Research progress on the association between maternal infection in pregnancy and autism in offspring and its mechanism

doi:10.19871/j.cnki.xfcrbzz.2024.02.014

Abstract

Abstract: Autism spectrum disorder (ASD) affects 1% of the world's population. It is a severe spectrum of neurodevelopmental disorders characterized by social difficulties, language difficulties, and stereotypical behaviors. These characteristics can appear before the age of three and last a lifetime. At present, the pathogenesis of autism has not been determined. Previous studies have shown that its pathogenesis is related to genetics, maternal pregnancy environment and perinatal immune status. In 1970 Stella proposed that maternal rubella virus infection was associated with autism in offspring. In recent years, there have been repeated studies proving that maternal infection during pregnancy is associated with autism in offspring. Fetal neurodevelopment can be affected in a variety of ways during pregnancy, including active infections and maternal immune response to infections. This article reviews some of the reported infectious factors associated with the etiology of autism, especially maternal infections during pregnancy, including bacterial、viral and toxoplasmosis, and further elaborates the mechanisms associated with different infectious diseases in autistic children.

Key words: Autism spectrum disorder, Infection during pregnancy, Pathogenesis

CLC Number:

R749
R714

Tian Liyue, Fan Meng, Chen Wenxiong, Wei Jianrui, Yin Xuntao. Research progress on the association between maternal infection in pregnancy and autism in offspring and its mechanism[J]. Electronic Journal of Emerging Infectious Diseases, 2024, 9(2): 68-72.

References

[1] BAXTER AJ, BRUGHA TS, ERSKINE HE, et al.The epidemiology and global burden of autism spectrum disorders[J]. Psychol Med, 2015,45(3): 601-613.
[2] XIONG N, YANG L, YU Y, et al.Investigation of raising burden of children with autism, physical disability and mental disability in China[J]. Res Dev Disabil, 2011, 32(1): 306-311.
[3] MANOLI DS, STATE MW.Autism Spectrum Disorder Genetics and the Search for Pathological Mechanisms[J]. Am J Psychiatry, 2021, 178(1): 30-38.
[4] HAN VX, PATEL S, JONES HF, et al.Maternal immune activation and neuroinflammation in human neurodevelopmental disorders[J]. Nat Rev Neurol, 2021, 17(9): 564-579.
[5] CHESS S.Autism in children with congenital rubella[J]. Autism Child Schizophr, 1971, 1(1): 33-47.
[6] BROWN AS, MEYER U.Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective[J]. Am J Psychiatry, 2018, 175(11): 1073-1083.
[7] CANETTA SE, BAO Y, Co MD, et al.Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring[J]. Am J Psychiatry, 2014, 171(5): 557-563.
[8] ASH S, SHARMA S.Pathogenic Infections during Pregnancy and the Consequences for Fetal Brain Development[J]. Pathogens, 2022, 11(2):193.
[9] CRYAN JF, DINAN TG.Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour[J]. Nat Rev Neurosci, 2012, 13(10): 701-712.
[10] KIM S, KIM H, YIM YS, et al.Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring[J]. Nature, 2017, 549(7673): 528-532.
[11] KANNER L.Autistic disturbances of affective contact[J]. Acta Paedopsychiatr, 1968, 35(4): 100-136.
[12] LAI MC, LOMBARDO MV, BARON-COHEN S.Autism[J]. Lancet, 2014, 383(9920): 896-910.
[13] AMERICAN PSYCHIATRIC ASSOCIATION.Diagnostic and statistical manual of mental disorders (5th ed)[M]. Arlington: American Psychiatric Publishing, 2013.
[14] AMERICAN PSYCHIATRIC ASSOCIATION.Diagnostic and statistical manual of mental disorders (5th ed., text rev.)[M]. Arlington: American Psychiatric Publishing, 2022.
[15] MEGLI CJ, COYNE CB.Infections at the maternal-fetal interface: an overview of pathogenesis and defence[J]. Nat Rev Microbiol, 2022, 20(2): 67-82.
[16] SHI L, FATEMI SH, SIDWELL RW, et al.Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring[J]. J Neurosci, 2003, 23(1): 297-302.
[17] CORDEIRO CN, TSIMIS M, BURD I.Infections and Brain Development[J]. Obstet Gynecol Surv, 2015, 70(10): 644-655.
[18] COLLIER SA, RASMUSSEN SA, FELDKAMP ML, et al.Prevalence of self-reported infection during pregnancy among control mothers in the National Birth Defects Prevention Study[J]. Birth Defects Res A Clin Mol Teratol, 2009, 85(3): 193-201.
[19] HORNIG M, BRESNAHAN MA, CHE X, et al.Prenatal fever and autism risk[J]. Mol Psychiatry,2018,23(3): 759-766.
[20] CROEN LA, QIAN Y, ASHWOOD P, et al.Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development[J]. Autism Res, 2019, 12(10): 1551-1561.
[21] DREIER JW, ANDERSN AM, BERG-BECKHOFF G.Systematic review and meta-analyses: fever in pregnancy and health impacts in the offspring[J]. Pediatrics,2014,133(3): e674-688.
[22] JONAKAIT GM.The effects of maternal inflammation on neuronal development: possible mechanisms[J]. Int J Dev Neurosci, 2007, 25(7): 415-425.
[23] TANG G, GUDSNUK K, KUO SH, et al.Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits[J]. Neuron, 2014, 83(5): 1131-1143.
[24] ZERBO O, QIAN Y, YOSHIDA C, et al.Maternal Infection During Pregnancy and Autism Spectrum Disorders[J]. J Autism Dev Disord, 2015, 45(12): 4015-4025.
[25] ATLADÓTTIR HO, THORSEN P, ØSTERGAARD L, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders[J]. J Autism Dev Disord, 2010, 40(12): 1423-1430.
[26] JONES KL, CROEN LA, YOSHIDA CK, et al.Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation[J]. Mol Psychiatry, 2017, 22(2): 273-279.
[27] PRATT L, NI L, PONZIO NM, et al.Maternal inflammation promotes fetal microglial activation and increased cholinergic expression in the fetal basal forebrain: role of interleukin-6[J]. Pediatr Res, 2013, 74(4): 393-401.
[28] OSKVIG DB, ELKAHLOUN AG, JOHNSON KR, et al.Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response[J]. Brain Behav Immun, 2012, 26(4): 623-634.
[29] HUGHES HK, MORENO RJ, ASHWOOD P.Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD)[J]. Brain Behav Immun, 2023,108: 245-254.
[30] VARGAS DL, NASCIMBENE C, KRISHNAN C, et al.Neuroglial activation and neuroinflammation in the brain of patients with autism[J]. Ann Neurol, 2005, 57(1): 67-81.
[31] AL-HADDAD BJS, JACOBSSON B, CHABRA S, et al.Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero[J]. JAMA Psychiatry, 2019, 76(6): 594-602.
[32] PATTERSON PH.Maternal infection and immune involvement in autism[J]. Trends Mol Med, 2011, 17(7): 389-394.
[33] ABDOLI A, DALIMI A, ARBABI M, et al.Neuropsychiatric manifestations of latent toxoplasmosis on mothers and their offspring[J]. J Matern Fetal Neonatal Med, 2014, 27(13): 1368-1374.
[34] MONTOYA JG, LIESENFELD O.Toxoplasmosis[J]. Lancet. 2004, 363(9425): 1965-1976.
[35] PRANDOVSZKY E, GASKELL E, MARTIN H, et al.The neurotropic parasite Toxoplasma gondii increases dopamine metabolism[J]. PLoS One, 2011, 6(9): e23866.
[36] NAKAMURA K, SEKINE Y, OUCHI Y, et al.Brain serotonin and dopamine transporter bindings in adults with high-functioning autism[J]. Arch Gen Psychiatry, 2010, 67(1): 59-68.
[37] SPANN MN, SOURANDER A, SURCEL HM, et al.Prenatal toxoplasmosis antibody and childhood autism[J]. Autism Res, 2017, 10(5): 769-777.
[38] AL MALKI JS, HUSSIEN NA, AL MALKI F.Maternal toxoplasmosis and the risk of childhood autism: serological and molecular small-scale studies[J]. BMC Pediatr, 2021, 21(1): 133.
[39] LAMBERT N, STREBEL P, ORENSTEIN W, et al.Rubella[J]. Lancet, 2015, 385(9984): 2297-2307.
[40] DESMOND MM, WILSON GS, MELNICK JL, et al.Congenital rubella encephalitis. Course and early sequelae[J]. J Pediatr, 1967, 71(3): 311-331.
[41] MAWSON AR, CROFT AM.Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism[J]. Int J Environ Res Public Health, 2019, 16(19):3543.
[42] TRAYLEN CM, PATEL HR, FONDAW W, et al.Virus reactivation: a panoramic view in human infections[J]. Future Virol, 2011, 6(4): 451-463.
[43] ABATE DA, WATANABE S, MOCARSKI ES.Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response[J]. J Virol, 2004, 78(20): 10995-11006.
[44] RACICOT K, MOR G.Risks associated with viral infections during pregnancy[J]. J Clin Invest, 2017, 127(5): 1591-1599.
[45] ANDRIESSE GI, WEERSINK AJ, DE BOER J.Visual impairment and deafness in young children: consider the diagnosis of congenital infection with cytomegalovirus, even years after birth[J]. Arch Ophthalmol, 2006, 124(5): 743.
[46] SAKAMOTO A, MORIUCHI H, MATSUZAKI J, et al.Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit[J]. Brain Dev, 2015, 37(2): 200-205.
[47] GAROFOLI F, LOMBARDI G, ORCESI S, et al.An Italian Prospective Experience on the Association Between Congenital Cytomegalovirus Infection and Autistic Spectrum Disorder[J]. J Autism Dev Disord, 2017, 47(5): 1490-1495 .
[48] SLAWINSKI BL, TALGE N, INGERSOLL B, et al.Maternal cytomegalovirus sero-positivity and autism symptoms in children[J]. Am J Reprod Immunol, 2018, 79(5): e12840.
[49] GERSHON MD. The enteric nervous system: a second brain[J]. Hosp Pract (1995), 1999, 34(7): 31-32, 35-38, 41-42.
[50] D'EUFEMIA P, CELLI M, FINOCCHIARO R, et al. Abnormal intestinal permeability in children with autism[J]. Acta Paediatr, 1996, 85(9): 1076-1079.
[51] IVANOV, II, ATARASHI K, MANEL N, et al.Induction of intestinal Th17 cells by segmented filamentous bacteria[J]. Cell, 2009, 139(3): 485-498.
[52] SHIN YIM Y, PARK A, BERRIOS J, et al.Reversing behavioural abnormalities in mice exposed to maternal inflammation[J]. Nature, 2017, 549(7673): 482-487.
[53] CHOI GB, YIM YS, WONG H, et al.The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring[J]. Science,2016, 351(6276): 933-939.