Table 1.

Summary of MIA model prenatal intervention studies.

Author Year Journal	Species Strain Sex	MIA Protocol MIA Validation	Intervention	Offspring Behavior Outcomes	Offspring Brain Outcomes
Alizadeh 2020 Behav Brain Res	Wistar rats	GD 15, 16 LPS 0.5 mg/kg Cytokine validation: No	Zinc supplementation (30mg/kg) administered through pregnancy via gavage Treatment groups: CON/VEH, CON/ZINC, MIA/VEH, MIA/ZINC	Y maze MIA<CON (males only) Zinc supplementation restored the alterations in working memory in MIA male rats	MIA males exhibited moderate decrease in GAD67 expression level in the male pups Zinc supplementation restored GAD67 mRNA level in the male rats
Vuillermot 2019 Molecular Autism	C57BL/6N mice	GD9 Poly(I:C) [Sigma] 5 mg/kg i.v./restraint Cytokine validation: Yes	Maternal administration of the active VitD hormone, 1,25OHD followed immediately by MIA Treatment groups: CON/VEH, CON/VITD, MIA/VEH, MIA/VITD	Pre-pubertal (PND30–40) EPM – no differences Social Approach MIA<CON, prevented by VitD Marble Burying MIA<CON, prevented by VitD Fear Conditioning MIA<CON, prevented by VitD	N/A
Luan 2018 Scientific Reports	C57BL/6N mice	GD9 Poly(I:C) [Sigma] 5mg/kg Subcutaneous Cytokine validation: No	Maternal administration of the active VitD hormone, 1,25OHD (400ng/kg/2ml) followed immediately by MIA Treatment groups: CON/VEH, CON/VITD, MIA/VEH, MIA/VITD	PPI: MIA/CON = MIA/VITD AMPH Induced Locomotor Activity: MIA>CON, prevented by VitD	CON/VITD, MIA/VEH and MIA/VITD had decreased mesDA progenitors at GD11. CON/VEH<CON/VITD mature mesDAs. VitD increased mature mesDA number. CON/VEH<MIA/VEH post-mitotic mesDAs, prevented by VitD.
Wang 2019 Autism Research	C57BL/6J mice	GD12.5 Poly(I:C) [Sigma] 20 mg/kg i.p. Cytokine validation: Yes	Oral probiotic administration formula (1.5g Probiotics Sachet Children’s Formula/100mL water) from E0.5 to PND21 Average dose intake was 1.5675 × 107 cfu Bifidobacteria and 5.28 × 108 cfu Lactobacillus helveticus per 24hr. Treatment groups: CON/VEH, CON/PRO, MIA/VEH, MIA/PRO	3-chamber SD: MIA<CON time sniffing, prevented by probiotics Self Grooming: MIA>CON time spent grooming, prevented by probiotics Forced Swim Test: MIA>CON immobility, prevented by probiotics Open-Field/EPM: MIA<CON time spent in center/open arms, prevented by probiotics	Probiotic groups had decreased cytokine levels. MIA<CON PFC PV+ neurons, prevented by probiotics. MIA<CON GABA and glutamate levels, prevented by probiotics.
Choi 2016 Neuroimmunology	Mice WT and RORγt-TKO (proinflammatory T-cell KO specific to IL-17a)	GD 12.5, 14.5 Poly(I:C) [Sigma] Cytokine validation: Yes	Maternal administration of IL-17 antibodies to WT and RORγ-tTKO mice Administration of IL-17 directly to dams during pregnancy Treatment groups: CON/VEH, CON/αIL-17, MIA/VEH, MIA/αIL-17, RORγt-TKO/VEH, RORγt-TKO/MIA	USVs: MIA>CON Marble Burying: MIA>CON Social Approach: MIA<CON social interaction percentage MIA+IL-17a antibody = CON phenotype MIA+RORγt-TKO = CON phenotype	MIA and IL-17a direct administration both cause cortical abnormalities (protrusions). MIA/αIL-17 and RORγt-TKO/MIA mice appeared similar to controls
Smith 2008 Neuroscience	C57BL/6J mice, IL-6 KO mice	GD 12.5 Poly(I:C) [Sigma] 20 mg/kg Cytokine validation: Yes	Dams were injected with IL-6, IFNγ, or vehicle. Treatment groups: CON/VEH, MIA/VEH, MIA/αIL-6, MIA/αIFNγ, MIA/αIL-1β	PPI: MIA<CON, prevented by αIL-6 and IL-6 KO Social Interaction: MIA<CON, prevented by αIL-6 and IL-6 KO Open Field: MIA<CON center time, prevented by αIL-6 and IL-6 KO Lateral Inhibition: αIFNγ>αIL-6	MIA rats with neutralizing antibodies are more genetically similar to CON/VEH rats than MIA/VEH rats.
Labrousse 2018 Brain, Behavior and Immunity	C57BL/6J mice, only male offspring behavior	GD 17 LPS [Sigma] 0.12 μg/mouse/100μL i.p. Cytokine validation: Yes	Dams were placed on diets with either deficient or balanced levels of n-3 PUFAs. Pups were continued on the same diet postnatally until adult behavior was taken. Treatment groups: CON/BAL, CON/DEF, MIA/BAL, MIA/DEF	Y Maze: MIA<CON time in novel arm MIA/DEF could not discriminate familiar from novel Novel Object Recognition: MIA<CON time exploring novel object *These effects were not seen when mice did not continue dietary intervention postnatally	DEF rats had less n-3 and more n-6 PUFAs. MIA decreased DHA and n-3 PUFAs. MIA<CON cFos+ cells in DG and CA1 regions of hippocampus, post Y-maze trial 2. DEF pups had fewer cFos+ cells than BAL pups. Microglia phenotypes and IL-6 receptor levels were unaffected by MIA or diet. PCA revealed negative relationship between n-3 PUFA levels and proinflammatory cytokine levels.
Cui K 2009 Schizophrenia Research	Sprague Dawley rats, only male offspring	GD 15, 16 (midgestation group) or GD 18, 19 (late-gestation group) Mid group dose 100 μg/kg LPS [Sigma]. Late group dose 50 μg/kg LPS [Sigma].	Dams were given Ibuprofen at 25 mg/kg shortly after MIA in some cohorts. All dams were injected with BrdU and NeuN markers to the dentate gyrus to assess cell proliferation and survival both immediately following and weeks from LPS exposure. Treatment groups: CON/VEH, MID/VEH, MID/IBU, LATE/VEH, LATE/IBU	N/A	Group 1: BrdU injection 4hrs post MIA, collection 4 weeks later. MID<LATE BrdU+ cells. Group 2: BrdU injection PND14/60, collection 2 hours later. MID<CON BrdU+ cells at PND14. No effect seen at PND60. Group 3: BrdU injection PND14/60, collection 4 weeks later. MID=LATE<CON BrdU+ cells. No effect seen at PD60. IBU prevented increase in body temperature from MIA. Pretreating dams with IBU did not prevent MIA phenotypes.