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Perinatal risk factors for autism


Clinical bottom line

Risk of autism was associated with smoking in early pregnancy, maternal birth outside Europe or North America, Caesarian delivery, small for dates, low Apgar and congenital malformations. The implications are that intrauterine and neonatal factors are important factors for autism.


CM Hultman et al. Perinatal risk factors for infantile autism. Epidemiology 2002 13: 417-423.


This was a comprehensive study of the medical birth register of the whole of Sweden, in which information had been prospectively entered since 1973, and where all pregnancies have a high degree of support, with up to nine ante-natal visits.

All infants born in Sweden from 1987 to 1994 with an ICD code for discharge with a diagnosis of infantile autism by age nine years were the cases. Controls were individually matched by sex, year and hospital of birth, with five controls per case. Controls were alive and had no diagnosis of autism at the time of case-subject diagnosis. Analysis included associations with maternal characteristics (age, smoking place of birth), pregnancy and delivery complications (hypertension during pregnancy, diabetes, vacuum or Caesarian delivery), and infant characteristics (gestational age, birth weight, season of birth).


The mean age at first diagnosis of autism was 4.4 years for boys and 4.6 years for girls, for a case-sample of 408 children (321 boys and 87 girls). Out of many associations examined, those with a statistically significant odds ratio are shown in Table 1.

Table 1: Significant associations with diagnosis of infantile autism

Maternal, delivery or infant characteristic

Odds ratio (95% CI)

Daily smoking during pregnancy

1.4 (1.1 to 1.8)

Maternal birth outside Europe or N America

3.0 (1.7 to 5.2)

Caesarean delivery

1.6 (1.1 to 2.3)

Small for gestational age

2.1 (1.1 to 3.9)

Apgar below 7 at five minutes

3.2 (1.2 to 8.2)

Presence of congenital malformation

1.8 (1.1 to 3.1)


Clearly intrauterine environmental factors are playing a part in the development of autism. It seems unlikely that there will be a single cause, genetic or environmental, but adverse intrauterine and neonatal conditions are likely to result in more frequent autism in infants.