Viewpoint on the Brain Disorder in Autism

Viewpoint on the Brain Disorder in Autism

  (based on a review of research papers in the medical literature)

Viewpoint on the brain disorder(2003) (View in 2000)

The auditory system The inferior colliculus Hemoglobin & the brain

Concepts of autism Autism spectrum Social responsibility

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Conrad Simon Memorial Research Initiative
Posted:  December 14, 2003
© Copyright 2003
Eileen Nicole Simon
Introduction | I. Brain damage at birth | II. Auditory system | III. Language
IV.  Childhood handicaps | V. Brainstem Damage | VI. References | Summaries
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Topics (section links):

Introduction

I. BRAIN DAMAGE AT BIRTH
1 - Asphyxia at Birth
2 - Hypoxic Birth
3 - Asphyxia Versus Hypoxia
4 - Human Conditions
5 - Stages of Asphyxia
6 - The Umbilical Cord Lifeline
7 - Developmental Delay
8 - Poor Manual Dexterity
9 - Progressive Degeneration
10 - Autism and Complications at Birth
11 - Mercury, and Other Toxic Factors

II. THE AUDITORY SYSTEM
12 - Metabolic Rank Order
13 - The Auditory System
14 - Auditory Dysfunction

III. LANGUAGE
15 - Language by Ear
16 - Verbal Auditory Agnosia
17 - Echolalic Speech
18 - Echolalic Speech is Pragmatic

IV. CHILDHOOD HANDICAPS
19 - Auditory and Motor Handicaps
20 - Increased Incidence of Autism
21 - Fetal to Postnatal Adaptation
22 - Forgotten History
23 - Worth Remembering
24 - Hemoglobin
25 - Infant Anemia
26 - Autism in Twins
27 - Male-Female Differences

V. BRAINSTEM DAMAGE
28 - Variable Vulnerability
29 - Patterns of Damage
30 - Wernicke's Encephalopathy
31 - Suffocation at the Molecular Level
32 - Thiamine Deficiency
33 - Brain-Gut Relationship

VI. REFERENCES
34 - Bibliography
35 - Autism and Complications at Birth
36 - Umbilical Cord Clamping

Summaries

[Site Links]


Overview (References):

The following references are grouped according to a wide range of subjects. My first priority was to understand brain mechanisms underlying language and how children learn to speak. Conrad was born pale and flaccid and did not cry for several minutes after birth. Nevertheless his development was normal, and he began speaking early – his older brother was his best friend and teacher! Conrad's nursery school teacher advised us to have him seen by a psychiatrist because of his echolalic manner of speaking, and the diagnosis was autism. No child fit Kanner's description of autism better than Conrad.

William Windle's article describing damage of the inferior colliculi by asphyxia at birth was the starting point, in 1969, for my personal quest to understand mechanisms by which language circuits in the brain can be damaged. The brain, not genes on chromosomes, is the most reasonable place to look for the cause of autism. The brain and how it is affected by all etiologies of autism should be the focus of research on autism.


. . . .

[Top]

VI. REFERENCES

34 - Bibliography

Asphyxia and Hypoxia at Birth
  1. Windle, W. F. (1969). Brain damage by asphyxia at birth. Scientific American, 221(#4), 76-84.
  2. Myers RE (1972) Two patterns of perinatal brain damage and their conditions of occurrence. American Journal of Obstetrics and Gynecology 112:246-276.

    Cerebral Blood Flow
  3. Landau WM, Freygang WH, Rowland LP, Sokoloff L, Kety SS (1955) The local circulation of the living brain; values in the unanesthetized and anesthetized cat. Transactions of the American Neurological Association 80:125-129.
  4. Kety SS (1962) Regional neurochemistry and its application to brain function. In French, JD, ed, Frontiers in Brain Research. New York: Columbia University Press, pp 97-120.
  5. Reivich M, Jehle J, Sokoloff L, Kety SS (1969) Measurement of regional cerebral blood flow with antipyrine-14C in awake cats. Journal Of Applied Physiology 27:296-300.
  6. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo-14-C-antipyrine. American Journal of Physiology, 234, H59-H66.

    Measures of Aerobic Metabolism (Deoxyglucose Uptake)
  7. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. Journal of Neurochemistry 28:897-916.
  8. Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Gallagher B, Hoffman E, Alavi A, Sokoloff L (1977) Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-d-glucose. Acta Neurologica Scandinavica. Supplementum 64:190-1

    Correlates of High Deoxyglucose Uptake
  9. Gross PM, Sposito NM, Pettersen SE, Panton DG, Fenstermacher JD. Topography of capillary density, glucose metabolism, and microvascular function within the rat inferior colliculus. J Cereb Blood Flow Metab. 1987 Apr;7(2):154-60.
  10. Rahner-Welsch S, Vogel J, Kuschinsky, W (1995) Regional congruence and divergence of glucose transporters (GLUT1) and capillaries in rat brains. Journal of Cerebral Blood Flow and Metabolism 15:681-686.
  11. Zeller K, Rahner-Welsch S, Kuschinsky W (1997) Distribution of Glut1 glucose transporters in different brain structures compared to glucose utilization and capillary density of adult rat brains. Journal of Cerebral Blood Flow and Metabolism 17:204-209.
  12. Calingasan NY, Baker H, Sheu KF, Gibson GE (1994) Distribution of the alpha-ketoglutarate dehydrogenase complex in rat brain. Journal Of Comparative Neurology 346:461-479.
  13. Hovda DA, Chugani HT, Villablanca JR, Badie B, Sutton RL (1992) Maturation of cerebral oxidative metabolism in the cat: a cytochrome oxidase histochemistry study. Journal of Cerebral Blood Flow and Metabolism 12:1039-1048
  14. Gonzalez-Lima F, Valla J, Matos-Collazo S (1997) Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients. Brain Research 752:117-126.

    Research on Blood Flow and Glucose Uptake
  15. Sokoloff L (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. Journal of Cerebral Blood Flow and Metabolism 1:7-36.
  16. Hakim AM and Pappius HM (1981) The effect of thiamine deficiency on local cerebral glucose utilization. Annals of Neurology 9:334-339.
  17. Vingan RD, Dow-Edwards ML, Riley EP (1986) Cerebral metabolic alterations in rats following prenatal alcohol exposure: a deoxyglucose study. Alcoholism, Clinical and Experimental Research 10:22-26.
  18. Bertoni JM and Sprenkle PM (1989) Lead acutely reduces glucose utilization in the rat brain especially in higher auditory centers. Neurotoxicology 9:235-242.
  19. Nehlig A, Pereira de Vasconcelos A, Boyet S (1989) Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C]iodoantipyrine technique in freely moving rats. Journal of Cerebral Blood Flow and Metabolism 9:579-588.
  20. Dow-Edwards DL, Freed LA, Fico TA (1990) Structural and functional effects of prenatal cocaine exposure in adult rat brain. Brain Research Developmental Brain Research 57:263-268.
  21. Kusumoto, M., Arai, H., Mori, K., & Sato, K. (1995). Resistance to cerebral ischemia in developing gerbils. Journal of Cerebral Blood Flow and Metabolism, 15, 886-891.
  22. Chugani HT, Hovda DA, Villablanca JR, Phelps ME, Xu, W-F (1991) Metabolic maturation of the brain: a study of local cerebral glucose utilization in the developing cat. Journal of Cerebral Blood Flow and Metabolism 11:35-47.
  23. Burchfield DJ, Abrams RM (1993). Cocaine depresses cerebral glucose utilization in fetal sheep. Developmental Brain Research 73:283-288.
  24. Grünwald F, Schröck H, Biersack HJ, Kuschinsky W (1993) Changes in local cerebral glucose utilization in the awake rat during acute and chronic administration of ethanol. Journal of Nuclear Medicine 34:793-798.
  25. Antonelli PJ, Gerhardt KJ, Abrams RM, Huang X. Fetal central auditory system metabolic response to cochlear implant stimulation. Otolaryngol Head Neck Surg. 2002 Sep;127(3):131-7.

    Early Research of Windle and Coworkers
  26. Ranck JB, Windle WF (1959). Brain damage in the monkey, Macaca mulatta, by asphyxia neonatorum. Experimental Neurology 1: 130-154.
  27. Jacobson HN & Windle WF (1960) Responses of foetal and new-born monkeys to asphyxia. The Journal of Physiology (London) 153:447-456.

    Circulatory Arrest in Adult Monkeyts
  28. Miller JR, Myers RE (1970) Neurological effects of systemic circulatory arrest in the monkey. Neurology 20:715-724.
  29. Miller JR, Myers RE (1972) Neuropathology of systemic circulatory arrest in adult monkeys. Neurology 22:888-904.

    Developmental Degeneration Following Asphyxia
  30. Faro MD & Windle WF (1969) Transneuronal degeneration in brains of monkeys asphyxiated at birth. Experimental Neurology 24:38-53.

    Biochemistry of Respiration
  31. Bohr C, Hasselbalch K, Krogh A (1904) Ueber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensaurespannung des Blutes auf dessen Sauerstoffbindung ubt. Skandinavishes Archiv fur Physiologie 16:402-412.
  32. Tigerstedt R (1911) Christian Bohr: Ein Nachruf. Skandinavishes Archiv fur Physiologie 25:v-xviii.
  33. Edsall JT (1980) Hemoglobin and the origins of the concept of allosterism. Federation Proceedings 39:226-35
  34. Dickerson RE, Geis I (1983) Hemoglobin: structure, function, evolution, and pathology. Menlo Park, California: Benjamin Cummings.
  35. Schaffartzik W, Spies C (1996) Christian Bohr -- ein vergessener Wegbereiter der Atemphysiologie. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 31:239-243
  36. Simon N (1998) Hemoglobin and the brain: a piece of the autism puzzle? Journal of Autism and Developmental Disorders 28:579-80.

    Brainstem Lesions in Human Infants
  37. Norman MG (1972) Antenatal neuronal loss and gliosis of the reticular formation, thalamus, and hypothalamus. A report of three cases. Neurology (Minneapolis) 22:910-916.
  38. Griffiths AD, Laurence KM (1974) The effect of hypoxia and hypoglycemia on the brain of the newborn human infant. Developmental Medicine and Child Neurology 16:308-319.
  39. Grunnet ML, Curless RG, Bray PF, Jung AL (1974) Brain changes in newborns from an intensive care unit. Developmental Medicine and Child Neurology 16:320-328.
  40. Schneider H, Ballowitz L, Schachinger H, Hanefield F, Droeszus J-U (1975) Anoxic encephalopathy with predominant involvement of basal ganglia, brain stem, and spinal cord in the perinatal period. Acta Neuropathologica (Berlin) 32:287-298.
  41. Leech RW, Alvord EC (1977) Anoxic-ischemic encephalopathy in the human neonatal period, the significance of brain stem involvement. Archives of Neurology 34:109-113.
  42. Roland EH, Hill A, Norman MG, Flodmark O, MacNab AJ (1988) Selective brainstem injury in an asphyxiated newborn. Annals of Neurology 23:89-92.
  43. Natsume J, Watanabe K, Kuno K, Hayakawa F, Hashizume Y (1995) Clinical, neurophysiologic, and neuropathological features of an infant with brain damage of total asphyxia type (Myers). Pediatric Neurology 13:61-64.

    Minimal Cerebral Dysfunction?
  44. Windle WF (1969) Asphyxial brain damage at birth, with reference to the minimally affected child. In Perinatal Factors Affecting Humn Development. Pan American Health Organization, proc. spec. session, 8th meeting, pp. 215-221
  45. Sechzer JA, Faro MD, Barker JN, Barsky D, Gutierrez S, Windle WF. Development behaviors: delayed appearance in monkeys asphyxiated at birth. Science. 1971 Mar 19;171(976):1173-5.
  46. Sechzer JA, Faro MD, Windle WF. Studies of monkeys asphyxiated at birth: implications for minimal cerebral dysfunction. Semin Psychiatry. 1973 Feb;5(1):19-34.

    Umbilical Cord Clamping
  47. Saigal S, Usher RH. Symptomatic neonatal plethora. Biol Neonate. 1977;32(1-2):62-72.
  48. American College of Obstetricians and Gynecologists Obstetric Practice Committee (1994) Utility of umbilical cord blood acid-base assessment. ACOG Committee Opinion: Committee on Obstetric Practice. Number 138--April 1994. International Journal of Gynaecology and Obstetrics 45:303-304.
  49. Wardrop CA, Holland BM. The roles and vital importance of placental blood to the newborn infant. J Perinat Med. 1995;23(1-2):139-43.
  50. Morley GM (1998) Cord Closure: Can Hasty Clamping Injure the Newborn? OBG MANAGEMENT July 1998; 29-36.
  51. Papagno L. Umbilical cord clamping. An analysis of a usual neonatological conduct. Acta Physiol Pharmacol Ther Latinoam. 1998;48(4):224-7.
  52. Rabe H, Wacker A, Hulskamp G, Hornig-Franz I, Schulze-Everding A, Harms E, Cirkel U, Louwen F, Witteler R, Schneider HP. A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants. Eur J Pediatr. 2000 Oct;159(10):775-7.
  53. Mercer JS. Current best evidence: a review of the literature on umbilical cord clamping. J Midwifery Womens Health. 2001 Nov-Dec;46(6):402-14.

    Bilirubin Only Gets into Oxygen-Deprived Tissues
  54. Lucey JF, Hibbard E, Behrman RE, Esquival FO, Windle WF (1964) Kernicterus in asphyxiated newborn monkeys. Experimental Neurology 9:43-58.

    Stages of Drowning
  55. Junger S (1998) The Perfect Storm. New York: HarperTorch/ HarperCollins, pp 179-185 (in the chapter: The Zero-Moment Point).

    Low 5-minute Apgar Score
  56. Thorngren-Jerneck K, Herbst A. Low 5-minute Apgar score: a population-based register study of 1 million term births. Obstet Gynecol. 2001 Jul;98(1):65-70.
  57. Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. 2002 Jul;13(4):417-23.

    Historical Textbooks on Obstetrics
  58. Swayne JG (1856) Obstetric Aphorisms: For the use of students commencing midwifery practice. London: John Churchill.
  59. Playfair WS (1880) A Treatise on the Science and Practice of Midwifery. Philadelphia: Henry C. Lea, p 283
  60. Lusk WT (1882) The Science and Art of Midwifery. New York: D Appleton and Company, pp 214-215
  61. Williams JW (1917) Obstetrics: A Text-Book for the Use of Students and Practicioners, Fourth Edition. New York & London: D. Appleton and Company, pp 342-343
  62. Williams JD (1930) Obstetrics: A Text-Book for the Use of Students and Practicioners, Sixth Edition. New York: D. Appleton-Century, pp 418-419
  63. Stander HJ (1941) Williams Obstetrics, Eighth Edition. New York, London: D. Appleton-Century company, pp 429-430.
  64. Eastman HJ (1950) Williams Obstetrics, Tenth Edition. New York: Appleton-Century-Crofts , pp 397-398
  65. Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC, Hankins GDV, Clark SL, Williams JW, (1997) Williams Obstetrics, Twentieth Edition. Stamford, Conn: Appleton & Lange, pp 336-337.

    Sound Localization
  66. Rose JE, Gross NB, Geisler CD, Hind JE (1966) Some neural mechanisms in the inferior colliculus of the cat which may be relevant to localization of a sound source. Journal of Neurophysiology 29:288-314.
  67. Brainard MS (1994) Neural substrates of sound localization. Current Opinion In Neurobiology 4:557-562
  68. Litovsky RY, Delgutte B. Neural correlates of the precedence effect in the inferior colliculus: effect of localization cues. J Neurophysiol. 2002 Feb;87(2):976-94.

    Large Handwriting (Macrographia)
  69. Beversdorf DQ et al. (2001) Macrographia in high functioning autism. Journal of Autism and Developmental Disorders 31:97-101.

    Neurotrophic Influences on Maturation
  70. VonHungen K, Roberts S, Hill DF (1974) Developmental and regional variations in neurotransmitter-sensitive adenylate cyclase systems in cell-free preparations from rat brain. Journal of Neurochemistry 22:811-819.
  71. Kungel M and Friauf E (1995). Somatostatin and leu-enkephalin in the rat auditory brainstem during fetal and postnatal development. Anatomy and Embryology, 191, 425-443.

    Brain Abnormalities in Autism
  72. Williams RS, Hauser S, Purpura DP, deLong GR, Swisher CN (1980) Autism and mental retardation: Neuropathologic studies performed in four retarded persons with autistic behavior. Archives of Neurology 37:748-753.
  73. Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A (1986) Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. American Journal of Psychiatry 143:862-6
  74. Jacobson R, LeCouteur A, Howlin P, Rutter M (1988) Selective subcortical abnormalities in autism. Psychological Medicine 18:39-48.
  75. Gaffney GR, Kuperman S, Tsai LY, Minchin S (1988) Morphological evidence for brainstem involvement in infantile autism. Biological Psychiatry 24:578-586.
  76. Egaas B, Courchesne E, Saitoh O (1995) Reduced size of corpus callosum in autism. Archives of Neurology 52:794-801.
  77. Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL (1988) Hypoplasia of cerebellar vermal lobules VI and VII in autism. New England Journal of Medicine 318:1349-1354.
  78. Hashimoto T, Tayama M, Murakawa K, Yoshimoto T, Miyazaki M, Harada M, Kuroda Y (1995) Development of the brainstem and cerebellum in autistic patients. Journal of Autism and Developmental Disorders 25:1-18.
  79. Rodier PM, Ingram JL, Tisdale B, Nelson S, Romano J (1996) Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. Journal of Comparative Neurology 370:247-261.
  80. Piven J, Bailey J, Ranson BJ, Arndt S (1997) An MRI study of the corpus callosum in autism. American Journal of Psychiatry 154:1051-1056
  81. Kemper TL, Bauman M (1998). Neuropathology of infantile autism. Journal of Neuropathology and Experimental Neurology 57:645-652 .
  82. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P (1998) A clinicopathological study of autism. Brain 121:889-905.

    Autism and Complications at Birth
  83. Lobascher ME, Kingerlee PE, Gubbay SS. Childhood autism: an investigation of aetiological factors in twenty-five cases. Br J Psychiatry. 1970;117:525-529.
  84. Finegan J-A, Quarrington B. Pre-, peri- and neonatal factors and infantile autism. J Child Psychol Psychiatry. 1979;20:119-128
  85. Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry. 1989 May;30(3):405-16.
  86. Lord C, Mulloy C, Wendelboe M, Schopler E. Pre- and perinatal factors in high-functioning females and males with autism. J Autism Dev Disord. 1991 Jun;21(2):197-209.
  87. Ghaziuddin M, Shakal J, Tsai L. Obstetric factors in Asperger syndrome: comparison with high-functioning autism. J Intellect Disabil Res. 1995 Dec;39 ( Pt 6):538-43.
  88. Bolton PF, Murphy M, Macdonald H, Whitlock B, Pickles A, Rutter M. Obstetric complications in autism: consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):272-81
  89. Burd L, Severud R, Kerbeshian J, Klug MG. Prenatal and perinatal risk factors for autism. J Perinat Med. 1999;27(6):441-50.
  90. Matsuishi T, Yamashita Y, Ohtani Y, Ornitz E, Kuriya N, Murakami Y, Fukuda S, Hashimoto T, Yamashita F. Brief report: incidence of and risk factors for autistic disorder in neonatal intensive care unit survivors. J Autism Dev Disord. 1999 Apr;29(2):161-6
  91. Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics. 2001 Apr;107(4):E63.
  92. Bodier C, Lenoir P, Malvy J, Barthélemy C, Wiss M, Sauvage D. (2001) Autisme et pathologies associées. Étude clinique de 295 cas de troubles envahissants du developpment. [Autism and associated pathologies. Clinical study of 295 cases involving development disorders] Presse Médicale 2001 Sep 1; 30(24 Pt 1):1199-203. French.
  93. Greenberg DA, Hodge SE, Sowinski J, Nicoll D. Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet 2001 Nov;69(5):1062-7
  94. Zwaigenbaum L, Szatmari P, Jones MB, Bryson SE, MacLean JE, Mahoney WJ, Bartolucci G, Tuff L. Pregnancy and birth complications in autism and liability to the broader autism phenotype. J Am Acad Child Adolesc Psychiatry 2002 May;41(5):572-9
  95. Wilkerson DS, Volpe AG, Dean RS, Titus JB. Perinatal complications as predictors of infantile autism. Int J Neurosci. 2002 Sep;112(9):1085-98.

    Cephalhematoma
  96. Towbin A (1970) Neonatal damage of the central nervous system. In Tedeschi CG (ed) Neuropathology: Methods and Diagnosis. Boston, Little, Brown & Co., pp 609-653.

    Controversy Over Mercury Preservatives in Vaccines
  97. Bernard S, Enayati A, Roger H, Binstock T, Redwood L. The role of mercury in the pathogenesis of autism. Mol Psychiatry. 2002;7 Suppl 2:S42-3.
  98. Blaxill MF. Any changes in prevalence of autism must be determined. BMJ. 2002 Feb 2;324(7332):296.
  99. Borchers AT, Keen CL, Shoenfeld Y, Silva J Jr, Gershwin ME. Vaccines, viruses, and voodoo. J Investig Allergol Clin Immunol. 2002;12(3):155-68.
  100. Kimmel SR. Vaccine adverse events: separating myth from reality. Am Fam Physician. 2002 Dec 1;66(11):2113-20.
  101. Wakefield AJ. Measles, mumps, and rubella vaccination and autism. N Engl J Med. 2003 Mar 6;348(10):951-4; author reply 951-4.

    Mercury Damages the Auditory System
  102. Oyanagi K, Ohama E, & Ikuta F. (1989). The auditory system in methyl mercurial intoxication: a neuropathological investigation on 14 autopsy cases in Niigata, Japan. Acta Neuropathologica (Berlin), 77, 561-568.

    Fluoro-deoxyglucose Brain Scans
  103. Asano E, Chugani DC, Muzik O, Behen M, Janisse J, Rothermel R, Mangner TJ, Chakraborty PK, Chugani HT. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology. 2001 Oct 9;57(7):1269-77.
  104. Haznedar MM, Buchsbaum MS, Wei TC, Hof PR, Cartwright C, Bienstock CA, Hollander E. Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry. 2000 Dec;157(12):1994-2001.
  105. Schifter T, Hoffman JM, Hatten HP Jr, Hanson MW, Coleman RE, DeLong GR. Neuroimaging in infantile autism. J Child Neurol. 1994 Apr;9(2):155-61.
  106. Siegel BV Jr, Asarnow R, Tanguay P, Call JD, Abel L, Ho A, Lott I, Buchsbaum MS. Regional cerebral glucose metabolism and attention in adults with a history of childhood autism. J Neuropsychiatry Clin Neurosci. 1992 Fall;4(4):406-14.
  107. Heh CW, Smith R, Wu J, Hazlett E, Russell A, Asarnow R, Tanguay P, Buchsbaum MS. Positron emission tomography of the cerebellum in autism. Am J Psychiatry. 1989 Feb;146(2):242-5.
  108. Horwitz B, Rumsey JM, Grady CL, Rapoport SI. The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization. Arch Neurol. 1988 Jul;45(7):749-55.
  109. De Volder A, Bol A, Michel C, Congneau M, Goffinet AM. Brain glucose metabolism in children with the autistic syndrome: positron tomography analysis. Brain Dev. 1987;9(6):581-7.
  110. Rumsey JM, Duara R, Grady C, Rapoport JL, Margolin RA, Rapoport SI, Cutler NR. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography. Arch Gen Psychiatry. 1985 May;42(5):448-55.

    Cardiac Arrest Encephalopathy
  111. Neubuerger KT (1954) Lesions of the human brain following circulatory arrest. Journal of Neuropathology and Experimental Neurology 13:144-160.
  112. Brierley JB (1961) Some neuropathological contributions to problems of hypoxia. In Gastaut H & Meyer JS, eds. Cerebral Anoxia and the Electroencephalogram. Charles C. Thomas, Springfield, Illinois.
  113. Gilles FH (1963) Selective symmetrical neuronal necrosis of certain brain stem tegmental nuclei in temporary cardiac standstill. Journal of Neuropathology and Experimental Neurology 22:318-318.
  114. Lindenberg R (1963) Patterns of CNS vulnerability in acute hypoxiaemia, including anaesthesia accidents. In Schade JP & McMenemey WH, eds. Selective Vulnerability of the Brain in Hypoxaemia. Blackwell Scientific Publications, Oxford.
  115. Adams JH, Brierley JB, Connor RC, Treip CS. (1966) The effects of systemic hypotension upon the human brain. Clinical and neuropathological observations in 11 cases. Brain 89:235-268.
  116. Gilles FH (1969) Hypotensive brain stem necrosis: selective symmetrical necrosis of tegmental neuronal aggregates following cardiac arrest. Archives of Pathology 88:32-41.
  117. Janzer RC, Friede RL. Hypotensive brain stem necrosis or cardiac arrest encephalopathy? Acta Neuropathol (Berl). 1980;50(1):53-6.

    Importance of the Auditory System
  118. Fisch L (1970) The selective and differential vulnerability of the auditory system. In GEW Wolstenholm and J Knight, (Eds), Sensorineural Hearing Loss: A Ciba Foundation Symposium (pp 101-116). London: Churchill.

    General Awareness and Consciousness
  119. Denny-Brown, D. (1962). The midbrain and motor integration. Proceedings of the Royal Society of Medicine, 55, 527-538.
  120. Jane JA, Masterton RB, Diamond IT (1965) The function of the tectum for attention to auditory stimuli in the cat. Journal of Comparative Neurology 125:165-192.
  121. Sprague JM, Chambers WW, Stellar, E (1961) Attentive, affective, and adaptive behavior in the cat. Science 133:165-173.

    Fast Acting Anesthesia
  122. Roth LJ, Barlow CE (1961) Drugs in the brain. Science 134:22-31.

    Kanner's Original Description
  123. Kanner L (1943) Autistic disturbances of affective contact. Nervous Child 2:217-250.

    Auditory Evoked Potentials
  124. Student M, Sohmer H (1978) Evidence from auditory nerve and brainstem evoked responses for an organic brain lesion in children with autistic traits. Journal of Autism and Childhood Schizophrenia 8:13-20.
  125. Rosenblum SM, Arick JR, Krug DA, Stubbs EG, Young NB, Pelson RO (1980) Auditory brainstem evoked responses in autistic children. Journal of Autism and Developmental Disorders 10:215-225.
  126. Skoff BF, Mirsky AF, Turner D (1980) Prolonged brainstem transmission time in autism. Psychiatry Research 2:157-166.
  127. Taylor MJ, Rosenblatt B, Linschoten L (1982) Auditory brainstem response abnormalities in autistic children. Canadian Journal of Neurological Sciences 9:429-433.
  128. Thivierge J, Bedard C, Cote R, Maziade M. Brainstem auditory evoked response and subcortical abnormalities in autism. Am J Psychiatry. 1990 Dec;147(12):1609-13.
  129. Wong V, Wong SN. Brainstem auditory evoked potential study in children with autistic disorder. J Autism Dev Disord. 1991 Sep;21(3):329-40.
  130. McClelland RJ, Eyre DG, Watson D, Calvert GJ, Sherrard E. Central conduction time in childhood autism. Br J Psychiatry. 1992 May;160:659-63.
  131. Bruneau N, Roux S, Adrien JL, Barthelemy C. Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave-T complex). Clin Neurophysiol. 1999 Nov;110(11):1927-34.
  132. Seri S, Cerquiglini A, Pisani F, Curatolo P. Autism in tuberous sclerosis: evoked potential evidence for a deficit in auditory sensory processing. Clin Neurophysiol. 1999 Oct;110(10):1825-30.
  133. Maziade M, Merette C, Cayer M, Roy MA, Szatmari P, Cote R, Thivierge J. Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives. Arch Gen Psychiatry. 2000 Nov;57(11):1077-83.
  134. Rosenhall U, Nordin V, Brantberg K, Gillberg C. Autism and auditory brain stem responses. Ear Hear. 2003 Jun;24(3):206-14.

    Evoked Potentials in Asphyxiated Monkeys
  135. Mirsky AF, Orren MM, Stanton L, Fullerton BC, Harris S, Myers RE (1979) Auditory evoked potentials and auditory behavior following prenatal and perinatal asphyxia in rhesus monkeys. Developmental Psychobiology 12:369-379

    Auditory Tests
  136. Church MW, Eldis F, Blakley BW, Bawle EV (1997) Hearing, language, speech, vestibular, and dentofacial disorders in fetal alcohol syndrome. Alcoholism, Clinical and Experimental Research 21:227-237.

    Inhibitory Transmitters
  137. Faingold CL, Gehlbach G, Caspary DM (1991) Functional pharmacology of inferior colliculus neurons. In R.A. Altschuler et al. Neurobiology of Hearing: The Central Auditory System. New York: Raven Press, pp 223-252 (chapter 10).
  138. Zhang H, Feng AS (1998) Sound direction modifies the inhibitory as well as the excitatory frequency tuning characteristics of single neurons in the frog torus semicircularis (inferior colliculus). Journal of Comparative Physiology. A, Sensory, Neural, and Behavioral Physiology 182:725-735
  139. Caspary DM, Milbrandt JC, Helfert RH (1995) Central auditory aging: GABA changes in the inferior colliculus. Experimental Gerontology 30:349-360.

    Early Myelination and Maturation of the Auditory System
  140. Langworthy OR (1933) Development of behavior patterns and myelinization of the nervous system in the human fetus and infant. Contributions to Embryology, no. 139 24:1-57.
  141. Yakovlev PI and Lecours A-R (1967) The myelogenetic cycles of regional maturation of the brain. In A. Minkowski (Ed.), Regional Development of the Brain in Early Life (pp. 3-70). Oxford: Blackwell Scientific Publications.
  142. Moore JK, Perazzo LM, Braun A (1995). Time course of axonal myelination in the human brainstem auditory pathway. Hearing Research 87:21-31, 91:208-209.

    Stressed Syllables and Learning to Speak
  143. Brown R, Bellugi U (1964) Three processes in the child's acquisition of syntax. Harvard Educational Review 34:133-151.
  144. Brown R (1973) A First Language: The Early Stages. Cambridge, MA: Harvard University Press.
  145. Brown R (1975) A collection of words and sentences, an autistic child. In R Brown RJ Herrnstein, Psychology (pp. 444-449). Boston: Little, Brown and Company.

    Verbal Auditory Agnosia
  146. Rapin I (1997) Autism. New England Journal of Medicine 337:97-104.

    Early Aging of the Auditory System
  147. Uecker A, Gonzalez-Lima F, Cada A, Reiman EM. Behavior and brain uptake of fluorodeoxyglucose in mature and aged C57BL/6 mice. Neurobiol Aging. 2000 Sep-Oct;21(5):705-18.

    Verbal Auditory Agnosia Following Damage of the Inferior Colliculi
  148. Meyer B, Kral T, Zentner J. (1996) Pure word deafness after resection of a tectal plate glioma with preservation of wave V of brain stem auditory evoked potentials. Journal of Neurology, Neurosurgery and Psychiatry. 61:423-424.
  149. Johkura K, Matsumoto S, Hasegawa O, Kuroiwa Y. (1998) Defective auditory recognition after small hemorrhage in the inferior colliculi. Journal of the Neurological Sciences. 161:91-96.
  150. Masuda S, Takeuchi K, Tsuruoka H, Ukai K, Sakakura Y. (2000) Word deafness after resection of a pineal body tumor in the presence of normal wave latencies of the auditory brain stem response. The Annals of otology, rhinology, and laryngology. 2000 Dec;109(12 Pt 1):1107-1112.

    Irrelevant and Metaphorical Language
  151. Kanner L (1946) Irrelevant and metaphorical language of early infantile autism. American Journal of Psychiatry 103:242-246.

    The Inferior Colliculus and Echolalic Speech
  152. Simon N (1975) Echolalic speech in childhood autism, consideration of possible underlying loci of brain damage. Archives of General Psychiatry 32:1439-1446.

    Non-genetic Predispositions for Autism:
    Prenatal Exposure to Drugs
  153. Nanson JL (1992) Autism in fetal alcohol syndrome: a report of six cases. Alcoholism, Clinical and Experimental Research 16:558-565.
  154. Harris SR, MacKay LL, Osborn JA (1995) Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports. Alcoholism, Clinical and Experimental Research 19:660-5
  155. Aronson M, Hagberg B, Gillberg C (1997) Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study. Developmental Medicine and Child Neurology 39:583-7
  156. Church MW, Eldis F, Blakley BW, Bawle EV (1997) Hearing, language, speech, vestibular, and dentofacial disorders in fetal alcohol syndrome. Alcoholism, Clinical and Experimental Research 21:227-237.
  157. Christianson AL, Chesler N, and Kromberg JGR (1994) Fetal valproate syndrome: clinical and neuro-developmental features in two sibling pairs. Developmental Medicine and Child Neurology 36:357-369.
  158. Williams PG & Hersh JH (1997) A male with fetal valproate syndrome and autism. Developmental Medicine and Child Neurology 39:632-634.
  159. Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH. (2001) Fetal valproate syndrome and autism: additional evidence of an association. Developmental Medicine and Child Neurology 43:202-206.
  160. Stromland K, Nordin V, Miller M, Akerstrom B, and Gillberg C (1994) Autism in thalidomide embryopathy: a population study. Developmental Medicine and Child Neurology 36:351-356.

    Infectious Encephalitis
  161. Desmond MM, Montgomery JR, Melnick JL, Cochran GG, Verniaud W (1969) Congenital rubella encephalitis. Effects on growth and early development. American Journal of Diseases of Children 118:30-31.
  162. Chess S (1971) Autism in children with congenital rubella. Journal of Autism and Childhood Schizophrenia 1:33-47.
  163. Chess S, Fernandez P, Korn S. (1978) Behavioral consequences of congenital rubella. Journal of Pediatrics. 93:699-703.
  164. Townsend JJ et al. (1975) Progressive rubella panencephalistis: Late onset after congenital rubella. New England Journal of Medicine 292:990.
  165. Weil et al. (1975) Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis. New England Journal of Medicine 292:994
  166. deLong GR, Bean SC, Brown FR (1981) Acquired reversible autistic syndrome in acute encephalopathic illness in children. Archives of Neurology 38:191-194
  167. Gillberg C (1986) Brief report: onset at age 14 of a typical autistic syndrome. A case report of a girl with herpes simplex encephalitis. Journal of Autism and Developmental Disorders 16: 369-375.
  168. Gillberg IC (1991) Autistic syndrome with onset at age 31 years: herpes encephalitis as a possible model for childhood autism. Developmental Medicine and Child Neurology 33:920-4
  169. Ghaziuddin M, Tsai LY, Eilers L, Ghaziuddin N. (1992) Brief report: autism and herpes simplex encephalitis. Journal of Autism and Developmental Disorders. 22:107-13.
  170. Greer MK, Lyons-Crews M, Mauldin LB, Brown FR 3rd. (1989) A case study of the cognitive and behavioral deficits of temporal lobe damage in herpes simplex encephalitis. Journal of Autism and Developmental Disorders 19:317-26.
  171. Domachowske JB, Cunningham CK, Cummings DL, Crosley CJ, Hannan WP, Weiner LB (1996) Acute manifestations and neurologic sequelae of Epstein-Barr virus encephalitis in children. Pediatric Infectious Disease Journal 15:871-5
  172. Thivierge J. (1986) A case of acquired aphasia in a child. Journal of Autism and Developmental Disorders. 16:507-12.
  173. Barak Y, Kimhi R, Stein D, Gutman J, Weizman A (1999) Autistic subjects with comorbid epilepsy: a possible association with viral infections. Child Psychiatry and Human Development 1999 Spring;29(3):245-51

    Lead Poisoning
  174. Cohen DJ, Johnson WT, Caparulo BK. Pica and elevated blood lead level in autistic and atypical children. Am J Dis Child. 1976 Jan;130(1):47-8
  175. Accardo P, Whitman B, Caul J, Rolfe U. Autism and plumbism. A possible association. Clin Pediatr (Phila). 1988 Jan;27(1):41-4.
  176. Eppright TD, Sanfacon JA, Horwitz EA. Attention deficit hyperactivity disorder, infantile autism, and elevated blood-lead: a possible relationship. Mo Med. 1996 Mar;93(3):136-8.

    Seizure Disorder/ Neurologic Damage
  177. Chugani HT, Da Silva E, Chugani DC (1996) Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography. Annals Of Neurology 39:643-649.
  178. daSilva EA, Chugani DC, Muzik O, Chugani HT (1997) Landau-Kleffner syndrome: metabolic abnormalities in temporal lobe are a common feature. Journal of Child Neurology 12:489-495.

    Intestinal Inflammation
  179. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA (1998) Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet Feb 28;351(9103):637-41.

    Genetic/Metabolic Predispositions for Autism:
    Neurolipidosis
  180. Creak M (1963) Childhood psychosis: A review of 100 cases. British Journal of Psychiatry 109:84-89.
  181. Darby JK (1976) Neuropathologic aspects of psychosis in children. Journal of Autism and Childhood Schizophrenia 6:339-352

    Tuberous Sclerosis
  182. Fisher W, Kerbeshian J, Burd L, Kolstoe P. (1986) Tuberous sclerosis and autism. Developmental Medicine and Child Neurology 28:814-815
  183. Bolton PF, Griffiths PD (1997) Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 349(9049):392-395
  184. Webb DW, Fryer AE, Osborne JP (1996) Morbidity associated with tuberous sclerosis: a population study. Developmental Medicine and Child Neurology 38:146-55
  185. Griffiths PD, Martland TR (1997) Tuberous Sclerosis Complex: the role of neuroradiology. Neuropediatrics 28:244-52
  186. Crino PB, Henske EP (1999) New developments in the neurobiology of the tuberous sclerosis complex. Neurology 53:1384-90
  187. Bolton PF, Park RJ, Higgins JN, Griffiths PD, Pickles A. (2002) Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 125:1247-1255

    Neurofibromatosis
  188. Gaffney GR, Kuperman S, Tsai LY, Minchin S. (1989) Forebrain structure in infantile autism. J Am Acad Child Adolesc Psychiatry. 28:534-537.
  189. Gaffney GR, Kuperman S, Tsai LY, Minchin S, Hassanein KM (1987a) Midsagittal magnetic resonance imaging of autism. British Journal of Psychiatry 151:831-3
  190. Gaffney GR, Tsai LY, Kuperman S, Minchin S (1987b) Cerebellar structure in autism. American Journal of Diseases of Children 141:1330-2
  191. Gillberg C, Coleman M (1996). Autism and medical disorders: a review of the literature. Developmental Medicine and Child Neurology 38:191-202.

    Phenyhlketonuria
  192. Lowe TL, Tanaka K, Seashore MR, Young JG, Cohen DJ (1980). Detection of phenylketonuria in autistic and psychotic children. Journal of the American Medical Association 243:126-128.
  193. Williams RS, Hauser S, Purpura DP, deLong GR, Swisher CN (1980) Autism and mental retardation: Neuropathologic studies performed in four retarded persons with autistic behavior. Archives of Neurology 37:748-753.
  194. Chen CH, Hsiao KJ (1989) A Chinese classic phenylketonuria manifested as autism. British Journal of Psychiatry 155:251-3
  195. Miladi N, Larnaout A, Kaabachi N, Helayem M, Ben Hamida M (1992) Phenylketonuria: an underlying etiology of autistic syndrome. A case report. Journal of Child Neurology 7:22-23.
  196. Leuzzi V, Trasimeni G, Gualdi GF, Antonozzi I (1995) Biochemical, clinical and neuroradiological (MRI) correlations in late-detected PKU patients. Journal of Inherited Metabolic Disease 18:624-634.

    Fragile X Syndrome
  197. Brown WT, Jenkins EC, Friedman E, Brooks J, Wisniewski K, Raguthu S, French J. (1982) Autism is associated with the fragile-X syndrome. Journal of Autism and Developmental Disorders. 12:303-8.
  198. Folstein SE, Rutter ML (1988) Autism: familial aggregation and genetic implications. Journal of Autism and Developmental Disorders. 18:3-30.

    Leber's Congenital Amaurosis
  199. Rogers SJ, Newhart-Larson S (1989) Characteristics of infantile autism in five children with Leber's congenital amaurosis. Developmental Medicine and Child Neurology 31:598-608
  200. Malamud N (1959) Heller's disease and childhood schizophrenia. American Journal of Psychiatry 116:215-218.

    Adenylosuccinate Lyase Defect
  201. Jaeken J, Van den Berghe G. (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet. Nov 10;2(8411):1058-61.
  202. Jaeken J, Wadman SK, Duran M, van Sprang FJ, Beemer FA, Holl RA, Theunissen PM, de Cock P, van den Bergh F, Vincent MF, et al. (1988) Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. European Journal of Pediatrics. 148:126-31.
  203. Barshop BA, Alberts AS, Gruber HE. (1989) Kinetic studies of mutant human adenylosuccinase. Biochimica et Biophysica Acta. 999:19-23.
  204. Van den Berghe G, Vincent MF, Jaeken J. (1997) Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. Journal of Inherited Metabolic Disease. 20:193-202.

    Lactic Acidosis
  205. Coleman M, Blass JP (1985) Autism and lactic acidosis. Journal of Autism and Developmental Disorders 15 1-8.
  206. Philippart M (1986) Clinical recognition of Rett syndrome. American Journal of Medical Genetics Supplement 1:111-8
  207. Lombard J (1998) Autism: a mitochondrial disorder? Medical Hypotheses 50:497-500.

    Krebs Cycle (aerobic metabolism) Defects
  208. Shaw W, Kassen E, Chaves E (1995) Increased urinary excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features. Clinical Chemistry 41:1094-1194.

    Mitochondrial Disorders
  209. Fillano JJ, Goldenthal MJ, Rhodes CH, Marin-Garcia J (2002) Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol. 2002 Jun;17(6):435-9.
  210. Graf WD, Marin-Garcia J, Gao HG, Pizzo S, Naviaux RK, Markusic D, Barshop BA,Courchesne E, Haas RH (2000) Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. J Child Neurol. 2000 Jun;15(6):357-61.

  211. Fetal to Postnatal Adaptation Mercer JS, Skovgaard RL. Neonatal transitional physiology: a new paradigm. J Perinat Neonatal Nurs. 2002 Mar;15(4):56-75.

    Infant Anemia
  212. Wilson EE, Windle WF, Alt HL (1941) Deprivation of placental blood as a cause of iron deficiency in infants. Am. J. Dis. Child. 62:320-327.
  213. Lozoff B, Jimenez E, Wolf AW (1991) Long-term developmental outcome of infants with iron deficiency. New England Journal of Medicine 325:687-694.
  214. Hurtado EK, Claussen AH, Scott KG (1999) Early childhood anemia and mild or moderate mental retardation. American Journal of Clinical Nutrition 69:115-119.

    Hierarchy of Human Needs
  215. Maslow AH (1970) Motivation and Personality, Second Edition. New York: Harper & Row.

    Biochemistry Textbooks
  216. White A, Handler P, Smith EL (1969) Principles of Biochemistry, Fourth Edition. New York: Blakiston Division, McGraw-Hill Book Company, Chapter 32, pp 758-776.
  217. Murray RK, Granner DK, Mayes PA, Rodwell VW (2000) Harper's Biochemistry, twenty-fifth edition. New York: McGraw-Hill Health Professions Division.

    Polycythemia
  218. Beutler E. Genetic disorders of human red blood cells. JAMA. 1975 Sep 15;233(11):1184-8.
  219. Kohli-Kumar M, Zwerdling T, Rucknagel DL. Hemoglobin F-Cincinnati, alpha 2G gamma 2 41(C7) Phe-->Ser in a newborn with cyanosis. Am J Hematol. 1995 May;49(1):43-7.
  220. Kralovics R, Prchal JT. Congenital and inherited polycythemia. Curr Opin Pediatr. 2000 Feb;12(1):29-34.
  221. Jellett H (1910) A Manual of Midwifery for Students and Practitioners. New York: William Wood & Company.
  222. White (1785) A Treatise on the Management of Pregnant and Lying-in Women, third edition, p 109 et seq. London. (cited by Jellett 1910)
  223. Schmidt (1894) Archiv f Gyn, vol xiv. (cited by Jellett 1910)

    Autism in Twins
  224. Folstein S, Rutter M (1977) Infantile autism: a genetic study of 21 twin pairs. Journal of Child Psychology and Psychiatry 30:405-416.
  225. Norman MG (1982) Mechanisms of brain damage in twins. The Canadian journal of neurological sciences 1982 Aug;9(3):339-44
  226. Davis JO, Phelps JA, Bracha HS (1995) Prenatal development of monozygotic twins and concordance for schizophrenia. Schizophrenia Bulletin 21:357-366. Published erratum appears in Schizophrenia Bulletin 21:539.
  227. Ritvo ER, Freeman BJ, Mason-Brothers A, Mo A, Ritvo AM (1985) Concordance for the syndrome of autism in 40 pairs of afflicted twins. American Journal of Psychiatry 142:74-7
  228. Migeon BR, Dunn MA, Thomas G, Schmeckpeper BJ, Naidu S (1995) Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosome is not involved in Rett syndrome. American Journal of Human Genetics 56:647-53.
  229. Subramaniam B, Naidu S, Reiss AL (1997) Neuroanatomy in Rett syndrome: cerebral cortex and posterior fossa. Neurology 48:399-407.
  230. Feekery C, Parry-Fielder B, Hopkins IJ (1993) Landau-Kleffner syndrome: six patients including discordant monozygotic twins. Pediatric Neurology 9:49-53.

    Neonatal Asphyxia in Laboratory Rats
  231. Simon N, Volicer L (1976) Neonatal asphyxia in the rat: greater vulnerability of males and persistent effects on brain monoamine synthesis. Journal of Neurochemistry 26:893-900.

    Categories of Mental Disorders
  232. American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, DSM-IV. Washington, DC: American Psychiatric Association.

    Adjustments Under Adverse Conditions
  233. Scremin OU, Shih TM, Corcoran KD (1991) Cerebral blood flow-metabolism coupling after administration of soman at nontoxic levels. Brain Research Bulletin 26:353-6
  234. Scremin OU, Shih TM, Li MG, Jenden DJ (1998) Mapping of cerebral metabolic activation in three models of cholinergic convulsions. Brain Research Bulletin 45:167-74
  235. Shih TM, Scremin OU (1992) Cerebral blood flow and metabolism in soman-induced convulsions. Brain Research Bulletin 28:735-42
  236. Kelly PA, Ritchie IM, McBean DE, Sharkey J, Olverman HJ (1995) Enhanced cerebrovascular responsiveness to hypercapnia following depletion of central serotonergic terminals. Journal of Cerebral Blood Flow and Metabolism 15:706-713

    Neuropathology in Alcoholism (Wernicke's Encephalopathy)
  237. Gamper (1928) Zur Frage der Polioencephalitis haemorrhagica der chronischen Alkoholiker. Anatomische Befunde beim alkoholischen Korsakow und ihre Beziehungen zum klinischen Bild. Deutsche Zeitschrift für Nervenheilkunde 102:122-129
  238. Kant F (1933) Die Pseudoencephalitis Wernicke der Alkoholiker. (polio-encephalitis haemorrhagica superior acuta). Archiv für Psychiatrie und Nervenkrankheiten 98:702-768.
  239. Malamud N, Skillicorn SA (1956). Relationship between the Wernicke and the Korsakoff Syndrome. Archives of Neurology and Psychiatry, 76, 585-596.
  240. Torvik A (1987) Topographic distribution and severity of brain lesions in Wernicke's encephalopathy. Clinical Neuropathology 6:25-29.
  241. Victor M, Adams RD, Collins GH (1989) The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition, 2nd ed, Contemporary Neurology Series v30. Philadelphia, PA : F.A. Davis Co.

    Moebius Syndrome (Bilateral Facial Palsy)
  242. Moebius PJ (1888) Ueber angeborenen doppelseitige Abducens-Facialis-Laemung. Münchener Medizinische Wochenschrift. 35: 91-94.
  243. Gillberg C, Steffenburg S (1989) Autistic behaviour in Moebius syndrome. Acta Paediatrica Scandinavica 78:314-316.
  244. Miller MT, Stromland K. (1999) The mobius sequence: a relook. Journal of AAPOS
  245. Lipson AH, Webster WS, Brown-Woodman PD, Osborn RA (1989) Moebius syndrome: animal model--human correlations and evidence for a brainstem vascular etiology. Teratology 40:339-50
  246. Fujita I, Koyanagi T, Kukita J, Yamashita H, Minami T, Nakano H, Ueda K (1991) Moebius syndrome with central hypoventilation and brainstem calcification: a case report. European Journal of Pediatrics 150:582-3
  247. Yoon K, Yoo SJ, Suh DC, Lee YA, Kim KS, Choe G (1997) Mobius syndrome with brain stem calcification: prenatal and neonatal sonographic findings. Pediatric Radiology 27:150-2
  248. Matsunaga Y, Amamoto N, Kondoh T, Ohtsuka Y, Miyazoe H, Kamimura N, Matsumoto T, Tsuji Y (1998) A severe case of Moebius syndrome with calcification on the fourth ventricular floor. Journal of Human Genetics 43:62-4.
  249. Pastuszak AL, Schuler L, Speck-Martins CE, Coelho KE, Cordello SM, Vargas F, Brunoni D, Schwarz IV, Larrandaburu M, Safattle H, Meloni VF, Koren G (1998) Use of misoprostol during pregnancy and Mobius' syndrome in infants. New England Journal of Medicine 338:1881-1885

    Wernicke-Gayet Encephalopathy
  250. Gayet M (1875) Affection encéphalique (encéphalite diffuse probable) localisée aux étages supérieurs des pédoncules cérébraux et aux couches optiques, ainsi qu’au plancher du quatrième ventricule et aux parois latérales du troisième. Archives de physiologie normale et pathologique série 2, 2:23-351.
  251. Wernicke C (1881) Die acute, haemorrhagische Poliencephalitis superior. Lehrbuch der Gehirnkrankheiten für Ärzte und Studirende,Band II. Kassel: Theodor Fischer, pp 229-242.
  252. Rosenblum WI, Feigin I. (1965) The hemorrhagic component of Wernicke's encephalopathy. Archives of Neurology 13:627-32.
  253. Brody IA, Wilkins RH. (1968) Wernicke's encephalopathy. Archives of Neurology. 19:228-32.
  254. Butterworth RF (1993) Pathophysiology of cerebellar dysfunction in the Wernicke-Korsakoff syndrome. Canadian Journal of Neurological Sciences 20 Suppl 3:S123-S126.
  255. Cavanagh JB, Holton JL, Nolan CC (1997) Selective damage to the cerebellar vermis in chronic alcoholism: a contribution from neurotoxicology to an old problem of selective vulnerability. Neuropathology and Applied Neurobiology 23:355-363.

    Pyrithiamine Enzyme Poison
  256. Troncoso JC, Johnston MV, Hess KM, Griffin JW, Price DL (1981) Model of Wernicke's encephalopathy. Archives Of Neurology 38:350-354.
  257. Irle E, Markowitsch HJ (1983) Widespread neuroanatomical damage and learning deficits following chronic alcohol consumption or vitamin B1 (thiamine) deficiency in rats. Behavioral Brain Research 9:277-284.
  258. Cogan DG, Witt ED, Goldman-Rakic PS (1985) Ocular signs in thiamine-deficient monkeys and in Wernicke's disease in humans. Archives of Ophthalmology 103:1212-1220.
  259. Hakim AM (1986) Effect of thiamine deficiency and its reversal on cerebral blood flow in the rat. Observations on the phenomena of hyperperfusion, "no reflow," and delayed hypoperfusion. Journal of Cerebral Blood Flow and Metabolism 6:79-85
  260. Leong DK, Le O, Oliva L, Butterworth RF (1994) Increased densities of binding sites for the "peripheral-type" benzodiazepine receptor ligand [3H]PK11195 in vulnerable regions of the rat brain in thiamine deficiency encephalopathy. Journal of Cerebral Blood Flow and Metabolism. 14:100-5.
  261. Chen Q, Okada S, Okeda R (1997) Causality of parenchymal and vascular changes in rats with experimental thiamine deficiency encephalopathy. Pathology International 47:748-756

    Toxic fumes, Methyl Bromide, and Alpha-chlorohydrin
  262. Bini, L. & Bollea, G. (1947). Fatal poisoning by lead-benzine (a clinico-pathologic study). Journal of Neuropathology and Experimental Neurology, 6, 271-285.
  263. Franken L (1959) Étude anatomique d'un cas d'intoxication par le bromure de méthyle. Acta Neurologica et Psychiatrica Belgica 59:375-383.
  264. Goulon M, Nouailhat R, Escourolle R, Zarranz-Imirizaldu JJ, Grosbuis S, Levy-Alcover MA (1975). Intoxication par le bromure de methyl: Trois observations, dont une mortelle. Etude neuro-pathologique d'un cas de stupeur avec myoclonies, suivi pendent cinq ans. Revue Neurologique (Paris) 131:445-468.
  265. Squier MV, Thompson J, Rajgopalan B. (1992) Case report: neuropathology of methyl bromide intoxication. Neuropathology and Applied Neurobiology 18: 579-584.
  266. Cavanagh JB (1992) Methyl bromide intoxication and acute energy deprivation syndromes. Neuropathology and Applied Neurobiology 18:575-578.
  267. Cavanagh JB, Nolan CC (1993) The neurotoxicity of alpha-chlorohydrin in rats and mice: II. Lesion topography and factors in selective vulnerability in acute energy deprivation syndromes. Neuropathology and Applied Neurobiology 19:471-479.

    Auditory System Impairment in Alzheimer Dementia
  268. Sinha UK, Hollen KM, Rodriguez R, Miller CA (1993) Auditory system degeneration in Alzheimer's disease. Neurology 43:779-85.

    Mitochondria and their vulnerability
  269. DeJong R (1944) Methyl bromide poisoning. Journal of the American Medical Association 125:702.
  270. Reijnders L (1975) The origin of mitochondria. Journal of Molecular Evolution 5:167-76
  271. Tipton KF, Singer TP. (1993) Advances in our understanding of the mechanisms of the neurotoxicity of MPTP and related compounds. Journal of Neurochemistry 61:1191-1206.
  272. Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS, Cortopassi GA, Jaber L, Rotter JI, et al (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature Genetics 4:289-294.
  273. Pandya A, Xia X, Radnaabazar J, Batsuuri J, Dangaansuren B, Fischel-Ghodsian N, Nance WE (1997) Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity. J Med Genet 1997 Feb;34(2):169-72
  274. Warner TT, Schapira AH (1997) Genetic counselling in mitochondrial diseases. Current Opinion in Neurology 10:408-412.
  275. Schapira AH (1998) Inborn and induced defects of mitochondria. Arch Neurol 55:1293-1296.
  276. Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482-1488.
  277. Gray MW, Burger G, Lang BF. (1999) Mitochondrial evolution. Science (Mar 5, 5407) 283:1476-1481.

    Disruption of Mitochondrial Function
  278. Cavanagh, J. B. & Harding, B. N. (1994). Pathogenic factors underlying the lesions in Leigh's disease. Tissue responses to cellular energy deprivation and their clinico-pathological consequences. Brain, 117(Pt 6), 1357-1376.
  279. Graf WD, Marin-Garcia J, Gao HG, Pizzo S, Naviaux RK, Markusic D, Barshop BA,Courchesne E, Haas RH (2000) Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. J Child Neurol. 2000 Jun;15(6):357-61.
  280. Fillano JJ, Goldenthal MJ, Rhodes CH, Marin-Garcia J (2002) Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol. 2002 Jun;17(6):435-9.

    Thiamine Deficiency
  281. Peters RA (1936) The biochemical lesion in vitamin B1 deficiency. Lancet, May 23, 1161-1165.
  282. Williams RR (1961) Toward the Conquest of Beriberi. Cambridge, MA: Harvard University Press.
  283. Dreyfus PM, Victor M (1961) Effects of thiamine deficiency on the central nervous system. American Journal of Clinical Nutrition 9: 414-425.
  284. Carpenter KJ (2000) Beriberi, White Rice, and Vitamin B: A Disease, a Cause, and a Cure. Berkeley: University of California Press.

    Thiamine Treatment
  285. Lonsdale D, Shamberger RJ, Audhya T. (2002) Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: A pilot study. Neuroendocrinology Letters 23:303-308.

    Thiamine Deficiency in Total Parenteral Nutrition
  286. Vortmeyer AO, Hagel C, Laas R (1992) Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition. Journal of Neurology, Neurosurgery and Psychiatry 55:826-829.
  287. Hahn JS, Berquist W, Alcorn DM, Chamberlain L, Bass D. Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage. Pediatrics. 1998 Jan;101(1):E10.

    Thiamine Deficiency in Animals
  288. Evans CA, Carlson WE, Green EG (1942) The pathology of Chastek paralysis in foxes. A counterpart of Wernicke's hemorrhagic polioencephalitis of man. American Journal of Pathology 18:79-90.
  289. Rinehart JF, Friedman M, Greenberg LD (1949) Effect of experimental thiamine deficiency on the nervous system of the rhesus monkey. Archives of Pathology 48:129-139.
  290. Jubb KV Saunders LZ, Coates HV (1956) Thiamine deficiency encephalopathy in cats. Journal of Comparative Pathology 66:217-227.
  291. Witt ED, Goldman-Rakic PS (1983) Intermittent thiamine deficiency in the rhesus monkey. I. Progression of neurological signs and neuroanatomical lesions. Annals of Neurology 13:376-395.

    Brainstem Control of Autonomic Functions
  292. Johnson RH, Eisenhofer G, Lambie DG. The effects of acute and chronic ingestion of ethanol on the autonomic nervous system. Drug Alcohol Depend. 1986 Dec;18(4):319-28.

    Wernicke's Encephalopathy in Gastrointestinal Disorders
  293. Korsakoff SS (1889) Psychic disorder in conjunction with multiple neuritis. Translated by Victor M & Yakovlev PI (1955) Korsakoff's psychic disorder in conjunction with peripheral neuritis: a translation of Korsakoff's original article with brief comments on the author and his contribution to clinical medicine, Neurology 5:394-405.
  294. Neubürger K (1937) Wernickesche Krankheit bei chronischer Gastritis. Ein Beitrag zu den Beziehungen zwischen Magen und Gehirn. Zeitschrift für die gesamte Neurologie und Psychiatrie 160:208-225.
  295. Albers JW, Nostrant TT, Riggs JE. Neurologic manifestations of gastrointestinal disease. Neurol Clin. 1989 Aug;7(3):525-48.
  296. Butterworth RF. Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. Metab Brain Dis. 1995 Mar;10(1):1-8.
  297. Kril JJ. Neuropathology of thiamine deficiency disorders. Metab Brain Dis. 1996 Mar;11(1):9-17.
  298. Holzer P, Michl T, Danzer M, Jocic M, Schicho R, Lippe IT. Surveillance of the gastrointestinal mucosa by sensory neurons. J Physiol Pharmacol 2001 Dec;52(4 Pt 1):505-21.

    Hypovolemic Shock at Birth
  299. Morley GM (2003) Neonatal Resuscitation: Life that Failed. http://www.obgyn.net/pb/pb.asp?page=/pb/articles/neonatal-resuscitation
  300. Hankins GD, Koen S, Gei AF, Lopez SM, Van Hook JW, Anderson GD (2002) Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstetrics and gynecology 99:688-91.

35 – Autism and Complications at Birth


  • "… 5 items were found to significantly predict group membership (prescriptions taken during pregnancy, length of labor, viral infection, abnormal presentation at delivery, and low birth weight)."
    Wilkerson DS, Volpe AG, Dean RS, Titus JB. Perinatal complications as predictors of infantile autism. Int J Neurosci. 2002 Sep;112(9):1085-98.

  • "Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results:The risk of autism was associated with daily smoking in early pregnancy (OR = 1.4; CI = 1.1-1.8), maternal birth outside Europe and North America (OR = 3.0; CI = 1.7-5.2), cesarean delivery (OR = 1.6; CI = 1.1-2.3), being small for gestational age (SGA; OR = 2.1; CI = 1.1-3.9), a 5-minute Apgar score below 7 (OR = 3.2, CI = 1.2-8.2), and congenital malformations (OR = 1.8, CI = 1.1-3.1)." Note: The OR and CI were both greatest for 5-min Apgar score below 7.
    Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. 2002 Jul;13(4):417-23.

  • "Children with autism spectrum disorders have lower optimality (higher rates of complications) than unaffected siblings…"
    Zwaigenbaum L, Szatmari P, Jones MB, Bryson SE, MacLean JE, Mahoney WJ, Bartolucci G, Tuff L. Pregnancy and birth complications in autism and liability to the broader autism phenotype. J Am Acad Child Adolesc Psychiatry 2002 May;41(5):572-9

  • "In a sample of families selected because each had exactly two affected sibs, we observed a remarkably high proportion of affected twin pairs, both MZ and DZ…"
    Greenberg DA, Hodge SE, Sowinski J, Nicoll D. Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet 2001 Nov;69(5):1062-7

  • "The highest OR [odds ratio] was found for vaginal breech delivery (OR 6.7), birth weights above 5 kg (OR 6.3), and second born twins (OR 4.1)."
    Thorngren-Jerneck K, Herbst A. Low 5-minute Apgar score: A population-based register study of 1 million term births. Obstet Gynecol 2001;98:65-70

  • "Among the children with a serious medical condition, 34.4% also had ante- or perinatal antecedents. Among the 33% without any medical factor, 77% also had ante- or perinatal antecedents."
    Bodier C, Lenoir P, Malvy J, Barthélemy C, Wiss M, Sauvage D. (2001) Autisme et pathologies associées. Étude clinique de 295 cas de troubles envahissants du developpment. [Autism and associated pathologies. Clinical study of 295 cases involving development disorders] Presse Médicale 2001 Sep 1; 30(24 Pt 1):1199-203.

  • "… specific complications that carried the highest risk of autism and PDD-NOS represented various forms of pathologic processes with no presently apparent unifying feature."
    Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics. 2001 Apr;107(4):E63.

  • "AD was identified in 18 of the 5,271 children and the incidence was 34 per 10,000 (0.34%). This value was more than twice the highest prevalence value previously reported in Japan. Children with AD had a significantly higher history of the meconium aspiration syndrome (p = .0010) than the controls. Autistic patients had different risk factors than CP." Note: CP (cerebral palsy) occurred in 57 of the 5,271 children.
    Matsuishi T, Yamashita Y, Ohtani Y, Ornitz E, Kuriya N, Murakami Y, Fukuda S, Hashimoto T, Yamashita F. Brief report: incidence of and risk factors for autistic disorder in neonatal intensive care unit survivors. J Autism Dev Disord. 1999 Apr;29(2):161-6

  • "…[obstetric] optimality score (OS), were compared in two groups: 78 families containing an autistic proband (ICD-10 criteria) and 27 families containing a down syndrome (DS) proband… RESULTS: Autistic and DS probands had a significantly elevated OS compared with unaffected siblings, regardless of birth order position. The elevation was mainly due to an increase in mild as opposed to severe obstetric adversities."
    Bolton PF, Murphy M, Macdonald H, Whitlock B, Pickles A, Rutter M. Obstetric complications in autism: consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):272-81

  • "Males with AS showed a trend toward lower Apgar scores at one minute …"
    Ghaziuddin M, Shakal J, Tsai L. Obstetric factors in Asperger syndrome: comparison with high-functioning autism. J Intellect Disabil Res. 1995 Dec;39 ( Pt 6):538-43.

  • "These data provide slight support for the contribution of nonspecific pre- and perinatal factors to other etiological bases of autism."
    Lord C, Mulloy C, Wendelboe M, Schopler E. Pre- and perinatal factors in high-functioning females and males with autism. J Autism Dev Disord. 1991 Jun;21(2):197-209.

  • In most of the pairs discordant for autism, the autistic twin had more perinatal stress.
    Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry. 1989 May;30(3):405-16.

  • "Abnormal presentation at birth is the only factor that occurred more frequently for the autistic sample…"
    Levy S, Zoltak B, Saelens T. A comparison of obstetrical records of autistic and nonautistic referrals for psychoeducational evaluations. J Autism Dev Disord. 1988 Dec;18(4):573-81.

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36 - Umbilical Cord Clamping

Clamping the umbilical cord at birth is a human invention. The umbilical cord is an infant's lifeline throughout gestation; it should go without saying that it remains the newborn's lifeline until lung function is established. Clamping the cord before a baby breathes can be expected to result in at least a brief period of oxygen deprivation.

Looking back at historical textbooks on obstetrics, waiting at least for the infant to breathe on its own was traditionally always required before cutting the cord [58-65].

From 1850 to 1930:
  • "A strong healthy child, as soon as it is born, will begin to breathe freely, and in most cases cry vigorously. As soon as it has thus given satisfactory proof of its respiratory power, you may at once proceed to separate it from its mother by tying and dividing the umbilical cord."
    Swayne JG (1856) Obstetric Aphorisms: For the use of students commencing midwifery practice. London: John Churchill, p 20.
  • "As soon as the child cries we may proceed to tie and separate the cord."
    Playfair WS (1880) A Treatise on the Science and Practice of Midwifery. Philadelphia: Henry C. Lea, p 283
  • "The cord should not be tied until the child has breathed vigorously a few times. When there is no occasion for haste, it is safer to wait until the pulsations of the cord have ceased altogether."
    Lusk WT (1882) The Science and Art of Midwifery. New York: D Appleton and Company, pp 214-215
  • "Immediately after its birth the child usually makes an inspiratory movement and then begins to cry. In such circumstances it should be placed between the patient's legs in such a manner to have the cord lax, and thus avoid traction upon it… Normally the cord should not be ligated until it has ceased to pulsate…"
    Williams JW (1917) Obstetrics: A Text-Book for the Use of Students and Practicioners, Fourth Edition. New York & London: D. Appleton and Company, pp 342-343
  • "As soon as the lungs begin to function, the circulation through the umbilical arteries normally ceases in from five to fifteen minutes after birth."
    Williams JW (1930) Obstetrics: A Text-Book for the Use of Students and Practicioners, Sixth Edition. New York: D. Appleton-Century, pp 418-419

By the 1940s a change of opinion is evident:

  • "We have adopted an intermediate course, feeling that to always wait for complete cessation of pulsation frequently interferes with the proper conduct of the third stage of labor, and at the same time, that most of the available blood in the cord had been incorporated in the fetal circulation during the few minutes immediately following delivery."
    Stander HJ (1941) Williams Obstetrics, Eighth Edition. New York, London: D. Appleton-Century company, pp 429-430.

  • "Whenever possible, clamping or ligating the umbilical cord should be deferred until its pulsations wane or, at least, for one or two minutes…
    There has been a tendency of late, for a number of reasons, to ignore this precept. In the first place the widespread use of analgesic drugs in labor has resulted in a number of infants whose respiratory efforts are sluggish at birth and whom the obstetrician wishes to turn over immediately to an assistant for aspiration of mucus, and if necessary, resuscitation. This readily leads to the habit of clamping all cords promptly."

    Eastman HJ (1950) Williams Obstetrics, Tenth Edition. New York: Appleton-Century-Crofts , pp 397-398

Would Williams recognize the 20th edition of his textbook?

  • "Although the theoretical risk of circulatory overloading from gross hypervolemia is formidable, especially in preterm and growth-retarded infants, addition of placental blood to the otherwise normal infant's circulation ordinarily does not cause difficulty… Our policy is to clamp the cord after first thoroughly clearing the infant's airway, all of which usually takes about 30 seconds."
    Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC, Hankins GDV, Clark SL, Williams JW, (1997) Williams Obstetrics, Twentieth Edition. Stamford, Conn: Appleton & Lange, pp 336-337.


Preventing jaundice

  • It appears that Saigal et al (1972) and Saigal & Usher (1977) may have initiated the fear that delayed clamping of the umbilical cord could result in circulatory overload, polycythemia (too many red blood cells) and jaundice. But polycythemia is more often a physiological response to abnormalities like methemoglobinemia, which results from a genetic or drug-induced abnormality of the hemoglobin molecule.

    Saigal S, O'Neill A, Surainder Y, Chua LB, Usher R. Placental transfusion and hyperbilirubinemia in the premature. Pediatrics. 1972 Mar;49(3):406-19.

    Saigal S, Usher RH. Symptomatic neonatal plethora. Biol Neonate. 1977;32(1-2):62-72.

  • Jellett (1910) in a Manual of Midwifery discussed the issue of polycythemia after stating, "The old dispute as to when the cord should be tied possesses now little more than an academic interest, as it is conclusively settled that this should not be done until all pulsations in the cord have ceased."

    Jellett cited research apparently well known in 1910: White (1785, 1773) had written about the absurdity of supposing that it was possible for the change from placental to pulmonary circulation, with all that this implies, to take place in a moment, "that this wonderful alteration in the human machine should be brought about in one instant of time, and at the will of a bystander?"

    Jellett further cited research by Schmidt (1894) in which it was found that 72 percent of children in whom immediate ligation of the cord was done were jaundiced, while only 42 percent were jaundiced when the cord was not tied until ten minutes after birth. It may be time to consider whether postnatal anemia isn't a greater risk for more infants than polycythemia and jaundice.

    Jellett H (1910) A Manual of Midwifery for Students and Practitioners. New York: William Wood & Company.

    White C (1773) A Treatise on the Management of Pregnant and Lying-In Women. Science History Publications/ Watson Publishing International, Canton MA, 1987.


A Radical Change

Whatever its motivation, the now routine clamping of the umbilical cord within 30 seconds following birth is a radical change from traditional practice. If an infant is breathing on its own at the time of cord clamping, the most important transition from fetal to neonatal life has taken place (see Mercer & Skovgaard, 2002). This transition has not taken place in an infant in need of resuscitation. It may be only a small minority of infants who do not breathe immediately at birth, but might this minority account for the increased prevalence of autism or other developmental disabilities?

Mercer JS, Skovgaard RL. Neonatal transitional physiology: a new paradigm. J Perinat Neonatal Nurs. 2002 Mar;15(4):56-75.
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