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1 - Neonatal encephalopathy: epidemiology and overview

from Section 1 - Epidemiology, pathophysiology, and pathogenesis of fetal and neonatal brain injury

Published online by Cambridge University Press:  12 January 2010

David K. Stevenson
Stanford University School of Medicine, California
William E. Benitz
Stanford University School of Medicine, California
Philip Sunshine
Stanford University School of Medicine, California
Susan R. Hintz
Stanford University School of Medicine, California
Maurice L. Druzin
Stanford University School of Medicine, California
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Since the publication of the first edition of this text in 1989, a great deal has been written regarding the issues of neonatal asphyxia and hypoxic–ischemic encephalopathy (HIE) in term and near-term infants. These manuscripts have addressed the incidence, etiology, pathophysiology, treatment, and outcome of such patients, often relating outcomes to the development of cerebral palsy (CP) and/or mental retardation in survivors. Much of the understanding of the pathophysiology has been the result of studies carried out in laboratory animals, which have been extrapolated to the human fetus and newborn. Additional studies of complications and outcome have been population-based, comparing the injured infant to carefully selected normal controls. These studies have added a great deal to our understanding of risk factors for brain injury, and have enhanced our ability to predict and to identify patients with increasing accuracy. This has become increasingly important, as newer modalities of treatment have evolved which require more precision in the early identification of these infants so that the validity of these therapies can be ascertained. As can be seen in Chapters 39, 41, and 42, early institution of treatment becomes of paramount importance if an improved outcome is to be achieved.

While some still believe that the major injuries in these patients occur in the intrapartum period, many studies suggest otherwise, and allude to the fact that many of the problems arise antenatally, and may be exacerbated in the intrapartum period.

Publisher: Cambridge University Press
Print publication year: 2009

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Stanley, F, Blair, E, Alberman, E. Cerebral Palsies: Epidemiology and Causal Pathways. Clinics in Developmental Medicine 151. London: MacKeith Press, 2000.Google Scholar
Nelson, KB, Leviton, A. How much of neonatal encephalopathy is due to birth asphyxia?Am J Dis Child 1991; 145: 1325–31.Google ScholarPubMed
Gaffney, G, Flavell, V, Johnson, A, et al. Cerebral palsy and neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 1994; 70: F195–200.CrossRefGoogle ScholarPubMed
Perlman, JM, Risser, R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers?Pediatrics 1996; 97: 456–62.Google ScholarPubMed
Badawi, N, Kurinczuk, JJ, Keogh, JM, et al. Intrapartum risk factor for newborn encephalopathy: the Western Australian case control study. BMJ 1998; 317: 1554–8.CrossRefGoogle ScholarPubMed
Nelson, KB, Grether, JK. Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight. Am J Obstet Gynecol 1998; 179: 507–13.CrossRefGoogle ScholarPubMed
MacLennan, A. A template for defining a causal relationship between acute intrapartum events and cerebral palsy: international consensus statement International Cerebral Palsy Task Force. BMJ 1999; 319: 1054–9.CrossRefGoogle Scholar
Phelan, JP, Kim, JO. Fetal heart rate observations in the brain damaged infant. Semin Perinatol 2000; 24: 221–9.CrossRefGoogle ScholarPubMed
Hankins, GDV, Speer, M. Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy. Obstet Gynecol 2003; 102: 628–36.Google ScholarPubMed
,American College of Obstetricians and Gynecologists, American Academy of Pediatrics. Neonatal Encephalopathy and Cerebral Palsy: Defining the Pathogenesis and Pathophysiology. Washington, DC: ACOG, 2003.Google Scholar
Cowan, F, Rutherford, M, Groenendaal, F, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003; 361: 736–42.CrossRefGoogle ScholarPubMed
Shevell, MI. The “Bermuda Triangle” of neonatal neurology: cerebral palsy, neonatal encephalopathy, and intrapartum asphyxia. Semin Pediatr Neurol 2004; 11: 24–30.CrossRefGoogle ScholarPubMed
Perlman, JM. Brain injury in the term infant. Semin Perinatol 2004; 28: 415–24.CrossRefGoogle ScholarPubMed
Ferriero, DM. Neonatal brain injury. N Engl J Med 2004; 351: 1985–95.CrossRefGoogle ScholarPubMed
Bartha, AI, Foster-Barber, A, Miller, SP, et al. Neonatal encephalopathy: association of cytokines and MR spectroscopy and outcome. Pediatr Res 2004; 56: 960–6.CrossRefGoogle Scholar
Becher, JC, Bell, JE, Keeling, JW, et al. The Scottish perinatal neuropathology study: clinicopathological correlation in early neonatal deaths. Arch Dis Child Fetal Neonatal Ed 2004; 89: F399–407.CrossRefGoogle ScholarPubMed
Low, JA. Determining the contribution of asphyxia to brain damage in the neonate. J Obstet Gynaecol Res 2004; 30: 276–86.CrossRefGoogle ScholarPubMed
Pierrat, V, Haouari, N, Liska, A, et al. Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population-based study. Arch Dis Child Fetal Neonatal Ed 2005; 90: F257–61.CrossRefGoogle ScholarPubMed
Badawi, N, Felix, JF, Kurinczuk, JJ, et al. Cerebral palsy following term newborn encephalopathy: a population-based study. Dev Med Child Neurol 2005; 47: 293–8.CrossRefGoogle ScholarPubMed
Foley, ME, Alarab, M, Daly, L, et al. Term neonatal asphyxial seizures and peripartum deaths: lack of correlation with a rising cesarean delivery rate. Am J Obstet Gynecol 2005; 192: 102–8.CrossRefGoogle ScholarPubMed
Haider, BA, Bhutta, ZA. Birth asphyxia in developing countries: Current status and public health implications. Curr Probl Pediatr Adolesc Health Care 2006; 36: 178–88.CrossRefGoogle Scholar
Thorngren-Jerneck, K, Herbst, A. Perinatal factors associated with cerebral palsy in children born in Sweden. Obstet Gynecol 2006; 108: 1499–505.CrossRefGoogle ScholarPubMed
Perlman, JM. Intrapartum asphyxia and cerebral palsy: is there a link?Clin Perinatol 2006; 33: 335–53.CrossRefGoogle Scholar
Bercher, JC, Stenson, B, Lyon, A. Is intrapartum asphyxia preventable?BJOG 2007; 114: 1442–4.CrossRefGoogle Scholar
Flidel-Rimon, O, Shinwell, ES. Neonatal aspects of the relationship between intrapartum events and cerebral palsy. Clin Perinatol 2007; 34: 439–49.CrossRefGoogle ScholarPubMed
Milsom, I, Ladfors, L, Thiringer, K, et al. Influence of maternal, obstetric and fetal risk factors on the prevelance of birth asphyxia at term in a Swedish urban population. Acta Obstet Gynecol Scand 2002; 81: 909–17.CrossRefGoogle Scholar
Hogan, L, Ingemarsson, I, Thorngren-Jerneck, K, et al. How often is a low 5-min Apgar score in term infants due to asphyxia?Eur J Obstet Gynecol Reprod Biol 2007; 130: 169–75.CrossRefGoogle ScholarPubMed
Rennie, JM, Hagmann, CF, Robertson, NJ. Outcome after intrapartum hypoxic ischemia at term. Semin Fetal Neonatal Med 2007; 12: 398–407.CrossRefGoogle ScholarPubMed
Volpe, JJ. Hypoxic–ischemic encephalopathy. In Volpe, JJ, Neurology of the Newborn, 4th edn. Philadelphia, PA: Saunders, 2001: 217–394.Google Scholar
Myers, RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet Gynecol 1972; 112: 246–76.CrossRefGoogle Scholar
Mallard, EC, Williams, CE, Johnston, BM, et al. Repeated episodes of umbilical cord occlusion in fetal sheep lead to preferential damage to the striatum and sensitize the heart to further insults. Pediatr Res 1995; 37: 707–13.CrossRefGoogle ScholarPubMed
Leung, AS, Leung, EK, Paul, RH. Uterine rupture after previous cesarean delivery: maternal and fetal consequences. Am J Obstet Gynecol 1993; 169: 945–50.CrossRefGoogle ScholarPubMed
Sarnat, HB, Sarnat, MS. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neurol 1976; 33: 696–705.CrossRefGoogle ScholarPubMed
Wu, YW, Backstrand, KH, Zhao, S, et al. Declining diagnosis of birth asphyxia in California: 1991–2000. Pediatrics 2004; 114: 1584–90.CrossRefGoogle ScholarPubMed
Martin, JA, Kochanek, KD, Strobino, DM, et al. Annual summary of vital statistics: 2003. Pediatrics 2005; 115: 619–34.CrossRefGoogle ScholarPubMed
Nelson, KB, Ellenberg, JH. Obstetric complications as risk factors for cerebral palsy or seizure disorders. JAMA 1984; 251: 1843–8.CrossRefGoogle ScholarPubMed
Blair, E, Al Asedy, F, Badawi, N, et al. Is cerebral palsy associated with birth defects other than cerebral defects?Dev Med Child Neurol 2007; 49: 252–8.CrossRefGoogle ScholarPubMed
Wu, YW, Escobar, GJ, Grether, JK, et al. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA 2003; 290: 2677–84.CrossRefGoogle ScholarPubMed
Tekgul, H, Yalaz, M, Kutukculer, N, et al. Value of biochemical markers for outcome in term infants with asphyxia. Pediatr Neurol 2004; 31: 326–32.CrossRefGoogle ScholarPubMed
Apgar, VA. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 1953; 32: 260–7.CrossRefGoogle ScholarPubMed
Dijxhoorn, MJ, Visser, GHV, Touwen, BC. Apgar score, meconium and acidemia at birth in small to gestational age infants born at term, and their relationship to neonatal neurological morbidity. Br J Obstet Gynaecol 1987; 94: 873–9.CrossRefGoogle Scholar
Grant, A, O'Brien, W, Joy, MT, et al. Cerebral palsy among children born during the Dublin randomised trial of intrapartum monitoring. Lancet 1989; 2: 1233–6.CrossRefGoogle ScholarPubMed
Chauhan, SP, Hendrix, NW, Magann, EF, et al. Neonatal organ dysfunction among newborns at gestational age ≥ 34 weeks, and umbilical arterial pH < 7.00. J Matern Fetal Neonatal Med 2005; 17: 261–8.CrossRefGoogle ScholarPubMed
Goodwin, TM, Belai, I, Hernandez, P, et al. Asphyxial complications in the term newborn with severe umbilical acidemia. Am J Obstet Gynecol 1992; 167: 1506–12.CrossRefGoogle ScholarPubMed
Belai, Y, Goodwin, TM, Durand, M, et al. Umbilical arteriovenous PO2 and PCO2 differences and neonatal morbidity in term infants with severe acidosis. Am J Obstet Gynecol 1998; 178: 13–19.CrossRefGoogle ScholarPubMed
Tekgul, H, Gauvreau, K, Soul, J, et al. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics 2006; 117: 1270–80.CrossRefGoogle ScholarPubMed
Silverstein, FS, Jensen, FE. Neonatal seizures. Ann Neurol 2007; 62: 112–20.CrossRefGoogle ScholarPubMed
Miller, SP, Weiss, J, Barnwell, A, et al. Seizure-associated brain injury in term newborns with perinatal asphyxia. Neurology 2002; 58: 542–8.CrossRefGoogle ScholarPubMed
Hankins, GDV, Koen, S, Gei, F, et al. Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstet Gynecol 2002; 99: 688–91.Google ScholarPubMed
Shah, P, Riphagen, S, Beyene, J, et al. Multiorgan dysfunction in infants with post-asphyxial hypoxic–ischemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2004; 89: F152–5.CrossRefGoogle Scholar
Carter, BS, Haverkamp, AD, Merenstein, GB. The definition of acute perinatal asphyxia. Clin Perinatol 1993; 20: 287–304.CrossRefGoogle ScholarPubMed
Clancy, RR, Sladky, JT, Rorke, LB. Hypoxic–ischemic spinal cord injury following perinatal asphyxia. Ann Neurol 1989; 25: 185–9.CrossRefGoogle ScholarPubMed
Phelan, JP, Ahn, MO, Korst, L, et al. Intrapartum fetal asphyxial brain injury with absent multi-organ system dysfunction. J Maternal Fetal Med 1998; 7: 19–22.Google Scholar
Trevisanuto, D, Picco, G, Golin, R, et al. Cardiac troponin I in asphyxiated neonates. Biol Neonate 2006; 89: 190–3.CrossRefGoogle ScholarPubMed
Thorngren-Jerneck, K, Alling, C, Herbst, A, et al. S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic ischemic encephalopathy. Pediatr Res 2004; 55: 406–12.CrossRefGoogle ScholarPubMed
Phelan, JP, Kirkendall, C, Korst, LM, et al. Nucleated red blood cell and platelet counts in asphyxiated neonates sufficient to result in permanent neurological impairment. J Matern Fetal Neonatal Med 2007; 20: 377–80.CrossRefGoogle Scholar
Miller, SP, Ramaswamy, V, Michelson, D, et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr 2005; 146: 453–60.CrossRefGoogle ScholarPubMed
Himmelmann, K, Hagberg, G, Beckung, E, et al. The changing panorama of cerebral palsy in Sweden. IX. Prevalence and origin in the birth year period 1995–1998. Acta Paediatr 2005; 94: 287–94.CrossRefGoogle ScholarPubMed
Bax, M, Tydeman, C, Flodmark, O. Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study. JAMA 2006; 296: 1602–8.CrossRefGoogle ScholarPubMed
Wu, YW, Croen, , Shah, SJ, et al. Cerebral palsy in a term population: risk factors and neuroimaging findings. Pediatrics 2006; 118: 690–7.CrossRefGoogle Scholar
Himmelmann, K, Hagberg, G, Wiklund, LM, et al. Dyskinetic cerebral palsy: a population-based study of children born between 1991 and 1998. Dev Med Child Neurol 2007; 49: 246–51.CrossRefGoogle ScholarPubMed
Nelson, KB. Can we prevent cerebral palsy?N Engl J Med 2003; 349: 1765–9.CrossRefGoogle ScholarPubMed
Nelson, KB. The epidemiology of cerebral palsy in term infants. Ment Retard Dev Disabil Res Rev 2002; 8: 146–50.CrossRefGoogle ScholarPubMed
Blair, E, Watson, L. Epidemiology of cerebral palsy. Semin Fetal Neonatal Med 2006; 11: 117–25.CrossRefGoogle ScholarPubMed
Clark, SL, Hankins, GDV. Temporal and demographic trends in cerebral palsy: fact and fiction. Am J Obstet Gynecol 2003; 188: 628–33.CrossRefGoogle ScholarPubMed
Landon, MB, Hauth, JC, Leveno, KJ, et al. Maternal and perinatal outcomes associated with a trial of labor after prior cesarean delivery. N Engl J Med 2004; 351: 2581–9.CrossRefGoogle ScholarPubMed
Hankins, GDV, Clark, SM, Munn, MB. Cesarean section on request at 39 weeks: impact on shoulder dystocia, fetal trauma, neonatal encephalopathy, and intrauterine demise. Semin Perinatol 2006; 30: 276–87.CrossRefGoogle Scholar
Hagberg, B, Kyllerman, M. Epidemiology of mental retardation: a Swedish survey. Brain Dev 1983; 5: 441–9.CrossRefGoogle ScholarPubMed
Robertson, CMT. Can hypoxic–ischemic encephalopathy (HIE) associated with term birth asphyxia lead to mental disability without cerebral palsy?Can J Neurol Sci 1999; 26: S36.Google Scholar
Gonzalez, FF, Miller, SP. Does perinatal asphyxia impair cognitive function without cerebral palsy?Arch Dis Child Fetal Neonatal Ed 2006; 91: F454–9.CrossRefGoogle ScholarPubMed
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