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Cited by 736Autism Spectrum Disorder ResearchMaternal Mental Health During Pregnancy and PostpartumPrenatal Substance Exposure Effects

Prenatal risk factors for autism: comprehensive meta-analysis

Open access
Gardener, Hannah, Spiegelman, Donna, Buka, Stephen L.·2009·British Journal of Psychiatry
DOI 10.1192/bjp.bp.108.051672PMC PMC3712619
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Abstract

Background: The aetiology of autism is unknown, although prenatal exposures have been the focus of epidemiological research for over 40 years. Aims: To provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism. Method: 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. Results: 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. Conclusions: 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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  • The prenatal factors associated with autism risk in the meta-analysis by Gardener et al. were advanced paternal and maternal age at birth, gestational diabetes, gestational bleeding, multiple birth, being first born compared to being third or after, and maternal birth abroad.

    “The prenatal factors associated with autism risk in the meta-analysis provided by Gardener et al. (52) were advanced paternal and maternal age at birth, gestational diabetes, gestational bleeding, multiple birth, being first born compared to being third or after, and maternal birth abroad.”

    From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [52]

  • Two meta-analyses underlined the lack of studies with psychiatric diagnosis of parents before the birth of children with autism, suggesting that depression during pregnancy may be underestimated.

    “two meta-analyses (52, 97) underlined the lack of studies with psychiatric diagnosis of parents before the birth of children with autism, suggesting that depression during pregnancy may be underestimated.”

    From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [52]

  • Exposure to intrauterine infections was associated with a significant increase in risk for autism in the analysis limited to the four studies that controlled for multiple covariates or used sibling controls.

    “Exposure to intrauterine infections was associated with a significant increase in risk for autism in the analysis limited to the four studies that controlled for multiple covariates or used sibling controls”

    From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [81]

  • In Nordic countries, increased risk was found for offspring of mothers born abroad.

    “in Nordic countries, for offspring of mothers born abroad”

    From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [81]

  • Autism risk was found to be significantly increased for the offspring of mothers born abroad in a meta-analysis.

    “autism risk was found to be significantly increased for the offspring of mothers born abroad in a meta-analysis”

    From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [81]

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Research works printed but not linked: 1

  1. [77]Orisni N Li R Wolk A Spiegelman D (draft) Meta-analysis for dose-response relationships: examples, an evaluation of approximations, and software PMC3244608 22135359

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Authors
Gardener, H., Spiegelman, D., & Buka, S. L.
Affiliations
  • Harvard University (US)
  • Brown University (US)
Corresponding author
Gardener, Hannah
ORCID
Venue
British Journal of Psychiatry
Publisher
Royal College of Psychiatrists
Published
2009-07
Volume
195
Issue
1
Pages
7-14
ISSN
  • 0007-1250 (ISSN-L)
  • 1472-1465
DOI
10.1192/bjp.bp.108.051672
PMC
PMC3712619
OpenAlex
W2151382043
Cited by
736
References
100
Citations by year
2026: 21 · 2025: 35 · 2024: 40 · 2023: 41 · 2022: 47 · 2021: 51 · 2020: 50 · 2019: 39 · 2018: 53 · 2017: 60 · 2016: 36 · 2015: 66 · 2014: 49 · 2013: 49 · 2012: 50
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
www.cambridge.org/core/terms (unspecified, 3107 d)
Locations
  • The British Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • Brigham and Women's Hospital
  • National Institute of Mental Health (T32 MH 17119, T32MH017119)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
Keywords
autism spectrum disorder, prenatal risk factors, pregnancy complications, autism etiology, advanced parental age, gestational diabetes mellitus, maternal migration, fetal death, preeclampsia, maternal hypertension, proteinuria
MeSH terms
Autistic Disorder, Birth Order, Emigration and Immigration, Female, Fetal Hypoxia, Humans, Parents, Pregnancy, Pregnancy Complications, Regression Analysis, Risk Factors, Prevalence, Diabetes, Gestational

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