Intended for healthcare professionals

Rapid response to:


The causes of autism spectrum disorders

BMJ 2003; 326 doi: (Published 25 January 2003) Cite this as: BMJ 2003;326:173

Rapid Response:

Asphyxia at Birth Merits Investigation as the Cause of Autism in Some Children

The brain abnormalities reported in some cases of autism can be
viewed as a variant of Wernicke’s encephalopathy: a bilaterally symmetric
pattern of damage involving subcortical nuclei and the cerebellum [1].
Wernicke’s encephalopathy is found in cases of chronic alcohol
intoxication and factors, like thiamine (vitamin B1) deficiency that
interfere with aerobic metabolism [2]. Prenatal exposure to alcohol is
one of the co-morbid conditions associated with autistic disorder [3].
Maternal use of alcohol during pregnancy should be investigated in every
case of autism, as should use of all other drugs, like the anti-seizure
medication valproic acid [4].

Asphyxia at birth of 8 minutes or more produces a variant of
Wernicke’s encephalopathy with prominent damage of the inferior colliculi
in the midbrain auditory pathway [5]; asphyxia was inflicted
experimentally in monkeys by preventing pulmonary respiration then
clamping the umbilical cord. Monkeys allowed to survive several years
following asphyxia of even shorter duration developed a
“transneuronal”.pattern of pathology involving the cerebellum,
hippocampus, amygdala, mammillary bodies, corpus callosum, and temporal
and frontal lobe radiations [6] – areas of the brain affected in some
cases of autism [7].

Monkeys subjected to umbilical cord clamping and prevented from
breathing displayed a transient “hypotonic cerebral palsy;” they recovered
normal motor functions but remained hypoactive and were impaired in tasks
of short-to-long term memory function [8]. Spastic cerebral palsy was
later produced in monkeys subjected to prolonged partial hypoxia during
gestation, which produced damage of the motor cortex long associated with
cerebral palsy [9].

Meconium aspiration was found associated with autism by Matsuishi et
al. [10]. Meconium aspiration is suggestive of an asphyxic insult with
increased buildup of carbon dioxide stimulating respiratory attempts in
utero. Bodier et al. found autism associated most strongly with
complications at birth in cases without other co-morbid causes [11].
Complications at birth are associated with autism and merit as much
attention as genetic or other environmental causes [12]. Immediate
clamping of the umbilical cord has become a standard practice [13]. Could
this explain the increased incidence of autism? Hypovolemia and several
minutes of asphyxia can result if the cord is cut before an infant is
breathing on his own.

The auditory system of the brain is prominently affected by asphyxia
at birth, and this deserves investigation as cause of echolalic speech,
hyperacusis, verbal auditory agnosia[14], and the auditory attention
deficit disorder of children with autism [15].

1. Torvik A. Topographic distribution and severity of brain lesions
in Wernicke's encephalopathy. Clin Neuropathol. 1987 Jan-Feb;6(1):25-9.

2. Vortmeyer AO, Hagel C, Laas R. Haemorrhagic thiamine deficient
encephalopathy following prolonged parenteral nutrition. J Neurol
Neurosurg Psychiatry. 1992 Sep;55(9):826-9.

3. Nanson JL. Autism in fetal alcohol syndrome: a report of six
cases. Alcohol Clin Exp Res. 1992 Jun;16(3):558-65.

4. Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH.
Fetal valproate syndrome and autism: additional evidence of an
association. Dev Med Child Neurol. 2001 Mar;43(3):202-6.

5. Windle WF. Brain damage by asphyxia at birth. Sci Am. 1969

6. Faro MD, Windle WF. Transneuronal degeneration in brains of
monkeys asphyxiated at birth. Exp Neurol. 1969 May;24(1):38-53.

7. Kemper TL, Bauman M. Neuropathology of infantile autism. J
Neuropathol Exp Neurol. 1998 Jul;57(7):645-52.

8. 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.

9. Myers RE. Two patterns of perinatal brain damage and their
conditions of occurrence. Am J Obstet Gynecol. 1972 Jan 15;112(2):246-76.

10. 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.

11. Bodier C, Lenoir P, Malvy J, Barthelemy C, Wiss M, Sauvage D.
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 Med. 2001 Sep
1;30(24 Pt 1):1199-203.

12. Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for
infantile autism. Epidemiology. 2002 Jul;13(4):417-23.

13. [No authors listed] Utility of umbilical cord blood acid-base
assessment. ACOG Committee Opinion: Committee on Obstetric Practice.
Number 138--April 1994.
Int J Gynaecol Obstet. 1994 Jun;45(3):303-4.

14. Rapin I. Autism. N Engl J Med. 1997 Jul 10;337(2):97-104.

15. Simon N. Echolalic speech in childhood autism. Consideration of
possible underlying loci of brain damage. Arch Gen Psychiatry. 1975

Competing interests:  
None declared

Competing interests: No competing interests

27 January 2003
[Eileen] Nicole Simon
Parent / private researcher 11 Hayes Avenue, Lexington, MA 02420-3521