Evidence of perinatal complications associated with autism
1. van Handel M, Swaab H, de Vries LS, Jongmans MJ.Long-term cognitive and
behavioral consequences of neonatal encephalopathy following perinatal asphyxia:
a review. Eur J Pediatr. 2007 Apr 11; [Epub ahead of print].
"Most outcome studies have focused on neurological functioning and
severe deficits in young children (<4 years). In general, very few children
with mild encephalopathy show neurological impairments or have
developed severe mental or motor retardation at preschool age. ... Only a
few studies looked at the behavioral consequences of NE. Those studies
found elevated rates of hyperactivity and autism in children with moderate
2. Kolevzon A, Gross R, Reichenberg A.Prenatal and perinatal risk factors for
autism: a review and integration of findings. Arch Pediatr Adolesc Med. 2007 Apr;
"According to our review, 3 parental characteristics and 2 obstetric
conditions emerge as potential risk factors for autism: namely, paternal
age, maternal age, maternal immigration, growth restriction, and newborn
hypoxia. In analyses that adjusted for confounding variables, these factors
usually remained statistically significant."
3. 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."
4. 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"
5. 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..."
6. Gillberg C, Cederlund M. Asperger syndrome: familial and pre- and perinatal
factors. J Autism Dev Disord. 2005 Apr;35(2):159-66.
"Five children had had an Apgar score of 6 or under at 1, 5 , or 10 minutes,
and 3 of these had scores of 1 or 2 (i.e., they had severe postnatal
asphyxia). ... Of the 100 individuals, 58 had one or more remarks in their
birth- or perinatal records about a serious problem in the peri-/neonatal
7. Cederlund M, Gillberg C. One hundred males with Asperger syndrome: a
clinical study of background and associated factors. Dev Med Child Neurol. 2004
For 58 of 99 children, some kind of abnormality was noted in their neonatal
record. ... Twenty-two had had hyperbilirubinemia (plasma bilirubin more
than 200μmol/l), ... Hyperbilirubinemia occurs in about 10% of newborn
infants... Forty-five of 92 children (49%) for whom fairly detailed data about
early language development were available, clearly did not have normal
language development at 2 years of age. It cannot be concluded that the
remainder had normal language development.
8. 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)."
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)."
10. Hultman CM et al. Perinatal risk factors for infantile autism. Epidemiology.
"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."
11. 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;
"Children with autism spectrum disorders have lower optimality (higher
rates of complications) than unaffected siblings…"
12. 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…"
13. 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."
14. 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."
15. 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):
"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."
16. 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."
17. 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
18. 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."
19. 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
20. 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):
"Abnormal presentation at birth is the only factor that occurred more
frequently for the autistic sample…"
21. 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)."