Are children born after assisted reproductive technology at increased risk of autism spectrum disorders? A systematic review

Hum Reprod. 2013 Dec;28(12):3316-27. doi: 10.1093/humrep/det380. Epub 2013 Oct 15.


Study question: Are children born after assisted reproductive technology (ART) at increased risk of autism spectrum disorders (ASD)?

Summary answer: There is no evidence that ART significantly increases the risk of ASD in the offspring.

What is known already: A few systematic reviews have explored the correlation between assisted conception and ASD with inconclusive results, partly due to the heterogeneity of diagnostic criteria and methodology in the different studies.

Study design, size, duration: Systematic review of 7 observational studies (2 cohort and 5 case-control) encompassing 9216 subjects diagnosed with ASD published since 2000.

Materials, setting, methods: Literature searches were conducted to retrieve observational studies on the risk of ASD in ART population. Databases searched included PubMed, EMBASE and PsycINFO. In order to obtain more consistent results, we only included the studies in which (i) subjects with either infantile autism or ASD could be identified according to international classification systems and (ii) the diagnosis was obtained from hospital records. Seven studies matched the inclusion criteria.

Main results and the role of chance: Four out of seven studies, including the two with the best quality scores, did not show an association between ART and ASD. The two papers supporting an increased risk of autism following ART had the lowest quality scores, due to major methodological limitations. Only one paper showed a protective role of ART.

Limitations, reasons for caution: In spite of the strict inclusion criteria applied as to the diagnosis of ASD, the papers selected are heterogeneous in many aspects including study design, definitions of ART, data source and analysed confounders.

Wider implications of the findings: At present, there is no evidence that ART is significantly associated with ASD and hence that current health policies should be modified. The divergent results of some of the studies suggest that further prospective, large and high-quality studies are still needed.

Study funding/competing interest(s): This work was supported, in part, by the Italian Ministry of Health and by Tuscany Region. The authors have no competing interests to declare.

Trial registration number: N/A.

Keywords: ART; ICSI; IVF; assisted conception; autism spectrum disorder.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Child
  • Child Development Disorders, Pervasive / etiology*
  • Cohort Studies
  • Female
  • Humans
  • Observational Studies as Topic
  • Reproductive Techniques, Assisted / adverse effects*
  • Risk