Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis

Jiang, Hai‐yin; Xu, Lianlian; Shao, Li; Xia, Rong-man; Yu, Zhenghe; Ling, Zongxin; Yang, Fan; Deng, Min; Ruan, Bing

doi:10.1016/j.bbi.2016.06.005

Cited by 272 publications

(214 citation statements)

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“…Likewise, sufficient observational studies on the role of maternal inflammation in ASD allow for meta-analyses in the hopes of resolving conflicting reports and clarifying issues about timing and source of infection (20). …”

Section: Genetics Of Autism and Sex Differences In The Brainmentioning

confidence: 99%

Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum Disorder

McCarthy

Wright

2017

Biological Psychiatry

126

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The male bias in autism spectrum disorder incidence is among the most extreme of all neuropsychiatric disorders, yet the origins of the sex difference remain obscure. Developmentally males are exposed to high levels of testosterone and its byproduct, estradiol. Together these steroids modify the course of brain development by altering neurogenesis, cell death, migration, differentiation, dendritic and axonal growth, synaptogenesis and synaptic pruning, all of which can be deleteriously impacted during the course of developmental neuropsychiatric disorders. Elucidating the cellular mechanisms by which steroids modulate brain development provides valuable insights into how these processes may go awry. An emerging theme is the role of inflammatory signaling molecules and the innate immune system in directing brain masculinization, the evidence for which we review here. Likewise evidence is emerging that the neuroimmune system is over-activated in individuals with autism spectrum disorder. These combined observations lead us to propose that the natural process of brain masculinization puts males at risk by moving them closer to a vulnerability threshold that could more easily be breached by inflammation during critical periods of brain development. Two brain regions are highlighted, the preoptic area and the cerebellum. Both are developmentally regulated by the inflammatory prostaglandin, PGE2, but in very different ways. Microglia, innate immune cells of the brain, and astrocytes are also critical contributors to masculinization and illustrate the importance of non-neuronal cells to the health of the developing brain.

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Section: Genetics Of Autism and Sex Differences In The Brainmentioning

confidence: 99%

Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum Disorder

McCarthy

Wright

2017

Biological Psychiatry

126

View full text Add to dashboard Cite

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“…Consequently, research is looking beyond exclusively genetic origins of ASD and considering environmental influences, particularly the connection to immune system perturbations. Epidemiological studies have found that gestational exposure to air pollutants associated with freeways can increase the risk for an ASD diagnoses in offspring (Raz et al, 2015; Volk et al, 2011), and maternal inflammation, most notably by viral or bacterial pathogen, during gestation can also affect neurodevelopment (Jiang et al, 2016). …”

Section: 0 Introductionmentioning

confidence: 99%

Behavioral impact of maternal allergic-asthma in two genetically distinct mouse strains

Schwartzer

Careaga

Coburn

et al. 2017

Brain, Behavior, and Immunity

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Recent population-based studies of expecting mothers identified a unique profile of immune markers that are associated with an increased risk of having a child diagnosed with autism spectrum disorder (ASD). This immune profile, including increased levels of maternal and placental interleukin (IL)-4 and IL-5, is consistent with an immune response found in an allergic-asthma phenotype. Allergies and asthma reflect an imbalance in immune responses including polarization towards T-helper type 2 (TH2) responses, with both genetic susceptibility and environmental factors affecting this T-cell polarization. Mouse strains provide a known and controlled source of genetic diversity to explore the role of genetic predisposition on environmental factors. In particular, the FVB background exhibits a skew towards TH2-mediated allergic-asthma response in traditional models of asthma whereas the C57 strain exhibits a more blunted TH2 polarized phenotype resulting in an attenuated allergic-asthma response. C57BL/6J (C57) and the sighted FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant (FVB/Ant) lines were selected based on their characteristic high sociability and differing sensitivity to TH2-mediated stimuli. Based on the distinct allergy-sensitive immune responses of these two strains we hypothesized that unique developmental consequences would occur in offspring following maternal allergy-asthma exposure. Female C57 and FVB/Ant dams were primed/sensitized with an exposure to ovalbumin (OVA) before pregnancy, then exposed to either aerosolized OVA or PBS-vehicle throughout gestation. Sera from pregnant dams were analyzed for changes in cytokine profiles using multiplex-arrays and offspring were assessed for changes in autism-like behavioral responses. Analysis of maternal sera revealed elevated IL-4 and IL-5 in OVA-treated dams of both strains but only C57 mice expressed increased levels of IL-1β, IL-6, TNFα, and IL-17. Behavioral assessments revealed strain-dependent changes in juvenile reciprocal social interaction in offspring of maternal allergic asthma dams. Moreover, mice of both strains showed decreased repetitive grooming and increased marble burying behavior when born to OVA-exposed dams. Together, these findings support the important role genetic predisposition plays in the effects of maternal immune activation and underscore differences in ASD-like behavioral outcomes across mouse strains.

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“…To the editor, Jiang et al (2016) conducted a meta-analysis to investigate the role of maternal infection and risk of offspring autism spectrum disorder (ASD). The authors reported that maternal infection during pregnancy increased the risk for offspring ASD, with several factors modifying the association including type of infectious agent, timing and site of infection, as well as maternal hospitalization status.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…The bacteria is regarded as a leading cause of nosocomial infection (Aloush et al, 2006), which may explain why Jiang et al (2016) found the risk for offspring ASD was "pronounced" when maternal hospitalization for infection was considered. Jiang et al (2016) ought to consider that their finding that not all infectious agents were significantly associated with an increased risk of offspring ASD may reveal substantial differences in pathogen physiology in addition to altered host immune response. More broadly, the author's novel suggestion here that ubiquitous exposure to environmental N 2 O may facilitate development of offspring neurodevelopmental impairment is not only consistent with extant literature about the role of air pollution in ASD but also presents a notable confounder to the role of MIA in ASD.…”

mentioning

confidence: 99%

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Maternal infection during pregnancy, risk of offspring autism, and the role of bacterial denitrification

Fluegge

2016

Brain, Behavior, and Immunity

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Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis

Cited by 272 publications

References 50 publications

Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum Disorder

Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum Disorder

Behavioral impact of maternal allergic-asthma in two genetically distinct mouse strains

Maternal infection during pregnancy, risk of offspring autism, and the role of bacterial denitrification

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