Page last updated at 23:00 GMT, Tuesday, 30 June 2009 00:00 UK
Problem pregnancy 'autism risk'
Boy with autism
There has been an increase in the number of autism diagnoses
Complications during pregnancy and giving birth later in life may increase the risk of having a child with autism, a review of dozens of studies suggests.
Researchers found the bulk of studies into maternal age and autism suggest the risk increases with age, and that fathers' age may play a role too.
The mothers of autistic children were also more likely to have suffered diabetes or bleeding during pregnancy.
The US review of 40 studies appears in the British Journal of Psychiatry.
The recorded number of children with autism has risen exponentially in the past 30 years but experts say this is largely due to improved detection and diagnosis, as well as a broadening of the criteria.
The cause of the condition is unclear, and the review team from the Harvard School of Public Health said there was "insufficient evidence" to point to any one prenatal factor as being significant.
They did however note that nine out of 13 studies suggested an increased risk for older mothers, a demographic group which has grown in the last three decades.
This ranged from a risk 27% higher for those aged between 30-34 compared to those aged 25-29, and over 100% higher for those over 40 compared to those under 30.
For fathers, every five years increased the chances of a child with autism by nearly 4%.
It is like trying to complete a huge jigsaw puzzle - we still just don't know how all the pieces fit together
The biological reasons for why this may be are unclear, but the researchers speculated that potential chromosomal abnormalities in the eggs of older women and mutations in the sperm of older men may be a factor.
Gestational diabetes - which affects four in 100 pregnancies - was associated with a two-fold increase in the risk of autism, while bleeding in pregnancy was alleged to carry an 81% increased risk.
However, the team noted that there was little information given about when in pregnancy bleeding occurred. Common and often inconsequential in early pregnancy, later on it can signify serious problems.
Such bleeding may deprive the baby of oxygen - a condition known as fetal hypoxia - and this is turn impacts upon the developing brain, potentially raising the risk of autism.
The team also found associations with medication use, with a particularly strong link with drugs for psychiatric problems.
However, they acknowledged it was impossible to tell whether this was a result of the medication itself or the genetic traits which may be shared between autism and conditions requiring such treatment.
Researchers said the key challenge was to work out how genetics and the environment interacted with each other to produce autism.
"The rising prevalence, coupled with the severe emotional and financial impact on the families, underscores the need for large, prospective, population-based studies with the goal of elucidating the modifiable risk factors, particularly those during the prenatal period," wrote lead author Hannah Gardner.
"Future investigations of prenatal exposures should also collect DNA to study potential gene-environment interactions."
Richard Mills of Research Autism said such reviews of existing studies were "very useful indeed".
"Age is a very interesting line of inquiry, but it is very hard to tease out one clear factor. It is like trying to complete a huge jigsaw puzzle - we still just don't know how all the pieces fit together."
The British Journal of Psychiatry (2009) 195: 7-14. doi: 10.1192/bjp.bp.108.051672
© 2009 The Royal College of Psychiatrists
Prenatal risk factors for autism: comprehensive meta-analysis
Hannah Gardener, ScD
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
Donna Spiegelman, ScD
Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts
Stephen L. Buka, ScD
Department of Community Health, Brown University, Providence, Rhode Island, USA
Correspondence: Hannah Gardener, Department of Neurology, University of Miami Miller School of Medicine, Post Office Box 016960 (M712), Miami, FL 33101, USA. Email: firstname.lastname@example.org
Declaration of interest
H.G. received a National Research Service Award grant from the Training Program in Psychiatric Epidemiology and Biostatistics (T32 MH17119). Partial funding was provided by the Stanley Medical Research Institute.
The aetiology of autism is unknown, although prenatal exposures have been the focus of epidemiological research for over 40 years.
To provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism.
PubMed, Embase and PsycINFO databases were searched for epidemiological studies that examined the association between pregnancy-related factors and autism. Forty studies were eligible for inclusion in the meta-analysis. Summary effect estimates were calculated for factors examined in multiple studies.
Over 50 prenatal factors have been examined. The factors associated with autism risk in the meta-analysis were advanced parental age at birth, maternal prenatal medication use, bleeding, gestational diabetes, being first born v. third or later, and having a mother born abroad. The factors with the strongest evidence against a role in autism risk included previous fetal loss and maternal hypertension, proteinuria, pre-eclampsia and swelling.
There is insufficient evidence to implicate any one prenatal factor in autism aetiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk.
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