatale Infektionsepidemiologie

OE6415 Abteilung für Gynäkologie und
Geburtshilfe

Abteilung für Kinderheilkunde, Pädiatrische Pneumologie und Neonatologie

Medizinische Hochschule Hannover

Carl-Neuberg-Str. 1

K24-C1, Raum 402

30625 Hannover

Phone: 0511/532-6825

Fax: 0511/532-6827

Email: dammann.olaf@mh-hannover.de