Autism, Viewpoint on the Brain Disorder

Maimburg RD, Vaeth M. Perinatal risk factors and infantile autism. Acta Psychiatr Scand.

2006

Oct;114(4):257-64.

We also found strong associations between children with infantile autism and

mothers with

foreign citizenship, children with congenital malformations and children

who needed

treatment at Neonatal Intensive Care Unit (NICU) after birth. When the

caesarean sections

were categorized into scheduled and unscheduled procedures, we

found only scheduled

caesarean sections to be associated with infantile autism.

2. Badawi N et al. Autism following a history of newborn encephalopathy: more than a

coincidence? Dev Med Child Neurol. 2006 Feb;48(2):85-9.

"... in a population-based study of moderate and severe term newborn encephalopathy

(NE) in

Western Australia ...infants with NE were 5.9

(95% CI 2.0–16.9)

times more likely

to be

diagnosed with an ASD than controls... this was not an expected association at the

outset of

the study"

3. Larsson HJ et al. Risk factors for autism: perinatal factors, parental psychiatric history,

and

socioeconomic status. Am J Epidemiol. 2005;161:916-25.

"In the unadjusted analyses, breech presentation, lowApgar score (less than or equal 7)

at 5

minutes, low birth weight (less than or equal 2,500 g), gestational age at birth of

less than 35

weeks, and being small for gestational age were associated with a

statistically significantly

increased risk of autism..."

Glasson EJ

et al

. Perinatal factors and the development of autism: a population study.

Arch Gen Psychiatry. 2004 Jun;61(6):618-27.

"Cases were more likely to have experienced fetal distress during labor

(OR, 1.64; 95%

CI, 1.15-2.34)

. Apgar scores calculated at 1 minute showed that significantly more

cases achieved a score of 6 or less

(54 [19.5%] of 277 cases with data recorded since

1991

..."

[12.9%] of 512 control subjects with data recorded since 1991)(OR, 1.6; 95% CI, 1.1-2.4),

and cases were more likely to have taken more than 1 minute before the onset of

spontaneous respiration

(OR, 1.4; 95% CI, 1.0-1.9)

Wilkerson DS

et al

. Perinatal complications as predictors of infantile autism. Int J

Neurosci. 2002 Sep;112(9):1085-98.

"… 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)."

Hultman CM

et al

. Perinatal risk factors for infantile autism. Epidemiology. 2002 Jul;13

(4):

417-23.

"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 (odds ratio) was greatest for 5-

min

Apgar score below 7.

. Zwaigenbaum L

et al

. 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

"Children with autism spectrum disorders have lower optimality (higher rates of

complications) than unaffected siblings…"

. Greenberg DA

et al

. 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

"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…"

. Bodier C

et al

. 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.

"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."

10.

Juul-Dam N

et al

. Prenatal, perinatal, and neonatal factors in autism, pervasive

developmental disorder-not otherwise specified, and the general population. Pediatrics.

2001 Apr;107(4):E63.

"… specific complications that carried the highest risk of autism and PDD-NOS

represented various forms of pathologic processes with no presently apparent

unifying

feature."

11.

Matsuishi T

et al

. 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

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.

. Bolton PF

et al

. Obstetric complications in autism: consequences or causes of the

condition? J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):272-81

"…[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.

. Ghaziuddin M

et al

. Obstetric factors in Asperger syndrome: comparison with high-

functioning autism. J Intellect Disabil Res. 1995 Dec;39 ( Pt 6):538-43.

"Males with AS showed a trend toward lower Apgar scores at one minute …"

. Lord C

et al

. Pre- and perinatal factors in high-functioning females and males with

autism. J Autism Dev Disord. 1991 Jun;21(2):197-209.

"These data provide slight support for the contribution of nonspecific pre- and

perinatal

factors to other etiological bases of autism."

. Steffenburg S

et al

. A twin study of autism in Denmark, Finland, Iceland, Norway and

Sweden. J Child Psychol Psychiatry. 1989 May;30(3):405-16.

In most of the pairs discordant for autism, the autistic twin had more perinatal stress.

. Levy S

et al

. A comparison of obstetrical records of autistic and nonautistic referrals

for

psychoeducational evaluations. J Autism Dev Disord. 1988 Dec;18(4):573-81.

"Abnormal presentation at birth is the only factor that occurred more frequently for

the

autistic sample…"

. Lobascher ME

et al

. Childhood autism: an investigation of aetiological factors in twenty-

five cases. Br J Psychiatry. 1970 Nov;117(540):525-9.

"There were more complications of labour in the experimental group than the controls

(p=0.001)

...Abnormal conditions of the child noted at delivery occurred significantly

more frequently in the experimental group, e.g. difficulty with resuscitation, cord around

neck, fractured skull, cyanosis, head moulding, bruising, jaundice

(p<0.0004).

2 - Perinatal complications
A lapse in respiration at birth has been shown to
interfere with metabolic activity in auditory nuclei like
the inferior colliculus [1]. Therefore the effects of birth
injury should be considered relevant in cases of
developmental language disorder. However, the
research with monkeys subjected to asphyxia is now
totally overlooked. The researchers themselves
described the brainstem lesions caused by asphyxia as
possibly responsible for “minimal cerebral dysfunction,”
a condition apparently not regarded to have potentially
bad long-term effects.

Ranck and Windle (1959) did note the similarity of the
brainstem lesions caused by asphyxia to the pattern of
brainstem nuclei stained by bilirubin in kernicterus [2].
Auditory problems of children with kernicterus (or
erythroblastosis fetalis) had been discussed in the
literature [3]. Gilles (1963) commented on the
similarity of brainstem lesions caused by asphyxia to
the neuropathology observed in Moebius syndrome,
and he proposed that impairment of auditory nuclei by
asphyxia at birth should be investigated as a possible
cause of aphasic disorders in childhood [4]. Gilles’
comments were published in a brief abstract of
conference proceedings, which is not even listed in the
online Index Medicus, PubMed, and he has not
published on this subject since.

Children normally learn to speak “by ear,” and more
easily than adults learn a second language before
learning to read. Auditory problems have long been
recognized in children with autism [5]. The possible
association of auditory system dysfunction and
difficulties learning to speak should therefore not be
neglected.

Perinatal complications have been documented more
frequently than any other medical condition in the
records of children with autism, yet still are not viewed
as a causal factor (see citations 5a-t in the previous
section, and 6a-s below). Difficulties at birth are most
often attributed to some vague hypothetical genetic
predisposition. Statistics are tabulated with at best
some brief remark about effects on the brain, with no
consideration of how the disabilities so characteristic of
autism might result.

Juul-Dam et al (2001) described the perinatal factors
associated with autism as "mild" and without any
unifying feature [6a]. But the unifying feature of all
perinatal complications is the possibility of a lapse in
respiration, and no lapse in oxygen delivery should
ever be viewed as "mild." Oxygen is the most essential
and urgent on-going need of all species dependent
upon aerobic metabolism.

Table 2 is a list of excerpts from papers that point to
complications at birth as a predisposition for
developing autism. Many of these papers attempt to
show that the problem at birth was due to some defect
in the fetus or the mother. But problems like abnormal
presentation, such as breech birth or being born with
the umbilical cord around the neck, can happen in any
birth. Birth has long been acknowledged to be
hazardous both for infant and mother. To place blame
on the fetus or mother is senseless and stigmatizing.
Children with classic autism (as described by Kanner)
are physically perfect. Children identified with “minor
birth defects” are likely those who suffered prenatal
infection or exposure to alcohol or other toxic
substances.

Bodier et al. (2001) in an investigation of 295 cases of
autism in France, found only one third had no
discernable medical condition, but perinatal problems
had occurred in 77 percent of the children without
other medical problems [6b].

Matsuishi et al. (1999) investigated the occurrence of
autistic disorder in 5,271 infants followed after
discharge from a neonatal intensive care unit in Japan
[23]. Of these infants, 18 were later diagnosed as
autistic and 57 with cerebral palsy. The incidence of
18 among 5,271 (34 per 10,000) was noted to be more
than twice the highest prevalence rate previously
reported in Japan. The most significant risk factor
associated with autism was meconium aspiration, which
might indicate a degree of asphyxiation great enough
for the infant to have begun gasping for air before
birth. Different risk factors were found for cerebral
palsy [6c].

1. Auditory system damage
caused by asphyxia at birth

Windle WF (1969) Brain
damage by asphyxia at birth.
Myers RE (1972) Two
patterns of perinatal brain
damage and their conditions
of occurrence.

2. Kernicterus-like damage
caused by asphyxia at birth

Ranck JB & Windle WF
(1959). Brain damage in the
monkey, Macaca mulatta, by
asphyxia neonatorum.

3. Auditory impairments in
kernicterus

Dublin WB (1951) Neurologic
lesions of erythroblastosis
fetalis in relation to nuclear
deafness.
Keleman G (1956)
Erythroblastosis fetalis

4. Childhood aphasic disorders?

Gilles FH (1963) Selective
symmetrical neuronal
necrosis of certain brain
stem tegmental nuclei in
temporary cardiac standstill.

5. Auditory impairments in autism

Hayes RW & Gordon AG
(1977) Auditory abnormalities
in autistic children.
Student M & Sohmer H
(1978) Evidence from
auditory nerve and brainstem
evoked responses for an
organic brain lesion in
children with autistic traits.
Skoff BF et al. (1980)
Prolonged brainstem
transmission time in autism.
Rosenblum SM et al. (1980)
Auditory brainstem evoked
responses in autistic
children.
Taylor MJ et al. (1982)
Auditory brainstem response
abnormalities in autistic
children.
Lenn, N.J et al (1986).
Auditory processing deficit in
a patient with Rett syndrome.
Seri S et al. (1999) Autism in
tuberous sclerosis: evoked
potential evidence for a deficit
in auditory sensory
processing.
Rosenhall U et al. (1999)
Autism and hearing loss.
Rosenhall U et al. (2003)
Autism and auditory brain
stem responses.
Siegal M & Blades M. (2003)
Language and auditory
processing in autism.
Tecchio F et al. (2003)
Auditory sensory processing
in autism: a
magnetoencephalographic
study.
Ceponiene R et al. (2003)
Speech-sound-selective
auditory impairment in
children with autism: they can
perceive but do not attend.
Gage NM et al. (2003)
Cortical auditory system
maturational abnormalities in
children with autism
disorder: an MEG
investigation.
Khalfa S et al. (2004).
Increased perception of
loudness in autism.
Teder-Salejarvi WA, et al
(2005) Auditory spatial
localization and attention
deficits in autistic adults.

6. Perinatal complications and
autism

Juul-Dam N et al (2001)
Prenatal, perinatal, and
neonatal factors in autism,
pervasive developmental
disorder-not otherwise
specified, and the general
population.
Bodier C et al. (2001)
[Autism and associated
pathologies. Clinical study of
295 cases involving
development disorders].
Matsuishi T et al (1999) Brief
report: incidence of and risk
factors for autistic disorder in
neonatal intensive care unit
survivors.

1. Auditory system damage caused by asphyxia at birth

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

2. Kernicterus-like damage caused by asphyxia at birth

Ranck JB, Windle WF (1959). Brain damage in the monkey, Macaca mulatta, by asphyxia
neonatorum. Experimental Neurology 1:130-154.

3. Auditory impairments in kernicterus

Dublin WB (1951) Neurologic lesions of erythroblastosis fetalis in relation to nuclear
deafness. Am J Clin Pathol. 1951 Oct;21(10):935-9
Keleman G (1956) Erythroblastosis fetalis. AMA Arch Otolaryngol. 1956 Apr;63(4):392-8.

4. Childhood aphasic disorders?

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.

5. Auditory impairments in autism

Hayes RW, Gordon AG (1977) Auditory abnormalities in autistic children. Lancet 1977 Oct
8; 2(8041):767.
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.
Skoff BF, Mirsky AF, Turner D (1980) Prolonged brainstem transmission time in autism.
Psychiatry Research 2:157-166.
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.
Taylor MJ, Rosenblatt B, Linschoten L (1982) Auditory brainstem response abnormalities
in autistic children. Canadian Journal of Neurological Sciences 9:429-433.
Lenn, N.J., Olsho, L.W., & Turk, W.R. (1986). Auditory processing deficit in a patient with
Rett syndrome. American Journal of Medical Genetics, 24, 153-156 (suppl 1)
Seri S, Cerquiglini A, Pisani F, Curatolo P (1999) Autism in tuberous sclerosis: evoked
potential evidence for a deficit in auditory sensory processing. Clinical Neurophysiology
110:1825-30.
Rosenhall U, Nordin V, Sandstrom M, Ahlsen G, Gillberg C. (1999) Autism and hearing
loss. Journal of Autism and Developmental Disorders 29:349-57.
Rosenhall U, Nordin V, Brantberg K, Gillberg C. (2003) Autism and auditory brain stem
responses. Ear Hear. 2003 Jun;24(3):206-14.
Siegal M, Blades M. (2003) Language and auditory processing in autism. Trends Cogn
Sci. 2003 Sep;7(9):378-380
Tecchio F, Benassi F, Zappasodi F, Gialloreti LE, Palermo M, Seri S, Rossini PM. (2003)
Auditory sensory processing in autism: a magnetoencephalographic study. Biol
Psychiatry. 2003 Sep 15;54(6):647-54.
Ceponiene R, Lepisto T, Shestakova A, Vanhala R, Alku P, Naatanen R, Yaguchi K.
Speech-sound-selective auditory impairment in children with autism: they can perceive
but do not attend. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5567-72.
Gage NM, Siegel B, Roberts TP. Cortical auditory system maturational abnormalities in
children with autism disorder: an MEG investigation. Brain Res Dev Brain Res. 2003 Sep
10;144(2):201-9.
Khalfa S, Bruneau N, Roge B, Georgieff N, Veuillet E, Adrien JL, Barthelemy C, Collet L.
Increased perception of loudness in autism. Hear Res. 2004 Dec;198(1-2):87-92.
Teder-Salejarvi WA, Pierce KL, Courchesne E, Hillyard SA. Auditory spatial localization
and attention deficits in autistic adults. Brain Res Cogn Brain Res. 2005 May;23(2-3):221-
34.

6. Perinatal complications and autism

Maimburg RD, Vaeth M. Perinatal risk factors and infantile autism. Acta Psychiatr Scand.
2006 Oct;114(4):257-64.
Badawi N, Novak I, McIntyre S, Edwards K, Raye S, deLacy M, Bevis E, Flett P, van
Essen P, Scott H, Tungaraza K, Sealy M, McCann V, Reddihough D, Reid S, Lanigan A,
Blair E, de Groot J, Watson L. Autism following a history of newborn encephalopathy:
more than a coincidence? Dev Med Child Neurol. 2006 Feb;48(2):85-9.
Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, Schendel D,
Thorsen P, Mortensen PB. Risk factors for autism: perinatal factors, parental psychiatric
history, and socioeconomic status. Am J Epidemiol. 2005 May 15;161(10):916-25;
discussion 926-8.
Gillberg C, Cederlund M. Asperger syndrome: familial and pre- and perinatal factors. J
Autism Dev Disord. 2005 Apr;35(2):159-66.
Glasson EJ, Bower C, Petterson B, de Klerk N, Chaney G, Hallmayer JF. Perinatal
factors and the development of autism: a population study. Arch Gen Psychiatry. 2004
Jun;61(6):618-27.
Wilkerson DS, Volpe AG, Dean RS, Titus JB. Perinatal complications as predictors of
infantile autism. Int J Neurosci. 2002 Sep;112(9):1085-98.
Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism.
Epidemiology. 2002 Jul;13(4):417-23.
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
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
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
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.
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.
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
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
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.
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.
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.
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.
Lobascher ME, Kingerlee PE, Gubbay SS. Childhood autism: an investigation of
aetiological factors in twenty-five cases. Br J Psychiatry. 1970 Nov;117(540):525-9.