Prenatal fever and autism risk
Open accessAbstract
Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.
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The link between MIA and enhanced risk for ASD is bolstered by large-scale population-based studies showing small but significantly increased risk due to maternal prenatal infections.
“The link between MIA and enhanced risk for ASD is bolstered by large-scale population-based studies showing small but significantly increased risk due to maternal prenatal infections [117–122].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [121]
Children with ASD and GI problems may be particularly likely to have been exposed to fever or infection in utero.
“with recent data suggesting that children with ASD and GI problems may be particularly likely to have been exposed [56, 67–70].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [67]
In utero exposure to fever or infection, particularly of viral origin, is a prominent environmental risk factor for ASD.
“A prominent environmental risk factor for ASD may be in utero exposure to fever or infection, particularly of viral origin, with recent data suggesting that children with ASD and GI problems may be particularly likely to have been exposed [56, 67–70].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [67]
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- Authors
- Hornig, M., Bresnahan, M. A., Che, X., Schultz, A. F., Ukaigwe, J. E., Eddy, M. L., Hirtz, D., Gunnes, N., Lie, K. K., Magnus, P., Mjaaland, S., Reichborn-Kjennerud, T., Schjølberg, S., Øyen, A.-S., Levin, B., Susser, E. S., Stoltenberg, C., & Lipkin, W. I.
- Affiliations
- Columbia University (US)
- New York State Psychiatric Institute (US)
- National Institutes of Health (US)
- Norwegian Institute of Public Health (NO)
- Corresponding author
- Hornig, M
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2017-06-13
- Volume
- 23
- Issue
- 3
- Pages
- 759-766
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5822459
- OpenAlex
- W2624811387
- Cited by
- 222
- References
- 54
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 23 · 2023: 34 · 2022: 19 · 2021: 23 · 2020: 33 · 2019: 24 · 2018: 25 · 2017: 6
- FWCI
- 13.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- BIBSYS Brage (BIBSYS (Norway)) (acceptedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Funders
- Simons Foundation Autism Research Initiative
- Helse- og Omsorgsdepartementet
- Norges Forskningsråd (196452, 190694, 189457)
- Utdannings- og forskningsdepartementet
- National Institutes of Health (1r56ns086122-01a1)
- National Institute of Neurological Disorders and Stroke (U01NS047537, R56 NS086122, NS47537)
- 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
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- autism spectrum disorder, maternal infection, prenatal infection, second trimester, dose-response relationship, innate immune response, maternal immune activation, autism risk
- MeSH terms
- Autism Spectrum Disorder, Adult, Autistic Disorder, Female, Fever, Gestational Age, Humans, Immunity, Innate, Infant, Infant, Newborn, Infections, Genetic Linkage, Male, Mothers, Norway, Pregnancy, Pregnancy Trimester, Second, Prenatal Exposure Delayed Effects, Prospective Studies, Surveys and Questionnaires, Registries, Risk Factors, Odds Ratio, Maternal Exposure
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