Maternal immunoreactivity to herpes simplex virus 2 and risk of autism spectrum disorder in male offspring
Open accessAbstract
The cause (or causes) of most cases of autism spectrum disorder is unknown. Evidence from epidemiological studies and work in animal models of neurodevelopmental disorders suggest that both genetic and environmental factors may be implicated. The latter include gestational infection and immune activation. In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection may contribute to the pathogenesis of autism spectrum disorder and have the potential to drive new efforts to monitor women more closely for cryptic gestational infection and to implement suppressive therapy during pregnancy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [68]
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 [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
Diagnostic and Statistical Manual of Mental Disorders, 5th ed.
Carter, M. J. (2014) · Therapeutic Recreation Journal · Cited by 15,154 · see citing works
Global Prevalence of Autism and Other Pervasive Developmental Disorders
Elsabbagh, M., Divan, G., Koh, Y., Kim, Y. S., Kauchali, S., Marcín, C., Montiel‐Nava, C., Patel, V., Paula, C. S., Wang, C., et al. (2012) · Autism Research · doi:10.1002/aur.239 · Cited by 2,636 · see citing works
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
Hallmayer, J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.76 · Cited by 1,970 · see citing works
Sex differences in autism spectrum disorders
Werling, D. M., & Geschwind, D. H. (2013) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32835ee548 · Cited by 1,245 · see citing works
Whitley, R. J., Kimberlin, D. W., & Roizman, B. (1998) · Clinical Infectious Diseases · doi:10.1086/514600 · Cited by 1,151 · see citing works
Cohort Profile Update: The Norwegian Mother and Child Cohort Study (MoBa).
Magnus, P., Birke, C., Vejrup, K., Haugan, A., Alsaker, E., Daltveit, A., Handal, M., Haugen, M., Høiseth, G., Knudsen, G., et al. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw029 · Cited by 936 · see citing works
Self-citationMaternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders
Atladóttir, H. Ó., Thorsen, P., Østergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., & Parner, E. T. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1006-y · Cited by 916 · see citing works
Maternal Intrauterine Infection, Cytokines, and Brain Damage in the Preterm Newborn
Dammann, O., & Leviton, A. (1997) · Pediatric Research · doi:10.1203/00006450-199707000-00001 · Cited by 886 · see citing works
Meyer, U., Nyffeler, M., Engler, A., Urwyler, A., Schedlowski, M., Knuesel, I., Yee, B. K., & Feldon, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-06.2006 · Cited by 774 · see citing works
Brown, Z. A., Wald, A., Morrow, R. A., Selke, S., Zeh, J., & Corey, L. (2003) · JAMA · doi:10.1001/jama.289.2.203 · Cited by 679 · see citing works
Malkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., & Patterson, P. H. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.01.011 · Cited by 662 · see citing works
Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons
Wald, A., Zeh, J. E., Selke, S., Warren, T. J., Ryncarz, A. J., Ashley, R. L., Krieger, J. N., & Corey, L. (2000) · New England Journal of Medicine · doi:10.1056/nejm200003233421203 · Cited by 580 · see citing works
The Co-Morbidity Burden of Children and Young Adults with Autism Spectrum Disorders
Kohane, I. S., McMurry, A., Weber, G., MacFadden, D., Rappaport, L., Kunkel, L., Bickel, J., Wattanasin, N., Spence, S., Murphy, S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033224 · Cited by 562 · see citing works
Maternal infection and immune involvement in autism
Patterson, P. H. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.03.001 · Cited by 520 · see citing works
Immune mediators in the brain and peripheral tissues in autism spectrum disorder
Estes, M. L., & McAllister, A. K. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3978 · Cited by 514 · see citing works
Maternal lifestyle and environmental risk factors for autism spectrum disorders
Lyall, K., Schmidt, R. J., & Hertz-Picciotto, I. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyt282 · Cited by 427 · see citing works
Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism
Brown, A. S. (2012) · Developmental Neurobiology · doi:10.1002/dneu.22024 · Cited by 420 · see citing works
Evidence-Based Assessment of Autism Spectrum Disorders in Children and Adolescents
Ozonoff, S. J., Goodlin‐Jones, B. L., & Solomon, M. (2005) · Journal of Clinical Child & Adolescent Psychology · doi:10.1207/s15374424jccp3403_8 · Cited by 417 · see citing works
Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders
Atladóttir, H. O., Pedersen, M. G., Thorsen, P., Mortensen, P. B., Deleuran, B., Eaton, W. W., & Parner, E. T. (2009) · Pediatrics · doi:10.1542/peds.2008-2445 · Cited by 404 · see citing works
Activation of the maternal immune system induces endocrine changes in the placenta via IL-6
Hsiao, E. Y., & Patterson, P. H. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.12.017 · Cited by 402 · see citing works
Transfer of Inflammatory Cytokines Across the Placenta
Zaretsky, M. V., Alexander, J. M., Byrd, W., & Bawdon, R. E. (2004) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000114980.40445.83 · Cited by 376 · see citing works
Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study
Atladóttir, H. Ó., Henriksen, T. B., Schendel, D. E., & Parner, E. T. (2012) · Pediatrics · doi:10.1542/peds.2012-1107 · Cited by 369 · see citing works
Maternal Autoimmune Diseases, Asthma and Allergies, and Childhood Autism Spectrum Disorders
Croen, L., Grether, J. K., Yoshida, C. K., Odouli, R., & de Water, J. V. (2005) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.159.2.151 · Cited by 360 · see citing works
Goines, P. E., Croen, L. A., Braunschweig, D., Yoshida, C. K., Grether, J., Hansen, R., Kharrazi, M., Ashwood, P., & Van de Water, J. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-13 · Cited by 351 · see citing works
Neu, N. M., Duchon, J. M., & Zachariah, P. (2014) · Clinics in Perinatology · doi:10.1016/j.clp.2014.11.001 · Cited by 291 · see citing works
Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness
Patterson, P. H. (2002) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(02)00299-4 · Cited by 269 · see citing works
Jones, K. L., Croen, L. A., Yoshida, C. K., Heuer, L., Hansen, R., Zerbo, O., DeLorenze, G. N., Kharrazi, M., Yolken, R., Ashwood, P., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.77 · Cited by 260 · see citing works
Fetal Inflammatory Response and Brain Injury in the Preterm Newborn
Malaeb, S. N., & Dammann, O. (2009) · Journal of Child Neurology · doi:10.1177/0883073809338066 · Cited by 245 · see citing works
An Inquiry into the Molecular Basis of HSV Latency and Reactivation
Roizman, B., & Whitley, R. J. (2013) · Annual Review of Microbiology · doi:10.1146/annurev-micro-092412-155654 · Cited by 235 · see citing works
Maternal Exposure to Herpes Simplex Virus and Risk of Psychosis Among Adult Offspring
Buka, S. L., Cannon, T. D., Torrey, E. F., & Yolken, R. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.09.022 · Cited by 233 · see citing works
Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism
Martin, L. A., Ashwood, P., Braunschweig, D., Cabanlit, M., Van de Water, J., & Amaral, D. G. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.12.007 · Cited by 231 · see citing works
Challis, J. R. G., Newnham, J. P., Petraglia, F., Yeganegi, M., & Bocking, A. D. (2012) · Placenta · doi:10.1016/j.placenta.2012.11.007 · Cited by 212 · see citing works
Abdallah, M. W., Larsen, N., Grove, J., Nørgaard-Pedersen, B., Thorsen, P., Mortensen, E. L., & Hougaard, D. M. (2013) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.639803 · Cited by 186 · see citing works
Johnston, C., & Corey, L. (2015) · Clinical Microbiology Reviews · doi:10.1128/cmr.00043-15 · Cited by 177 · see citing works
Brimberg, L., Sadiq, A., Gregersen, P. K., & Diamond, B. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.101 · Cited by 172 · see citing works
Jenum, P. A., Stray‐Pedersen, B., Melby, K. K., et al. (1998) · Journal of Clinical Microbiology · doi:10.1128/jcm.36.10.2900-2906.1998 · Cited by 169 · see citing works
Brown, Z. A., Wald, A., Morrow, R. A., et al. (2003) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000070126.90718.7b · Cited by 159 · see citing works
The Role of Cytokines and Inflammatory Cells in Perinatal Brain Injury
McAdams, R. M., & Juul, S. E. (2012) · Neurology Research International · doi:10.1155/2012/561494 · Cited by 148 · see citing works
Avgil, M., & Ornoy, A. (2005) · Reproductive Toxicology · doi:10.1016/j.reprotox.2004.11.014 · Cited by 146 · see citing works
The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness
Hornig, M. (2013) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32836208de · Cited by 138 · see citing works
Self-citationVogel, N., Kirisits, M., Michael, E., et al. (1996) · Clinical Infectious Diseases · doi:10.1093/clinids/23.5.1055 · Cited by 132 · see citing works
Risk factors in autism: Thinking outside the brain
Matelski, L., & van de Water, J. A. (2015) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.11.003 · Cited by 127 · see citing works
The Autism Birth Cohort: a paradigm for gene–environment–timing research
Stoltenberg, C., Schjølberg, S., Bresnahan, M., Hornig, M., Hirtz, D., Dahl, C., Lie, K. K., Reichborn-Kjennerud, T., Schreuder, P., Alsaker, E., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.143 · Cited by 119 · see citing works
Self-citationYeganegi, M., Watson, C. S., Martins, A. J., et al. (2009) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2008.12.032 · Cited by 115 · see citing works
Fetal Gender Differences in Preterm Birth: Findings in a North American Cohort
McGregor, J., Leff, M., Orleans, M., et al. (1992) · American Journal of Perinatology · doi:10.1055/s-2007-994668 · Cited by 109 · see citing works
Miranda, J. D., Yaddanapudi, K., Hornig, M., Villar, G., Serge, R., & Lipkin, W. I. (2010) · mBio · doi:10.1128/mbio.00176-10 · Cited by 102 · see citing works
Self-citationChow, S. S. W., Craig, M. E., Jones, C., Hall, B., Catteau, J., Lloyd, A. R., & Rawlinson, W. D. (2008) · Cytokine · doi:10.1016/j.cyto.2008.06.009 · Cited by 97 · see citing works
Neonatal Herpes Simplex Virus Infections: Where Are We Now?
Thompson, C., & Whitley, R. J. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-7185-2_15 · Cited by 83 · see citing works
Sl, S., Griffiths, P. D., Corey, L., et al. (2004) · Antiviral Research · doi:10.1016/j.antiviral.2004.06.004 · Cited by 81 · see citing works
Examination of the association between male gender and preterm delivery
Brettell, R., Yeh, P., & Impey, L. W. M. (2008) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2008.07.030 · Cited by 78 · see citing works
Changes of serum immunoglobulins IgG, IgA, IgM, and IgE during pregnancy.
Amino, N., Tanizawa, O., Miyai, K., et al. (1978) · PubMed · Cited by 77 · see citing works
Steeb, H., Ramsey, J. M., Guest, P. C., Stocki, P., Cooper, J. D., Rahmoune, H., Ingudomnukul, E., Bonnie Auyeung, B., Ruta, L., Baron‐Cohen, S., et al. (2014) · Molecular Autism · doi:10.1186/2040-2392-5-4 · Cited by 72 · see citing works
Virologic and Immunologic Evidence of Multifocal Genital Herpes Simplex Virus 2 Infection
Johnston, C., Zhu, J., Jing, L., et al. (2014) · Journal of Virology · doi:10.1128/jvi.03285-13 · Cited by 63 · see citing works
Congenital and Perinatal Infections: Throwing New Light with an Old TORCH
Shet, A. (2010) · The Indian Journal of Pediatrics · doi:10.1007/s12098-010-0254-3 · Cited by 62 · see citing works
Enright, A. M., & Prober, C. G. (2004) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2004.03.005 · Cited by 52 · see citing works
Potter, J. A., Garg, M., Girard, S., & Abrahams, V. M. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.114.124032 · Cited by 35 · see citing works
Eskild, A., Jeansson, S. L., Stray‐Pedersen, B., et al. (2002) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2002.01534.x · Cited by 32 · see citing works
Chemla, C., Villena, I., Aubert, D., et al. (2002) · Clinical and Vaccine Immunology · doi:10.1128/cdli.9.2.489-490.2002 · Cited by 32 · see citing works
CONGENITAL TOXOPLASMOSIS AFTER A PRECONCEPTIONAL OR PERICONCEPTIONAL MATERNAL INFECTION
Robert-Gangneux, F., Yera, H., D’Hervé, D., et al. (2009) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e3181966020 · Cited by 30 · see citing works
Congenital toxoplasma chorioretinitis transmitted by preconceptionally immune women
Dollfus, H., Dureau, P., Hennequin, C., et al. (1998) · British Journal of Ophthalmology · doi:10.1136/bjo.82.12.1444 · Cited by 27 · see citing works
Olsen, A. O., Ørstavik, I., Dillner, J., et al. (1998) · Apmis · doi:10.1111/j.1699-0463.1998.tb01366.x · Cited by 25 · see citing works
Functional genomics approaches to understand cytomegalovirus replication, latency and pathogenesis
Landais, I., & Nelson, J. A. (2013) · Current Opinion in Virology · doi:10.1016/j.coviro.2013.06.002 · Cited by 23 · see citing works
Yasuhara, M., Tamaki, H., Iyama, S., et al. (1992) · PubMed · Cited by 17 · see citing works
Prevalence of herpes simplex virus 1 and 2 antibodies in patients with autism spectrum disorders.
Gentile, I., Zappulo, E., Bonavolta, R., Maresca, R., Riccio, M. P., Buonomo, A. R., Portella, G., Vallefuoco, L., Settimi, A., Pascotto, A., et al. (2014) · PubMed · Cited by 15 · see citing works
Fernandez, S., Gillgrass, A. E., & Kaushic, C. (2007) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2007.00482.x · Cited by 15 · see citing works
Gentile, I., Zappulo, E., Bonavolta, R., Maresca, R., Messana, T., Buonomo, A. R., Portella, G., Sorrentino, R., Settimi, A., Pascotto, A., et al. (2014) · PubMed · Cited by 14 · see citing works
Eskild, A., Jenum, P. A., & Bruu, A. (2005) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/j.0001-6349.2005.00796.x · Cited by 14 · see citing works
Nason, M., Patel, E. U., Kirkpatrick, A. R., et al. (2016) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofw073 · Cited by 11 · see citing works
Defining normal IgG changes throughout pregnancy
Taylor, J., Conklin, J., Hunter, S. K., et al. (2013) · Proceedings in Obstetrics and Gynecology · doi:10.17077/2154-4751.1213 · Cited by 7 · see citing works
Eskild, A. (2002) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1016/s1470-0328(02)01934-1 · Cited by 7 · see citing works
[Changes in the immunoglobulins IgG, IgA and IgM in pregnancy and the puerperium].
Miller, E. C., & Abel, W. (1984) · PubMed · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The unique immunological and microbial aspects of pregnancy
Mor, G., Aldo, P., & Alvero, A. B. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.64 · Cited by 1,041 · see citing works
Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders
Israelyan, N., & Margolis, K. G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.020 · Cited by 122 · see citing works
Alteration of gut microbiota-associated epitopes in children with autism spectrum disorders
Wang, M., Zhou, J., He, F., Cai, C., Wang, H., Wang, Y., Lin, Y., Rong, H., Cheng, G., Xu, R., et al. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.10.006 · Cited by 77 · see citing works
- Authors
- Mahic, M., Mjaaland, S., Bøvelstad, H. M., Gunnes, N., Susser, E., Bresnahan, M., Øyen, A.-S., Levin, B., Che, X., Hirtz, D., Reichborn-Kjennerud, T., Schjølberg, S., Roth, C., Magnus, P., Stoltenberg, C., Surén, P., Hornig, M., & Lipkin, W. I.
- Affiliations
- Norwegian Institute of Public Health (NO)
- New York State Psychiatric Institute (US)
- Columbia University (US)
- National Institutes of Health (US)
- Norwegian Institute of Public Health, Oslo, Norway
- Corresponding author
- Lipkin, W. Ian
- ORCID
- Venue
- mSphere
- Publisher
- American Society for Microbiology
- Published
- 2017-02-22
- Volume
- 2
- Issue
- 1
- ISSN
- 2379-5042 (ISSN-L)
- PMC
- PMC5322345
- OpenAlex
- W2590171645
- Cited by
- 56
- References
- 72
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 10 · 2017: 5
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-04-12)
- Open access
- gold
- doi.org
- Licence
- Locations
- mSphere (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BIBSYS Brage (BIBSYS (Norway)) (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Funders
- Jane Bostford Johnson Foundation
- Simons Foundation Autism Research Initiative
- Norwegian Ministry of Education and Research
- Research Council of Norway (189457, 190694, 196452)
- Norwegian Ministry of Health and Care Services
- HHS | National Institutes of Health (NS47537, NS086122)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- autism spectrum disorder, herpes simplex virus type 2, maternal antibodies, gestational infection, immune activation, male offspring, neurodevelopmental disorders, prenatal infection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
