Prenatal Arbovirus Infection, Autism Spectrum Disorder, and Attention Deficit and Hyperactivity Disorder: A Scoping Review
Main Article Content
Abstract
Many arbovirus infections have well-known risks of vertical transmission, causing congenital anomalies, therefore being a concern for women who are either planning a pregnancy or are already pregnant. Research on the effects of prenatal exposure to arbovirus infection on long-term neurodevelopment is limited. Of particular concern is the potential association of prenatal infections as risk factors for Autism Spectrum Disorder (ASD) and Attention Deficit and Hyperactivity Disorder (ADHD). In this scoping review, we’ve researched studies that investigate the impact of arbovirus infection on ASD and ADHD through published case-control, cohort, case series, cross-sectional, and experimental study designs. Sixteen articles met our inclusion criteria, five experimental in vitro, one experimental in vivo, one both in vitro and in vivo, and nine in humans. Evidence of a possible association between arboviral infection and ASD was observed in seven articles, and almost all had prenatal exposure to ZIKV. No specific research on prenatal arboviral infection and ADHD was located. However, the similarity of the neurological pathways shared by these two disorders suggests the need for specific investigations in this field.
Article Details
How to Cite
GOMES, Tomás A.M.; SCHULER-FACCINI, Lavínia.
Prenatal Arbovirus Infection, Autism Spectrum Disorder, and Attention Deficit and Hyperactivity Disorder: A Scoping Review.
Medical Research Archives, [S.l.], v. 13, n. 10, oct. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6998>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i10.6998.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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29. Gazeta RE, Bertozzi APAP, Dezena R de C de AB, et al. Three-year clinical follow-up of children intrauterine exposed to zika virus. Viruses. 2021;13(3). doi:10.3390/v13030523
30. Grant R, Fléchelles O, Tressières B, et al. In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study. BMC Med. 2021;19(1). doi:10.1186/s12916-020-01888-0
31. Abtibol-Bernardino MR, Peixoto L de FA de A, Castilho M da C, et al. Would Zika virus Infection in Pregnancy Be a Sentence of Poor Neurological Prognosis for Exposed Children? Neurodevelopmental Outcomes in a Cohort from Brazilian Amazon. Viruses. 2022;14(12). doi:10.3390/v14122659
32. Toizumi M, Vu CN, Huynh HT, et al. A Birth Cohort Follow-Up Study on Congenital Zika Virus Infection in Vietnam. Viruses. 2023;15(9). doi:10.3390/v15091928
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40. Reiersen AM, Constantino JN, Todd RD. Co-occurrence of motor problems and autistic symptoms in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2008;47(6):662-672. doi:10.1097/CHI.0b013e31816bff88
41. Daniel B, Acquaviva E, Bader-Meunier B, et al. Predictive factors of comorbid attention-deficit/hyperactivity disorder in early systemic autoimmune and auto-inflammatory disorders. Pediatric Rheumatology. 2025;23(1). doi:10.1186/s12969-025-01103-5
42. Upthegrove R, Corsi-Zuelli F, Couch A, Barnes N, Vernon A. Current Position and Future Direction of Inflammation in Neuropsychiatric Disorders: a Review. JAMA Psychiatry. Published online July 9, 2025. doi:10.1001/jamapsychiatry.2025.1369
43. Nielsen T, Nassar N, Shand A, et al. Association of Maternal Autoimmune Disease with Attention-Deficit/Hyperactivity Disorder in Children. JAMA Pediatr. 2021;175(3). doi:10.1001/jamapediatrics.2020.5487
44. Zengeler KE, Lukens JR. Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders. Nat Rev Immunol. 2021;21(7):454-468. doi:10.1038/s41577-020-00487-7
45. Younger S, Boutros S, Cargnin F, et al. Behavioral Phenotypes of Foxg1 Heterozygous Mice. Front Pharmacol. 2022;13. doi:10.3389/fphar.2022.927296
46. Miyoshi G, Ueta Y, Natsubori A, et al. FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes. Nat Commun. 2021;12(1). doi:10.1038/s41467-021-23987-z
47. Rosa-Fernandes L, Cugola FR, Russo FB, et al. Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons. Front Cell Neurosci. 2019;13. doi:10.3389/fncel.2019.00064
48. Schuler-Faccini L, Ribeiro E, Feitosa I, et al. Possible Association between Zika Virus Infection and Microcephaly - Brazil, 2015. Vol 65. Centers for Disease Control and Prevention (CDC); 2016. doi:10.3201/eid2110.150847
49. Redfield RR, Kent CK, Leahy MA, et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years-Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Morb Mortal Wkly Rep. Published online April 27, 2018.
50. Arlington V. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 5th ed.; 2013.
2. Leal MC, van der Linden V, Bezerra TP, et al. Characteristics of dysphagia in infants with microcephaly caused by congenital zika virus infection, Brazil, 2015. Emerg Infect Dis. 2017;23(8): 1253-1259. doi:10.3201/eid2308.170354
3. Pereira HVFS, dos Santos SP, Amâncio APRL, et al. Neurological outcomes of congenital Zika syndrome in toddlers and preschoolers: a case series. Lancet Child Adolesc Health. 2020;4(5):378-387. doi:10.1016/S2352-4642(20)30041-9
4. Ribeiro MFM, Prudente COM, de Queiróz KBP. Motor development of children exposed to the zika virus: systematic review. Revista Brasileira de Saude Materno Infantil. 2022;22(4):739-751. doi:10.1590/1806-9304202200040002
5. Gerzson LR, de Almeida CS, da Silva JH, Feitosa MMA, de Oliveira LN, Schuler-Faccini L. Neurodevelopment of Nonmicrocephalic Children, After 18 Months of Life, Exposed Prenatally to Zika Virus. J Child Neurol. 2020;35(4):278-282. doi:10.1177/0883073819892128
6. Moreira MEL, Nielsen-Saines K, Brasil P, et al. Neurodevelopment in Infants Exposed to Zika Virus In Utero. New England Journal of Medicine. 2018;379 (24):2377-2379. doi:10.1056/nejmc1800098
7. Santi L, Riesgo RS, Quincozes-Santos A, et al. Zika Virus Infection Associated with Autism Spectrum Disorder: A Case Report. Neuroimmunomodulation. 2021;28(4):229-232. doi:10.1159/000516560
8. Miyake A, Friedman NP. The nature and organization of individual differences in executive functions: Four general conclusions. Curr Dir Psychol Sci. 2012;21(1):8-14. doi:10.1177/0963721411429458
9. Halstead SB. Seminar Dengue. Vol 370.; 2007. www.thelancet.com
10. Weaver SC, Lecuit M. Chikungunya Virus and the Global Spread of a Mosquito-Borne Disease. New England Journal of Medicine. 2015;372(13):1231-1239. doi:10.1056/nejmra1406035
11. Zhang Y, Liu X, Wu Z, et al. Oropouche virus: A neglected global arboviral threat. Virus Res. 2024;341. doi:10.1016/j.virusres.2024.199318
12. Wilder-Smith A. Yellow Fever in Travelers. Curr Infect Dis Rep. 2019;21(11). doi:10.1007/s11908-019-0701-x
13. Gérardin P, Sampériz S, Ramful D, et al. Neurocognitive Outcome of Children Exposed to Perinatal Mother-to-Child Chikungunya Virus Infection: The CHIMERE Cohort Study on Reunion Island. PLoS Negl Trop Dis. 2014;8(7). doi:10.1371/ journal.pntd.0002996
14. Bentlin MR, de Barros Almeida RAM, Coelho KIR, et al. Perinatal Transmission of Yellow Fever, Brazil, 2009. Emerging Infections Diseases. 2011;17(9):1389-1393. doi:10.1099/jmm.0.2008/003632-0
15. das Neves Martins FE, Chiang JO, Nunes BTD, et al. Newborns with microcephaly in Brazil and potential vertical transmission of Oropouche virus: a case series. Lancet Infect Dis. Published online February 1, 2024. doi:10.1016/S1473-3099(24)00617-0
16. Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med. 2018;169(7):467-473. doi:10.7326/M18-0850
17. Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Systematic Reviews. 2022;18(2). doi:10.1002/cl2.1230
18. Watanabe M, Buth JE, Vishlaghi N, et al. Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection. Cell Rep. 2017;21(2):517-532. doi:10.1016/j.celrep.2017.09.047
19. Beys-da-Silva WO, Rosa RL, Santi L, et al. Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases. Mol Neurobiol. 2019;56(7): 4708-4717. doi:10.1007/s12035-018-1417-x
20. Lottini G, Baggiani M, Chesi G, et al. Zika virus induces FOXG1 nuclear displacement and downregulation in human neural progenitors. Stem Cell Reports. 2022;17 (7):1683-1698. doi:10.1016/j.stemcr.2022.05.008
21. Benazzato C, Lojudice F, Pöehlchen F, et al. Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome. Sci Rep. 2024;14(1). doi:10.1038/s41598-024-65392-8
22. Ohki CMY, Benazzato C, van der Linden V, et al. Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome. Biochim Biophys Acta Mol Basis Dis. 2024;1870(5). doi:10.1016/j.bbadis.2024.167097
23. Nani J V., Krenn V, Christoff RR, Rabello T, Garcez PP, Hayashi MAF. RNA-seq transcriptome of ZIKV-infected brain organoids reanalysis implicates Ndel1 oligopeptidase and its cytoskeleton protein binding partners in the infection pathogenesis and recovery following interferon treatment. Brain Res. 2025;1850. doi:10.1016/j.brainres.2024.149371
24. Ma L, Wang J, Ge J, et al. Reversing neural circuit and behavior deficit in mice exposed to maternal inflammation by Zika virus. EMBO Rep. 2021;22(8). doi:10.15252/embr.202051978
25. Abtibol-Bernardino MR, de Almeida Peixoto L de FA, de Oliveira GA, et al. Neurological findings in children without congenital microcephaly exposed to zika virus in utero: A case series study. Viruses. 2020;12(11). doi:10.3390/v12111335
26. Mulkey SB, Corn E, Williams ME, et al. Neurodevelopmental Outcomes of Preschoolers with Antenatal Zika Virus Exposure Born in the United States. Pathogens. 2024;13(7). doi:10.3390/pathogens13070542
27. Roth NM, Delgado-López C, Wiggins LD, et al. Notes from the Field: Autism Spectrum Disorder Among Children with Laboratory Evidence of Prenatal Zika Virus Exposure — Puerto Rico, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):802-804. doi:10.15585/mmwr.mm7229a5
28. Nielsen-Saines K, Brasil P, Kerin T, et al. Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children. Nat Med. 2019;25(8):1213-1217. doi:10.1038/s41591-019-0496-1
29. Gazeta RE, Bertozzi APAP, Dezena R de C de AB, et al. Three-year clinical follow-up of children intrauterine exposed to zika virus. Viruses. 2021;13(3). doi:10.3390/v13030523
30. Grant R, Fléchelles O, Tressières B, et al. In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study. BMC Med. 2021;19(1). doi:10.1186/s12916-020-01888-0
31. Abtibol-Bernardino MR, Peixoto L de FA de A, Castilho M da C, et al. Would Zika virus Infection in Pregnancy Be a Sentence of Poor Neurological Prognosis for Exposed Children? Neurodevelopmental Outcomes in a Cohort from Brazilian Amazon. Viruses. 2022;14(12). doi:10.3390/v14122659
32. Toizumi M, Vu CN, Huynh HT, et al. A Birth Cohort Follow-Up Study on Congenital Zika Virus Infection in Vietnam. Viruses. 2023;15(9). doi:10.3390/v15091928
33. Tun MMN, Moriuchi M, Toizumi M, et al. Congenital zika virus infection in a birth cohort in Vietnam, 2017-2018. American Journal of Tropical Medicine and Hygiene. 2020;103(5):2059-2064. doi:10.4269/ajtmh.20-0286
34. Brasil P, Pereira JP, Moreira ME, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro. New England Journal of Medicine. 2016;375(24):2321-2334. doi:10.1056/nejmoa1602412
35. Mulkey SB, Ansusinha E, Cristante C, et al. Complexities of zika diagnosis and evaluation in a u.s. congenital zika program. American Journal of Tropical Medicine and Hygiene. 2021;104(6):2210-2219. doi:10.4269/ajtmh.20-1256
36. Halfon N, Houtrow A, Larson K, Newacheck PW. The Changing Landscape of Disability in Childhood. Vol 22.; 2014. http://www.jstor.orgURL:http://www.jstor.org/stable/41475645
37. Boyle CA, Boulet S, Schieve LA, et al. Trends in the prevalence of developmental disabilities in US children, 1997-2008. Pediatrics. 2011;127(6):1034-1042. doi:10.1542/peds.2010-2989
38. Schuler-Faccini L, del Campo M, García-Alix A, et al. Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects. Front Genet. 2022;13. doi:10.3389/fgene.2022.758715
39. Yates EF, Mulkey SB. Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned. Pediatr Res. 2024;96(1):64-72. doi:10.1038/s41390-024-03145-z
40. Reiersen AM, Constantino JN, Todd RD. Co-occurrence of motor problems and autistic symptoms in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2008;47(6):662-672. doi:10.1097/CHI.0b013e31816bff88
41. Daniel B, Acquaviva E, Bader-Meunier B, et al. Predictive factors of comorbid attention-deficit/hyperactivity disorder in early systemic autoimmune and auto-inflammatory disorders. Pediatric Rheumatology. 2025;23(1). doi:10.1186/s12969-025-01103-5
42. Upthegrove R, Corsi-Zuelli F, Couch A, Barnes N, Vernon A. Current Position and Future Direction of Inflammation in Neuropsychiatric Disorders: a Review. JAMA Psychiatry. Published online July 9, 2025. doi:10.1001/jamapsychiatry.2025.1369
43. Nielsen T, Nassar N, Shand A, et al. Association of Maternal Autoimmune Disease with Attention-Deficit/Hyperactivity Disorder in Children. JAMA Pediatr. 2021;175(3). doi:10.1001/jamapediatrics.2020.5487
44. Zengeler KE, Lukens JR. Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders. Nat Rev Immunol. 2021;21(7):454-468. doi:10.1038/s41577-020-00487-7
45. Younger S, Boutros S, Cargnin F, et al. Behavioral Phenotypes of Foxg1 Heterozygous Mice. Front Pharmacol. 2022;13. doi:10.3389/fphar.2022.927296
46. Miyoshi G, Ueta Y, Natsubori A, et al. FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes. Nat Commun. 2021;12(1). doi:10.1038/s41467-021-23987-z
47. Rosa-Fernandes L, Cugola FR, Russo FB, et al. Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons. Front Cell Neurosci. 2019;13. doi:10.3389/fncel.2019.00064
48. Schuler-Faccini L, Ribeiro E, Feitosa I, et al. Possible Association between Zika Virus Infection and Microcephaly - Brazil, 2015. Vol 65. Centers for Disease Control and Prevention (CDC); 2016. doi:10.3201/eid2110.150847
49. Redfield RR, Kent CK, Leahy MA, et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years-Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Morb Mortal Wkly Rep. Published online April 27, 2018.
50. Arlington V. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 5th ed.; 2013.